Alloimmunity to Class 2 Human Leucocyte Antigens May Reduce HIV-1 Acquisition - A Nested Case-Control Study in HIV-1 Serodiscordant Couples.

Enveloped viruses, including the Human Immunodeficiency Virus-1 (HIV), incorporate host proteins such as human leucocyte antigens (HLA) into their envelope. Pre-existing antibodies against HLA, termed HLA antibodies, may bind to these surface proteins and reduce viral infectivity. Related evidence includes macaque studies which suggest that xenoimmunization with HLA antigens may protect against simian immunodeficiency virus infection. Since HIV gp120 shows homology with class 2 HLA, including shared affinity for binding to CD4, class 2 HLA antibodies may influence HIV acquisition via binding to gp120 on the viral envelope. We conducted a nested case-control study on HIV serodiscordant couples, comparing the frequency of HLA antibodies among highly exposed persistently seronegative controls with those who went on to acquire HIV (HIV-seroconverters). We first performed low resolution HLA typing on 143 individuals who were HIV-infected at enrollment (index partners) and their corresponding sexual partners (115 highly exposed persistently seronegative individuals and 28 HIV-seroconverters). We then measured HLA class 1 and 2 antibodies in the highly exposed persistently seronegative individuals and HIV-seroconverters at early and late timepoints. We analyzed whether such antibodies were directed at HLA specificities of their HIV-infected index partners, and whether autoantibodies or complement-fixing class 2 HLA antibodies were present. Seventy-nine percent of highly exposed persistently seronegative individuals had HLA antibodies; 56% against class 1 and 50% against class 2 alleles. Half of the group of highly exposed persistently seronegative individuals, prior to seroconversion, expressed class 2 HLA antibodies, compared with only 29% of controls (p=0.05). HIV infection was a sensitizing event leading to de novo development of antibodies against HLA-A and HLA-B loci, but not against class 2 loci. HLA autoantibodies were present in 27% of highly exposed persistently seronegative individuals. Complement-fixing class 2 HLA antibodies did not differ significantly between highly exposed persistently seronegative individuals and seroconverters. In multivariable regression, presence of class 2 HLA antibodies at early timepoints was associated with reduced odds of HIV acquisition (odds ratio 0.330, confidence interval 0.112-0.976, p=0.045). These epidemiological data suggest that pre-existing class 2 HLA antibodies were associated with reduced odds of HIV acquisition.

Using an adaptive, codesign approach to strengthen clinic-level immunisation services in Khayelitsha, Western Cape Province, South Africa.

INTRODUCTION: Optimal immunisation programme service delivery and childhood vaccine coverage remains an ongoing challenge in South Africa. Previous health systems approaches have made recommendations on how to address identified barriers but detailed local implementation studies are lacking. This study aimed to improve immunisation service delivery in children under 24 months in Khayelitsha, Western Cape Province using an adaptive, co-design approach to assess and improve childhood immunisation service delivery at the clinic level. METHODS: A rapid, adaptive approach to identification of barriers and assessment of current childhood immunisation service delivery was developed with three clinics in Khayelitsha, Western Cape Province. This informed a short co-design process with key stakeholders and service providers to develop local interventions targeted at high priority barriers. Interventions were implemented for 4-6 months and evaluated using theory-based evaluation tools. Clinic service delivery, satisfaction and changes to clinic processes and parent engagement and knowledge were measured. RESULTS: Interventions developed included weekly community immunisation education radio sessions, daily clinic health talks, immunisation education and promotion materials and service provider and parent quality checklists. Evaluation post-intervention showed improvement in parents'/guardians' knowledge about immunisation, parent engagement and service provider commitment to improvement in service quality. Radio sessions and immunisation education and communication materials were deemed most useful by parents and providers. CONCLUSION: Immunisation service delivery can be strengthened using an adaptive, clinic-led assessment process which can effectively identify barriers, inform co-designed interventions and be evaluated over a short period. This approach provides a framework to guide future local participatory action research to more effectively improve childhood immunisation service delivery and other child health services in under-resourced settings.

The penile microbiota of Black South African men: relationship with human papillomavirus and HIV infection.

BACKGROUND: To date, the microbiota of the human penis has been studied mostly in connection with circumcision, HIV risk and female partner bacterial vaginosis (BV). These studies have shown that male circumcision reduces penile anaerobic bacteria, that greater abundance of penile anaerobic bacteria is correlated with increased cytokine levels and greater risk of HIV infection, and that the penile microbiota is an important harbour for BV-associated bacteria. While circumcision has been shown to significantly reduce the risk of acquiring human papillomavirus (HPV) infection, the relationship of the penile microbiota with HPV is still unknown. In this study, we examined the penile microbiota of HPV-infected men as well as the impact of HIV status. RESULTS: The penile skin microbiota of 238 men from Cape Town (South Africa) were profiled using Illumina sequencing of the V3-V4 hypervariable regions of the 16S rRNA gene. Corynebacterium and Prevotella were found to be the most abundant genera. Six distinct community state types (CSTs) were identified. CST-1, dominated by Corynebacterium, corresponded to less infections with high-risk HPV (HR-HPV) relative to CSTs 2-6. Men in CST-5 had greater relative abundances of Prevotella, Clostridiales, and Porphyromonas and a lower relative abundance of Corynebacterium. Moreover, they were significantly more likely to have HPV or HR-HPV infections than men in CST-1. Using a machine learning approach, we identified greater relative abundances of the anaerobic BV-associated bacteria (Prevotella, Peptinophilus, and Dialister) and lower relative abundance of Corynebacterium in HR-HPV-infected men compared to HR-HPV-uninfected men. No association was observed between HIV and CST, although the penile microbiota of HIV-infected men had greater relative abundances of Staphylococcus compared to HIV-uninfected men. CONCLUSIONS: We found significant differences in the penile microbiota composition of men with and without HPV and HIV infections. HIV and HR-HPV infections were strongly associated with greater relative abundances of Staphylococcus and BV-associated bacterial taxa (notably Prevotella, Peptinophilus and Dialister), respectively. It is possible that these taxa could increase susceptibility to HIV and HR-HPV acquisition, in addition to creating conditions in which infections persist. Further longitudinal studies are required to establish causal relationships and to determine the extent of the effect.

Factors associated with the composition and diversity of the cervical microbiota of reproductive-age Black South African women: a retrospective cross-sectional study.

BACKGROUND: Lactobacillus spp. are common bacteria in the cervical and vaginal microbiota (CVM) and are thought to represent a "healthy" cervicovaginal state. Several studies have found an independent association between ethnicity/race and cervical and vaginal microbiota (CVM) composition. Women of sub-Saharan African descent appear to be significantly more likely to have non-Lactobacillus-dominated CVM compared to women of European descent. The factors contributing to these differences remain to be fully elucidated. The CVM of Black South African women and factors influencing their CVM remain understudied. In this study, we characterized the cervical microbiota of reproductive-age South African women and assessed the associations of these microbiota with participants' metadata. METHODS: The cervical microbiota from cervical DNA of 62 reproductive-age women were profiled by Ion Torrent sequencing the V4 hypervariable region of the bacterial 16S ribosomal RNA (rRNA) gene and analyzed with the Quantitative Insights Into Microbial Ecology (QIIME), UPARSE, and metagenomeSeq tools. Associations between cervical microbiota and participants' metadata were assessed using GraphPad Prism, R packages and an in-house script. RESULTS: The cervical microbiota clustered into three distinct community state types (CSTs): Lactobacillus iners-dominated cervical microbiota (CST I (38.7%, 24/62)), unclassified Lactobacillus-dominated cervical microbiota (CST II (4.8%, 3/62)), and diverse cervical microbiota (CST III (56.5%, 35/62)) with an array of heterogeneous bacteria, predominantly the bacterial vaginosis (BV)-associated Gardnerella, Prevotella, Sneathia, and Shuttleworthia. CST III was associated with BV (p = 0.001). Women in CST I were more likely to be on hormonal contraception, especially progestin-based, compared to women in CST III (odds ratio: 5.2 (95% CI [1.6-17.2]); p = 0.005). Women on hormonal contraception had a significantly lower alpha (Shannon indices: 0.9 (0.2-1.9) versus 2.3 (0.6-2.3); p = 0.025) and beta (permutational multivariate analysis of variance (PERMANOVA) pseudo-F statistic =4.31, p = 0.019) diversity compared to non-users. There was no significant difference in the alpha (Shannon indices: 1.0 (0.3-2.2) versus 1.9 (0.3-2.2); p = 0.483) and beta (PERMANOVA pseudo-F statistic = 0.89, p = 0.373) diversity in women with versus without human papillomavirus infection. CONCLUSIONS: The majority of Black women in our study had non-Lactobacillus-dominated cervical microbiota. Additional studies are needed to examine whether such microbiota represent abnormal, intermediate or variant states of health. Lastly, the association of hormonal contraception with L. iners dominance requires further in-depth research to confirm this association, determine its biological mechanism and whether it has a beneficial effect on the cervicovaginal health.

Partner HIV Serostatus Impacts Viral Load, Genital HIV Shedding, and Immune Activation in HIV-Infected Individuals.

Studies of seronegative individuals in HIV discordant relationships provide important insights into the effects of HIV exposure on the seronegative partner, but few have examined the impact of partner serostatus on disease progression in seropositive individuals. We investigated the impact of HIV serostatus on clinical and biological factors influencing HIV disease progression in 337 HIV-infected heterosexual individuals in stable long-term HIV-seroconcordant or HIV-serodiscordant relationships. Seroconcordant individuals had significantly higher plasma viral loads (pVLs) than HIV-infected partners in serodiscordant partnerships [4.4 log10 copies RNA/mL (interquartile range 3.7-5.0) versus 3.9 (3.3-4.5), P < 0.0001], irrespective of gender. pVLs correlated inversely with CD4 T-cell counts, although CD4 counts did not differ significantly between seroconcordant and serodiscordant individuals. HIV+ seroconcordant individuals had higher frequencies of CCR5 CD4 and CD8 T cells (P = 0.03 and P = 0.02, respectively) than HIV+ individuals in serodiscordant relationships and higher concentrations of plasma IL-1ß (P = 0.04), TNF-α (P = 0.02), and IL-10 (P = 0.02). Activated CD4 T-cell frequencies and TNF-α were the most influential in determining variation in pVLs, independently of CD4 counts. In addition, HIV+ seroconcordant women had significantly higher genital VLs (gVLs) than HIV+ women in serodiscordant relationships (P < 0.001), with pVLs correlating significantly with gVLs (Rho = 0.65, P < 0.0001). Cervical and blood T-cell activation tended to correlate positively, although partner seroconcordance did not influence genital T-cell activation. We conclude that HIV+ seroconcordant individuals have higher frequencies of activated, CCR5-expressing T cells in blood and higher pVLs and gVLs than their HIV+ counterparts in discordant relationships, which could translate to faster disease progression or larger viral reservoir.

The cervical microbiota in reproductive-age South African women with and without human papillomavirus infection.

In this study we examined potential associations of HPV infection with the cervical microbiota. Cervical samples were collected from 87 HIV-seronegative reproductive-age Black South African women. Microbiota were characterized by Illumina sequencing of the V3-V4 hypervariable regions of the bacterial 16S rRNA gene. Thirty seven (42.5%) and 30 (34.5%) of the women had prevalent HPV and high-risk (HR)-HPV, respectively. Only 23 women (26.4%) had cervical microbiota dominated by a single Lactobacillus species (L. crispatus (2/87 (2.3%)), L. jensenii (2/87 (2.3%)), and L. iners (19/87 (21.8%)). The majority of the women (56/87 (64.4%)) had diverse cervical microbiota consisting of mainly bacterial vaginosis-associated bacteria. The remaining women (8/87 (9.2%)) had microbiota dominated by Aerococcus, Streptococcus, Chlamydia or Corynebacterium. Women with HR-HPV had significantly higher relative abundances of Aerococcaceae, Pseudomonadaceae and Bifidobacteriaceae compared to those with low-risk (LR)-HPV or no HPV-infection (LDA score >2.0, p < 0.05, q < 0.2). Gardnerella, Sneathia, and Atopobium were also found at greater relative abundances in HR-HPV-infected women compared to those with low-risk (LR)-HPV or no HPV-infection (LDA score >2.0, p < 0.05), although the difference was not significant after FDR-adjustment (q > 0.2). Further investigations of the bacterial taxa significantly enriched in HR-HPV-infected women are warranted.

Morbidity and mortality from road traffic crashes in children in Metro West, City of Cape Town - 2014.

The road traffic crash injury burden significantly impacts the lives of South African children. This study aimed to assess the fatal and non-fatal pattern of road traffic crash injury of children under 13 years old from Metro West, City of Cape Town, from 1 January until 31 December 2014. The data were stratified by age, sex and mechanism of road traffic crash. The overall mortality rate was 8.7 per 100 000 population and pedestrians contributed the most to this burden (72.5%). There were more male children involved in a road traffic crash (p = 0.0001). The greatest proportion of fatal and non-fatal road traffic crash injuries was observed in children aged 5-9 years. Fractures contributed to the greatest rate of years lived with disability (3.0 years of life lived with disability per 100 000). Our study found that the burden of road traffic crashes primarily affects male pedestrians aged 5-9 years old.

Maternal Decision-Making and Uptake of Health Services for the Prevention of Mother-to-Child HIV Transmission: A Secondary Analysis.

Objectives We investigated whether a woman's role in household decision-making was associated with receipt of services to prevent mother-to-child HIV transmission (PMTCT). Methods We conducted a secondary analysis of the PEARL study, an evaluation of PMTCT effectiveness in Cameroon, Cote d'Ivoire, South Africa, and Zambia. Our exposure of interest was the women's role (active vs. not active) in decision-making about her healthcare, large household purchases, children's schooling, and children's healthcare (i.e., four domains). Our primary outcomes were self-reported engagement at three steps in PMTCT: maternal antiretroviral use, infant antiretroviral prophylaxis, and infant HIV testing. Associations found to be significant in univariable logistic regression were included in separate multivariable models. Results From 2008 to 2009, 613 HIV-infected women were surveyed and provided information about their decision-making roles. Of these, 272 (44.4%) women reported antiretroviral use; 281 (45.9%) reported infant antiretroviral prophylaxis; and 194 (31.7%) reported infant HIV testing. Women who reported an active role were more likely to utilize infant HIV testing services, across all four measured domains of decision-making (adjusted odds ratios [AORs] 2.00-2.89 all p < .05). However, associations between decision-making and antiretroviral use-for both mother and infant-were generally not significant. An exception was active decision-making in a woman's own healthcare and reported maternal antiretroviral use (AOR 1.69, p < 0.05). Conclusions for Practice Associations between decision-making and PMTCT engagement were inconsistent and may be related to specific characteristics of individual health-seeking behaviors. Interventions seeking to improve PMTCT uptake should consider the type of health-seeking behavior to better optimize health services.

Relationship between socioeconomic status and HIV infection: findings from a survey in the Free State and Western Cape Provinces of South Africa.

BACKGROUND: Studies have shown a mixed association between socioeconomic status (SES) and prevalent HIV infection across and within settings in sub-Saharan Africa. In general, the relationship between years of formal education and HIV infection changed from a positive to a negative association with maturity of the HIV epidemic. Our objective was to determine the association between SES and HIV in women of reproductive age in the Free State (FSP) and Western Cape Provinces (WCP) of South Africa (SA). STUDY DESIGN: Cross-sectional. SETTING: SA. METHODS: We conducted secondary analysis on 1906 women of reproductive age from a 2007 to 2008 survey that evaluated effectiveness of Prevention of Mother-to-Child HIV Transmission Programmes. SES was measured by household wealth quintiles, years of formal education and employment status. Our analysis principally used logistic regression for survey data. RESULTS: There was a significant negative trend between prevalent HIV infection and wealth quintile in WCP (P<0.001) and FSP (P=0.025). In adjusted analysis, every additional year of formal education was associated with a 10% (adjusted OR (aOR) 0.90 (95% CI 0.85 to 0.96)) significant reduction in risk of prevalent HIV infection in WCP but no significant association was observed in FSP (aOR 0.99; 95% CI 0.89 to 1.11). There was no significant association between employment and prevalent HIV in each province: (aOR 1.54; 95% CI 0.84 to 2.84) in WCP and (aOR 0.96; 95% CI 0.71 to 1.30) in FSP. CONCLUSION: The association between HIV infection and SES differed by province and by measure of SES and underscores the disproportionately higher burden of prevalent HIV infection among poorer and lowly educated women. Our findings suggest the need for re-evaluation of whether current HIV prevention efforts meet needs of the least educated (in WCP) and the poorest women (both WCP and FSP), and point to the need to investigate additional or tailored strategies for these women.

High diversity of alpha, beta and gamma human papillomaviruses in genital samples from HIV-negative and HIV-positive heterosexual South African men.

BACKGROUND: This study investigated the prevalence of HPVs in heterosexual South African men and the impact of HIV co-infection. METHODS: HPV was detected in penile swabs from 195 HIV-infected and 140 HIV-uninfected men using PCR with FAP59/64 primers and Roche Linear Array HPV genotyping (LA). Genotyping of FAP positive specimens was achieved by high-throughput sequencing of amplicons. RESULTS: HPV was detected by FAP PCR and LA in 79% (266/335) of the men. Men with HIV co-infection and men with HIV infected sexual partners had a significantly (p<0.0001) higher HPV infection risk (adjusted odds ratio 4.0 (2.1-8.2) and 3.7 (2.1-6.7), respectively). LA genotyping and 454 sequencing of 218 FAP positive specimens detected 45 known α-HPV types, 45 ß-HPV types (34 known, 10 putative and 1 novel putative), and 91 γ-HPV types (26 known, 51 putative and 14 novel putative). Alpha, beta and gamma types were detected in 89.8%, 51.4% and 62.4% of the 218 men with HPV-62, HPV-5 and HPV-121 most common in each genus, respectively. CONCLUSION: A great diversity of known and novel alpha, beta and gamma HPV types were detected with higher prevalence in HIV co-infected men and unknown associations, if any, with genital lesions and cancers.

Influence of HIV and other risk factors on tuberculosis.

BACKGROUND: Tuberculosis (TB) notification in South Africa has increased six-fold over the past two decades, mainly because of the HIV epidemic. OBJECTIVES: To describe the sociodemographic and outcome characteristics of TB patients, and to identify risk factors associated with TB treatment outcomes stratified by HIV status. METHODS: A cross-sectional study was used to analyse data from the Cape Town Metro East geographical service area (GSA) electronic TB register (ETR.Net), including adult patients aged ≥15 years who initiated TB treatment between 1 July 2011 and 30 June 2012. RESULTS: TB case notification in the GSA was 922 per 100 000 population. Of the 12 672 TB patients registered, 50.5% were co-infected with HIV. The death rate in co-infected patients was 5.4% v. 2.8% in HIV-negative patients, the rate of treatment success 66.6% v. 73.5%, and the rate of unfavourable treatment outcome 28.1% v. 23.7%. The Khayelitsha subdistrict had the highest proportion of TB burden (37.0%) and co-infection (47.6%). Fourteen percent of patients had extrapulmonary TB, 65.9% of whom were co-infected with HIV. In the multivariate analysis, HIV infection (relative risk (RR) 1.2), retreatment (RR 1.4) and sputum smear microscopy not done (RR 1.4) were significantly associated with unfavourable treatment outcome. The Eastern (RR 0.9) and Northern (RR 0.7) subdistricts were less likely to have unfavourable outcomes compared with Khayelitsha. In the stratified analysis, retreatment and smear not done were significant risk factors for an unfavourable treatment outcome in both co-infected and HIV-negative patients. CONCLUSIONS: The burdens of both TB and co-infection were high in this community, although HIV prevalence varied. Mortality was higher and treatment completion lower in co-infected patients than in those who were HIV-negative. Co-infection, previous TB treatment and smear not done were significant risk factors for an unfavourable outcome in all patients.

CCR5 expression, haplotype and immune activation in protection from infection in HIV-exposed uninfected individuals in HIV-serodiscordant relationships.

Several host factors have been implicated in resistance to HIV infection in individuals who remain HIV-seronegative despite exposure. In a cohort of HIV-serodiscordant heterosexual couples, we investigated interactions between systemic inflammation and T-cell activation in resistance to HIV infection. Males and females in stable long-term relationships with either HIV-infected or uninfected partners were recruited, blood T-cell activation (CD38, HLA-DR, CCR5 and Ki67) and plasma cytokine concentrations were evaluated. The HIV-negative exposed individuals had significantly lower frequencies of CCR5+ CD4+ and CD8+ T cells than unexposed individuals. Mean fluorescence intensity of CCR5 expression on CD4+ T cells was significantly lower in HIV-negative exposed than unexposed individuals. Protective CCR5 haplotypes (HHA/HHF*2, HHF*2/HHF*2, HHC/HHF*2, HHA/HHA, HHA/HHC and HHA/HHD) tended to be over-represented in exposed compared with unexposed individuals (38% versus 28%, P = 0·58) whereas deleterious genotypes (HHC/HHD, HHC/HHE, HHD/HHE, HHD/HHD and HHE/HHE) were under-represented (26% versus 44%; P = 0·16). Plasma concentrations of interleukin-2 (P = 0·02), interferon-γ (P = 0·05) and granulocyte-macrophage colony-stimulating factor (P = 0·006) were lower in exposed compared with unexposed individuals. Activation marker expression and systemic cytokine concentrations were not influenced by gender. We conclude that the dominant signature of resistance to HIV infection in this cohort of exposed but uninfected individuals was lower T-cell CCR5 expression and plasma cytokine concentrations.

Child deaths in South Africa: Lessons from the child death review pilot.

South Africa (SA) has not met the child mortality target for the Millennium Development Goals, despite having invested substantially in programmes and policies to achieve these targets. The scale-up of the prevention of mother-to-child transmission programmes reduced HIV transmission from mother to child, but this has not been sustained owing to limitations in community-based child health services. Child mortality has declined, but has now plateaued. Children continue to die from preventable and treatable causes of death. Current data sources are incomplete, and do not provide information on deaths occurring out of health facilities. The child death review (CDR) pilot explores the pattern of child deaths and informs prevention strategies to improve child survival in SA. In this editorial we draw on the conclusions of the CDR pilot, where multiagency teams were established to investigate non-natural and unexpected deaths referred to two mortuary sites in order to strengthen child health and protection response systems and to prevent child deaths.

The South African child death review pilot: A multiagency approach to strengthen healthcare and protection for children.

BACKGROUND: Child mortality trends in South Africa (SA) show a decrease, but remain high and appear to have plateaued. To attain the new sustainable development goals, we need a better understanding of causes of death and the associated factors. OBJECTIVES: To describe the SA child death review (CDR) pilot, the pattern of child deaths reviewed and the factors associated with these deaths. METHODS: CDR teams were established at two pilot sites, Salt River mortuary (Western Cape Province) and Phoenix mortuary (KwaZulu-Natal Province). All child deaths were reviewed by a multidisciplinary team at the pilot sites for the period 1 January 2014 - 31 December 2014. RESULTS: The CDR pilot reviewed 711 cases. Over half (53.3%) were natural deaths, as opposed to 42.6% non-natural deaths. Most infant deaths (83.9%) were due to natural causes, while 91.7% of deaths in the 15 - 17-year-old age group were due to injuries. The leading cause of deaths reviewed (30.8%) was respiratory tract infection (RTI), mainly among infants (51.6%). Homicide was the second most common cause of death and affected children of all ages, with the highest burden (52.8%) in the 15 - 17-year age group. Child abuse and neglect accounted for 11.3% of deaths. RTI was shown to be more likely after the neonatal period (odds ratio (OR) 2.92; p<0.000) and in preterm infants (OR 1.98; p=0.005). CONCLUSIONS: CDR teams have been effective in improving identification of the causes of out-of-hospital deaths, as well as by identifying remediable factors critical to reducing child deaths further.

Female genital tract inflammation, HIV co-infection and persistent mucosal Human Papillomavirus (HPV) infections.

BACKGROUND: Persistent genital infections with high-risk HPV types increase risk of cervical disease and cancer. Since genital inflammation increases HIV acquisition risk and cancer progression, we evaluated whether HPV infection induces cytokine expression in the reproductive tract. METHODS: Genital cytokines concentrations were measured in 93 HIV-infected and 72 uninfected women. HPV typing was done by Roche Linear array. Persistence and clearance of HPV were evaluated using longitudinal data. RESULTS: Infection with HPV did not influence genital cytokine concentrations. In contrast, HIV-infected women had higher IL-1α, IL-6, IL-8, IP-10, MCP-1 and G-CSF concentrations compared to HIV-uninfected women, and HPV-infections that were more prevalent, persistent and multi-type. CONCLUSION: HPV did not influence inflammatory cytokine levels in the genital tract, although immune suppression may favor persistence.

Linking mortuary data improves vital statistics on cause of death of children under five years in the Western Cape Province of South Africa.

OBJECTIVES: Reducing child mortality requires good information on its causes. Whilst South African vital registration data have improved, the quality of cause-of-death data remains inadequate. To improve this, data from death certificates were linked with information from forensic mortuaries in Western Cape Province. METHODS: A local mortality surveillance system was established in 2007 by the Western Cape Health Department to improve data quality. Cause-of-death data were captured from copies of death notification forms collected at Department of Home Affairs Offices. Using unique identifiers, additional forensic mortuary data were linked with mortality surveillance system records. Causes of death were coded to the ICD-10 classification. Causes of death in children under five were compared with those from vital registration data for 2011. RESULTS: Cause-of-death data were markedly improved with additional data from forensic mortuaries. The proportion of ill-defined causes was halved (25-12%), and leading cause rankings changed. Lower respiratory tract infections moved above prematurity to rank first, accounting for 20.8% of deaths and peaking in infants aged 1-3 months. Only 11% of deaths from lower respiratory tract infections occurred in hospital, resulting in 86% being certified in forensic mortuaries. Road traffic deaths increased from 1.1-3.1% (27-75) and homicides from 3 to 28. CONCLUSIONS: The quality and usefulness of cause-of-death information for children in the WC was enhanced by linking mortuary and vital registration data. Given the death profile, interventions are required to prevent and manage LRTI, diarrhoea and injuries and to reduce neonatal deaths.

Human papillomavirus prevalence in South African women and men according to age and human immunodeficiency virus status.

BACKGROUND: Both cervical cancer and human immunodeficiency virus (HIV) are major public health problems in Sub-Saharan Africa. The objectives of the study were to investigate human papillomavirus (HPV) prevalence according to age, HIV status and gender. METHODS: Participants were 208 HIV-negative women, 278 HIV-positive women, 325 HIV-negative men and 161 HIV-positive men between the ages of 18-66 years. HPV types were determined in cervical and penile cells by Roche Linear Array HPV genotyping assay. RESULTS: HPV prevalence was 36.7 % (76/207; 95 % confidence intervals (CI): 30.4-43.4 %) in HIV-negative women, with the highest prevalence of 61.0 % (25/41; 95 % CI: 45.7-74.4 %) in women aged 18-25 years. HPV prevalence was 74.0 % (205/277; 95 % CI: 68.5-78.8 %) in HIV-positive women, with the highest prevalence of 86.4 % (38/44; 95 % CI: 72.9-94.0 %) in women aged 18-25 years. HPV prevalence was found to decrease with increasing age in HIV-negative women (P = 0.0007), but not in HIV-positive women (P = 0.898). HPV prevalence was 50.8 % (159/313; 95 % CI: 45.3-56.3 %) in HIV-negative men, with the highest prevalence of 77.0 % (27/35; 95 % CI: 60.7-88.2 %) in men aged 18-25 years. HPV prevalence was 76.6 % (121/158; 95 % CI: 69.2-82.9 %) in HIV-positive men, with the highest prevalence of 87.5 % (7/8; 95 % CI: 50.8-99.9 %) in men 18-25 years of age. HPV prevalence was found to decrease with increasing age in HIV-negative men (P = 0.004), but not in HIV-positive men (P = 0.385). HIV-positive women had a significantly higher prevalence of one or more HPV type(s) in the bivalent (HPV-16/18: 20 % 55/277, 9 % 12/207; P <0.001), quadrivalent (HPV-6/11/16/18: 26 % 71/277, 12 % 24/207; P = 0.001) and nonavalent vaccine (HPV-6/11/16/18/31/33/52/56/58: 65 % 181/277, 24 % 50/207; P <0.001) compared to HIV-negative women. Similar observation were observed in men for bivalent (20 % 32/158, 10 % 30/313; P = 0.001), quadrivalent (35 % 56/158, 13 % 41/313; P <0.001) and nonavalent vaccine (75 % 119/158, 28 % 87/313; P <0.001). CONCLUSIONS: This study demonstrated high HPV prevalence among HIV-positive women and men in all age groups. The high prevalence of HPV types found in bivalent, quadrivalent and nonavalent vaccines in South African HIV-positive and HIV-negative women and men demonstrate that this population will greatly benefit from current HPV vaccines.

Superior virologic and treatment outcomes when viral load is measured at 3 months compared to 6 months on antiretroviral therapy.

INTRODUCTION: Routine viral load (VL) monitoring is utilized to assess antiretroviral therapy (ART) adherence and virologic failure, and it is currently scaled-up in many resource-constrained settings. The first routine VL is recommended as late as six months after ART initiation for early detection of sub-optimal adherence. We aimed to assess the optimal timing of first VL measurement after initiation of ART. METHODS: This was a retrospective, cohort analysis of routine monitoring data of adults enrolled at three primary care clinics in Khayelitsha, Cape Town, between January 2002 and March 2009. Primary outcomes were virologic failure and switch to second-line ART comparing patients in whom first VL done was at three months (VL3M) and six months (VL6M) after ART initiation. Adjusted hazard ratios (aHR) were estimated using Cox proportional hazard models. RESULTS: In total, 6264 patients were included for the time to virologic failure and 6269 for the time to switch to second-line ART analysis. Patients in the VL3M group had a 22% risk reduction of virologic failure (aHR 0.78, 95% CI 0.64-0.95; p=0.016) and a 27% risk reduction of switch to second-line ART (aHR 0.73, 95% CI 0.58-0.92; p=0.008) when compared to patients in the VL6M group. For each additional month of delay of the first VL measurement (up to nine months), the risk of virologic failure increased by 9% (aHR 1.09, 95% CI 1.02-1.15; p=0.008) and switch to second-line ART by 13% (aHR 1.13, 95% CI 1.05-1.21; p<0.001). CONCLUSIONS: A first VL at three months rather than six months with targeted adherence interventions for patients with high VL may improve long-term virologic suppression and reduce switches to costly second-line ART. ART programmes should consider the first VL measurement at three months after ART initiation.

Implementation and Operational Research: Reconstructing the PMTCT Cascade Using Cross-sectional Household Survey Data: The PEARL Study.

BACKGROUND: Given the ambitious targets to reduce pediatric AIDS worldwide, ongoing assessment of programs to prevent mother-to-child HIV transmission (PMTCT) is critical. The concept of a "PMTCT cascade" has been used widely to identify bottlenecks in program implementation; however, most efforts to reconstruct the cascade have relied on facility-based approaches that may limit external validity. METHODS: We analyzed data from the PEARL household survey, which measured PMTCT effectiveness in 26 communities across Zambia, South Africa, Cote d'Ivoire, and Cameroon. We recruited women who reported a delivery in the past 2 years. Among mothers confirmed to be HIV infected at the time of survey, we reconstructed the PMTCT cascade with self-reported participant information. We also analyzed data about the child's vital status; for those still alive, HIV testing was performed by DNA polymerase chain reaction testing. RESULTS: Of the 976 eligible women, only 355 (36%) completed every step of the PMTCT cascade. Among the 621 mother-child pairs who did not, 22 (4%) reported never seeking antenatal care, 103 (17%) were not tested for HIV during pregnancy, 395 (64%) reported testing but never received their HIV-positive result, 48 (8%) did not receive maternal antiretroviral prophylaxis, and 53 (9%) did not receive infant antiretroviral prophylaxis. The lowest prevalence of infant HIV infection or death was observed in those completing the cascade (10%, 95% confidence interval: 7% to 12%). CONCLUSIONS: Future efforts to measure population PMTCT impact should incorporate dimensions explored in the PEARL study-including HIV testing of HIV-exposed children in household surveys-to better understand program effectiveness.