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Purpose: We aimed to review available data on the incidence of herpes simplex virus (HSV) keratitis and other HSV ocular disease and to estimate the global burden of HSV ocular disease. Methods: We searched Medline and Embase databases to October 2020 for studies reporting on the incidence of HSV ocular disease. Study quality was evaluated using a four-point checklist. Pooled estimates were applied to 2016 population data to estimate global HSV ocular disease burden. Numbers with uniocular vision impairment (any visual acuity <6/12) were estimated by applying published risks to case numbers. Results: Fourteen studies had incidence data; seven met our quality criteria. In 2016, an estimated 1.7 (95% confidence interval, 95% CI 1.0–3.0) million people had HSV keratitis, based on a pooled incidence of 24.0 (95% CI 14.0–41.0; N = 2; I2 = 97.7%) per 100,000 person-years. The majority had epithelial keratitis (pooled incidence 16.1 per 100,000; 95% CI 11.6–22.3; N = 3; I2 = 92.6%). Available studies were few and limited to the USA and Europe. Data were even more limited for HSV uveitis and retinitis, although these conditions may collectively contribute a further >0.1 million cases. Based on global incidence, some 230,000 people may have newly acquired uniocular vision impairment associated with HSV keratitis in 2016. Conclusion: Over 1.8 million people may have herpetic eye disease annually. Preventing HSV infection could therefore have an important impact on eye health. Herpetic eye disease burden is likely to have been underestimated, as many settings outside of the USA and Europe have higher HSV-1 prevalence and poorer access to treatment. [ABSTRACT FROM AUTHOR]

Background: Chlamydia is the most common sexually transmitted bacterial infection in Scotland, and is associated with potentially serious reproductive outcomes, including pelvic inflammatory disease (PID) and tubal factor infertility (TFI) in women. Chlamydia testing in Scotland is currently targeted towards symptomatic individuals, individuals at high risk of existing undetected infection, and young people. The cost-effectiveness of testing and treatment to prevent PID and TFI in Scotland is uncertain. Methods: A compartmental deterministic dynamic model of chlamydia infection in 15-24 year olds in Scotland was developed. The model was used to estimate the impact of a change in testing strategy from baseline (16.8% overall testing coverage; 0.4 partners notified and tested/treated per treated positive index) on PID and TFI cases. Cost-effectiveness calculations informed by best-available estimates of the quality-adjusted life years (QALYs) lost due to PID and TFI were also performed. Results: Increasing overall testing coverage by 50% from baseline to 25.2% is estimated to result in 21% fewer cases in young women each year (PID: 703 fewer; TFI: 88 fewer). A 50% decrease to 8.4% would result in 20% more PID (669 additional) and TFI (84 additional) cases occurring annually. The cost per QALY gained of current testing activities compared to no testing is £40,034, which is above the £20,000-£30,000 cost-effectiveness threshold. However, calculations are hampered by lack of reliable data. Any increase in partner notification from baseline would be cost-effective (incremental cost per QALY gained for a partner notification efficacy of 1 compared to baseline: £5,119), and would increase the cost-effectiveness of current testing strategy compared to no testing, with threshold cost-effectiveness reached at a partner notification efficacy of 1.5. However, there is uncertainty in the extent to which partner notification is currently done, and hence the amount by which it could potentially be increased. Conclusions: Current chlamydia testing strategy in Scotland is not cost-effective under the conservative model assumptions applied. However, with better data enabling some of these assumptions to be relaxed, current coverage could be cost-effective. Meanwhile, increasing partner notification efficacy on its own would be a cost-effective way of preventing PID and TFI from current strategy. [ABSTRACT FROM AUTHOR]

Objectives: We aimed to explore patient pathways using a chlamydia/gonorrhoea point-of-care (POC) nucleic acid amplification test (NAAT), and estimate and compare the costs of the proposed POC pathways with the current pathways using standard laboratory-based NAAT testing. Design/participants: Workshops were conducted with healthcare professionals at four sexual health clinics representing diverse models of care in the UK. They mapped out current pathways that used chlamydia/gonorrhoea tests, and constructed new pathways using a POC NAAT. Healthcare professionals' time was assessed in each pathway. Outcome measure: The proposed POC pathways were then priced using a model built in Microsoft Excel, and compared to previously published costs for pathways using standard NAAT-based testing in an off-site laboratory. Results: Pathways using a POC NAAT for asymptomatic and symptomatic patients and chlamydia/gonorrhoea-only tests were shorter and less expensive than most of the current pathways. Notably, we estimate that POC testing as part of a sexual health screen for symptomatic patients, or as stand-alone chlamydia/gonorrhoea testing, could reduce costs per patient by as much as £16 or £6, respectively. In both cases, healthcare professionals' time would be reduced by approximately 10 min per patient. Conclusions: POC testing for chlamydia/gonorrhoea in a clinical setting may reduce costs and clinician time, and may lead to more appropriate and quicker care for patients. Further study is warranted on how to best implement POC testing in clinics, and on the broader clinical and cost implications of this technology. [ABSTRACT FROM AUTHOR]

Background: A national chlamydia screening programme is currently being rolled out in the UK and other countries. However, much of the epidemiology remains poorly understood. In this paper we present a stochastic, individual based, dynamic sexual network model of chlamydia transmission and its parameterisation. Mathematical models provide a theoretical framework for understanding the key epidemiological features of chlamydia: sexual behaviour, health care seeking and transmission dynamics. Results: The model parameters were estimated either directly or by systematic fitting to a variety of appropriate data sources. The fitted model was representative of sexual behaviour, chlamydia epidemiology and health care use in England. We were able to recapture the observed age distribution of chlamydia prevalence. Conclusion: Estimating parameters for models of sexual behaviour and transmission of chlamydia is complex. Most of the parameter values are highly correlated, highly variable and there is little empirical evidence to inform estimates. We used a novel approach to estimate the rate of active treatment seeking, by combining data sources, which improved the credibility of the model results. The model structure is flexible and is broadly applicable to other developed world settings and provides a practical tool for public health decision makers. [ABSTRACT FROM AUTHOR]

Objective To generate global and regional estimates for the prevalence and incidence of herpes simplex virus (HSV) type 1 and type 2 infection for 2016. Methods To obtain data, we undertook a systematic review to identify studies up to August 2018. Adjustments were made to account for HSV test sensitivity and specificity. For each World Health Organization (WHO) region, we applied a constant incidence model to pooled prevalence by age and sex to estimate the prevalence and incidence of HSV types 1 and 2 infections. For HSV type 1, we apportioned infection by anatomical site using pooled estimates of the proportions that were oral and genital. Findings In 2016, an estimated 491.5 million people (95% uncertainty interval, UI: 430.4 million--610.6 million) were living with HSV type 2 infection, equivalent to 13.2% of the world's population aged 15--49 years. An estimated 3752.0 million people (95% UI: 3555.5 million--3854.6 million) had HSV type 1 infection at any site, equivalent to a global prevalence of 66.6% in 0--49-year-olds. Differing patterns were observed by age, sex and geographical region, with HSV type 2 prevalence being highest among women and in the WHO African Region. Conclusion An estimated half a billion people had genital infection with HSV type 2 or type 1, and several billion had oral HSV type 1 infection. Millions of people may also be at higher risk of acquiring human immunodeficiency virus (HIV), particularly women in the WHO African Region who have the highest HSV type 2 prevalence and exposure to HIV. [ABSTRACT FROM AUTHOR]

Antibiotic use (ABU) plays an important role in the proliferation of antimicrobial resistance (AMR). Global antimicrobial consumption in food production is projected to rise by 67% from 2010 to 2030, but available estimates are limited by the scarcity of ABU data and absence of global surveillance systems. The WHO South-East Asia (WHO SEA) region is at high risk of emergence of AMR, likely driven by intensifying farm operations and worsening ABU hotspots. However, little is known about farm-level ABU practices in the region. To summarize emerging evidence and research gaps, we conducted a scoping review of ABU practices following the Arksey and O'Malley methodological framework. We included studies published between 2010 and 2021 on farm-level ABU/AMR in the 11 WHO SEA member states, and databases were last searched on 31 October 2021. Our search strategy identified 184 unique articles, and 25 publications underwent full-text eligibility assessment. Seventeen studies, reported in 18 publications, were included in the scoping review. We found heterogeneity in the categorizations, definitions, and ABU characterization methods used across studies and farm types. Most studies involved poultry, pig, and cattle farms, and only one study examined aquaculture. Most studies evaluated ABU prevalence by asking respondents about the presence or absence of ABU in the farm. Only two studies quantified antibiotic consumption, and sampling bias and lack of standardized data collection methods were identified as key limitations. Emerging evidence that farm workers had difficulty differentiating antibiotics from other substances contributed to the uncertainty about the reliability of self-reported data without other validation techniques. ABU for growth promotion and treatment were prevalent. We found a large overlap in the critically important antibiotics used in farm animals and humans. The ease of access to antibiotics compounded by the difficulties in accessing quality veterinary care and preventive services likely drive inappropriate ABU in complex ways., (© 2022 The Authors.)

Background: Biological and epidemiological evidence suggest that herpes simplex virus type 2 (HSV-2) elevates HIV acquisition and transmission risks. We improved previous estimates of the contribution of HSV-2 to HIV infections by using a dynamic transmission model., Setting: World Health Organization regions., Methods: We developed a mathematical model of HSV-2/HIV transmission among 15- to 49-year-old heterosexual, non-drug-injecting populations, calibrated using region-specific demographic and HSV-2/HIV epidemiological data. We derived global and regional estimates of the contribution of HSV-2 to HIV infection over 10 years [the transmission population-attributable fraction (tPAF)] under 3 additive scenarios, assuming: (1) HSV-2 increases only HIV acquisition risk (conservative); (2) HSV-2 also increases HIV transmission risk (liberal); and (3) HIV or antiretroviral therapy (ART) also modifies HSV-2 transmission risk, and HSV-2 decreases ART effect on HIV transmission risk (fully liberal)., Results: Under the conservative scenario, the predicted tPAF was 37.3% (95% uncertainty interval: 33.4%-43.2%), and an estimated 5.6 (4.5-7.0) million incident heterosexual HIV infections were due to HSV-2 globally over 2009-2018. The contribution of HSV-2 to HIV infections was largest for the African region [tPAF = 42.6% (38.0%-51.2%)] and lowest for the European region [tPAF = 11.2% (7.9%-13.8%)]. The tPAF was higher among female sex workers, their clients, and older populations, reflecting their higher HSV-2 prevalence. The tPAF was approximately 50% and 1.3- to 2.4-fold higher for the liberal or fully liberal scenario than the conservative scenario across regions., Conclusion: HSV-2 may have contributed to at least 37% of incident HIV infections in the past decade worldwide, and even more in Africa, and may continue to do so despite increased ART access unless future improved HSV-2 control measures, such as vaccines, become available., Competing Interests: K.J.L. and K.M.E.T. report a grant from GSK outside the submitted work. This work was funded by the World Health Organization, through the UNDP-UNFPAUNICEF-WHO-World Bank Special Program of Research, Development, and Research Training in Human Reproduction, a cosponsored program executed by the WHO, and through support from the US National Institute of Allergy and Infectious Diseases, part of the US National Institutes of Health (NIH) (NIH U01 AI108543). This work was partly supported by the HPTN Modelling Centre, which is funded by the NIH (NIH UM1 AI068617) through the HPTN Statistical and Data Management Center. R.S., H.L.C., R.F.B., J.S., L.S., and M.C.B. acknowledged funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth, and Development Office (FCDO), under the MRC/FCDO Concordat agreement and are also part of the EDCTP2 program supported by the European Union. S.G. acknowledged additional funding support from NIH (U01AI139547). K.J.L. and K.M.E.T. thank the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Evaluation of Interventions at the University of Bristol, in partnership with Public Health England (PHE), for research support. RH received funding from the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement, which is also part of the EDCTP2 program supported by the European Union. Grant Ref: MR/R010161/1. R.F.B. is supported by a Wellcome Trust Institutional Strategic Support Fund Fellowship (204801/Z/16/Z). P.V. also acknowledged support from the NIHR Health Protection Research Unit in Behavioural Science and Evaluation at University of Bristol. The authors alone are responsible for the views expressed in this article, and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated, the WHO, the NHS, the NIHR the Department of Health and Social Care, or Public Health England. The remaining authors have no conflicts of interest to disclose., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Antibacterial resistance (ABR) is a major global health security threat, with a disproportionate burden on lower-and middle-income countries (LMICs). It is not understood how 'One Health', where human health is co-dependent on animal health and the environment, might impact the burden of ABR in LMICs. Thailand's 2017 "National Strategic Plan on Antimicrobial Resistance" (NSP-AMR) aims to reduce AMR morbidity by 50% through 20% reductions in human and 30% in animal antibacterial use (ABU). There is a need to understand the implications of such a plan within a One Health perspective., Methods: A model of ABU, gut colonisation with extended-spectrum beta-lactamase (ESBL)-producing bacteria and transmission was calibrated using estimates of the prevalence of ESBL-producing bacteria in Thailand. This model was used to project the reduction in human ABR over 20 years (2020-2040) for each One Health driver, including individual transmission rates between humans, animals and the environment, and to estimate the long-term impact of the NSP-AMR intervention., Results: The model predicts that human ABU was the most important factor in reducing the colonisation of humans with resistant bacteria (maximum 65.7-99.7% reduction). The NSP-AMR is projected to reduce human colonisation by 6.0-18.8%, with more ambitious targets (30% reductions in human ABU) increasing this to 8.5-24.9%., Conclusions: Our model provides a simple framework to explain the mechanisms underpinning ABR, suggesting that future interventions targeting the simultaneous reduction of transmission and ABU would help to control ABR more effectively in Thailand., Competing Interests: Declarations of interest: none, (© 2021 The Authors.)

Pertussis, or whooping cough, is an important respiratory infection causing considerable infant mortality worldwide. Recently, incidence has risen in countries with strong vaccine programmes and there are concerns about antigenic shift resulting in vaccine evasion. Interactions between pertussis and non-vaccine-preventable strains will play an important role in the evolution and population dynamics of pertussis. In particular, if we are to understand the role strain replacement plays in vaccinated settings, it will be essential to understand how strains or variants of pertussis interact. Here we explore under what conditions we would expect strain replacement to be of concern in pertussis. We develop a dynamic transmission model that allows for coinfection between Bordetella pertussis (the main causative agent of pertussis) and a strain or variant unaffected by the vaccine. We incorporate both neutrality (in the sense of ecological/population genetic neutrality) and immunity into the model, leaving the specificity of the immune response flexible. We find that strain replacement may be considerable when immunity is non-specific. This is in contrast to previous findings where neutrality was not considered. We conclude that the extent to which models reflect ecological neutrality can have a large impact on conclusions regarding strain replacement. This will likely have onward consequences for estimates of vaccine efficacy and cost-effectiveness., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: 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., Objective: To study the effectiveness and cost-effectiveness of traditional and new partner notification technologies for curable sexually transmitted infections (STIs)., Design: Secondary data analysis of clinical audit data; systematic reviews of randomised controlled trials (MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials) published from 1 January 1966 to 31 August 2012 and of studies of health-related quality of life (HRQL) [MEDLINE, EMBASE, ISI Web of Knowledge, NHS Economic Evaluation Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA)] published from 1 January 1980 to 31 December 2011; static models of clinical effectiveness and cost-effectiveness; and dynamic modelling studies to improve parameter estimation and examine effectiveness., Setting: General population and genitourinary medicine clinic attenders., Participants: Heterosexual women and men., Interventions: Traditional partner notification by patient or provider referral, and new partner notification by expedited partner therapy (EPT) or its UK equivalent, accelerated partner therapy (APT)., Main Outcome Measures: Population prevalence; index case reinfection; and partners treated per index case., Results: Enhanced partner therapy reduced reinfection in index cases with curable STIs more than simple patient referral [risk ratio (RR) 0.71; 95% confidence interval (CI) 0.56 to 0.89]. There are no randomised trials of APT. The median number of partners treated for chlamydia per index case in UK clinics was 0.60. The number of partners needed to treat to interrupt transmission of chlamydia was lower for casual than for regular partners. In dynamic model simulations, >10% of partners are chlamydia positive with look-back periods of up to 18 months. In the presence of a chlamydia screening programme that reduces population prevalence, treatment of current partners achieves most of the additional reduction in prevalence attributable to partner notification. Dynamic model simulations show that cotesting and treatment for chlamydia and gonorrhoea reduce the prevalence of both STIs. APT has a limited additional effect on prevalence but reduces the rate of index case reinfection. Published quality-adjusted life-year (QALY) weights were of insufficient quality to be used in a cost-effectiveness study of partner notification in this project. Using an intermediate outcome of cost per infection diagnosed, doubling the efficacy of partner notification from 0.4 to 0.8 partners treated per index case was more cost-effective than increasing chlamydia screening coverage., Conclusions: There is evidence to support the improved clinical effectiveness of EPT in reducing index case reinfection. In a general heterosexual population, partner notification identifies new infected cases but the impact on chlamydia prevalence is limited. Partner notification to notify casual partners might have a greater impact than for regular partners in genitourinary clinic populations. Recommendations for future research are (1) to conduct randomised controlled trials using biological outcomes of the effectiveness of APT and of methods to increase testing for human immunodeficiency virus (HIV) and STIs after APT; (2) collection of HRQL data should be a priority to determine QALYs associated with the sequelae of curable STIs; and (3) standardised parameter sets for curable STIs should be developed for mathematical models of STI transmission that are used for policy-making., Funding: The National Institute for Health Research Health Technology Assessment programme.

Objectives: The common seasonality of incidence of invasive pneumococcal disease (IPD) and viral respiratory infections has long been recognized, however, the extent to which this affects the association between the pathogens is unknown. We have analysed weekly surveillance data of IPD, influenza and respiratory syncytial virus (RSV), using ambient temperature and hours of sunshine as measures of seasonality., Methods: Reported cases of influenza, IPD and RSV, were collected in England and Wales, from week 1 (January) 1996 to week 23 (June) 2009. The associations between IPD and respiratory viral infections were analysed using several statistical methods, including correlation coefficients and both additive and multiplicative regression models., Results: 6-7.5% of cases of IPD are attributable to influenza and 3-4% attributable to RSV. Correlation coefficients reported considerably stronger associations between IPD and the viral infections compared to regression models., Conclusions: A small but potentially important percentage of IPD may be attributable to influenza and RSV when adjusted for seasonality by temperature. Jointly these viral infections may lead to over 10% of IPD cases. Therefore, prevention of viral respiratory infections may offer some additional benefit in reducing invasive pneumococcal infections., (Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Chlamydia trachomatis is the most common bacterial sexually transmitted infection (STI) in many developed countries. The highest prevalence rates are found among young adults who have frequent partner change rates. Three published individual-based models have incorporated a detailed description of age-specific sexual behaviour in order to quantify the transmission of C. trachomatis in the population and to assess the impact of screening interventions. Owing to varying assumptions about sexual partnership formation and dissolution and the great uncertainty about critical parameters, such models show conflicting results about the impact of preventive interventions. Here, we perform a detailed evaluation of these models by comparing the partnership formation and dissolution dynamics with data from Natsal 2000, a population-based probability sample survey of sexual attitudes and lifestyles in Britain. The data also allow us to describe the dispersion of C. trachomatis infections as a function of sexual behaviour, using the Gini coefficient. We suggest that the Gini coefficient is a useful measure for calibrating infectious disease models that include risk structure and highlight the need to estimate this measure for other STIs.

Background: The program eBURST uses multilocus sequence typing data to divide bacterial populations into groups of closely related strains (clonal complexes), predicts the founding genotype of each group, and displays the patterns of recent evolutionary descent of all other strains in the group from the founder. The reliability of eBURST was evaluated using populations simulated with different levels of recombination in which the ancestry of all strains was known., Results: For strictly clonal simulations, where all allelic change is due to point mutation, the groups of related strains identified by eBURST were very similar to those expected from the true ancestry and most of the true ancestor-descendant relationships (90-98%) were identified by eBURST. Populations simulated with low or moderate levels of recombination showed similarly high performance but the reliability of eBURST declined with increasing recombination to mutation ratio. Populations simulated under a high recombination to mutation ratio were dominated by a single large straggly eBURST group, which resulted from the incorrect linking of unrelated groups of strains into the same eBURST group. The reliability of the ancestor-descendant links in eBURST diagrams was related to the proportion of strains in the largest eBURST group, which provides a useful guide to when eBURST is likely to be unreliable., Conclusion: Examination of eBURST groups within populations of a range of bacterial species showed that most were within the range in which eBURST is reliable, and only a small number (e.g. Burkholderia pseudomallei and Enterococcus faecium) appeared to have such high rates of recombination that eBURST is likely to be unreliable. The study also demonstrates how three simple tests in eBURST v3 can be used to detect unreliable eBURST performance and recognise populations in which there appears to be a high rate of recombination relative to mutation.

Such are the challenges, and the potential, presented by complete genome sequences that the eventual erosion of the boundaries between biochemistry, ecology, bioinformatics, population biology, epidemiology and medical microbiology will perhaps be the most profound legacy of the genomics revolution. The development of nucleotide sequence-based typing schemes (multilocus sequence typing (MLST)) represents a similar synthesis, for this technique both matches the practical requirements for a highly portable standard for strain characterisation whilst also being firmly grounded in the population biology principles of multilocus enzyme electrophoresis (MLEE). Contrary to recent claims that population biology analyses of public health-oriented MLST data 'obscures its utility in applied microbiology' [Maiden MC. Multilocus sequence typing of bacteria. Annu Rev Microbiol 2006;60:561-88.], we argue that such an emphasis is essential for full interpretation of the data. Here we note a pertinent case in point; how a consideration of the rates of genetic recombination can help to explain why MLST data tend to correlate with virulence properties in some species (Neisseria meningitidis) but not in others (Staphylococcus aureus). We also discuss how the argument applies to the identification of recently emerged methicillin-resistant S. aureus (MRSA) clones using MLST. We conclude with a speculative rationale for promoting the 'clonal complexes' of S. aureus to species status.