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Background: Community-based peer support has been shown to be effective in improving exclusive breastfeeding rates in a variety of settings. Methods: We conducted a cost analysis of a community cluster randomised-controlled trial (Promise-EBF), aimed at promoting exclusive infant feeding in three sites in South Africa. The costs were considered from the perspective of health service providers. Peer supporters in this trial visited women to support exclusive infant feeding, once antenatally and four times postpartum. Results: The total economic cost of the Promise-EBF intervention was US$393 656, with average costs per woman and per visit of US$228 and US$52, respectively. The average costs per woman and visit in an operational ‘non research’ scenario were US$137 and US$32 per woman and visit, respectively. Investing in the promotion of exclusive infant feeding requires substantial financial commitment from policy makers. Extending the tasks of multi-skilled community health workers (CHWs) to include promoting exclusive infant feeding is a potential option for reducing these costs. In order to avoid efficiency losses, we recommend that the time requirements for delivering the promotion of exclusive infant feeding are considered when integrating it within the existing activities of CHWs. Discussion: This paper focuses on interventions for exclusive infant feeding, but its findings more generally illustrate the importance of documenting and quantifying factors that affect the feasibility and sustainability of community-based interventions, which are receiving increased focus in low income settings. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to develop and validate, by consensus, the construct and content of an observations chart for nurses incorporating a modified early warning scoring (MEWS) system for physiological parameters to be used for bedside monitoring on general wards in a public hospital in South Africa. Methods: Delphi and modified face-to-face nominal group consensus methods were used to develop and validate a prototype observations chart that incorporated an existing UK MEWS. This informed the development of the Cape Town ward MEWS chart. Participants: One specialist anaesthesiologist, one emergency medicine specialist, two critical care nurses and eight senior ward nurses with expertise in bedside monitoring (N = 12) were purposively sampled for consensus development of the MEWS. One general surgeon declined and one neurosurgeon replaced the emergency medicine specialist in the final round. Results: Five consensus rounds achieved ≥70% agreement for cut points in five of seven physiological parameters respiratory and heart rates, systolic BP, temperature and urine output. For conscious level and oxygen saturation a relaxed rule of <70% agreement was applied. A reporting algorithm was established and incorporated in the MEWS chart representing decision rules determining the degree of urgency. Parameters and cut points differed from those in MEWS used in developed countries. Conclusions: A MEWS for developing countries should record at least seven parameters. Experts from developing countries are best placed to stipulate cut points in physiological parameters. Further research is needed to explore the ability of the MEWS chart to identify physiological and clinical deterioration. [ABSTRACT FROM AUTHOR]

Background: The scale-up of voluntary medical male circumcision (VMMC) services in South Africa has been rapid, in an attempt to achieve the national government target of 4.3 million adult male circumcisions for HIV prevention by 2016. This study assesses the effect of the scale-up on the quality of the VMMC program. Methods and Findings: This analysis compares the quality of services at 15 sites operational in 2011 to (1) the same 15 sites in 2012 and (2) to a set of 40 sites representing the expanded program in 2012. Trained clinicians scored each site on 29 items measuring readiness to provide quality services (abbreviated version of the WHO Quality Assessment [QA] Guide) and 29 items to assess quality of surgical care provided (pre-op, surgical technique and post-op) based on the observation of VMMC procedures at each site. Declines in quality far outnumbered improvements. The negative effects in terms of readiness to provide quality services were most evident in expanded sites, whereas the declines in provision of quality services tended to affect both repeat sites and expanded sites equally. Areas of notable concern included the monitoring of adverse events, external supervision, post-operative counselling, and some infection control issues. Scores on quality of surgical technique tended to be among the highest across the 58 items observed, and the South Africa program has clearly institutionalized three “best practices” for surgical efficiency. Conclusions: These findings demonstrate the challenges of rapidly developing large numbers of new VMMC sites with the necessary equipment, supplies, and protocols. The scale-up in South Africa has diluted human resources, with negative effects for both the original sites and the expanded program. [ABSTRACT FROM AUTHOR]

Introduction: The seasonal variability in hospitalization for tuberculosis may in part relate to super-imposed bacterial or predisposing respiratory viral infections. We aimed to study the temporal association between hospitalization for culture-confirmed pulmonary tuberculosis (PTB), invasive pneumococcal disease (IPD) and influenza virus epidemics in South African children. Methods: We undertook a retrospective analysis which examined seasonal trends, from 2005 to 2008, for hospitalization for culture-confirmed PTB and IPD among children in relation to the influenza epidemics in Soweto, South Africa. Original time-series of the influenza virus epidemics and hospitalization rates for PTB and IPD were decomposed into three components: a trend cycle component, a seasonal component and an irregular component using the X-11 seasonal adjustment method. To compare the seasonality amongst the three series, the trend and irregular components were removed and only seasonal components examined. Results: Across the study period, the influenza virus epidemics peaked during May to July (winter) months, which was closely followed by an increase in the incidence of hospitalization for IPD (August to October) and PTB (August to November). Discussion: Within- and between-year temporal changes associated with childhood TB hospitalization may in part be driven by factors which influence temporal changes in pneumococcal disease, including potential variability in the severity of influenza virus epidemics in temperate climates. The dynamics of the interplay between the host and these infectious agents appears to be complex and multifactorial. [ABSTRACT FROM AUTHOR]

Background: Patients with Addison's disease (AD) in Scandinavia have an increased risk for premature death due to cardiovascular disease (CVD). Serum lipids are important risk factors for CVD and vascular mortality. Replacement doses of hydrocortisone have historically been higher in Sweden than South Africa. The primary aim was to study the lipid profiles in a large group of patients with AD with the hypothesis that the lipid profile in patients in Sweden would be worse than in South Africa. Methods: In a cross-sectional study, 110 patients with AD (55 from South Africa, 55 from Sweden) matched for age, gender, ethnicity and BMI were studied. Anthropometric measures, blood pressure, lipids, highly sensitive C-reactive protein (hs-CRP) and adiponectin were studied. Results: All patients were Caucasian and the majority were women N = 36 (65.5%). Mean (standard deviation; SD) ages of the Swedish and South African patients were 52.9 (13.0) and 52.6 (14.4) years and BMI 25.3 (3.2) and 25.8 (4.1) kg/m2, respectively. The mean total daily hydrocortisone dose was greater in the Swedish patients than the South African patients, [33.0 (8.1) versus 24.3 (8.0) mg; p<0.0001]. South African patients had higher median (interquartilerange; IQR) triglycerides (TG) [1.59 (1.1–2.46) versus 0.96 (0.74–1.6) mmol/l; p<0.001], total cholesterol (TC) [6.02(1.50) versus 5.13 (0.87) mmol/l; p<0.001], LDL-C [4.43 (1.44) versus 2.75 (0.80) mmol/l; p<0.001] and median hs-CRP [2.15 (0.93–5.45) versus 0.99 (0.57–2.10) mg/L; p<0.003] and lower HDL-C [0.80 (0.40) versus 1.86 (0.46) mmol/l; p<0.001] than the Swedish patients. Approximately 20% of the patients in both cohorts had hypertension and diabetes mellitus. Conclusions: South African patients with AD have worse lipid profiles and higher hs-CRP compared to their matched Swedish patients, despite lower doses of hydrocortisone. It is uncertain at this time whether these are due to genetic or environmental factors. [ABSTRACT FROM AUTHOR]

Background: The current study aims to investigate how the ability to accurately gauge risk factors associated with contracting HIV while taking into consideration various individual and community level socio-demographic characteristics (e.g., race and poverty) predicts the nature of stigmatizing attitudes toward persons with HIV. Methods: Data from a sample of 1,347 Cape Town area youth who participated in the Cape Area Panel Study (CAPS) Wave 2a were used. Latent Class Analysis was conducted to ascertain whether response patterns regarding knowledge of HIV contraction suggest the presence of subgroups within the sample. Results: Findings indicate that there are four latent classes representing unique response pattern profiles regarding knowledge of HIV contraction. Additionally, our results suggest that those in South Africa who are classified as “white,” live in more affluent communities, and have more phobic perceptions of HIV risk are also more likely to have the most stigmatizing attitudes toward those who are HIV positive. Conclusion: Implications of these findings include extending HIV knowledge, education, and awareness programs to those who are not traditionally targeted in an attempt to increase levels of knowledge about HIV and, consequently, decrease stigma. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis is a major health concern in prisons, particularly where HIV prevalence is high. Our objective was to determine the undiagnosed pulmonary tuberculosis (“undiagnosed tuberculosis”) prevalence in a representative sample of prisoners in a South African prison. In addition we investigated risk factors for undiagnosed tuberculosis, to explore if screening strategies could be targeted to high risk groups, and, the performance of screening tools for tuberculosis. Methods and Findings: In this cross-sectional survey, male prisoners were screened for tuberculosis using symptoms, chest radiograph (CXR) and two spot sputum specimens for microscopy and culture. Anonymised HIV antibody testing was performed on urine specimens. The sensitivity, specificity and predictive values of symptoms and investigations were calculated, using Mycobacterium tuberculosis isolated on sputum culture as the gold standard. From September 2009 to October 2010, 1046 male prisoners were offered enrolment to the study. A total of 981 (93.8%) consented (median age was 32 years; interquartile range [IQR] 27–37 years) and were screened for tuberculosis. Among 968 not taking tuberculosis treatment and with sputum culture results, 34 (3.5%; 95% confidence interval [CI] 2.4–4.9%) were culture positive for Mycobacterium tuberculosis. HIV prevalence was 25.3% (242/957; 95% CI 22.6–28.2%). Positive HIV status (adjusted odds ratio [aOR] 2.0; 95% CI 1.0–4.2) and being an ex-smoker (aOR 2.6; 95% CI 1.2–5.9) were independently associated with undiagnosed tuberculosis. Compared to the gold standard of positive sputum culture, cough of any duration had a sensitivity of 35.3% and specificity of 79.6%. CXR was the most sensitive single screening modality (sensitivity 70.6%, specificity 92.2%). Adding CXR to cough of any duration gave a tool with sensitivity of 79.4% and specificity of 73.8%. Conclusions: Undiagnosed tuberculosis and HIV prevalence was high in this prison, justifying routine screening for tuberculosis at entry into the prison, and intensified case finding among existing prisoners. [ABSTRACT FROM AUTHOR]

Novel tuberculosis vaccines are in varying stages of pre-clinical and clinical development. This study seeks to estimate the potential cost-effectiveness of a BCG booster vaccine, while accounting for costs of large-scale clinical trials, using the MVA85A vaccine as a case study for estimating potential costs. We conducted a decision analysis from the societal perspective, using a 10-year time frame and a 3% discount rate. We predicted active tuberculosis cases and tuberculosis-related costs for a hypothetical cohort of 960,763 South African newborns (total born in 2009). We compared neonatal vaccination with bacille Calmette-Guérin alone to vaccination with bacille Calmette-Guérin plus a booster vaccine at 4 months. We considered booster efficacy estimates ranging from 40% to 70%, relative to bacille Calmette-Guérin alone. We accounted for the costs of Phase III clinical trials. The booster vaccine was assumed to prevent progression to active tuberculosis after childhood infection, with protection decreasing linearly over 10 years. Trial costs were prorated to South Africa's global share of bacille Calmette-Guérin vaccination. Vaccination with bacille Calmette-Guérin alone resulted in estimated tuberculosis-related costs of $89.91 million 2012 USD, and 13,610 tuberculosis cases in the birth cohort, over the 10 years. Addition of the booster resulted in estimated cost savings of $7.69–$16.68 million USD, and 2,800–4,160 cases averted, for assumed efficacy values ranging from 40%–70%. A booster tuberculosis vaccine in infancy may result in net societal cost savings as well as fewer active tuberculosis cases, even if efficacy is relatively modest and large scale Phase III studies are required. [ABSTRACT FROM AUTHOR]

Background: For the first time in the history of HIV, new bio-medical interventions have been shown to be effective in preventing HIV transmission. For these new HIV prevention technologies (NPTs) to have an impact on the epidemic, they must be widely used. This study uses a discrete choice experiment (DCE) to: understand the relative strength of women’s preferences for product characteristics, understand the implications for substitution away from male condoms, and inform realistic modelling of their potential impact and cost-effectiveness. Methods: A DCE was conducted among 1017 women in urban South Africa. Women were presented with choices between potential women’s NPTs (microbicides, diaphragm, female condom) and ‘what I did last time’ (use or not use a condom) with different HIV and pregnancy prevention effectiveness’ and prices. Choice probabilities are estimated using the nested logit model and used to predict uptake. Results: In this high HIV prevalence setting, HIV prevention effectiveness is the main driver of uptake followed by pregnancy prevention effectiveness. For example a microbicide with poor effectiveness would have niche appeal at just 11% predicted uptake, while a highly effective microbicide (95% effective against HIV and pregnancy) would have far wider appeal (56% predicted uptake). Though women who reported not using condoms were more likely to choose the NPTs, at current very high rates of male condom use in South Africa (60%), about half of microbicide uptake is projected to be among those currently not using condoms. Conclusions: Women are very interested in NPTs, especially if highly effective in preventing HIV and pregnancy. Women in greatest need were also most likely to switch to the new products. Where products are not yet available for distribution, proxy data, such as that generated by DCEs, can bring realism to overly optimistic uptake scenarios found in many current impact models. [ABSTRACT FROM AUTHOR]

Objective: To determine the frequency and patterns of acquired antiretroviral drug resistance in a rural primary health care programme in South Africa. Design: Cross-sectional study nested within HIV treatment programme. Methods: Adult (≥18 years) HIV-infected individuals initially treated with a first-line stavudine- or zidovudine-based antiretroviral therapy (ART) regimen and with evidence of virological failure (one viral load >1000 copies/ml) were enrolled from 17 rural primary health care clinics. Genotypic resistance testing was performed using the in-house SATuRN/Life Technologies system. Sequences were analysed and genotypic susceptibility scores (GSS) for standard second-line regimens were calculated using the Stanford HIVDB 6.0.5 algorithms. Results: A total of 222 adults were successfully genotyped for HIV drug resistance between December 2010 and March 2012. The most common regimens at time of genotype were stavudine, lamivudine and efavirenz (51%); and stavudine, lamivudine and nevirapine (24%). Median duration of ART was 42 months (interquartile range (IQR) 32–53) and median duration of antiretroviral failure was 27 months (IQR 17–40). One hundred and ninety one (86%) had at least one drug resistance mutation. For 34 individuals (15%), the GSS for the standard second-line regimen was <2, suggesting a significantly compromised regimen. In univariate analysis, individuals with a prior nucleoside reverse-transcriptase inhibitor (NRTI) substitution were more likely to have a GSS <2 than those on the same NRTIs throughout (odds ratio (OR) 5.70, 95% confidence interval (CI) 2.60–12.49). Conclusions: There are high levels of drug resistance in adults with failure of first-line antiretroviral therapy in this rural primary health care programme. Standard second-line regimens could potentially have had reduced efficacy in about one in seven adults involved. [ABSTRACT FROM AUTHOR]

Background: The proposed waist-to-height ratio (WHtR) cut-off of 0.5 is less optimal for cardiometabolic risk screening in children in many settings. The purpose of this study was to determine the optimal WHtR for children from South Africa, and investigate variations by gender, ethnicity and residence in the achieved value. Methods: Metabolic syndrome (MetS) components were measured in 1272 randomly selected learners, aged 10–16 years, comprising of 446 black Africans, 696 mixed-ancestry and 130 Caucasians. The Youden’s index and the closest-top-left (CTL) point approaches were used to derive WHtR cut-offs for diagnosing any two MetS components, excluding the waist circumference. Results: The two approaches yielded similar cut-off in girls, 0.465 (sensitivity 50.0, specificity 69.5), but two different values in boys, 0.455 (42.9, 88.4) and 0.425 (60.3, 67.7) based on the Youden’s index and the CTL point, respectively. Furthermore, WHtR cut-off values derived differed substantially amongst the regions and ethnic groups investigated, whereby the highest cut-off was observed in semi-rural and white children, respectively, Youden’s index0.505 (31.6, 87.1) and CTL point 0.475 (44.4, 75.9). Conclusion: The WHtR cut-off of 0.5 is less accurate for screening cardiovascular risk in South African children. The optimal value in this setting is likely gender and ethnicity-specific and sensitive to urbanization. [ABSTRACT FROM AUTHOR]

Background: South Africa shows one of the highest global burdens of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB). Since 2002, MDR-TB in South Africa has been treated by a standardized combination therapy, which until 2010 included ofloxacin, kanamycin, ethionamide, ethambutol and pyrazinamide. Since 2010, ethambutol has been replaced by cycloserine or terizidone. The effect of standardized treatment on the acquisition of XDR-TB is not currently known. Methods: We genetically characterized a random sample of 4,667 patient isolates of drug-sensitive, MDR and XDR-TB cases collected from three South African provinces, namely, the Western Cape, Eastern Cape and KwaZulu-Natal. Drug resistance patterns of a subset of isolates were analyzed for the presence of commonly observed resistance mutations. Results: Our analyses revealed a strong association between distinct strain genotypes and the emergence of XDR-TB in three neighbouring provinces of South Africa. Strains predominant in XDR-TB increased in proportion by more than 20-fold from drug-sensitive to XDR-TB and accounted for up to 95% of the XDR-TB cases. A high degree of clustering for drug resistance mutation patterns was detected. For example, the largest cluster of XDR-TB associated strains in the Eastern Cape, affecting more than 40% of all MDR patients in this province, harboured identical mutations concurrently conferring resistance to isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin, ethionamide, kanamycin, amikacin and capreomycin. Conclusions: XDR-TB associated genotypes in South Africa probably were programmatically selected as a result of the standard treatment regimen being ineffective in preventing their transmission. Our findings call for an immediate adaptation of standard treatment regimens for M/XDR-TB in South Africa. [ABSTRACT FROM AUTHOR]

Background: Two World Health Organization comparative assessments rated the quality of South Africa’s 1996 mortality data as low. Since then, focussed initiatives were introduced to improve civil registration and vital statistics. Furthermore, South African cause-of-death data are widely used by research and international development agencies as the basis for making estimates of cause-specific mortality in many African countries. It is hence important to assess the quality of more recent South African data. Methods: We employed nine criteria to evaluate the quality of civil registration mortality data. Four criteria were assessed by analysing 5.38 million deaths that occurred nationally from 1997–2007. For the remaining five criteria, we reviewed relevant legislation, data repositories, and reports to highlight developments which shaped the current status of these criteria. Findings: National mortality statistics from civil registration were rated satisfactory for coverage and completeness of death registration, temporal consistency, age/sex classification, timeliness, and sub-national availability. Epidemiological consistency could not be assessed conclusively as the model lacks the discriminatory power to enable an assessment for South Africa. Selected studies and the extent of ill-defined/non-specific codes suggest substantial shortcomings with single-cause data. The latter criterion and content validity were rated unsatisfactory. Conclusion: In a region marred by mortality data absences and deficiencies, this analysis signifies optimism by revealing considerable progress from a dysfunctional mortality data system to one that offers all-cause mortality data that can be adjusted for demographic and health analysis. Additionally, timely and disaggregated single-cause data are available, certified and coded according to international standards. However, without skillfully estimating adjustments for biases, a considerable confidence gap remains for single-cause data to inform local health planning, or to fill gaps in sparse-data countries on the continent. Improving the accuracy of single-cause data will be a critical contribution to the epidemiologic and population health evidence base in Africa. [ABSTRACT FROM AUTHOR]

Bovine tuberculosis (BTB) is a chronic, highly infectious disease that affects humans, cattle and numerous species of wildlife. In developing countries such as South Africa, the existence of extensive wildlife-human-livestock interfaces poses a significant risk of Mycobacterium bovis transmission between these groups, and has far-reaching ecological, economic and public health impacts. The African buffalo (Syncerus caffer), acts as a maintenance host for Mycobacterium bovis, and maintains and transmits the disease within the buffalo and to other species. In this study we aimed to investigate genetic susceptibility of buffalo for Mycobacterium bovis infection. Samples from 868 African buffalo of the Cape buffalo subspecies were used in this study. SNPs (n = 69), with predicted functional consequences in genes related to the immune system, were genotyped in this buffalo population by competitive allele-specific SNP genotyping. Case-control association testing and statistical analyses identified three SNPs associated with BTB status in buffalo. These SNPs, SNP41, SNP137 and SNP144, are located in the SLC7A13, DMBT1 and IL1α genes, respectively. SNP137 remained significantly associated after permutation testing. The three genetic polymorphisms identified are located in promising candidate genes for further exploration into genetic susceptibility to BTB in buffalo and other bovids, such as the domestic cow. These polymorphisms/genes may also hold potential for marker-assisted breeding programmes, with the aim of breeding more BTB-resistant animals and herds within both the national parks and the private sector. [ABSTRACT FROM AUTHOR]

Background: Measurement of the level and composition of maternal mortality depends on the definition used, with inconsistencies leading to inflated rates and invalid comparisons across settings. This study investigates the differences in risk of death for women in their reproductive years during and outside the maternal risk period (pregnancy, delivery, puerperium), focusing on specific causes of infectious, non-communicable and external causes of death after separating out direct obstetrical causes. Methods: Data on all deaths of women aged 15–49 years that occurred in the Agincourt sub-district between 1992 and 2010 were obtained from the Agincourt health and socio-demographic surveillance system (HDSS) located in rural South Africa. Causes of death were assessed using a validated verbal autopsy instrument. Analysis included 2170 deaths, of which 137 occurred during the maternal risk period. Findings: Overall, women had significantly lower mortality during the maternal risk period than outside it (age-standardized RR = 0.75; 95% CI = 0.63–0.89). This was true in most age groups with the exception of adolescents aged 15–19 years where the risk of death was higher. Mortality from most causes, other than obstetric causes, was lower during the maternal risk period except for malaria, cardiovascular diseases and violence where there were no differences. Lower mortality was significant for HIV/AIDS (RR = 0.29, P<0.0001), cancers (RR = 0.10, P<0.023), and accidents (RR = 0, P<0.0001). Interpretation: In this rural setting typical of much of Southern Africa, pregnancy was largely protective against the risk of death, most likely because of a strong selection effect amongst those women who conceived successfully. The concept of indirect cause of maternal death needs to be re-examined. [ABSTRACT FROM AUTHOR]

Background: HIV prevalence differs by more than an order of magnitude between South Africa's racial groups. Comparing the sexual behaviors and other risk factors for HIV transmission between the different races may shed light on the determinants of South Africa's generalized HIV epidemic. Methods: Five nationally representative and one city-representative population-based surveys of sexual behavior were used to assess the extent to which various risk factors co-varied with HIV prevalence by race in South Africa. Results: In 2004, the prevalence of HIV was 0.5%, 1%, 3.2% and 19.9% in 15–49 year old whites, Indians, coloureds and blacks respectively. The risk factors which co-varied with HIV prevalence by race in the six surveys were age of sexual debut (in five out of five surveys for men and three out of six surveys for women), age gap (zero surveys in men and three in women), mean number of sex partners in the previous year (five surveys in men and three in women) and concurrent partnerships (five surveys in men and one in women). Condom usage and circumcision were both more prevalent in the high HIV prevalence groups. The reported prevalence of concurrency was 6 to 17 times higher in the black as opposed to the white men in the five surveys. Conclusions: The differences in sexual behavior in general, and the prevalence of concurrency and the number of sexual partners in particular, offer a plausible and parsimonious cause to explain a part of the differing prevalences of HIV between South Africa's racial groups. [ABSTRACT FROM AUTHOR]

Background: The World Health Organisation and the Joint United Nations Programme in 2006 reaffirmed the earlier recommendation of 2000 that all HIV-exposed infants in resource-poor countries should commence cotrimoxazole (CTX) prophylaxis at 6-weeks of life. CTX prophylaxis should be continued until the child is confirmed HIV-uninfected and there is no further exposure to breastmilk transmission. We determined CTX coverage and explored factors associated with CTX administration in HIV-exposed infants at a primary health clinic in South Africa. Methods: In a cross-sectional study of HIV-exposed infants 6–18 months of age attending a child immunisation clinic, data from the current visit and previous visits related to CTX prophylaxis, feeding practice and infant HIV testing were extracted from the child's immunisation record. Further information related to the administration of CTX prophylaxis was obtained from an interview with the child's mother. Results: One-third (33.0%) HIV-exposed infants had not initiated CTX at all and breastfed infants were more likely to have commenced CTX prophylaxis as compared to their non-breastfed counterparts (78.7% vs 63.4%) (p = 0.008). Availability of infant's HIV status was strongly associated with continuation or discontinuation of CTX after 6 months of age or after breastfeeding cessation. Maternal self-reports indicated that only 52.5% (95%CI 47.5–57.5) understood the reason for CTX prophylaxis, 126 (47%) did not dose during weekends; 55 (21%) dosed their infants 3 times a day and 70 (26%) dosed their infants twice daily. Conclusion: A third of HIV-exposed children attending a primary health care facility in this South African setting did not receive CTX prophylaxis. Not commencing CTX prophylaxis was strongly associated with infants not breastfeeding and unnecessary continued exposure to CTX in this paediatric population was due to limited availability of early infant diagnosis. Attendance at immunization clinics can be seen as missed opportunities for early infant diagnosis of HIV and related care. [ABSTRACT FROM AUTHOR]

Background: Routine screening for HIV infection leads to early detection and treatment. We examined patient characteristics associated with repeated screening in a high prevalence country. Methods: We analyzed data from a cohort of 5,229 adults presenting for rapid HIV testing in the outpatient departments of 2 South African hospitals from November 2006 to August 2010. Patients were eligible if they were ≥18 years, reported no previous diagnosis with HIV infection, and not pregnant. Before testing, participants completed a questionnaire including gender, age, HIV testing history, health status, and knowledge about HIV and acquaintances with HIV. Enrollment HIV test results and CD4 counts were abstracted from the medical record. We present prevalence of HIV infection and median CD4 counts by HIV testing history (first-time vs. repeat). We estimated adjusted relative risks (ARR’s) for repeat testing by demographics, health status, and knowledge of HIV and others with HIV in a generalized linear model. Results: Of 4,877 participants with HIV test results available, 26% (N = 1258) were repeat testers. Repeat testers were less likely than first-time testers to be HIV-infected (34% vs. 54%, p<0.001). Median CD4 count was higher among repeat than first-time testers (201/uL vs. 147/uL, p<0.001). Among those HIV negative at enrollment (N = 2,499), repeat testing was more common among those with family or friends living with HIV (ARR 1.50, 95% CI: 1.33–1.68), women (ARR: 1.24, 95% CI: 1.11–1.40), and those self-reporting very good health (ARR: 1.28, 95% CI: 1.12–1.45). Conclusions: In this high prevalence setting, repeat testing was common among those undergoing HIV screening, and was associated with female sex, lower prevalence of HIV infection, and higher CD4 counts at diagnosis. [ABSTRACT FROM AUTHOR]

Background: A major concern with using antiretroviral (ARV)-based products for HIV prevention is the potential spread of drug resistance, particularly from individuals who are HIV-infected but unaware of their status. Limited data exist on the prevalence of HIV infection or drug resistance among potential users of ARV-based prevention products. Methods: A cross-sectional study of reproductive-aged women who presented to screen for an HIV prevention trial was conducted at 7 clinical sites in Durban, South Africa. CD4+T cell counts, HIV-1 RNA levels and population sequencing of the protease and reverse transcriptase genes were performed for all women with 2 positive HIV rapid tests. Resistance mutations were identified using the Stanford Calibrated Population Resistance Tool. Results: Of the 1073 evaluable women, 400(37%) were confirmed as HIV-infected. Of those, plasma HIV-1 RNA was detectable in 365/400(91%) and undetectable(<40 copies/ml) in 35/400(9%) women. 156 women(39%) were eligible for antiretroviral therapy (CD4+T cell counts<350 cells/mm3) and 50(13%) met criteria for AIDS(CD4<200 cells/mm3). Of 352 plasma samples(>200 copies/ml) analyzed for drug resistance, 26(7.4%) had nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) drug resistance mutations. Among those with resistance, 18/26 participants(62%) had single-class NNRTI resistance and 5/26(19%) had dual-class NRTI/NNRTI. Major mutations in reverse transcriptase included K65R(n = 1), L74I(n = 1), K103N(n = 19), V106M(n = 4), Y181C(n = 2), M184V(n = 4), and K219E/R(n = 2). Major PI-resistance mutations were rare: M46L(n = 1) and I85V(n = 1). All participants were infected with subtype C virus, except one infected with subtype A. Conclusions: In women from Durban, South Africa screening for an HIV prevention trial, the HIV prevalence was high (37%) and HIV drug resistance prevalence was above 5%. This study highlights the potential challenges faced when implementing an ARV-based prevention product that overlaps with first-line antiretroviral therapy. Effective screening to exclude HIV infection among women interested in uptake of ARV-based HIV prevention will be essential in limiting the spread of ARV resistance. [ABSTRACT FROM AUTHOR]

Background: In South Africa the estimated incidence of all forms of tuberculosis (TB) for 2008 was 960/100000. It was reported that all South Africans lived in districts with Directly Observed Therapy, Short-course. However, the 2011 WHO report indicated South Africa as the only country in the world where the TB incidence is still rising. Aims: To report the results of a TB prevalence survey and to determine the speed of TB case detection in the study communities. Methods: In 2005 a TB prevalence survey was done to inform the sample size calculation for the ZAMSTAR (Zambia South Africa TB and AIDS Reduction) trial. It was a cluster survey with clustering by enumeration area; all households were visited within enumeration areas and informed consent obtained from eligible adults. A questionnaire was completed and a sputum sample collected from each adult. Samples were inoculated on both liquid mycobacterium growth indicator tube (MGIT) and Löwenstein-Jensen media. A follow-up HIV prevalence survey was done in 2007. Results: In Community A, the adjusted prevalence of culture positive TB was 32/1000 (95%CI 25–41/1000) and of smear positive TB 8/1000 (95%CI 5–13/1000). In Community B, the adjusted prevalence of culture positive TB was 24/1000 (95%CI 17–32/1000) and of smear positive TB 9/1000 (95%CI 6–15/1000). In Community A the patient diagnostic rate was 0.38/person-year while in community B it was 0.30/person-year. In both communities the adjusted HIV prevalence was 25% (19–30%). Discussion: In both communities a higher TB prevalence than national estimates and a low patient diagnostic rate was calculated, suggesting that cases are not detected at a sufficient rate to interrupt transmission. These findings may contribute to the rising TB incidence in South Africa. The TB epidemic should therefore be addressed rapidly and effectively, especially in the presence of the concurrently high HIV prevalence. [ABSTRACT FROM AUTHOR]

Background: Tuberculosis (TB) is a major public health problem globally. Little is known about TB incidence in adolescents who are a proposed target group for new TB vaccines. We conducted a study to determine the TB incidence rates and risk factors for TB disease in a cohort of school-going adolescents in a high TB burden area in South Africa. Methods: We recruited adolescents aged 12 to 18 years from high schools in Worcester, South Africa. Demographic and clinical information was collected, a tuberculin skin test (TST) performed and blood drawn for a QuantiFERON TB Gold assay at baseline. Screening for TB cases occurred at follow up visits and by surveillance of registers at public sector TB clinics over a period of up to 3.8 years after enrolment. Results: A total of 6,363 adolescents were enrolled (58% of the school population targeted). During follow up, 67 cases of bacteriologically confirmed TB were detected giving an overall incidence rate of 0.45 per 100 person years (95% confidence interval 0.29–0.72). Black or mixed race, maternal education of primary school or less or unknown, a positive baseline QuantiFERON assay and a positive baseline TST were significant predictors of TB disease on adjusted analysis. Conclusion: The adolescent TB incidence found in a high burden setting will help TB vaccine developers plan clinical trials in this population. Latent TB infection and low socio-economic status were predictors of TB disease. [ABSTRACT FROM AUTHOR]

Genetically related Mycobacterium tuberculosis strains with alterations at codon 516 in the rpoB gene were observed amongst a substantial number of patients with drug resistant tuberculosis in the Eastern Cape Province (ECP) of South Africa. Mutations at codon 516 are usually associated with lower level rifampicin (RIF) resistance, while susceptibility to rifabutin (RFB) remains intact. This study was conducted to assess the rationale for using RFB as a substitution for RIF in the treatment of MDR and XDR tuberculosis outbreaks. Minimum inhibitory concentrations (MICs) of 34 drug resistant clinical isolates of M tuberculosis were determined by MGIT 960 and correlated with rpoB mutations. RFB MICs ranged from 0.125 to 0.25 µg/ml in the 34 test isolates thereby confirming phenotypic susceptibility as per critical concentration (CC) of 0.5 µg/ml. The corresponding RIF MICs ranged between 5 and 15 µg/ml, which is well above the CC of 1.0 µg/ml. Molecular-based drug susceptibility testing provides important pharmacogenetic insight by demonstrating a direct correlation between defined rpoB mutation and the level of RFB susceptibility. We suggest that isolates with marginally reduced susceptibility as compared to the epidemiological cut-off for wild-type strains (0.064 µg/ml), but lower than the current CC (≤0.5 µg/ml), are categorised as intermediate. Two breakpoints (0.064 µg/ml and 0.5 µg/ml) are recommended to distinguish between susceptible, intermediate and RFB resistant strains. This concept may assist clinicians and policy makers to make objective therapeutic decisions, especially in situations where therapeutic options are limited. The use of RFB in the ECP may improve therapeutic success and consequently minimise the risk of ongoing transmission of drug resistant M. tuberculosis strains. [ABSTRACT FROM AUTHOR]

Objective: This study aims to describe the virological, immunological and clinical efficacy of protease inhibitor (PI)-based second-line antiretroviral therapy (ART) in rural South Africa. Methods: An observational cohort study was performed on 210 patients (including 39 children) who initiated PI-based second-line therapy at least 12 months prior to data collection. Biannual clinical, immunological and virological monitoring was performed. Primary endpoints were adequate virological response (plasma HIV-1 RNA<400 copies/ml), full virological suppression (plasma HIV-1 RNA<50 copies/ml) and treatment failure (virological failure (plasma HIV-1 RNA>1000 after initial virological response) or on-going viremia (plasma HIV-1 RNA never<400 copies/ml for more than six months)). Data were analyzed by an on-treatment (OT) and intention-to-treat (ITT) approach. Analyses were primarily performed on the group of patients who switched following first-line virological failure. Results: Median duration of follow-up after switch to second-line treatment was 20 months [IQR 11–35]. 191 patients had switched to second-line ART due to first-line virological failure. 139/191 of them (72.8%, ITT) were in care and on treatment at the end of follow-up and 11/191 (5.8%, ITT) had died. After twelve months, an adequate virological response was seen in 92/128 patients (71.9%, OT), of which 78/128 (60.9%, OT) experienced full virological suppression. Virological response remained stable after 24 months. Virological efficacy was similar amongst adult and pediatric patients. As in first-line ART, we observed a lack of correlation between virological failure and WHO-defined immunological failure. Conclusions: Good virological outcomes following first-line failure can be achieved with PI-based, second-line antiretroviral therapy in both adult and pediatric patients in rural South Africa. Retention rates were high and virological outcomes were sustainable during the two-year follow-up period, although persisting low-level viremia occurred in a subset of patients. The observed viro-immunological dissociation emphasizes the need for virological monitoring. [ABSTRACT FROM AUTHOR]

Objectives: To determine the proportion, characteristics and outcomes of patients who transfer-out from an antiretroviral therapy (ART) service in a South African township. Methods: This retrospective cohort study included all patients aged ≥15 years who enrolled between September 2002 and December 2009. Follow-up data were censored in December 2010. Kaplan-Meier survival analysis was used to describe time to transfer-out and cox proportional hazard analysis was used to determine associated risk factors. Results: 4511 patients (4003 ART-naïve and 508 non-naïve at baseline) received ART during the study period. Overall, 597 (13.2%) transferred out. The probability of transferring out by one year of ART steadily increased from 1.4% in 2002/2004 cohort to 8.9% for the 2009 cohort. Independent risk factors for transfer-out were more recent calendar year of enrolment, younger age (≤25 years) and being ART non-naïve at baseline (i.e., having previously transferred into this clinic from another facility). The proportions of patients transferred out who had a CD4 cell count <200 cells/µL and/or a viral load ≥1000 copies/mL were 19% and 20%, respectively. Conclusions: With scale-up of ART over time, an increasing proportion of patients are transferring between ART services and information systems are needed to track patients. Approximately one-fifth of these have viral loads >1000 copies/mL around the time of transfer, suggesting the need for careful adherence counseling and assessment of medication supplies among those planning transfer. [ABSTRACT FROM AUTHOR]

Setting: Public Health Facilities in South Africa. Objective: To assess the current integration of TB and HIV services in South Africa, 2011. Design: Cross-sectional study of 49 randomly selected health facilities in South Africa. Trained interviewers administered a standardized questionnaire to one staff member responsible for TB and HIV in each facility on aspects of TB/HIV policy, integration and recording and reporting. We calculated and compared descriptive statistics by province and facility type. Results: Of the 49 health facilities 35 (71%) provided isoniazid preventive therapy (IPT) and 35 (71%) offered antiretroviral therapy (ART). Among assessed sites in February 2011, 2,512 patients were newly diagnosed with HIV infection, of whom 1,913 (76%) were screened for TB symptoms, and 616 of 1,332 (46%) of those screened negative for TB were initiated on IPT. Of 1,072 patients newly registered with TB in February 2011, 144 (13%) were already on ART prior to Tb clinical diagnosis, and 451 (42%) were newly diagnosed with HIV infection. Of those, 84 (19%) were initiated on ART. Primary health clinics were less likely to offer ART compared to district hospitals or community health centers (p<0.001). Conclusion: As of February 2011, integration of TB and HIV services is taking place in public medical facilities in South Africa. Among these services, IPT in people living with HIV and ART in TB patients are the least available. [ABSTRACT FROM AUTHOR]

Objective: To describe an outbreak of multi-resistant Pseudomonas aeruginosa bloodstream infections (MRPA-BSI) that occurred in the haematology ward of a tertiary academic hospital in Cape Town, South Africa, and determine risk factors for acquisition of MRPA-BSI. Methods: The outbreak investigation included a search for additional cases, review of patient records, environmental and staff screening, molecular typing using pulsed-field gel electrophoresis (PFGE) and Multi-locus sequencing (MLST) and a retrospective case-control study. Results: Ten MRPA-BSI cases occurred in the haematology ward between January 2010 and January 2011. The case fatality rate was 80%. Staff screening specimens were negative for MRPA and an environmental source was not identified. PFGE showed that 9/10 isolates were related. MLST showed that 3 of these 9 isolates belonged to Sequence type (ST) 233 while the unrelated isolate belonged to ST260. Conclusion: We have described an outbreak of MRPA-BSI occurring over an extended period of time among neutropenic haematology patients. Molecular typing confirms that the outbreak was predominantly due to a single strain. The source of the outbreak was not identified, but the outbreak appears to have been controlled following intensive infection control measures. [ABSTRACT FROM AUTHOR]

Objectives: Mortality in patients starting antiretroviral therapy (ART) is higher in Malawi and Zambia than in South Africa. We examined whether different monitoring of ART (viral load [VL] in South Africa and CD4 count in Malawi and Zambia) could explain this mortality difference. Design:: Mathematical modelling study based on data from ART programmes. Methods: We used a stochastic simulation model to study the effect of VL monitoring on mortality over 5 years. In baseline scenario A all parameters were identical between strategies except for more timely and complete detection of treatment failure with VL monitoring. Additional scenarios introduced delays in switching to second-line ART (scenario B) or higher virologic failure rates (due to worse adherence) when monitoring was based on CD4 counts only (scenario C). Results are presented as relative risks (RR) with 95% prediction intervals and percent of observed mortality difference explained. Results: RRs comparing VL with CD4 cell count monitoring were 0.94 (0.74–1.03) in scenario A, 0.94 (0.77–1.02) with delayed switching (scenario B) and 0.80 (0.44–1.07) when assuming a 3-times higher rate of failure (scenario C). The observed mortality at 3 years was 10.9% in Malawi and Zambia and 8.6% in South Africa (absolute difference 2.3%). The percentage of the mortality difference explained by VL monitoring ranged from 4% (scenario A) to 32% (scenarios B and C combined, assuming a 3-times higher failure rate). Eleven percent was explained by non-HIV related mortality. Conclusions: VL monitoring reduces mortality moderately when assuming improved adherence and decreased failure rates. [ABSTRACT FROM AUTHOR]

Background: Patients with prevalent or incident tuberculosis (TB) in antiretroviral treatment (ART) programmes in sub-Saharan Africa have high mortality risk. However, published data are contradictory as to whether TB is a risk factor for mortality that is independent of CD4 cell counts and other patient characteristics. Methods/Findings: This observational ART cohort study was based in Cape Town, South Africa. Deaths from all causes were ascertained among patients receiving ART for up to 8 years. TB diagnoses and 4-monthly CD4 cell counts were recorded. Mortality rates were calculated and Poisson regression models were used to calculate incidence rate ratios (IRR) and identify risk factors for mortality. Of 1544 patients starting ART, 464 patients had prevalent TB at baseline and 424 developed incident TB during a median of 5.0 years follow-up. Most TB diagnoses (73.6%) were culture-confirmed. A total of 208 (13.5%) patients died during ART and mortality rates were 8.84 deaths/100 person-years during the first year of ART and decreased to 1.14 deaths/100 person-years after 5 years. In multivariate analyses adjusted for baseline and time-updated risk factors, both prevalent and incident TB were independent risk factors for mortality (IRR 1.7 [95% CI, 1.2–2.3] and 2.7 [95% CI, 1.9–3.8], respectively). Adjusted mortality risks were higher in the first 6 months of ART for those with prevalent TB at baseline (IRR 2.33; 95% CI, 1.5–3.5) and within the 6 months following diagnoses of incident TB (IRR 3.8; 95% CI, 2.6–5.7). Conclusions: Prevalent TB at baseline and incident TB during ART were strongly associated with increased mortality risk. This effect was time-dependent, suggesting that TB and mortality are likely to be causally related and that TB is not simply an epiphenomenon among highly immunocompromised patients. Strategies to rapidly diagnose, treat and prevent TB prior to and during ART urgently need to be implemented. [ABSTRACT FROM AUTHOR]

Background: Since 1995, measles vaccination at nine and 18 months has been routine in South Africa; however, coverage seldom reached >95%. We describe the epidemiology of laboratory-confirmed measles case-patients and assess the impact of the nationwide mass vaccination campaign during the 2009 to 2011 measles outbreak in South Africa. Methods: Serum specimens collected from patients with suspected-measles were tested for measles-specific IgM antibodies using an enzyme-linked immunosorbent assay and genotypes of a subset were determined. To estimate the impact of the nationwide mass vaccination campaign, we compared incidence in the seven months pre- (1 September 2009–11 April 2010) and seven months post-vaccination campaign (24 May 2010–31 December 2010) periods in seven provinces of South Africa. Results: A total of 18,431 laboratory-confirmed measles case-patients were reported from all nine provinces of South Africa (cumulative incidence 37 per 100,000 population). The highest cumulative incidence per 100,000 population was in children aged <1 year (603), distributed as follows: <6 months (302/100,000), 6 to 8 months (1083/100,000) and 9 to 11 months (724/100,000). Forty eight percent of case-patients were ≥5 years (cumulative incidence 54/100,000). Cumulative incidence decreased with increasing age to 2/100,000 in persons ≥40 years. A single strain of measles virus (genotype B3) circulated throughout the outbreak. Prior to the vaccination campaign, cumulative incidence in the targeted vs. non-targeted age group was 5.9-fold higher, decreasing to 1.7 fold following the campaign (P<0.001) and an estimated 1,380 laboratory-confirmed measles case-patients were prevented. Conclusion: We observed a reduction in measles incidence following the nationwide mass vaccination campaign even though it was conducted approximately one year after the outbreak started. A booster dose at school entry may be of value given the high incidence in persons >5 years. [ABSTRACT FROM AUTHOR]

Background: There is an urgent need to improve the evidence base for provision of second-line antiretroviral therapy (ART) following first-line virological failure. This is particularly the case in Sub-Saharan Africa where 70% of all people living with HIV/AIDS (PHA) reside. The aim of this study was to simulate the potential risks and benefits of treatment simplification in second-line therapy compared to the current standard of care (SOC) in a lower-middle income and an upper-middle income country in Sub-Saharan Africa. Methods: We developed a microsimulation model to compare outcomes associated with reducing treatment discontinuations between current SOC for second-line therapy in South Africa and Nigeria and an alternative regimen: ritonavir-boosted lopinavir (LPV/r) combined with raltegravir (RAL). We used published studies and collaborating sites to estimate efficacy, adverse effect and cost. Model outcomes were reported as incremental cost effectiveness ratios (ICERs) in 2011 USD per quality adjusted life year ($/QALY) gained. Results: Reducing treatment discontinuations with LPV/r+RAL resulted in an additional 0.4 discounted QALYs and increased the undiscounted life expectancy by 0.8 years per person compared to the current SOC. The average incremental cost was $6,525 per treated patient in Nigeria and $4,409 per treated patient in South Africa. The cost-effectiveness ratios were $16,302/QALY gained and $11,085/QALY gained for Nigeria and South Africa, respectively. Our results were sensitive to the probability of ART discontinuation and the unit cost for RAL. Conclusions: The combination of raltegravir and ritonavir-boosted lopinavir was projected to be cost-effective in South Africa. However, at its current price, it is unlikely to be cost-effective in Nigeria. [ABSTRACT FROM AUTHOR]

Introduction: Providing private antiretroviral therapy (ART) care for public sector patients could increase access to ART in low- and middle-income countries. We compared the costs and outcomes of a private-care and a public-care ART program in South Africa. Methods: A novel Markov model was developed from the public-care program. Patients were first tunneled for 6 months in their baseline CD4 category before being distributed into a dynamic CD4 and viral load model. Patients were allowed to return to ART care from loss to follow up (LTFU). We then populated this modeling framework with estimates derived from the private-care program to externally validate the model. Results: Baseline characteristics were similar in the two programs. Clinic visit utilization was higher and death rates were lower in the first few years on ART in the public-care program. After 10 years on ART we estimated the following outcomes in the public-care and private-care programs respectively: viral load <1000 copies/ml 89% and 84%, CD4 >500 cells/μl 33% and 37%, LTFU 14% and 14%, and death 27% and 32%. Lifetime undiscounted survival estimates were 14.1 (95%CI 13.2–14.9) and (95%CI 12.7–14.5) years with costs of 18,734 (95%CI 12,588–14,022) and 13,062 (95%CI 12,077–14,047) USD in the private-care and public-care programs respectively. When clinic visit utilization in the public-care program was reduced by two thirds after the initial 6 months on ART, which is similar to their current practice, the costs were comparable between the programs. Conclusions: Using a novel Markov model, we determined that the private-care program had similar outcomes but lower costs than the public-care program, largely due to lower visit frequencies. These findings have important implications for increasing and sustaining coverage of patients in need of ART care in resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: Forensic medicine has been largely by-passed by the tide of health systems research and evidence based medicine. Murder victims form a central part of forensic medical examiners' case load, and women murdered by intimate partners are an important subgroup, representing the most severe form and consequence of intimate partner violence. Our aim was to describe the epidemiology of female murder in South Africa (by intimate and non-intimate partners); and to describe and compare autopsy findings, forensic medical management of cases and the contribution of these to legal outcomes. Methods: We did a retrospective national study in a proportionate random sample of 25 medico-legal laboratories to identify all homicides in 1999 of women aged 14 years and over. Data were abstracted from the mortuary file and autopsy report, and collected from a police interview. Findings: In 21.5% of cases the perpetrator was convicted. Factors associated with a conviction for the female murders included having a history of intimate partner violence 1.18 (95%CI: 0.16-2.20), weapon recovered 1.36 (95% CI:0.58-2.15) and a detective visiting the crime scene 1.57 (95% CI:0.14-3.00). None of the forensic medical activities increased the likelihood of a conviction. Conclusion: The findings raise important questions about the role of forensic medicine in these cases. [ABSTRACT FROM AUTHOR]