Prevalence, incidence and determinants of QuantiFERONTM positivity in South African schoolchildren.

BACKGROUND: TB control requires the understanding and disruption of TB transmission. We describe prevalence, incidence and risk factors associated with childhood TB infection in Cape Town, South Africa. METHODS: We report cross-sectional baseline and prospective incidence data from a large trial among primary school children living in high TB burden communities. Prevalent infection was defined as QuantiFERON™-TB Gold Plus (QFT-Plus) positivity as assessed at baseline. Subsequent conversion to QFT-Plus positivity was measured 3 years later among those QFT-Plus-negative at baseline. Multivariable logistic regression models examined factors associated with TB infection. RESULTS: QuantiFERON-positivity at baseline (prevalence: 22.6%, 95% CI 20.9-24.4), was independently associated with increasing age (aOR 1.24 per additional year, 95% CI 1.15-1.34) and household exposure to TB during the participant's lifetime (aOR 1.87, 95% CI 1.46-2.40). QFT-Plus conversion at year 3 (12.2%, 95% CI 10.5-14.0; annual infection rate: 3.95%) was associated with household exposure to an index TB case (aOR 2.74, 95% CI 1.05-7.18). CONCLUSION: Rates of QFT-diagnosed TB infection remain high in this population. The strong association with household TB exposure reinforces the importance of contact tracing, preventative treatment and early treatment of infectious disease to reduce community transmission.

CONTEXTE: La lutte contre la TB nécessite la compréhension et la perturbation de la transmission de la TB. Nous décrivons la prévalence, l'incidence et les facteurs de risque associés à l'infection tuberculeuse infantile au Cap, en Afrique du Sud. MÉTHODES: Nous rapportons des données transversales de référence et d'incidence prospective provenant d'un vaste essai mené auprès d'enfants d'écoles primaires vivant dans des communautés à forte charge de morbidité tuberculeuse. La prévalence de l'infection a été définie comme la positivité au QuantiFERON™-TB Gold Plus (QFT-Plus) telle qu'évaluée au départ. La conversion subséquente en QFT-Plus positif a été mesurée 3 ans plus tard chez les QFT-Plus négatifs au départ. Des modèles de régression logistique multivariée ont examiné les facteurs associés à l'infection tuberculeuse. RÉSULTATS: La positivité QuantiFERON-au départ (prévalence : 22,6%, IC à 95% 20,9­24,4), était indépendamment associée à l'augmentation de l'âge (aOR 1,24 par année supplémentaire, IC à 95% 1,15­1,34) et à l'exposition du ménage à la TB au cours de la vie du participant (aOR 1,87 ; IC à 95% 1,46­2,40). La conversion QFT-Plus à l'année 3 (12,2%, IC à 95% 10,5­14,0 ; taux d'infection annuel : 3,95%) était associée à l'exposition du ménage à un cas de tuberculose index (aOR 2,74 ; IC à 95% 1,05­7,18). CONCLUSION: Les taux d'infection tuberculeuse diagnostiquée par QFT restent élevés dans cette population. La forte association avec l'exposition à la TB dans les ménages renforce l'importance de la recherche des contacts, du traitement préventif et du traitement précoce des maladies infectieuses pour réduire la transmission communautaire.

Acceptability, feasibility and cost of point of care testing for sexually transmitted infections among South African adolescents where syndromic management is standard of care.

BACKGROUND: Young people (YP) in southern Africa are at substantial risk of HIV and sexually transmitted infections (STIs). Despite the epidemiological and biological link between STIs and HIV transmission and acquisition, infections such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) remain widely undiagnosed. Syndromic STI management is the standard of care in low- and middle-income countries (LMICs) despite a high prevalence of asymptomatic infections. We conducted an observational study to explore the acceptability, feasibility, and cost of a STI test-and-treat service for YP in Cape Town. METHODS: YP attending a mobile clinic (MC) and a youth centre clinic (YC) were offered STI screening. Urine testing for CT and NG using a 90-min molecular point-of-care (POC) test on the GeneXpert platform was conducted and treatment provided. Data were collated on demographics, sexual behaviour, presence of symptoms, uptake of same-day treatment, prevalence of CT/NG, and service acceptability. RESULTS: Three hundred sixty six participants were enrolled (median age 20, 83% female).57% (209/366) of participants tested positive for either CT (126/366, 34%) or NG (57/366, 16%) or co-infection (26/366, 7%). Clinical symptoms were a poor predictor of GeneXpert diagnosed CT or NG, with a sensitivity of 46.8% and 54.0% for CT and NG respectively. Although half of participants initially chose to receive same day results and treatment, only a third waited for results on the day. The majority of participants (91%) rated the service highly via a post-visit acceptability questionnaire. CONCLUSION: Curable STIs are highly prevalent in this population. STI screening using POC testing was feasible and acceptability was high. The study provides further impetus for moving policy beyond syndromic management of STIs in South Africa.

Goals for girls: a cluster-randomized trial to investigate a school-based sexual health programme amongst female learners in South Africa.

The delivery of comprehensive sexuality education to adolescents at school is recognized as a long-term strategy to support adolescent health. Suboptimal sexual and reproductive health (SRH) outcomes among South African adolescents necessitate the ongoing development and optimization of SRH education and promotion models. We conducted a cluster-randomized controlled trial amongst secondary schools (n = 38) in Cape Town, South Africa, to evaluate a sport-based, near-peer-led SRH curriculum, SKILLZ, amongst female learners (n = 2791). Biomedical (sexually transmitted infections [STIs], human immunodeficiency virus [HIV] and pregnancy) and socio-behavioural (social support, gender norms and self-concept) outcomes were assessed pre and post intervention. Attendance at SKILLZ was low and intervention participants did not show an improvement in SRH outcomes, with HIV and pregnancy incidence remaining stable and STI prevalence remaining high and increasing in both control and intervention arms. Although evidence of positive socio-behavioural measures was present at baseline, participants with high attendance showed further improvement in positive gender norms. SKILLZ did not demonstrate the capacity to significantly impact clinical SRH outcomes. Modest improvements in outcomes amongst high attenders suggest that the impact may be possible with improved attendance; however, in the absence of optimal attendance, alternative intervention strategies may be required to improve SRH outcomes amongst adolescents.

Sisonke phase 3B open-label study: Lessons learnt for national and global vaccination scale-up during epidemics.

Sisonke is a multicentre, open-label, single-arm phase 3B vaccine implementation study of healthcare workers (HCWs) in South Africa, with prospective surveillance for 2 years. The primary endpoint is the rate of severe COVID­19, including hospitalisations and deaths. The  Sisonke study enrolled and vaccinated participants nationally at potential vaccination roll-out sites between 17 February and 26 May 2021. After May 2021, additional HCWs were vaccinated as part of a sub-study at selected clinical research sites. We discuss 10 lessons learnt to strengthen national and global vaccination strategies:(i) consistently advocate for vaccination to reduce public hesitancy; (ii) an electronic vaccination data system (EVDS) is critical; (iii) facilitate access to a choice of vaccination sites, such as religious and community centres, schools, shopping malls and drive-through centres; (iv) let digitally literate people help elderly and marginalised people to register for vaccination; (v) develop clear 'how to' guides for vaccine storage, pharmacy staff and vaccinators; (vi) leverage instant messaging platforms, such as WhatsApp, for quick communication among staff at vaccination centres; (vii) safety is paramount - rapid health assessments are needed at vaccination centres to identify people at high risk of serious adverse events, including anaphylaxis or thrombosis with thrombocytopenia syndrome. Be transparent about adverse events and contextualise vaccination benefits, while acknowledging the small risks; (viii) provide real-time, responsive support to vaccinees post vaccination and implement an accessible national vaccine adverse events surveillance system; (ix) develop efficient systems to monitor and investigate COVID­19 breakthrough infections; and (x) flexibility and teamwork are essential in vaccination centres across national, provincial and district levels and between public and private sectors.

Uptake and acceptability of medical male circumcision among young males in two culturally distinct settings in South Africa: A longitudinal, community-based study (the MACHO study).

BACKGROUND: Young South Africans experience high rates of HIV infection. While nationally scaled medical male circumcision (MMC) can help to curb HIV infection rates in countries such as South Africa (SA), MMC uptake has not been consistent or universal, suggesting variable acceptability among men. Both MMC and traditional male circumcision (TMC) are practised in SA. For male circumcision to be most effective for HIV prevention, it should be performed prior to sexual debut with complete removal of the foreskin. OBJECTIVES: The MACHO (Male Adolescent Choices for HIV Prevention Options) study investigated uptake of and preference for MMC v. TMC in two culturally distinct settings in SA. METHODS: This observational, longitudinal, cohort study investigated circumcision preferences and uptake in 100 males (aged 14 - 17 years) and their legal guardians in Cape Town (Western Cape Province) and Soweto (Gauteng Province). Data were collected via surveys administered every 4 months over a 24-month period. RESULTS: A total of 100 uncircumcised adolescent boys (Cape Town n=50, Soweto n=50; mean (interquartile range) age 15 (14 - 16) years) and their guardians were enrolled. At baseline, 42 boys from Soweto (84%) and none from Cape Town expressed a preference for MMC over TMC. Sowetan participants were more likely to elect circumcision (MMC n=11 (22%), TMC n=1 (2%)) than those from Cape Town (TMC n=1 (2%), MMC n=0) over 13.6 months of follow-up (hazard ratio 18.9; 95% confidence interval 2.37 - 150.71; p=0.006). CONCLUSIONS: MMC was the preferred option for young men in Soweto compared with those in Cape Town, and this translated into practice. Despite knowledge of the benefits of early MMC, many participants delayed uptake, potentially reducing the MMC benefits before sexual debut. Programmes promoting circumcision should consider the influence of local practices. To realise full HIV prevention benefits, efforts should be made to ensure that circumcision is promoted, and that all circumcision is safe, performed prior to sexual debut, and contextually responsive.

Combined HIV Adolescent Prevention Study (CHAPS): comparison of HIV pre-exposure prophylaxis regimens for adolescents in sub-Saharan Africa-study protocol for a mixed-methods study including a randomised controlled trial.

BACKGROUND: HIV remains a major public health issue, especially in Eastern and Southern Africa. Pre-exposure prophylaxis is highly effective when adhered to, but its effectiveness is limited by cost, user acceptability and uptake. The cost of a non-inferiority phase III trial is likely to be prohibitive, and thus, it is essential to select the best possible drug, dose and schedule in advance. The aim of this study, the Combined HIV Adolescent PrEP and Prevention Study (CHAPS), is to investigate the drug, dose and schedule of pre-exposure prophylaxis (PrEP) required for the protection against HIV and the acceptability of PrEP amongst young people in sub-Saharan Africa, and hence to inform the choice of intervention for future phase III PrEP studies and to improve strategies for PrEP implementation. METHODS: We propose a mixed-methods study amongst young people aged 13-24 years. The first component consists of qualitative research to identify the barriers and motivators towards the uptake of PrEP amongst young people in South Africa, Uganda and Zimbabwe. The second component is a randomised clinical trial (ClinicalTrials.gov NCT03986970, June 2019) using a novel ex vivo HIV challenge method to investigate the optimal PrEP treatment (FTC-TDF vs FTC-TAF), dose and schedule. We will recruit 144 amongst HIV-negative uncircumcised men aged 13-24 years from voluntary male medical circumcision clinics in two sites (South Africa and Uganda) and randomise them into one of nine arms. One group will receive no PrEP prior to surgery; the other arms will receive either FTC-TDF or FTC-TAF, over 1 or 2 days, and with the final dose given either 6 or 20 h prior to surgery. We will conduct an ex vivo HIV challenge on their resected foreskin tissue. DISCUSSION: This study will provide both qualitative and quantitative results to help decide the optimum drug, dose and schedule for a future phase III trial of PrEP. The study will also provide crucial information on successful strategies for providing PrEP to young people in sub-Saharan Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT03986970 . Registered on 14 June 2019.

Safety and tolerability of injectable Rilpivirine LA in HPTN 076: A phase 2 HIV pre-exposure prophylaxis study in women.

BACKGROUND: Daily oral TDF/FTC is protective against HIV infection when used for pre-exposure prophylaxis (PrEP). However, daily adherence to oral PrEP is difficult for many; therefore, finding alternative PrEP strategies remains a priority. HPTN 076 evaluated the long-acting injectable form of rilpivirine (RPV), known as RPV LA for safety, pharmacokinetics and acceptability. METHODS: HPTN 076 (NTC 02165202) was a phase 2, double-blind, 2:1 randomized trial comparing the safety of 1200mg RPV LA (LA) to placebo (P). The study included a 28-day oral run-in phase of daily, self- administered oral RPV (25 mg), with directly observed oral dosing about six times. Of 136 enrolled sexually active, HIV-uninfected, low HIV-risk African (100) and US (36) adult women, injectable product was administered in two gluteal, intramuscular (IM) injections once every eight weeks to 122 participants following the oral run-in phase. A maximum of six injection time points occurred over a 48-week period. Acceptability, safety, tolerability and pharmacokinetic (PK) data were collected throughout the study. This paper includes primary endpoint data collected up to the week 52 post enrollment. FINDINGS: The median age of the enrolled population was 31 years (IQR: 25,38), median weight 75 kg (IQR: 64, 89), median body mass index (BMI) 30 (IQR: 27, 35), 46% married, 94% Black and 60% unemployed. A total of 122 (80 LA, 42 P) women received at least one injection and 98 (64 LA, 34 P) received all six injections. During the injection phase, three women withdrew from the study (2 LA, 1 P) and 16 women discontinued study product (10 LA, 6 P). Fourteen women (11 LA and 3 P) discontinued oral study product and did not enter the injection phase. Study product discontinuations were not significantly different between the two arms throughout. Of the product discontinuations in the injection phase, 8% in LA and 5% in P arm were due to adverse events (AEs), including one randomized to the P arm with prolonged QTc interval on EKG. The proportion of women who experienced Grade 2 or higher AEs during the injection phase as the primary outcome was not significantly different between the two arms [73.8%, 95% CI: (63.2%, 82.1%) for LA and 73.8%, 95% CI: (58.9%, 84.7%), p>0.99]. Transient Grade ≥2 liver abnormalities occurred in 14% of women in the LA arm compared with 12% in P arm. Three LA women (4%) developed Grade 3 injection site reactions compared with none in P arm. In participants who received at least 1 injection, the geometric mean of overall RPV trough concentrations (Ctrough) was 62.2 ng/mL. In participants who received all six injections, the geometric mean of CTrough through the injection phase and after the last injection were 72.8 ng/mL and 100.9 ng/mL, respectively. At week 52 (eight weeks after last injection), the geometric mean of RPV Ctrough was 75.0 ng/mL. At the last injection visit (Week 44), 80 % of women who answered acceptability questions strongly agreed that they would think about using- and 68% that they would definitely use a PrEP injectable in the future. INTERPRETATION: RPV LA IM injections every eight weeks in African and US women were safe and acceptable. Overall, despite more injection site reactions and pain in the participants receiving RPV LA the injections were well tolerated. Data from this study support the further development of injectable PrEP agents.

What do South African adolescents want in a sexual health service? Evidence from the South African Studies on HIV in Adolescents (SASHA) project.

BACKGROUND: Young people in sub-Saharan Africa (SSA) are disproportionately affected by HIV, sexually transmitted infections and unplanned pregnancies. The provision of accessible sexual and reproductive health services (SRHS) for young people in SSA is vital to reduce this burden. OBJECTIVES: To examine the needs of South African (SA) adolescents with regard to differentiated, accessible and adolescent-responsive SRHS. METHODS: Data were drawn from a larger project examining the feasibility of conducting HIV vaccine trials in adolescents. Fifteen focus group discussions were conducted across five research sites in four SA provinces with 120 male and female adolescent human papillomavirus vaccine trial participants aged 12 - 19 years from low-income areas with a high incidence of HIV. Transcribed data were double-coded using framework analysis. RESULTS: Three main themes emerged on how best to improve SRHS for adolescents in resource-limited settings: adolescent-friendly services, availability of developmentally appropriate and tailored information, and improved relationships between healthcare workers and clinic attendees. Participants wanted more flexible opening hours at SRHS to account for travel time to clinics from school and home. They suggested that services include contraception, counselling, educational materials, links to adoption services, emergency vehicles, pre- and postnatal care, and improved service quality from clinic staff. CONCLUSIONS: While dedicated adolescent SRHS might best meet the needs of young people in SA, the study suggests that failing this, existing SRHS should be more responsive to adolescent use. Innovations such as mobile outreach services, self-testing and flexible hours will help SRHS respond to adolescents' needs.

Feasibility and acceptability of conducting HIV vaccine trials in adolescents in South Africa: Going beyond willingness to participate towards implementation.

BACKGROUND: HIV/AIDS remains a leading cause of death in adolescents (aged 15 - 25 years), and in sub-Saharan Africa HIV-related deaths continue to rise in this age group despite a decline in both adult and paediatric populations. This is attributable in part to high adolescent infection rates and supports the urgent need for more efficacious prevention strategies. In particular, an even partially effective HIV vaccine, given prior to sexual debut, is predicted to significantly curb adolescent infection rates. While adolescents have indicated willingness to participate in HIV vaccine trials, there are concerns around safety, uptake, adherence, and ethical and logistic issues. OBJECTIVES: To initiate a national, multisite project with the aim of identifying obstacles to conducting adolescent HIV vaccine trials in South Africa (SA). METHOD: A simulated HIV vaccine trial was conducted in adolescents aged 12 - 17 years across five SA research sites, using the already licensed Merck human papillomavirus vaccine Gardasil as a proxy for an HIV vaccine. Adolescents were recruited at community venues and, following a vaccine discussion group, invited to participate in the trial. Consent for trial enrolment was obtained from a parent or legal guardian, and participants aged 16 - 17 years were eligible only if sexually active. Typical vaccine trial procedures were applied during the five study visits, including the administration of vaccination injections at study visits 2, 3 and 4. RESULTS: The median age of participants was 14 years (interquartile range 13 - 15), with 81% between the ages of 12 and 15 years at enrolment. Overall, 98% of screened participants opted to receive the vaccine, 588 participants enrolled, and 524 (89%) attended the final visit. CONCLUSIONS: This trial showed that adolescents can be recruited, enrolled and retained in clinical prevention trials with parental support. While promising, these results were tempered by the coupling of sexual-risk eligibility criteria and the requirement for parental/guardian consent, which was probably a barrier to the enrolment of high-risk older adolescents. Further debate around appropriate consent approaches for such adolescents in HIV prevention studies is required.

HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa.

OBJECTIVES: Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. METHODS: We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. RESULTS: A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre-ART VL, 4.0 log10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL ≤ 1000 and ≤ 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL < 50, 50-1000 and > 1000 copies/mL at delivery, respectively (P < 0.001). CONCLUSIONS: High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention.

The mass miniature chest radiography programme in Cape Town, South Africa, 1948 - 1994: The impact of active tuberculosis case finding.

BACKGROUND: Tuberculosis (TB) control programmes rely mainly on passive detection of symptomatic individuals. The resurgence of TB has rekindled interest in active case finding. Cape Town (South Africa) had a mass miniature radiography (MMR) screening programme from 1948 to 1994. OBJECTIVE: To evaluate screening coverage, yield and secular trends in TB notifications during the MMR programme. METHODS: We performed an ecological analysis of the MMR programme and TB notification data from the City of Cape Town Medical Officer of Health reports for 1948 - 1994. RESULTS: Between 1948 and 1962, MMR screening increased to 12% of the population per annum with yields of 14 cases per 1 000 X-rays performed, accounting for >20% of total annual TB notifications. Concurrent with increasing coverage (1948 - 1965), TB case notification decreased in the most heavily TB-burdened non-European population from 844/100 000 population to 415/100 000. After 1966, coverage declined and TB notifications that initially remained stable (1967 - 1978) subsequently increased to 525/100 000. MMR yields remained low in the European population but declined rapidly in the non-European population after 1966, coincidental with forced removals from District 6. An inverse relationship between screening coverage and TB notification rates was observed in the non-European adult population. Similar secular trends occurred in infants and young children who were not part of the MMR screening programme. CONCLUSION: MMR of a high-burdened population may have significantly contributed to TB control and was temporally associated with decreased transmission to infants and children. These historical findings emphasise the importance of re-exploring targeted active case finding strategies as part of population TB control.

An integrated community TB-HIV adherence model provides an alternative to DOT for tuberculosis patients in Cape Town.

SETTING: Cape Town, South Africa. OBJECTIVE: To evaluate anti-tuberculosis treatment outcomes and rate of antiretroviral therapy (ART) initiation using weekly community-based adherence support compared to daily directly observed therapy (DOT). METHODS: This was a retrospective analysis comparing two cohorts treated for tuberculosis (TB) in 70 TB clinics during 6-month periods before and after the introduction of a new adherence model comprising treatment literacy sessions during 2 weeks of DOT, followed by weekly home visits by community care workers to eligible patients managing their own treatment. Odds ratios (ORs) of treatment success and ART initiation were calculated using multivariable random effects logistic regression models. Hazard ratios (HRs) of default and death were calculated using multivariable random effects Cox regression models. RESULTS: The pre-intervention cohort comprised 11 896 patients with TB and the post-intervention cohort 11 314. There was no difference in pre- and post-intervention anti-tuberculosis treatment success rates (respectively 82.8% and 82.5%, adjusted OR [aOR] 1.02, 95%CI 0.89-1.17, P = 0.76) nor an increased hazard of death (adjusted HR [aHR] 0.98, 95%CI 0.80-1.21, P = 0.87) or default (aHR 0.97, 95%CI 0.81-1.15, P = 0.69). The ART initiation rate increased from 67% to 74% (aOR 1.43; 95%CI 1.01-1.85, P < 0.01). CONCLUSION: Weekly community-based adherence support was a viable alternative to daily DOT, with no deterioration in anti-tuberculosis treatment outcomes and an increase in ART initiation.

Pre-exposure prophylaxis for South African adolescents: What evidence?

Adolescents and young women, particularly in South Africa, are at increased risk of HIV acquisition. To date, we have had limited primary prevention options to offer. Oral pre-exposure prophylaxis (PrEP) is an additional prevention modality that has now been proven to reduce HIV acquisition in those who take it consistently during periods of HIV infection exposure. We review the PrEP evidence in adolescents and highlight some of the research gaps. Our recommendation is to increase the number of demonstration projects and other scale-up opportunities to offer oral PrEP to at-risk adolescents, and monitor carefully to answer the outstanding questions.

Isoniazid preventive therapy for tuberculosis in South Africa: an assessment of the local evidence base.

Worldwide, South Africa (SA) has the worst tuberculosis (TB) epidemic. In SA, there are > 6.1 million people living with HIV (PLWH) and the country now has the largest antiretroviral treatment programme with > 2 million people receiving combination therapy. While there has been a marked recent decline in HIV-associated deaths, > 50% of TB cases still continue to be diagnosed in PWLH. The current TB control strategy based on passive case finding, chemotherapy of childhood TB contacts and directly observed therapy has clearly failed to control endemic TB in SA. Two recent meta-analyses have shown a > 60% reduction in TB in HIV-infected adults after isoniazid preventive therapy (IPT). SA has implemented the World Health Organization policy and IPT is now recommended for HIV-positive people for up to 36 months. Originally, there was only one SA study included in the evidence base supporting this policy, but subsequently four randomised controlled trials have been conducted in SA populations. These studies, together with local observational studies, are the subject of this local, evidence-based review.

Integration of TB and ART services fails to improve TB treatment outcomes: comparison of ART/TB primary healthcare services in Cape Town, South Africa.

BACKGROUND: The combined tuberculosis (TB) and HIV epidemics in South Africa (SA) have created enormous operational challenges for a health service that has traditionally run vertical programmes for TB treatment and antiretroviral therapy (ART) in separate facilities. This is particularly problematic for TB/HIV co-infected patients who need to access both services. OBJECTIVE: To determine whether integrated TB facilities had better TB treatment outcomes than single-service facilities in Cape Town, SA. METHODS: TB treatment outcomes were determined for newly registered, adult TB patients (aged > or = 18 years) at 13 integrated ART/TB primary healthcare (PHC) facilities and four single-service PHC facilities from 1 January 2009 to 30 June 2010. A chi2 test adjusted for a cluster sample design was used to compare outcomes by type of facility. RESULTS: Of 13,542 newly registered patients, 10,030 received TB treatment in integrated facilities and 3,512 in single-service facilities. There was no difference in baseline characteristics between the two groups with HIV status determined for 9,351 (93.2%) and 3,227 (91.9%) patients, of whom 6 649 (66.3%) and 2,213 (63%) were HIV-positive in integrated facilities and single-service facilities, respectively. The median CD4+ count of HIV-positive patients was 152 cells/microl (interquartile range (IQR) 71-277) for integrated facilities and 148 cells/microl (IQR 67-260) for single-service facilities. There was no statistical difference in the TB treatment outcome profile between integrated and single-service facilities for all TB patients (p = 0.56) or for the sub-set of HIV-positive TB patients (p = 0.58) CONCLUSION: This study did not demonstrate improved TB treatment outcomes in integrated PHC facilities and showed that the provision of ART in the same facility as TB services was not associated with lower TB death and default rates.

Impact of human immunodeficiency virus and CD4 count on tuberculosis diagnosis: analysis of city-wide data from Cape Town, South Africa.

BACKGROUND: The impact of human immunodeficiency virus (HIV) infection and CD4 count on the diagnosis of tuberculosis (TB) at population level is incompletely defined. OBJECTIVE: To determine how HIV infection and CD4 count affect disease site, sputum smear status and overall rate of laboratory confirmation (sputum smear microscopy or culture) of TB cases under routine programme conditions. DESIGN: Retrospective analysis of the 2009 electronic TB register for Cape Town, South Africa. RESULTS: Of 29,478 TB cases notified in 2009, HIV status was known for 25,744 (87.3%) cases, of whom 13,237 (51.4%) were HIV-positive. Of these, 61.2% had CD4 cell counts of <200 cells/µl and 82.7% had counts of <350 cells/µl. Laboratory confirmation of TB (by smear or culture) was obtained less frequently in HIV-infected than non-HIV-infected adult cases (53.9% vs. 74.3%, P< 0.001). HIV infection was associated with a higher proportion of sputum smear-negative and extra-pulmonary TB and lower grades of sputum smear positivity even among those with CD4 counts of ≥ 500 cells/µl. However, the relationship between the proportion of smear-positive cases and CD4 count was non-linear. CONCLUSION: Much TB is not laboratory-confirmed in this setting despite good laboratory services. HIV-associated TB is more difficult to diagnose even at high CD4 cell counts of >500 cells/µl, suggesting early impact after HIV seroconversion.