Publications
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Fragaszy EB, Warren-Gash C, White PJ, et al., 2018, Effects of seasonal and pandemic influenza on health-related quality of life, work and school absence in England: results from the Flu Watch cohort study, Influenza and Other Respiratory Viruses, Vol: 12, Pages: 171-182, ISSN: 1750-2640
BACKGROUND: Estimates of health-related quality of life (HRQoL) and work/school absences for influenza are typically based on medically-attended cases or those meeting influenza-like-illness (ILI) case definitions, and thus biased towards severe disease. Although community influenza cases are more common, estimates of their effects on HRQoL and absences are limited. OBJECTIVES: To measure Quality-Adjusted Life Days and Years (QALDs and QALYs) lost and work/school absences among community cases of acute respiratory infections (ARI), ILI and influenza A and B and to estimate community burden of QALY loss and absences from influenza. PATIENTS/ METHODS: Flu Watch was a community cohort in England from 2006-2011. Participants were followed-up weekly. During respiratory illness they prospectively recorded daily symptoms, work/school absences and EQ-5D-3L data and submitted nasal swabs for RT-PCR influenza testing. RESULTS: Average QALD lost was 0.26, 0.93, 1.61 and 1.84 for ARI, ILI, H1N1pdm09 and influenza B cases respectively. 40% of influenza A cases and 24% of influenza B cases took time off work/school with an average duration of 3.6 days and 2.4 days respectively. In England, community influenza cases lost 24,300 QALYs in 2010/11 and had an estimated 2.9 million absences per season based on data from 2006/07 - 2009/10. CONCLUSIONS: Our QALDs and QALYs lost and work and school absence estimates are lower than previous estimates because we focus on community cases, most of which are mild, may not meet ILI definitions and do not result in healthcare consultations. Nevertheless, they contribute a substantial loss of HRQoL on a population level. This article is protected by copyright. All rights reserved.
Gubay F, Staunton R, Metzig C, et al., 2017, Assessing uncertainty in the burden of Hepatitis C Virus: comparison of estimated disease burden and treatment costs in the UK, Journal of Viral Hepatitis, Vol: 25, Pages: 514-523, ISSN: 1352-0504
Hepatitis C virus (HCV) is a major and growing public health concern. We need to know the expected health burden and treatment cost, and understand uncertainty in those estimates, to inform policymaking and future research. Two models that have been important in informing treatment guidelines and assessments of HCV burden were compared by simulating cohorts of individuals with chronic HCV infection initially aged 20, 35 and 50 years. One model predicts that health losses (measured in quality‐adjusted life‐years [QALYs]) and treatment costs decrease with increasing initial age of the patients, whilst the other model predicts that below 40 years, costs increase and QALY losses change little with age, and above 40 years, they decline with increasing age. Average per‐patient costs differ between the models by up to 38%, depending on the patients' initial age. One model predicts double the total number, and triple the peak annual incidence, of liver transplants compared to the other model. One model predicts 55%‐314% more deaths than the other, depending on the patients' initial age. The main sources of difference between the models are estimated progression rates between disease states and rates of health service utilization associated with different disease states and, in particular, the age dependency of these parameters. We conclude that decision‐makers need to be aware that uncertainties in the health burden and economic cost of HCV disease have important consequences for predictions of future need for care and cost‐effectiveness of interventions to avert HCV transmission, and further quantification is required to inform decisions.
Birger R, Saunders J, Estcourt C, et al., 2017, Should we screen for the sexually-transmitted infection Mycoplasma genitalium? Evidence synthesis using a transmission-dynamic model, Scientific Reports, Vol: 7, ISSN: 2045-2322
There is increasing concern about Mycoplasma genitalium as a cause of urethritis, cervicitis, pelvic inflammatory disease (PID), infertility and ectopic pregnancy. Commercial nucleic acid amplification tests (NAATs) are becoming available, and their use in screening for M. genitalium has been advocated, but M. genitalium’s natural history is poorly-understood, making screening’s effectiveness unclear. We used a transmission-dynamic compartmental model to synthesise evidence from surveillance data and epidemiological and behavioural studies to better understand M. genitalium’s natural history, and then examined the effects of implementing NAAT testing. Introducing NAAT testing initially increases diagnoses, by finding a larger proportion of infections; subsequently the diagnosis rate falls, due to reduced incidence. Testing only symptomatic patients finds relatively little infection in women, as a large proportion is asymptomatic. Testing both symptomatic and asymptomatic patients has a much larger impact and reduces cumulative PID incidence in women due to M. genitalium by 31.1% (95% range:13.0%-52.0%) over 20 years. However, there is important uncertainty in M. genitalium’s natural history parameters, leading to uncertainty in the absolute reduction in PID and sequelae. Empirical work is required to improve understanding of key aspects of M. genitalium’s natural history before it will be possible to determine the effectiveness of screening.
Whittles L, White PJ, Didelot X, 2017, Estimating the fitness cost and benefit of cefixime resistance in Neisseria gonorrhoeae to inform prescription policy: a modelling study, PLoS Medicine, Vol: 14, ISSN: 1549-1277
BackgroundGonorrhoea is one of the most common bacterial sexually transmitted infections in England. Over 41,000 cases were recorded in 2015, more than half of which occurred in men who have sex with men (MSM). As the bacterium has developed resistance to each first-line antibiotic in turn, we need an improved understanding of fitness benefits and costs of antibiotic resistance to inform control policy and planning. Cefixime was recommended as a single-dose treatment for gonorrhoea from 2005 to 2010, during which time resistance increased, and subsequently declined.Methods and findingsWe developed a stochastic compartmental model representing the natural history and transmission of cefixime-sensitive and cefixime-resistant strains of Neisseria gonorrhoeae in MSM in England, which was applied to data on diagnoses and prescriptions between 2008 and 2015. We estimated that asymptomatic carriers play a crucial role in overall transmission dynamics, with 37% (95% credible interval CrI 24%–52%) of infections remaining asymptomatic and untreated, accounting for 89% (95% CrI 82%–93%) of onward transmission. The fitness cost of cefixime resistance in the absence of cefixime usage was estimated to be such that the number of secondary infections caused by resistant strains is only about half as much as for the susceptible strains, which is insufficient to maintain persistence. However, we estimated that treatment of cefixime-resistant strains with cefixime was unsuccessful in 83% (95% CrI 53%–99%) of cases, representing a fitness benefit of resistance. This benefit was large enough to counterbalance the fitness cost when 31% (95% CrI 26%–36%) of cases were treated with cefixime, and when more than 55% (95% CrI 44%–66%) of cases were treated with cefixime, the resistant strain had a net fitness advantage over the susceptible strain. Limitations include sparse data leading to large intervals on key model parameters and necessary assumptions in the m
White PJ, Abubakar I, Aldridge RW, et al., 2017, Post-migration follow-up of migrants at risk of tuberculosis, Lancet Infectious Diseases, Vol: 17, Pages: 1124-1124, ISSN: 1473-3099
White PJ, 2017, Increases in gonorrhoea incidence and GUM clinic waiting times: are we in a vicious circle like the late 1990s and early 2000s, but now exacerbated by drug resistance?, Sexually Transmitted Infections, Vol: 93, Pages: 471-471, ISSN: 1368-4973
Lewis J, White PJ, 2017, Estimating local chlamydia incidence and prevalence using surveillance data, Epidemiology, Vol: 28, Pages: 492-502, ISSN: 1531-5487
Background: 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.Methods: We present a method for estimating local prevalence by modeling the infection, testing and treatment processes. Prior probability distributions for parameters describing natural history and treatment-seeking behavior are informed by the literature or calibrated using national prevalence estimates. By combining them with surveillance data on numbers of chlamydia tests and diagnoses, we obtain estimates of local screening rates, incidence and prevalence. We illustrate the method by application to data from England.Results: Our estimates of national prevalence by age group agree with the Natsal-3 survey. They could be improved by additional information on the number of diagnosed cases that were asymptomatic. There is substantial local-level variation in prevalence, with more infection in deprived areas. Incidence in each sex is strongly correlated with prevalence in the other. Importantly, we find that positivity (the proportion of tests which were positive) does not provide a reliable proxy for prevalence.Conclusion: This approach provides local chlamydia prevalence estimates from surveillance data, which could inform analyses to identify and understand local prevalence patterns and assess local programs. Estimates could be more accurate if surveillance systems recorded additional information, including on symptoms.
Sutton AJ, Roberts TE, Jackson L, et al., 2017, Cost-effectiveness of microscopy of urethral smears for asymptomatic Mycoplasma genitalium urethritis in men in England, International Journal of STD & AIDS, Vol: 29, Pages: 72-79, ISSN: 1758-1052
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.
Lewis JEA, Price MJ, Horner PJ, et al., 2017, Genital C. trachomatis infections clear more slowly in men than women, but are less likely to become established., Journal of Infectious Diseases, Vol: 216, Pages: 237-244, ISSN: 1537-6613
BackgroundRigorous 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.MethodsWe used data from published studies of chlamydia-infected men who were retested at a later date without having received treatment. Our analysis allowed new infections to take one of 1, 2, or 3 courses, each clearing at a different rate. We determined which of these 3 models had the most empirical support.ResultsThe best-fitting model had 2 courses of infection in men, as was previously found for women: “slow-clearing” and “fast-clearing.” Only 68% (57%–78%) (posterior median and 95% credible interval [CrI]) of incident infections in men were slow-clearing, vs 77% (69%–84%) in women. The slow clearance rate in men (based on 6 months’ follow-up) was 0.35 (.05–1.15) year-1 (posterior median and 95% CrI), corresponding to mean infection duration 2.84 (.87–18.79) years. This compares to 1.35 (1.13–1.63) years in women.ConclusionsOur estimated clearance rate is slower than previously assumed. Fewer infections become established in men than women but once established, they clear more slowly. This study provides an improved description of chlamydia’s natural history to inform public health decision making. We describe how further data collection could reduce uncertainty in estimates.
Metzig C, Surey J, Francis M, et al., 2017, Impact of Hepatitis C treatment as prevention for people who inject drugs is sensitive to contact network, Scientific Reports, Vol: 7, ISSN: 2045-2322
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.
Elmes JAR, Skovdal M, Nhongo K, et al., 2017, 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, PLOS One, Vol: 12, ISSN: 1932-6203
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 previousl
Estcourt C, Sutcliffe L, Mercer CH, et al., 2016, The Ballseye programme: a mixed-methods programme of research in traditional sexual health and alternative community settings to improve the sexual health of men in the UK, Programme Grants for Applied Research, Vol: 4, ISSN: 2050-4330
BackgroundSexually transmitted infection (STI) diagnoses are increasing and efforts to reduce transmission have failed. There are major uncertainties in the evidence base surrounding the delivery of STI care for men.AimTo improve the sexual health of young men in the UK by determining optimal strategies for STI testing and careObjectivesTo develop an evidence-based clinical algorithm for STI testing in asymptomatic men; model mathematically the epidemiological and economic impact of removing microscopy from routine STI testing in asymptomatic men; conduct a pilot randomised controlled trial (RCT) of accelerated partner therapy (APT; new models of partner notification to rapidly treat male sex partners of people with STIs) in primary care; explore the acceptability of diverse venues for STI screening in men; and determine optimal models for the delivery of screening.DesignSystematic review of the clinical consequences of asymptomatic non-chlamydial, non-gonococcal urethritis (NCNGU); case–control study of factors associated with NCNGU; mathematical modelling of the epidemiological and economic impact of removing microscopy from asymptomatic screening and cost-effectiveness analysis; pilot RCT of APT for male sex partners of women diagnosed with Chlamydia trachomatis infection in primary care; stratified random probability sample survey of UK young men; qualitative study of men’s views on accessing STI testing; SPORTSMART pilot cluster RCT of two STI screening interventions in amateur football clubs; and anonymous questionnaire survey of STI risk and previous testing behaviour in men in football clubs.SettingsGeneral population, genitourinary medicine clinic attenders, general practice and community contraception and sexual health clinic attenders and amateur football clubs.ParticipantsMen and women.InterventionsPartner notification interventions: APTHotline [telephone assessment of partner(s)] and APTPharmacy [community pharmacist assessment of partner(s)
Aldridge RW, Zenner D, White PJ, et al., 2016, 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, Lancet, Vol: 388, Pages: 2510-2518, ISSN: 1474-547X
BACKGROUND: 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. METHODS: As part of a pilot pre-entry screening programme for tuberculosis in 15 countries with a high incidence of the disease, the International Organization for Migration screened all applicants for UK visas aged 11 years or older who intended to stay for more than 6 months. Applicants underwent a chest radiograph, and any with results suggestive of tuberculosis underwent sputum testing and culture testing (when available). We tracked the development of tuberculosis in those who tested negative for the disease and subsequently migrated to England, Wales, and Northern Ireland with the Enhanced Tuberculosis Surveillance system. Primary outcomes were cases of all forms of tuberculosis (including clinically diagnosed cases), and bacteriologically confirmed pulmonary tuberculosis. FINDINGS: Our study cohort was 519 955 migrants who were screened for tuberculosis before entry to the UK between Jan 1, 2006, and Dec 31, 2012. Cases notified on the Enhanced Tuberculosis Surveillance system between Jan 1, 2006, and Dec 31, 2013, were included. 1873 incident cases of all forms of tuberculosis were identified, and, on the basis of data for England, Wales, and Northern Ireland, the estimated incidence of all forms of tuberculosis in migrants screened before entry was 147 per 100 000 person-years (95% CI 140-154). The estimated incidence of bacteriologically confirmed pulmonary tuberculosis in migrants screened before entry was 49 per 100 000 person-years (95% CI 45-53). Migrants whose chest radiographs were compatible with active tuberculosis but with negative pre-entry microbiological results were at increased risk of tuberculosis com
Smieszek T, Castell S, Barrat A, et al., 2016, Contact diaries versus wearable proximity sensors in measuring contact patterns at a conference: method comparison and participants' attitudes, BMC Infectious Diseases, Vol: 16, ISSN: 1471-2334
BACKGROUND: 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. METHODS: We investigated the contact network of one day of an epidemiology conference in September 2014. Seventy-six participants wore proximity sensors throughout the day while concurrently recording their contacts with other study participants in a paper-diary; they also reported on method acceptability. RESULTS: There were 329 contact reports in the paper diaries, corresponding to 199 contacts, of which 130 were noted by both parties. The sensors recorded 316 contacts, which would have resulted in 632 contact reports if there had been perfect concordance in recording. We estimated the probabilities that a contact was reported in a diary as: P = 72 % for <5 min contact duration (significantly lower than the following, p < 0.05), P = 86 % for 5-15 min, P = 89 % for 15-60 min, and P = 94 % for >60 min. The sets of sensor-measured and self-reported contacts had a large intersection, but neither was a subset of the other. Participants' aggregated contact duration was mostly substantially longer in the diary data than in the sensor data. Twenty percent of respondents (>1 reported contact) stated that filling in the diary was too much work, 25 % of respondents reported difficulties in remembering contacts, and 93 % were com
Didelot X, Dordel J, Whittles LK, et al., 2016, Genomic analysis and comparison of two gonorrhoea outbreaks, mBio, Vol: 7, ISSN: 2150-7511
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.
White PJ, Abubakar I, 2016, Improving control of tuberculosis in low-burden countries: insights from mathematical modeling, Frontiers in Microbiology, Vol: 7, ISSN: 1664-302X
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.
Stagg HR, White PJ, Riekstina V, et al., 2016, Decreased Time to Treatment Initiation for Multidrug-Resistant Tuberculosis Patients after Use of Xpert MTB/RIF Test, Latvia, Emerging Infectious Diseases, Vol: 22, Pages: 482-490, ISSN: 1080-6059
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.
Aldridge RW, Zenner D, White PJ, et al., 2016, Prevalence of and risk factors for active tuberculosis in migrants screened before entry to the UK: a population-based cross-sectional study., Lancet Infectious Diseases, Vol: 16, Pages: 962-970, ISSN: 1473-3099
BACKGROUND: 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. METHODS: We did a population-based cross-sectional study of applicants for long-term visas who were screened for tuberculosis before entry to the UK in a pilot programme between Oct 1, 2005, and Dec 31, 2013. The primary outcome was prevalence of bacteriologically confirmed tuberculosis. We used Poisson regression to estimate crude prevalence and created a multivariable logistic regression model to identify risk factors for the primary outcome. FINDINGS: 476 455 visa applicants were screened, and the crude prevalence of bacteriologically confirmed tuberculosis was 92 (95% CI 84-101) per 100 000 individuals. After adjustment for age and sex, factors that were strongly associated with an increased risk of bacteriologically confirmed disease at pre-entry screening were self-report of close or household contact with an individual with tuberculosis (odds ratio 11·6, 95% CI 7·0-19·3; p<0·0001) and being an applicant for settlement and dependant visas (1·3, 1·0-1·6; p=0·0203). INTERPRETATION: Migrants reporting contact with an individual with tuberculosis had the highest risk of tuberculosis at pre-entry screening. To tackle this disease burden in migrants, a comprehensive and collaborative approach is needed between countries with pre-entry screening programmes, health services in the countries of origin and migration, national tuberculosis control programmes, and international public health bodies. FUNDING: Wellcome Trust, Medical Research Council, and UK National Institute for Health Research.
Aldridge R, Zenner D, White P, et al., 2016, Pre-entry screening of tuberculosis in migrants to the UK: a population-based cohort study, Spring Meeting on Clinician Scientists in Training, Publisher: ELSEVIER SCIENCE INC, Pages: 11-11, ISSN: 0140-6736
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Smieszek T, White PJ, 2016, Apparently-Different Clearance Rates from Cohort Studies of Mycoplasma genitalium Are Consistent after Accounting for Incidence of Infection, Recurrent Infection, and Study Design., PLOS One, Vol: 11, ISSN: 1932-6203
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 0.80p.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 3.44p.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.
Stagg HR, Brown J, Ibraim E, et al., 2015, Drug Susceptibility Patterns in MDR-TB Patients: Challenges for Future Regimen Design. A Cross-Sectional Study, PLOS One, Vol: 10, ISSN: 1932-6203
Globally, there is substantial concern regarding the challenges of treating complex drugresistance patterns in multidrug resistant tuberculosis cases. Utilising data from three differentsettings (Estonia, Latvia, Romania) we sought to contrast drug susceptibility profiles formultidrug resistant tuberculosis cases, highlight the difficulties in designing universal regimen,and inform future regimen selection. Demographic and microbiological surveillancedata for multidrug resistant tuberculosis cases from 2004–13 were analysed. High levels ofadditional resistance to currently recommended second line drugs were seen in all settings,with extensive variability between countries. Accurate drug susceptibility testing and drugsusceptibility testing data are vital to inform the development of comprehensive, flexible,multidrug resistant tuberculosis guidance.
Grad YH, Goldstein E, Lipsitch M, et al., 2015, Improving control of antibiotic resistant gonorrhea by integrating research agendas across disciplines: key questions arising from mathematical modeling, Journal of Infectious Diseases, Vol: 213, Pages: 883-890, ISSN: 1537-6613
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.
Aldridge RW, Yates TA, Zenner D, et al., 2015, 'Pre-entry screening for tuberculosis' commentary: authors' response, PATHOGENS AND GLOBAL HEALTH, Vol: 109, Pages: 166-167, ISSN: 2047-7724
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Drobniewski F, Cooke M, Jordan J, et al., 2015, Systematic review, meta-analysis and economic modelling of molecular diagnostic tests for antibiotic resistance in tuberculosis, Health Technology Assessment, Vol: 19, ISSN: 1366-5278
Cassell JA, Dodds J, Estcourt C, et al., 2015, Sexually transmitted infections in the UK, Health Technology Assessment, Vol: 19, Pages: 1-117, ISSN: 1366-5278
Zhang X-S, Pebody R, De Angelis D, et al., 2014, The Possible Impact of Vaccination for Seasonal Influenza on Emergence of Pandemic Influenza via Reassortment, PLOS One, Vol: 9, ISSN: 1932-6203
Background: One pathway through which pandemic influenza strains mightemerge is reassortment from coinfection of different influenza A viruses. Seasonalinfluenza vaccines are designed to target the circulating strains, which intuitivelydecreases the prevalence of coinfection and the chance of pandemic emergencedue to reassortment. However, individual-based analyses on 2009 pandemicinfluenza show that the previous seasonal vaccination may increase the risk ofpandemic A(H1N1) pdm09 infection. In view of pandemic influenza preparedness, itis essential to understand the overall effect of seasonal vaccination on pandemicemergence via reassortment.Methods and Findings: In a previous study we applied a population dynamicsapproach to investigate the effect of infection-induced cross-immunity on reducingsuch a pandemic risk. Here the model was extended by incorporating vaccinationfor seasonal influenza to assess its potential role on the pandemic emergence viareassortment and its effect in protecting humans if a pandemic does emerge. Thevaccination is assumed to protect against the target strains but only partially againstother strains. We find that a universal seasonal vaccine that provides full-spectrumcross-immunity substantially reduces the opportunity of pandemic emergence.However, our results show that such effectiveness depends on the strength ofinfection-induced cross-immunity against any novel reassortant strain. If it is weak,the vaccine that induces cross-immunity strongly against non-target resident strains but weakly against novel reassortant strains, can further depress the pandemicemergence; if it is very strong, the same kind of vaccine increases the probability ofpandemic emergence.Conclusions: Two types of vaccines are available: inactivated and live attenuated,only live attenuated vaccines can induce heterosubtypic immunity. Currentvaccines are effective in controlling circulating strains; they cannot always helprestrain pandemic emergence because of the u
Rönn M, White PJ, Hughes G, et al., 2014, Developing a Conceptual Framework of Seroadaptive Behaviors in HIV-Diagnosed Men Who Have Sex With Men, Journal of Infectious Diseases, Vol: 210, Pages: S586-S593, ISSN: 1537-6613
Background. 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. Methods. A literature review of seroadaptive behaviors in HIV-diagnosed MSM was conducted. The literature was synthesized using a social epidemiological perspective. Results. Seroadaptive behaviors are adopted by MSM in high-income countries and are a way for HIV-diagnosed men to manage and enjoy their sexual lives. Influences are apparent at structural, community, interpersonal, and intrapersonal levels. There is little evidence of whether and when the behavior forms part of a premeditated strategy; it seems dependent on the social context and on time since HIV diagnosis. Social rules of HIV disclosure and perception of risk depend on the setting where partners are encountered. Conclusions. Seroadaptive behaviors are strongly context dependent and can reduce or increase transmission risk for different infectious diseases. Further data collection and mathematical modeling can help us explore the specific conditions in more detail.
White PJ, Fox J, Weber J, et al., 2014, 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, Journal of Infectious Diseases, Vol: 210, Pages: S594-S599, ISSN: 1537-6613
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-effectivecombination prevention package. MSM report significantly reduced transmission risk behavior following HIVdiagnosis. To assess the effectiveness of HIV diagnosis in averting transmission during highly infectious primaryHIV infection (PHI), we developed a stochastic individual-based model to calculate the number of HIVtransmissionevents expected to occur from a cohort of recently infected MSM with and those without the behaviorchanges 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 afterinfection depends on PHI duration and testing frequency. If PHI lasts for 3 months and testing is performedmonthly, 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 ofinfections averted. Diagnosing HIV during PHI can markedly reduce transmission by changing transmissionriskbehavior. Because of the high infectivity but short duration of PHI, even short-term behavior change cansignificantly reduce transmission. Our quantification of the number of infections averted is an essential componentof assessment of the cost-effectiveness of strategies to increase detection and diagnoses of PHI.
Elmes J, Nhongo K, Ward H, et al., 2014, The Price of Sex: Condom Use and the Determinants of the Price of Sex Among Female Sex Workers in Eastern Zimbabwe, JOURNAL OF INFECTIOUS DISEASES, Vol: 210, Pages: S569-S578, ISSN: 0022-1899
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Pelat C, Ferguson NM, White PJ, et al., 2014, Optimizing the Precision of Case Fatality Ratio Estimates Under the Surveillance Pyramid Approach, AMERICAN JOURNAL OF EPIDEMIOLOGY, Vol: 180, Pages: 1036-1046, ISSN: 0002-9262
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- Citations: 8
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