register interest

Dr Buddha Basnyat

Research Area: Global Health
Scientific Themes: Tropical Medicine & Global Health and Immunology & Infectious Disease
Keywords: Infectious disease, Rickettsial Illness, tropical medicine and global health
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Patan Hospital, Kathmandu

Patan Hospital, Kathmandu

Helping a patient with enteric fever in her home

Helping a patient with enteric fever in her home

Oxford University Clinical Research Unit-Nepal (OUCRU-NP) is hosted by Patan Hospital and the Patan Academy of Health Sciences in Kathmandu Nepal and works in close collaboration with the Nepal Health Research Council at the Nepalese Ministry of Health and Population. Our mission within the Patan Hospital, the Patan Academy of Health Sciences and OUCRU-NP is to build a strong critical mass of young Nepalese clinician scientists who can help build Nepal's scientific and clinical future.

OUCRU-NP was initiated in the summer of 2003 following a visit to Nepal by Professor Jeremy Farrar (who headed OUCRU-Vietnam at that time) after an exchange of letters with Dr Buddha Basnyat (Consultant, Patan Hospital) in the New England Journal of Medicine, subsequent to a review article by Professor Farrar and colleagues on enteric fever.

In this period of about 13 years, this Unit at Patan Hospital has published many ground-breaking randomized controlled trials (RCTs) on enteric fever in well-respected infectious disease journals like the Lancet Infectious Diseases. This Unit has also clearly documented other causes of undifferentiated febrile illness besides enteric fever. Recent research from our Unit showed that typhus commonly mimics typhoid and that, importantly, the treatment is different. The spin-offs of these RCTs have included the study of the epidemiology of enteric fever and crucially research in antimicrobial resistance, an understated problem in South Asia. Very recently we have also been involved in public engagement throughout the country with the Epidemiology and Disease Control Division of the Government of Nepal so that our research findings are not just confined to academia.

Dr Banyat's research interest lies in working with and helping young clinicians in the study of high altitude illness and undifferentiated febrile illness in the tropics, both common but neglected problems in Nepal.

Name Department Institution Country
Professor Guy Thwaites Tropical Medicine Oxford University, Ho Chi Minh City Vietnam
Professor Stephen Baker Tropical Medicine Oxford University, Ho Chi Minh City Vietnam
Dr Marcel Wolbers Tropical Medicine Oxford University, Ho Chi Minh City Vietnam
Keyes LE, Sallade TD, Duke C, Starling J, Sheets A, Pant S, Young DS, Twillman D, Regmi N, Phelan B et al. 2017. Blood Pressure and Altitude: An Observational Cohort Study of Hypertensive and Nonhypertensive Himalayan Trekkers in Nepal. High Alt Med Biol, | Show Abstract | Read more

Keyes, Linda E, Thomas Douglas Sallade, Charles Duke, Jennifer Starling, Alison Sheets, Sushil Pant, David S. Young, David Twillman, Nirajan Regmi, Benoit Phelan, Purshotam Paudel, Matthew McElwee, Luke Mather, Devlin Cole, Theodore McConnell, and Buddha Basnyat. Blood pressure and altitude: an observational cohort study of hypertensive and nonhypertensive Himalayan trekkers in Nepal. High Alt Med Biol 00:000-000, 2017. OBJECTIVES: To determine how blood pressure (BP) changes with altitude in normotensive versus hypertensive trekkers. Secondary aims were to evaluate the prevalence of severe hypertension (BP ≥180/100 mmHg) and efficacy of different antihypertensive agents at high altitude. METHODS: This was an observational cohort study of resting and 24-hour ambulatory BP in normotensive and hypertensive trekkers at 2860, 3400, and 4300 m in Nepal. RESULTS: We enrolled 672 trekkers age 18 years and older, 60 with a prior diagnosis of hypertension. Mean systolic and diastolic BP did not change between altitudes in normotensive or hypertensive trekkers, but was higher in those with hypertension. However, there was large interindividual variability. At 3400 m, the majority (60%, n = 284) of normotensive participants had a BP within 10 mmHg of their BP at 2860 m, while 21% (n = 102) increased and 19% (n = 91) decreased. The pattern was similar between 3400 and 4300 m (64% [n = 202] no change, 21% [n = 65] increased, 15% [n = 46] decreased). BP decreased in a greater proportion of hypertensive trekkers versus normotensives (36% [n = 15] vs. 21% at 3400 m, p = 0.01 and 30% [n = 7] vs. 15% at 4300 m, p = 0.05). Severe hypertension occurred in both groups, but was asymptomatic. In a small subset of participants, 24-hour ambulatory BP monitoring showed that nocturnal BP decreased in normotensive (n = 4) and increased in hypertensive trekkers (n = 4). CONCLUSIONS: Most travelers, including those with well-controlled hypertension, can be reassured that their BP will remain relatively stable at high altitude. Although extremely elevated BP may be observed at high altitude in normotensive and hypertensive people, it is unlikely to be symptomatic. The ideal antihypertensive regimen at high altitude remains unclear.

Reisman J, Deonarain D, Basnyat B. 2017. Impact of a Newly Constructed Motor Vehicle Road on Altitude Illness in the Nepal Himalayas. Wilderness Environ Med, | Show Abstract | Read more

OBJECTIVE: This study investigated the impact that motor vehicle travel along a newly constructed road has on altitude illness (including acute mountain sickness, high-altitude cerebral edema, and high-altitude pulmonary edema). The new road from Besisahar (760 m) to Manang (3540 m) in Nepal was completed in December 2014. METHODS: We enrolled all patients diagnosed with altitude illness at the Himalayan Rescue Association Manang clinic in fall 2016. Phi coefficients were calculated to test for an association between Nepali ethnicity and rapid ascent by motor vehicle. A retrospective review looked at all patients with altitude illness from fall (September-November) 2010 to spring (February-May) 2016. RESULTS: In fall 2016, more than half (54%) of patients with altitude illness traveled to Manang by motor vehicle, and one-third (33%) reached Manang from low altitude (Besisahar) in less than 48 hours. Nepali nationality had a significant association with motor vehicle travel (phi +0.69, P < .0001) as well as with rapid ascent to Manang (phi +0.72, P < .0001). Compared to previous seasons, fall 2016 saw the most patients diagnosed with altitude illness. The proportion of people with altitude illness who traveled by vehicle and reached Manang in less than 48 hours was significantly greater than the proportion prior to completion of the road (P < .0001 for both). CONCLUSIONS: Rapid ascent by the newly constructed road from Besisahar to Manang appears to be related to a significant increase in the number of patients with all forms of altitude illness, especially among Nepalis. The authors believe that educational interventions emphasizing prevention are urgently needed.

Janocha AJ, Comhair SAA, Basnyat B, Neupane M, Gebremedhin A, Khan A, Ricci KS, Zhang R, Erzurum SC, Beall CM. 2017. Antioxidant defense and oxidative damage vary widely among high-altitude residents. Am J Hum Biol, | Show Abstract | Read more

OBJECTIVES: People living at high altitude experience unavoidable low oxygen levels (hypoxia). While acute hypoxia causes an increase in oxidative stress and damage despite higher antioxidant activity, the consequences of chronic hypoxia are poorly understood. The aim of the present study is to assess antioxidant activity and oxidative damage in high-altitude natives and upward migrants. METHODS: Individuals from two indigenous high-altitude populations (Amhara, n = 39), (Sherpa, n = 34), one multigenerational high-altitude population (Oromo, n = 42), one upward migrant population (Nepali, n = 12), and two low-altitude reference populations (Amhara, n = 29; Oromo, n = 18) provided plasma for measurement of superoxide dismutase (SOD) activity as a marker of antioxidant capacity, and urine for measurement of 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a marker of DNA oxidative damage. RESULTS: High-altitude Amhara and Sherpa had the highest SOD activity, while highland Oromo and Nepalis had the lowest among high-altitude populations. High-altitude Amhara had the lowest DNA damage, Sherpa intermediate levels, and high-altitude Oromo had the highest. CONCLUSIONS: High-altitude residence alone does not associate with high antioxidant defenses; residence length appears to be influential. The single-generation upward migrant sample had the lowest defense and nearly the highest DNA damage. The two high-altitude resident samples with millennia of residence had higher defenses than the two with multiple or single generations of residence.

Thapa SS, Basnyat B. 2017. Chronic Diarrhea in a Traveler: Cyclosporiasis. Am J Med, | Read more

Darton TC, Meiring JE, Tonks S, Khan MA, Khanam F, Shakya M, Thindwa D, Baker S, Basnyat B, Clemens JD et al. 2017. The STRATAA study protocol: a programme to assess the burden of enteric fever in Bangladesh, Malawi and Nepal using prospective population census, passive surveillance, serological studies and healthcare utilisation surveys. BMJ Open, 7 (6), pp. e016283. | Show Abstract | Read more

INTRODUCTION: Invasive infections caused by Salmonella enterica serovar Typhi and Paratyphi A are estimated to account for 12-27 million febrile illness episodes worldwide annually. Determining the true burden of typhoidal Salmonellae infections is hindered by lack of population-based studies and adequate laboratory diagnostics.The Strategic Typhoid alliance across Africa and Asia study takes a systematic approach to measuring the age-stratified burden of clinical and subclinical disease caused by typhoidal Salmonellae infections at three high-incidence urban sites in Africa and Asia. We aim to explore the natural history of Salmonella transmission in endemic settings, addressing key uncertainties relating to the epidemiology of enteric fever identified through mathematical models, and enabling optimisation of vaccine strategies. METHODS/DESIGN: Using census-defined denominator populations of ≥100 000 individuals at sites in Malawi, Bangladesh and Nepal, the primary outcome is to characterise the burden of enteric fever in these populations over a 24-month period. During passive surveillance, clinical and household data, and laboratory samples will be collected from febrile individuals. In parallel, healthcare utilisation and water, sanitation and hygiene surveys will be performed to characterise healthcare-seeking behaviour and assess potential routes of transmission. The rates of both undiagnosed and subclinical exposure to typhoidal Salmonellae (seroincidence), identification of chronic carriage and population seroprevalence of typhoid infection will be assessed through age-stratified serosurveys performed at each site. Secondary attack rates will be estimated among household contacts of acute enteric fever cases and possible chronic carriers. ETHICS AND DISSEMINATION: This protocol has been ethically approved by the Oxford Tropical Research Ethics Committee, the icddr,b Institutional Review Board, the Malawian National Health Sciences Research Committee and College of Medicine Research Ethics Committee and Nepal Health Research Council. The study is being conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice. Informed consent was obtained before study enrolment. Results will be submitted to international peer-reviewed journals and presented at international conferences. TRIAL REGISTRATION NUMBER: ISRCTN 12131979. ETHICS REFERENCES: Oxford (Oxford Tropical Research Ethics Committee 39-15).Bangladesh (icddr,b Institutional Review Board PR-15119).Malawi (National Health Sciences Research Committee 15/5/1599).Nepal (Nepal Health Research Council 306/2015).

Phillips L, Basnyat B, Chang Y, Swenson ER, Harris NS. 2017. Findings of Cognitive Impairment at High Altitude: Relationships to Acetazolamide Use and Acute Mountain Sickness. High Alt Med Biol, 18 (2), pp. 121-127. | Show Abstract | Read more

Phillips, Lara, Buddha Basnyat, Yuchiao Chang, Erik R. Swenson, and N. Stuart Harris. Findings of cognitive impairment at high altitude: relationships to acetazolamide use and acute mountain sickness. High Alt Med Biol. 18:121-127, 2017. OBJECTIVE: Acute mountain sickness (AMS) is defined by patient-reported symptoms using the Lake Louise Score (LLS), which provides limited insight into any possible underlying central nervous system (CNS) dysfunction. Some evidence suggests AMS might coexist with altered neural functioning. Cognitive impairment (CI) may go undetected unless a sensitive test is applied. Our hypothesis was that a standardized test for mild CI would provide an objective measure of CNS dysfunction, which may correlate with the symptoms of AMS and so provide a potential new tool to better characterize altitude-related CNS dysfunction. We compared a cognitive screening tool with the LLS to see if it correlated with CNS dysfunction. METHODS: Adult native English-speaking subjects visiting Himalayan Rescue Association aid stations in Nepal at 3520 m (11,548 ft) and 4550 m (14,927 ft) were recruited. Subjects were administered the LLS and a slightly modified version of the environmental Quick mild cognitive impairment screen (eQmci). Medication use for altitude illness was recorded. Scores were compared using the Spearman's correlation coefficient. Data also included medication use. RESULTS: Seventy-nine subjects were enrolled. A cut-off of three or greater was used for the LLS to diagnose AMS and 67 or less for the eQmci to diagnose CI. There were 22 (28%) subjects who met criteria for AMS and 17 (22%) subjects who met criteria for CI. There was a weak correlation (r(2) = 0.06, p = 0.04) between eQmci score and LLS. In matched subjects with identical LLS, recent acetazolamide use was associated with significantly more CI. CONCLUSION: Field assessment of CI using a rapid standardized tool demonstrated that a substantial number of subjects were found to have mild CI following rapid ascent to 3520-4550 m (11,548-14,927 ft). The weak correlation between the LLS and eQmci suggests that AMS does not result in CI. Use of acetazolamide appears to be associated with CI at all levels of AMS severity.

Saad NJ, Bowles CC, Grenfell BT, Basnyat B, Arjyal A, Dongol S, Karkey A, Baker S, Pitzer VE. 2017. The impact of migration and antimicrobial resistance on the transmission dynamics of typhoid fever in Kathmandu, Nepal: A mathematical modelling study. PLoS Negl Trop Dis, 11 (5), pp. e0005547. | Show Abstract | Read more

BACKGROUND: A substantial proportion of the global burden of typhoid fever occurs in South Asia. Kathmandu, Nepal experienced a substantial increase in the number of typhoid fever cases (caused by Salmonella Typhi) between 2000 and 2003, which subsequently declined but to a higher endemic level than in 2000. This epidemic of S. Typhi coincided with an increase in organisms with reduced susceptibility against fluoroquinolones, the emergence of S. Typhi H58, and an increase in the migratory population in Kathmandu. METHODS: We devised a mathematical model to investigate the potential epidemic drivers of typhoid in Kathmandu and fit this model to weekly data of S. Typhi cases between April 1997 and June 2011 and the age distribution of S. Typhi cases. We used this model to determine if the typhoid epidemic in Kathmandu was driven by heightened migration, the emergence of organisms with reduced susceptibility against fluoroquinolones or a combination of these factors. RESULTS: Models allowing for the migration of susceptible individuals into Kathmandu alone or in combination with the emergence of S. Typhi with reduced susceptibility against fluoroquinolones provided a good fit for the data. The emergence of organisms with reduced susceptibility against fluoroquinolones organisms alone, either through an increase in disease duration or increased transmission, did not fully explain the pattern of S. Typhi infections. CONCLUSIONS: Our analysis is consistent with the hypothesis that the increase in typhoid fever in Kathmandu was associated with the migration of susceptible individuals into the city and aided by the emergence of reduced susceptibility against fluoroquinolones. These data support identifying and targeting migrant populations with typhoid immunization programmes to prevent transmission and disease.

Kanaan NC, Peterson AL, Pun M, Holck PS, Starling J, Basyal B, Freeman TF, Gehner JR, Keyes L, Levin DR et al. 2017. Prophylactic Acetaminophen or Ibuprofen Result in Equivalent Acute Mountain Sickness Incidence at High Altitude: A Prospective Randomized Trial. Wilderness Environ Med, 28 (2), pp. 72-78. | Show Abstract | Read more

OBJECTIVE: Recent trials have demonstrated the usefulness of ibuprofen in the prevention of acute mountain sickness (AMS), yet the proposed anti-inflammatory mechanism remains unconfirmed. Acetaminophen and ibuprofen were tested for AMS prevention. We hypothesized that a greater clinical effect would be seen from ibuprofen due to its anti-inflammatory effects compared with acetaminophen's mechanism of possible symptom reduction by predominantly mediating nociception in the brain. METHODS: A double-blind, randomized trial was conducted testing acetaminophen vs ibuprofen for the prevention of AMS. A total of 332 non-Nepali participants were recruited at Pheriche (4371 m) and Dingboche (4410 m) on the Everest Base Camp trek. The participants were randomized to either acetaminophen 1000 mg or ibuprofen 600 mg 3 times a day until they reached Lobuche (4940 m), where they were reassessed. The primary outcome was AMS incidence measured by the Lake Louise Questionnaire score. RESULTS: Data from 225 participants who met inclusion criteria were analyzed. Twenty-five participants (22.1%) in the acetaminophen group and 18 (16.1%) in the ibuprofen group developed AMS (P = .235). The combined AMS incidence was 19.1% (43 participants), 14 percentage points lower than the expected AMS incidence of untreated trekkers in prior studies at this location, suggesting that both interventions reduced the incidence of AMS. CONCLUSIONS: We found little evidence of any difference between acetaminophen and ibuprofen groups in AMS incidence. This suggests that AMS prevention may be multifactorial, affected by anti-inflammatory inhibition of the arachidonic-acid pathway as well as other analgesic mechanisms that mediate nociception. Additional study is needed.

Kayastha GK, Ranjitkar N, Gurung R, Kc RK, Karki S, Shrestha R, Rajbhandari P, Thapa RK, Poudyal B, Acharya P et al. 2017. The use of Imatinib resistance mutation analysis to direct therapy in Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia patients failing Imatinib treatment, in Patan Hospital, Nepal. Br J Haematol, 177 (6), pp. 1000-1007. | Show Abstract | Read more

Philadelphia chromosome/BCR-ABL1 positive chronic myeloid leukaemia (CML) can be successfully treated with Glivec (Imatinib), which is available free of cost through the Glivec International Patient Assistance programme (GIPAP) to patients with proven CML without means to pay for the drug. We review the acquired mutations in the tyrosine kinase encoded by the BCR-ABL1 gene underlying Glivec failure or resistance in a cohort of 388 imatinib-treated CML patients (149 Female and 239 male) registered between February 2003 and June 2016 in Nepal. Forty-five patients (11 female 34 male) were studied; 18 different BCR-ABL1 mutations were seen in 33 patients. P-loop mutation, Kinase domain and A-loop mutations were seen in 9, 16 and 4 patients respectively. Other mutations were seen in five patients. A T315I mutation was the most common mutation, followed by F359V and M244V. Sixteen mutations showed intermediate activity to complete resistance to Glivec. Among the 45 patients evaluated for BCR-ABL1 mutations, 4 were lost to follow-up, 14 died and 27 are still alive. Among the surviving patients, 16 are receiving Nilotinib, 5 Dasatinib and 3 Ponatinib, while 3 patients were referred to India, one of who received allogenic bone marrow transplantation. Understanding the spectrum of further acquired mutations in BCR-ABL1 may help to choose more specific targeted tyrosine kinase inhibitors that can be provided by GIPAP.

Jeong C, Peter BM, Basnyat B, Neupane M, Beall CM, Childs G, Craig SR, Novembre J, Di Rienzo A. 2017. A longitudinal cline characterizes the genetic structure of human populations in the Tibetan plateau. PLoS One, 12 (4), pp. e0175885. | Show Abstract | Read more

Indigenous populations of the Tibetan plateau have attracted much attention for their good performance at extreme high altitude. Most genetic studies of Tibetan adaptations have used genetic variation data at the genome scale, while genetic inferences about their demography and population structure are largely based on uniparental markers. To provide genome-wide information on population structure, we analyzed new and published data of 338 individuals from indigenous populations across the plateau in conjunction with worldwide genetic variation data. We found a clear signal of genetic stratification across the east-west axis within Tibetan samples. Samples from more eastern locations tend to have higher genetic affinity with lowland East Asians, which can be explained by more gene flow from lowland East Asia onto the plateau. Our findings corroborate a previous report of admixture signals in Tibetans, which were based on a subset of the samples analyzed here, but add evidence for isolation by distance in a broader geospatial context.

Laxminarayan R, Kakkar M, Horby P, Malavige GN, Basnyat B. 2017. Emerging and re-emerging infectious disease threats in South Asia: status, vulnerability, preparedness, and outlook. BMJ, 357 pp. j1447. | Read more

Kayastha GK, Ranjitkar N, Gurung R, Kc RK, Karki S, Shrestha R, Thapa RK, Rajbhandari P, Poudyal B, Acharya P et al. 2017. Treating Philadelphia chromosome/BCR-ABL1 positive patients with Glivec (Imatinib mesylate): 10 years' experience at Patan Hospital, Nepal. Br J Haematol, 177 (6), pp. 991-999. | Show Abstract | Read more

The Glivec International Patient Assistance Programme makes Glivec (Imatinib mesylate) available to Philadelphia chromosome/BCR-ABL1 positive patients with chronic myeloid leukaemia (CML) in Lower and Middle Income Countries (LMIC). We have established a large cohort of 211 CML patients who are eligible for Imatinib, in Kathmandu, Nepal. Thirty-one patients were lost to follow-up. We report on 180 CML patients with a median age of 38 years (range 9-81). Of these 180 patients, 162 underwent cytogenetic testing and 110 were investigated by reverse transcription polymerase chain reaction. One hundred and thirty-nine of the 180 patients (77·2%) had at least one optimal response. Taken together, our cohort has a 95% overall survival rate and 78% of the patients were still taking Glivec at a median time of 48·8 months (range 3-140 months). The number of patients who actually failed therapy, as defined by the LeukaemiaNet 2013 criteria, was 39 (21·7%). While our cohort has some differences with those in North America or Europe, we have shown Glivec is effective in inducing an optimal response in our patients in Nepal and that it is possible to deliver a clinical service for CML patients using tyrosine kinase inhibitors in resource-poor settings.

Griva K, Stygall J, Wilson MH, Martin D, Levett D, Mitchell K, Mythen M, Montgomery HE, Grocott MP, Aref-Adib G et al. 2017. Caudwell Xtreme Everest: A prospective study of the effects of environmental hypoxia on cognitive functioning PLOS ONE, 12 (3), pp. e0174277-e0174277. | Show Abstract | Read more

© 2017 Griva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Background: The neuropsychological consequences of exposure to environmental hypobaric hypoxia (EHH) remain unclear. We thus investigated them in a large group of healthy volunteers who trekked to Mount Everest base camp (5,300 m). Methods: A neuropsychological (NP) test battery assessing memory, language, attention, and executive function was administered to 198 participants (age 44.5±13.7 years; 60% male). These were studied at baseline (sea level), 3,500 m (Namche Bazaar), 5,300 m (Everest Base Camp) and on return to 1,300 m (Kathmandu) (attrition rate 23.7%). A comparable control group (n = 25; age 44.5±14.1 years; 60% male) for comparison with trekkers was tested at/or near sea level over an equivalent timeframe so as to account for learning effects associated with repeat testing. The Reliable Change Index (RCI) was used to calculate changes in cognition and neuropsychological function during and after exposure to EHH relative to controls. Results: Overall, attention, verbal ability and executive function declined in those exposed to EHH when the performance of the control group was taken into account (RCI .05 to -.95) with decline persisting at descent. Memory and psychomotor function showed decline at highest ascent only (RCI -.08 to -.56). However, there was inter-individual variability in response: whilst NP performance declined in most, this improved in some trekkers. Cognitive decline was greater amongst older people (r = .42; p < .0001), but was otherwise not consistently associated with socio-demographic, mood, or physiological variables. Conclusions: After correcting for learning effects, attention, verbal abilities and executive functioning declined with exposure to EHH. There was considerable individual variability in the response of brain function to sustained hypoxia with some participants not showing any effects of hypoxia. This might have implications for those facing sustained hypoxia as a result of any disease.

Zafren K, Pun M, Regmi N, Bashyal G, Acharya B, Gautam S, Jamarkattel S, Lamichhane SR, Acharya S, Basnyat B. 2017. High altitude illness in pilgrims after rapid ascent to 4380 M. Travel Med Infect Dis, 16 pp. 31-34. | Show Abstract | Read more

BACKGROUND: The goal of the study was to characterize high altitude illness in Nepali pilgrims. METHODS: We kept standardized records at the Himalayan Rescue Association (HRA) Temporary Health Camp at Gosainkund Lake (4380 m) in the Nepal Himalaya during the annual Janai Purnima Festival in 2014. Records included rate of ascent and Lake Louise Score (LLS). We defined High Altitude Headache (HAH) as headache alone or LLS = 2. Acute Mountain Sickness (AMS) was LLS≥3. High Altitude Cerebral Edema (HACE) was AMS with ataxia or altered mental status. RESULTS: An estimated 10,000 pilgrims ascended rapidly, most in 1-2 days, from Dhunche (1960 m) to Gosainkund Lake (4380 m). We saw 769 patients, of whom 86 had HAH. There were 226 patients with AMS, including 11 patients with HACE. We treated patients with HACE using dexamethasone and supplemental oxygen prior to rapid descent. Each patient with HACE descended carried by a porter. There were no fatalities due to HACE. There were no cases of High Altitude Pulmonary Edema (HAPE). CONCLUSIONS: HAH and AMS were common in pilgrims ascending rapidly to 4380 m. There were 11 cases of HACE, treated with dexamethasone, supplemental oxygen and descent. There were no fatalities.

Thompson CN, Karkey A, Dongol S, Arjyal A, Wolbers M, Darton T, Farrar JJ, Thwaites GE, Dolecek C, Basnyat B, Baker S. 2017. Treatment Response in Enteric Fever in an Era of Increasing Antimicrobial Resistance: An Individual Patient Data Analysis of 2092 Participants Enrolled into 4 Randomized, Controlled Trials in Nepal. Clin Infect Dis, 64 (11), pp. 1522-1531. | Show Abstract | Read more

Background.: Enteric fever, caused by Salmonella Typhi and Salmonella Paratyphi A, is the leading cause of bacterial febrile disease in South Asia. Methods.: Individual data from 2092 patients with enteric fever randomized into 4 trials in Kathmandu, Nepal, were pooled. All trials compared gatifloxacin with 1 of the following comparator drugs: cefixime, chloramphenicol, ofloxacin, or ceftriaxone. Treatment outcomes were evaluated according to antimicrobial if S. Typhi/Paratyphi were isolated from blood. We additionally investigated the impact of changing bacterial antimicrobial susceptibility on outcome. Results.: Overall, 855 (41%) patients had either S. Typhi (n = 581, 28%) or S. Paratyphi A (n = 274, 13%) cultured from blood. There were 139 (6.6%) treatment failures with 1 death. Except for the last trial with ceftriaxone, the fluoroquinolone gatifloxacin was associated with equivalent or better fever clearance times and lower treatment failure rates in comparison to all other antimicrobials. However, we additionally found that the minimum inhibitory concentrations (MICs) against fluoroquinolones have risen significantly since 2005 and were associated with increasing fever clearance times. Notably, all organisms were susceptible to ceftriaxone throughout the study period (2005-2014), and the MICs against azithromycin declined, confirming the utility of these alternative drugs for enteric fever treatment. Conclusion.: The World Health Organization and local government health ministries in South Asia still recommend fluoroquinolones for enteric fever. This policy should change based on the evidence provided here. Rapid diagnostics are urgently required given the large numbers of suspected enteric fever patients with a negative culture.

Bhandari SS, Koirala P, Lohani S, Phuyal P, Basnyat B. 2017. Breathlessness at High Altitude: First Episode of Bronchoconstriction in an Otherwise Healthy Sojourner. High Alt Med Biol, 18 (2), pp. 179-181. | Show Abstract | Read more

Bhandari, Sanjeeb Sudarshan, Pranawa Koirala, Sadichhya Lohani, Pratibha Phuyal, and Buddha Basnyat. Breathlessness at high altitude: first episode of bronchoconstriction in an otherwise healthy sojourner. High Alt Med Biol.. 18:179-181, 2017-High-altitude illness is a collective term for less severe acute mountain sickness and more severe high-altitude pulmonary edema (HAPE) and high-altitude cerebral edema, which we can experience while traveling to high altitude. These get better when we get down to the lower altitudes. People with many comorbidities also have been traveling to high altitudes from the dawn of civilization. Obstructive airway diseases can be confused with HAPE at high altitude. Asthma is one of those obstructive pulmonary diseases, but it is shown to get better with travel to the altitudes higher than the residing altitude. We present a case of 55-year-old nonsmoker, athletic, female, a lowland resident who developed difficulty breathing for the first time at high altitude. She did not get better with the descent to lower altitude and timely intake of acetazolamide. Her pulmonary function test showed obstructive airway pattern, which got better with salbutamol/ipratropium nebulization and oxygen.

Dobinson HC, Gibani MM, Jones C, Thomaides-Brears HB, Voysey M, Darton TC, Waddington CS, Campbell D, Milligan I, Zhou L et al. 2017. Evaluation of the Clinical and Microbiological Response to Salmonella Paratyphi A Infection in the First Paratyphoid Human Challenge Model. Clin Infect Dis, 64 (8), pp. 1066-1073. | Show Abstract | Read more

Background: To expedite the evaluation of vaccines against paratyphoid fever, we aimed to develop the first human challenge model of Salmonella enterica serovar Paratyphi A infection. Methods: Two groups of 20 participants underwent oral challenge with S. Paratyphi A following sodium bicarbonate pretreatment at 1 of 2 dose levels (group 1: 1-5 × 103 colony-forming units [CFU] and group 2: 0.5-1 × 103 CFU). Participants were monitored in an outpatient setting with daily clinical review and collection of blood and stool cultures. Antibiotic treatment was started when prespecified diagnostic criteria were met (temperature ≥38°C for ≥12 hours and/or bacteremia) or at day 14 postchallenge. Results: The primary study objective was achieved following challenge with 1-5 × 103 CFU (group 1), which resulted in an attack rate of 12 of 20 (60%). Compared with typhoid challenge, paratyphoid was notable for high rates of subclinical bacteremia (at this dose, 11/20 [55%]). Despite limited symptoms, bacteremia persisted for up to 96 hours after antibiotic treatment (median duration of bacteremia, 53 hours [interquartile range, 24-85 hours]). Shedding of S. Paratyphi A in stool typically preceded onset of bacteremia. Conclusions: Challenge with S. Paratyphi A at a dose of 1-5 × 103 CFU was well tolerated and associated with an acceptable safety profile. The frequency and persistence of bacteremia in the absence of clinical symptoms was notable, and markedly different from that seen in previous typhoid challenge studies. We conclude that the paratyphoid challenge model is suitable for the assessment of vaccine efficacy using endpoints that include bacteremia and/or symptomatology. Clinical Trials Registration: NCT02100397.

Cho JI, Basnyat B, Jeong C, Di Rienzo A, Childs G, Craig SR, Sun J, Beall CM. 2017. Ethnically Tibetan women in Nepal with low hemoglobin concentration have better reproductive outcomes. Evol Med Public Health, 2017 (1), pp. 82-96. | Show Abstract | Read more

Background and objectives: Tibetans have distinctively low hemoglobin concentrations at high altitudes compared with visitors and Andean highlanders. This study hypothesized that natural selection favors an unelevated hemoglobin concentration among Tibetans. It considered nonheritable sociocultural factors affecting reproductive success and tested the hypotheses that a higher percent of oxygen saturation of hemoglobin (indicating less stress) or lower hemoglobin concentration (indicating dampened response) associated with higher lifetime reproductive success. Methodology: We sampled 1006 post-reproductive ethnically Tibetan women residing at 3000-4100 m in Nepal. We collected reproductive histories by interviews in native dialects and noninvasive physiological measurements. Regression analyses selected influential covariates of measures of reproductive success: the numbers of pregnancies, live births and children surviving to age 15. Results: Taking factors such as marriage status, age of first birth and access to health care into account, we found a higher percent of oxygen saturation associated weakly and an unelevated hemoglobin concentration associated strongly with better reproductive success. Women who lost all their pregnancies or all their live births had hemoglobin concentrations significantly higher than the sample mean. Elevated hemoglobin concentration associated with a lower probability a pregnancy progressed to a live birth. Conclusions and implications: These findings are consistent with the hypothesis that unelevated hemoglobin concentration is an adaptation shaped by natural selection resulting in the relatively low hemoglobin concentration of Tibetans compared with visitors and Andean highlanders.

Karki M, Pandit S, Baker S, Basnyat B. 2016. Cotrimoxazole treats fluoroquinolone-resistant Salmonella typhi H58 infection. BMJ Case Rep, 2016 pp. bcr2016217223-bcr2016217223. | Show Abstract | Read more

A woman aged 20 years presented with fever and no localising signs. She was treated with cotrimoxazole and the subsequent blood culture was positive for Salmonella typhi (S. typhi), which was resistant to fluoroquinolones but susceptible to cotrimoxazole. Genotyping identified an FQ-R subclade of H58 S. typhi Fever clearance time was 4 days after starting the antibiotics, and no relapses were noted on 2 months of follow-up. This inexpensive, well-known and easily available antimicrobial could be suitably redeployed for fluoroquinolone-resistant enteric fever in South Asia.

Basnyat B. 2016. Typhoid versus typhus fever in post-earthquake Nepal. Lancet Glob Health, 4 (8), pp. e516-e517. | Read more

Wong VK, Baker S, Connor TR, Pickard D, Page AJ, Dave J, Murphy N, Holliman R, Sefton A, Millar M et al. 2016. An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid. Nat Commun, 7 pp. 12827. | Show Abstract | Read more

The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.

Basnyat B. 2016. Aftershocks of scrub typhus in Nepal LANCET GLOBAL HEALTH, 4 (10), pp. E688-E688.

Basnyat B. 2016. Aftershocks of scrub typhus in Nepal - Author's reply. Lancet Glob Health, 4 (10), pp. e688. | Read more

International Typhoid Consortium, Wong VK, Holt KE, Okoro C, Baker S, Pickard DJ, Marks F, Page AJ, Olanipekun G, Munir H et al. 2016. Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa. PLoS Negl Trop Dis, 10 (9), pp. e0004781. | Show Abstract | Read more

BACKGROUND: The burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children. METHODS: A total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance. RESULTS: Several distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi. CONCLUSIONS: These data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid.

Donegani E, Paal P, Küpper T, Hefti U, Basnyat B, Carceller A, Bouzat P, van der Spek R, Hillebrandt D. 2016. Drug Use and Misuse in the Mountains: A UIAA MedCom Consensus Guide for Medical Professionals. High Alt Med Biol, 17 (3), pp. 157-184. | Show Abstract | Read more

Donegani, Enrico, Peter Paal, Thomas Küpper, Urs Hefti, Buddha Basnyat, Anna Carceller, Pierre Bouzat, Rianne van der Spek, and David Hillebrandt. Drug use and misuse in the mountains: a UIAA MedCom consensus guide for medical professionals. High Alt Med Biol. 17:157-184, 2016.-Aims: The aim of this review is to inform mountaineers about drugs commonly used in mountains. For many years, drugs have been used to enhance performance in mountaineering. It is the UIAA (International Climbing and Mountaineering Federation-Union International des Associations d'Alpinisme) Medcom's duty to protect mountaineers from possible harm caused by uninformed drug use. The UIAA Medcom assessed relevant articles in scientific literature and peer-reviewed studies, trials, observational studies, and case series to provide information for physicians on drugs commonly used in the mountain environment. Recommendations were graded according to criteria set by the American College of Chest Physicians. RESULTS: Prophylactic, therapeutic, and recreational uses of drugs relevant to mountaineering are presented with an assessment of their risks and benefits. CONCLUSIONS: If using drugs not regulated by the World Anti-Doping Agency (WADA), individuals have to determine their own personal standards for enjoyment, challenge, acceptable risk, and ethics. No system of drug testing could ever, or should ever, be policed for recreational climbers. Sponsored climbers or those who climb for status need to carefully consider both the medical and ethical implications if using drugs to aid performance. In some countries (e.g., Switzerland and Germany), administrative systems for mountaineering or medication control dictate a specific stance, but for most recreational mountaineers, any rules would be unenforceable and have to be a personal decision, but should take into account the current best evidence for risk, benefit, and sporting ethics.

Keyes LE, Mather L, Duke C, Regmi N, Phelan B, Pant S, Starling J, McElwee M, Cole D, McConnell T et al. 2016. Older age, chronic medical conditions and polypharmacy in Himalayan trekkers in Nepal: an epidemiologic survey and case series. J Travel Med, 23 (6), pp. taw052-taw052. | Show Abstract | Read more

BACKGROUND: The number of tourists in Nepal doubled between 2003 and 2013 is nearly 800 000. With the increased popularity of trekking, the number of those with pre-existing medical conditions requiring access to healthcare is likely to increase. We therefore sought to characterize the demographics and health status of trekkers on the Everest Base Camp route in the Solukhumbu Valley. In addition, we report cases that illustrate the potential complications of an ageing and medicated population of trekkers with underlying diseases. METHODS: Trekkers over 18 years were enrolled in a larger observational cohort study on blood pressure at high altitude at 2860 m. They answered a questionnaire regarding demographics, medical history and current medications. Acute medical problems relating to medication use that were brought to the attention of investigators were documented and are presented as case reports. RESULTS: We enrolled 670 trekkers, 394 (59%) male, with a mean age of 48 years (range 18-76). Pre-existing medical conditions were reported by 223 participants (33%). The most frequent conditions included hypertension, hypercholesterolemia, migraines and thyroid dysfunction. A total of 276 participants (41%) reported taking one or more medications. The most common medications were acetazolamide (79, 12%), antihypertensives (50, 8%) and NSAIDs (47, 7%), with 30 classes of drugs represented. Excluding acetazolamide, older trekkers (age >50 years) were more likely than younger ones to take medications (OR = 2.17; 95% CI 1.57-3.00; P <0.05). Acetazolamide use was not related to age. CONCLUSIONS: Our findings illustrate a wide variety of medical conditions present in trekkers in Nepal with wide-ranging potential complications that could pose difficulties in areas where medical care is scarce and evacuation difficult. Our cases illustrate the potential problems polypharmacy poses in trekkers, and the need for local and expedition healthcare workers to be aware of, and prepared for the common medical conditions present.

Khor CC, Do T, Jia H, Nakano M, George R, Abu-Amero K, Duvesh R, Chen LJ, Li Z, Nongpiur ME et al. 2016. Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma. Nat Genet, 48 (5), pp. 556-562. | Show Abstract | Read more

Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

Arjyal A, Basnyat B, Nhan HT, Koirala S, Giri A, Joshi N, Shakya M, Pathak KR, Mahat SP, Prajapati SP et al. 2016. Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial. Lancet Infect Dis, 16 (5), pp. 535-545. | Show Abstract | Read more

BACKGROUND: Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever. METHODS: We did an open-label, randomised, controlled, superiority trial at two hospitals in the Kathmandu valley, Nepal. Eligible participants were children (aged 2-13 years) and adult (aged 14-45 years) with criteria for suspected enteric fever (body temperature ≥38·0°C for ≥4 days without a focus of infection). We randomly assigned eligible patients (1:1) without stratification to 7 days of either oral gatifloxacin (10 mg/kg per day) or intravenous ceftriaxone (60 mg/kg up to 2 g per day for patients aged 2-13 years, or 2 g per day for patients aged ≥14 years). The randomisation list was computer-generated using blocks of four and six. The primary outcome was a composite of treatment failure, defined as the occurrence of at least one of the following: fever clearance time of more than 7 days after treatment initiation; the need for rescue treatment on day 8; microbiological failure (ie, blood cultures positive for Salmonella enterica serotype Typhi, or Paratyphi A, B, or C) on day 8; or relapse or disease-related complications within 28 days of treatment initiation. We did the analyses in the modified intention-to-treat population, and subpopulations with either confirmed blood-culture positivity, or blood-culture negativity. The trial was powered to detect an increase of 20% in the risk of failure. This trial was registered at ClinicalTrials.gov, number NCT01421693, and is now closed. FINDINGS: Between Sept 18, 2011, and July 14, 2014, we screened 725 patients for eligibility. On July 14, 2014, the trial was stopped early by the data safety and monitoring board because S Typhi strains with high-level resistance to ciprofloxacin and gatifloxacin had emerged. At this point, 239 were in the modified intention-to-treat population (120 assigned to gatifloxacin, 119 to ceftriaxone). 18 (15%) patients who received gatifloxacin had treatment failure, compared with 19 (16%) who received ceftriaxone (hazard ratio [HR] 1·04 [95% CI 0·55-1·98]; p=0·91). In the culture-confirmed population, 16 (26%) of 62 patients who received gatifloxacin failed treatment, compared with four (7%) of 54 who received ceftriaxone (HR 0·24 [95% CI 0·08-0·73]; p=0·01). Treatment failure was associated with the emergence of S Typhi exhibiting resistance against fluoroquinolones, requiring the trial to be stopped. By contrast, in patients with a negative blood culture, only two (3%) of 58 who received gatifloxacin failed treatment versus 15 (23%) of 65 who received ceftriaxone (HR 7·50 [95% CI 1·71-32·80]; p=0·01). A similar number of non-serious adverse events occurred in each treatment group, and no serious events were reported. INTERPRETATION: Our results suggest that fluoroquinolones should no longer be used for treatment of enteric fever in Nepal. Additionally, under our study conditions, ceftriaxone was suboptimum in a high proportion of patients with culture-negative enteric fever. Since antimicrobials, specifically fluoroquinolones, are one of the only routinely used control measures for enteric fever, the assessment of novel diagnostics, new treatment options, and use of existing vaccines and development of next-generation vaccines are now a high priority. FUNDING: Wellcome Trust and Li Ka Shing Foundation.

Basnyat B. 2016. Letter from Nepal: Post-earthquake Nepal: Acute-on-chronic problems National Medical Journal of India, 29 (1), pp. 27.

Basnyat B. 2016. Post-earthquake Nepal: Acute-on-chronic problems. Natl Med J India, 29 (1), pp. 27.

Paudyal B, Shakya M, Basnyat B. 2016. Spontaneous hypoglycaemia in a patient with Graves' disease. BMJ Case Rep, 2016 pp. bcr2016214801-bcr2016214801. | Show Abstract | Read more

A 23-year-old man, on treatment for Graves' disease, presented to the emergency department, with 2 separate episodes of loss of consciousness. During the first episode, the initial serum glucose was 19 mg/mL, and 44 mg/dL during the second episode. The patient was non-diabetic, and had elevated blood insulin, C peptide and insulin antibody levels. His abdominal radiographic findings were normal. He was diagnosed with Hirata disease, and put on propylthiouracil as a replacement for carbimazole. Hypoglycaemia was managed with dextrose infusions and frequent meals. The patient's condition improved and he had no further episodes of hypoglycaemia during the follow-up period.

Pham Thanh D, Karkey A, Dongol S, Ho Thi N, Thompson CN, Rabaa MA, Arjyal A, Holt KE, Wong V, Tran Vu Thieu N et al. 2016. A novel ciprofloxacin-resistant subclade of H58 Salmonella Typhi is associated with fluoroquinolone treatment failure. Elife, 5 (MARCH2016), pp. e14003. | Show Abstract | Read more

The interplay between bacterial antimicrobial susceptibility, phylogenetics and patient outcome is poorly understood. During a typhoid clinical treatment trial in Nepal, we observed several treatment failures and isolated highly fluoroquinolone-resistant Salmonella Typhi (S. Typhi). Seventy-eight S. Typhi isolates were genome sequenced and clinical observations, treatment failures and fever clearance times (FCTs) were stratified by lineage. Most fluoroquinolone-resistant S. Typhi belonged to a specific H58 subclade. Treatment failure with S. Typhi-H58 was significantly less frequent with ceftriaxone (3/31; 9.7%) than gatifloxacin (15/34; 44.1%)(Hazard Ratio 0.19, p=0.002). Further, for gatifloxacin-treated patients, those infected with fluoroquinolone-resistant organisms had significantly higher median FCTs (8.2 days) than those infected with susceptible (2.96) or intermediately resistant organisms (4.01)(pS. Typhi clade internationally, but there are no data regarding disease outcome with this organism. We report an emergent new subclade of S. Typhi-H58 that is associated with fluoroquinolone treatment failure.

Paudyal B, Paudel K, Shakya M, Basnyat B. 2016. Paradoxical reaction to antitubercular treatment in a case of pulmonary tuberculosis. BMJ Case Rep, 2016 pp. bcr2015214285-bcr2015214285. | Show Abstract | Read more

A 51-year-old man presented with intermittent fever, mild cough and loss of appetite of 1-month duration. His sputum smear was positive for acid-fast bacilli and his chest radiograph revealed apical infiltrations. The patient was treated with antitubercular therapy (ATT), recovered and was well for 1 month, after which he suddenly developed focal seizures. MRI of the brain with gadolinium enhancement showed high intensity nodular foci in the frontal, parietal and occipital regions. The patient was diagnosed as a case of paradoxical reaction to ATT, and was successfully managed with continued ATT and adjunctive steroid therapy.

Karkey A, Jombart T, Walker AW, Thompson CN, Torres A, Dongol S, Tran Vu Thieu N, Pham Thanh D, Tran Thi Ngoc D, Voong Vinh P et al. 2016. The Ecological Dynamics of Fecal Contamination and Salmonella Typhi and Salmonella Paratyphi A in Municipal Kathmandu Drinking Water. PLoS Negl Trop Dis, 10 (1), pp. e0004346. | Show Abstract | Read more

One of the UN sustainable development goals is to achieve universal access to safe and affordable drinking water by 2030. It is locations like Kathmandu, Nepal, a densely populated city in South Asia with endemic typhoid fever, where this goal is most pertinent. Aiming to understand the public health implications of water quality in Kathmandu we subjected weekly water samples from 10 sources for one year to a range of chemical and bacteriological analyses. We additionally aimed to detect the etiological agents of typhoid fever and longitudinally assess microbial diversity by 16S rRNA gene surveying. We found that the majority of water sources exhibited chemical and bacterial contamination exceeding WHO guidelines. Further analysis of the chemical and bacterial data indicated site-specific pollution, symptomatic of highly localized fecal contamination. Rainfall was found to be a key driver of this fecal contamination, correlating with nitrates and evidence of S. Typhi and S. Paratyphi A, for which DNA was detectable in 333 (77%) and 303 (70%) of 432 water samples, respectively. 16S rRNA gene surveying outlined a spectrum of fecal bacteria in the contaminated water, forming complex communities again displaying location-specific temporal signatures. Our data signify that the municipal water in Kathmandu is a predominant vehicle for the transmission of S. Typhi and S. Paratyphi A. This study represents the first extensive spatiotemporal investigation of water pollution in an endemic typhoid fever setting and implicates highly localized human waste as the major contributor to poor water quality in the Kathmandu Valley.

Izopet J, Labrique AB, Basnyat B, Dalton HR, Kmush B, Heaney CD, Nelson KE, Ahmed ZB, Zaman K, Mansuy JM et al. 2015. Hepatitis E virus seroprevalence in three hyperendemic areas: Nepal, Bangladesh and southwest France. J Clin Virol, 70 pp. 39-42. | Show Abstract | Read more

BACKGROUND: Hepatitis E causes a significant burden of disease in developing countries and has recently been increasingly recognized in developed countries. Comparing population anti-hepatitis E virus (HEV) seroprevalence across populations has been difficult. OBJECTIVES: The aim of this study was to compare the anti-HEV IgG seroprevalence in both adults and children in three hyper-endemic areas (Nepal, Bangladesh and southwest France) using a sensitive, commercial anti-HEV IgG assay. STUDY DESIGN: Serum or plasma from adults and children in Nepal (n=498), Bangladesh (n=1,009) and Southwest France (n=1031) were tested for anti-HEV IgG using the Wantai assay. RESULTS: After age-standardization, anti-HEV IgG seroprevalence was 47.1%, 49.8% and 34.0% in Nepal, Bangladesh and southwest France, respectively. There was no difference in seroprevalence by gender in any of the countries. A paucity of infections in children 1-10 years-old was consistently observed (less than 15%) at all 3 locations. CONCLUSIONS: Surprisingly similar high rates of anti-HEV antibodies were detected using a common, sensitive assay. Despite differences in the epidemiology and circulating genotype of HEV in Nepal, Bangladesh and southwest France, this study found more similarities in population seroprevalence than expected.

Basnyat B. 2015. Tackle Nepal's typhoid problem now. Nature, 524 (7565), pp. 267. | Read more

Kingston HW, Blacksell SD, Tanganuchitcharnchai A, Laongnualpanich A, Basnyat B, Day NP, Paris DH. 2015. Comparative Accuracy of the InBios Scrub Typhus Detect IgM Rapid Test for the Detection of IgM Antibodies by Using Conventional Serology. Clin Vaccine Immunol, 22 (10), pp. 1130-1132. | Show Abstract | Read more

This study investigated the comparative accuracy of a recombinant 56-kDa type-specific antigen-based rapid diagnostic test (RDT) for scrub typhus for the detection of IgM antibodies by using conventional serology in well-characterized serum samples from undifferentiated febrile illness patients. The RDT showed high specificity and promising comparative accuracy, with 82% sensitivity and 98% specificity for samples defined positive at an IgM indirect immunofluorescence assay positivity cutoff titer of ≥1:1,600 versus 92% and 95% at ≥1:6,400, respectively.

Basnyat B, Starling JM. 2015. Infectious Diseases at High Altitude. Microbiol Spectr, 3 (4), | Show Abstract | Read more

Travel to elevations above 2,500 m is an increasingly common activity undertaken by a diverse population of individuals. These may be trekkers, climbers, miners in high-altitude sites in South America, and more recently, soldiers deployed for high-altitude duty in remote areas of the world. What is also being increasingly recognized is the plight of the millions of pilgrims, many with comorbidities, who annually ascend to high-altitude sacred areas. There are also 400 million people who reside permanently in high mountain ranges, which cover one-fifth of the Earth's surface. Many of these high-altitude areas are in developing countries, for example, the Himalayan range in South Asia. Although high-altitude areas may not harbor any specific infectious disease agents, it is important to know about the pathogens encountered in the mountains to be better able to help both the ill sojourner and the native high-altitude dweller. Often the same pathogens prevalent in the surrounding lowlands are found at high altitude, but various factors such as immunomodulation, hypoxia, poor physiological adaptation, and harsh environmental stressors at high altitude may enhance susceptibility to these pathogens. Against this background, various gastrointestinal, respiratory, dermatological, neurological, and other infections encountered at high altitude are discussed.

Parry CM, Thieu NT, Dolecek C, Karkey A, Gupta R, Turner P, Dance D, Maude RR, Ha V, Tran CN et al. 2015. Erratum for Parry et al., Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A. Antimicrob Agents Chemother, 59 (7), pp. 4364. | Read more

Parry CM, Thieu NTV, Dolecek C, Karkey A, Gupta R, Turner P, Dance D, Maude RR, Ha V, Tran CN et al. 2015. Clinically and Microbiologically Derived Azithromycin Susceptibility Breakpoints for Salmonella enterica Serovars Typhi and Paratyphi A (vol 59, pg 2756, 2015) ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 59 (7), pp. 4364-4364. | Read more

Basnyat B, Dalton HR, Kamar N, Rein DB, Labrique A, Farrar J, Piot P, 21 signatories. 2015. Nepali earthquakes and the risk of an epidemic of hepatitis E. Lancet, 385 (9987), pp. 2572-2573. | Read more

Basnyat B, Pokharel P, Dixit S, Giri S. 2015. Antibiotic Use, Its Resistance in Nepal and Recommendations for Action: A Situation Analysis. J Nepal Health Res Counc, 13 (30), pp. 102-111. | Show Abstract

Antibiotics are crucial, life-saving medicines in the fight against infectious disease, but resistance to these drugs is growing all over. This article presents key findings from a detailed situation analysis produced by the Global Antibiotic Resistance Partnership (GARP)-Nepal working group. In the absence of nationally-representative surveillance, it is not possible to fully describe antibiotic resistance in the country, but many important bacterial pathogens are highly resistant to most first-line and some second-line antibiotics, according to available reports. In credible studies, more than half of Escherichia coli, Klebsiella pneumoniae and Streptococcus pneumoniae isolates tested, and over 30 percent of some Shigella spp. and Vibrio cholerae isolates were resistant to first-line antibiotics. The findings for Neisseria gonorrheae and hospital-acquired Staphylococcus aureus are similar. Antibiotic use in animal food is poorly documented in Nepal, but it is commonly acknowledged to be widespread, contributing to the overall antibiotic resistance burden. The volume of veterinary antibiotic sales in Nepal rose over 50 percent from 2008 to 2012, most through retailers without veterinarian prescription. Antibiotics are necessary to treat infections in animals, but they are also used extensively for preventing disease, a use that can be restricted without jeopardizing animal or human health. They may also be used for promoting animal growth, which can be eliminated with no health consequences. Nepal has made important advances in reducing mortality and morbidity and increasing health coverage, but has not yet taken steps to address antibiotic resistance. The GARP-Nepal working group outlines the components of a national strategy on antibiotic resistance, consistent with the recent call by the World Health Organization for national action plans, to be developed collaboratively with stakeholders and partners from government and all relevant sectors.

Koirala P, Wolpin S, Phuyal P, Basnyat B, Zafren K. 2015. A Pain in the Neck. Clay shoveler's fracture due to cervical spine trauma. Wilderness Environ Med, 26 (3), pp. 430-432. | Read more

Parry CM, Thieu NT, Dolecek C, Karkey A, Gupta R, Turner P, Dance D, Maude RR, Ha V, Tran CN et al. 2015. Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A. Antimicrob Agents Chemother, 59 (5), pp. 2756-2764. | Show Abstract | Read more

Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 μg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤ 16 μg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P < 0.001) for S. Paratyphi A. A zone size of ≥ 13 mm to a 5-μg azithromycin disk identified S. Typhi isolates with an MIC of ≤ 16 μg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤ 16 μg/ml or disk inhibition zone size of ≥ 13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 μg/ml and to determine MIC and disk breakpoints for S. Paratyphi A.

Phuyal P, Koirala P, Basnyat B, Zafren K. 2015. An itchy situation. Wilderness Environ Med, 26 (1), pp. 89-90. | Read more

Thompson CN, Blacksell SD, Paris DH, Arjyal A, Karkey A, Dongol S, Giri A, Dolecek C, Day N, Baker S et al. 2015. Undifferentiated febrile illness in Kathmandu, Nepal. Am J Trop Med Hyg, 92 (4), pp. 875-878. | Show Abstract | Read more

Undifferentiated febrile illnesses (UFIs) are common in low- and middle-income countries. We prospectively investigated the causes of UFIs in 627 patients presenting to a tertiary referral hospital in Kathmandu, Nepal. Patients with microbiologically confirmed enteric fever (218 of 627; 34.8%) randomized to gatifloxacin or ofloxacin treatment were previously reported. We randomly selected 125 of 627 (20%) of these UFI patients, consisting of 96 of 409 (23%) cases with sterile blood cultures and 29 of 218 (13%) cases with enteric fever, for additional diagnostic investigations. We found serological evidence of acute murine typhus in 21 of 125 (17%) patients, with 12 of 21 (57%) patients polymerase chain reaction (PCR)-positive for Rickettsia typhi. Three UFI cases were quantitative PCR-positive for Rickettsia spp., two UFI cases were seropositive for Hantavirus, and one UFI case was seropositive for Q fever. Fever clearance time (FCT) for rickettsial infection was 44.5 hours (interquartile range = 26-66 hours), and there was no difference in FCT between ofloxacin or gatifloxacin. Murine typhus represents an important cause of predominantly urban UFIs in Nepal, and fluoroquinolones seem to be an effective empirical treatment.

Shrestha P, Arjyal A, Caws M, Prajapati KG, Karkey A, Dongol S, Pathak S, Prajapati S, Basnyat B. 2015. The Application of GeneXpert MTB/RIF for Smear-Negative TB Diagnosis as a Fee-Paying Service at a South Asian General Hospital. Tuberc Res Treat, 2015 pp. 102430. | Show Abstract | Read more

The GeneXpert MTB/RIF assay (Xpert) is a novel automated diagnostic tool for tuberculosis but its optimal placement in the healthcare system has not been determined. The objective of this study was to determine the possibility of additional case detection for pulmonary tuberculosis (PTB) by offering Xpert to smear-negative patients in a low-HIV burden setting with no Mycobacterium tuberculosis (M.tb.) culture facilities. Patients routinely presenting with symptoms suggestive of PTB with negative smears were offered single Xpert test on a fee-paying basis. Data were retrospectively reviewed to determine case detection in patients tested from February to December 2013. Symptoms associated with a positive test were analysed to determine if refinement of clinical criteria would reduce unnecessary testing. 258 smear-negative patients were included and M.tb. was detected in 55 (21.32%, n = 55/258). Using standard clinical assessment for selection, testing 5 patients detected one case of smear-negative PTB. These results demonstrate that fee-paying Xpert service in low-income setting can increase TB case confirmation substantially and further systematic studies of health economic implications should be conducted to determine optimal implementation models to increase access to Xpert in low- and middle-income countries.

MacKinney TG, Soti KR, Shrestha P, Basnyat B. 2015. Camphor: an herbal medicine causing grand mal seizures. BMJ Case Rep, 2015 (jun11 1), pp. bcr2014209101-bcr2014209101. | Show Abstract | Read more

Camphor is usually used in the USA to repel insects, but it is widely used in other countries as an herb. We report the case of a 52-year-old previously healthy Nepali man who ingested approximately 10 g of pure camphor with therapeutic intention. He developed grand mal seizures, and was evaluated in an emergency room. He failed to recall the camphor ingestion initially, and was treated with phenytoin for new-onset idiopathic seizures. Examining physicians only later found out about his camphor ingestion. Finding the cause of new-onset seizures is often challenging for emergency room physicians, internists and neurologists. In addition to other well-reported causes of secondary seizures, herbal medications and supplements must also be explored.

Shrestha P, Paudyal B, Basnyat B. 2015. GeneXpert MTB/RIF assay as initial test for diagnosis of tuberculous meningitis. BMJ Case Rep, 2015 (jun11 2), pp. bcr2014207502-bcr2014207502. | Show Abstract | Read more

Tuberculous meningitis (TBM) remains the most dangerous form of tuberculosis with high mortality and potential complications. The prompt diagnosis and treatment of this condition remains a key for better prognosis. A 39-year-old woman presented with severe headache, fever, nausea and vomiting, with a history of headache for a month. On examination, confusion, neck rigidity, ptosis and upward plantar reflexes were present. After 7 days of empiric treatment without resolution of her symptoms, she had another spinal tap performed. The diagnosis of TBM was performed by the GeneXpert MTB/RIF assay from her cerebrospinal fluid (CSF). Antitubercular chemotherapy was started. The patient subsequently improved. Where available, the GeneXpert assay should be used immediately in CSF samples of patients suspected of TBM as an adjunct to clinical algorithms to increase the chance of a prompt diagnosis and treatment.

Pant S, Keyes LE, Sharma R, Basnyat B. 2015. A trekker in Nepal with painful skin blisters. BMJ Case Rep, 2015 (jun18 1), pp. bcr2015210560-bcr2015210560. | Show Abstract | Read more

The authors present a case of a 27-year-old woman trekker with painful, slightly itchy eruptions on the dorsum of both hands for 5 days. On examination, she had a papulovesicular rash with some haemorrhagic vesicles over the dorsum of her hands and thumbs.

Neupane M, Basnyat B, Fischer R, Froeschl G, Wolbers M, Rehfuess EA. 2015. Sustained use of biogas fuel and blood pressure among women in rural Nepal. Environ Res, 136 pp. 343-351. | Show Abstract | Read more

BACKGROUND: More than two fifths of the world's population cook with solid fuels and are exposed to household air pollution (HAP). As of now, no studies have assessed whether switching to alternative fuels like biogas could impact cardiovascular health among cooks previously exposed to solid fuel use. METHODS: We conducted a propensity score matched cross-sectional study to explore if the sustained use of biogas fuel for at least ten years impacts blood pressure among adult female cooks of rural Nepal. We recruited one primary cook ≥ 30 years of age from each biogas (219 cooks) and firewood (300 cooks) using household and measured their systolic (SBP) and diastolic blood pressure (DBP). Household characteristics, kitchen ventilation and 24-h kitchen carbon monoxide were assessed. We matched cooks by age, body mass index and socio-economic status score using propensity scores and investigated the effect of biogas use through multivariate regression models in two age groups, 30-50 years and >50 years to account for any post-menopausal changes. RESULTS: We found substantially reduced 24-h kitchen carbon monoxide levels among biogas-using households. After matching and adjustment for smoking, kitchen characteristics, ventilation status and additional fuel use, the use of biogas was associated with 9.8 mmHg lower SBP [95% confidence interval (CI), -20.4 to 0.8] and 6.5 mmHg lower DBP (95% CI, -12.2 to -0.8) compared to firewood users among women >50 years of age. In this age group, biogas use was also associated with 68% reduced odds [Odds ratio 0.32 (95% CI, 0.14 to 0.71)] of developing hypertension. These effects, however, were not identified in younger women aged 30-50 years. CONCLUSIONS: Sustained use of biogas for cooking may protect against cardiovascular disease by lowering the risk of high blood pressure, especially DBP, among older female cooks. These findings need to be confirmed in longitudinal or experimental studies.

Basnyat B, Baker S. 2015. Typhoid carriage in the gallbladder. Lancet, 386 (9998), pp. 1074. | Read more

Basnyat B, Tabin C, Nutt C, Farmer P. 2015. Post-earthquake Nepal: the way forward. Lancet Glob Health, 3 (12), pp. e731-e732. | Read more

Mendelson M, Røttingen JA, Gopinathan U, Hamer DH, Wertheim H, Basnyat B, Butler C, Tomson G, Balasegaram M. 2016. Maximising access to achieve appropriate human antimicrobial use in low-income and middle-income countries. Lancet, 387 (10014), pp. 188-198. | Show Abstract | Read more

Access to quality-assured antimicrobials is regarded as part of the human right to health, yet universal access is often undermined in low-income and middle-income countries. Lack of access to the instruments necessary to make the correct diagnosis and prescribe antimicrobials appropriately, in addition to weak health systems, heightens the challenge faced by prescribers. Evidence-based interventions in community and health-care settings can increase access to appropriately prescribed antimicrobials. The key global enablers of sustainable financing, governance, and leadership will be necessary to achieve access while preventing excess antimicrobial use.

Koirala P, Wolpin S, Phuyal P, Basnyat B, Zafren K. 2015. A Pain in the Neck Wilderness and Environmental Medicine, 26 (3), pp. 430-432. | Read more

Basnyat B, Baker S. 2015. Typhoid carriage in the gallbladder The Lancet, 386 (9998), pp. 1074. | Read more

Chung The H, Karkey A, Pham Thanh D, Boinett CJ, Cain AK, Ellington M, Baker KS, Dongol S, Thompson C, Harris SR et al. 2015. A high-resolution genomic analysis of multidrug-resistant hospital outbreaks of Klebsiella pneumoniae. EMBO Mol Med, 7 (3), pp. 227-239. | Show Abstract | Read more

Multidrug-resistant (MDR) Klebsiella pneumoniae has become a leading cause of nosocomial infections worldwide. Despite its prominence, little is known about the genetic diversity of K. pneumoniae in resource-poor hospital settings. Through whole-genome sequencing (WGS), we reconstructed an outbreak of MDR K. pneumoniae occurring on high-dependency wards in a hospital in Kathmandu during 2012 with a case-fatality rate of 75%. The WGS analysis permitted the identification of two MDR K. pneumoniae lineages causing distinct outbreaks within the complex endemic K. pneumoniae. Using phylogenetic reconstruction and lineage-specific PCR, our data predicted a scenario in which K. pneumoniae, circulating for 6 months before the outbreak, underwent a series of ward-specific clonal expansions after the acquisition of genes facilitating virulence and MDR. We suggest that the early detection of a specific NDM-1 containing lineage in 2011 would have alerted the high-dependency ward staff to intervene. We argue that some form of real-time genetic characterisation, alongside clade-specific PCR during an outbreak, should be factored into future healthcare infection control practices in both high- and low-income settings.

Wong VK, Baker S, Pickard DJ, Parkhill J, Page AJ, Feasey NA, Kingsley RA, Thomson NR, Keane JA, Weill FX et al. 2015. Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events. Nat Genet, 47 (6), pp. 632-639. | Show Abstract | Read more

The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.

Basnyat B. 2014. High altitude pilgrimage medicine. High Alt Med Biol, 15 (4), pp. 434-439. | Show Abstract | Read more

Religious pilgrims have been going to high altitude pilgrimages long before trekkers and climbers sojourned in high altitude regions, but the medical literature about high altitude pilgrimage is sparse. Gosainkunda Lake (4300 m) near Kathmandu, Nepal, and Shri Amarnath Yatra (3800 m) in Sri Nagar, Kashmir, India, are the two sites in the Himalayas from where the majority of published reports of high altitude pilgrimage have originated. Almost all travels to high altitude pilgrimages are characterized by very rapid ascents by large congregations, leading to high rates of acute mountain sickness (AMS). In addition, epidemiological studies of pilgrims from Gosainkunda Lake show that some of the important risk factors for AMS in pilgrims are female sex and older age group. Studies based on the Shri Amarnath Yatra pilgrims show that coronary artery disease, complications of diabetes, and peptic ulcer disease are some of the common, important reasons for admission to hospital during the trip. In this review, the studies that have reported these and other relevant findings will be discussed and appropriate suggestions made to improve pilgrims' safety at high altitude.

Basnyat B. 2014. Pro: pulse oximetry is useful in predicting acute mountain sickness. High Alt Med Biol, 15 (4), pp. 440-441. | Read more

Basnyat B. 2014. Rebuttal to the con statement. High Alt Med Biol, 15 (4), pp. 444. | Read more

Basnyat B. 2014. High Altitude Pilgrimage Medicine HIGH ALTITUDE MEDICINE & BIOLOGY, 15 (4), pp. 434-439. | Read more

Bruno RM, Cogo A, Ghiadoni L, Duo E, Pomidori L, Sharma R, Thapa GB, Basnyat B, Bartesaghi M, Picano E et al. 2014. Cardiovascular function in healthy Himalayan high-altitude dwellers. Atherosclerosis, 236 (1), pp. 47-53. | Show Abstract | Read more

BACKGROUND: Residents of the Himalayan valleys uniquely adapted to their hypoxic environment in terms of pulmonary vasculature, but their systemic vascular function is still largely unexplored. The aim of the study was to investigate vascular function and structure in rural Sherpa population, permanently living at high altitude in Nepal (HA), in comparison with control Caucasian subjects (C) living at sea level. METHODS AND RESULTS: 95 HA and 64 C were enrolled. Cardiac ultrasound, flow-mediated dilation (FMD) of the brachial artery, carotid geometry and stiffness, and aortic pulse wave velocity (PWV) were performed. The same protocol was repeated in 11 HA with reduced FMD, after 1-h 100% O2 administration. HA presented lower FMD (5.18 ± 3.10 vs. 6.44  ±  2.91%, p = 0.02) and hyperemic velocity than C (0.61 ± 0.24 vs. 0.75 ± 0.28 m/s, p = 0.008), while systolic pulmonary pressure was higher (29.4 ± 5.5 vs. 23.6 ± 4.8 mmHg, p < 0.0001). In multiple regression analysis performed in HA, hyperemic velocity remained an independent predictor of FMD, after adjustment for baseline brachial artery diameter, room temperature and pulse pressure, explaining 8.7% of its variance. On the contrary, in C brachial artery diameter remained the only independent predictor of FMD, after adjustment for confounders. HA presented also lower carotid IMT than C (0.509 ± 0.121 vs. 0.576 ± 0.122 mm, p < 0.0001), higher diameter (6.98 ± 1.07 vs. 6.81 ± 0.85 mm, p = 0.004 adjusted for body surface area) and circumferential wall stress (67.6 ± 13.1 vs. 56.4 ± 16.0 kPa, p < 0.0001), while PWV was similar. O2 administration did not modify vascular variables. CONCLUSIONS: HA exhibit reduced NO-mediated dilation in the brachial artery, which is associated to reduced hyperemic response, indicating microcirculatory dysfunction. A peculiar carotid phenotype, characterized by reduced IMT and enlarged diameter, was also found.

Basnyat B. 2014. Antibiotic resistance needs global solutions. Lancet Infect Dis, 14 (7), pp. 549-550. | Read more

Näsström E, Vu Thieu NT, Dongol S, Karkey A, Voong Vinh P, Ha Thanh T, Johansson A, Arjyal A, Thwaites G, Dolecek C et al. 2014. Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever. Elife, 3 | Show Abstract | Read more

The host-pathogen interactions induced by Salmonella Typhi and Salmonella Paratyphi A during enteric fever are poorly understood. This knowledge gap, and the human restricted nature of these bacteria, limit our understanding of the disease and impede the development of new diagnostic approaches. To investigate metabolite signals associated with enteric fever we performed two dimensional gas chromatography with time-of-flight mass spectrometry (GCxGC/TOFMS) on plasma from patients with S. Typhi and S. Paratyphi A infections and asymptomatic controls, identifying 695 individual metabolite peaks. Applying supervised pattern recognition, we found highly significant and reproducible metabolite profiles separating S. Typhi cases, S. Paratyphi A cases, and controls, calculating that a combination of six metabolites could accurately define the etiological agent. For the first time we show that reproducible and serovar specific systemic biomarkers can be detected during enteric fever. Our work defines several biologically plausible metabolites that can be used to detect enteric fever, and unlocks the potential of this method in diagnosing other systemic bacterial infections.

Maeder MM, Basnyat B, Harris NS. 2014. From Matterhorn to Mt Everest: empowering rescuers and improving medical care in Nepal. Wilderness Environ Med, 25 (2), pp. 177-181. | Show Abstract | Read more

This article describes a private initiative in which professional Swiss rescuers, based at the foot of the Matterhorn, trained Nepalese colleagues in advanced high altitude helicopter rescue and medical care techniques. What started as a limited program focused on mountain safety has rapidly developed into a comprehensive project to improve rescue and medical care in the Mt Everest area for both foreign travelers and the local Nepalese people.

Childs G, Craig S, Beall CM, Basnyat B. 2014. Depopulating the Himalayan Highlands: Education and Outmigration From Ethnically Tibetan Communities of Nepal MOUNTAIN RESEARCH AND DEVELOPMENT, 34 (2), pp. 85-94. | Show Abstract | Read more

Communities that have thrived for centuries in Nepal's rugged mountain environments are facing rapid population declines caused by the outmigration of youths, both males and females in nearly equal numbers, who are sent by parents to distant boarding schools and monasteries for secular and religious education. This paper documents the magnitude of outmigration, migration destinations, migration's impact on the age-sex composition of sending communities, the effect of migration on fertility, and projected trends of population decline and aging. The authors conclude by discussing potential long-term threats to the viability of ethnically Tibetan communities in the Himalayan highlands, including outmigration's effect on agricultural production, the family-based care system for the elderly, socioeconomic inequalities, and human capital. © 2014 by the authors.

Thapa GB, Neupane M, Strapazzon G, Basnyat B, Elsenshon F, Brodmann Maeder M, Brugger H. 2014. Nepalese mountain rescue development project. High Alt Med Biol, 15 (1), pp. 91-92. | Read more

Jeong C, Alkorta-Aranburu G, Basnyat B, Neupane M, Witonsky DB, Pritchard JK, Beall CM, Di Rienzo A. 2014. Admixture facilitates genetic adaptations to high altitude in Tibet. Nat Commun, 5 pp. 3281. | Show Abstract | Read more

Admixture is recognized as a widespread feature of human populations, renewing interest in the possibility that genetic exchange can facilitate adaptations to new environments. Studies of Tibetans revealed candidates for high-altitude adaptations in the EGLN1 and EPAS1 genes, associated with lower haemoglobin concentration. However, the history of these variants or that of Tibetans remains poorly understood. Here we analyse genotype data for the Nepalese Sherpa, and find that Tibetans are a mixture of ancestral populations related to the Sherpa and Han Chinese. EGLN1 and EPAS1 genes show a striking enrichment of high-altitude ancestry in the Tibetan genome, indicating that migrants from low altitude acquired adaptive alleles from the highlanders. Accordingly, the Sherpa and Tibetans share adaptive haemoglobin traits. This admixture-mediated adaptation shares important features with adaptive introgression. Therefore, we identify a novel mechanism, beyond selection on new mutations or on standing variation, through which populations can adapt to local environments.

Shrestha P, Pun M, Basnyat B. 2014. High altitude pulmonary edema (HAPE) in a Himalayan trekker: a case report. Extrem Physiol Med, 3 (1), pp. 6. | Show Abstract | Read more

INTRODUCTION: High altitude pulmonary edema is a non-cardiogenic form of pulmonary edema that develops in unacclimatized individuals at altitudes over 2500 m. Early recognition of symptoms and immediate descent are important for successful treatment. Despite early signs and symptoms of high altitude illness, many trekkers tend to push themselves to the maximum limit. Some of them, such as the case reported here, choose to ascend on horse-back which is extremely dangerous and can be fatal. CASE PRESENTATION: A 55 years of age Indian ethnic South African lady was emergency air-lifted from 4410 m altitude in the Nepal Himalayas to Kathamandu (1300 m) with a suspected case of high altitude pulmonary edema. She had continued ascending despite experiencing mild altitude symptoms at Namche (3440 m), and these symptoms worsened considerably at Tengboche (3860 m). At the very start of her trek, just after Lukla (2800 m), she suffered from sore throat, and had consequently begun a course of antibiotics (azithromycin) for a suspected throat infection. She had planned to continue ascending on horse back to complete the trek, however her condition deteriorated further and she had to be medically evacuated.On admission to the clinic her axillary temperature was 99.4 F, blood pressure 120/60 mmHg, pulse rate 72/min, respiratory rate of 25 breaths/min, and pulse oximeter showed saturation of 90% on room air at rest. Right sided crackles on the axillary and posterior region were heard on chest auscultation. Heel to toe test showed no signs of ataxia. The chest radiograph showed patchy infiltrates on the right side. An echocardiogram was done which revealed a high pulmonary artery pressure of 50 mm of Hg. She was diagnosed as resolving high altitude pulmornay edema. She was treated with bed rest, supplemental oxygen and sustained release nifedipine 20 mg (orally) twice a day. On the third day her crackles had cleared significantly and repeat chest radiograph as shown showed remarkable improvement. She felt much better. A repeat echocardiogram revealed a normal pulmonary artery pressure. CONCLUSION: The case report highlights numerous points:1) Many high altitude trekkers have invested significant time, money and physical efforts in in their ventures and are determined to ascend despite early warning and illnesses. 2) Despite no history of altitude illnesses in previous altitude exposure,inter-current illness (in this case a nonspecific respiratory tract infection) may contribute to the development of high altitude pulmonary edema. 3) Continuing ascent using other transport means, whilst suffering from symptoms of high altitude illness, worsens the condition and could be life threatening. 4) Acetazolamide does not prevent high altitude pulmonary edema-perhaps more so in the cases that have inter-current illness. 5) Descent is the golden rule in all altitude illnesses. Actually 'descent' is advised in any undiagnosed illness at high altitude among sojourners. 6) Finally, an experienced guide who has mountain medicine training is essential. They can be crucial in noticing early signs and symptoms of altitude illnesses to inform the client's safety as in this case.

Basnyat B. 2014. Letters: On India, offshore accounts, climate change, Japan, illegal booze, SWAT teams Economist (United Kingdom), 410 (8879),

Dunstan SJ, Hue NT, Han B, Li Z, Tram TT, Sim KS, Parry CM, Chinh NT, Vinh H, Lan NP et al. 2014. Variation at HLA-DRB1 is associated with resistance to enteric fever. Nat Genet, 46 (12), pp. 1333-1336. | Show Abstract | Read more

Enteric fever affects more than 25 million people annually and results from systemic infection with Salmonella enterica serovar Typhi or Paratyphi pathovars A, B or C(1). We conducted a genome-wide association study of 432 individuals with blood culture-confirmed enteric fever and 2,011 controls from Vietnam. We observed strong association at rs7765379 (odds ratio (OR) for the minor allele = 0.18, P = 4.5 × 10(-10)), a marker mapping to the HLA class II region, in proximity to HLA-DQB1 and HLA-DRB1. We replicated this association in 595 enteric fever cases and 386 controls from Nepal and also in a second independent collection of 151 cases and 668 controls from Vietnam. Imputation-based fine-mapping across the extended MHC region showed that the classical HLA-DRB1*04:05 allele (OR = 0.14, P = 2.60 × 10(-11)) could entirely explain the association at rs7765379, thus implicating HLA-DRB1 as a major contributor to resistance against enteric fever, presumably through antigen presentation.

Panthi S, Basnyat B. 2013. High altitude pulmonary oedema (HAPE) in an Indian pilgrim. J Assoc Physicians India, 61 (11), pp. 846-848. | Show Abstract

Increasing number of Hindu pilgrims visit the Himalayas where some of them suffer from high altitude illness including the life threatening forms, high altitude pulmonary oedema (HAPE) and high altitude cerebral oedema. Compared to tourists and trekkers, pilgrims are usually ignorant about altitude illness. This is a case of a pilgrim who suffered from HAPE on his trip to Kailash-Mansarovar and is brought to a tertiary level hospital in Kathmandu. This report emphasises on how to treat a patient with HAPE, a disease which is increasingly being seen in the high altitude pilgrim population.

Panthi S, Basnyat B. 2013. High altitude pulmonary oedema (HAPE) in an Indian pilgrim Journal of Association of Physicians of India, 61 (NOV), pp. 846-848. | Show Abstract

Increasing number of Hindu pilgrims visit the Himalayas where some of them suffer from high altitude illness including the life threatening forms, high altitude pulmonary oedema (HAPE) and high altitude cerebral oedema. Compared to tourists and trekkers, pilgrims are usually ignorant about altitude illness. This is a case of a pilgrim who suffered from HAPE on his trip to Kailash-Mansarovar and is brought to a tertiary level hospital in Kathmandu. This report emphasises on how to treat a patient with HAPE, a disease which is increasingly being seen in the high altitude pilgrim population. © JAPI.

Basnyat B. 2013. Acute High-Altitude Illnesses New England Journal of Medicine, 369 (17), pp. 1664-1667. | Read more

Basnyat B. 2013. Acute high-altitude illnesses. N Engl J Med, 369 (17), pp. 1666. | Read more

Tanner JB, Tanner SM, Thapa GB, Chang Y, Watson KL, Staunton E, Howarth C, Basnyat B, Harris NS. 2013. A randomized trial of temazepam versus acetazolamide in high altitude sleep disturbance. High Alt Med Biol, 14 (3), pp. 234-239. | Show Abstract | Read more

This study is the first comparative trial of sleep medications at high altitude. We performed a randomized, double-blind trial of temazepam and acetazolamide at an altitude of 3540 meters. 34 healthy trekkers with self-reports of high-altitude sleep disturbance were randomized to temazepam 7.5 mg or acetazolamide 125 mg taken at bedtime for one night. The primary outcome was sleep quality on a 100 mm visual analog scale. Additional measurements were obtained with actigraphy; pulse oximetry; and questionnaire evaluation of sleep, daytime drowsiness, daytime sleepiness, and acute mountain sickness. Sixteen subjects were randomized to temazepam and 18 to acetazolamide. Sleep quality on the 100 mm visual analog scale was higher for temazepam (59.6, SD 20.1) than acetazolamide (46.2, SD 20.2; p=0.048). Temazepam also demonstrated higher subjective sleep quality on the Groningen Sleep Quality Scale (3.5 vs. 6.8, p=0.009) and sleep depth visual analog scale (60.3 vs. 41.4, p=0.028). The acetazolamide group reported significantly more awakenings to urinate (1.8 vs. 0.5, p=0.007). No difference was found with regards to mean nocturnal oxygen saturation (84.1 vs. 84.4, p=0.57), proportion of the night spent in periodic breathing, relative desaturations, sleep onset latency, awakenings, wake after sleep onset, sleep efficiency, Stanford Sleepiness Scale scores, daytime drowsiness, or change in self-reported Lake Louise Acute Mountain Sickness scores. We conclude that, at current recommended dosing, treatment of high-altitude sleep disturbance with temazepam is associated with increased subjective sleep quality compared to acetazolamide.

Basnyat B. 2013. Con: All dwellers at high altitude are persons of impaired physical and mental powers: the view from the Himalayas. High Alt Med Biol, 14 (3), pp. 214-215. | Read more

Basnyat B. 2013. Rebuttal to pro statements. High Alt Med Biol, 14 (3), pp. 219. | Read more

Johnson PL, Johnson CC, Poudyal P, Regmi N, Walmsley MA, Basnyat B. 2013. Continuous positive airway pressure treatment for acute mountain sickness at 4240 m in the Nepal Himalaya. High Alt Med Biol, 14 (3), pp. 230-233. | Show Abstract | Read more

Acute mountain sickness (AMS) is very common at altitudes above 2500 m. There are few treatment options in the field where electricity availability is limited, and medical assistance or oxygen is unavailable or difficult to access. Positive airway pressure has been used to treat AMS at 3800 m. We hypothesized that continuous positive airway pressure (CPAP) could be used under field conditions powered by small rechargeable batteries. Methods Part 1. 5 subjects trekked to 3500 m from 2800 m in one day and slept there for one night, ascending in the late afternoon to 3840 m, where they slept using CPAP 6-7 cm via mask. The next morning they descended to 3500 m, spent the day there, ascended in late afternoon to 3840 m, and slept the night without CPAP. Continuous overnight oximetry was recorded and the Lake Louise questionnaire for AMS administered both mornings. Methods Part 2. 14 trekkers with symptoms of AMS were recruited at 4240 m. All took acetazolamide. The Lake Louise questionnaire was administered, oximetry recorded, and CPAP 6-7 cm was applied for 10-15 min. CPAP was used overnight and oximetry recorded continuously. In the morning the Lake Louise questionnaire was administered, and oximetry recorded for 10-15 min. The equipment used in both parts was heated, humidified Respironics RemStar® machines powered by Novuscell™ rechargeable lithium ion batteries. Oximetry was recorded using Embletta™ PDS. Results Part 1. CPAP improved overnight Sao2 and eliminated AMS symptoms in the one subject who developed AMS. CPAP was used for 7-9 h and the machines operated for >8 h using the battery. Results Part 2. CPAP use improved Sao2 when used for 10-15 min at the time of recruitment and overnight CPAP use resulted in significantly reduced AMS symptoms. Conclusion. CPAP with rechargeable battery may be a useful treatment option for trekkers and climbers who develop AMS.

Giri A, Arjyal A, Koirala S, Karkey A, Dongol S, Thapa SD, Shilpakar O, Shrestha R, van Tan L, Thi Thuy Chinh BN et al. 2013. Aetiologies of central nervous system infections in adults in Kathmandu, Nepal: a prospective hospital-based study. Sci Rep, 3 (1), pp. 2382. | Show Abstract | Read more

We conducted a prospective hospital based study from February 2009-April 2011 to identify the possible pathogens of central nervous system (CNS) infections in adults admitted to a tertiary referral hospital (Patan Hospital) in Kathmandu, Nepal. The pathogens of CNS infections were confirmed in cerebrospinal fluid (CSF) using molecular diagnostics, culture (bacteria) and serology. 87 patients were recruited for the study and the etiological diagnosis was established in 38% (n = 33). The bacterial pathogens identified were Neisseria meningitidis (n = 6); Streptococcus pneumoniae (n = 5) and Staphylococcus aureus (n = 2) in 13/87(14%). Enteroviruses were found in 12/87 (13%); Herpes Simplex virus (HSV) in 2/87(2%). IgM against Japanese encephalitis virus (JEV) was detected in the CSF of 11/73 (15%) tested samples. This is the first prospective molecular and serology based CSF analysis in adults with CNS infections in Kathmandu, Nepal. JEV and enteroviruses were the most commonly detected pathogens in this setting.

Charles RC, Sultana T, Alam MM, Yu Y, Wu-Freeman Y, Bufano MK, Rollins SM, Tsai L, Harris JB, LaRocque RC et al. 2013. Identification of immunogenic Salmonella enterica serotype Typhi antigens expressed in chronic biliary carriers of S. Typhi in Kathmandu, Nepal. PLoS Negl Trop Dis, 7 (8), pp. e2335. | Show Abstract | Read more

BACKGROUND: Salmonella enterica serotype Typhi can colonize and persist in the biliary tract of infected individuals, resulting in a state of asymptomatic chronic carriage. Chronic carriers may act as persistent reservoirs of infection within a community and may introduce infection to susceptible individuals and new communities. Little is known about the interaction between the host and pathogen in the biliary tract of chronic carriers, and there is currently no reliable diagnostic assay to identify asymptomatic S. Typhi carriage. METHODOLOGY/PRINCIPAL FINDINGS: To study host-pathogen interactions in the biliary tract during S. Typhi carriage, we applied an immunoscreening technique called in vivo-induced antigen technology (IVIAT), to identify potential biomarkers unique to carriers. IVIAT identifies humorally immunogenic bacterial antigens expressed uniquely in the in vivo environment, and we hypothesized that S. Typhi surviving in the biliary tract of humans may express a distinct antigenic profile. Thirteen S. Typhi antigens that were immunoreactive in carriers, but not in healthy individuals from a typhoid endemic area, were identified. The identified antigens included a number of putative membrane proteins, lipoproteins, and hemolysin-related proteins. YncE (STY1479), an uncharacterized protein with an ATP-binding motif, gave prominent responses in our screen. The response to YncE in patients whose biliary tract contained S. Typhi was compared to responses in patients whose biliary tract did not contain S. Typhi, patients with acute typhoid fever, and healthy controls residing in a typhoid endemic area. Seven of 10 (70%) chronic carriers, 0 of 8 bile culture-negative controls (0%), 0 of 8 healthy Bangladeshis (0%), and 1 of 8 (12.5%) Bangladeshis with acute typhoid fever had detectable anti-YncE IgG in blood. IgA responses were also present. CONCLUSIONS/SIGNIFICANCE: Further evaluation of YncE and other antigens identified by IVIAT could lead to the development of improved diagnostic assays to identify asymptomatic S. Typhi carriers.

Gertsch JH, Holck PS, Basnyat B, Corbett BM. 2013. In reply to "ibuprofen for prevention of acute mountain sickness-is bigger really better?". Wilderness Environ Med, 24 (2), pp. 178-179. | Read more

Andrews JR, Prajapati KG, Eypper E, Shrestha P, Shakya M, Pathak KR, Joshi N, Tiwari P, Risal M, Koirala S et al. 2013. Evaluation of an electricity-free, culture-based approach for detecting typhoidal Salmonella bacteremia during enteric fever in a high burden, resource-limited setting. PLoS Negl Trop Dis, 7 (6), pp. e2292. | Show Abstract | Read more

BACKGROUND: In many rural areas at risk for enteric fever, there are few data on Salmonella enterica serotypes Typhi (S. Typhi) and Paratyphi (S. Paratyphi) incidence, due to limited laboratory capacity for microbiologic culture. Here, we describe an approach that permits recovery of the causative agents of enteric fever in such settings. This approach involves the use of an electricity-free incubator based upon use of phase-change materials. We compared this against conventional blood culture for detection of typhoidal Salmonella. METHODOLOGY/PRINCIPAL FINDINGS: Three hundred and four patients with undifferentiated fever attending the outpatient and emergency departments of a public hospital in the Kathmandu Valley of Nepal were recruited. Conventional blood culture was compared against an electricity-free culture approach. Blood from 66 (21.7%) patients tested positive for a Gram-negative bacterium by at least one of the two methods. Sixty-five (21.4%) patients tested blood culture positive for S. Typhi (30; 9.9%) or S. Paratyphi A (35; 11.5%). From the 65 individuals with culture-confirmed enteric fever, 55 (84.6%) were identified by the conventional blood culture and 60 (92.3%) were identified by the experimental method. Median time-to-positivity was 2 days for both procedures. The experimental approach was falsely positive due to probable skin contaminants in 2 of 239 individuals (0.8%). The percentages of positive and negative agreement for diagnosis of enteric fever were 90.9% (95% CI: 80.0%-97.0%) and 96.0% (92.7%-98.1%), respectively. After initial incubation, Salmonella isolates could be readily recovered from blood culture bottles maintained at room temperature for six months. CONCLUSIONS/SIGNIFICANCE: A simple culture approach based upon a phase-change incubator can be used to isolate agents of enteric fever. This approach could be used as a surveillance tool to assess incidence and drug resistance of the etiologic agents of enteric fever in settings without reliable local access to electricity or local diagnostic microbiology laboratories.

Basnyat B. 2013. Rejuvenation time. High Alt Med Biol, 14 (1), pp. 1-2. | Read more

Pun M, Basnyat B. 2013. International hypoxia symposium XVIII: 26 February-02 March 2013. Extrem Physiol Med, 2 (1), pp. 32. | Show Abstract | Read more

The 18th International Hypoxia Symposia, Lake Louise, Alberta, Canada, February 26-March 02, 2013, covered molecular basis of hypoxic responses (e.g., hypoxia inducible factor, nitrite, nitrate, and hemoglobin) and integrative physiology (e.g., exercise physiology, cerebral blood flow responses, live-high train-low, and population genetics). Free communications and poster sessions covered scientific areas from controlled lab settings to field settings of high altitudes (Andes to Himalayas).

Karkey A, Thompson CN, Tran Vu Thieu N, Dongol S, Le Thi Phuong T, Voong Vinh P, Arjyal A, Martin LB, Rondini S, Farrar JJ et al. 2013. Differential epidemiology of Salmonella Typhi and Paratyphi A in Kathmandu, Nepal: a matched case control investigation in a highly endemic enteric fever setting. PLoS Negl Trop Dis, 7 (8), pp. e2391. | Show Abstract | Read more

BACKGROUND: Enteric fever, a systemic infection caused by the bacteria Salmonella Typhi and Salmonella Paratyphi A, is endemic in Kathmandu, Nepal. Previous work identified proximity to poor quality water sources as a community-level risk for infection. Here, we sought to examine individual-level risk factors related to hygiene and sanitation to improve our understanding of the epidemiology of enteric fever in this setting. METHODOLOGY AND PRINCIPAL FINDINGS: A matched case-control analysis was performed through enrollment of 103 blood culture positive enteric fever patients and 294 afebrile community-based age and gender-matched controls. A detailed questionnaire was administered to both cases and controls and the association between enteric fever infection and potential exposures were examined through conditional logistic regression. Several behavioral practices were identified as protective against infection with enteric fever, including water storage and hygienic habits. Additionally, we found that exposures related to poor water and socioeconomic status are more influential in the risk of infection with S. Typhi, whereas food consumption habits and migration play more of a role in risk of S. Paratyphi A infection. CONCLUSIONS AND SIGNIFICANCE: Our work suggests that S. Typhi and S. Paratyphi A follow different routes of infection in this highly endemic setting and that sustained exposure to both serovars probably leads to the development of passive immunity. In the absence of a polyvalent vaccine against S. Typhi and S. Paratyphi A, we advocate better systems for water treatment and storage, improvements in the quality of street food, and vaccination with currently available S. Typhi vaccines.

Parry CM, Basnyat B, Crump JA. 2013. The management of antimicrobial-resistant enteric fever. Expert Rev Anti Infect Ther, 11 (12), pp. 1259-1261. | Read more

Koirala S, Basnyat B, Arjyal A, Shilpakar O, Shrestha K, Shrestha R, Shrestha UM, Agrawal K, Koirala KD, Thapa SD et al. 2013. Gatifloxacin versus ofloxacin for the treatment of uncomplicated enteric fever in Nepal: an open-label, randomized, controlled trial. PLoS Negl Trop Dis, 7 (10), pp. e2523. | Show Abstract | Read more

BACKGROUND: Fluoroquinolones are the most commonly used group of antimicrobials for the treatment of enteric fever, but no direct comparison between two fluoroquinolones has been performed in a large randomised trial. An open-label randomized trial was conducted to investigate whether gatifloxacin is more effective than ofloxacin in the treatment of uncomplicated enteric fever caused by nalidixic acid-resistant Salmonella enterica serovars Typhi and Paratyphi A. METHODOLOGY AND PRINCIPAL FINDINGS: Adults and children clinically diagnosed with uncomplicated enteric fever were enrolled in the study to receive gatifloxacin (10 mg/kg/day) in a single dose or ofloxacin (20 mg/kg/day) in two divided doses for 7 days. Patients were followed for six months. The primary outcome was treatment failure in patients infected with nalidixic acid resistant isolates. 627 patients with a median age of 17 (IQR 9-23) years were randomised. Of the 218 patients with culture confirmed enteric fever, 170 patients were infected with nalidixic acid-resistant isolates. In the ofloxacin group, 6 out of 83 patients had treatment failure compared to 5 out of 87 in the gatifloxacin group (hazard ratio [HR] of time to failure 0.81, 95% CI 0.25 to 2.65, p = 0.73). The median time to fever clearance was 4.70 days (IQR 2.98-5.90) in the ofloxacin group versus 3.31 days (IQR 2.29-4.75) in the gatifloxacin group (HR = 1.59, 95% CI 1.16 to 2.18, p = 0.004). The results in all blood culture-confirmed patients and all randomized patients were comparable. CONCLUSION: Gatifloxacin was not superior to ofloxacin in preventing failure, but use of gatifloxacin did result in more prompt fever clearance time compared to ofloxacin. TRIAL REGISTRATION: ISRCTN 63006567 (www.controlled-trials.com).

Ramachandran S, Singhal M, McKenzie KG, Osborn JL, Arjyal A, Dongol S, Baker SG, Basnyat B, Farrar J, Dolecek C et al. 2013. A Rapid, Multiplexed, High-Throughput Flow-Through Membrane Immunoassay: A Convenient Alternative to ELISA. Diagnostics (Basel), 3 (2), pp. 244-260. | Show Abstract | Read more

This paper describes a rapid, high-throughput flow-through membrane immunoassay (FMIA) platform. A nitrocellulose membrane was spotted in an array format with multiple capture and control reagents for each sample detection area, and assay steps were carried out by sequential aspiration of sample and reagents through each detection area using a 96-well vacuum manifold. The FMIA provides an alternate assay format with several advantages over ELISA. The high surface area of the membrane permits high label concentration using gold labels, and the small pores and vacuum control provide rapid diffusion to reduce total assay time to ~30 min. All reagents used in the FMIA are compatible with dry storage without refrigeration. The results appear as colored spots on the membrane that can be quantified using a flatbed scanner. We demonstrate the platform for detection of IgM specific to lipopolysaccharides (LPS) derived from Salmonella Typhi. The FMIA format provides analytical results comparable to ELISA in less time, provides integrated assay controls, and allows compensation for specimen-to-specimen variability in background, which is a particular challenge for IgM assays.

Cushing TA, McIntosh SE, Keyes LE, Rodway GW, Schoene RB, Basnyat B, Freer L. 2012. Performance-enhancing drugs-commentaries. Wilderness Environ Med, 23 (3), pp. 207-211. | Read more

Basnyat B. 2012. Acclimatizing with acetazolamide. J Travel Med, 19 (5), pp. 281-283. | Read more

Shrestha P, Basnyat B, Küpper T, van der Giet S. 2012. Cerebral venous sinus thrombosis at high altitude. High Alt Med Biol, 13 (1), pp. 60-62. | Show Abstract | Read more

Cerebral venous sinus thrombosis (CVST) is a rare but potentially life-threatening medical condition. We describe a case of a 47-year-old woman who presented with headache, speech defects, and visual disturbances, and was later diagnosed with cerebral venous sinus thrombosis. The article describes a possible risk of such thrombotic events with exposure to high altitude environment in patients with coagulation defects such as Factor V Leiden mutation. Besides, such neurological conditions can occur independent of altitude illness and need to be recognized as their management differs.

Koirala KD, Thanh DP, Thapa SD, Arjyal A, Karkey A, Dongol S, Shrestha UM, Farrar JJ, Basnyat B, Baker S. 2012. Highly resistant Salmonella enterica serovar Typhi with a novel gyrA mutation raises questions about the long-term efficacy of older fluoroquinolones for treating typhoid fever. Antimicrob Agents Chemother, 56 (5), pp. 2761-2762. | Show Abstract | Read more

As a consequence of multidrug resistance, clinicians are highly dependent on fluoroquinolones for treating the serious systemic infection typhoid fever. While reduced susceptibility to fluoroquinolones, which lessens clinical efficacy, is becoming ubiquitous, comprehensive resistance is exceptional. Here we report ofloxacin treatment failure in typhoidal patient infected with a novel, highly fluoroquinolone-resistant isolate of Salmonella enterica serovar Typhi. The isolation of this organism has serious implications for the long-term efficacy of ciprofloxacin and ofloxacin for typhoid treatment.

Hanaoka M, Droma Y, Basnyat B, Ito M, Kobayashi N, Katsuyama Y, Kubo K, Ota M. 2012. Genetic variants in EPAS1 contribute to adaptation to high-altitude hypoxia in Sherpas. PLoS One, 7 (12), pp. e50566. | Show Abstract | Read more

Sherpas comprise a population of Tibetan ancestry in the Himalayan region that is renowned for its mountaineering prowess. The very small amount of available genetic information for Sherpas is insufficient to explain their physiological ability to adapt to high-altitude hypoxia. Recent genetic evidence has indicated that natural selection on the endothelial PAS domain protein 1 (EPAS1) gene was occurred in the Tibetan population during their occupation in the Tibetan Plateau for millennia. Tibetan-specific variations in EPAS1 may regulate the physiological responses to high-altitude hypoxia via a hypoxia-inducible transcription factor pathway. We examined three significant tag single-nucleotide polymorphisms (SNPs, rs13419896, rs4953354, and rs4953388) in the EPAS1 gene in Sherpas, and compared these variants with Tibetan highlanders on the Tibetan Plateau as well as with non-Sherpa lowlanders. We found that Sherpas and Tibetans on the Tibetan Plateau exhibit similar patterns in three EPAS1 significant tag SNPs, but these patterns are the reverse of those in non-Sherpa lowlanders. The three SNPs were in strong linkage in Sherpas, but in weak linkage in non-Sherpas. Importantly, the haplotype structured by the Sherpa-dominant alleles was present in Sherpas but rarely present in non-Sherpas. Surprisingly, the average level of serum erythropoietin in Sherpas at 3440 m was equal to that in non-Sherpas at 1300 m, indicating a resistant response of erythropoietin to high-altitude hypoxia in Sherpas. These observations strongly suggest that EPAS1 is under selection for adaptation to the high-altitude life of Tibetan populations, including Sherpas. Understanding of the mechanism of hypoxia tolerance in Tibetans is expected to provide lights to the therapeutic solutions of some hypoxia-related human diseases, such as cardiovascular disease and cancer.

Dongol S, Thompson CN, Clare S, Nga TV, Duy PT, Karkey A, Arjyal A, Koirala S, Khatri NS, Maskey P et al. 2012. The microbiological and clinical characteristics of invasive salmonella in gallbladders from cholecystectomy patients in kathmandu, Nepal. PLoS One, 7 (10), pp. e47342. | Show Abstract | Read more

Gallbladder carriage of invasive Salmonella is considered fundamental in sustaining typhoid fever transmission. Bile and tissue was obtained from 1,377 individuals undergoing cholecystectomy in Kathmandu to investigate the prevalence, characteristics and relevance of invasive Salmonella in the gallbladder in an endemic area. Twenty percent of bile samples contained a Gram-negative organism, with Salmonella Typhi and Salmonella Paratyphi A isolated from 24 and 22 individuals, respectively. Gallbladders that contained Salmonella were more likely to show evidence of acute inflammation with extensive neutrophil infiltrate than those without Salmonella, corresponding with higher neutrophil and lower lymphocyte counts in the blood of Salmonella positive individuals. Antimicrobial resistance in the invasive Salmonella isolates was limited, indicating that gallbladder colonization is unlikely to be driven by antimicrobial resistance. The overall role of invasive Salmonella carriage in the gallbladder is not understood; here we show that 3.5% of individuals undergoing cholecystectomy in this setting have a high concentration of antimicrobial sensitive, invasive Salmonella in their bile. We predict that such individuals will become increasingly important if current transmission mechanisms are disturbed; prospectively identifying these individuals is, therefore, paramount for rapid local and regional elimination.

Gertsch JH, Corbett B, Holck PS, Mulcahy A, Watts M, Stillwagon NT, Casto AM, Abramson CH, Vaughan CP, Macguire C et al. 2012. Altitude Sickness in Climbers and Efficacy of NSAIDs Trial (ASCENT): randomized, controlled trial of ibuprofen versus placebo for prevention of altitude illness. Wilderness Environ Med, 23 (4), pp. 307-315. | Show Abstract | Read more

OBJECTIVE: To study the effectiveness of ibuprofen versus placebo in preventing acute mountain sickness (AMS) and high altitude headache (HAH). METHODS: Double-blind, randomized, placebo-controlled trial. RESULTS: Two hundred ninety-four healthy Western trekkers were recruited on the Everest approach at 4280 m or 4358 m and randomly assigned to receive either 600 mg of ibuprofen or placebo 3 times daily before and during ascent to 4928 m. One hundred eighty-three of 294 participants completed the trial. Of the participants who did not complete the trial, 62 were lost to follow-up and another 49 broke trial protocol. In an intent-to-treat analysis (232 participants), ibuprofen was found to be more effective than placebo in reducing the incidence of AMS (24.4% vs 40.4%; P = .01) and the incidence of HAH (42.3% vs 60.5%; P < .01). Ibuprofen was also superior to placebo in reducing the severity of HAH (4.9% vs 14.7%; P = .01). The end point of oxygen saturation was also higher in the ibuprofen group (80.8 % vs 82.4%; P = .035). For the 183 participants who completed the trial and conformed to the protocol, the incidence of AMS between placebo and treatment groups was not significant (32.9% vs 22.7%; P = .129 for AMS incidence, 9.6% vs 8.2%; P = .74 for AMS severity, 54.8% vs 42.7%; P = .11 for HAH incidence, and 8.2% vs 3.6%; P = .18 for HAH severity). CONCLUSIONS: Ibuprofen was found to be effective in preventing AMS in the intent-to-treat analysis group but not in those who completed the trial. This loss of significance in the subjects who completed the trial may be explained by persons in the placebo group having a higher burden of illness and associated decreased compliance with the protocol. An important limitation of this study may be the possibility that ibuprofen can mask headache, which is a compulsory criterion for the diagnosis of AMS.

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Gertsch JH, Corbett B, Holck PS, Mulcahy A, Watts M, Stillwagon NT, Casto AM, Abramson CH, Vaughan CPA, MacGuire C et al. 2012. Altitude sickness in climbers and efficacy of NSAIDs trial (ASCENT): Randomized, controlled trial of ibuprofen versus placebo for prevention of altitude illness Wilderness and Environmental Medicine, 23 (4), pp. 307-315. | Show Abstract | Read more

Objective: To study the effectiveness of ibuprofen versus placebo in preventing acute mountain sickness (AMS) and high altitude headache (HAH). Methods: Double-blind, randomized, placebo-controlled trial. Results: Two hundred ninety-four healthy Western trekkers were recruited on the Everest approach at 4280 m or 4358 m and randomly assigned to receive either 600 mg of ibuprofen or placebo 3 times daily before and during ascent to 4928 m. One hundred eighty-three of 294 participants completed the trial. Of the participants who did not complete the trial, 62 were lost to follow-up and another 49 broke trial protocol. In an intent-to-treat analysis (232 participants), ibuprofen was found to be more effective than placebo in reducing the incidence of AMS (24.4% vs 40.4%; P =.01) and the incidence of HAH (42.3% vs 60.5%; P < .01). Ibuprofen was also superior to placebo in reducing the severity of HAH (4.9% vs 14.7%; P =.01). The end point of oxygen saturation was also higher in the ibuprofen group (80.8 % vs 82.4%; P =.035). For the 183 participants who completed the trial and conformed to the protocol, the incidence of AMS between placebo and treatment groups was not significant (32.9% vs 22.7%; P =.129 for AMS incidence, 9.6% vs 8.2%; P =.74 for AMS severity, 54.8% vs 42.7%; P =.11 for HAH incidence, and 8.2% vs 3.6%; P =.18 for HAH severity). Conclusions: Ibuprofen was found to be effective in preventing AMS in the intent-to-treat analysis group but not in those who completed the trial. This loss of significance in the subjects who completed the trial may be explained by persons in the placebo group having a higher burden of illness and associated decreased compliance with the protocol. An important limitation of this study may be the possibility that ibuprofen can mask headache, which is a compulsory criterion for the diagnosis of AMS. © 2012 Wilderness Medical Society.

Küpper T, Milledge JS, Hillebrandt D, Kubalová J, Hefti U, Basnyat B, Gieseler U, Pullan R, Schöffl V. 2011. Work in hypoxic conditions--consensus statement of the Medical Commission of the Union Internationale des Associations d'Alpinisme (UIAA MedCom). Ann Occup Hyg, 55 (4), pp. 369-386. | Show Abstract | Read more

OBJECTIVES: The Commission gives recommendations on how to provide health and safety for employees in different kinds of low oxygen atmospheres. So far, no recommendations exist that take into account the several factors we have outlined in this report. METHODS: The health and safety recommendations of several countries were analysed for their strength and deficiencies. The scientific literature was checked (Medline, etc.) and evaluated for relevance of the topic. Typical situations of work in hypoxia were defined and their specific risks described. Specific recommendations are provided for any of these situations. RESULTS: We defined four main groups with some subgroups (main risk in brackets): short exposure (pressure change), limited exposure (acute altitude disease), expatriates (chronic altitude disease), and high-altitude populations (re-entry pulmonary oedema). For healthy unacclimatized persons, an acute but limited exposure down to 13% O(2) does not cause a health risk. Employees should be advised to leave hypoxic areas for any break, if possible. Detailed advice is given for any other situation and pre-existing diseases. CONCLUSIONS: If the specific risk of the respective type of hypoxia is taken into account, a pragmatic approach to provide health and safety for employees is possible. In contrast to other occupational exposures, a repeated exposure as often as possible is of benefit as it causes partial acclimatization. The consensus statement was approved by written consent in lieu of a meeting in July 2009.

Arjyal A, Basnyat B, Koirala S, Karkey A, Dongol S, Agrawaal KK, Shakya N, Shrestha K, Sharma M, Lama S et al. 2011. Gatifloxacin versus chloramphenicol for uncomplicated enteric fever: an open-label, randomised, controlled trial. Lancet Infect Dis, 11 (6), pp. 445-454. | Show Abstract | Read more

BACKGROUND: We aimed to investigate whether gatifloxacin, a new generation and affordable fluoroquinolone, is better than chloramphenicol for the treatment of uncomplicated enteric fever in children and adults. METHODS: We did an open-label randomised superiority trial at Patan Hospital, Kathmandu, Nepal, to investigate whether gatifloxacin is more effective than chloramphenicol for treating uncomplicated enteric fever. Children and adults clinically diagnosed with enteric fever received either gatifloxacin (10 mg/kg) once a day for 7 days, or chloramphenicol (75 mg/kg per day) in four divided doses for 14 days. Patients were randomly allocated treatment (1:1) in blocks of 50, without stratification. Allocations were placed in sealed envelopes opened by the study physician once a patient was enrolled into the trial. Masking was not possible because of the different formulations and ways of giving the two drugs. The primary outcome measure was treatment failure, which consisted of at least one of the following: persistent fever at day 10, need for rescue treatment, microbiological failure, relapse until day 31, and enteric-fever-related complications. The primary outcome was assessed in all patients randomly allocated treatment and reported separately for culture-positive patients and for all patients. Secondary outcome measures were fever clearance time, late relapse, and faecal carriage. The trial is registered on controlled-trials.com, number ISRCTN 53258327. FINDINGS: 844 patients with a median age of 16 (IQR 9-22) years were enrolled in the trial and randomly allocated a treatment. 352 patients had blood-culture-confirmed enteric fever: 175 were treated with chloramphenicol and 177 with gatifloxacin. 14 patients had treatment failure in the chloramphenicol group, compared with 12 in the gatifloxacin group (hazard ratio [HR] of time to failure 0·86, 95% CI 0·40-1·86, p=0·70). The median time to fever clearance was 3·95 days (95% CI 3·68-4·68) in the chloramphenicol group and 3·90 days (3·58-4·27) in the gatifloxacin group (HR 1·06, 0·86-1·32, p=0·59). At 1 month only, three of 148 patients were stool-culture positive in the chloramphenicol group and none in the gatifloxacin group. At the end of 3 months only one person had a positive stool culture in the chloramphenicol group. There were no other positive stool cultures even at the end of 6 months. Late relapses were noted in three of 175 patients in the culture-confirmed chloramphenicol group and two of 177 in the gatifloxacin group. There were no culture-positive relapses after day 62. 99 patients (24%) experienced 168 adverse events in the chloramphenicol group and 59 (14%) experienced 73 events in the gatifloxacin group. INTERPRETATION: Although no more efficacious than chloramphenicol, gatifloxacin should be the preferred treatment for enteric fever in developing countries because of its shorter treatment duration and fewer adverse events. FUNDING: Wellcome Trust.

Basnyat B. 2011. Malaria-attributed death rates in India. Lancet, 377 (9770), pp. 993. | Read more

Jansen GF, Basnyat B. 2011. Brain blood flow in Andean and Himalayan high-altitude populations: evidence of different traits for the same environmental constraint. J Cereb Blood Flow Metab, 31 (2), pp. 706-714. | Show Abstract | Read more

Humans have populated the Tibetan plateau much longer than the Andean Altiplano. It is thought that the difference in length of occupation of these altitudes has led to different responses to the stress of hypoxia. As such, Andean populations have higher hematocrit levels than Himalayans. In contrast, Himalayans have increased circulation to certain organ systems to meet tissue oxygen demand. In this study, we hypothesize that cerebral blood flow (CBF) is higher in Himalayans than in Andeans. Using a MEDLINE and EMBASE search, we included 10 studies that investigated CBF in Andeans and Himalayans between 3,658 and 4,330 m altitude. The CBF values were corrected for differences in hematocrit and arterial oxygen saturation. The data of these studies show a mean hematocrit of 50% in Himalayans and 54.1% in Andeans. Arterial oxygen saturation was 86.9% in Andeans and 88.4% in Himalayans. The CBF in Himalayans was slightly elevated compared with sea-level subjects, and was 24% higher compared with Andeans. After correction for hematorit and arterial oxygen saturation, CBF was ∼20% higher in Himalayans compared with Andeans. Altered brain metabolism in Andeans, and/or increased nitric oxide availability in Himalayans may have a role to explain this difference in brain blood flow.

Basnyat B, Holck PS, Pun M, Halverson S, Szawarski P, Gertsch J, Steif M, Powell S, Khanal S, Joshi A et al. 2011. Spironolactone does not prevent acute mountain sickness: a prospective, double-blind, randomized, placebo-controlled trial by SPACE Trial Group (spironolactone and acetazolamide trial in the prevention of acute mountain sickness group). Wilderness Environ Med, 22 (1), pp. 15-22. | Show Abstract | Read more

OBJECTIVES: Over the last 20 years a number of small trials have reported that spironolactone effectively prevents acute mountain sickness (AMS), but to date there have been no large randomized trials investigating the efficacy of spironolactone in prevention of AMS. Hence, a prospective, double-blind, randomized, placebo-controlled trial was conducted to evaluate the efficacy of spironolactone in the prevention of AMS. METHODS: Participants were sampled from a diverse population of western trekkers recruited at 4300 m on the Mount Everest base camp approach (Nepal side) en route to the study endpoint at 5000 m. Three hundred and eleven healthy trekkers were enrolled, and 251 completed the trial from October to November 2007. Participants were randomly assigned to receive at least 3 doses of spironolactone 50 mg BID, acetazolamide 250 mg BID, or visually matched placebo. A Lake Louise AMS Score of 3 or more, together with the presence of headache and 1 other symptom, was used to evaluate the incidence and severity of AMS. Secondary outcome measures were blood oxygen content and the incidence and severity of high altitude headache (HAH). RESULTS: Acetazolamide was more effective than spironolactone in preventing AMS (OR = 0.28, 95% CI 0.12-0.60, p < 0.01). Spironolactone was not significantly different from placebo in the prevention of AMS. AMS incidence for placebo was 20.3%, acetazolamide 10.5%, and spironolactone 29.4%. Oxygen saturation was also significantly increased in the acetazolamide group (83% ± 0.04) vs spironolactone group (80% ± 0.05, p < 0.01). CONCLUSIONS: Spironolactone (50 mg BID) was ineffective in comparison to acetazolamide (250 mg BID) in the prevention of AMS in partially acclimatized western trekkers ascending to 5000 m in the Nepali Himalaya.

Baker S, Holt KE, Clements AC, Karkey A, Arjyal A, Boni MF, Dongol S, Hammond N, Koirala S, Duy PT et al. 2011. Combined high-resolution genotyping and geospatial analysis reveals modes of endemic urban typhoid fever transmission. Open Biol, 1 (2), pp. 110008. | Show Abstract | Read more

Typhoid is a systemic infection caused by Salmonella Typhi and Salmonella Paratyphi A, human-restricted bacteria that are transmitted faeco-orally. Salmonella Typhi and S. Paratyphi A are clonal, and their limited genetic diversity has precluded the identification of long-term transmission networks in areas with a high disease burden. To improve our understanding of typhoid transmission we have taken a novel approach, performing a longitudinal spatial case-control study for typhoid in Nepal, combining single-nucleotide polymorphism genotyping and case localization via global positioning. We show extensive clustering of typhoid occurring independent of population size and density. For the first time, we demonstrate an extensive range of genotypes existing within typhoid clusters, and even within individual households, including some resulting from clonal expansion. Furthermore, although the data provide evidence for direct human-to-human transmission, we demonstrate an overwhelming contribution of indirect transmission, potentially via contaminated water. Consistent with this, we detected S. Typhi and S. Paratyphi A in water supplies and found that typhoid was spatially associated with public water sources and low elevation. These findings have implications for typhoid-control strategies, and our innovative approach may be applied to other diseases caused by other monophyletic or emerging pathogens.

Subedi BH, Pokharel J, Goodman TL, Amatya S, Freer L, Banskota N, Johnson E, Basnyat B. 2010. Complications of steroid use on Mt. Everest. Wilderness Environ Med, 21 (4), pp. 345-348. | Show Abstract | Read more

Steroids are used for the prevention and treatment of high-altitude illnesses. However, these agents can cause significant side effects. We report a case of altered mental status, gastrointestinal bleeding, skin rash, and avascular necrosis in a climber taking prophylactic dexamethasone prior to an attempt to climb Mt Everest. High-altitude cerebral edema (HACE), steroid toxicity, and acute adrenal crisis can have similar clinical presentations. Differentiating between these life-threatening conditions at high altitude is essential for successful treatment.

Parry CM, Thuy CT, Dongol S, Karkey A, Vinh H, Chinh NT, Duy PT, Thieu Nga TV, Campbell JI, Van Minh Hoang N et al. 2010. Suitable disk antimicrobial susceptibility breakpoints defining Salmonella enterica serovar Typhi isolates with reduced susceptibility to fluoroquinolones. Antimicrob Agents Chemother, 54 (12), pp. 5201-5208. | Show Abstract | Read more

Infections with Salmonella enterica serovar Typhi isolates that have reduced susceptibility to ofloxacin (MIC ≥ 0.25 μg/ml) or ciprofloxacin (MIC ≥ 0.125 μg/ml) have been associated with a delayed response or clinical failure following treatment with these antimicrobials. These isolates are not detected as resistant using current disk susceptibility breakpoints. We examined 816 isolates of S. Typhi from seven Asian countries. Screening for nalidixic acid resistance (MIC ≥ 16 μg/ml) identified isolates with an ofloxacin MIC of ≥0.25 μg/ml with a sensitivity of 97.3% (253/260) and specificity of 99.3% (552/556). For isolates with a ciprofloxacin MIC of ≥0.125 μg/ml, the sensitivity was 92.9% (248/267) and specificity was 98.4% (540/549). A zone of inhibition of ≤28 mm around a 5-μg ofloxacin disc detected strains with an ofloxacin MIC of ≥0.25 μg/ml with a sensitivity of 94.6% (246/260) and specificity of 94.2% (524/556). A zone of inhibition of ≤30 mm detected isolates with a ciprofloxacin MIC of ≥0.125 μg/ml with a sensitivity of 94.0% (251/267) and specificity of 94.2% (517/549). An ofloxacin MIC of ≥0.25 μg/ml and a ciprofloxacin MIC of ≥0.125 μg/ml detected 74.5% (341/460) of isolates with an identified quinolone resistance-inducing mutation and 81.5% (331/406) of the most common mutant (carrying a serine-to-phenylalanine mutation at codon 83 in the gyrA gene). Screening for nalidixic acid resistance or ciprofloxacin and ofloxacin disk inhibition zone are suitable for detecting S. Typhi isolates with reduced fluoroquinolone susceptibility.

Basnyat B. 2010. Neglected hepatitis E and typhoid vaccines. Lancet, 376 (9744), pp. 869. | Read more

Gertsch JH, Lipman GS, Holck PS, Merritt A, Mulcahy A, Fisher RS, Basnyat B, Allison E, Hanzelka K, Hazan A et al. 2010. Prospective, double-blind, randomized, placebo-controlled comparison of acetazolamide versus ibuprofen for prophylaxis against high altitude headache: the Headache Evaluation at Altitude Trial (HEAT). Wilderness Environ Med, 21 (3), pp. 236-243. | Show Abstract | Read more

OBJECTIVE: High altitude headache (HAH) is the most common neurological complaint at altitude and the defining component of acute mountain sickness (AMS). However, there is a paucity of literature concerning its prevention. Toward this end, we initiated a prospective, double-blind, randomized, placebo-controlled trial in the Nepal Himalaya designed to compare the effectiveness of ibuprofen and acetazolamide for the prevention of HAH. METHODS: Three hundred forty-three healthy western trekkers were recruited at altitudes of 4280 m and 4358 m and assigned to receive ibuprofen 600 mg, acetazolamide 85 mg, or placebo 3 times daily before continued ascent to 4928 m. Outcome measures included headache incidence and severity, AMS incidence and severity on the Lake Louise AMS Questionnaire (LLQ), and visual analog scale (VAS). RESULTS: Two hundred sixty-five of 343 subjects completed the trial. HAH incidence was similar when treated with acetazolamide (27.1%) or ibuprofen (27.5%; P = .95), and both agents were significantly more effective than placebo (45.3%; P = .01). AMS incidence was similar when treated with acetazolamide (18.8%) or ibuprofen (13.7%; P = .34), and both agents were significantly more effective than placebo (28.6%; P = .03). In fully compliant participants, moderate or severe headache incidence was similar when treated with acetazolamide (3.8%) or ibuprofen (4.7%; P = .79), and both agents were significantly more effective than placebo (13.5%; P = .03). CONCLUSIONS: Ibuprofen and acetazolamide were similarly effective in preventing HAH. Ibuprofen was similar to acetazolamide in preventing symptoms of AMS, an interesting finding that implies a potentially new approach to prevention of cerebral forms of acute altitude illness.

Subedi BH, Pokharel J, Thapa R, Banskota N, Basnyat B. 2010. Frostbite in a Sherpa. Wilderness Environ Med, 21 (2), pp. 127-129. | Show Abstract | Read more

Frostbite is frequently seen in high altitude climbers. Many Sherpas, members of an ethnic community living high in the Himalayas in Nepal, help the climbers as a guide or an assistant. They often seem to undertake few precautionary measures thus suffer more from frostbite. A young Sherpa, who had reached the top of Mt Kanchenjunga in March 2009, suffered from deep frostbite in his fingers. Fortunately, he recovered well with generous treatment. Though there is no evidence whether Sherpas are more or less prone to frostbite, simple techniques for adequate prevention of hypoxia, hypothermia and dehydration will benefit any climber to the high altitudes.

Holt KE, Baker S, Dongol S, Basnyat B, Adhikari N, Thorson S, Pulickal AS, Song Y, Parkhill J, Farrar JJ et al. 2010. High-throughput bacterial SNP typing identifies distinct clusters of Salmonella Typhi causing typhoid in Nepalese children. BMC Infect Dis, 10 (1), pp. 144. | Show Abstract | Read more

BACKGROUND: Salmonella Typhi (S. Typhi) causes typhoid fever, which remains an important public health issue in many developing countries. Kathmandu, the capital of Nepal, is an area of high incidence and the pediatric population appears to be at high risk of exposure and infection. METHODS: We recently defined the population structure of S. Typhi, using new sequencing technologies to identify nearly 2,000 single nucleotide polymorphisms (SNPs) that can be used as unequivocal phylogenetic markers. Here we have used the GoldenGate (Illumina) platform to simultaneously type 1,500 of these SNPs in 62 S. Typhi isolates causing severe typhoid in children admitted to Patan Hospital in Kathmandu. RESULTS: Eight distinct S. Typhi haplotypes were identified during the 20-month study period, with 68% of isolates belonging to a subclone of the previously defined H58 S. Typhi. This subclone was closely associated with resistance to nalidixic acid, with all isolates from this group demonstrating a resistant phenotype and harbouring the same resistance-associated SNP in GyrA (Phe83). A secondary clone, comprising 19% of isolates, was observed only during the second half of the study. CONCLUSIONS: Our data demonstrate the utility of SNP typing for monitoring bacterial populations over a defined period in a single endemic setting. We provide evidence for genotype introduction and define a nalidixic acid resistant subclone of S. Typhi, which appears to be the dominant cause of severe pediatric typhoid in Kathmandu during the study period.

Thapa R, Banskota N, Pokharel J, Subedi BH, Basnyat B. 2010. Another typhoid patient from Japan. J Travel Med, 17 (3), pp. 199-200. | Show Abstract | Read more

Typhoid treatment was empirically started in a Japanese patient with undifferentiated fever in Nepal since Japanese tourists, unlike most Americans and Europeans to South Asia, are unable to obtain typhoid vaccination in Japan even for travel to this area of high endemicity. Subsequently, his blood culture grew out Salmonella typhi.

Basnyat B. 2010. Typhoid fever in the United States and antibiotic choice. JAMA, 303 (1), pp. 34. | Read more

Nga TV, Karkey A, Dongol S, Thuy HN, Dunstan S, Holt K, Tu LETP, Campbell JI, Chau TT, Chau NV et al. 2010. The sensitivity of real-time PCR amplification targeting invasive Salmonella serovars in biological specimens. BMC Infect Dis, 10 (1), pp. 125. | Show Abstract | Read more

BACKGROUND: PCR amplification for the detection of pathogens in biological material is generally considered a rapid and informative diagnostic technique. Invasive Salmonella serovars, which cause enteric fever, can be commonly cultured from the blood of infected patients. Yet, the isolation of invasive Salmonella serovars from blood is protracted and potentially insensitive. METHODS: We developed and optimised a novel multiplex three colour real-time PCR assay to detect specific target sequences in the genomes of Salmonella serovars Typhi and Paratyphi A. We performed the assay on DNA extracted from blood and bone marrow samples from culture positive and negative enteric fever patients. RESULTS: The assay was validated and demonstrated a high level of specificity and reproducibility under experimental conditions. All bone marrow samples tested positive for Salmonella, however, the sensitivity on blood samples was limited. The assay demonstrated an overall specificity of 100% (75/75) and sensitivity of 53.9% (69/128) on all biological samples. We then tested the PCR detection limit by performing bacterial counts after inoculation into blood culture bottles. CONCLUSIONS: Our findings corroborate previous clinical findings, whereby the bacterial load of S. Typhi in peripheral blood is low, often below detection by culture and, consequently, below detection by PCR. Whilst the assay may be utilised for environmental sampling or on differing biological samples, our data suggest that PCR performed directly on blood samples may be an unsuitable methodology and a potentially unachievable target for the routine diagnosis of enteric fever.

Karkey A, Arjyal A, Anders KL, Boni MF, Dongol S, Koirala S, My PV, Nga TV, Clements AC, Holt KE et al. 2010. The burden and characteristics of enteric fever at a healthcare facility in a densely populated area of Kathmandu. PLoS One, 5 (11), pp. e13988. | Show Abstract | Read more

Enteric fever, caused by Salmonella enterica serovars Typhi and Paratyphi A (S. Typhi and S. Paratyphi A) remains a major public health problem in many settings. The disease is limited to locations with poor sanitation which facilitates the transmission of the infecting organisms. Efficacious and inexpensive vaccines are available for S. Typhi, yet are not commonly deployed to control the disease. Lack of vaccination is due partly to uncertainty of the disease burden arising from a paucity of epidemiological information in key locations. We have collected and analyzed data from 3,898 cases of blood culture-confirmed enteric fever from Patan Hospital in Lalitpur Sub-Metropolitan City (LSMC), between June 2005 and May 2009. Demographic data was available for a subset of these patients (n = 527) that were resident in LSMC and who were enrolled in trials. We show a considerable burden of enteric fever caused by S. Typhi (2,672; 68.5%) and S. Paratyphi A (1,226; 31.5%) at this Hospital over a four year period, which correlate with seasonal fluctuations in rainfall. We found that local population density was not related to incidence and we identified a focus of infections in the east of LSMC. With data from patients resident in LSMC we found that the median age of those with S. Typhi (16 years) was significantly less than S. Paratyphi A (20 years) and that males aged 15 to 25 were disproportionately infected. Our findings provide a snapshot into the epidemiological patterns of enteric fever in Kathmandu. The uneven distribution of enteric fever patients within the population suggests local variation in risk factors, such as contaminated drinking water. These findings are important for initiating a vaccination scheme and improvements in sanitation. We suggest any such intervention should be implemented throughout the LSMC area.

Khatri NS, Maskey P, Poudel S, Jaiswal VK, Karkey A, Koirala S, Shakya N, Agrawal K, Arjyal A, Basnyat B et al. 2009. Gallbladder carriage of Salmonella paratyphi A may be an important factor in the increasing incidence of this infection in South Asia. Ann Intern Med, 150 (8), pp. 567-568. | Read more

Zafren K, Basnyat B, Basnyat G. 2009. Clinical Images Wilderness & Environmental Medicine, 20 (1), pp. 81-82. | Read more

Zafren K, Basnyat B, Basnyat G. 2009. Clinical images: a pneumonic confusion. Wilderness Environ Med, 20 (1), pp. 81-82. | Read more

Droma Y, Ota M, Hanaoka M, Katsuyama Y, Basnyat B, Neupane P, Arjyal A, Pandit A, Sharma D, Ito M, Kubo K. 2008. Two hypoxia sensor genes and their association with symptoms of acute mountain sickness in Sherpas. Aviat Space Environ Med, 79 (11), pp. 1056-1060. | Show Abstract | Read more

INTRODUCTION: Hypoxia-inducible factor (HIF) and von Hippel-Lindau tumor suppressor protein (VHL) are hypoxia sensors that control cellular responses to hypoxia. Although many Sherpas live at high altitudes for their entire lives, some of them manifest symptoms of acute mountain sickness (AMS) during mountaineering at extremely high altitudes. We hypothesize that the two hypoxia sensor genes might associate with the occurrence of AMS symptoms in Sherpas at extremely high altitude. METHODS: In a village at an altitude of 3440 m, 104 Sherpas who had mountaineered at extremely high altitudes (over 5000 m) were divided into two groups: Sherpas with (N = 45) and without (N = 59) histories of AMS symptoms. The rs11549465 SNP in the HIF-1alpha gene (HIF1A) and the rs28940298, rs779805, rs779808, rs1678607, and 1149A > G SNPs in the VHL gene (VHL) were identified in the two Sherpa groups using PCR following RFLP. RESULTS: There were no significant differences in ei-ther the genotype distributions or the allele frequencies of the HIF1A and VHL genetic variants between the two Sherpa groups. CONCLUSION: These genetic variants of HIF1A and VHL are not associated with AMS symptoms that occur in Sherpas at extremely high altitudes. It seems unlikely that HIF1A and VHL are associated with hypoxic sensing sensitivity in Sherpas.

Zimmerman MD, Murdoch DR, Rozmajzl PJ, Basnyat B, Woods CW, Richards AL, Belbase RH, Hammer DA, Anderson TP, Reller LB. 2008. Murine typhus and febrile illness, Nepal. Emerg Infect Dis, 14 (10), pp. 1656-1659. | Show Abstract | Read more

Murine typhus was diagnosed by PCR in 50 (7%) of 756 adults with febrile illness seeking treatment at Patan Hospital in Kathmandu, Nepal. Of patients with murine typhus, 64% were women, 86% were residents of Kathmandu, and 90% were unwell during the winter. No characteristics clearly distinguished typhus patients from those with blood culture-positive enteric fever.

Taylor RR, Basnyat B, Scott RM. 2008. A diplomatic disease. J Travel Med, 15 (3), pp. 200-201. | Show Abstract | Read more

A 43-year-old diplomat was diagnosed with probable hepatitis C while vacationing in Europe. However, on return to her post in Nepal, she was actually found to have hepatitis E. The differential diagnosis, importance, and prevention of hepatitis E are highlighted.

Maskey AP, Basnyat B, Thwaites GE, Campbell JI, Farrar JJ, Zimmerman MD. 2008. Emerging trends in enteric fever in Nepal: 9124 cases confirmed by blood culture 1993-2003. Trans R Soc Trop Med Hyg, 102 (1), pp. 91-95. | Show Abstract | Read more

This was a retrospective study in an urban hospital in Kathmandu, Nepal to determine the changing burden of salmonella septicaemia, the proportion of Salmonella paratyphi A, and the emergence of drug-resistant organisms. The participants were outpatients and inpatients over the period 1993-2003, and the main outcome measures were blood culture isolates and antibiotic sensitivity testing. The results showed that of 82467 blood cultures performed, a bacterium was isolated from 12252. Salmonella accounted for 9124 (74.5%) of the positive blood cultures: 6447 (70.7%) were Salmonella enterica serotype Typhi (S. typhi) and 2677 (29.3%) were Paratyphi A (S. paratyphi A). In comparing the period 1997-2000 to the period 2001-2003, we found that, as a proportion of total blood cultures taken, salmonella septicaemia more than doubled, from 6.2 to 13.6% (P<0.001). From the first half of the study (1993-1998) to the second half (1999-2003), S. paratyphi A as a proportion of all salmonella isolates rose from 23 to 34% (P<0.001), which paralleled its increased resistance to ciprofloxacin. Despite the introduction of new antibiotics, enteric fever continues to grow as a cause for hospital presentation in Nepal. Salmonella paratyphi A contributes an increasingly large proportion of cases, and ciprofloxacin resistance is also emerging more rapidly in S. paratyphi A.

Karkey A, Aryjal A, Basnyat B, Baker S. 2008. Kathmandu, Nepal: still an enteric fever capital of the world. J Infect Dev Ctries, 2 (6), pp. 461-465. | Show Abstract

Kathmandu, the capital city of Nepal, has been previously coined an enteric fever capital of the world. Several studies have poignantly emphasized the significant burden of enteric fever within the local population and in travellers visiting the area. The population of Kathmandu is increasing and available figures suggest that enteric fever caused by Salmonella serovars Typhi and Paratyphi A show no significant signs of decreasing. Furthermore, our recent research demonstrates that the ratio of disease caused by these two organisms is shifting towards S. Paratyphi A. Here, we outline some of the major features of enteric fever in Kathmandu, including diagnosis, seasonal variation, transmission, and some characteristics of the infecting organisms. Our findings highlight the requirement for better understanding of the disease within the city; in turn, this will aid development of a targeted control strategy.

Dolecek C, Tran TP, Nguyen NR, Le TP, Ha V, Phung QT, Doan CD, Nguyen TB, Duong TL, Luong BH et al. 2008. A multi-center randomised controlled trial of gatifloxacin versus azithromycin for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. PLoS One, 3 (5), pp. e2188. | Show Abstract | Read more

BACKGROUND: Drug resistant typhoid fever is a major clinical problem globally. Many of the first line antibiotics, including the older generation fluoroquinolones, ciprofloxacin and ofloxacin, are failing. OBJECTIVES: We performed a randomised controlled trial to compare the efficacy and safety of gatifloxacin (10 mg/kg/day) versus azithromycin (20 mg/kg/day) as a once daily oral dose for 7 days for the treatment of uncomplicated typhoid fever in children and adults in Vietnam. METHODS: An open-label multi-centre randomised trial with pre-specified per protocol analysis and intention to treat analysis was conducted. The primary outcome was fever clearance time, the secondary outcome was overall treatment failure (clinical or microbiological failure, development of typhoid fever-related complications, relapse or faecal carriage of S. typhi). PRINCIPAL FINDINGS: We enrolled 358 children and adults with suspected typhoid fever. There was no death in the study. 287 patients had blood culture confirmed typhoid fever, 145 patients received gatifloxacin and 142 patients received azithromycin. The median FCT was 106 hours in both treatment arms (95% Confidence Interval [CI]; 94-118 hours for gatifloxacin versus 88-112 hours for azithromycin), (logrank test p = 0.984, HR [95% CI] = 1.0 [0.80-1.26]). Overall treatment failure occurred in 13/145 (9%) patients in the gatifloxacin group and 13/140 (9.3%) patients in the azithromycin group, (logrank test p = 0.854, HR [95% CI] = 0.93 [0.43-2.0]). 96% (254/263) of the Salmonella enterica serovar Typhi isolates were resistant to nalidixic acid and 58% (153/263) were multidrug resistant. CONCLUSIONS: Both antibiotics showed an excellent efficacy and safety profile. Both gatifloxacin and azithromycin can be recommended for the treatment of typhoid fever particularly in regions with high rates of multidrug and nalidixic acid resistance. The cost of a 7-day treatment course of gatifloxacin is approximately one third of the cost of azithromycin in Vietnam. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN67946944.

Basnyat B, Hargrove J, Holck PS, Srivastav S, Alekh K, Ghimire LV, Pandey K, Griffiths A, Shankar R, Kaul K et al. 2008. Acetazolamide fails to decrease pulmonary artery pressure at high altitude in partially acclimatized humans. High Alt Med Biol, 9 (3), pp. 209-216. | Show Abstract | Read more

In this randomized, double-blind placebo controlled trial our objectives were to determine if acetazolamide is capable of preventing high altitude pulmonary edema (HAPE) in trekkers traveling between 4250 m (Pheriche)\4350 m (Dingboche) and 5000 m (Lobuje) in Nepal; to determine if acetazolamide decreases pulmonary artery systolic pressures (PASP) at high altitude; and to determine if there is an association with PASP and signs and symptoms of HAPE. Participants received either acetazolamide 250 mg PO BID or placebo at Pheriche\Dingboche and were reassessed in Lobuje. The Lake Louise Consensus Criteria were used for the diagnosis of HAPE, and cardiac ultrasonography was used to measure the velocity of tricuspid regurgitation and estimate PASP. Complete measurements were performed on 339 of the 364 subjects (164 in the placebo group, 175 in the acetazolamide group). No cases of HAPE were observed in either study group nor were differences in the signs and symptoms of HAPE found between the two groups. Mean PASP values did not differ significantly between the acetazolamide and placebo groups (31.3 and 32.6 mmHg, respectively). An increasing number of signs and symptoms of HAPE was associated with elevated PASP (p < 0.01). The efficacy of acetazolamide against acute mountain sickness, however, was significant with a 21.9% incidence in the placebo group compared to 10.2 % in the acetazolamide group (p < 0.01). Given the lack of cases of HAPE in either group, we can draw no conclusions about the efficacy of acetazolamide in preventing HAPE, but the absence of effect on PASP suggests that any effect may be minor possibly owing to partial acclimatization during the trek up to 4200 m.

Pandit A, Arjyal A, Paudyal B, Campbell JC, Day JN, Farrar JJ, Basnyat B. 2008. A patient with paratyphoid A fever: an emerging problem in Asia and not always a benign disease. J Travel Med, 15 (5), pp. 364-365. | Show Abstract | Read more

A 15-year-old Nepalese boy with fever was thought to have enteric fever and started on cefixime. His blood culture grew Salmonella paratyphoid A. On the sixth day, he developed gastrointestinal bleeding, disseminated intravascular coagulation, and later, acute respiratory distress syndrome. He succumbed to his illness despite treatment in the intensive care unit with ceftriaxone, intravenous fluids, and mechanical ventilation. Salmonella paratyphoid A, for which there is no commercial vaccine, may not be a benign disease as perceived, and cefixime that is recommended for enteric fever may be an ineffective choice.

Surayya T, Krishna Kumar KN, Sharma R, Kalra S, Kujur SS, Bala S, Basnyat B. 2008. Sericulture-based micro enterprise as a source of rural livelihood and poverty alleviation: A case study of Anantapur District (Andhra Pradesh) Journal of Rural Development, 27 (1), pp. 149-176. | Show Abstract

Sericulture is one of the integral parts of Indian agriculture. Being an agro-based industry it is highly suitable to the Indian rural people where large number of people are jobless, landless and labourers. It is mainly a labour-intensive programme requiring relatively low investment and acting as a source of survival and high profit earner. And it also accounts for a sizable quantum of foreign exchange earnings. An attempt was made to study the contributions of a Silk production Micro-Enterprise, for livelihood of rural people of select villages in Anantapur district of Andhra Pradesh State. Sericulture is an important economic activity of margainal and landless farmers (rural poor) in the Anantapur region. A farmer on an average, on a two and half acres piece of land with a total cost of Rs. 53250 (61 per cent of which is labour cost) can realise Rs. 93600 (76 per cent return on total cost) from sericulture cultivation whereas with a total cost of Rs. 23680 (49 per cent of which is labour cost) only Rs. 27000 (14 per cent return on cost) can be realised from paddy cultivation. As the area is drought-prone, the poor farmers preferring sericulture to paddy, and the other supply chain members like weavers and other value adders especially women, who are largely involved in the supply chain are, in need of financial and capacity building (for maintaining quality and effective designing) assistance, hence all possible assistance should be extended by the concerned agencies. A large chunk of consumer price spread ranging from 33.3 to 66.7 per cent, is accounted for middlemen with minimum risk, measures should be initiated to ensure that farmers and weavers who are also more risk bearers get their due share. Most of the weavers cannot access the banks for loans for entrepreneurial activities due to lack of physical collateral. Hence interventions like promotion of SHGs to meet the micro-financial requirement for value additions and provision for sophisticated cost-efficient value addition technology, should be initiated by Government and NGO agencies. Market linkages through weaver cluster formation etc., will enhance the benefits to the weavers.

Droma Y, Hanaoka M, Basnyat B, Arjyal A, Neupane P, Pandit A, Sharma D, Ito M, Miwa N, Katsuyama Y et al. 2008. Adaptation to high altitude in Sherpas: association with the insertion/deletion polymorphism in the Angiotensin-converting enzyme gene. Wilderness Environ Med, 19 (1), pp. 22-29. | Show Abstract | Read more

OBJECTIVE: Sherpas are well-known for their physical strength at high altitudes. They adapt to high altitude so well that little acute or chronic mountain sickness has been documented in them. The possible genetic basis for this adaptation is, however, unclear. The objective of this study was to elucidate the genetic background underlying this characteristic among Sherpas with respect to the angiotension-converting enzyme (ACE) gene. METHODS: We enrolled 105 Sherpa volunteers in Namche Bazaar (3440 meters) and 111 non-Sherpa Nepalese volunteers in Kathmandu Valley (1330 meters) in Nepal. Information about high-altitude exposure and physiological phenotypes was obtained via fieldwork investigation. The genotype of the insertion/deletion (I/D) polymorphism in the ACE gene was identified by polymerase chain reaction. Serum ACE activity was also measured. RESULTS: The distribution of the I dominant genotype (II & ID) and the I allelic frequency were significantly more prevalent in Sherpas (II & ID: 94.3%, I allele: 73.3%) than in non-Sherpas (II & ID: 85.6%, P = .035; I allele: 64.0%, P = .036). Moreover, despite residing at high altitude, the circulating ACE levels of Sherpas were statistically similar to those of non-Sherpas at low altitudes (Sherpas: 14.5 +/- 0.4 IU/L/37 degrees C; non-Sherpas: 14.7 +/- 0.4 IU/L/37 degrees C; P = .755). CONCLUSIONS: These findings suggest that the overrepresented I allele of the ACE gene in Sherpas might be one of the fundamental genetic factors responsible for maintaining physiological low-altitude ACE activity at high altitude, which may have an advantageous physiological role in adapting to a high-altitude environment.

Basnyat B, Gertsch JH, Holck PC. 2008. Low-dose acetylsalicylic Acid analog and acetazolamide for prevention of acute mountain sickness. High Alt Med Biol, 9 (4), pp. 349. | Read more

Chau TT, Campbell JI, Galindo CM, Van Minh Hoang N, Diep TS, Nga TT, Van Vinh Chau N, Tuan PQ, Page AL, Ochiai RL et al. 2007. Antimicrobial drug resistance of Salmonella enterica serovar typhi in asia and molecular mechanism of reduced susceptibility to the fluoroquinolones. Antimicrob Agents Chemother, 51 (12), pp. 4315-4323. | Show Abstract | Read more

This study describes the pattern and extent of drug resistance in 1,774 strains of Salmonella enterica serovar Typhi isolated across Asia between 1993 and 2005 and characterizes the molecular mechanisms underlying the reduced susceptibilities to fluoroquinolones of these strains. For 1,393 serovar Typhi strains collected in southern Vietnam, the proportion of multidrug resistance has remained high since 1993 (50% in 2004) and there was a dramatic increase in nalidixic acid resistance between 1993 (4%) and 2005 (97%). In a cross-sectional sample of 381 serovar Typhi strains from 8 Asian countries, Bangladesh, China, India, Indonesia, Laos, Nepal, Pakistan, and central Vietnam, collected in 2002 to 2004, various rates of multidrug resistance (16 to 37%) and nalidixic acid resistance (5 to 51%) were found. The eight Asian countries involved in this study are home to approximately 80% of the world's typhoid fever cases. These results document the scale of drug resistance across Asia. The Ser83-->Phe substitution in GyrA was the predominant alteration in serovar Typhi strains from Vietnam (117/127 isolates; 92.1%). No mutations in gyrB, parC, or parE were detected in 55 of these strains. In vitro time-kill experiments showed a reduction in the efficacy of ofloxacin against strains harboring a single-amino-acid substitution at codon 83 or 87 of GyrA; this effect was more marked against a strain with a double substitution. The 8-methoxy fluoroquinolone gatifloxacin showed rapid killing of serovar Typhi harboring both the single- and double-amino-acid substitutions.

Malacrida S, Katsuyama Y, Droma Y, Basnyat B, Angelini C, Ota M, Danieli GA. 2007. Association between human polymorphic DNA markers and hypoxia adaptation in Sherpa detected by a preliminary genome scan. Ann Hum Genet, 71 (Pt 5), pp. 630-638. | Show Abstract | Read more

Genetic determinants of resistance to hypobaric hypoxia in the Sherpa are still unknown. Since adaptive gene variants must still be subjected to positive selection, linkage disequilibrium between such variants and specific alleles of flanking DNA markers is expected. Following this line of reasoning, we performed a human genome scan using 998 polymorphic DNA markers in 7 unrelated Sherpa porters living in the Solu-Khumbu area. This minimalist approach succeeded in detecting 8 DNA markers showing homozygosity for the same shared allele. Analysis of additional DNA samples from 2 more Sherpa porters focused our attention on three polymorphic DNA markers (D6S1697, D14S274, D17S1795) showing homozygosity for the same shared allele in 8 out 9 tested individuals. Analysis of DNA samples from Sherpa and non-Sherpa populations of Nepal proved HW equilibrium in both populations for markers D14S274 and D17S1795, while an excess of heterozygotes was observed in the Sherpa population for marker D6S1697. A significant difference in allele frequencies for D14S274 and D17S1795 between the two populations was observed. These findings exclude the possibility that homozygosity for 3 specific loci in 8 unrelated individuals might be ascribed to inbreeding or recent genetic drift. We therefore conclude that the chromosomal segments detected by such DNA markers may include genes involved in adaptation to hypobaric hypoxia.

Jansen GF, Krins A, Basnyat B, Odoom JA, Ince C. 2007. Role of the altitude level on cerebral autoregulation in residents at high altitude. J Appl Physiol (1985), 103 (2), pp. 518-523. | Show Abstract | Read more

Cerebral autoregulation is impaired in Himalayan high-altitude residents who live above 4,200 m. This study was undertaken to determine the altitude at which this impairment of autoregulation occurs. A second aim of the study was to test the hypothesis that administration of oxygen can reverse this impairment in autoregulation at high altitudes. In four groups of 10 Himalayan high-altitude dwellers residing at 1,330, 2,650, 3,440, and 4,243 m, arterial oxygen saturation (Sa(O(2))), blood pressure, and middle cerebral artery blood velocity were monitored during infusion of phenylephrine to determine static cerebral autoregulation. On the basis of these measurements, the cerebral autoregulation index (AI) was calculated. Normally, AI is between zero and 1. AI of 0 implies absent autoregulation, and AI of 1 implies intact autoregulation. At 1,330 m (Sa(O(2)) = 97%), 2,650 m (Sa(O(2)) = 96%), and 3,440 m (Sa(O(2)) = 93%), AI values (mean +/- SD) were, respectively, 0.63 +/- 0.27, 0.57 +/- 0.22, and 0.57 +/- 0.15. At 4,243 m (Sa(O(2)) = 88%), AI was 0.22 +/- 0.18 (P < 0.0005, compared with AI at the lower altitudes) and increased to 0.49 +/- 0.23 (P = 0.008, paired t-test) when oxygen was administered (Sa(O(2)) = 98%). In conclusion, high-altitude residents living at 4,243 m have almost total loss of cerebral autoregulation, which improved during oxygen administration. Those people living at 3,440 m and lower have still functioning cerebral autoregulation. This study showed that the altitude region between 3,440 and 4,243 m, marked by Sa(O(2)) in the high-altitude dwellers of 93% and 88%, is a transitional zone, above which cerebral autoregulation becomes critically impaired.

Ota M, Droma Y, Basnyat B, Katsuyama Y, Asamura H, Sakai H, Fukuhsima H. 2007. Allele frequencies for 15 STR loci in Tibetan populations from Nepal. Forensic Sci Int, 169 (2-3), pp. 234-238. | Show Abstract | Read more

Samples from 105 unrelated healthy Sherpa in Namche Bazaar and 111 unrelated non-Sherpa in Kathmandu valley from Nepal were used to obtain allele frequency data for 15 short tandem repeat (STR) loci (CSF1PO, D2S1338, D3S1358, D5S818, D7S820, D8S1179, D13S317, D16S539, D18S51, D19S433, D21S11, FGA, TH01, TPOX and vWA) included in the AmpFLSTR Identifiler kit. No deviations from Hardy-Weinberg equilibrium were observed, but only after applying a Bonferroni correction in the case of D5S818 in the Sherpa population and D7S820 in the Kathmandu population. Genetic parameters of forensic interest were calculated and genetic differentiation between the two populations tested.

Pandit A, Arjyal A, Day JN, Paudyal B, Dangol S, Zimmerman MD, Yadav B, Stepniewska K, Campbell JI, Dolecek C et al. 2007. An Open Randomized Comparison of Gatifloxacin versus Cefixime for the Treatment of Uncomplicated Enteric Fever PLOS ONE, 2 (6), | Read more

Basnyat B. 2007. Reducing the incidence of high-altitude pulmonary edema. Ann Intern Med, 146 (8), pp. 613. | Read more

Basnyat B. 2007. The treatment of enteric fever. J R Soc Med, 100 (4), pp. 161-162. | Read more

Pandit A, Arjyal A, Day JN, Paudyal B, Dangol S, Zimmerman MD, Yadav B, Stepniewska K, Campbell JI, Dolecek C et al. 2007. An open randomized comparison of gatifloxacin versus cefixime for the treatment of uncomplicated enteric fever. PLoS One, 2 (6), pp. e542. | Show Abstract | Read more

OBJECTIVE: To assess the efficacy of gatifloxacin versus cefixime in the treatment of uncomplicated culture positive enteric fever. DESIGN: A randomized, open-label, active control trial with two parallel arms. SETTING: Emergency Room and Outpatient Clinics in Patan Hospital, Lagankhel, Lalitpur, Nepal. PARTICIPANTS: Patients with clinically diagnosed uncomplicated enteric fever meeting the inclusion criteria. INTERVENTIONS: Patients were allocated to receive one of two drugs, Gatifloxacin or Cefixime. The dosages used were Gatifloxacin 10 mg/kg, given once daily for 7 days, or Cefixime 20 mg/kg/day given in two divided doses for 7 days. OUTCOME MEASURES: The primary outcome measure was fever clearance time. The secondary outcome measure was overall treatment failure (acute treatment failure and relapse). RESULTS: Randomization was carried out in 390 patients before enrollment was suspended on the advice of the independent data safety monitoring board due to significant differences in both primary and secondary outcome measures in the two arms and the attainment of a priori defined endpoints. Median (95% confidence interval) fever clearance times were 92 hours (84-114 hours) for gatifloxacin recipients and 138 hours (105-164 hours) for cefixime-treated patients (Hazard Ratio[95%CI] = 2.171 [1.545-3.051], p<0.0001). 19 out of 70 (27%) patients who completed the 7 day trial had acute clinical failure in the cefixime group as compared to 1 out of 88 patients (1%) in gatifloxacin group(Odds Ratio [95%CI] = 0.031 [0.004 - 0.237], p<0.001). Overall treatment failure patients (relapsed patients plus acute treatment failure patients plus death) numbered 29. They were determined to be (95% confidence interval) 37.6 % (27.14%-50.2%) in the cefixime group and 3.5% (2.2%-11.5%) in the gatifloxacin group (HR[95%CI] = 0.084 [0.025-0.280], p<0.0001). There was one death in the cefixime group. CONCLUSIONS: Based on this study, gatifloxacin is a better treatment for uncomplicated enteric fever as compared to cefixime. TRIAL REGISTRATION: Current Controlled Trials ISRCTN75784880.

Woods CW, Murdoch DR, Zimmerman MD, Glover WA, Basnyat B, Wolf L, Belbase RH, Reller LB. 2006. Emergence of Salmonella enterica serotype Paratyphi A as a major cause of enteric fever in Kathmandu, Nepal. Trans R Soc Trop Med Hyg, 100 (11), pp. 1063-1067. | Show Abstract | Read more

We performed pulsed-field gel electrophoresis (XbaI) on 114 bloodstream isolates of Salmonella enterica serotype Paratyphi A and S. enterica serotype Typhi collected from febrile patients in Kathmandu, Nepal. Of the 56 S. Paratyphi A isolates, 51 (91%) were indistinguishable, which suggests the emergence of a single clone. In contrast, only 21 (36%) of the 58 S. Typhi isolates exhibited a common genotype, which is consistent with endemic disease from multiple sources.

Larner MJ, Larner AJ. 2006. Normal pressure hydrocephalus: false positives Practical Neurology, 6 (4), pp. 264-264. | Read more

Basnyat B, Belbase RH, Zimmerman MD, Woods CW, Reller LB, Murdoch DR. 2006. Clinical features of scrub typhus. Clin Infect Dis, 42 (10), pp. 1505-1506. | Read more

Maskey AP, Day JN, Phung QT, Thwaites GE, Campbell JI, Zimmerman M, Farrar JJ, Basnyat B. 2006. Salmonella enterica serovar Paratyphi A and S. enterica serovar Typhi cause indistinguishable clinical syndromes in Kathmandu, Nepal. Clin Infect Dis, 42 (9), pp. 1247-1253. | Show Abstract | Read more

BACKGROUND: Enteric fever is a major global problem. Emergence of antibacterial resistance threatens to render current treatments ineffective. There is little research or public health effort directed toward Salmonella enterica serovar Paratyphi A, because it is assumed to cause less severe enteric fever than does S. enterica serovar Typhi. There are few data on which to base this assumption, little is known of the serovar's antibacterial susceptibilities, and there is no readily available tolerable vaccination. METHODS: A prospective study was conducted of 609 consecutive cases of enteric fever (confirmed by blood culture) to compare the clinical phenotypes and antibacterial susceptibilities in S. Typhi and S. Paratyphi A infections. Variables independently associated with either infection were identified to develop a diagnostic rule to distinguish the infections. All isolates were tested for susceptibility to antibacterials. RESULTS: Six hundred nine patients (409 with S. Typhi infection and 200 with S. Paratyphi A infection) presented during the study period. The infections were clinically indistinguishable and had equal severity. Nalidixic acid resistance, which predicts a poor response to fluoroquinolone treatment, was extremely common (75.25% of S. Paratyphi A isolates and 50.5% of S. Typhi isolates; P < .001). S. Paratyphi A was more likely to be resistant to ofloxacin (3.6% vs. 0.5%; P = .007) or to have intermediate susceptibility to ofloxacin (28.7% vs. 1.8%; P < .001) or ciprofloxacin (39.4% vs. 8.2%; P < .001). MICs for S. Paratyphi A were higher than for S. Typhi (MIC of ciprofloxacin, 0.75 vs. 0.38 microg/mL [P < .001]; MIC of ofloxacin, 2.0 vs. 0.75 microg/mL [P < .001]). CONCLUSIONS: The importance of S. Paratyphi A has been underestimated. Infection is common, the agent causes disease as severe as that caused by S. Typhi and is highly likely to be drug resistant. Drug resistance and lack of effective vaccination suggest that S. Paratyphi A infection may become a major world health problem.

Pandit A, Arjyal A, Farrar J, Basnyat B. 2006. Nepal Practical Neurology, 6 (2), pp. 129-133. | Read more

Basnyat B, Gertsch JH, Holck PS, Johnson EW, Luks AM, Donham BP, Fleischman RJ, Gowder DW, Hawksworth JS, Jensen BT et al. 2006. Acetazolamide 125 mg BD is not significantly different from 375 mg BD in the prevention of acute mountain sickness: the prophylactic acetazolamide dosage comparison for efficacy (PACE) trial. High Alt Med Biol, 7 (1), pp. 17-27. | Show Abstract | Read more

750 mg per day of acetazolamide in the prevention of acute mountain sickness (AMS), as recommended in the meta-analysis published in 2000 in the British Medical Journal, may be excessive and is controversial. To determine if the efficacy of low-dose acetazolamide 125 mg bd (250 mg), as currently used in the Himalayas, is significantly different from 375 mg bd (750 mg) of acetazolamide in the prevention of AMS, we designed a prospective, double-blind, randomized, placebo-controlled trial. The participants were sampled from a diverse population of (non-Nepali) trekkers at Namche Bazaar (3440 m) in Nepal on the Everest trekking route as they ascended to study midpoints (4280 m/4358 m) and the endpoint, Lobuje (4928 m), where data were collected. Participants were randomly assigned to receive 375 mg bd of acetazolamide (82 participants), 125 mg bd of acetazolamide (74 participants), or a placebo (66 participants), beginning at 3440 m for up to 6 days as they ascended to 4928 m. The results revealed that composite AMS incidence for 125 mg bd was similar to the incidence for 375 mg bd (24% vs. 21%, 95% confidence interval, -12.6%, 19.8%), in contrast to significantly greater AMS (51%) observed in the placebo group (95% confidence interval for differences: 8%, 46%; 12%, 49% for low and high comparisons, respectively). Both doses of acetazolamide improved oxygenation equally (82.9% for 250 mg daily and 82.8% for 750 mg daily), while placebo endpoint oxygen saturation was significantly less at 80.7% (95% confidence interval for differences: 0.5%, 3.9% and 0.4%, 3.7% for low and high comparisons, respectively). There was also more paresthesia in the 375-mg bd group (p < 0.02). We conclude that 125 mg bd of acetazolamide is not significantly different from 375 mg bd in the prevention of AMS; 125 mg bd should be considered the preferred dosage when indicated for persons ascending to altitudes above 2500 m.

Basnyat B. 2006. The pilgrim at high altitude. High Alt Med Biol, 7 (3), pp. 183-184. | Read more

Droma Y, Hanaoka M, Basnyat B, Arjyal A, Neupane P, Pandit A, Sharma D, Miwa N, Ito M, Katsuyama Y et al. 2006. Genetic contribution of the endothelial nitric oxide synthase gene to high altitude adaptation in sherpas. High Alt Med Biol, 7 (3), pp. 209-220. | Show Abstract | Read more

The Sherpas' adaptation to high altitude has been hypothesized as being due to a genetic basis since the beginning of the last century, but this has yet to be demonstrated. We randomly enrolled 105 Sherpas in Namche Bazaar (3440 m) and 111 non-Sherpa Nepalis in Kathmandu (1330 m) in Nepal. The genotypes of Glu298Asp and eNOS4b/a polymorphisms of the endothelial nitric oxide synthase (eNOS) gene were identified. The metabolites of nitric oxide (NO( x ): nitrite and nitrate) in serum were measured. The frequencies of the Glu and eNOS4b alleles were significantly higher in Sherpas (Glu: 87.5%; eNOS4b: 96.7%) than in non-Sherpas (Glu: 77.9%, p = 0.036; eNOS4b: 90.5%, p = 0.009). In addition, the combination of the wild types of Glu298Glu and eNOS4b/b was significantly greater in Sherpas (66.7%) than non-Sherpas (47.7%, p = 0.008). However, the serum NO( x ) was significantly lower in Sherpas (53.2 +/- 4.6 micromol/L) than in non-Sherpas (107.3 +/- 9.0 micromol/L, p < 0.0001). The wild alleles of the Glu298Asp and eNOS4b/a polymorphisms of the eNOS gene may be a benefit for the Sherpas' adaptation to high altitude. The nitric oxide metabolites (NO( x )) in serum vary individually, thus it is not a reliable indicator for endogenous nitric oxide production.

Shah MB, Braude D, Crandall CS, Kwack H, Rabinowitz L, Cumbo TA, Basnyat B, Bhasyal G. 2006. Changes in metabolic and hematologic laboratory values with ascent to altitude and the development of acute mountain sickness in Nepalese pilgrims. Wilderness Environ Med, 17 (3), pp. 171-177. | Show Abstract | Read more

OBJECTIVE: During August of each year, thousands of Nepalese religious pilgrims ascend from 2050 m to 4500 m in 1 to 3 days. Our objectives were to evaluate the incidence of acute mountain sickness (AMS) among this large group of native people, to explore changes in serum electrolytes as subjects ascend to high altitude, and to attempt to determine whether decreased effective circulating volume is associated with the development of AMS. METHODS: This was a prospective study with 2 parts. In the first part, demographic, physiologic, and laboratory data were collected from a cohort of 34 pilgrims at both moderate (2050 m) and high altitude (4500 m). Changes that occurred with ascent were compared in subjects who did and did not develop AMS. The second part was a cross sectional study of a different group of 57 pilgrims at the high-altitude site to further determine variables associated with AMS. RESULTS: In the cohort of 34 subjects, Lake Louise score, heart rate, respiratory rate, blood urea nitrogen (BUN), BUN:creatinine ratio, and pH increased at high altitude, whereas oxygen saturation, bicarbonate, creatinine, and PCO2 decreased. Sixteen of these 34 subjects (42%) were diagnosed with AMS; these patients had a statistically significantly lower hematocrit, oxygen saturation, and self-reported water consumption than those without AMS. Of the 57 subjects enrolled in the cross sectional study, 31 (54%) were diagnosed with AMS. These pilgrims had higher heart rates and BUNs than did their non-AMS counterparts. CONCLUSIONS: Fifty-two percent of the subjects developed AMS. With ascent to altitude, subjects showed some evidence of decreased effective circulating volume, though there were no clinically significant changes. The data did not show whether decreased circulating volume is a significant risk factor in the development of AMS at high altitude.

Droma Y, Hanaoka M, Basnyat B, Arjyal A, Neupane P, Pandit A, Sharma D, Kubo K. 2006. Symptoms of acute mountain sickness in Sherpas exposed to extremely high altitude. High Alt Med Biol, 7 (4), pp. 312-314. | Show Abstract | Read more

Droma, Yunden, Masayuki Hanaoka, Buddha Basnyat, Amit Arjyal, Pritam Neupane, Anil Pandit, Dependra Sharma, and Keishi Kubo. Symptoms of acute mountain sickness in Sherpas exposed to extremely high altitude. High Alt. Med. Biol. 7:312-314, 2006.--The aim of this field interview was to investigate the current state of affairs concerning acute mountain sickness (AMS) in high-altitude residents, specifically the Sherpas at 3440 m above sea level, when they are exposed rapidly to altitudes significantly higher than their residing altitudes. Out of 105 Sherpas (44 men and 61 women, 31.2 +/- 0.8 yr), 104 had mountain-climbing experiences to 5701.4 +/- 119.1-m altitude in average 3.5 times each year. On the other hand, only 68 out of 111 non-Sherpas (29.9 +/- 0.8 yr) had experience of 1.4 +/- 1.5 climbs to an average 2688.6 +/- 150.4-m altitude in their mountaineering histories (p < 0.0001). Among the 104 Sherpas, 45 (43.3%) complained of at least one AMS symptom (headache, gastrointestinal symptoms, weakness, dizziness, and difficulty sleeping) in their experiences of mountaineering at an average 5518.9 +/- 195.9-m altitude. And 16 out of the 68 non-Sherpas (23.5%) reported the AMS symptoms at a mean altitude of 2750.0 +/- 288.8 m. Moreover, we also noticed that the Sherpa women showed a significantly higher Sa(O(2) ) (93.9 +/- 0.2%) than did Sherpa men (92.4 +/- 0.3%, p = 0.0001) at an altitude of 3440 m. The brief field interview evidenced that Sherpas might suffer from AMS when exposed to altitudes significantly higher than their residing altitude.

Bhattacharya AK, Basnyat B. 2005. Decentralisation and community forestry programmes in Nepal: issues and challenges International Forestry Review, 7 (2), pp. 147-155. | Show Abstract | Read more

This paper critically examines the application of a decentralisation principle in the community forestry (CF) programme of Nepal and discusses the implications of decentralisation efforts. Decentralisation applied in the forestry sector is devolution, which involves the transfer of functions or decision-making authority. The Local Self-Governance Act (LSGA) 1999 provides the framework for decentralised governance in Nepal. While assessing the LSGA 1999 and Forest Act 1993, it emerges that in many instances, forest legislation bypasses the local government. There exist conflicts and contradictions between the FA 1993 and LSGA 1999 which adds further confusion in the community forestry programme. Local government (LG) has always claimed any natural resources lying within its jurisdiction and initiated claiming ownership of the forest situated in their jurisdiction as per LSGA 1999. But local communities or community forestry user groups (CFUGs) reject any move of the government leading towards handing over of the forests to the LGs. Nevertheless they want an active role of the LGs in the community forestry programme, mainly in user group identification. Sustainable management of the forests is unlikely without the constructive support, cooperation and active role of the LGs. Thus, role clarification between different actors and stakeholders of CFs, especially LGs, user groups and District Forest Officers with regard to CF is essential to put decentralisation into practice.

Basnyat B, Maskey AP, Zimmerman MD, Murdoch DR. 2005. Enteric (typhoid) fever in travelers. Clin Infect Dis, 41 (10), pp. 1467-1472. | Show Abstract | Read more

The incidence of enteric (typhoid) fever in travelers is estimated to be approximately 3-30 cases per 100,000 travelers to developing countries. Recently, it is become clear that travelers who are visiting friends and relatives, especially travelers to the Indian subcontinent, seem to be the most vulnerable to enteric fever and require special attention for prevention. Recent concerns are the increasing incidence of paratyphoid fever in Asia, which is not covered by available typhoid vaccines, and the emergence of infections caused by antibiotic-resistant strains (including strains resistant to fluoroquinolones). Typhoid vaccination is recommended for most travelers to moderate- to high-risk countries. Because of the nonspecific clinical presentation of enteric fever, a high index of suspicion is important in febrile travelers who have traveled to areas of endemicity.

Hasan R, Cooke FJ, Nair S, Harish BN, Wain J. 2005. Typhoid and paratyphoid fever. Lancet, 366 (9497), pp. 1603-1604. | Read more

Basnyat B. 2005. Typhoid and paratyphoid fever. Lancet, 366 (9497), pp. 1603. | Read more

Basnyat B. 2005. A different kind of medicine. Natl Med J India, 18 (6), pp. 321.

Basnyat B. 2005. High altitude cerebral and pulmonary edema. Travel Med Infect Dis, 3 (4), pp. 199-211. | Show Abstract | Read more

Altitude illness, which comprises of acute mountain sickness (AMS) and its life threatening complications, high altitude cerebral edema (HACE) and high altitude pulmonary edema (HAPE) is now a well recognized disease process. AMS and HACE are generally thought to be a continuum. Some historical facts about the illness, its new intriguing pathophysiological processes, and clinical picture are discussed here. Although the review deals with both HACE and HAPE, HAPE is covered in greater detail due to the recent important findings related to its pathophysiology and prevention mechanisms. Relevant clinical correlation, the differential diagnosis of altitude sickness for a more sophisticated approach to the disease phenomenon, the possibility of dehydration being a risk factor for altitude sickness, the hypothetical role of angiogenesis in cerebral edema, and the emphasis on some vulnerable groups at high altitude are some of the other newer material discussed in this review. A clear-cut treatment and basic prevention guidelines are included in two panels, and finally the limited literature on the role of genetic factors on susceptibility to altitude sickness is briefly discussed.

Cumbo TA, Braude D, Basnyat B, Rabinowitz L, Lescano AG, Shah MB, Radder DJ, Bashyal G, Gambert SR. 2005. Higher venous bicarbonate concentration associated with hypoxemia, not acute mountain sickness, after ascent to moderate altitude. J Travel Med, 12 (4), pp. 184-189. | Show Abstract | Read more

BACKGROUND: The pathophysiology underlying acute mountain sickness (AMS) and excessive hypoxemia at high altitudes is not fully understood. Previous work by our group has demonstrated a significant association between urinary measures of dehydration and bicarbonate retention in subjects developing excessive hypoxemia and AMS at high altitudes. To further characterize these findings, we returned to our original testing site to examine the hypothesis that subjects with lower levels of oxygen saturation and/or AMS would possess higher levels of venous bicarbonate. METHODS: Medical history inquiry, clinical examination, Lake Louise scoring, and the collection of venous levels of bicarbonate concentration and base excess were performed on 52 lowland-dwelling persons after they completed a religious pilgrimage in the Nepal Himalayas to approximately 4,250 m. RESULTS: Oxygen saturation levels were strongly and inversely correlated with serum levels of venous bicarbonate and base excess, whereas AMS and Lake Louise scores were not associated with these measures of alkalosis. CONCLUSIONS: Our data suggest an association between measures of serum bicarbonate anion retention and decreasing oxygen saturation. Our data do not demonstrate an association between AMS or Lake Louise scores and measures of serum bicarbonate level. We propose that excessive hypoxemia at high altitudes may be associated with a compromised ability of the kidney to metabolically compensate for an altitude-induced hypocapnic alkalosis.

Basnyat B. 2005. The physiologic basis of high-altitude diseases. Ann Intern Med, 142 (7), pp. 591. | Read more

Basnyat B, Pandit A, Pun M, West JB. 2005. The physiologic basis of high-altitude diseases [3] (multiple letters) Annals of Internal Medicine, 142 (7), pp. 591-592.

Basnyat B. 2005. The Khumbu cure. High Alt Med Biol, 6 (4), pp. 342-345. | Read more

Gertsch JH. 2004. Ginkgo biloba and acetazolamide for acute mountain sickness: Authors' reply BMJ, 329 (7458), pp. 172-172. | Read more

Adams J. 2004. Ginkgo biloba and acetazolamide for acute mountain sickness: exclusion of high risk, low status groups perpetuates discrimination and inequalities. BMJ, 329 (7458), pp. 171. | Read more

Murdoch DR, Woods CW, Zimmerman MD, Dull PM, Belbase RH, Keenan AJ, Scott RM, Basnyat B, Archibald LK, Reller LB. 2004. The etiology of febrile illness in adults presenting to Patan hospital in Kathmandu, Nepal. Am J Trop Med Hyg, 70 (6), pp. 670-675. | Show Abstract

In Nepal, many infections remain poorly characterized, partly due to limited diagnostic facilities. We studied consecutive febrile adults presenting to a general hospital in Kathmandu, Nepal. Of the 876 patients enrolled, enteric fever and pneumonia were the most common clinical diagnoses. Putative pathogens were identified in 323 (37%) patients, the most common being Salmonella enterica serotype Typhi and S. enterica serotype Paratyphi A (117), Rickettsia typhi (97), Streptococcus pneumoniae (53), Leptospira spp. (36), and Orientia tsutsugamushi (28). Approximately half of the Salmonella isolates were resistant to nalidixic acid. No clinical predictors were identified to reliably distinguish between the different infections. These findings confirm the heavy burden of enteric fever and pneumonia in Kathmandu, and highlight the importance of murine typhus, scrub typhus, and leptospirosis. Given the lack of reliable clinical predictors, the development of cheap and accurate diagnostic tests are likely to be of great clinical utility in this setting.

Marconi C, Marzorati M, Grassi B, Basnyat B, Colombini A, Kayser B, Cerretelli P. 2004. Second generation Tibetan lowlanders acclimatize to high altitude more quickly than Caucasians. J Physiol, 556 (Pt 2), pp. 661-671. | Show Abstract | Read more

Tibetan highlanders develop at altitude peak aerobic power levels close to those of Caucasians at sea level. In order to establish whether this feature is genetic and, as a consequence, retained by Tibetan lowlanders, altitude-induced changes of peak aerobic performance were assessed in four groups of volunteers with different ethnic, altitude exposure and fitness characteristics, i.e. eight untrained second-generation Tibetans (Tib 2) born and living at 1300 m; seven altitude Sherpas living at approximately 2800-3500 m; and 10 untrained and five trained Caucasians. Measurements were carried out at sea level or at Kathmandu (1300 m, Nepal) (PRE), and after 2-4 (ALT1), 14-16 (ALT2), and 26-28 (ALT3) days at 5050 m. At ALT3, of untrained and trained Caucasians was -31% and -46%, respectively. By contrast, of Tib 2 and Sherpas was -8% and -15%, respectively. At ALT3, peak heart rate (HR(peak)) of untrained and trained Caucasians was 148 +/- 11 and 149 +/- 7 beats min(-1), respectively; blood oxygen saturation at peak exercise was 76 +/- 6% and 73 +/- 6%, and haemoglobin concentration ([Hb]) was 19.4 +/- 1.0 and 18.6 +/- 1.2 g dl(-1), respectively. Compared to Caucasians, Tib 2 and Sherpas exhibited at ALT3 higher HR(peak) (179 +/- 9 and 171 +/- 4 beats min(-1), P < 0.001), lower [Hb] (16.6 +/- 0.6 and 17.4 +/- 0.9 g dl(-1), respectively, P < 0.001), and slightly but non-significantly greater average values (82 +/- 6 and 80 +/- 7%). The above findings and the time course of adjustment of the investigated variables suggest that Tibetan lowlanders acclimatize to chronic hypoxia more quickly than Caucasians, independent of the degree of fitness of the latter.

Mahajan KC, Nishtar S, Rajpara SM, Parmar MS, Desapriya EBR, Charles AR, Srivastava RN, Abeygunasekera AM, Chryssafidou E, Arvanitis TN et al. 2004. South Asian health: What is to be done? (multiple letters) British Medical Journal, 328 (7443), pp. 837-839.

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Gertsch JH, Basnyat B, Johnson EW, Onopa J, Holck PS. 2004. Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: The prevention of high altitude illness trial (PHAIT) BMJ, 328 (7443), pp. 797. | Show Abstract | Read more

Objective To evaluate the efficacy of ginkgo biloba, acetazolamide, and their combination as prophylaxis against acute mountain sickness. Design Prospective, double blind, randomised, placebo controlled trial. Setting Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002. Participants 614 healthy western trekkers (487 completed the trial) assigned to receive ginkgo, acetazolamide, combined acetazolamide and ginkgo, or placebo, initially taking at least three or four doses before continued ascent. Main outcome measures Incidence measured by Lake Louise acute mountain sickness score ≥ 3 with headache and one other symptom. Secondary outcome measures included blood oxygen content, severity of syndrome (Lake Louise scores ≥ 5), incidence of headache, and severity of headache. Results Ginkgo was not significantly different from placebo for any outcome; however participants in the acetazolamide group showed significant levels of protection. The incidence of acute mountain sickness was 34% for placebo, 12% for acetazolamide (odds ratio 3.76, 95% confidence interval 1.91 to 7.39, number needed to treat 4), 35% for ginkgo (0.95, 0.56 to 1.62), and 14% for combined ginkgo and acetazolamide (3.04, 1.62 to 5.69). The proportion of patients with increased severity of acute mountain sickness was 18% for placebo, 3% for acetazoalmide (6.46, 2.15 to 19.40, number needed to treat 7), 18% for ginkgo (1, 0.52 to 1.90), and 7% for combined ginkgo and acetazolamide (2.95, 1.30 to 6.70). Conclusions When compared with placebo, ginkgo is not effective at preventing acute mountain sickness. Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness. © 2004, BMJ Publishing Group Ltd. All rights reserved.

Basnyat B, Rajapaksa LC. 2004. Cardiovascular and infectious diseases in South Asia: the double whammy. BMJ, 328 (7443), pp. 781. | Read more

Gertsch JH, Basnyat B, Johnson EW, Onopa J, Holck PS. 2004. Randomised, double blind, placebo controlled comparison of ginkgo biloba and acetazolamide for prevention of acute mountain sickness among Himalayan trekkers: the prevention of high altitude illness trial (PHAIT). BMJ, 328 (7443), pp. 797. | Show Abstract | Read more

OBJECTIVE: To evaluate the efficacy of ginkgo biloba, acetazolamide, and their combination as prophylaxis against acute mountain sickness. DESIGN: Prospective, double blind, randomised, placebo controlled trial. SETTING: Approach to Mount Everest base camp in the Nepal Himalayas at 4280 m or 4358 m and study end point at 4928 m during October and November 2002. PARTICIPANTS: 614 healthy western trekkers (487 completed the trial) assigned to receive ginkgo, acetazolamide, combined acetazolamide and ginkgo, or placebo, initially taking at least three or four doses before continued ascent. MAIN OUTCOME MEASURES: Incidence measured by Lake Louise acute mountain sickness score > or = 3 with headache and one other symptom. Secondary outcome measures included blood oxygen content, severity of syndrome (Lake Louise scores > or = 5), incidence of headache, and severity of headache. RESULTS: Ginkgo was not significantly different from placebo for any outcome; however participants in the acetazolamide group showed significant levels of protection. The incidence of acute mountain sickness was 34% for placebo, 12% for acetazolamide (odds ratio 3.76, 95% confidence interval 1.91 to 7.39, number needed to treat 4), 35% for ginkgo (0.95, 0.56 to 1.62), and 14% for combined ginkgo and acetazolamide (3.04, 1.62 to 5.69). The proportion of patients with increased severity of acute mountain sickness was 18% for placebo, 3% for acetazoalmide (6.46, 2.15 to 19.40, number needed to treat 7), 18% for ginkgo (1, 0.52 to 1.90), and 7% for combined ginkgo and acetazolamide (2.95, 1.30 to 6.70). CONCLUSIONS: When compared with placebo, ginkgo is not effective at preventing acute mountain sickness. Acetazolamide 250 mg twice daily afforded robust protection against symptoms of acute mountain sickness.

Basnyat B. 2004. South Asian health: what is to be done? Better understanding is achievable. BMJ, 328 (7443), pp. 839. | Read more

Basnyat B, Tingay D, Basnyat G. 2004. Clinical images. A mystery. Wilderness Environ Med, 15 (1), pp. 53-55.

Basnyat B, Wu T, Gertsch JH. 2004. Neurological conditions at altitude that fall outside the usual definition of altitude sickness. High Alt Med Biol, 5 (2), pp. 171-179. | Show Abstract | Read more

Altitude sickness in its commonly recognized forms consists of acute mountain sickness and the two life-threatening forms, high altitude cerebral and pulmonary edema. Less well known are other conditions, chiefly neurological, that may arise completely outside the usual definition of altitude sickness. These, often focal, neurological conditions are important to recognize so that they do not become categorized as altitude sickness because, besides oxygen and descent, treatment may be vastly different. Transient ischemic attacks, cerebral venous thrombosis, seizures, syncope, double vision, and scotomas are some of the well-documented neurological disturbances at high altitude discussed here in order to enhance their recognition and treatment.

Basnyat B. 2004. "Preliminary report of the beneficial effect of chloromycetin in the treatment of typhoid fever"--a commentary. Wilderness Environ Med, 15 (3), pp. 216-217. | Read more

Tingay DG, Tsimnadis P, Basnyat B. 2003. A blurred view from Everest. Lancet, 362 (9400), pp. 1978. | Read more

Dumont L, Tramer MR, Lysakowski C, Mardirosoff C, Kayser B. 2003. Efficacy of low-dose acetazolamide for the prophylaxis of acute mountain sickness. High Alt Med Biol, 4 (3), pp. 399. | Read more

Basnyat B. 2003. Letter from Nepal [2] National Medical Journal of India, 16 (5), pp. 276-277.

Basnyat B. 2003. Steadfast to the summit: living and climbing at altitude. Natl Med J India, 16 (5), pp. 276-277.

Basnyat B, Murdoch DR. 2003. High-altitude illness. Lancet, 361 (9373), pp. 1967-1974. | Show Abstract | Read more

High-altitude illness is the collective term for acute mountain sickness (AMS), high-altitude cerebral oedema (HACE), and high-altitude pulmonary oedema (HAPE). The pathophysiology of these syndromes is not completely understood, although studies have substantially contributed to the current understanding of several areas. These areas include the role and potential mechanisms of brain swelling in AMS and HACE, mechanisms accounting for exaggerated pulmonary hypertension in HAPE, and the role of inflammation and alveolar-fluid clearance in HAPE. Only limited information is available about the genetic basis of high-altitude illness, and no clear associations between gene polymorphisms and susceptibility have been discovered. Gradual ascent will always be the best strategy for preventing high-altitude illness, although chemoprophylaxis may be useful in some situations. Despite investigation of other agents, acetazolamide remains the preferred drug for preventing AMS. The next few years are likely to see many advances in the understanding of the causes and management of high-altitude illness.

Basnyat B. 2003. Typhoid fever. N Engl J Med, 348 (12), pp. 1182-1184.

Basnyat B. 2003. Minimum pesticide list for the developing world. Lancet, 361 (9353), pp. 259-260. | Read more

Janssen van Doorn K, Pierard D, Verbeelen D. 2003. Typhoid fever. N Engl J Med, 348 (12), pp. 1182-1184. | Read more

Basnyat B, Gertsch JH, Johnson EW, Castro-Marin F, Inoue Y, Yeh C. 2003. Efficacy of low-dose acetazolamide (125 mg BID) for the prophylaxis of acute mountain sickness: a prospective, double-blind, randomized, placebo-controlled trial. High Alt Med Biol, 4 (1), pp. 45-52. | Show Abstract | Read more

The objective of this study was to determine the efficacy of low-dose acetazolamide (125 mg twice daily) for the prevention of acute mountain sickness (AMS). The design was a prospective, double-blind, randomized, placebo-controlled trial in the Mt. Everest region of Nepal between Pheriche (4243 m), the study enrollment site, and Lobuje (4937 m), the study endpoint. The participants were 197 healthy male and female trekkers of diverse background, and they were evaluated with the Lake Louise Acute Mountain Sickness Scoring System and pulse oximetry. The main outcome measures were incidence and severity of AMS as judged by the Lake Louise Questionnaire score at Lobuje. Of the 197 participants enrolled, 155 returned their data sheets at Lobuje. In the treatment group there was a statistically significant reduction in incidence of AMS (placebo group, 24.7%, 20 out of 81 subjects; acetazolamide group, 12.2%, 9 out of 74 subjects). Prophylaxis with acetazolamide conferred a 50.6% relative risk reduction, and the number needed to treat in order to prevent one instance of AMS was 8. Of those with AMS, 30% in the placebo group (6 of 20) versus 0% in the acetazolamide group (0 of 9) experienced a more severe degree of AMS as defined by a Lake Louise Questionnaire score of 5 or greater (p = 0.14). Secondary outcome measures associated with statistically significant findings favoring the treatment group included decrease in headache and a greater increase in final oxygen saturation at Lobuje. We concluded that acetazolamide 125 mg twice daily was effective in decreasing the incidence of AMS in this Himalayan trekking population.

Caumes E, Bricaire F, Basnyat B, Ryan ET, Wilson ME, Kain KC. 2002. Illness after International Travel New England Journal of Medicine, 347 (24), pp. 1984-1984. | Read more

Basnyat B. 2002. Illness after international travel. N Engl J Med, 347 (24), pp. 1984.

Jansen GF, Kagenaar DA, Basnyat B, Odoom JA. 2002. Basilar artery blood flow velocity and the ventilatory response to acute hypoxia in mountaineers. Respir Physiol Neurobiol, 133 (1-2), pp. 65-74. | Show Abstract | Read more

Hypoxic ventilatory response is higher in successful extreme-altitude climbers than in controls. We hypothesized that these climbers have lower brainstem blood flow secondary to hypoxia which may possibly cause retention of medullary CO(2) and greater ventilatory drive. Using transcranial Doppler, basilar artery blood flow velocity (Vba) was measured at sea level in 7 extreme-altitude climbers and 10 controls in response to 10 min sequential exposures to inspired oxygen fractions (FI(O(2))) of 0.21 (baseline), 0.13, 0.11, 0.10, 0.09, 0.08 and 0.07. Sa(O(2)) was higher in climbers at FI(O(2)) of 0.11 (P<0.05), 0.08 and 0.07 (both P<0.0001). Expired ventilation (VE) increased more (n.s.), and PET(CO(2)) decreased more (n.s.) in the climbers than in controls. Vba did not significantly change in both groups at FI(O(2)) of 0.13-0.09. At FI(O(2)) of 0.08 and 0.07, Vba decreased 21% (P<0.03) and 27% (P<0.01), respectively, in climbers, and increased 29% (P<0.01) and 27% (P<0.01), respectively, in controls. The conflicting effects of hypoxia and hypocapnia on both medullary blood flow and ventilatory drive thus balance out, giving climbers a greater drive and higher Sa(O(2)), despite lower PET(CO(2)) and lower brain stem blood flow.

Basnyat B. 2002. Salmeterol for the prevention of high-altitude pulmonary edema. N Engl J Med, 347 (16), pp. 1282-1285. | Read more

Cumbo TA, Basnyat B, Lescano AG, Edelman R. 2002. Preventing and treating infection in patients who travel to high places Journal of Respiratory Diseases, 23 (10), pp. 490-493.

Cumbo TA, Basnyat B, Graham J, Lescano AG, Gambert S. 2002. Acute mountain sickness, dehydration, and bicarbonate clearance: preliminary field data from the Nepal Himalaya. Aviat Space Environ Med, 73 (9), pp. 898-901. | Show Abstract

BACKGROUND: In 1999, Basnyat et al. published preliminary data demonstrating an inverse correlation between hydration status and acute mountain sickness during an epidemiological study performed in the vicinity of Mount Everest. To expand on these findings, we have re turned to the Langtang area of the Nepal Himalaya to perform more specific studies of altitude illness related to dehydration and hypoxemia using urine studies, pulse oximetry, and physical examination. HYPOTHESIS: Dehydration will incite physiological changes aimed at the preservation of vascular volume homeostasis characterized by the production of sodium and water sparing hormones. As sodium is reabsorbed in the kidney, bicarbonate anion is also reabsorbed resulting in insufficient bicarbonate anion excretion by the kidney leading to an incomplete compensation for altitude induced hypocapnic alkalosis and the development of clinical disease. METHODS: Estimates of intravascular volume (urine specific gravity), oxygen saturation (pulse oximetry), urinary bi carbonate excretion (urine pH), and AMS (Lake Louise Score) were collected from Hindu pilgrims at 4243 m during an annual sacred festival at Lake Gosinkunda. RESULTS: Worsening altitude illness approx imated by increasing Lake Louise Score was associated with increasing urine specific gravity (p = 0.043), decreasing oxygen saturation (p = 0.020), and decreasing urine pH (p = 0.040) after rapid ascent to 4243 m. CONCLUSIONS: Worsening altitude illness, indicated by increasing Lake Louise score, was associated with increasing measures of dehydration, hypoxemia, and urine acidity.

Basnyat B. 2002. Mountain sickness. Natl Med J India, 15 (5), pp. 294-295.

Basnyat B, Rolla G, Nebiolo F, Bucca C, Bärisch P, Maggiorini M, Mairbäurl H, Vock P, Swenson ER, Cremona G. 2002. Pulmonary extravascular fluid accumulation in climbers [4] (multiple letters) Lancet, 360 (9332), pp. 570-572.

Basnyat B. 2002. Pulmonary extravascular fluid accumulation in climbers. Lancet, 360 (9332), pp. 570. | Read more

Basnyat B. 2002. A developing country perspective. Lancet, 359 (9322), pp. 2026. | Read more

Basnyat B. 2002. Pilgrimage medicine. BMJ, 324 (7339), pp. 745. | Read more

Basnyat B. 2002. Scientific English for non-English speakers. Lancet, 359 (9309), pp. 896. | Read more

Basnyat B. 2002. Neck irradiation or surgery may predispose to severe acute mountain sickness. J Travel Med, 9 (2), pp. 105.

Basnyat B. 2002. Delirium at high altitude. High Alt Med Biol, 3 (1), pp. 69-71. | Show Abstract | Read more

A 35-year-old man on a trek to the Mount Everest region of Nepal presented with a sudden, acute confusional state at an altitude of about 5000 m. Although described at higher altitudes, delirium presenting alone has not been documented at 5000 m or at lower high altitudes. The differential diagnosis which includes acute mountain sickness and high altitude cerebral edema is discussed. Finally, the importance of travelling with a reliable partner and using proper insurance is emphasized in treks to the Himalayas.

Basnyat B. 2002. Pleural tuberculosis in a Nepali trekker. Wilderness Environ Med, 13 (2), pp. 129-130. | Read more

Basnyat B. 2002. It's OK, it's TB. Wilderness Environ Med, 13 (3), pp. 218-220. | Read more

Schepens B, Basnyat B, Willems PA, Heglund NC. 2001. Measurement of the loads carried by porters in Nepal Archives of Physiology and Biochemistry, 109 (SUPPL.), pp. 72.

Basnyat B, Cumbo TA, Edelman R. 2001. Infections at high altitude. Clin Infect Dis, 33 (11), pp. 1887-1891. | Show Abstract | Read more

Every year, thousands of outdoor trekkers worldwide visit high-altitude (>2500 m) destinations. Although high-altitude areas per se do not harbor any specific agents, it is important to know the pathogens encountered in the mountains to be better able to help the ill sojourner at high altitude. These are the same pathogens prevalent in the surrounding lowlands, but various factors such as immunomodulation, hypoxia, physiological adaptation, and harsh environmental stressors at high altitude may enhance susceptibility to these pathogens. Against this background, various gastrointestinal, respiratory, dermatological, neurological, and other infections encountered at high altitude are discussed. Because there are few published data on infections at high altitude, this review is largely anecdotal and based on personal experience.

Basnyat B. 2001. Short stay at high altitude: risk factor for thrombosis. Natl Med J India, 14 (6), pp. 379.

Basnyat B. 2001. High-altitude illness. N Engl J Med, 345 (17), pp. 1279. | Read more

Basnyat B, Zimmerman MD, Shrestha Y, Scott RM, Endy TP. 2001. Persistent Japanese encephalitis in Kathmandu: the need for immunization. J Travel Med, 8 (5), pp. 270-271. | Read more

Basnyat B, Graham L, Lee SD, Lim Y. 2001. A language barrier, abdominal pain, and double vision. Lancet, 357 (9273), pp. 2022. | Read more

Bärtsch P, Straub PW, Haeberli A. 2001. Hypobaric hypoxia. Lancet, 357 (9260), pp. 955-956. | Read more

Basnyat B. 2001. Hypobaric hypoxia. Lancet, 357 (9260), pp. 956. | Read more

Basnyat B. 2001. Letters to the editor: Seizures at high altitude in a patient on antiseizure medications[1] Wilderness and Environmental Medicine, 12 (2), pp. 153-154.

Basnyat B. 2001. Letter from Dolpa. High Alt Med Biol, 2 (1), pp. 71-73. | Read more

Graham LE, Basnyat B. 2001. Cerebral edema in the Himalayas: too high, too fast! Wilderness Environ Med, 12 (1), pp. 62. | Read more

Basnyat B. 2001. Seizures at high altitude in a patient on antiseizure medications. Wilderness Environ Med, 12 (2), pp. 153-154. | Read more

Basnyat B. 2001. Isolated facial and hypoglossal nerve palsies at high altitude. High Alt Med Biol, 2 (2), pp. 301-303. | Show Abstract | Read more

A variety of neurological disorders other than high altitude cerebral edema have been described at high altitude. This report documents isolated facial and hypoglossal nerve palsies that occurred in two travellers at high altitude in the Nepal Himalaya. The possible pathophysiological mechanisms of these neurological deficits are discussed.

Basnyat B, Schepens B. 2001. The burden of the Himalayan porter. High Alt Med Biol, 2 (2), pp. 315-316. | Read more

Litch JA, Bishop RA, Ripley R. 2000. Medical emergencies at high altitude. Wilderness Environ Med, 11 (4), pp. 297-299.

Basnyat B. 2000. High-altitude emergency medicine. Lancet, 356 Suppl (9248), pp. s1. | Read more

Basnyat B, Scott RM. 2000. Update in hepatology. Ann Intern Med, 133 (9), pp. 747. | Read more

Jansen GF, Krins A, Basnyat B, Bosch A, Odoom JA. 2000. Cerebral autoregulation in subjects adapted and not adapted to high altitude. Stroke, 31 (10), pp. 2314-2318. | Show Abstract | Read more

BACKGROUND AND PURPOSE: Impaired cerebral autoregulation (CA) from high-altitude hypoxia may cause high-altitude cerebral edema in newcomers to a higher altitude. Furthermore, it is assumed that high-altitude natives have preserved CA. However, cerebral autoregulation has not been studied at altitude. METHODS: We studied CA in 10 subjects at sea level and in 9 Sherpas and 10 newcomers at an altitude of 4243 m by evaluating the effect of an increase of mean arterial blood pressure (MABP) with phenylephrine infusion on the blood flow velocity in the middle cerebral artery (Vmca), using transcranial Doppler. Theoretically, no change of Vmca in response to an increase in MABP would imply perfect autoregulation. Complete loss of autoregulation is present if Vmca changes proportionally with changes of MABP. RESULTS: In the sea-level group, at a relative MABP increase of 23+/-4% during phenylephrine infusion, relative Vmca did not change essentially from baseline Vmca (2+/-7%, P=0.36), which indicated intact autoregulation. In the Sherpa group, at a relative MABP increase of 29+/-7%, there was a uniform and significant increase of Vmca of 24+/-9% (P<0.0001) from baseline Vmca, which indicated loss of autoregulation. The newcomers showed large variations of Vmca in response to a relative MABP increase of 21+/-6%. Five subjects showed increases of Vmca of 22% to 35%, and 2 subjects showed decreases of Vmca of 21% and 23%. CONCLUSIONS: All Sherpas and the majority of the newcomers showed impaired CA. It indicates that an intact autoregulatory response to changes in blood pressure is probably not a hallmark of the normal human cerebral vasculature at altitude and that impaired CA does not play a major role in the occurrence of cerebral edema in newcomers to the altitude.

Basnyat B. 2000. North and South: bridging the information gap. Lancet, 356 (9234), pp. 1036. | Read more

Basnyat B, Pokhrel G, Ferguson G, Shlim DR. 2000. Tropical sprue as a cause of traveler's diarrhea [3] (multiple letters) Wilderness and Environmental Medicine, 11 (2), pp. 140-141.

Basnyat B, Savard GK, Zafren K. 2000. Erratum: Trends in the workload of the two high altitude aid posts in the Nepal Himalayas (Journal of Travel Medicine (1999) 6 (217-222)) Journal of Travel Medicine, 7 (1),

Basnyat B, Pokhrel G, Cohen Y. 2000. The Japanese need travel vaccinations. J Travel Med, 7 (1), pp. 37. | Show Abstract

At a travel clinic in Kathmandu we reviewed the vaccination records from March 1997 to March 1998 for all travelers to developing countries like Nepal, for two important vaccines, namely, typhoid and hepatitis A. These travelers visited the clinic for various medical problems. One of the reasons for doing this study was that in previous years we saw a disproportionate number of Japanese travelers with hepatitis A, who had not taken the hepatitis A vaccine or immune gamma globulin for prevention of this illness. We hypothesized, therefore, that one of the reasons that Japanese patients visiting our clinic had higher rates of hepatitis A was because they were not vaccinated against this disease. There were 765 tourists for that time period out of which about 10% were Japanese. The rest were Americans, British, Israelis, Canadians, Australians, Danish and a small miscellaneous group from other countries.

Basnyat B, Sleggs J, Spinger M. 2000. Seizures and delirium in a trekker: the consequences of excessive water drinking? Wilderness Environ Med, 11 (1), pp. 69-70. | Read more

Goodman T, Basnyat B. 2000. A tragic report of probable high-altitude pulmonary edema in the Himalayas: preventive implications. Wilderness Environ Med, 11 (2), pp. 99-101. | Show Abstract | Read more

High-altitude pulmonary edema (HAPE) is a well-recognized disease entity in trekkers to the Nepal Himalayas. We present the case of a patient who had clinical features consistent with HAPE but did not descend the mountain on time, which contributed to his death. The important factors of the diagnosis, the descent, and the follow-up in Kathmandu are examined.

Basnyat B, Subedi D, Sleggs J, Lemaster J, Bhasyal G, Aryal B, Subedi N. 2000. Disoriented and ataxic pilgrims: an epidemiological study of acute mountain sickness and high-altitude cerebral edema at a sacred lake at 4300 m in the Nepal Himalayas. Wilderness Environ Med, 11 (2), pp. 89-93. | Show Abstract | Read more

OBJECTIVE: To determine the incidence of high-altitude cerebral edema (HACE), acute mountain sickness (AMS), and high-altitude pulmonary edema (HAPE) in pilgrims. Although it is well known that western trekkers suffer from acute mountain sickness (AMS) in the Himalayas, not much is documented about the incidence of AMS in the local population of Nepal that go to high altitude. METHODS: The design was a randomized study set at a sacred high-altitude lake at 4300 m at Gosainkund in the Nepal Himalayas. There was a control study at 1300 m at Pashupatinath in Kathmandu, Nepal. The subjects were pilgrims of different ethnic Nepali backgrounds. The Lake Louise consensus for AMS, HACE, and HAPE was used, and oxygen saturation with a pulse oximeter was performed on HACE subjects. RESULTS: Out of 5000 pilgrims, 228 were randomly chosen. Sixty-eight percent had AMS, 31% had HACE, and 5% had HAPE. The mean oxygen saturation of HACE subjects at that altitude was 77%, 87% being normal for 4300 m altitude. Seventy-three percent of the study population were men, yet women had a significantly higher rate of AMS (odds ratio, 4.34; 95% confidence interval, 1.83-10.68), HACE (odds ratio 3.15, confidence interval 1.62-6.12), and HAPE (odds ratio, 5.2; 95% confidence interval, 1.24-24.73). CONCLUSIONS: Such a high incidence of HACE in an epidemiological study using the Lake Louise criteria has, to our knowledge, not been reported before. High-altitude pilgrims, especially women pilgrims in this study, seem to be a very susceptible group. Preventive measures in these pilgrims need to be adopted to avoid AMS, specifically life-threatening HACE and HAPE.

Basnyat B, Pokhrel G, Ferguson G. 2000. Tropical sprue as a cause of traveler's diarrhea. Wilderness Environ Med, 11 (2), pp. 140-141.

Basnyat B, Sill D, Gupta V. 2000. Myocardial infarction or high-altitude pulmonary edema? Wilderness Environ Med, 11 (3), pp. 196-198. | Show Abstract | Read more

We report the case of a 60-year-old European man with myocardial infarction at high altitude (4000 m). Myocardial infarction is an uncommonly encountered problem in high-altitude trekking in the Himalayas. The paucity of coronary artery disease at high altitude (hypoxia, exercise, and age not-withstanding) is discussed. Finally, the importance of recognizing disease entities that mimic acute mountain sickness in this environment is emphasized.

Basnyat B, Cumbo TA, Edelman R. 2000. Acute medical problems in the Himalayas outside the setting of altitude sickness. High Alt Med Biol, 1 (3), pp. 167-174. | Show Abstract | Read more

Well-recognized medical threats at high altitude (>2,500 m) include acute mountain sickness (AMS), high altitude pulmonary edema (HAPE), and high altitude cerebral edema (HACE). Thousands of travelers in the Himalayas are exposed annually to these often life-threatening syndromes. Their recognition and treatment has advanced considerably in recent years. In the Himalayas, we frequently see acute medical problems outside the setting of AMS and the two types of altitude edemas. Many of these other conditions are also hypoxia related and sometimes may mimic the classic high altitude illnesses of AMS, HAPE, and HACE. Although the vast majority of these medical problems are neurological, pulmonary and other organ system dysfunction also occur. These "non-high altitude sickness" disease entities in persons who sojourn to remote mountainous environments are reviewed in this paper to enhance their recognition, diagnosis, and treatment.

Basnyat B, Savard GK, Zafren K. 1999. Trends in the workload of the two high altitude aid posts in the Nepal Himalayas. J Travel Med, 6 (4), pp. 217-222. | Show Abstract | Read more

BACKGROUND: Acute mountain sickness (AMS), High altitude pulmonary edema (HAPE) and High Altitude Cerebral Edema (HACE) are well known problems in the high altitude region of the Nepal Himalayas. To assess the proportion of AMS, HAPE, and HACE from 1983 to 1995 in the Himalaya Rescue Association (HRA) aid posts' patients at the Everest (Pheriche 4,243 m) and Annapurna (Manang 3,499 m) regions, the two most popular trekking areas in the Himalayas. A retrospective study was conducted at the HRA medical aid posts in Manang (3,499 m) and Pheriche (4,243 m) in the Himalayas, where 4,655 trekkers (tourists, mostly Caucasians) and 4,792 Nepalis (mostly porters and villagers) were seen at the two high-altitude clinics from 1983 to 1995, for a variety of medical problems, including AMS. METHODS: The number of trekking permits issued for entering the two most popular regions in the Himalayas was calculated and referenced to the proportion of trekkers with medical conditions. Well established guidelines like the Lake Louise Diagnostic Criteria were used in the assessment of AMS, HAPE and HACE. Linear regression analyses were performed on data collected from the two aid posts to determine the effect of time on each variable. For comparison between the aid posts, angular transformation (arcsine) and analysis of variance (ANOVA) were performed on all proportional (incidence) data. RESULTS: Approximately 20% of all visitors (Nepali plus trekkers) who visited the higher Pheriche aid post were diagnosed with AMS compared to around 6% at the lower Manang aid post. There was a linear increase over time in the number of trekkers entering the Everest (r=0.904, p<.001) and the Annapurna (r=0.887, p<.001) regions. The proportion of trekker patients with any medical condition visiting the two HRA aid posts at Manang and Pheriche, expressed as a function of the total number of trekkers entering the Everest and Annapurna regions, was not significantly different between Pheriche (average 4%) and Manang (average 1%). However, the proportion of AMS, HAPE and HACE in patients (Nepali plus trekkers) to the aid posts was greater in those visiting the higher Pheriche aid post compared to the lower Manang aid post (f=56.74, n=13; p<. 001). Importantly, only the proportion of AMS (r=0.568; p<.05) and not HAPE or HACE increased over time in Pheriche, alongside an unchanged proportion of trekker patients, amongst all Pheriche aid post patients. There was no increase of AMS, HAPE or HACE in Manang. CONCLUSIONS: HAPE and HACE are the life-threatening forms of AMS and although there is a linear increase of trekkers entering the Himalayas in Nepal, the findings revealed that HAPE and HACE have not increased over time. One possible explanation may be that awareness drives by organizations like the Himalayan Rescue Association may be effective in preventing the severe forms of AMS.

Basnyat B, Lemaster J, Litch JA. 1999. Everest or bust: a cross sectional, epidemiological study of acute mountain sickness at 4243 meters in the Himalayas. Aviat Space Environ Med, 70 (9), pp. 867-873. | Show Abstract

BACKGROUND: Thousand of tourists trek in the Himalayas every season and risk acute mountain sickness (AMS). Prior studies have shown that the rate of ascent is one of the primary risk factors for the development of AMS but the role of body hydration, age, gender, alcohol and medication usage, body weight, and altitude of residence continues to be in question. This study estimates the incidence of AMS at 4234 m at Pheriche in the Everest region, explores a number of risk factors predisposing trekkers to a diagnosis of AMS and attempts to quantify the relationship between the Lake Louise AMS diagnostic criteria and oxygen saturation. METHODS: Demographic data and information about risk factors felt to place trekkers at increased risk of AMS was collected from 550 trekkers for 1 mo in the fall of 1996 at 4234 m in the Everest region. RESULTS: Diagnosis of AMS was made in 29.8% (159 trekkers) of the study population. Low water intake (odds ratio 1.57; 95% confidence interval,1.02-2.40), the presence of respiratory symptoms (odds ratio 2.21; 95% confidence interval, 1.43-3.40), and an oxygen saturation below 85% at 4243 m (odds ratio 2.35; 95% confidence interval, 1.55-3.56) were identified as independent risk factors for AMS diagnosis in this sample. In addition, AMS risk decreased 18.7% (95% confidence interval, 3.8-31.2%) for each additional night spent between Lukla (2804 m) and the study site at 4243 m. CONCLUSION: Increased reported fluid intake decreased the risk of AMS in this cross sectional prospective study. Further studies need to be done to confirm this finding before recommendations can be made. In addition the rise in the risk of AMS as the rate of ascent increased along this popular Everest trek was quantified for the first time. Finally, AMS was also associated with respiratory symptoms and with a lower oxygen saturation.

Basnyat B, Zimmerman M, Sleggs J, Vaidhya H. 1999. Jhum-jhum is a symptom (multiple letters) [11] Lancet, 353 (9169), pp. 2074.

Basnyat B, Zimmerman M, Sleggs J, Vaidhya H. 1999. Jhum-jhum is a symptom. Lancet, 353 (9169), pp. 2074. | Read more

Bologna M, Gherardi CR, Goto Y, Kantemir E, Khan AJ, Kim JP, Kumana CR, Livaditou A, Vilardell-Tarres M, Vidmar I et al. 1999. The firing of Dr Lundberg [1] (multiple letters) Journal of the American Medical Association, 281 (19), pp. 1789-1793. | Read more

Basnyat B, Pokhrel G. 1999. The firing of Dr Lundberg. JAMA, 281 (19), pp. 1791.

Basnyat B. 1999. High-altitude cerebral edema. JAMA, 281 (19), pp. 1794. | Read more

Basnyat B. 1999. Mixed malaria infection. J Travel Med, 6 (1), pp. 50-51. | Read more

Jansen GF, Krins A, Basnyat B. 1999. Cerebral vasomotor reactivity at high altitude in humans. J Appl Physiol (1985), 86 (2), pp. 681-686. | Show Abstract

The purpose of this study was twofold: 1) to determine whether at high altitude cerebral blood flow (CBF) as assessed during CO2 inhalation and during hyperventilation in subjects with acute mountain sickness (AMS) was different from that in subjects without AMS and 2) to compare the CBF as assessed under similar conditions in Sherpas at high altitude and in subjects at sea level. Resting control values of blood flow velocity in the middle cerebral artery (VMCA), pulse oxygen saturation (SaO2), and transcutaneous PCO2 were measured at 4,243 m in 43 subjects without AMS, 17 subjects with AMS, 20 Sherpas, and 13 subjects at sea level. Responses of CO2 inhalation and hyperventilation on VMCA, SaO2, and transcutaneous PCO2 were measured, and the cerebral vasomotor reactivity (VMR = DeltaVMCA/PCO2) was calculated as the fractional change of VMCA per Torr change of PCO2, yielding a hypercapnic VMR and a hypocapnic VMR. AMS subjects showed a significantly higher resting control VMCA than did no-AMS subjects (74 +/- 22 and 56 +/- 14 cm/s, respectively; P < 0.001), and SaO2 was significantly lower (80 +/- 8 and 88 +/- 3%, respectively; P < 0.001). Resting control VMCA values in the sea-level group (60 +/- 15 cm/s), in the no-AMS group, and in Sherpas (59 +/- 13 cm/s) were not different. Hypercapnic VMR values in AMS subjects were 4.0 +/- 4.4, in no-AMS subjects were 5.5 +/- 4. 3, in Sherpas were 5.6 +/- 4.1, and in sea-level subjects were 5.6 +/- 2.5 (not significant). Hypocapnic VMR values were significantly higher in AMS subjects (5.9 +/- 1.5) compared with no-AMS subjects (4.8 +/- 1.4; P < 0.005) but were not significantly different between Sherpas (3.8 +/- 1.1) and the sea-level group (2.8 +/- 0.7). We conclude that AMS subjects have greater cerebral hemodynamic responses to hyperventilation, higher VMCA resting control values, and lower SaO2 compared with no-AMS subjects. Sherpas showed a cerebral hemodynamic pattern similar to that of normal subjects at sea level.

Cogo A, Basnyat B, Legnani D, Allegra L. 1998. Bronchial asthma and airway hyperresponsiveness at high altitude Pneumologie, 52 (11), pp. 666.

Basnyat B. 1998. Fatal grand mal seizure in a Dutch trekker. J Travel Med, 5 (4), pp. 221-222. | Show Abstract | Read more

A 35-year-old healthy Dutch woman went on a trek (Lang Tang) in Nepal up to an approximate altitude of about 3800 meters. She had no prior history of any medical problems except attacks of generalized epilepsy when she was 19 years old, which had been controlled with antiepileptic medications. She had had no attacks after the age of 20. A CT scan done around that time had apparently been normal. On this trek she had developed diarrhea which had been cured with norfloxacin 400 mg two times per day for 3 days. Two days later, while descending, she developed a grand mal seizure at an altitude of 3300 meters, after which she developed a classic postictal phase but gradually recovered. She developed grand mal seizures again the next day, but when she went to a travel clinic in Kathmandu, she had been seizure free for 72 hours. She also revealed that she had not suffered from acute mountain sickness on the trek. She also had a prior history of gastroenteritis at high altitude which improved significantly with norfloxacin, a quinolone antibiotic. This was corroborated by her party. Upon examination she was fully conscious and oriented to person, place and time. Her pulse was 70 beats per minute and her BP was 110/80 mm of Hg. Her fundi and cranial nerves exam were completely normal. Her abstract thinking, gait, power, tone, reflexes and other facets of her neurologic exam revealed absolutely no abnormalities. Her cardiovascular exam revealed a normal rhythm with no murmurs or bruits. The rest of her exam was also normal. She revealed that she played tennis on a regular basis and was an outdoor person. She had not trekked before in the Himalayas and it was uncertain if she had been to high altitude before. She was on no medications at the time. There was no history of drug abuse. She did not smoke and consumed few alcoholic beverages. She had not consumed any alcohol on the trek. She was advised to get a CT scan (she declined as she was going home to Holland in 2 days) and she was prescribed a loading dose of phenytoin 1 g orally spread over several hours and it was recommended she take 300 mg of phenytoin per day. She was going to see her neurologist in Holland on arrival there. She went to her hotel in Kathmandu while her friends went to fill the prescription of phenytoin. When her friends returned to the hotel she was having another grand mal seizure. Medical help was sought, but she died before the doctor arrived to control her seizures. When the doctor did arrive and carried out CPR for half an hour it was to no avail as she continued to have no pulse or blood pressure.

Basnyat B, Sherpa N, Basyal G, Adhirikari P. 1998. Children in the mountains. Advice given was too conservative. BMJ, 317 (7157), pp. 540.

Basnyat B. 1998. Death due to diphtheria. J Travel Med, 5 (2), pp. 101. | Read more

Fiorina A, Legnani D, Fasano V, Cogo A, Basnyat B, Passalacqua G, Scordamaglia A. 1998. Pollen, mite and mould samplings by a personal collector at high altitude in Nepal. J Investig Allergol Clin Immunol, 8 (2), pp. 85-88. | Show Abstract

The new personal portable sampler for detection of environmental biologic particles (Partrap FA52, Coppa, Biella, Italy) was used to evaluate both atmospheric and indoor biologic particles in bedding at high altitudes during two Italian scientific expeditions in Nepal, in 1994 and 1996 respectively. The sampling was performed outdoors and indoors at the following altitudes: Katmandu 1,330 meters (m), LuKla 2,800 m, Namche 3,500 m, Pericle 4,200 m and Piramide 5,050 m. In both expeditions each sample of outdoor and indoor air was obtained by sucking air into the sampler either against the wind during a 6-h period, from 9 am to 3 pm, or from bedding of inhabitants resident at the different altitudes for 5 min. The number of pollens, moulds and mites trapped in each sample were assessed. The statistical analysis of the results by Spearman correlation test revealed a significant inverse correlation (p < 0.02) between altitude and the number of the considered biologic particles for sampling carried out during both the 1994 and 1996 expeditions. Moreover, Wilcoxon paired test showed no significant difference between the biologic sampling obtained in the two expeditions. These results confirm the decrease of the environmental biologic charge in relation to the increase of altitude and prove the efficacy of Partrap FA52 in obtaining reproducible quantitative data.

Basnyat B, Shrestha Y. 1998. Travel medicine and Sherlock Holmes. J Travel Med, 5 (1), pp. 42-43. | Read more

Basnyat B. 1998. Costs of amphotericin B lipid complex for kala-azar. Ann Intern Med, 128 (4), pp. 326. | Read more

Basnyat B, Sherpa N, Basyal G, Adhirikari P, Pollard AJ, Murdoch DR, Bartsch P. 1998. Children in the mountains (multiple letters) [6] British Medical Journal, 317 (7157), pp. 540.

Basnyat B. 1998. Acetazolamide for tourists to Lhasa. Wilderness Environ Med, 9 (3), pp. 191. | Read more

Basnyat B. 1997. Seizure and hemiparesis at high-altitude outside the setting of acute mountain sickness. Wilderness Environ Med, 8 (4), pp. 221-222. | Show Abstract | Read more

Neurologic problems at high altitudes are well known. What is probably less emphasized are neurologic problems at altitude outside the setting of high-altitude cerebral edema. Because neurologic symptoms for these kinds of problems at high altitude are often transient, neuroradiologic scanning for these problems is usually not done or reported. Furthermore, diagnostic testing facilities may be unavailable in these remote high-altitude settings. A patient is described here with transient seizure and right-sided hemiparesis at high altitude with no preceding symptoms of acute mountain sickness. Computed tomography of the head was obtained in a hospital at lower altitude where the patient was taken promptly. The findings of the scan revealed probable focal cerebral edema in the left parietal lobe in keeping with his temporary right-sided weakness. Possible treatment modalities on the mountain for this problem are also discussed.

Litch JA, Basnyat B, Zimmerman M. 1997. Subarachnoid hemorrhage at high altitude. West J Med, 167 (3), pp. 180-181.

Basnyat B, Litch J. 1997. Another patient with neck irradiation and increased susceptibility to acute mountain sickness. Wilderness Environ Med, 8 (3), pp. 176. | Read more

Basnyat B, Litch JA. 1997. Medical problems of porters and trekkers in the Nepal Himalaya. Wilderness Environ Med, 8 (2), pp. 78-81. | Show Abstract | Read more

The purpose of this study was to assess the incidence of medical illness among members of trekking groups in the Nepal Himalaya. The design was a cohort study using interview and clinical examination by a single physician. The setting was the Manaslu area in the central Nepal Himalaya along a 22-day trekking route with elevations ranging from 487 m to 5100 m. Subjects were 155 members of commercial trekking groups: 102 Nepali porters, 31 Nepali trek staff, and 22 Western trekkers. We found that medical problems occurred in 45% of party members. The porter cohort contained the highest diversity and severity of illness. The relatively larger porter cohort experienced 77% of the medical problems recorded compared with 17% among Western trekkers and 6% among trek staff. The incidence of medical problems was not significantly different in the porter staff (52%) and Western trekkers (55%) and was significantly lower for the trek staff (13%). High-altitude pharyngitis/bronchitis was the most common illness in the party (12%) followed by acute mountain sickness (8%) and gastroenteritis (6%). Other conditions included anxiety (3%), cellulitis (3%), scabies (3%), snow blindness (3%), acute alcohol intoxication (2%), conjunctivitis (2%), fever (2%), lacerations (2%), and hemorrhoids (1%). Illness with infectious etiologies comprised 33% of the medical problems. The incidence of altitude illness was not significantly less in the Nepali porter staff than in the Western trekkers. Evacuation was required in 5% of party members, all from the porter group. This study should alert expedition medical providers and trip leaders of the need to be observant for and prepared to treat the frequent and diverse medical problems among the porter staff in their party, in addition to the Western members. Medical problems are common in remote mountainous areas, indicating that trip physicians should be experienced in primary care.

Cogo A, Basnyat B, Legnani D, Allegra L. 1997. Bronchial asthma and airway hyperresponsiveness at high altitude. Respiration, 64 (6), pp. 444-449. | Show Abstract | Read more

The mountain climate can modify respiratory function and bronchial responsiveness of asthmatic subjects. Hypoxia, hyperventilation of cold and dry air and physical exertion may worsen asthma or enhance bronchial hyperresponsiveness while a reduction in pollen and pollution may play an important role in reducing bronchial inflammation. At moderate altitude (1,500-2,500 m), the main effect is the absence of allergen and pollutants. We studied bronchial hyperresponsiveness to both hyposmolar aerosol and methacholine at sea level (SL) and at high altitude (HA; 5,050 m) in 11 adult subjects (23-48 years old, 8 atopic, 3 nonatopic) affected by mild asthma. Basal FEV1 at SL and HA were not different (p = 0.09), whereas the decrease in FEV1 induced by the challenge was significantly higher at SL than at HA. (1) Hyposmolar aerosol: at SL the mean FEV1 decreased by 28% from 4.32 to 3.11 liters; at 5,050 m by 7.2% from 4.41 to 4.1 liters (p < 0.001). (2) Methacholine challenge: at SL PD20-FEV1 was 700 micrograms and at HA > 1,600 micrograms (p < 0.005). In 3 asthmatic and 5 nonasthmatic subjects plasma levels of cortisol were also measured. The mean value at SL was 265 nmol and 601 nmol at HA (p < 0.005). We suppose that the reduction in bronchial response might be mainly related to the protective role carried out by the higher levels of cortisol and, as already known, catecholamines.

Kayser B, Marconi C, Amatya T, Basnyat B, Colombini A, Broers B, Cerretelli P. 1994. The metabolic and ventilatory response to exercise in Tibetans born at low altitude. Respir Physiol, 98 (1), pp. 15-26. | Show Abstract | Read more

The exercise response of 20 Tibetans (T) born and living in Kathmandu, Nepal (1300 m) was compared to that of 21 age- and sex-matched local lowlanders. The subjects carried out an incremental exercise protocol on a bicycle ergometer (30 watt steps every 4 min) until exhaustion. The kinetics of readjustment of VO2 measured as half time (t-on) upon a 90 watt constant load exercise was also determined. Breath-by-breath gas exchange, heart rate (HR) and blood lactate concentration ([La]) were measured at rest, at the end of each load and during recovery. The slope of the straight line relating VO2 to work load was 10.8 ml.watt-1 in both groups which corresponds to a mechanical efficiency of 0.26 (assuming a RQ of 0.89 and an energy equivalent of 20.9 kJ.L-1 O2). At submaximal loads T were characterized by higher VE (P < 0.05), VE.VO2(-1) (P < 0.01) and VCO2 levels (P < 0.001) than N. The found higher VE in T, resulting from a lower tidal volume coupled to a higher respiratory frequency, led to higher PETO2 (P < 0.001) and SaO2 (P < 0.001) at all work levels. Absolute VO2max in the two investigated groups were 1977 +/- 72 (T) and 2095 +/- 80 (N) ml.min-1 (NS). Specific (i.e. per kg body weight) VO2max were identical (37.0 +/- 1.1 [T] vs. 36.7 +/- 1.1 ml.kg-1.min-1 [N]). [La]max were 11.4 +/- 0.4 (T) vs. 12.3 +/- 0.4 (N) mM (NS). [La] accumulation in blood as a function of workload and its rate of disappearance during recovery were similar. t-on at 90 watt was 30.7 +/- 2.4 sec in T and 28.9 +/- 2.3 sec in N (NS). The corresponding average contracted O2 deficit were 971 ml for T and 994 ml for N (NS). In conclusion, Tibetans born at low altitude do not seem to differ from lowlanders with regard to their metabolic response whereas their ventilatory response to exercise is greater.

Basnyat B. 1993. Acute mountain sickness in local pilgrims to a high altitude lake (4154 m) in Nepal Journal of Wilderness Medicine, 4 (3), pp. 286-292. | Show Abstract | Read more

There is a significant collection of literature on acute mountain sickness (AMS) in foreign trekkers to Nepal. However, reports on altitude sickness among native Nepalis besides Sherpas is almost non-existent. This is a preliminary study sponsored by the Himalayan Rescue Association of AMS among pilgrims to a holy lake (Gosaikunda) at 4154 m in Nepal. The study was done using a standard AMS questionnaire form. It revealed that out of 5163 pilgrims who came to the lake, 229 (4.4%) developed AMS. The severity of the illness correlated with the rapidity of ascent, but there was no difference in severity between men and women. Five pilgrims who were ataxic were put in the hyperbaric bag. Subjective improvement was noted in all five cases. This study of AMS among non-Sherpa pilgrims suggests that various Nepali ethnic groups may be just as vulnerable to AMS as are tourists. © 1993, Wilderness Medical Society. All rights reserved.

Arjyal A, Basnyat B, Nhan HT, Koirala S, Giri A, Joshi N, Shakya M, Pathak KR, Mahat SP, Prajapati SP et al. 2016. Gatifloxacin versus ceftriaxone for uncomplicated enteric fever in Nepal: an open-label, two-centre, randomised controlled trial. Lancet Infect Dis, 16 (5), pp. 535-545. | Show Abstract | Read more

BACKGROUND: Because treatment with third-generation cephalosporins is associated with slow clinical improvement and high relapse burden for enteric fever, whereas the fluoroquinolone gatifloxacin is associated with rapid fever clearance and low relapse burden, we postulated that gatifloxacin would be superior to the cephalosporin ceftriaxone in treating enteric fever. METHODS: We did an open-label, randomised, controlled, superiority trial at two hospitals in the Kathmandu valley, Nepal. Eligible participants were children (aged 2-13 years) and adult (aged 14-45 years) with criteria for suspected enteric fever (body temperature ≥38·0°C for ≥4 days without a focus of infection). We randomly assigned eligible patients (1:1) without stratification to 7 days of either oral gatifloxacin (10 mg/kg per day) or intravenous ceftriaxone (60 mg/kg up to 2 g per day for patients aged 2-13 years, or 2 g per day for patients aged ≥14 years). The randomisation list was computer-generated using blocks of four and six. The primary outcome was a composite of treatment failure, defined as the occurrence of at least one of the following: fever clearance time of more than 7 days after treatment initiation; the need for rescue treatment on day 8; microbiological failure (ie, blood cultures positive for Salmonella enterica serotype Typhi, or Paratyphi A, B, or C) on day 8; or relapse or disease-related complications within 28 days of treatment initiation. We did the analyses in the modified intention-to-treat population, and subpopulations with either confirmed blood-culture positivity, or blood-culture negativity. The trial was powered to detect an increase of 20% in the risk of failure. This trial was registered at ClinicalTrials.gov, number NCT01421693, and is now closed. FINDINGS: Between Sept 18, 2011, and July 14, 2014, we screened 725 patients for eligibility. On July 14, 2014, the trial was stopped early by the data safety and monitoring board because S Typhi strains with high-level resistance to ciprofloxacin and gatifloxacin had emerged. At this point, 239 were in the modified intention-to-treat population (120 assigned to gatifloxacin, 119 to ceftriaxone). 18 (15%) patients who received gatifloxacin had treatment failure, compared with 19 (16%) who received ceftriaxone (hazard ratio [HR] 1·04 [95% CI 0·55-1·98]; p=0·91). In the culture-confirmed population, 16 (26%) of 62 patients who received gatifloxacin failed treatment, compared with four (7%) of 54 who received ceftriaxone (HR 0·24 [95% CI 0·08-0·73]; p=0·01). Treatment failure was associated with the emergence of S Typhi exhibiting resistance against fluoroquinolones, requiring the trial to be stopped. By contrast, in patients with a negative blood culture, only two (3%) of 58 who received gatifloxacin failed treatment versus 15 (23%) of 65 who received ceftriaxone (HR 7·50 [95% CI 1·71-32·80]; p=0·01). A similar number of non-serious adverse events occurred in each treatment group, and no serious events were reported. INTERPRETATION: Our results suggest that fluoroquinolones should no longer be used for treatment of enteric fever in Nepal. Additionally, under our study conditions, ceftriaxone was suboptimum in a high proportion of patients with culture-negative enteric fever. Since antimicrobials, specifically fluoroquinolones, are one of the only routinely used control measures for enteric fever, the assessment of novel diagnostics, new treatment options, and use of existing vaccines and development of next-generation vaccines are now a high priority. FUNDING: Wellcome Trust and Li Ka Shing Foundation.

Basnyat B. 2015. Tackle Nepal's typhoid problem now. Nature, 524 (7565), pp. 267. | Read more

Basnyat B, Dalton HR, Kamar N, Rein DB, Labrique A, Farrar J, Piot P, 21 signatories. 2015. Nepali earthquakes and the risk of an epidemic of hepatitis E. Lancet, 385 (9987), pp. 2572-2573. | Read more

Thompson CN, Blacksell SD, Paris DH, Arjyal A, Karkey A, Dongol S, Giri A, Dolecek C, Day N, Baker S et al. 2015. Undifferentiated febrile illness in Kathmandu, Nepal. Am J Trop Med Hyg, 92 (4), pp. 875-878. | Show Abstract | Read more

Undifferentiated febrile illnesses (UFIs) are common in low- and middle-income countries. We prospectively investigated the causes of UFIs in 627 patients presenting to a tertiary referral hospital in Kathmandu, Nepal. Patients with microbiologically confirmed enteric fever (218 of 627; 34.8%) randomized to gatifloxacin or ofloxacin treatment were previously reported. We randomly selected 125 of 627 (20%) of these UFI patients, consisting of 96 of 409 (23%) cases with sterile blood cultures and 29 of 218 (13%) cases with enteric fever, for additional diagnostic investigations. We found serological evidence of acute murine typhus in 21 of 125 (17%) patients, with 12 of 21 (57%) patients polymerase chain reaction (PCR)-positive for Rickettsia typhi. Three UFI cases were quantitative PCR-positive for Rickettsia spp., two UFI cases were seropositive for Hantavirus, and one UFI case was seropositive for Q fever. Fever clearance time (FCT) for rickettsial infection was 44.5 hours (interquartile range = 26-66 hours), and there was no difference in FCT between ofloxacin or gatifloxacin. Murine typhus represents an important cause of predominantly urban UFIs in Nepal, and fluoroquinolones seem to be an effective empirical treatment.

Basnyat B, Tabin C, Nutt C, Farmer P. 2015. Post-earthquake Nepal: the way forward. Lancet Glob Health, 3 (12), pp. e731-e732. | Read more

Basnyat B. 2014. High altitude pilgrimage medicine. High Alt Med Biol, 15 (4), pp. 434-439. | Show Abstract | Read more

Religious pilgrims have been going to high altitude pilgrimages long before trekkers and climbers sojourned in high altitude regions, but the medical literature about high altitude pilgrimage is sparse. Gosainkunda Lake (4300 m) near Kathmandu, Nepal, and Shri Amarnath Yatra (3800 m) in Sri Nagar, Kashmir, India, are the two sites in the Himalayas from where the majority of published reports of high altitude pilgrimage have originated. Almost all travels to high altitude pilgrimages are characterized by very rapid ascents by large congregations, leading to high rates of acute mountain sickness (AMS). In addition, epidemiological studies of pilgrims from Gosainkunda Lake show that some of the important risk factors for AMS in pilgrims are female sex and older age group. Studies based on the Shri Amarnath Yatra pilgrims show that coronary artery disease, complications of diabetes, and peptic ulcer disease are some of the common, important reasons for admission to hospital during the trip. In this review, the studies that have reported these and other relevant findings will be discussed and appropriate suggestions made to improve pilgrims' safety at high altitude.

Giri A, Arjyal A, Koirala S, Karkey A, Dongol S, Thapa SD, Shilpakar O, Shrestha R, van Tan L, Thi Thuy Chinh BN et al. 2013. Aetiologies of central nervous system infections in adults in Kathmandu, Nepal: a prospective hospital-based study. Sci Rep, 3 (1), pp. 2382. | Show Abstract | Read more

We conducted a prospective hospital based study from February 2009-April 2011 to identify the possible pathogens of central nervous system (CNS) infections in adults admitted to a tertiary referral hospital (Patan Hospital) in Kathmandu, Nepal. The pathogens of CNS infections were confirmed in cerebrospinal fluid (CSF) using molecular diagnostics, culture (bacteria) and serology. 87 patients were recruited for the study and the etiological diagnosis was established in 38% (n = 33). The bacterial pathogens identified were Neisseria meningitidis (n = 6); Streptococcus pneumoniae (n = 5) and Staphylococcus aureus (n = 2) in 13/87(14%). Enteroviruses were found in 12/87 (13%); Herpes Simplex virus (HSV) in 2/87(2%). IgM against Japanese encephalitis virus (JEV) was detected in the CSF of 11/73 (15%) tested samples. This is the first prospective molecular and serology based CSF analysis in adults with CNS infections in Kathmandu, Nepal. JEV and enteroviruses were the most commonly detected pathogens in this setting.

Basnyat B, Murdoch DR. 2003. High-altitude illness. Lancet, 361 (9373), pp. 1967-1974. | Show Abstract | Read more

High-altitude illness is the collective term for acute mountain sickness (AMS), high-altitude cerebral oedema (HACE), and high-altitude pulmonary oedema (HAPE). The pathophysiology of these syndromes is not completely understood, although studies have substantially contributed to the current understanding of several areas. These areas include the role and potential mechanisms of brain swelling in AMS and HACE, mechanisms accounting for exaggerated pulmonary hypertension in HAPE, and the role of inflammation and alveolar-fluid clearance in HAPE. Only limited information is available about the genetic basis of high-altitude illness, and no clear associations between gene polymorphisms and susceptibility have been discovered. Gradual ascent will always be the best strategy for preventing high-altitude illness, although chemoprophylaxis may be useful in some situations. Despite investigation of other agents, acetazolamide remains the preferred drug for preventing AMS. The next few years are likely to see many advances in the understanding of the causes and management of high-altitude illness.

Basnyat B, Graham L, Lee SD, Lim Y. 2001. A language barrier, abdominal pain, and double vision. Lancet, 357 (9273), pp. 2022. | Read more

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