Prof Ben Cooper

Research Area: Bioinformatics & Stats (inc. Modelling and Computational Biology)
Technology Exchange: Bioinformatics, Computational biology and Medical statistics
Scientific Themes: Tropical Medicine & Global Health and Immunology & Infectious Disease

Ben Cooper holds an MRC senior non-clinical research fellowship and is based at the Mahidol-Oxford Tropical Medicine Research Unit in Bangkok.  

His work uses mathematical modelling and statistical techniques to help understand infectious disease dynamics and evaluate potential control measures.  This involves developing mathematical models to help evaluate the likely impact and cost-effectiveness of control measures,  developing and applying new statistical approaches based on mechanistic  models for the analysis of longitudinal infectious disease data (increasingly making use of whole genome sequence data), and  designing and analysing epidemiological studies.  The major focus of this work is on antibiotic-resistant bacteria in resource-limited hospital settings.

Additional projects include within-host dynamics of Plasmodium vivax, ecological interactions of the nasopharyngeal flora, cost-effectiveness of seasonal influenza vaccination in Thailand, and dynamics and control of Hepatitis E infections in refugee camps.

 

Name Department Institution Country
Dr Paul Turner Tropical Medicine University of Oxford United Kingdom
Prof Lisa J White Tropical Medicine University of Oxford United Kingdom
Dr Direk Limmathurotsakul Tropical Medicine University of Oxford United Kingdom
Dr Sharon J Peacock Tropical Medicine University of Oxford United Kingdom
Dr Jonathan D Edgeworth Guy’s and St Thomas’ NHS Foundation Trust United Kingdom
Prof Marc Bonten University Medical Center Utrecht Netherlands
Prof Angela McLean Department of Zoology University of Oxford United Kingdom
Dr Craig MacLean Department of Zoology University of Oxford United Kingdom
Prof Nicholoas Graves QUT Australia
Dr Aronrag C Meeyai Mahidol University Thailand

Vlek AL, Cooper BS, Kypraios T, Cox A, Edgeworth JD, Auguet OT. 2013. Clustering of antimicrobial resistance outbreaks across bacterial species in the intensive care unit. Clin Infect Dis, 57 (1), pp. 65-76. Read abstract | Read more

There are frequent reports of intensive care unit (ICU) outbreaks due to transmission of particular antibiotic-resistant bacteria. Less is known about the burden of outbreaks of resistance due to horizontal transfer of mobile genetic elements between species. Moreover, the potential of existing statistical software as a preliminary means for detecting such events has never been assessed. This study uses a software package to determine the burden of species and resistance outbreaks in 2 adjacent ICUs and to look for evidence of clustering of resistance outbreaks consistent with interspecies transmission of resistance elements. Hide abstract

Worby CJ, Jeyaratnam D, Robotham JV, Kypraios T, O'Neill PD, De Angelis D, French G, Cooper BS. 2013. Estimating the effectiveness of isolation and decolonization measures in reducing transmission of methicillin-resistant Staphylococcus aureus in hospital general wards. Am J Epidemiol, 177 (11), pp. 1306-1313. Read abstract | Read more

Infection control for hospital pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) often takes the form of a package of interventions, including the use of patient isolation and decolonization treatment. Such interventions, though widely used, have generated controversy because of their significant resource implications and the lack of robust evidence with regard to their effectiveness at reducing transmission. The aim of this study was to estimate the effectiveness of isolation and decolonization measures in reducing MRSA transmission in hospital general wards. Prospectively collected MRSA surveillance data from 10 general wards at Guy's and St. Thomas' hospitals, London, United Kingdom, in 2006-2007 were used, comprising 14,035 patient episodes. Data were analyzed with a Markov chain Monte Carlo algorithm to model transmission dynamics. The combined effect of isolation and decolonization was estimated to reduce transmission by 64% (95% confidence interval: 37, 79). Undetected MRSA-positive patients were estimated to be the source of 75% (95% confidence interval: 67, 86) of total transmission events. Isolation measures combined with decolonization treatment were strongly associated with a reduction in MRSA transmission in hospital general wards. These findings provide support for active methods of MRSA control, but further research is needed to determine the relative importance of isolation and decolonization in preventing transmission. Hide abstract

Meeyai A, Cooper B, Coker R, Pan W, Akarasewie P, Iamsirithaworn S. 2012. The effective reproduction number of Pandemic 2009 H1N1 influenza in Thailand: a spatiotemporal analysis INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 16 pp. E353-E354. | Read more

Cooper BS, Kypraios T, Batra R, Wyncoll D, Tosas O, Edgeworth JD. 2012. Quantifying type-specific reproduction numbers for nosocomial pathogens: evidence for heightened transmission of an Asian sequence type 239 MRSA clone. PLoS Comput Biol, 8 (4), pp. e1002454. Read abstract | Read more

An important determinant of a pathogen's success is the rate at which it is transmitted from infected to susceptible hosts. Although there are anecdotal reports that methicillin-resistant Staphylococcus aureus (MRSA) clones vary in their transmissibility in hospital settings, attempts to quantify such variation are lacking for common subtypes, as are methods for addressing this question using routinely-collected MRSA screening data in endemic settings. Here we present a method to quantify the time-varying transmissibility of different subtypes of common bacterial nosocomial pathogens using routine surveillance data. The method adapts approaches for estimating reproduction numbers based on the probabilistic reconstruction of epidemic trees, but uses relative hazards rather than serial intervals to assign probabilities to different sources for observed transmission events. The method is applied to data collected as part of a retrospective observational study of a concurrent MRSA outbreak in the United Kingdom with dominant endemic MRSA clones (ST22 and ST36) and an Asian ST239 MRSA strain (ST239-TW) in two linked adult intensive care units, and compared with an approach based on a fully parametric transmission model. The results provide support for the hypothesis that the clones responded differently to an infection control measure based on the use of topical antiseptics, which was more effective at reducing transmission of endemic clones. They also suggest that in one of the two ICUs patients colonized or infected with the ST239-TW MRSA clone had consistently higher risks of transmitting MRSA to patients free of MRSA. These findings represent some of the first quantitative evidence of enhanced transmissibility of a pandemic MRSA lineage, and highlight the potential value of tailoring hospital infection control measures to specific pathogen subtypes. Hide abstract

Birrell PJ, Ketsetzis G, Gay NJ, Cooper BS, Presanis AM, Harris RJ, Charlett A, Zhang XS, White PJ, Pebody RG, De Angelis D. 2011. Bayesian modeling to unmask and predict influenza A/H1N1pdm dynamics in London. Proc Natl Acad Sci U S A, 108 (45), pp. 18238-18243. Read abstract | Read more

The tracking and projection of emerging epidemics is hindered by the disconnect between apparent epidemic dynamics, discernible from noisy and incomplete surveillance data, and the underlying, imperfectly observed, system. Behavior changes compound this, altering both true dynamics and reporting patterns, particularly for diseases with nonspecific symptoms, such as influenza. We disentangle these effects to unravel the hidden dynamics of the 2009 influenza A/H1N1pdm pandemic in London, where surveillance suggests an unusual dominant peak in the summer. We embed an age-structured model into a bayesian synthesis of multiple evidence sources to reveal substantial changes in contact patterns and health-seeking behavior throughout the epidemic, uncovering two similar infection waves, despite large differences in the reported levels of disease. We show how this approach, which allows for real-time learning about model parameters as the epidemic progresses, is also able to provide a sequence of nested projections that are capable of accurately reflecting the epidemic evolution. Hide abstract

Robotham JV, Graves N, Cookson BD, Barnett AG, Wilson JA, Edgeworth JD, Batra R, Cuthbertson BH, Cooper BS. 2011. Screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus in intensive care units: cost effectiveness evaluation BRITISH MEDICAL JOURNAL, 343 (oct05 3), pp. d5694-d5694. Read abstract | Read more

To assess the cost effectiveness of screening, isolation, and decolonisation strategies in the control of meticillin resistant Staphylococcus aureus (MRSA) in intensive care units.Economic evaluation based on a dynamic transmission model.England and Wales. Population Theoretical population of patients on an intensive care unit.Infections, deaths, costs, quality adjusted life years (QALYs), incremental cost effectiveness ratios for alternative strategies, and net monetary benefits.All decolonisation strategies improved health outcomes and reduced costs. Although universal decolonisation (regardless of MRSA status) was the most cost effective in the short term, strategies using screening to target MRSA carriers may be preferred owing to the reduced risk of selecting for resistance. Among such targeted strategies, universal admission and weekly screening with polymerase chain reaction coupled with decolonisation using nasal mupirocin was the most cost effective. This finding was robust to the size of intensive care units, prevalence of MRSA on admission, proportion of patients classified as high risk, and precise value of willingness to pay for health benefits. All strategies using isolation but not decolonisation improved health outcomes but costs were increased. When the prevalence of MRSA on admission to the intensive care unit was 5% and the willingness to pay per QALY gained was between £20,000 (€23,000; $32,000) and £30,000, the best such strategy was to isolate only those patients at high risk of carrying MRSA (either pre-emptively or after identification by admission and weekly screening for MRSA using chromogenic agar). Universal admission and weekly screening using polymerase chain reaction based detection of MRSA coupled with isolation was unlikely to be cost effective unless prevalence was high (10% of patients colonised with MRSA on admission).MRSA control strategies that use decolonisation are likely to be cost saving in an intensive care unit setting provided resistance is lacking, and combining universal screening using polymerase chain reaction with decolonisation is likely to represent good value for money if untargeted decolonisation is considered unacceptable. In intensive care units where decolonisation is not implemented, evidence is insufficient to support universal screening for MRSA outside high prevalence settings. Hide abstract

Batra R, Cooper BS, Whiteley C, Patel AK, Wyncoll D, Edgeworth JD. 2010. Efficacy and limitation of a chlorhexidine-based decolonization strategy in preventing transmission of methicillin-resistant Staphylococcus aureus in an intensive care unit. Clin Infect Dis, 50 (2), pp. 210-217. Read abstract | Read more

Surface-active antiseptics, such as chlorhexidine, are increasingly being used as part of intervention programs to prevent methicillin-resistant Staphylococcus aureus (MRSA) transmission, despite limited evidence and potential for resistance. We report on the effect of an antiseptic protocol on acquisition of both endemic MRSA and an outbreak strain of MRSA sequence type 239 (designated TW). Hide abstract

Kypraios T, O'Neill PD, Huang SS, Rifas-Shiman SL, Cooper BS. 2010. Assessing the role of undetected colonization and isolation precautions in reducing methicillin-resistant Staphylococcus aureus transmission in intensive care units. BMC Infect Dis, 10 (1), pp. 29. Read abstract | Read more

Screening and isolation are central components of hospital methicillin-resistant Staphylococcus aureus (MRSA) control policies. Their prevention of patient-to-patient spread depends on minimizing undetected and unisolated MRSA-positive patient days. Estimating these MRSA-positive patient days and the reduction in transmission due to isolation presents a major methodological challenge, but is essential for assessing both the value of existing control policies and the potential benefit of new rapid MRSA detection technologies. Recent methodological developments have made it possible to estimate these quantities using routine surveillance data. Hide abstract

de Smet AMGA, Kluytmans JAJW, Cooper BS, Mascini EM, Benus RFJ, van der Werf TS, van der Hoeven JG, Pickkers P et al. 2009. Decontamination of the Digestive Tract and Oropharynx in ICU Patients New England Journal of Medicine, 360 (1), pp. 20-31. Read abstract | Read more

Selective digestive tract decontamination (SDD) and selective oropharyngeal decontamination (SOD) are infection-prevention measures used in the treatment of some patients in intensive care, but reported effects on patient outcome are conflicting.We evaluated the effectiveness of SDD and SOD in a crossover study using cluster randomization in 13 intensive care units (ICUs), all in The Netherlands. Patients with an expected duration of intubation of more than 48 hours or an expected ICU stay of more than 72 hours were eligible. In each ICU, three regimens (SDD, SOD, and standard care) were applied in random order over the course of 6 months. Mortality at day 28 was the primary end point. SDD consisted of 4 days of intravenous cefotaxime and topical application of tobramycin, colistin, and amphotericin B in the oropharynx and stomach. SOD consisted of oropharyngeal application only of the same antibiotics. Monthly point-prevalence studies were performed to analyze antibiotic resistance.A total of 5939 patients were enrolled in the study, with 1990 assigned to standard care, 1904 to SOD, and 2045 to SDD; crude mortality in the groups at day 28 was 27.5%, 26.6%, and 26.9%, respectively. In a random-effects logistic-regression model with age, sex, Acute Physiology and Chronic Health Evaluation (APACHE II) score, intubation status, and medical specialty used as covariates, odds ratios for death at day 28 in the SOD and SDD groups, as compared with the standard-care group, were 0.86 (95% confidence interval [CI], 0.74 to 0.99) and 0.83 (95% CI, 0.72 to 0.97), respectively.In an ICU population in which the mortality rate associated with standard care was 27.5% at day 28, the rate was reduced by an estimated 3.5 percentage points with SDD and by 2.9 percentage points with SOD. (Controlled Clinical Trials number, ISRCTN35176830.) Hide abstract

Cooper BS, Medley GF, Bradley SJ, Scott GM. 2008. An augmented data method for the analysis of nosocomial infection data. Am J Epidemiol, 168 (5), pp. 548-557. Read abstract | Read more

The analysis of nosocomial infection data for communicable pathogens is complicated by two facts. First, typical pathogens more commonly cause asymptomatic colonization than overt disease, so transmission can be only imperfectly observed through a sequence of surveillance swabs, which themselves have imperfect sensitivity. Any given set of swab results can therefore be consistent with many different patterns of transmission. Second, data are often highly dependent: the colonization status of one patient affects the risk for others, and, in some wards, repeated admissions are common. Here, the authors present a method for analyzing typical nosocomial infection data consisting of results from arbitrarily timed screening swabs that overcomes these problems and enables simultaneous estimation of transmission and importation parameters, duration of colonization, swab sensitivity, and ward- and patient-level covariates. The method accounts for dependencies by using a mechanistic stochastic transmission model, and it allows for uncertainty in the data by imputing the imperfectly observed colonization status of patients over repeated admissions. The approach uses a Markov chain Monte Carlo algorithm, allowing inference within a Bayesian framework. The method is applied to illustrative data from an interrupted time-series study of vancomycin-resistant enterococci transmission in a hematology ward. Hide abstract

White RG, Ben SC, Kedhar A, Orroth KK, Biraro S, Baggaley RF, Whitworth J, Korenromp EL, Ghani A, Boily MC, Hayes RJ. 2007. Quantifying HIV-1 transmission due to contaminated injections. Proc Natl Acad Sci U S A, 104 (23), pp. 9794-9799. Read abstract | Read more

Assessments of the importance of different routes of HIV-1 (HIV) transmission are vital for prioritization of control efforts. Lack of consistent direct data and large uncertainty in the risk of HIV transmission from HIV-contaminated injections has made quantifying the proportion of transmission caused by contaminated injections in sub-Saharan Africa difficult and unavoidably subjective. Depending on the risk assumed, estimates have ranged from 2.5% to 30% or more. We present a method based on an age-structured transmission model that allows the relative contribution of HIV-contaminated injections, and other routes of HIV transmission, to be robustly estimated, both fully quantifying and substantially reducing the associated uncertainty. To do this, we adopt a Bayesian perspective, and show how prior beliefs regarding the safety of injections and the proportion of HIV incidence due to contaminated injections should, in many cases, be substantially modified in light of age-stratified incidence and injection data, resulting in improved (posterior) estimates. Applying the method to data from rural southwest Uganda, we show that the highest estimates of the proportion of incidence due to injections are reduced from 15.5% (95% credible interval) (0.7%, 44.9%) to 5.2% (0.5%, 17.0%) if random mixing is assumed, and from 14.6% (0.7%, 42.5%) to 11.8% (1.2%, 32.5%) under assortative mixing. Lower, and more widely accepted, estimates remain largely unchanged, between 1% and 3% (0.1-6.3%). Although important uncertainty remains, our analysis shows that in rural Uganda, contaminated injections are unlikely to account for a large proportion of HIV incidence. This result is likely to be generalizable to many other populations in sub-Saharan Africa. Hide abstract

Cooper B. 2006. Poxy models and rash decisions. Proc Natl Acad Sci U S A, 103 (33), pp. 12221-12222. | Read more

Cooper BS, Pitman RJ, Edmunds WJ, Gay NJ. 2006. Delaying the international spread of pandemic influenza. PLoS Med, 3 (6), pp. e212. Read abstract | Read more

The recent emergence of hypervirulent subtypes of avian influenza has underlined the potentially devastating effects of pandemic influenza. Were such a virus to acquire the ability to spread efficiently between humans, control would almost certainly be hampered by limited vaccine supplies unless global spread could be substantially delayed. Moreover, the large increases that have occurred in international air travel might be expected to lead to more rapid global dissemination than in previous pandemics. Hide abstract

Cooper BS, Medley GF, Stone SP, Kibbler CC, Cookson BD, Roberts JA, Duckworth G, Lai R, Ebrahim S. 2004. Methicillin-resistant Staphylococcus aureus in hospitals and the community: stealth dynamics and control catastrophes. Proc Natl Acad Sci U S A, 101 (27), pp. 10223-10228. Read abstract | Read more

Methicillin-resistant Staphylococcus aureus (MRSA) represents a serious threat to the health of hospitalized patients. Attempts to reduce the spread of MRSA have largely depended on hospital hygiene and patient isolation. These measures have met with mixed success: although some countries have almost eliminated MRSA or remained largely free of the organism, others have seen substantial increases despite rigorous control policies. We use a mathematical model to show how these increases can be explained by considering both hospital and community reservoirs of MRSA colonization. We show how the timing of the intervention, the level of resource provision, and chance combine to determine whether control measures succeed or fail. We find that even control measures able to repeatedly prevent sustained outbreaks in the short-term can result in long-term control failure resulting from gradual increases in the community reservoir. If resources do not scale with MRSA prevalence, isolation policies can fail "catastrophically." Hide abstract

Cooper B, Lipsitch M. 2004. The analysis of hospital infection data using hidden Markov models. Biostatistics, 5 (2), pp. 223-237. Read abstract | Read more

Surveillance data for communicable nosocomial pathogens usually consist of short time series of low-numbered counts of infected patients. These often show overdispersion and autocorrelation. To date, almost all analyses of such data have ignored the communicable nature of the organisms and have used methods appropriate only for independent outcomes. Inferences that depend on such analyses cannot be considered reliable when patient-to-patient transmission is important. We propose a new method for analysing these data based on a mechanistic model of the epidemic process. Since important nosocomial pathogens are often carried asymptomatically with overt infection developing in only a proportion of patients, the epidemic process is usually only partially observed by routine surveillance data. We therefore develop a 'structured' hidden Markov model where the underlying Markov chain is generated by a simple transmission model. We apply both structured and standard (unstructured) hidden Markov models to time series for three important pathogens. We find that both methods can offer marked improvements over currently used approaches when nosocomial spread is important. Compared to the standard hidden Markov model, the new approach is more parsimonious, is more biologically plausible, and allows key epidemiological parameters to be estimated. Hide abstract

Cooper BS, Stone SP, Kibbler CC, Cookson BD, Roberts JA, Medley GF, Duckworth G, Lai R, Ebrahim S. 2004. Isolation measures in the hospital management of methicillin resistant Staphylococcus aureus (MRSA): systematic review of the literature. BMJ, 329 (7465), pp. 533. Read abstract | Read more

To evaluate the evidence for the effectiveness of isolation measures in reducing the incidence of methicillin resistant Staphylococcus aureus (MRSA) colonisation and infection in hospital inpatients. Hide abstract

Lipsitch M, Cohen T, Cooper B, Robins JM, Ma S, James L, Gopalakrishna G, Chew SK et al. 2003. Transmission dynamics and control of severe acute respiratory syndrome. Science, 300 (5627), pp. 1966-1970. Read abstract | Read more

Severe acute respiratory syndrome (SARS) is a recently described illness of humans that has spread widely over the past 6 months. With the use of detailed epidemiologic data from Singapore and epidemic curves from other settings, we estimated the reproductive number for SARS in the absence of interventions and in the presence of control efforts. We estimate that a single infectious case of SARS will infect about three secondary cases in a population that has not yet instituted control measures. Public-health efforts to reduce transmission are expected to have a substantial impact on reducing the size of the epidemic. Hide abstract

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