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Peter J White - Top 30 Publications

Genital Chlamydia trachomatis Infections Clear More Slowly in Men Than Women, but Are Less Likely to Become Established.

Rigorous estimates for clearance rates of untreated chlamydia infections are important for understanding chlamydia epidemiology and designing control interventions, but were previously only available for women.

Cost-effectiveness of microscopy of urethral smears for asymptomatic Mycoplasma genitalium urethritis in men in England.

The objective was to determine whether or not the limited use of urethral microscopy to diagnose asymptomatic and symptomatic non-chlamydial, non-gonococcal urethritis (NCNGU) in men is a cost-effective strategy to avert pelvic inflammatory disease (PID), ectopic pregnancy or infertility in female partners. Outputs from a transmission dynamic model of NCNGU in a population of 16-30 year olds in England simulating the number of consultations, PID cases and patients treated over time amongst others, were used along with secondary data to undertake a cost-effectiveness analysis carried out from a health care provider perspective. The main outcome measure was cost per case of PID averted. A secondary outcome measure was cost per major outcome averted, where a major outcome is a case of symptomatic PID, ectopic pregnancy, or infertility. Offering a limited number of asymptomatic men urethral microscopy was more effective than the current practice of no microscopy in terms of reducing the number of cases of PID with an incremental cost-effectiveness ratio of £15,700, meaning that an investment of £15,800 is required to avert one case of PID. For major outcomes averted, offering some asymptomatic men urethral microscopy was again found to be more effective than no microscopy, but here an investment of £49,900 is required to avert one major outcome. Testing asymptomatic men for NCNGU in a small number of genitourinary medicine settings in England is not cost-effective, and thus by maintaining the current practice of not offering this patient group microscopy, this continues to make savings for the health care provider.

Impact of Hepatitis C Treatment as Prevention for People Who Inject Drugs is sensitive to contact network structure.

Treatment as Prevention (TasP) using directly-acting antivirals has been advocated for Hepatitis C Virus (HCV) in people who inject drugs (PWID), but treatment is expensive and TasP's effectiveness is uncertain. Previous modelling has assumed a homogeneously-mixed population or a static network lacking turnover in the population and injecting partnerships. We developed a transmission-dynamic model on a dynamic network of injecting partnerships using data from survey of injecting behaviour carried out in London, UK. We studied transmission on a novel exponential-clustered network, as well as on two simpler networks for comparison, an exponential unclustered and a random network, and found that TasP's effectiveness differs markedly. With respect to an exponential-clustered network, the random network (and homogeneously-mixed population) overestimate TasP's effectiveness, whereas the exponential-unclustered network underestimates it. For all network types TasP's effectiveness depends on whether treated patients change risk behaviour, and on treatment coverage: higher coverage requires fewer total treatments for the same health gain. Whilst TasP can greatly reduce HCV prevalence, incidence of infection, and incidence of reinfection in PWID, assessment of TasP's effectiveness needs to take account of the injecting-partnership network structure and post-treatment behaviour change, and further empirical study is required.

Estimating Local Chlamydia Incidence and Prevalence Using Surveillance Data.

Understanding patterns of chlamydia prevalence is important for addressing inequalities and planning cost-effective control programs. Population-based surveys are costly; the best data for England come from the Natsal national surveys, which are only available once per decade, and are nationally representative but not powered to compare prevalence in different localities. Prevalence estimates at finer spatial and temporal scales are required.

A reconfiguration of the sex trade: How social and structural changes in eastern Zimbabwe left women involved in sex work and transactional sex more vulnerable.

Understanding the dynamic nature of sex work is important for explaining the course of HIV epidemics. While health and development interventions targeting sex workers may alter the dynamics of the sex trade in particular localities, little has been done to explore how large-scale social and structural changes, such as economic recessions-outside of the bounds of organizational intervention-may reconfigure social norms and attitudes with regards to sex work. Zimbabwe's economic collapse in 2009, following a period (2000-2009) of economic decline, within a declining HIV epidemic, provides a unique opportunity to study community perceptions of the impact of socio-economic upheaval on the sex trade. We conducted focus group discussions with 122 community members in rural eastern Zimbabwe in January-February 2009. Groups were homogeneous by gender and occupation and included female sex workers, married women, and men who frequented bars. The focus groups elicited discussion around changes (comparing contemporaneous circumstances in 2009 to their memories of circumstances in 2000) in the demand for, and supply of, paid sex, and how sex workers and clients adapted to these changes, and with what implications for their health and well-being. Transcripts were thematically analyzed. The analysis revealed how changing economic conditions, combined with an increased awareness and fear of HIV-changing norms and local attitudes toward sex work-had altered the demand for commercial sex. In response, sex work dispersed from the bars into the wider community, requiring female sex workers to employ different tactics to attract clients. Hyperinflation meant that sex workers had to accept new forms of payment, including sex-on-credit and commodities. Further impacting the demand for commercial sex work was a poverty-driven increase in transactional sex. The economic upheaval in Zimbabwe effectively reorganized the market for sex by reducing previously dominant forms of commercial sex, while simultaneously providing new opportunities for women to exchange sex in less formal and more risky transactions. Efforts to measure and respond to the contribution of sex work to HIV transmission need to guard against unduly static definitions and consider the changing socioeconomic context and how this can cause shifts in behavior.

Tuberculosis in migrants moving from high-incidence to low-incidence countries: a population-based cohort study of 519 955 migrants screened before entry to England, Wales, and Northern Ireland.

Tuberculosis elimination in countries with a low incidence of the disease necessitates multiple interventions, including innovations in migrant screening. We examined a cohort of migrants screened for tuberculosis before entry to England, Wales, and Northern Ireland and tracked the development of disease in this group after arrival.

Contact diaries versus wearable proximity sensors in measuring contact patterns at a conference: method comparison and participants' attitudes.

Studies measuring contact networks have helped to improve our understanding of infectious disease transmission. However, several methodological issues are still unresolved, such as which method of contact measurement is the most valid. Further, complete network analysis requires data from most, ideally all, members of a network and, to achieve this, acceptance of the measurement method. We aimed at investigating measurement error by comparing two methods of contact measurement - paper diaries vs. wearable proximity sensors - that were applied concurrently to the same population, and we measured acceptability.

Genomic Analysis and Comparison of Two Gonorrhea Outbreaks.

Gonorrhea is a sexually transmitted disease causing growing concern, with a substantial increase in reported incidence over the past few years in the United Kingdom and rising levels of resistance to a wide range of antibiotics. Understanding its epidemiology is therefore of major biomedical importance, not only on a population scale but also at the level of direct transmission. However, the molecular typing techniques traditionally used for gonorrhea infections do not provide sufficient resolution to investigate such fine-scale patterns. Here we sequenced the genomes of 237 isolates from two local collections of isolates from Sheffield and London, each of which was resolved into a single type using traditional methods. The two data sets were selected to have different epidemiological properties: the Sheffield data were collected over 6 years from a predominantly heterosexual population, whereas the London data were gathered within half a year and strongly associated with men who have sex with men. Based on contact tracing information between individuals in Sheffield, we found that transmission is associated with a median time to most recent common ancestor of 3.4 months, with an upper bound of 8 months, which we used as a criterion to identify likely transmission links in both data sets. In London, we found that transmission happened predominantly between individuals of similar age, sexual orientation, and location and also with the same HIV serostatus, which may reflect serosorting and associated risk behaviors. Comparison of the two data sets suggests that the London epidemic involved about ten times more cases than the Sheffield outbreak.

Improving Control of Tuberculosis in Low-Burden Countries: Insights from Mathematical Modeling.

Tuberculosis control and elimination remains a challenge for public health even in low-burden countries. New technology and novel approaches to case-finding, diagnosis, and treatment are causes for optimism but they need to be used cost-effectively. This in turn requires improved understanding of the epidemiology of TB and analysis of the effectiveness and cost-effectiveness of different interventions. We describe the contribution that mathematical modeling can make to understanding epidemiology and control of TB in different groups, guiding improved approaches to public health interventions. We emphasize that modeling is not a substitute for collecting data but rather is complementary to empirical research, helping determine what are the key questions to address to maximize the public-health impact of research, helping to plan studies, and making maximal use of available data, particularly from surveillance, and observational studies. We provide examples of how modeling and related empirical research inform policy and discuss how a combination of these approaches can be used to address current questions of key importance, including use of whole-genome sequencing, screening and treatment for latent infection, and combating drug resistance.

Prevalence of and risk factors for active tuberculosis in migrants screened before entry to the UK: a population-based cross-sectional study.

An increasing number of countries with low incidence of tuberculosis have pre-entry screening programmes for migrants. We present the first estimates of the prevalence of and risk factors for tuberculosis in migrants from 15 high-incidence countries screened before entry to the UK.

The Technical and Performance Characteristics of a Low-Cost, Simply Constructed, Black Light Moth Trap.

The universal mercury vapor black light trap is an effective device used for collecting moth specimens in a wide variety of habitats; yet, they can present challenges for researchers. The mercury vapor trap is often powered by a heavy automotive battery making it difficult to conduct extensive surveys in remote regions. The mercury vapor trap also carries a considerable financial cost per trap unit, making trapping challenging with low research budgets. Here, we describe the development and trapping properties of a lighter, simply constructed, and less expensive trap. The LED funnel trap consists of a funnel, soda bottles with plastic vanes, and is powered by rechargeable 9-V batteries. Two strips of low-wavelength LEDs are used as attractants. We tested the trapping parameters of this trap design compared to a standard mercury vapor trap over 10 trap nights in a suburban woodlot in the summer of 2015. The mercury vapor trap caught significantly more moth individuals than the LED trap (average of 78 vs 40 moths per trap night; P < 0.05), and significantly more species than the LED trap (23 vs 15 per trap night; P < 0.05); the mercury vapor trap caught a total of 104 macromoth species over the duration of the study, compared to a total of 87 by the LED trap. Despite the lower yields, the low cost of the LED trap (<$30 ea.) makes it superior to the mercury vapor trap in cost-acquisition per moth species and per moth individual trapped. The LED trap may be a viable alternative to the standard mercury vapor trap, facilitating insect trapping in more diverse settings.

Apparently-Different Clearance Rates from Cohort Studies of Mycoplasma genitalium Are Consistent after Accounting for Incidence of Infection, Recurrent Infection, and Study Design.

Mycoplasma genitalium is a potentially major cause of urethritis, cervicitis, pelvic inflammatory disease, infertility, and increased HIV risk. A better understanding of its natural history is crucial to informing control policy. Two extensive cohort studies (students in London, UK; Ugandan sex workers) suggest very different clearance rates; we aimed to understand the reasons and obtain improved estimates by making maximal use of the data from the studies. As M. genitalium is a sexually-transmitted infectious disease, we developed a model for time-to-event analysis that incorporates the processes of (re)infection and clearance, and fitted to data from the two cohort studies to estimate incidence and clearance rates under different scenarios of sexual partnership dynamics and study design (including sample handling and associated test sensitivity). In the London students, the estimated clearance rate is 0.80 p.a. (mean duration 15 months), with incidence 1.31%-3.93% p.a. Without adjusting for study design, corresponding estimates from the Ugandan data are 3.44 p.a. (mean duration 3.5 months) and 58% p.a. Apparent differences in clearance rates are probably mostly due to lower testing sensitivity in the Uganda study due to differences in sample handling, with 'true' clearance rates being similar, and adjusted incidence in Uganda being 28% p.a. Some differences are perhaps due to the sex workers having more-frequent antibiotic treatment, whilst reinfection within ongoing sexual partnerships might have caused some of the apparently-persistent infection in the London students. More information on partnership dynamics would inform more accurate estimates of natural-history parameters. Detailed studies in men are also required.

Decreased Time to Treatment Initiation for Multidrug-Resistant Tuberculosis Patients after Use of Xpert MTB/RIF Test, Latvia.

Few studies have examined whether the Xpert MTB/RIF test improves time to treatment initiation for persons with multidrug-resistant tuberculosis (MDR TB). We determined the impact of this test in Latvia, where it was introduced in 2010. After descriptive analyses of pulmonary MDR TB patients in Latvia during 2009-2012, time to treatment initiation was calculated, and univariate and multivariable accelerated failure time models were constructed. Univariate results showed strong evidence of an association between having rifampin-resistant TB detected by Xpert MTB/RIF and reduced time to treatment initiation versus the test not being used. A multivariable model stratifying by previous TB showed similar results. Our finding that in Latvia, time to treatment initiation was decreased for MDR TB cases that were rifampin-resistant TB by XpertMTB/RIF has implications for the use of this test in other settings with a high burden of MDR TB in which rifampin resistance is highly predictive of MDR TB.

Drug Susceptibility Patterns in MDR-TB Patients: Challenges for Future Regimen Design. A Cross-Sectional Study.

Globally, there is substantial concern regarding the challenges of treating complex drug resistance patterns in multidrug resistant tuberculosis cases. Utilising data from three different settings (Estonia, Latvia, Romania) we sought to contrast drug susceptibility profiles for multidrug resistant tuberculosis cases, highlight the difficulties in designing universal regimen, and inform future regimen selection. Demographic and microbiological surveillance data for multidrug resistant tuberculosis cases from 2004-13 were analysed. High levels of additional resistance to currently recommended second line drugs were seen in all settings, with extensive variability between countries. Accurate drug susceptibility testing and drug susceptibility testing data are vital to inform the development of comprehensive, flexible, multidrug resistant tuberculosis guidance.

Improving Control of Antibiotic-Resistant Gonorrhea by Integrating Research Agendas Across Disciplines: Key Questions Arising From Mathematical Modeling.

The rise in gonococcal antibiotic resistance and the threat of untreatable infection are focusing attention on strategies to limit the spread of drug-resistant gonorrhea. Mathematical models provide a framework to link the natural history of infection and patient behavior to epidemiological outcomes and can be used to guide research and enhance the public health impact of interventions. While limited knowledge of key disease parameters and networks of spread has impeded development of operational models of gonococcal transmission, new tools in gonococcal surveillance may provide useful data to aid tracking and modeling. Here, we highlight critical questions in the management of gonorrhea that can be addressed by mathematical models and identify key data needs. Our overarching aim is to articulate a shared agenda across gonococcus-related fields from microbiology to epidemiology that will catalyze a comprehensive evidence-based clinical and public health strategy for management of gonococcal infections and antimicrobial resistance.

Challenges Presented by Re-Emerging Sexually Transmitted Infections in HIV Positive Men who have Sex with Men: An Observational Study of Lymphogranuloma Venereum in the UK.

United Kingdom has reported the largest documented outbreak of lymphogranuloma venereum (LGV), a re-emerging sexually transmitted infection (STI) which is primarily seen in HIV-positive men who have sex with men (MSM). A diagnostic service was established in response to the outbreak linked to a voluntary LGV Enhanced Surveillance system. We examined the performance of this novel surveillance system to identify utility in tracking a re-emerging infection.

'Pre-entry screening for tuberculosis' commentary: authors' response.

Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis.

Drug-resistant tuberculosis (TB), especially multidrug-resistant (MDR, resistance to rifampicin and isoniazid) disease, is associated with a worse patient outcome. Drug resistance diagnosed using microbiological culture takes days to weeks, as TB bacteria grow slowly. Rapid molecular tests for drug resistance detection (1 day) are commercially available and may promote faster initiation of appropriate treatment.

The Possible Impact of Vaccination for Seasonal Influenza on Emergence of Pandemic Influenza via Reassortment.

One pathway through which pandemic influenza strains might emerge is reassortment from coinfection of different influenza A viruses. Seasonal influenza vaccines are designed to target the circulating strains, which intuitively decreases the prevalence of coinfection and the chance of pandemic emergence due to reassortment. However, individual-based analyses on 2009 pandemic influenza show that the previous seasonal vaccination may increase the risk of pandemic A(H1N1) pdm09 infection. In view of pandemic influenza preparedness, it is essential to understand the overall effect of seasonal vaccination on pandemic emergence via reassortment.

Pre-entry screening programmes for tuberculosis in migrants to low-incidence countries: a systematic review and meta-analysis.

Several high-income countries have pre-entry screening programmes for tuberculosis. We aimed to establish the yield of pre-entry screening programmes to inform evidence-based policy for migrant health screening.

How Many HIV infections may be averted by targeting primary infection in men who have sex with men? Quantification of changes in transmission-risk behavior, using an individual-based model.

In the United Kingdom, human immunodeficiency virus (HIV) transmission among men who have sex with men (MSM) is not under control, despite readily available treatment, highlighting the need to design a cost-effective combination prevention package. MSM report significantly reduced transmission risk behavior following HIV diagnosis. To assess the effectiveness of HIV diagnosis in averting transmission during highly infectious primary HIV infection (PHI), we developed a stochastic individual-based model to calculate the number of HIV-transmission events expected to occur from a cohort of recently infected MSM with and those without the behavior changes reported after diagnosis. The model incorporates different types of sex acts, incorporates condom use, and distinguishes between regular and casual sex partners. The impact on transmission in the 3 months after infection depends on PHI duration and testing frequency. If PHI lasts for 3 months and testing is performed monthly, then behavior changes after diagnosis would have reduced estimated transmission events by 49%-52%, from 31-45 to 15-23 events; a shorter duration of PHI and/or a lower testing frequency reduces the number of infections averted. Diagnosing HIV during PHI can markedly reduce transmission by changing transmission-risk behavior. Because of the high infectivity but short duration of PHI, even short-term behavior change can significantly reduce transmission. Our quantification of the number of infections averted is an essential component of assessment of the cost-effectiveness of strategies to increase detection and diagnoses of PHI.

Developing a conceptual framework of seroadaptive behaviors in HIV-diagnosed men who have sex with men.

Seroadaptive behaviors are strategies employed by men who have sex with men (MSM) to reduce the transmission risk for human immunodeficiency virus (HIV). It has been suggested that they contribute to the increasing diagnoses of sexually transmitted infections in HIV-diagnosed MSM. To understand the context in which the reemerging sexually transmitted infections appear, we developed a social epidemiological model incorporating the multiple factors influencing seroadaptive behaviors.

The price of sex: condom use and the determinants of the price of sex among female sex workers in eastern Zimbabwe.

Higher prices for unprotected sex threaten the high levels of condom use that contributed to the decline in Zimbabwe's human immunodeficiency virus (HIV) epidemic. To improve understanding of financial pressures competing against safer sex, we explore factors associated with the price of commercial sex in rural eastern Zimbabwe.

Optimizing the precision of case fatality ratio estimates under the surveillance pyramid approach.

In the management of emerging infectious disease epidemics, precise and accurate estimation of severity indices, such as the probability of death after developing symptoms-the symptomatic case fatality ratio (sCFR)-is essential. Estimation of the sCFR may require merging data gathered through different surveillance systems and surveys. Since different surveillance strategies provide different levels of precision and accuracy, there is need for a theory to help investigators select the strategy that maximizes these properties. Here, we study the precision of sCFR estimators that combine data from several levels of the severity pyramid. We derive a formula for the standard error, which helps us find the estimator with the best precision given fixed resources. We further propose rules of thumb for guiding the choice of strategy: For example, should surveillance of a particular severity level be started? Which level should be preferred? We derive a formula for the optimal allocation of resources between chosen surveillance levels and provide a simple approximation that can be used in thinking more heuristically about planning surveillance. We illustrate these concepts with numerical examples corresponding to 3 influenza pandemic scenarios. Finally, we review the equally important issue of accuracy.

Is the pain visual analogue scale linear and responsive to change? An exploration using Rasch analysis.

Pain visual analogue scales (VAS) are commonly used in clinical trials and are often treated as an interval level scale without evidence that this is appropriate. This paper examines the internal construct validity and responsiveness of the pain VAS using Rasch analysis.

The spatiotemporal association of non-prescription retail sales with cases during the 2009 influenza pandemic in Great Britain.

To assess whether retail sales of non-prescription products can be used for syndromic surveillance and whether it can detect influenza activity at different spatial scales. A secondary objective was to assess whether changes in purchasing behaviour were related to public health advice or levels of media or public interest.

Effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections: observational study, systematic reviews and mathematical modelling.

Partner notification is essential to the comprehensive case management of sexually transmitted infections. Systematic reviews and mathematical modelling can be used to synthesise information about the effects of new interventions to enhance the outcomes of partner notification.

Testing two methods that relate herbivorous insects to host plants.

Insect herbivores are integral to terrestrial ecosystems. They provide essential food for higher trophic levels and aid in nutrient cycling. In general, research tends to relate individual insect herbivore species to host plant identity, where a species will show preference for one host over another. In contrast, insect herbivore assemblages are often related to host plant richness where an area with a higher richness of hosts will also have a higher richness of herbivores. In this study, the ability of these two approaches (host plant identity/abundance vs. host plant richness) to describe the diversity, richness, and abundance of an herbivorous Lepidoptera assemblage in temperate forest fragments in southern Canada is tested. Analyses indicated that caterpillar diversity, richness, and abundance were better described by quadrat-scale host plant identity and abundance than by host plant richness. Most host plant-herbivore studies to date have only considered investigating host plant preferences at a species level; the type of assemblage level preference shown in this study has been rarely considered. In addition, host plant replacement simulations indicate that increasing the abundance of preferred host plants could increase Lepidoptera richness and abundance by as much as 30% and 40% respectively in disturbed remnant forest fragments. This differs from traditional thinking that suggests higher levels of insect richness can be best obtained by maximizing plant richness. Host plant species that are highly preferred by the forest-dwelling caterpillar assemblage should be given special management and conservation considerations to maximize biodiversity in forest communities.

Co-circulation of influenza A virus strains and emergence of pandemic via reassortment: the role of cross-immunity.

Reassortment is an important evolutionary route for influenza A viruses to generate pandemic strains. The pre-requisite for reassortment to occur is co-infection of different influenza virus strains in the same host population. Empirical evidence suggests that co-circulation of influenza A virus strains is common and co-infection in patients has been reported. Whether a novel virus can successfully spread among a host population is determined by its life-history (infectivity and infectious period). It is also well known that different influenza A strains interfere through the immune response of human body cells. The reassortant virus strain generated from co-infections deviates dramatically in antigenic and genetic properties from its parental strains such that human populations have limited immunity against it. We consider a mathematical model which includes two strains of influenza virus within a standard SIR model and integrate life history and cross-immunity into the evolutionary dynamics of influenza virus. We assume that, following primary infection by one strain and recovery, individuals are susceptible to secondary infection by the other strain only but with reduced probability due to cross-immunity. Co-infection is included to examine how life-history and cross-immunity interplay to regulate the co-circulation and co-infection of different influenza A virus strains in human populations. Further, we introduce novel strains via reassortment and investigate how the opportunities of a reassortant strain developing into a pandemic are constrained by its life-history and the residual immunity within human populations. We find that though the probability of pandemic emergence via reassortment increases with transmissibility of reassortant strains and the rate of reassortment, the existence of cross-immunity acquired through previous infections or vaccination can greatly constrain pandemic emergence.