Search results
Found 41409 matches for
New research from the Big Data Institute, in collaboration with the George Institute has revealed that the health implications of obesity extend much further than diabetes and heart disease, increasing the risk of death from diseases of the kidneys, lungs and liver.
Enhanced data quality to improve malaria surveillance in Papua, Indonesia
Abstract Background Papua has a high burden of malaria, with an annual parasite incidence 300 times the national average. A key component of malaria elimination strategies is robust surveillance which is essential for monitoring trends in case numbers, guiding public health interventions, and prioritizing resource allocation. This study aimed to enhance malaria surveillance in Central Papua, Indonesia, by improving data collection, record-keeping, and treatment practices. Methods The study was conducted at five public clinics in Central Papua province, Indonesia, as part of a wider health systems strengthening programme to promote safer and more effective anti-malarial treatment (The SHEPPI Study). Clinical and laboratory details of patients with malaria and their treatment were documented in clinic registers which were digitalized into an electronic database. Automated reports were generated each month and used to provide regular feedback to clinic staff. Continuous Quality Improvement (CQI) workshops were conducted with clinic staff using the Plan-Do-Study-Act approach to address challenges and drive sustained improvements. Results Between January 2019 and December 2023, a total of 314,561 patients were tested for malaria, of whom 41.9% (131,948) had peripheral parasitaemia detected. The first round of Continuous Quality Improvement (CQI) workshops were held in May 2019 and improved data quality significantly, increasing data completeness from 46.3% (4540/9802) in the initial period (Jan–May 2019) to 71.5% (9053/12,665) after the first CQI (Jun–Oct 2019), p < 0.001. The second CQI round reduced DHP prescribing errors from 17.1% (1111/6489) in the initial period to 5.7% (607/10,669) after the second CQI (Sep 2019–Jan 2020) and PQ prescribing errors from 17.4% (552/3175) to 3.4% (160/4659) over the same time interval, p < 001. In total, 347 patients were prescribed fewer than the recommended number of PQ tablets during the initial period, 89 (25.6%) of whom were erroneously given only a single dose. Over the 4 year study period, a total of 11 workshops were conducted, driving continuous improvements in data quality and prescribing practices. Conclusion One or two rounds of CQI, supported by regular follow-up, can enhance the quality of malariometric surveillance, however interventions needed to be tailored to address specific needs of participating clinics. Improvements in data quality and prescribing practices have potential to contribute to better malaria management, improved clinical outcomes, and strengthened trust in healthcare providers.
FocaL mass drug Administration for Plasmodium vivax Malaria Elimination (FLAME): study protocol for an open-label cluster randomized controlled trial in Peru.
BACKGROUND: Outside of sub-Saharan Africa, Plasmodium vivax has become the dominant species of malaria. Focal mass drug administration (fMDA) is a potential strategy to support elimination efforts, but controlled studies are lacking. METHODS: The FocaL mass drug Administration for Plasmodium vivax Malaria Elimination (FLAME) study is a 3-year cluster randomized controlled trial to determine the impact and safety of fMDA to reduce P. vivax transmission. The study will be conducted in Loreto, Peru, where standard interventions have reduced P. vivax cases, but transmission persists due to a high proportion of subclinical infections. Thirty low transmission communities (API < 250 cases/1000 population) will be randomized 1:1 to fMDA versus control using a restricted randomization. All communities will receive Peruvian national standard malaria control measures. In the intervention arm, high-risk individuals (living within 200 meters of a P. vivax case reported in the prior two years) without contraindication to study medications, including G6PD deficiency, will receive three cycles of fMDA over a two-year period. Each cycle will include two rounds of directly observed therapy delivered 2 months apart. The fMDA regimen will include 25mg/kg chloroquine (CQ) plus a single 300mg dose of tafenoquine (TQ) for individuals age ≥16 years, and 25mg/kg of CQ plus 7 days of 0.5mg/kg/day of primaquine (PQ) if younger. The primary outcome is the cumulative incidence of symptomatic P. vivax malaria. The sample size provides 80% power to detect at least a 68% relative reduction in cumulative P. vivax incidence, based on alpha of 0.05 and a coefficient of variation (k) of 0.87. Secondary outcomes include safety, cost-effectiveness, and infection prevalence and seroprevalence which will be assessed in annual cross-sectional surveys. Safety will be assessed in passive and active pharmacovigilance, including post-treatment screening for G6PD-associated hemolysis by assessing for anemia and hematuria in a sample. DISCUSSION: The trial will generate evidence regarding fMDA for P. vivax and inform malaria elimination efforts in Peru and similarly endemic settings. Findings will be in peer-reviewed publications and through stakeholder meetings in Peruvian and international policy and research forums. TRIAL REGISTRATION: Clinicaltrials.gov NCT05690841. This trial was registered on 09 January 2023.
Does mass chloroquine treatment have any role in the elimination of Plasmodium vivax ?
Countries in the Greater Mekong sub-region (GMS) have been encouraged to deploy mass chloroquine treatments given monthly for four months to reduce the burden of vivax malaria. This paper summarizes briefly current knowledge on Plasmodium vivax epidemiology, the biology of vivax relapse and previous experience using dihydroartemisinin-piperaquine mass treatments in the GMS to show why this approach would be extremely cost-ineffective. Around 800 full treatment courses in 200 people would be needed to prevent one symptomatic case. Mass chloroquine treatment will contribute little or nothing to the elimination of vivax malaria in this area.
Using Abattoir-Based Surveillance to Establish Foot-and-Mouth Disease Non-Structural Protein Seropositivity in Cattle and Pigs in Cambodia
Foot-and-mouth disease (FMD) is a contagious transboundary animal disease that causes economic loss and obstacles to international trade. Frequent FMD outbreaks in Cambodia negatively impact farmers’ and smallholders’ incomes. This study aimed to estimate the seroprevalence of FMD Non-Structural Protein (NSP) antibodies, which are an indicator of FMD antibodies raised during a natural infection rather than those produced following vaccination, that were detected using a commercial enzyme-linked immunosorbent assay (ELISA). Sample collection from cattle and pigs (n = 2238) was performed at ten abattoirs in seven provinces between October 2019 and December 2020. Overall seroprevalence in cattle and pigs was 43.2% (363/839; 95% CI 39.8–46.7), and 0.6% (9/1399; 95% CI 0.2–1.2), respectively. Only the cattle dataset was included in the risk factor analysis, as the prevalence of sero-reactors was too low in the pig dataset to be analyzed. Significant risk factors identified by the logistic regression model included the province of origin (p = 0.02), body condition score (BCS) (p = 0.0002) and sex (p = 0.0007). Odds ratios of the significant risk factors were 7.05 (95% CI 1.43–34.67; p = 0.02) for cattle that originated from Kampong Thom, 1.41 (95% CI 1.05–1.89; p = 0.02) for female cattle, and 3.28 (95% CI 1.06–10.12; p = 0.04) for animals with BCS of 3/5. The study revealed that the seroprevalence of FMD NSP in cattle presented at the abattoirs was high, while the FMD NSP seroprevalence in abattoir pigs was very low. Further investigation is required to map the disease distribution in Cambodia, especially the serotypes and strains causing clinical disease. These findings call for the extension of work on effective disease prevention measures.
Engineering TCR-controlled fuzzy logic into CAR T cells enhances therapeutic specificity.
Chimeric antigen receptor (CAR) T cell immunotherapy represents a breakthrough in the treatment of hematological malignancies, but poor specificity has limited its applicability to solid tumors. By contrast, natural T cells harboring T cell receptors (TCRs) can discriminate between neoantigen-expressing cancer cells and self-antigen-expressing healthy tissues but have limited potency against tumors. We used a high-throughput platform to systematically evaluate the impact of co-expressing a TCR and CAR on the same CAR T cell. While strong TCR-antigen interactions enhanced CAR activation, weak TCR-antigen interactions actively antagonized their activation. Mathematical modeling captured this TCR-CAR crosstalk in CAR T cells, allowing us to engineer dual TCR/CAR T cells targeting neoantigens (HHATL8F/p53R175H) and human epithelial growth factor receptor 2 (HER2) ligands, respectively. These T cells exhibited superior anti-cancer activity and minimal toxicity against healthy tissue compared with conventional CAR T cells in a humanized solid tumor mouse model. Harnessing pre-existing inhibitory crosstalk between receptors, therefore, paves the way for the design of more precise cancer immunotherapies.
Correlation between large rearrangements and patient phenotypes in NF1 deletion syndrome: an update and review
AbstractAbout 5–10% of neurofibromatosis type 1 (NF1) patients exhibit large genomic germline deletions that remove the NF1 gene and its flanking regions. The most frequent NF1 large deletion is 1.4 Mb, resulting from homologous recombination between two low copy repeats. This “type-1” deletion is associated with a severe clinical phenotype in NF1 patients, with several phenotypic manifestations including learning disability, a much earlier development of cutaneous neurofibromas, an increased tumour risk, and cardiovascular malformations. NF1 adjacent co-deleted genes could act as modifier loci for the specific clinical manifestations observed in deleted NF1 patients. Furthermore, other genetic modifiers (such as CNVs) not located at the NF1 locus could also modulate the phenotype observed in patients with large deletions. In this study, we analysed 22 NF1 deletion patients by genome-wide array-CGH with the aim (1) to correlate deletion length to observed phenotypic features and their severity in NF1 deletion syndrome, and (2) to identify whether the deletion phenotype could also be modulated by copy number variations elsewhere in the genome. We then review the role of co-deleted genes in the 1.4 Mb interval of type-1 deletions, and their possible implication in the main clinical features observed in this high-risk group of NF1 patients.
International review of blood donation screening for anti‐HBc and occult hepatitis B virus infection
AbstractBackgroundHepatitis B core antibody (anti‐HBc) screening has been implemented in many blood establishments to help prevent transmission of hepatitis B virus (HBV), including from donors with occult HBV infection (OBI). We review HBV screening algorithms across blood establishments globally and their potential effectiveness in reducing transmission risk.Materials and MethodsA questionnaire on HBV screening and follow‐up strategies was distributed to members of the International Society of Blood Transfusion working party on transfusion‐transmitted infectious diseases. Screening data from 2022 were assimilated and analyzed.ResultsA total of 30 unique responses were received from 25 countries. Sixteen respondents screened all donations for anti‐HBc, with 14 also screening all donations for HBV DNA. Anti‐HBc prevalence was 0.42% in all blood donors and 1.19% in new donors in low‐endemic countries; however, only 44% of respondents performed additional anti‐HBc testing to exclude false reactivity. 0.68% of anti‐HBc positive, HBsAg‐negative donors had detectable HBV DNA. Ten respondents did universal HBV DNA screening without anti‐HBc, whereas four respondents did not screen for either. Deferral strategies for anti‐HBc positive donors were highly variable. One transfusion‐transmission from an anti‐HBc negative donor was reported.DiscussionAnti‐HBc screening identifies donors with OBI but also results in the unnecessary deferral of a significant number of donors with resolved HBV infection and donors with false‐reactive anti‐HBc results. Whilst confirmation of anti‐HBc results could be improved to reduce donor deferral, transmission risks associated with anti‐HBc negative OBI donors must be considered. In high‐endemic areas, highly sensitive HBV DNA testing is required to identify infectious donors.
Pneumococcal serotype epidemiology
This chapter summarizes the relative prevalences of the most common serotypes prior to and following the introduction of the heptavalent pneumococcal capsular polysaccharide vaccine (PCV-7). It provides thoughts about the selection of serotypes for future-generation conjugate vaccines. A remarkable feature of the global epidemiology of pneumococcal carriage is the consistency of the dominant carriage serotypes in very different environments and at different times. Invasive disease potential, or invasiveness, is a measure of the ability of pneumococci to progress from nasopharyngeal carriage to invasive disease in humans. It differs from virulence in that the latter is often used to describe the ability of a pathogen to cause disease in laboratory animals. The 11-valent formulation prevented vaccine-related otitis media and was also shown to elicit antibodies with functional immunogenicity (opsonophagocytic activity) against 6A comparable to that seen with PCV-7. The incidence of invasive pneumococcal disease (IPD) due to vaccine serotypes has decreased substantially since the introduction of PCV-7 in the United States, in vaccinated children as well as all other age groups, indicating that pneumococcal transmission was interrupted as a result of the reduction in carriage in the vaccinated pediatric population. For mucosal disease, otitis media and nonbacteremic pneumonia, it is less clear which serotypes it would be most valuable to add since there appear to be less clearcut differences in invasiveness among serotypes. The only certain way of preventing mucosal disease is to sterilize the nasopharynx with respect to pneumococci.
SARS-CoV-2 infection enhancement by amphotericin B: implications for disease management.
Severe coronavirus disease 2019 (COVID-19) patients who require hospitalization are at high risk of invasive pulmonary mucormycosis. Amphotericin B (AmB), which is the first-line therapy for invasive pulmonary mucormycosis, has been shown to promote or inhibit replication of a spectrum of viruses. In this study, we first predicted that AmB and nystatin had strong interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) proteins using in silico screening, indicative of drugs with potential therapeutic activity against this virus. Subsequently, we investigated the impact of AmB, nystatin, natamycin, fluconazole, and caspofungin on SARS-CoV-2 infection and replication in vitro. Results showed that AmB and nystatin actually increased SARS-CoV-2 replication in Vero E6, Calu-3, and Huh7 cells. At optimal concentrations, AmB and nystatin increase SARS-CoV-2 replication by up to 100- and 10-fold in Vero E6 and Calu-3 cells, respectively. The other antifungals tested had no impact on SARS-CoV-2 infection in vitro. Drug kinetic studies indicate that AmB enhances SARS-CoV-2 infection by promoting viral entry into cells. Additionally, knockdown of genes encoding for interferon-induced transmembrane (IFITM) proteins 1, 2, and 3 suggests AmB enhances SARS-CoV-2 cell entry by overcoming the antiviral effect of the IFITM3 protein. This study further elucidates the role of IFITM3 in viral entry and highlights the potential dangers of treating COVID-19 patients, with invasive pulmonary mucormycosis, using AmB.IMPORTANCEAmB and nystatin are common treatments for fungal infections but were predicted to strongly interact with SARS-CoV-2 proteins, indicating their potential modulation or inhibition against the virus. However, our tests revealed that these antifungals, in fact, enhance SARS-CoV-2 infection by facilitating viral entry into cells. The magnitude of enhancement could be up to 10- or 100-fold, depending on cell lines used. These findings indicate that AmB and nystatin have the potential to enhance disease when given to patients infected with SARS-CoV-2 and therefore should not be used for treatment of fungal infections in active COVID-19 cases.
Epithelial GREMLIN1 disrupts intestinal epithelial-mesenchymal crosstalk to induce a wnt-dependent ectopic stem cell niche through stromal remodelling
Abstract In homeostasis, counterbalanced morphogen signalling gradients along the vertical axis of the intestinal mucosa regulate the fate and function of epithelial and stromal cell compartments. Here, we use a disease-positioned mouse and human tissue to explore the consequences of pathological BMP signalling dysregulation on epithelial-mesenchymal interaction. Aberrant pan-epithelial expression of the secreted BMP antagonist Grem1 results in ectopic crypt formation, with lineage tracing demonstrating the presence of Lgr5(−) stem/progenitor cells. Isolated epithelial cell Grem1 expression has no effect on individual cell fate, indicating an intercompartmental impact of mucosal-wide BMP antagonism. Treatment with an anti-Grem1 antibody abrogates the polyposis phenotype, and triangulation of specific pathway inhibitors defines a pathological sequence of events, with Wnt-ligand-dependent ectopic stem cell niches forming through stromal remodelling following BMP disruption. These data support an emerging co-evolutionary model of intestinal cell compartmentalisation based on bidirectional regulation of epithelial-mesenchymal cell fate and function.
The limitations of mobile phone data for measuring movement patterns of populations at risk of malaria.
BACKGROUND: As global mobile phone adoption increases, mobile phone data has been increasingly used to measure movement patterns of populations at risk of malaria. However, the representativeness of mobile phone data for populations at risk of malaria has not been assessed. This study aimed to assess this representativeness using prospectively collected data on mobile phone ownership and use from malaria patients in Lao PDR. METHODS: A prospective observational study was conducted from 2017 to 2021. 6320 patients with confirmed malaria in 107 health facilities in the five southernmost provinces of Lao PDR were surveyed regarding their demographics, mobile phone ownership and use. Data on the demographics of mobile phone owners and users in the general population of Lao PDR were obtained from the 2017 Lao Social Indicator Survey II, which was a nationally representative survey sample. Descriptive analysis was performed, and logistic regression with weights on aggregate data was used to compare the demographic distribution of mobile phone ownership and use in malaria patients with that in the general population. RESULTS: Most patients with malaria (76%) did not own or use a mobile phone. From 2017 to 2021, mobile phone usage in the general population consistently ranged between 53 and 67%, whereas among malaria patients, usage remained significantly lower, fluctuating between 20 and 28%. At the district level, log malaria incidence rate (API) was weakly negatively correlated with the proportion of mobile owners (R2 = 0.3, p = 0.005). Mobile phone ownership and usage among malaria patients were significantly lower than in the general population (p-value