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Author(s): Chiara Chiavenna 1,*, Anne M. Presanis 1, Andre Charlett 2, Simon de Lusignan 3, Shamez Ladhani 2, Richard G. Pebody 2, Daniela De Angelis 1,2,* Introduction Just one century [...], Background Measures of the contribution of influenza to Streptococcus pneumoniae infections, both in the seasonal and pandemic setting, are needed to predict the burden of secondary bacterial infections in future pandemics to inform stockpiling. The magnitude of the interaction between these two pathogens has been difficult to quantify because both infections are mainly clinically diagnosed based on signs and symptoms; a combined viral-bacterial testing is rarely performed in routine clinical practice; and surveillance data suffer from confounding problems common to all ecological studies. We proposed a novel multivariate model for age-stratified disease incidence, incorporating contact patterns and estimating disease transmission within and across groups. Methods and findings We used surveillance data from England over the years 2009 to 2017. Influenza infections were identified through the virological testing of samples taken from patients diagnosed with influenza-like illness (ILI) within the sentinel scheme run by the Royal College of General Practitioners (RCGP). Invasive pneumococcal disease (IPD) cases were routinely reported to Public Health England (PHE) by all the microbiology laboratories included in the national surveillance system. IPD counts at week t, conditional on the previous time point t-1, were assumed to be negative binomially distributed. Influenza counts were linearly included in the model for the mean IPD counts along with an endemic component describing some seasonal background and an autoregressive component mimicking pneumococcal transmission. Using age-specific counts, Akaike information criterion (AIC)-based model selection suggested that the best fit was obtained when the endemic component was expressed as a function of observed temperature and rainfall. Pneumococcal transmission within the same age group was estimated to explain 33.0% (confidence interval [CI] 24.9%-39.9%) of new cases in the elderly, whereas 50.7% (CI 38.8%-63.2%) of incidence in adults aged 15-44 years was attributed to transmission from another age group. The contribution of influenza on IPD during the 2009 pandemic also appeared to vary greatly across subgroups, being highest in school-age children and adults (18.3%, CI 9.4%-28.2%, and 6.07%, CI 2.83%-9.76%, respectively). Other viral infections, such as respiratory syncytial virus (RSV) and rhinovirus, also seemed to have an impact on IPD: RSV contributed 1.87% (CI 0.89%-3.08%) to pneumococcal infections in the 65+ group, whereas 2.14% (CI 0.87%-3.57%) of cases in the group of 45- to 64-year-olds were attributed to rhinovirus. The validity of this modelling strategy relies on the assumption that viral surveillance adequately represents the true incidence of influenza in the population, whereas the small numbers of IPD cases observed in the younger age groups led to significant uncertainty around some parameter estimates. Conclusions Our estimates suggested that a pandemic wave of influenza A/H1N1 with comparable severity to the 2009 pandemic could have a modest impact on school-age children and adults in terms of IPD and a small to negligible impact on infants and the elderly. The seasonal impact of other viruses such as RSV and rhinovirus was instead more important in the older population groups.

Introduction: The HIV epidemic in England is largely concentrated among heterosexuals who are predominately black African and men who have sex with men (MSM). We present for the first time trends in annual HIV incidence for adults attending sexual health clinics, where 80% of all HIV diagnoses are made. Methods: We identified newly diagnosed incident HIV using a recent infection testing algorithm (RITA) consisting of a biomarker (AxSYM assay, modified to determine antibody avidity), epidemiological and clinical information. We estimated HIV incidence using the WHO RITA formula for cross-sectional studies, with HIV testing data from sexual health clinics as the denominator. Results: From 2009 to 2013, each year, between 9,700 and 26,000 black African heterosexuals (of between 161,000 and 231,000 heterosexuals overall) were included in analyses. For the same period, annually between 19,000 and 55,000 MSM were included. Estimates of HIV incidence among black Africans increased slightly (although non-significantly) from 0.15% (95% C.I.0.05%-0.26%) in 2009 to 0.19% (95% C.I.0.04%-0.34%) in 2013 and was 4-5-fold higher than among all heterosexuals among which it remained stable between 0.03% (95% C.I.0.02%-0.05%) and 0.05% (95% C.I.0.03%-0.07%) over the period. Among MSM incidence was highest and increased (non-significantly) from 1.24% (95%C.I 0.96–1.52%) to 1.46% (95% C.I 1.23%-1.70%) after a peak of 1.52% (95%C.I 1.30%-1.75%) in 2012. Conclusion: These are the first nationwide estimates for trends in HIV incidence among black African and heterosexual populations in England which show black Africans, alongside MSM, remain disproportionately at risk of infection. Although people attending sexual health clinics may not be representative of the general population, nearly half of black Africans and MSM had attended in the previous 5 years. Timely and accurate incidence estimates will be critical in monitoring the impact of the reconfiguration of sexual health services in England, and any prevention programmes such as pre-exposure prophylaxis. [ABSTRACT FROM AUTHOR]

Background: One pathway through which pandemic influenza strains might emerge is reassortment from coinfection of different influenza A viruses. Seasonal influenza vaccines are designed to target the circulating strains, which intuitively decreases the prevalence of coinfection and the chance of pandemic emergence due to reassortment. However, individual-based analyses on 2009 pandemic influenza show that the previous seasonal vaccination may increase the risk of pandemic A(H1N1) pdm09 infection. In view of pandemic influenza preparedness, it is essential to understand the overall effect of seasonal vaccination on pandemic emergence via reassortment. Methods and Findings: In a previous study we applied a population dynamics approach to investigate the effect of infection-induced cross-immunity on reducing such a pandemic risk. Here the model was extended by incorporating vaccination for seasonal influenza to assess its potential role on the pandemic emergence via reassortment and its effect in protecting humans if a pandemic does emerge. The vaccination is assumed to protect against the target strains but only partially against other strains. We find that a universal seasonal vaccine that provides full-spectrum cross-immunity substantially reduces the opportunity of pandemic emergence. However, our results show that such effectiveness depends on the strength of infection-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 pandemic emergence; if it is very strong, the same kind of vaccine increases the probability of pandemic emergence. Conclusions: Two types of vaccines are available: inactivated and live attenuated, only live attenuated vaccines can induce heterosubtypic immunity. Current vaccines are effective in controlling circulating strains; they cannot always help restrain pandemic emergence because of the uncertainty of the oncoming reassortant strains, however. This urges the development of universal vaccines for prevention of pandemic influenza. [ABSTRACT FROM AUTHOR]

Our objective in this study was to estimate the probability that a Chlamydia trachomatis (CT) infection will cause an episode of clinical pelvic inflammatory disease (PID) and the reduction in such episodes among women with CT that could be achieved by annual screening. We reappraised evidence from randomized controlled trials of screening and controlled observational studies that followed untreated CT-infected and -uninfected women to measure the development of PID. Data from these studies were synthesized using a continuous-time Markov model which takes into account the competing risk of spontaneous clearance of CT. Using a 2-step piecewise homogenous Markov model that accounts for the distinction between prevalent and incident infections, we investigated the possibility that the rate of PID due to CT is greater during the period immediately following infection. The available data were compatible with both the homogenous and piecewise homogenous models. Given a homogenous model, the probability that a CT episode will cause clinical PID was 0.16 (95% credible interval (CrI): 0.06, 0.25), and annual screening would prevent 61% (95% CrI: 55, 67) of CT-related PID in women who became infected with CT. Assuming a piecewise homogenous model with a higher rate during the first 60 days, corresponding results were 0.16 (95% CrI: 0.07, 0.26) and 55% (95% CrI: 32, 72), respectively. [ABSTRACT FROM PUBLISHER]

Aims To investigate childhood influences on onset of injection drug use. Design Matched case-control study. Setting Edinburgh, Scotland. Participants A total of 432 individuals presenting at a community health facility with injection drug use and 432 age- and sex-matched non-injecting controls recruited through the same facility. Measurements Main exposures considered were family structure and experience of public care, carer substance use, physical and sexual victimization and conduct problems, all measured at personal interview. The outcome was history of adult injection drug use recorded in medical records corroborated at personal interview. Findings Compared to two-parent families all other family structures were associated with increased risk of injection drug use, the greatest increased risk being associated with public care. Violence, criminality and financial problems in the family were also associated with increased risk, as were all types of carer substance use. The greatest increased risk was associated with markers of early conduct problems, particularly school exclusion and childhood contact with the criminal justice system. In multivariable analyses the strongest risk factors for later injecting were always having lived with a relative or family friend (not always a parent) and in care/adopted/foster home at any point [odds ratio ( OR) = 2.66, 95% confidence interval ( CI): 1.02-6.92 and OR = 2.17, 95% CI: 0.91-5.17, respectively], experienced violence from parent or carer ( OR = 2.06, 95% CI: 1.26, 3.38) and early evidence of conduct problems [ever excluded from school ( OR = 2.73, 95% CI: 1.68, 4.45); childhood criminality (ever arrested by police pre-adult OR = 3.05, 95% CI: 1.90, 4.89, ever been in borstal/young offenders/list D school OR = 4.70, 95% CI: 2.02, 10.94)]. After adjustment for family structure and conduct problems, sexual victimization was associated weakly with injecting onset ( OR = 1.29, 95% CI: 0.76-2.19). More than 70% of injection drug use onset appeared attributable to the risk factors identified. Conclusions Injection drug use in adults is associated strongly with prior childhood adversity, in particular not living with both parents and early conduct problems. Prevention initiatives should also consider these risk factors. [ABSTRACT FROM AUTHOR]

ABSTRACT Aims To investigate whether opiate substitution therapy (OST) and needle and syringe programmes (NSP) can reduce hepatitis C virus (HCV) transmission among injecting drug users (IDUs). Design Meta-analysis and pooled analysis, with logistic regression allowing adjustment for gender, injecting duration, crack injecting and homelessness. Setting Six UK sites (Birmingham, Bristol, Glasgow, Leeds, London and Wales), community recruitment. Participants A total of 2986 IDUs surveyed during 2001-09. Measurement Questionnaire responses were used to define intervention categories for OST (on OST or not) and high NSP coverage (≥100% versus <100% needles per injection). The primary outcome was new HCV infection, measured as antibody seroconversion at follow-up or HCV antibody-negative/RNA-positive result in cross-sectional surveys. Findings Preliminary meta-analysis showed little evidence of heterogeneity between the studies on the effects of OST ( I2 = 48%, P = 0.09) and NSP ( I2 = 0%, P = 0.75), allowing data pooling. The analysis of both interventions included 919 subjects with 40 new HCV infections. Both receiving OST and high NSP coverage were associated with a reduction in new HCV infection [adjusted odds ratios (AORs) = 0.41, 95% confidence interval (CI): 0.21-0.82 and 0.48, 95% CI: 0.25-0.93, respectively]. Full harm reduction (on OST plus high NSP coverage) reduced the odds of new HCV infection by nearly 80% (AOR = 0.21, 95% CI: 0.08-0.52). Full harm reduction was associated with a reduction in self-reported needle sharing by 48% (AOR 0.52, 95% CI: 0.32-0.83) and mean injecting frequency by 20.8 injections per month (95% CI: −27.3 to −14.4). Conclusions There is good evidence that uptake of opiate substitution therapy and high coverage of needle and syringe programmes can substantially reduce the risk of hepatitis C virus transmission among injecting drug users. Research is now required on whether the scaling-up of intervention exposure can reduce and limit hepatitis C virus prevalence in this population. [ABSTRACT FROM AUTHOR]

Changes in hepatitis C virus (HCV) prevalence from 1992 to 2006 were examined by using 24,311 records from unlinked anonymous surveillance of injecting drug users in England and Wales. Bayesian logistic regression was used to estimate annual prevalence, accounting for changing recruitment patterns (age, gender, injecting duration, geographic region, interactions) and the sensitivity and specificity of different oral fluid testing devices. After controlling for these differences, the authors found that the adjusted HCV prevalence decreased from 70% (95% credible interval: 62, 78) in 1992 to 47% (95% credible interval: 43, 51) in 1998 before rising again to 53% (95% credible interval: 48, 58) in 2006. Women injecting drug users had a higher HCV risk than did men (odds ratio = 1.50, 95% credible interval: 1.31, 1.73). Two regions (London and North West) had a markedly higher HCV prevalence than did the rest of England and Wales. Among individuals who had injected for less than 1 year, the adjusted HCV prevalence in 2006 was higher than that in 1992 (28% vs. 19%, respectively). HCV infection can be prevented. The public health challenge in England and Wales is to increase action in order to regain a downward trend in HCV risk and the benefit that has been lost since 1998. [ABSTRACT FROM PUBLISHER]

In this paper, the authors propose a method for estimating the incidence of heroin use by adjusting reported numbers of heroin users visiting drug treatment agencies for the time lag between onset of heroin use and first treatment request (lag distribution). The adjusted incidence is relative, since it represents the number of individuals beginning heroin use in each year whose cases will be reported within 8 years of starting use. Users with longer lag times or whose cases are never reported are excluded. Utilizing data from southeastern England (1991-1998), the authors analyzed the effects of covariates (sex, age group, ethnic group, route of consumption, and year of onset of drug use) on the lag distribution. Trends in the adjusted incidence of heroin use were very different for injectors and noninjectors: Incidence among injectors seemed to be stable, while in noninjectors it increased twofold between 1991 and 1996-1997. These results must be interpreted cautiously, especially in relation to the wider context of underlying trends in the population. Potential biases derive from underreporting and from changes in the proportion of heroin users in treatment. The lag correction method adds substantially to the value of routine treatment data, at least for heroin use, and is potentially the best method for obtaining estimates of incidence. Am J Epidemiol 2001;153:632-41. [ABSTRACT FROM AUTHOR]