114 results found
Whittles LK, White PJ, Didelot X, 2020, Assessment of the Potential of Vaccination to Combat Antibiotic Resistance in Gonorrhea: A Modeling Analysis to Determine Preferred Product Characteristics., Clin Infect Dis
BACKGROUND: Gonorrhea incidence is increasing rapidly in many countries, whilst antibiotic resistance is making treatment more difficult. Combined with evidence that MeNZB and Bexsero meningococcal vaccines are likely partially-protective against gonorrhea, this has renewed interest in a gonococcal vaccine, and several candidates are in development. Key questions are how protective a vaccine needs to be, how long protection needs to last, and how should it be targeted. We assessed vaccination's potential impact, and the feasibility of achieving WHO's target 90% reduction in gonorrhea incidence 2016-2030, by comparing realistic vaccination strategies under a range of scenarios of vaccine efficacy and duration of protection, and emergence of extensively-resistant gonorrhea. METHODS: We developed a stochastic transmission-dynamic model, incorporating asymptomatic and symptomatic infection and heterogeneous sexual behavior in men-who-have-sex-with-men (MSM). We used data from England, which has a comprehensive, consistent nationwide surveillance system. Using particle Markov Chain Monte Carlo methods we fitted the model to gonorrhea incidence in 2008-17, and then used Bayesian forecasting to examine an extensive range of scenarios. RESULTS: Even in the worst-case scenario of untreatable infection emerging, the WHO target is achievable if all MSM attending sexual health clinics receive a vaccine offering ≥52% protection for ≥6 years. A vaccine conferring 31% protection (as estimated for MeNZB) for 2-4 years, could reduce incidence in 2030 by 45% in the worst-case scenario, and by 75% if >70% of resistant gonorrhea remains treatable. CONCLUSIONS: Even a partially-protective vaccine, delivered through a realistic targeting strategy, could substantially reduce gonorrhea incidence, despite antibiotic resistance.
White P, Lewis J, 2019, Response to Kounali et al.’s letter of response, Epidemiology and Infection, Vol: 147, ISSN: 0950-2688
White P, Lewis J, 2019, Letter to editor in response to Has Chlamydia trachomatis prevalence in young women in England, Scotland and Wales changed? Evidence from national probability surveys, Epidemiology and Infection, Vol: 147, ISSN: 0950-2688
Lewis J, White PJ, Understanding relationships between chlamydial infection, symptoms and testing behavior: an analysis of data from Natsal-3, Epidemiology, ISSN: 1044-3983
Background: Genital chlamydial infection is the most commonly-diagnosed sexually- transmitted infection worldwide, and can have serious long-term sequelae. Numerous countries invest substantially in testing but evidence for programs’ effectiveness is inconclusive. The effects of testing programs in different groups of people need to be understood. Methods: We analyzed data on sexual behavior and chlamydia testing from 16-24-year-olds in Britain’s third National Survey of Sexual Attitudes and Lifestyles, considering test setting, reason and result. We conducted descriptive analysis accounting for the survey design using design variables and nonresponse weightings, and Bayesian analysis using a mathematical model of chlamydial infection and testing. Results: Most men testing due to symptoms tested in sexual health settings (63.1%; 95% confidence interval 42.5-83.6%) but most women testing due to symptoms were tested by GPs (59.3%; 42.9-75.8%). Within behavioral groups, positivity of chlamydia screens (tests not prompted by symptoms or partner notification) was similar to population prevalence. Screening rates were higher in women and in those reporting more partners: median (95% credible interval) rates per year in those reporting 0, 1 and ≥2 new partners in the last year were 0.30(0.24-0.35), 0.45(0.37-0.53) and 0.59(0.48-0.71) (men) and 0.59(0.52-0.68), 0.88(0.74-1.03) 20 and 1.16(0.97-1.39) (women). Conclusions: The proportion of testing occurring in sexual health is not a proxy for the proportion prompted by symptoms. Test positivity depends on a combination of force of infection and screening rate and does not simply reflect prevalence or behavioral risk. The analysis highlights the value of recording testing reason and behavioral characteristics to inform cost-effective control.
Green N, Sherrard-Smith E, Tanton C, et al., 2019, Assessing local chlamydia screening performance by combining survey and administrative data to account for differences in local population characteristics, Scientific Reports, Vol: 9, ISSN: 2045-2322
Reducing health inequalities requires improved understanding of the causes of variation. Local-level variation reflects differences in local population characteristics and health system performance. Identifying low- and high-performing localities allows investigation into these differences. We used Multilevel Regression with Post-stratification (MRP) to synthesise data from multiple sources, using chlamydia testing as our example. We used national probability survey data to identify individual-level characteristics associated with chlamydia testing and combined this with local-level census data to calculate expected levels of testing in each local authority (LA) in England, allowing us to identify LAs where observed chlamydia testing rates were lower or higher than expected, given population characteristics. Taking account of multiple covariates, including age, sex, ethnicity, student and cohabiting status, 5.4% and 3.5% of LAs had testing rates higher than expected for 95% and 99% posterior credible intervals, respectively; 60.9% and 50.8% had rates lower than expected. Residual differences between observed and MRP expected values were smallest for LAs with large proportions of non-white ethnic populations. London boroughs that were markedly different from expected MRP values (90% posterior exceedance probability) had actively targeted risk groups. This type of synthesis allows more refined inferences to be made at small-area levels than previously feasible.
Takwoingi Y, Whitworth H, Rees-Roberts M, et al., 2019, Interferon gamma release assays for diagnostic evaluation of active tuberculosis (IDEA): test accuracy study and economic evaluation, Health Technology Assessment, Vol: 23, ISSN: 1366-5278
BackgroundInterferon gamma release assays (IGRAs) are blood tests recommended for the diagnosis of tuberculosis (TB) infection. There is currently uncertainty about the role and clinical utility of IGRAs in the diagnostic workup of suspected active TB in routine NHS clinical practice.ObjectivesTo compare the diagnostic accuracy and cost-effectiveness of T-SPOT.TB® (Oxford Immunotec, Abingdon, UK) and QuantiFERON® TB GOLD In-Tube (Cellestis, Carnegie, VIC, Australia) for diagnosis of suspected active TB and to estimate the diagnostic accuracy of second-generation IGRAs.DesignProspective within-patient comparative diagnostic accuracy study.SettingSecondary care.ParticipantsAdults (aged ≥ 16 years) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB.InterventionsThe index tests [T-SPOT.TB and QuantiFERON GOLD In-Tube (QFT-GIT)] and new enzyme-linked immunospot assays utilising novel Mycobacterium tuberculosis antigens (Rv3615c, Rv2654, Rv3879c and Rv3873) were verified against a composite reference standard applied by a panel of clinical experts blinded to IGRA results.Main outcome measuresSensitivity, specificity, predictive values and likelihood ratios were calculated to determine diagnostic accuracy. A decision tree model was developed to calculate the incremental costs and incremental health utilities [quality-adjusted life-years (QALYs)] of changing from current practice to using an IGRA as an initial rule-out test.ResultsA total of 363 patients had active TB (culture-confirmed and highly probable TB cases), 439 had no active TB and 43 had an indeterminate final diagnosis. Comparing T-SPOT.TB and QFT-GIT, the sensitivities [95% confidence interval (CI)] were 82.3% (95% CI 77.7% to 85.9%) and 67.3% (95% CI 62.1% to 72.2%), respectively, whereas specificities were 82.6% (95% CI 78.6% to 86.1%) and 80.4% (95% CI 76.1% to 84.1%), respectively. T-SPOT.TB was mor
Whittles L, White P, Didelot X, 2019, A dynamic power-law sexual network model of gonorrhoea outbreaks, PLoS Computational Biology, Vol: 15, ISSN: 1553-734X
Human networks of sexual contacts are dynamic by nature, with partnerships forming and breaking continuously over time. Sexual behaviours are also highly heterogeneous, so that the number of partners reported by individuals over a given period of time is typically distributed as a power-law. Both the dynamism and heterogeneity of sexual partnerships are likely to have an effect in the patterns of spread of sexually transmitted diseases. To represent these two fundamental properties of sexual networks, we developed a stochastic process of dynamic partnership formation and dissolution, which results in power-law numbers of partners over time. Model parameters can be set to produce realistic conditions in terms of the exponent of the power-law distribution, of the number of individuals without relationships and of the average duration of relationships. Using an outbreak of antibiotic resistant gonorrhoea amongst men have sex with men as a case study, we show that our realistic dynamic network exhibits different properties compared to the frequently used static networks or homogeneous mixing models. We also consider an approximation to our dynamic network model in terms of a much simpler branching process. We estimate the parameters of the generation time distribution and offspring distribution which can be used for example in the context of outbreak reconstruction based on genomic data. Finally, weinvestigate the impact of a range of interventions against gonorrhoea, including increased condom use, more frequent screening and immunisation, concluding that the latter shows great promise to reduce the burden of gonorrhoea, even if the vaccine was only partially effective or applied to only a random subset of the population.
Story A, Aldridge RW, Smith CM, et al., 2019, Smartphone-enabled video-observed versus directly observed treatment for tuberculosis: a multicentre, analyst-blinded, randomised, controlled superiority trial, Lancet, Vol: 393, Pages: 1216-1224, ISSN: 0140-6736
BACKGROUND: Directly observed treatment (DOT) has been the standard of care for tuberculosis since the early 1990s, but it is inconvenient for patients and service providers. Video-observed therapy (VOT) has been conditionally recommended by WHO as an alternative to DOT. We tested whether levels of treatment observation were improved with VOT. METHODS: We did a multicentre, analyst-blinded, randomised controlled superiority trial in 22 clinics in England (UK). Eligible participants were patients aged at least 16 years with active pulmonary or non-pulmonary tuberculosis who were eligible for DOT according to local guidance. Exclusion criteria included patients who did not have access to charging a smartphone. We randomly assigned participants to either VOT (daily remote observation using a smartphone app) or DOT (observations done three to five times per week in the home, community, or clinic settings). Randomisation was done by the SealedEnvelope service using minimisation. DOT involved treatment observation by a health-care or lay worker, with any remaining daily doses self-administered. VOT was provided by a centralised service in London. Patients were trained to record and send videos of every dose ingested 7 days per week using a smartphone app. Trained treatment observers viewed these videos through a password-protected website. Patients were also encouraged to report adverse drug events on the videos. Smartphones and data plans were provided free of charge by study investigators. DOT or VOT observation records were completed by observers until treatment or study end. The primary outcome was completion of 80% or more scheduled treatment observations over the first 2 months following enrolment. Intention-to-treat (ITT) and restricted (including only patients completing at least 1 week of observation on allocated arm) analyses were done. Superiority was determined by a 15% difference in the proportion of patients with the primary outcome (60% vs 75%). This trial
Halliday A, Jain P, Hoang L, et al., Validation of new technologies for the diagnostic evaluation of active tuberculosis (VANTDET), Efficacy and Mechanism Evaluation, ISSN: 2050-4365
Background: Tuberculosis (TB) is a devastating disease for which new diagnostic tests are desperately needed. Objective: To validate promising new technologies (namely whole blood transcriptomics, proteomics, flow cytometry and qRT-PCR) and existing signatures for detection of active TB in samples obtained from individuals suspected of active TB. Design: Four sub-studies, each of which used the samples from biobank collected as part of the IDEA study, which was a prospective cohort of patients recruited with suspected TB. Setting: secondary care Participants: Adults (aged ≥ 16 years old) presenting as inpatients or outpatients at 12 NHS hospital trusts in London, Slough, Oxford, Leicester and Birmingham with suspected active TB. Interventions: New tests using either: genome-wide gene expression microarray (transcriptomics); SELDI TOF/ LC-MS (proteomics), flow cytometry, qRT-PCR. Main outcome measures: Area under the curve (AUC), sensitivity and specificity, were calculated to determine diagnostic accuracy. Positive and negative predictive values were calculated in some cases. A decision tree model was developed to calculate the incremental costs and quality-adjusted life-years (QALYs) of changing from current practice to using the novels tests. Results: The project and 4 sub-studies which assessed the previous published signatures measured using each of the new technologies, and a health economic analysis where the best performing tests were evaluated for cost effectiveness. The diagnostic accuracy of the transcriptomic tests ranged from AUC=0.81-0.84 for detecting all TB in our cohort. The performance for detecting culture confirmed TB or pulmonary TB (PTB) was better than for highly probable TB or extrapulmonary TB (EPTB) respectively, but not high enough to be clinically useful. None of the previously described serum proteomic signatures for active TB provided good diagnostic accuracy, not did the candidate rule-out tests. Four of six previously described cell
Story A, Aldridge RW, Smith CM, et al., Smartphone-enabled video observed versus directly observed treatment for tuberculosis: a randomised controlled trial, Lancet, ISSN: 0140-6736
BackgroundDirectly observed treatment (DOT) has been the standard of care for tuberculosissince the early 1990s, but delivery entails substantial inconvenience to patients andservice providers. Remote video observed therapy (VOT) has recently beenconditionally recommended by the WHO as an alternative to DOT. We testedwhether levels of treatment observation were improved with VOT.MethodsWe conducted a randomised controlled trial of VOT (daily remote observation using asmartphone app) compared to DOT (three or five-weekly observation in home,community or clinic settings). Tuberculosis patients eligible for DOT at 22 clinics inEngland were allocated to trial arms by the SealedEnvelopeTM service usingrandomisation by minimisation. The primary outcome was completion of 80% or morescheduled treatment observations over the first two months following enrolment.Intention-to-treat and restricted (including only patients with at least one week ofobservation on allocated arm) analyses were conducted. The trial is registered withthe ISRCTN, number ISRCTN26184967.FindingsBetween September 1, 2014 and October 1, 2016, we enrolled 226 patients; 112randomised to VOT and 114 to DOT. Overall, 58% (131 of 226) had a history ofhomelessness, imprisonment, drug use, alcohol problems or mental health problems.Seventy percent of patients on VOT (78 of 112) had the primary outcome comparedto 31% (35 of 114) of those on DOT (adjusted odds ratio 5·48; 95% confidenceinterval 3·10-9·68; p<0·0001). Drop-out during the first week of observation was lessfor VOT (10%, 11 of 112) than DOT (51%, 58 of 114). High observation levels weresustained throughout treatment for VOT patients, but declined rapidly for DOTpatients.4InterpretationVOT is a more effective approach to observation of tuberculosis treatment than clinic-, community- or home-based DOT.
White PJ, Lewis J, 2018, Estimating chlamydia prevalence: more difficult than modelling suggests – Authors' reply, Lancet Public Health, Vol: 3, Pages: e417-e417, ISSN: 2468-2667
Whittles L, White PJ, Paul J, et al., 2018, Epidemiological trends of antibiotic resistant gonorrhoea in the United Kingdom, Antibiotics, Vol: 7, ISSN: 2079-6382
Gonorrhoea is one of the most common sexually-transmitted bacterial infections, globally and in the United Kingdom. The levels of antibiotic resistance in gonorrhoea reported in recent years represent a critical public health issue. From penicillins to cefixime, the gonococcus has become resistant to all antibiotics that have been previously used against it, in each case only a matter of years after introduction as a first-line therapy. After each instance of resistance emergence, the treatment recommendations have required revision, to the point that only a few antibiotics can reliably be prescribed to treat infected individuals. Most countries, including the UK, now recommend that gonorrhoea be treated with a dual therapy combining ceftriaxone and azithromycin. While this treatment is still currently effective for the vast majority of cases, there are concerning signs that this will not always remain the case, and there is no readily apparent alternative. Here, we review the use of antibiotics and epidemiological trends of antibiotic resistance in gonorrhoea from surveillance data over the past 15 years in the UK and describe how surveillance could be improved.
Menzies N, Wolf E, Connors D, et al., 2018, Progression from latent infection to active disease in dynamic TB transmission models: a systematic review of the validity of modelling assumptions, Lancet Infectious Diseases, Vol: 18, Pages: e228-e238, ISSN: 1473-3099
Mathematical modelling is commonly used to evaluate infectious disease control policy, and is influential in shaping policy and budgets. Mathematical models necessarily make assumptions about disease natural history, and if these assumptions are not valid the results of these studies may be biased. We conducted a systematic review of published TB transmission models, to assess the validity of assumptions about progression to active disease following initial infection (PROSPERO ID CRD42016030009). We searched PubMed, Web of Science, Embase, Biosis, and Cochrane Library, and included studies from the earliest available date (1962) to August 31st 2017. We identified 312 studies that met inclusion criteria. Predicted TB incidence varied widely across studies for each risk factor investigated. For population groups with no individual risk factors, annual incidence varied by several orders of magnitude, and 20-year cumulative incidence ranged from close to 0% to 100%. A substantial fraction of modelled results were inconsistent with empirical evidence—for 10-year cumulative incidence 40% of modelled results were more than double or less than half the empirical estimates. These results demonstrate substantial disagreement between modelling studies on a central feature of TB natural history. Greater attention to reproducing known features of TB epidemiology would strengthen future TB modelling studies, and readers of modelling studies are recommended to assess how well those studies demonstrate their validity.
Whittles L, Didelot X, Grad Y, et al., 2018, Testing for gonorrhoea should routinely include the pharynx, Lancet Infectious Diseases, Vol: 18, Pages: 716-717, ISSN: 1473-3099
The profile of Kit Fairley by Tony Kirby1 highlighted his work on the potentially important role of kissing among men who have sex with men (MSM) in gonorrhoea transmission. The role of pharyngeal infection in gonorrhoea transmission, and in the emergence and spread of antimicrobial resistance, is poorly characterised, which represents an important knowledge gap.2 Intimate kissing is a risk factor for meningococcal carriage,3 indicating other Neisseria spp can transmit via this route. Pharyngeal gonococcal infection is predominantly asymptomatic, frequently undetected, and often exposed to suboptimal antibiotic concentrations in therapy;2,4 hence infection might be persistent.
Braham C, White P, Arinaminpathy N, 2018, Management of tuberculosis by healthcare practitioners in Pakistan: A systematic review, PLoS ONE, Vol: 13, ISSN: 1932-6203
Objective:To assess the quality of tuberculosis (TB) care in Pakistan, through determining comparison of healthcare practitioners’ knowledge and practices to national and international TB care guidelines.Methods:Studies reporting on knowledge, attitudes and practices of public and private practitioners with TB patients were selected through searching electronic databases and grey literature.Findings:Of 1458 reports, 20 full-texts were assessed, of which 11 met the eligibility and quality criteria; all studies focused on private sector care. Heterogeneity precluded meta-analysis. In 3 of 4 studies, over 50% of practitioners correctly identified a cough as the main TB symptom. However, 4 out of 6 studies showed practitioners’ compliance to be low (under 50%) for the use of sputum microscopy in diagnosis. The poorest quality care occurred in the later stages of treatment, with low compliance in prescribing practices for continuation-phase care and in monitoring and recording treatment progress, the latter of which is particularly critical for treatment success.Conclusion:TB care was variable and generally inadequate, with both a lack of knowledge and a small ‘know-do’ gap evident—practitioners did not use methods that they know they should use. A lack of recent evidence found suggests that the quality of current practices may not be fully captured and further research is needed, especially on non-allopathic, rural and public-sector contexts. Improved training of practitioners, greater availability of recommended diagnostic tools and expansion of public-private partnerships are suggestions for improving the quality of TB care in Pakistan.
Lewis JEA, White P, 2018, Changes in chlamydia prevalence and duration of infection inferred from testing and diagnosis rates in England: an evidence synthesis using surveillance data, 2000-2015, Lancet Public Health, Vol: 3, Pages: E271-E278, ISSN: 2468-2667
Background: Chlamydia screening programmes have been implemented in several countries, but the effects of screening on incidence, prevalence and reproductive sequelae remain unclear. In England, despite increases in testing with the roll-out of the National Chlamydia Screening Programme (2003-2008), prevalence estimated in population-based surveys was similar in 1999-2001 and 2010-12 – although the precision of the estimates was limited. Methods: We used newly-published annual figures for chlamydia test coverage and diagnoses in England before, during and after the scale-up of national screening, with recently-developed statistical methods which account for symptomatic chlamydia testing and asymptomatic screening, to infer changes in prevalence and average duration of infections in each year. Findings: The data provided numbers of tests and diagnoses in 15-19 and 20-24-year-old men and women in England each year from 2000 to 2015, allowing annual – rather than ten-yearly – estimates of prevalence change. We inferred reductions in prevalence and average infection duration in both sexes once screening was fully implemented. From 2008 to 2010, inferred prevalence reductions were 0.7(0.3,1.4) and 0.8(0.4-1.3) percentage points in 15-24-year-old men and women, respectively (posterior median; 95% credible interval), and average duration of infection fell by 74(17-247) days in men and 30(22-40) days in women. Progress has recently reversed with declining testing. Interpretation: Our analysis provides the first evidence for a reduction in chlamydia prevalence in England concurrent with large-scale population testing. It also shows a consistent decline in the average duration of infections: a measure of screening effectiveness that is unaffected by behavioural changes.
Lewis J, White PJ, Changes in chlamydia prevalence and duration of infection estimated from testing and diagnosis rates in England: a model-based analysis using surveillance data, 2000–15, Lancet Public Health, ISSN: 2468-2667
Background:Chlamydia screening programmes have been implemented in several countries, but the effects of screening on incidence, prevalence, and reproductive sequelae remain unclear. In England, despite increases in testing with the rollout of the National Chlamydia Screening Programme (NCSP; 2003–08), prevalence estimated in 10-yearly population-based surveys was similar before (1999–2001) and after (2010–12) the programme. However, the precision of these previous estimates was limited by the low numbers of infections. We aimed to establish annual, rather than 10-yearly, estimates of chlamydia prevalence and infection duration.Methods:In this model-based analysis, we used previously published minimum and maximum estimates and Public Health England data for chlamydia test coverage and diagnoses in men and women aged 15–24 years in England, before, during, and after the scale-up of national chlamydia screening. We used a mechanistic model, which accounted for symptomatic chlamydia testing and asymptomatic screening, to estimate changes in prevalence and average duration of infections for each year. We describe estimates derived from the maximum and minimum numbers of tests and diagnoses as maximum and minimum estimates, regardless of their relative magnitude.FindingsThe data included numbers of tests and diagnoses in men and women aged 15–19 years and 20–24 years in England each year from 2000 to 2015. We estimated reductions in prevalence and average infection duration in both sexes once screening was fully implemented. From 2008 to 2010, estimated posterior median prevalence reductions in people aged 15–24 years were 0·68 percentage points (95% credible interval 0·26–1·40; minimum) and 0·66 percentage points (0·25–1·37; maximum) for men and 0·77 percentage points (0·45–1·27) for women (minimum and maximum estimates were the same for women). Ove
White PJ, Abubakar I, 2018, Hepatitis C virus treatment as prevention in people who inject drugs, Lancet Infectious Diseases, Vol: 18, Pages: 379-379, ISSN: 1473-3099
Rhead R, Elmes J, Otobo E, et al., 2018, Do female sex workers have lower uptake of HIV treatment services than non-sex-workers? A cross-sectional study from East Zimbabwe, BMJ Open, Vol: 8, ISSN: 2044-6055
Objective Globally, HIV disproportionately affects female sex workers (FSWs) yet HIV treatment coverage is suboptimal. To improve uptake of HIV services by FSWs, it is important to identify potential inequalities in access and use of care and their determinants. Our aim is to investigate HIV treatment cascades for FSWs and non-sex workers (NSWs) in Manicaland province, Zimbabwe, and to examine the socio-demographic characteristics and intermediate determinants that might explain differences in service uptake.Methods Data from a household survey conducted in 2009–2011 and a parallel snowball sample survey of FSWs were matched using probability methods to reduce under-reporting of FSWs. HIV treatment cascades were constructed and compared for FSWs (n=174) and NSWs (n=2555). Determinants of service uptake were identified a priori in a theoretical framework and tested using logistic regression.Results HIV prevalence was higher in FSWs than in NSWs (52.6% vs 19.8%; age-adjusted OR (AOR) 4.0; 95% CI 2.9 to 5.5). In HIV-positive women, FSWs were more likely to have been diagnosed (58.2% vs 42.6%; AOR 1.62; 1.02–2.59) and HIV-diagnosed FSWs were more likely to initiate ART (84.9% vs 64.0%; AOR 2.33; 1.03–5.28). No difference was found for antiretroviral treatment (ART) adherence (91.1% vs 90.5%; P=0.9). FSWs’ greater uptake of HIV treatment services became non-significant after adjusting for intermediate factors including HIV knowledge and risk perception, travel time to services, physical and mental health, and recent pregnancy.Conclusion FSWs are more likely to take up testing and treatment services and were closer to achieving optimal outcomes along the cascade compared with NSWs. However, ART coverage was low in all women at the time of the survey. FSWs’ need for, knowledge of and proximity to HIV testing and treatment facilities appear to increase uptake.
Bradshaw CS, Horner PJ, Jensen JS, et al., 2018, Syndromic management of STIs and the threat of untreatable Mycoplasma genitalium, Lancet Infectious Diseases, Vol: 18, Pages: 251-252, ISSN: 1473-3099
Mugwagwa T, Stagg H, Abubakar I, et al., 2018, Comparing different technologies for active TB case-finding among the homeless: a transmission-dynamic modelling study, Scientific Reports, Vol: 8, ISSN: 2045-2322
Homeless persons have elevated risk of tuberculosis (TB) and are under-served by conventional health services. Approaches to active case-finding (ACF) and treatment tailored to their needs are required. A transmission-dynamic model was developed to assess the effectiveness and efficiency of screening with mobile Chest X-ray, GeneXpert, or both. Effectiveness of ACF depends upon the prevalence of infection in the population (which determines screening ‘yield’), patient willingness to wait for GeneXpert results, and treatment adherence. ACF is efficient when TB prevalence exceeds 78/100,000 and 46% of drug sensitive TB cases and 33% of multi-drug resistant TB cases complete treatment. This threshold increases to 92/100,000 if additional post-ACF enhanced case management (ECM) increases treatment completion to 85%. Generally, the most efficient option is one-step screening of all patients with GeneXpert, but if too many patients (>27% without ECM, >19% with ECM) are unwilling to wait the 90 minutes required then two-step screening using chest X-ray (which is rapid) followed by GeneXpert for confirmation of TB is the most efficient option. Targeted ACF and support services benefit health through early successful treatment and averting TB transmission and disease. The optimal strategy is setting-specific, requiring careful consideration of patients’ needs regarding testing and treatment.
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
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 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.
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.
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