How can we objectively categorise partnership type? A novel classification of population survey data to inform epidemiological research and clinical practice.

BACKGROUND: Partnership type is a determinant of STI risk; yet, it is poorly and inconsistently recorded in clinical practice and research. We identify a novel, empirical-based categorisation of partnership type, and examine whether reporting STI diagnoses varies by the resulting typologies. METHODS: Analyses of probability survey data collected from 15 162 people aged 16-74 who participated in Britain's third National Survey of Sexual Attitudes and Lifestyles were undertaken during 2010-2012. Computer-assisted self-interviews asked about participants' ≤3 most recent partners (N=14 322 partners/past year). Analysis of variance and regression tested for differences in partnership duration and perceived likelihood of sex again across 21 'partnership progression types' (PPTs) derived from relationship status at first and most recent sex. Multivariable regression examined the association between reporting STI diagnoses and partnership type(s) net of age and reported partner numbers (all past year). RESULTS: The 21 PPTs were grouped into four summary types: 'cohabiting', 'now steady', 'casual' and 'ex-steady' according to the average duration and likelihood of sex again. 11 combinations of these summary types accounted for 94.5% of all men; 13 combinations accounted for 96.9% of all women. Reporting STI diagnoses varied by partnership-type combination, including after adjusting for age and partner numbers, for example, adjusted OR: 6.03 (95% CI 2.01 to 18.1) for men with two 'casual' and one 'now steady' partners versus men with one 'cohabiting' partner. CONCLUSIONS: This typology provides an objective method for measuring partnership type and demonstrates its importance in understanding STI risk, net of partner numbers. Epidemiological research and clinical practice should use these methods and results to maximise individual and public health benefit.

Painful sex (dyspareunia) in women: prevalence and associated factors in a British population probability survey.

OBJECTIVE: To estimate the prevalence of painful sex among women in Britain, and to explore associated sexual, relationship and health factors that should be considered in assessment. DESIGN: Multi-stage, clustered and stratified population probability sample survey, using computer-assisted self-interview. Sample frame was the British Postcode Address File. SETTING: Participants interviewed at home between 2010 and 2012. SAMPLE: A total of 15 162 adults aged 16-74 years (8869 women). Data reported from 6669 sexually active women. METHODS: Age-adjusted logistic regressions to examine associations between painful sex and indicators of sexual, relational, mental and physical health. MAIN OUTCOME MEASURE: Physical pain as a result of sex for ≥3 months in the past year, plus measures of symptom severity. RESULTS: Painful sex was reported by 7.5% (95% CI 6.7-8.3) of sexually active women, of whom one-quarter experienced symptoms very often or always, for ≥6 months, and causing distress. Reporting painful sex was strongly associated with other sexual function problems, notably vaginal dryness (age adjusted odds ratio 7.9; 6.17-10.12), anxiety about sex (6.34; 4.76-8.46) and lacking enjoyment in sex (6.12; 4.81-7.79). It was associated with sexual relationship factors [such as not sharing same level of interest in sex (2.56; 1.97-3.33)], as well as with adverse experiences such as non-volitional sex (2.17; 1.68-2.80). Associations were also found with measures of psychological and physical health, including depressive symptoms (1.68; 1.28-2.21). CONCLUSION: Painful sex is reported by a sizeable minority of women in Britain. Health professionals should be supported to undertake holistic assessment and treatment which takes account of the sexual, relationship and health context of symptoms. TWEETABLE ABSTRACT: Painful sex-reported by 7.5% of women in Britain-is linked to poorer sexual, physical, relational and mental health.

The prospective evaluation of the TB strain typing service in England: a mixed methods study.

BACKGROUND: In response to rising TB notification rates in England, universal strain typing was introduced in 2010. We evaluated the acceptability, effectiveness and cost-effectiveness of the TB strain typing service (TB-STS). METHODS: We conducted a mixed-methods evaluation using routine laboratory, clinic and public health data. We estimated the effect of the TB-STS on detection of false positive Mycobacterium tuberculosis diagnoses (2010-2012); contact tracing yield (number of infections or active disease per pulmonary TB case); and diagnostic delay. We developed a deterministic age-structured compartmental model to explore the effectiveness of the TB-STS, which informed a cost-effectiveness analysis. RESULTS: Semi-structured interviews explored user experience. Strain typing identified 17 additional false positive diagnoses. The TB-STS had no significant effect on contact tracing yield or diagnostic delay. Mathematical modelling suggested increasing the proportion of infections detected would have little value in reducing TB incidence in the white UK-born population. However, in the non-white UK-born and non-UK-born populations, over 20 years, if detection of latent infection increases from 3% to 13% per year, then TB incidence would decrease by 11%; reducing diagnostic delay by one week could lead to 25% reduction in incidence. The current TB-STS was not predicted to be cost-effective over 20 years (£95 628/quality-adjusted life-years). Interviews found people had mixed experiences, but identified broader benefits, of the TB-STS. CONCLUSIONS: To reduce costs, improve efficiency and increase effectiveness, we recommend changes to the TB-STS, including discontinuing routine cluster investigations and focusing on reducing diagnostic delay across the TB programme. This evaluation of a complex intervention informs the future of strain typing in the era of rapidly advancing technologies.

Prevalence of infertility and help seeking among 15 000 women and men.

STUDY QUESTION: What is the prevalence of infertility and of help seeking among women and men in Britain? SUMMARY ANSWER: One in eight women and one in ten men aged 16-74 years had experienced infertility, defined by unsuccessfully attempting pregnancy for a year or longer, and little more than half of these people sought medical or professional help. WHAT IS KNOWN ALREADY: Estimates of infertility and help seeking in Britain vary widely and are not easily comparable because of different definitions and study populations. STUDY DESIGN, SIZE, DURATION: A cross-sectional population survey was conducted between 2010 and 2012 with a sample of 15 162 women and men aged 16-74 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants completed the Natsal-3 questionnaire, using computer-assisted personal interviewing (CAPI) and computer-assisted self-interview (CASI). MAIN RESULTS AND THE ROLE OF CHANCE: The reported prevalence of infertility was 12.5% (CI 95% 11.7-13.3) among women and 10.1% (CI 95% 9.2-11.1) among men. Increased prevalence was associated with later cohabitation with a partner, higher socio-economic status and, for those who had a child, becoming parents at older ages. The reported prevalence of help seeking was 57.3% (CI 95% 53.6-61.0) among women and 53.2% (CI 95% 48.1-58.1) among men. Help seekers were more likely to be better educated and in higher status occupations and, among those who had a child, to have become parents later in life. LIMITATIONS, REASONS FOR CAUTION: These data are cross-sectional so it is not possible to establish temporality or infer causality. Self-reported data may be subject to recall bias. WIDER IMPLICATIONS OF THE FINDINGS: The study provides estimates of infertility and help seeking in Britain and the results indicate that the prevalence of infertility is higher among those delaying parenthood. Those with higher educational qualifications and occupational status are more likely to consult with medical professionals for fertility problems than others and these inequalities in help seeking should be considered by clinical practice and public health. STUDY FUNDING/COMPETING INTERESTS: Funding was provided by grants from the Medical Research Council and the Wellcome Trust, with support from the Economic and Social Research Council and the Department of Health. AMJ is a Governor of the Wellcome Trust. Other authors have no competing interests.

Human papillomavirus DNA in men who have sex with men: type-specific prevalence, risk factors and implications for vaccination strategies.

BACKGROUND: Human papillomavirus (HPV) vaccination of girls will have relatively little effect on HPV-related disease in men who have sex with men (MSM). We determined HPV prevalence and risk factors in MSM to inform the potential effectiveness of vaccinating MSM. METHODS: Cross-sectional study of 522 MSM aged 18-40 attending a London sexual health clinic who completed a computer-assisted self-interview. Urine and two swabs (anal and penile/scrotal/perianal) were collected and tested using an in-house Luminex-based HPV genotyping system. RESULTS: Prevalence of DNA of the vaccine-preventable HPV types in ano-genital specimens of men was 87/511 (17.0%), 166/511 (32.5%) and 232/511 (45.4%) for the bivalent (HPV16/18), quadrivalent (HPV6/11/16/18) and nonavalent (HPV6/11/16/18/31/33/45/52/58) vaccine types, respectively. A total of 25.1% had one of the quadrivalent types, and 7.4% had 2+ types. Median age at first anal sex was 19 (IQR 17-23) and at first clinic attendance was 24 (IQR 20-27). The increase in the odds of any HPV infection per year of age was 4.7% (95% CI 1.2-8.4). CONCLUSIONS: On the basis of the current infection status, most MSM, even among a high-risk population attending a sexual health clinic, are not currently infected with the vaccine-type HPV. A targeted vaccination strategy for MSM in the UK could have substantial benefits.

Conceptualizing Sexual Wellbeing: A Qualitative Investigation to Inform Development of a Measure (Natsal-SW).

Despite increasing scientific and policy interest in sexual wellbeing, it remains poorly conceptualized. Many studies purporting to measure it instead measure related but distinct concepts, such as sexual satisfaction. This lack of conceptual clarity impedes understanding, measuring, and improving sexual wellbeing. We present qualitative research from multi-stage, mixed-methods work to develop a new measure of sexual wellbeing (Natsal-SW) for the fourth British National Survey of Sexual Attitudes & Lifestyles. Literature review and discussion generated a conceptual framework with seven proposed domains: respect, self-esteem, comfort, self-determination, safety and security, forgiveness, and resilience. Semi-structured interviews with 40 adults aged 18-64 then explored whether and how these domains aligned with participants' own understandings, experiences, and language of sexual wellbeing. Data were analyzed thematically. Participants conceptualized sexual wellbeing as distinct from sexual satisfaction and sexual health and as multidimensional, dynamic, and socially and structurally influenced. All seven proposed domains resonated with accounts of sexual wellbeing as a general construct. The personal salience of different domains and their dimensions varied between individuals (especially by gender and sexual orientation) and fluctuated individually over time. This study clarifies dimensions of domains that participants considered important, providing an empirical basis to inform development of a new measure of sexual wellbeing.

Salivary Testosterone and Sexual Function and Behavior in Men and Women: Findings from the Third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

Using data from the third British National Survey of Sexual Attitudes and Lifestyles (Natsal-3) we examined associations between salivary testosterone (Sal-T) and sexual function and behavior. Single morning saliva samples were self-collected from a subsample of participants aged 18-74 years and analyzed using mass spectrometry. 1,599 men and 2,123 women were included in the analysis (40.6% of those invited to provide a sample). We adjusted for confounders in a stepwise manner: in model 1 we adjusted for age only; model 2 for age, season and relationship status, and model 3 we added BMI and self-reported health. In the fully adjusted models, among men, Sal-T was positively associated with both partnered sex (vaginal sex and concurrent partners) and masturbation. Among women, Sal-T was positively associated with masturbation, the only association with partnered sex was with ever experience of same-sex sex. We found no clear association between Sal-T and sexual function. Our study contributes toward addressing the sparsity of data outside the laboratory on the differences between men and women in the relationship between T and sexual function and behavior. To our knowledge, this is the first population study, among men and women, using a mass spectrometry Sal-T assay to do so.

TB outcomes and mortality risk factors in adult migrants at the Thailand-Myanmar border.

BACKGROUND: Cross-border migrants at the Thailand-Myanmar border are an underserved and vulnerable population. We aimed to identify the causes and risk factors for TB mortality at a migrant-friendly TB programme.METHODS: Routinely collected data on TB cases, treatment outcomes and causes of death were analysed for adult TB cases diagnosed between January 2013 and April 2017. Mortality in the 6 months post-diagnosis was calculated and risk factors were identified using multivariable Poisson regression.RESULTS: Of the 1344 TB cases diagnosed, 1005 started treatment and 128 died. Case fatality rate was 9.5% and the TB mortality rate was 2.4/100 person-months. The number of pre-treatment deaths (33/128) and losses to follow-up (9.0%) were high. Among cases enrolled in treatment, the treatment success rate was 79.8%. When stratified by HIV status, case fatality was higher in HIV-positive cases not on antiretroviral therapy (ART) (90.3%) or with unknown HIV status (31.8%) than those on ART (14.3%) or HIV-negative (8.6%).CONCLUSION: This TB programme achieved high treatment success rates in a population with a substantial burden of TB-HIV coinfection. Expanding access to HIV testing and ART is crucial to reduce mortality. Striving towards same-day TB diagnosis and treatment could reduce death and loss to follow-up.

An evaluation of the completeness of reporting of childhood tuberculosis.

The sensitivity of the Enhanced Tuberculosis Surveillance (ETS) scheme for monitoring tuberculosis in children is unknown. We used the British Paediatric Surveillance Unit (BPSU) reporting scheme to conduct a prospective observational study of tuberculosis in children aged <16 yrs in the UK. Reported cases were then matched with records from the ETS database. A total of 320 cases were reported to the BPSU between January and December 2004. We estimated that there were 557 paediatric cases in England, Wales and Northern Ireland in 2004: 222 (40%) cases reported to both BPSU and ETS, 98 (18%) reported to BPSU but not ETS and 237 (42%) reported to ETS but not BPSU. Children aged <5 yrs were significantly less likely to be reported to ETS compared with older children (p<0.01). There is substantial under-reporting of childhood tuberculosis, especially of children aged <5 yrs. ETS provides a representative picture of the demographics but may miss approximately 20% of cases. This should be taken into account when planning training and resource requirements for tuberculosis. Increased efforts are needed to ensure that all paediatric cases are reported to ETS.

Molecular epidemiology of tuberculosis in England, 1998.

SETTING: England. OBJECTIVE: To investigate the proportion of tuberculosis (TB) cases attributable to recent transmission and factors associated with clustering. DESIGN: Demographic, clinical and microbiological surveillance data were collated from all new culture-confirmed cases in 1998. Using insertion sequence (IS) 6110 restriction fragment length polymorphism (RFLP) typing, strains were classified as clustered (identical patterns) or unique and risk factors were determined using multivariable logistic regression. RESULTS: RFLP patterns were available for 2265 of 3713 (61%) cases: 1808 had >or=5 IS6110 copies, while 372 cases were in 152 clusters, giving an estimated proportion due to recent transmission of 12.2%.Pulmonary disease (aOR 1.6; 95%CI 1.1-2.2), previous treatment (aOR 3.7; 2.2-6.5) and homelessness (aOR 5.5; 1.2-24.1) were independent risk factors for clustering. Fourteen per cent of patients of Indian subcontinent origin were clustered compared with 27% of white patients. Many clusters spanned ethnic groups (45%) and geographical regions (47%). CONCLUSION: The calculated proportion of TB cases due to recent transmission is low.Adjusting for missed cases and study duration, it increases to 27.6%. Many cases may arise from reactivation or acquisition outside England. Transmission within England accounted for approximately one in four cases and occurred over wide geographic areas, between ethnic groups and among the homeless. Molecular epidemiology can inform local and national public health action.

Salivary Testosterone Levels and Health Status in Men and Women in the British General Population: Findings from the Third National Survey of Sexual Attitudes and Lifestyles (Natsal-3).

CONTEXT: Salivary T (Sal-T) measurement by liquid chromatography-tandem mass spectroscopy resents the opportunity to examine health correlates of Sal-T in a large-scale population survey. OBJECTIVE: This study sought to examine associations between Sal-T and health-related factors in men and women age 18-74 years. DESIGN AND SETTING: Morning saliva samples were obtained from participants in a cross-sectional probability-sample survey of the general British population (Natsal-3). Self-reported health and lifestyle questions were administered as part of a wider sexual health interview. PARTICIPANTS: Study participants included 1599 men and 2123 women. METHODS: Sal-T was measured using liquid chromatography-tandem mass spectroscopy. Linear regression was used to examine associations between health factors and mean Sal-T. RESULTS: In men, mean Sal-T was associated with a range of health factors after age adjustment, and showed a strong independent negative association with body mass index (BMI) in multivariable analysis. Men reporting cardiovascular disease or currently taking medication for depression had lower age-adjusted Sal-T, although there was no association with cardiovascular disease after adjustment for BMI. The decline in Sal-T with increasing age remained after adjustment for health-related factors. In women, Sal-T declined with increasing age; however, there were no age-independent associations with health-related factors or specific heath conditions with the exception of higher Sal-T in smokers. CONCLUSIONS: Sal-T levels were associated, independently of age, with a range of self-reported health markers, particularly BMI, in men but not women. The findings support the view that there is an age-related decline in Sal-T in men and women, which cannot be explained by an increase in ill health. Our results demonstrate the potential of Sal-T as a convenient measure of tissue androgen exposure for population research.

Identification of cell subsets expressing intracytoplasmic cytokines within HIV-1-infected lymph nodes.

OBJECTIVE: To describe the endogenous cytokine profile of HIV-1-infected lymph nodes (LN) and to identify the phenotype of individual cells expressing intracytoplasmic cytokines. DESIGN AND METHODS: Whole LN biopsies were collected from three HIV-seronegative controls and four HIV-1-positive individuals with persistent generalized lymphadenopathy. Three had established infection (Centers for Disease Control and Prevention 1993 criteria, stages A2, C1 and C3) and one was undergoing seroconversion illness. A combination of three methods was used to assess the impact of HIV-1 on LN architecture and endogenous cytokine expression. Immunocytochemistry was used to locate follicular dendritic cells (FDC), interdigitating cells and T and B cells. Reverse transcriptase-polymerase chain reaction was used to assess mRNA for interleukin (IL)-1 beta, IL-2, IL-4, IL-6, IL-10, tumour necrosis factor (TNF)-alpha and interferon (IFN)-gamma in collagenase-digested LN cells. Three-colour flow cytometry was used to identify intracytoplasmic cytokine expression within cell subsets. RESULTS: Germinal center (GC) hyperplasia was observed in LN from two patients with established HIV-1 infection, and the third, coinfected with Mycobacterium tuberculosis, showed extensive necrosis. In the patient undergoing seroconversion, there was an extensive FDC network within the expanded and confluent GC which covered expansive areas of the LN. There was varied expression of IL-1 beta, IL-4, IL-6, IL-10 and TNF-alpha mRNA from the four HIV-1-infected LN and the patient undergoing seroconversion showed evidence for a mixed cytokine profile, which also included IL-2 and IFN-gamma. Flow cytometry revealed intracytoplasmic IL-1 beta protein restricted to cells expressing CD19, CD21 and CD38 antigens. CONCLUSIONS: Cytokines were detected in freshly isolated HIV-1-infected LN cells without requiring an exogenous stimulus. Seroconversion was associated with an expanded FDC network within enlarged GC, bounded by defined mantle zones containing B cells. There was diverse cytokine mRNA expression and IL-1 beta protein was restricted to cells expressing B-cell-associated antigens.

Dual infective pathology in patients with cryptococcal meningitis.

Coinfection of the nervous system by two distinct nonviral organisms is uncommon and often undiagnosed. Medical teaching emphasizes that a single pathologic process should be sought; however, in the presence of severe immunocompromise this approach may not hold true. We describe seven HIV-1 seropositive patients with cryptococcal meningitis, three of whom had a proven nervous system infection with a second organism: concurrent tuberculous meningitis, a tuberculoma, and the first documented case of cryptococcal meningitis and neurosyphilis.

Genetic characterization of HIV type 1 from migrant workers in three South African gold mines.

The phylogenetic relationships between 44 HIV-1 isolates from 43 infected subjects employed by three adjacent South African gold mines were investigated. The patients were migrant workers originating from rural areas of South Africa and the neighboring countries of Lesotho, Botswana, Swaziland, and Mozambique. Proviral HIV-1 DNA was subtyped using a heteroduplex mobility assay (HMA) based on the 700-bp V3-V5 region of the env gene. DNA sequence analysis was used to confirm the subtype designation and to determine phylogenetic relationships between isolates. All 44 HIV-1 isolates were identified as env subtype C using both HMA and phylogenetic analysis. These isolates did not show a distinct phylogenetic relatedness based on the geographic origins of the migrant workers or show close homology to other subtype C sequences from southern Africa or India. However, five clusters of closely related sequences were identified, mainly involving miners of disparate geographic origins, suggesting possible epidemiological linkage in these few cases. The characteristic tetrapeptide sequence, GPGQ, at the tip of the V3 loop of subtype C viruses was conserved in the predicted amino acid sequences of most isolates. The heterogeneity of HIV-1 sequences among migrant workers in a mining cohort suggests multiple introductions of HIV-1 subtype C into this population that are not apparently linked to the geographic origins of the patients.

The effect of dosage cards on compliance with directly observed tuberculosis therapy in hospital.

We evaluated the effect of a dosage card signed by both patient and health worker on compliance in a tuberculosis ward. Compliance was assessed by testing a urine specimen from each patient for the presence of isoniazid and rifampicin pre-intervention and at two weeks, six weeks and 16 months post-intervention. Pre-intervention compliance was 62% and increased to 88%, 91% and 93% in the short, medium and long-term, respectively (P = 0.03, P = 0.02, P < 0.01). The assumption that directly observed therapy is successfully practised in hospital is not always correct. Simple inexpensive measures can improve compliance and have an impact on tuberculosis control.

Meningitis in a community with a high prevalence of tuberculosis and HIV infection.

OBJECTIVES: To evaluate the spectrum of aetiologies, and distinguishing clinical and laboratory features, of meningeal infection in a community with a high prevalence of tuberculosis (TB) and HIV infection. SETTING: A hospital serving mineworkers, originating from rural areas of Southern Africa. DESIGN: Prospective cohort of 60 consecutive lumbar punctures (LPs), performed for suspected meningitis. MEASUREMENTS: Clinical history and examination; concurrent cerebrospinal fluid (CSF) and blood samples; mortality status six months after entry to study. RESULTS: 38 of 57 patients (66.7%) were HIV-1 positive, 59.5% of whom had a CD4 count <200 cells/mm3. Nine patients had tuberculous meningitis (TBM) and two had tuberculomas; four developed disease while on TB therapy. There was one case of multidrug, and two of isoniazid-resistant TBM. There were nine episodes of cryptococcal meningitis (seven patients), nine of aseptic meningitis, two of neurosyphilis and 20 normal LPs, including four with AIDS dementia complex (ADC). Ten patients with meningococcal infection, part of a larger outbreak, were significantly younger (p=0.004). All patients with tuberculous, cryptococcal (most immune-suppressed p<0.001) and aseptic meningitis were HIV-1 positive. Within six months, 19 patients had died. Death was associated with HIV positivity (p=0.004), low CD4 count (p<0.001) and a diagnosis of cryptococcal meningitis, CNS TB or ADC. CONCLUSION: HIV has a major impact on the burden of disease and mortality, with a predominance of opportunistic chronic meningitides, despite a meningococcal outbreak, in this community. Of concern is the development of TBM despite therapy, and the emergence of drug-resistant strains.

Tuberculosis treatment failure and drug resistance--same strain or reinfection?

Tuberculosis patients may have Mycobacterium tuberculosis in their sputum at the end of treatment, and may show new drug resistance, due to either inadequate treatment of the original episode or reinfection with a new strain during therapy. In a cohort study of mineworkers with tuberculosis in South Africa, 57 of 438 patients had positive sputum cultures 6 months after recruitment in 1995. Of the 31 patients who initially had fully sensitive strains, 3 developed multidrug resistance (MDR) and 3 single-drug resistance (SDR). Of the 6 who started with SDR, 3 became MDR. HIV infection was not associated with drug resistance at enrollment or 6 months later. We compared pairs of DNA fingerprints from isolates of M. tuberculosis at recruitment and 6 months later in the 48 patients for whom we had both available. In 45, the pairs were identical. In 1 patient, although both isolates were fully sensitive, the later fingerprint had 1 less band (transposition). In 2 pairs, the fingerprint patterns were completely different: one seemed to be the result of laboratory error and the other was a true reinfection with an MDR strain. Despite a high risk of infection, with a moderate proportion of background drug-resistant strains (11% SDR, 6% MDR), reinfection is not a common cause of treatment failure or drug resistance at 6 months.

Quantifying errors in the estimation of tuberculosis mortality in a population of South African miners.

BACKGROUND: All-cause mortality, based on national tuberculosis programme (NTP) register deaths, may under- or overestimate tuberculosis (TB) specific mortality in the population. OBJECTIVE: To assess the factors influencing this measurement in a single large population with high TB prevalence and mortality. METHODS: Routinely collected data on TB cases and treatment outcomes were linked to population data from a cohort of South African miners from 1995 to 2008. Vital status and cause of death were determined from multiple sources, including the TB programme, death register and autopsy. RESULTS: The TB mortality rate, based on 430 deaths on the TB register, was 192/100,000 person-years (py). Many of these deaths (57%) were not caused by TB, and 483 TB deaths were identified outside the programme. Overall, there were 674 TB-specific deaths; the TB-specific mortality rate was 302/100,000 py. These deaths included 191 (28%) on the TB register, 23 (3%) among defaulters/transfers, 153 (23%) after anti-tuberculosis treatment and 307 (46%) in men who had never been on the programme. CONCLUSIONS: This study highlights methodological issues in estimating TB mortality. In this population, a method using the product of TB incidence and case fatality consistently underestimated TB mortality. Accurate estimates of TB-specific mortality are crucial for the proper evaluation of TB control programmes.

Human immunodeficiency virus associated tuberculosis more often due to recent infection than reactivation of latent infection.

BACKGROUND: It is unclear whether human immunodeficiency virus (HIV) increases the risk of tuberculosis (TB) mainly through reactivation or following recent Mycobacterium tuberculosis (re)infection. Within a DNA fingerprint-defined cluster of TB cases, reactivation cases are assumed to be the source of infection for subsequent secondary cases. As HIV-positive TB cases are less likely to be source cases, equal or higher clustering in HIV-positives would suggest that HIV mainly increases the risk of TB following recent infection. METHODS: A systematic review was conducted to identify all studies on TB clustering and HIV infection in HIV-endemic populations. Available individual patient data from eligible studies were pooled to analyse the association between clustering and HIV. RESULTS: Of seven eligible studies, six contributed individual patient data on 2116 patients. Clustering was as, or more, likely in the HIV-positive population, both overall (summary OR 1.26, 95%CI 1.0-1.5), and within age groups (OR 1.50, 95%CI 0.9-2.3; OR 1.00, 95%CI 0.8-1.3 and OR 2.57, 95%CI 1.4-5.7) for ages 15-25, 26-50 and >50 years, respectively. CONCLUSIONS: Our results suggest that HIV infection mainly increases the risk of TB following recent M. tuberculosis transmission, and that TB control measures in HIV-endemic settings should therefore focus on controlling M. tuberculosis transmission rather than treating individuals with latent M. tuberculosis infection.