Incidence of self-reported tuberculosis treatment with community-wide universal testing and treatment for HIV and tuberculosis screening in Zambia and South Africa: A planned analysis of the HPTN 071 (PopART) cluster-randomised trial.

BACKGROUND: HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. METHODS AND FINDINGS: HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value ≤0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. CONCLUSIONS: In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01900977.

The effect of systematic screening of the general population on TB case notification rates.

BACKGROUND: Understanding how TB case notification rates (TB-CNR) change with TB screening and their association with underlying TB incidence/prevalence could inform how they are best used to monitor screening impact.METHODS: We undertook a systematic review to identify articles published between 1 January 1980 and 13 April 2020 on TB-CNR trends associated with TB screening in the general-population. Using a simple compartmental TB transmission model, we modelled TB-CNRs, incidence and prevalence dynamics during 5 years of screening.RESULTS: Of 27,282 articles, seven before/after studies were eligible. Two involved population-wide screening, while five used targeted screening. The data suggest screening was associated with initial increases in TB-CNRs. Increases were greatest with population-wide screening, where screening identified a large proportion of notified people with TB. Only one study reported on sustained screening; TB-CNR trends were compatible with model simulations. Model simulations always showed a peak in TB-CNRs with screening. Following the peak, TB-CNRs declined but were typically sustained above baseline during the intervention. Incidence and prevalence decreased during the intervention; the relative decline in incidence was smaller than the decline in prevalence.CONCLUSIONS: Published data on TB-CNR trends with TB screening are limited. These data are needed to identify generalisable patterns and enable method development for inferring underlying TB incidence/prevalence from TB-CNR trends.

Does tuberculosis screening improve individual outcomes? A systematic review.

BACKGROUND: To determine if tuberculosis (TB) screening improves patient outcomes, we conducted two systematic reviews to investigate the effect of TB screening on diagnosis, treatment outcomes, deaths (clinical review assessing 23 outcome indicators); and patient costs (economic review). METHODS: Pubmed, EMBASE, Scopus and the Cochrane Library were searched between 1/1/1980-13/4/2020 (clinical review) and 1/1/2010-14/8/2020 (economic review). As studies were heterogeneous, data synthesis was narrative. FINDINGS: Clinical review: of 27,270 articles, 18 (n=3 trials) were eligible. Nine involved general populations. Compared to passive case finding (PCF), studies showed lower smear grade (n=2/3) and time to diagnosis (n=2/3); higher pre-treatment losses to follow-up (screened 23% and 29% vs PCF 15% and 14%; n=2/2); and similar treatment success (range 68-81%; n=4) and case fatality (range 3-11%; n=5) in the screened group. Nine reported on risk groups. Compared to PCF, studies showed lower smear positivity among those culture-confirmed (n=3/4) and time to diagnosis (n=2/2); and similar (range 80-90%; n=2/2) treatment success in the screened group. Case fatality was lower in n=2/3 observational studies; both reported on established screening programmes. A neonatal trial and post-hoc analysis of a household contacts trial found screening was associated with lower all-cause mortality. Economic review: From 2841 articles, six observational studies were eligible. Total costs (n=6) and catastrophic cost prevalence (n=4; range screened 9-45% vs PCF 12-61%) was lower among those screened. INTERPRETATION: We found very limited patient outcome data. Collecting and reporting this data must be prioritised to inform policy and practice. FUNDING: WHO and EDCTP.

Association between cervical dysplasia and female genital schistosomiasis diagnosed by genital PCR in Zambian women.

BACKGROUND: Female genital schistosomiasis (FGS) is a neglected tropical gynaecological disease that affects millions of women in sub-Saharan Africa (SSA). FGS is caused by Schistosoma haematobium, a parasitic carcinogen involved in the pathogenesis of squamous cell carcinoma of the bladder. Cervical cancer incidence and mortality are highest in SSA, where pre-cancerous cervical dysplasia is often detected on screening with visual inspection with acetic acid (VIA). There are no studies evaluating the association between VIA positivity and FGS diagnosed by genital PCR. METHODS: Women were recruited from the Bilharzia and HIV (BILHIV) study in Zambia a community-based study comparing genital self-sampling to provider obtained cervicovaginal-lavage for the diagnosis of FGS in women aged 18-31. FGS was defined as positive Schistosoma DNA from any genital PCR. Urogenital schistosomiasis diagnostics included urine circulating anodic antigen, urine microscopy and portable colposcopy. Participants were offered cervical cancer screening using VIA at Livingstone Central Hospital. Associations of PCR confirmed FGS and other diagnostics with VIA positivity were assessed using multivariable logistic regression. RESULTS: VIA results were available from 237 BILHIV participants. A positive Schistosoma PCR in any genital specimen was detected in 14 women (5.9%), 28.6% (4/14) of these women had positive VIA compared to 9.0% without PCR evidence of schistosome infection (20/223). Schistosoma PCR positivity in any genital specimen was strongly associated with VIA positivity (OR: 6.08, 95% CI: 1.58-23.37, P = 0.02). CONCLUSIONS: This is the first study to find an association between FGS and positive VIA, a relationship that may be causal. Further longitudinal studies are needed.

Beyond the barrier: Female Genital Schistosomiasis as a potential risk factor for HIV-1 acquisition.

Female genital schistosomiasis (FGS) results from egg-deposition in the female reproductive tract primarily by the waterborne parasite Schistosoma (S.) haematobium, and less commonly by Schistosoma (S.) mansoni. FGS affects an estimated 20-56 million women worldwide, mostly in sub-Saharan Africa. There is cross-sectional evidence of increased HIV-1 prevalence in schistosomiasis-infected women, but a causal relationship between FGS and either HIV-1 acquisition or transmission has not been fully established. Beyond the pathognomonic breach in the cervicovaginal barrier caused by FGS, this narrative review explores potential mechanisms for a synergistic relationship between S. haematobium infection, FGS, and HIV-1 acquisition through vaginal inflammation and target cell recruitment.

Genetic architecture of tipburn resistance in lettuce.

KEY MESSAGE: Two major QTLs for tipburn were identified in LGs 1 and 5 contributing to resistance in cv. Salinas. The findings suggest pleiotropic effects between leaf crinkliness/savoy and tipburn. Tipburn is a physiological disorder in lettuce that is thought to be caused by a localized deficiency of calcium in leaf tissues. To elucidate the genetic architecture of resistance to tipburn in lettuce, seven recombinant inbred line populations were analyzed in multiple environments and years to identify quantitative trait loci (QTLs) for tipburn. Core height, head firmness, head closure, leaf crinkliness, plant fresh weight, and leaf savoy were also analyzed to investigate whether QTLs for these morphological traits collocated with QTLs for tipburn, which would be indicative of pleiotropic effects. Twenty-three major, intermediate, and minor unique QTLs for tipburn were identified in one or more populations scattered throughout the genome. Two major QTLs for tipburn incidence were identified in linkage groups (LGs) 1 and 5, which determined up to 45 and 66% of the phenotypic variance. The major QTL in LG 1 collocated with the head firmness QTL. The major QTL in LG 5 collocated with the QTL for core height, leaf crinkliness, and head firmness. Further research is needed to determine whether these associations are due to pleiotropic effects of the same gene or if the genes determining these traits are tightly linked. The beneficial alleles at the QTLs in LGs 1 and 5 are present in Lactuca sativa cv. Salinas, the genotype sequenced for the reference genome assembly. Therefore, these QTLs are good targets to identify genes causing tipburn as well as regions for marker-assisted selection to improve resistance to tipburn in lettuce.

Robust analysis of stepped wedge trials using cluster-level summaries within periods.

In stepped-wedge trials (SWTs), the intervention is rolled out in a random order over more than 1 time-period. SWTs are often analysed using mixed-effects models that require strong assumptions and may be inappropriate when the number of clusters is small. We propose a non-parametric within-period method to analyse SWTs. This method estimates the intervention effect by comparing intervention and control conditions in a given period using cluster-level data corresponding to exposure. The within-period intervention effects are combined with an inverse-variance-weighted average, and permutation tests are used. We present an example and, using simulated data, compared the method to (1) a parametric cluster-level within-period method, (2) the most commonly used mixed-effects model, and (3) a more flexible mixed-effects model. We simulated scenarios where period effects were common to all clusters, and when they varied according to a distribution informed by routinely collected health data. The non-parametric within-period method provided unbiased intervention effect estimates with correct confidence-interval coverage for all scenarios. The parametric within-period method produced confidence intervals with low coverage for most scenarios. The mixed-effects models' confidence intervals had low coverage when period effects varied between clusters but had greater power than the non-parametric within-period method when period effects were common to all clusters. The non-parametric within-period method is a robust method for analysing SWT. The method could be used by trial statisticians who want to emphasise that the SWT is a randomised trial, in the common position of being uncertain about whether data will meet the assumptions necessary for mixed-effect models.

Identification of pathogenicity-related genes in the vascular wilt fungus Verticillium dahliae by Agrobacterium tumefaciens-mediated T-DNA insertional mutagenesis.

Verticillium dahliae is the causal agent of vascular wilt in many economically important crops worldwide. Identification of genes that control pathogenicity or virulence may suggest targets for alternative control methods for this fungus. In this study, Agrobacterium tumefaciens-mediated transformation (ATMT) was applied for insertional mutagenesis of V. dahliae conidia. Southern blot analysis indicated that T-DNAs were inserted randomly into the V. dahliae genome and that 69% of the transformants were the result of single copy T-DNA insertion. DNA sequences flanking T-DNA insertion were isolated through inverse PCR (iPCR), and these sequences were aligned to the genome sequence to identify the genomic position of insertion. V. dahliae mutants of particular interest selected based on culture phenotypes included those that had lost the ability to form microsclerotia and subsequently used for virulence assay. Based on the virulence assay of 181 transformants, we identified several mutant strains of V. dahliae that did not cause symptoms on lettuce plants. Among these mutants, T-DNA was inserted in genes encoding an endoglucanase 1 (VdEg-1), a hydroxyl-methyl glutaryl-CoA synthase (VdHMGS), a major facilitator superfamily 1 (VdMFS1), and a glycosylphosphatidylinositol (GPI) mannosyltransferase 3 (VdGPIM3). These results suggest that ATMT can effectively be used to identify genes associated with pathogenicity and other functions in V. dahliae.

Molecular variation among isolates of Verticillium dahliae and polymerase chain reaction-based differentiation of races.

Verticillium dahliae is a soilborne fungal pathogen that causes vascular wilt in a variety of economically important crops worldwide. There are two races of V. dahliae that infect tomato and lettuce. Although race-1-specific resistance has been identified in both tomato and lettuce, no resistant sources are available for race 2. Molecular analyses were employed to characterize the genetic variability and race structure of 101 isolates of V. dahliae from a variety of hosts, mainly from central and coastal California, and 10 isolates exotic to this area. Analyses of the 16 simple sequence repeat (SSR) markers illustrated that tomato subpopulations from central California were distinct relative to the marigold subpopulations. In contrast, cotton and olive isolates showed admixture with tomato isolates. Analyses of both the ribosomal DNA intergenic spacer regions and SSR markers revealed high genetic variability among isolates but were unable to delineate races of V. dahliae. However, a polymerase chain reaction (PCR) assay was applied to amplify a race-1-specific amplicon from the isolates in many hosts from different geographic areas, and was coupled with virulence assays for validation of the data. Results of the PCR assay showed 100% concordance with the virulence assay to differentiate race 1 from race 2 of 48 isolates from tomato. The results indicate that the PCR assay can be applied to differentiate the two races to support our related aim of breeding host resistance, and further reveal insights into the distribution of races in tomato and lettuce cropping systems in California.

Do behavioural differences help to explain variations in HIV prevalence in adolescents in sub-Saharan Africa?

OBJECTIVE: To compare adolescent risk factors for HIV infection in two countries with high adolescent HIV prevalence and two lower prevalence countries with the aim of identifying risk factors that may help explain differences in adolescent HIV prevalence. METHODS: Data were available from two nationally representative surveys (South Africa, Zimbabwe), two behavioural intervention trials (Tanzania, Zimbabwe) and one population-based cohort (Uganda). Data on variables known or postulated to be risk factors for HIV infection were compared. RESULTS: Few risk behaviours were markedly more common in the high HIV prevalence populations. Risk factors more common in high HIV prevalence settings were genital ulcers and discharge, and women were more likely to report older male partners. DISCUSSION: Age mixing may be an important determinate of HIV prevalence in adolescents. Potential reasons for the general lack of association between other adolescent risk factors and adolescent HIV prevalence include adult HIV prevalence, misreported behaviour, different survey methods and other unmeasured adolescent behaviours. If adult factors dominate adolescent HIV risk, it would help explain the failure of behavioural interventions targeted at adolescents and suggests future interventions should include adults.

Prevalent infectious tuberculosis in Harare, Zimbabwe: burden, risk factors and implications for control.

SETTING: Harare's high density suburbs. OBJECTIVES: To investigate the burden, duration and risk factors for prevalent tuberculosis (TB) and explore potential control strategies. METHODS: Randomly selected adults had TB culture, symptom screen and human immunodeficiency virus (HIV) serology. Prevalent TB was defined as undiagnosed or still culture-positive. Notification data and HIV prevalence in TB out-patients were used to estimate duration of infectiousness (prevalence/estimated incidence). RESULTS: Among 10 092 participants, 40 (0.40%, 95%CI 0.28-0.54) had prevalent smear-positive TB. HIV (adjusted odds ratio [aOR] 3.1, 95%CI 1.6-6.3, population attributable fraction [PAF] 33%), male sex (aOR 3.1, 95%CI 1.5-6.4, PAF 40%), and overcrowding (PAF 34%) were significant risk factors, with past TB treatment significant for HIV-negative participants only (PAF 7%). Recent household TB contact was not significant (PAF 10%). HIV prevalence was 21.1%; 76.9% of HIV-positive participants were previously untested. Duration of infectiousness was at least 18 weeks in HIV-positive and approximately 1 year in HIV-negative patients. CONCLUSIONS: Overcrowding, male sex and HIV infection were major risk factors for prevalent smear-positive TB. Reducing diagnostic delay may have greater potential to improve the control of prevalent TB than interventions targeted at household contacts, TB treatment outcomes, or TB-HIV interventions under current levels of awareness of HIV status.

Population-level effect of HSV-2 therapy on the incidence of HIV in sub-Saharan Africa.

BACKGROUND: Herpes simplex virus type 2 (HSV-2) infection increases acquisition and transmission of HIV, but the results of trials measuring the impact of HSV-2 therapy on HIV genital shedding and HIV acquisition are mixed, and the potential impact of HSV-2 therapy on the incidence of HIV at the population level is unknown. METHODS: The effects of episodic and suppressive HSV-2 therapy were simulated using the individual-level model STDSIM fitted to data from Cotonou, Benin (relatively low HIV prevalence) and Kisumu, Kenya (high HIV prevalence). Clinician- and patient-initiated episodic therapy, started when symptomatic, were assumed to reduce ulcer duration. Suppressive therapy, given regardless of symptoms, was also assumed to reduce ulcer frequency and HSV-2 infectiousness. RESULTS: Clinician-initiated episodic therapy in the general population had almost no effect on the incidence of HIV. The impact of patient-initiated therapy was higher because of earlier treatment initiation, but still low (<5%) unless symptom recognition and treatment-seeking behaviour were very high. Suppressive therapy given to female sex workers (FSW) in Kisumu had little effect on population HIV incidence. In Cotonou, suppressive therapy in FSW with high coverage and long duration reduced population HIV incidence by >20% in the long term. Impact was increased in both cities by also treating a proportion of their clients. Long-term suppressive therapy with high coverage in the general population could reduce HIV incidence by more than 30%. CONCLUSIONS: These results show that HSV-2 therapy could potentially have a population-level impact on the incidence of HIV, especially in more concentrated epidemics. However, a substantial impact requires high coverage and long duration therapy, or very high symptom recognition and treatment-seeking behaviour.

Low effectiveness of syndromic treatment services for curable sexually transmitted infections in rural South Africa.

OBJECTIVES: Syndromic sexually transmitted infection (STI) treatment remains a cost-saving HIV prevention intervention in many countries in Africa. We estimate the effectiveness of syndromic treatment for curable STIs in rural KwaZulu-Natal, South Africa, and the trend in STI prevalences before and after the introduction of syndromic treatment in 1995. METHODS: Data were available from various clinical studies, surveys of public and private health providers, the general population and women attending antenatal, family planning and child immunisation clinics in rural northern KwaZulu-Natal between 1987 and 2004. Overall effectiveness was defined as the estimated proportion of the annual number of symptomatic curable STI episodes cured by syndromic treatment based on separate estimates for six curable STI aetiologies by gender. RESULTS: Median overall effectiveness was 13.1% (95% CI 8.9 to 17.8%) of symptomatic curable STI episodes cured. Effectiveness increased to 25.0% (95% CI 17.3 to 33.8%), 47.6% (95% CI 44.5 to 50.8%) or 14.3% (95% CI 9.9 to 19.4%) if 100% treatment seeking, 100% correct treatment provision or 100% cure were assumed, respectively. Time-trends were difficult to assess formally but there was little evidence of decreasing STI prevalences. Including incurable but treatable herpes simplex virus (HSV)-2 ulcers in the effectiveness calculation would halve the proportion of ulcers cured or correctly treated, but this reduction could be entirely countered by including episodic antiviral treatment in the national guidelines. CONCLUSION: Overall effectiveness of syndromic treatment for curable STIs in rural KwaZulu-Natal remains low and there is little evidence of reduced curable STI prevalences. As syndromic treatment is likely to be a cost-saving HIV prevention intervention in South Africa, innovative strategies are urgently needed to increase rates of treatment seeking and correct treatment provision.

A randomised placebo-controlled trial to explore the effect of suppressive therapy with acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 among Zimbabwean sex workers.

OBJECTIVES: To determine the effect of daily acyclovir on genital shedding of HIV-1 and herpes simplex virus type 2 (HSV-2) in a randomised placebo-controlled trial among rural Zimbabwean sex workers. METHODS: 214 women were recruited and tested for HIV-1 and HSV-2 antibodies, HIV plasma viral load, CD4 lymphocyte count and genital swabs for qualitative detection of HIV-1 and HSV-2 genital shedding. Women were randomly assigned to acyclovir 400 mg twice a day for 12 weeks or matching placebo and were followed weekly to detect HIV-1 or HSV-2 genital shedding. Shedding analyses were only undertaken on 125 women co-infected with HSV-2 and HIV-1. Data were analysed using logistic regression, with random effects modelling used to account for repeated measurements on the same women. RESULTS: All women were randomly assigned to acyclovir or placebo; 125 of whom were co-infected with HIV-1 and HSV-2. 69 women were randomly assigned to acyclovir and 56 to placebo. Although twice daily acyclovir reduced rates of HSV-2 genital shedding, (adjusted odds ratio (AOR) 0.24; 95% CI 0.12 to 0.48; less than p<0.001), it had no effect on the proportion of visits at which HIV-1 shedding was detected (AOR 1.08; 95% CI 0.48 to 2.42; p = 0.9). Adherence varied between participants but even when adherence was high (as determined by pill count and extent of HSV-2 suppression) HIV-1 shedding was not reduced. CONCLUSION: Among these HIV-1 and HSV-2-seropositive women, suppressive acyclovir therapy had no effect on the rate of HIV genital shedding despite a reduction in genital HSV-2. Treatment adherence and its measurement clearly affect the interpretation of these results.

Contribution of reinfection to recurrent tuberculosis in South African gold miners.

SETTING: A gold mine in South Africa. OBJECTIVE: To investigate incidence and risk factors for tuberculosis (TB) recurrence and the relative contribution of reinfection and relapse to recurrence. DESIGN: Prospective cohort study. METHODS: Employees cured of a first episode of culture-positive TB were followed up for recurrence, which was classified as reinfection or relapse by restriction fragment length polymorphism using an insertion sequence (IS) 6110 probe. RESULTS: Among 609 patients, 57 experienced recurrence during a median follow-up period of 1.02 years, corresponding to a recurrence rate of 7.89 per 100 person-years (py). The culture positive recurrence rate was 5.79/100 py, and was higher in human immunodeficiency virus (HIV) infected patients (8.86/100 py in HIV-infected vs. 3.35/100 py in non-HIV-infected). Among HIV-infected patients, the risk of culture-positive recurrence was higher with decreasing CD4 count (compared with CD4 < 200, hazard ratios for recurrence among individuals with CD4 200-500 and CD4 > 500 were 0.40 [95%CI 0.14-1.09] and 0.14 [95%CI 0.02-1.10], respectively, Ptrend = 0.01). IS6110 genotyping was available on both the initial and subsequent isolate for 16/42 (38%, 14 HIV-infected) patients with culture-positive recurrence, and showed reinfection in 11 (69%). CONCLUSION: HIV-infected gold miners, particularly those who are more immunosuppressed, are at higher risk of TB recurrence. TB control strategies need to take into account reinfection as an important cause of recurrent TB.

A process evaluation of a school-based adolescent sexual health intervention in rural Tanzania: the MEMA kwa Vijana programme.

This study is a process evaluation of the school component of the adolescent sexual health programme MEMA kwa Vijana (MkV), which was implemented in 62 primary schools in rural Mwanza, Tanzania from 1999 to 2001. The MkV curriculum was a teacher-led and peer-assisted programme based on the Social Learning Theory. Process evaluation included observation of training sessions, monitoring and supervision, annual surveys of implementers, group discussions and 158 person-weeks of participant observation. Most teachers taught curriculum content well, but sometimes had difficulty adopting new teaching styles. Peer educators performed scripted dramas well, but were limited as informal educators and behavioural models. The intervention appeared successful in addressing some cognitions, e.g. knowledge of risks and benefits of behaviours, but not others, e.g. perceived susceptibility to risk. MkV shared the characteristics of other African school-based programmes found to be successful, and similarly found significant improvements in self-reported behaviour in surveys. However, a substantial proportion of MkV survey self-reports were inconsistent, there was no consistent impact on biological markers and extensive process evaluation found little impact on several key theoretical determinants of behaviour. Improvements in self-reported survey data alone may provide only a very limited-and perhaps invalid-indication of adolescent sexual health programme success.

Rationale and design of the MEMA kwa Vijana adolescent sexual and reproductive health intervention in Mwanza Region, Tanzania.

Large-scale innovative, integrated, multifaceted adolescent sexual and reproductive health (ASRH) interventions are urgently needed in sub-Saharan Africa. Implementation through schools and health facilities may maximize intervention coverage and sustainability, however the impact of the use of these structures on intervention content and delivery is not well documented. This paper describes the rationale and design of a large-scale multifaceted ASRH intervention, which was developed and evaluated over three years in rural communities in Mwanza Region, North West Tanzania. The intervention comprised community mobilization, participatory reproductive health education in primary schools, youth-friendly reproductive health services and community-based condom provision for youth. We examine the effect of socioeconomic, cultural and infrastructural factors on intervention content and implementation. This paper demonstrates the means by which such interventions can be feasibly and sustainably implemented to a high standard through existing government health and school structures. However, the use of these structures involves compromise on some key aspects of intervention design and requires the development of complementary strategies to access out-of-school youth and the wider community.

Screening for tuberculosis prior to isoniazid preventive therapy among HIV-infected gold miners in South Africa.

SETTING: Human immunodeficiency virus (HIV) clinic for employees of a gold mine, Free State, South Africa. OBJECTIVE: To evaluate the process of screening for active tuberculosis (TB) prior to commencing TB preventive therapy in HIV-infected individuals. DESIGN: Cross-sectional study comparing performance of various combinations of screening tests for TB against a gold standard diagnosis of TB based on symptoms, chest radiograph (CXR), sputum microscopy and culture. RESULTS: Of 899 individuals, 44 (4.9%) had TB. The most sensitive symptom combination (59.1%) was any of night sweats, new or worsening cough or reported weight loss; measured weight loss > 5% or abnormal CXR increased sensitivity to 90.9%. Sputum microscopy did not increase sensitivity further, but including World Health Organization HIV clinical staging or CD4 count did. As the specificity of all these combinations was low, many individuals required further investigation to rule out TB. TB prevalence was high (11.7%) among individuals with a CD4 count < 200/mm3. CONCLUSION: CXR greatly increased the sensitivity of screening for TB in this population. Sputum microscopy conferred no additional benefit among asymptomatic patients with a normal CXR. The high prevalence of TB amongst those with a low CD4 count underlines the importance of screening for active TB prior to commencing TB preventive therapy, and before antiretroviral therapy.

Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta-analysis.

OBJECTIVES: Male circumcision is associated with reduced risk of HIV infection. This may be partly because of a protective effect of circumcision on other sexually transmitted infections (STI), especially those causing genital ulcers, but evidence for such protection is unclear. Our objective was to conduct a systematic review and meta-analyses of the associations between male circumcision and infection with herpes simplex virus type 2 (HSV-2), Treponema pallidum, or Haemophilus ducreyi. METHODS: Electronic databases (1950-2004) were searched using keywords and text terms for herpes simplex, syphilis, chancroid, ulcerative sexually transmitted diseases, or their causative agents, in conjunction with terms to identify epidemiological studies. References of key articles were hand searched, and data were extracted using standardised forms. Random effects models were used to summarise relative risk (RR) where appropriate. RESULTS: 26 articles met the inclusion criteria. Most syphilis studies reported a substantially reduced risk among circumcised men (summary RR = 0.67, 95% confidence interval (CI) 0.54 to 0.83), although there was significant between study heterogeneity (p = 0.01). The reduced risk of HSV-2 infection was of borderline statistical significance (summary RR = 0.88, 95% CI 0.77 to 1.01). Circumcised men were at lower risk of chancroid in six of seven studies (individual study RRs: 0.12 to 1.11). CONCLUSIONS: This first systematic review of male circumcision and ulcerative STI strongly indicates that circumcised men are at lower risk of chancroid and syphilis. There is less association with HSV-2. Potential male circumcision interventions to reduce HIV in high risk populations may provide additional benefit by protecting against other STI.