Killer-cell Immunoglobulin-like Receptor (KIR) gene profiles modify HIV disease course, not HIV acquisition in South African women.

BACKGROUND: Killer-cell Immunoglobulin-like Receptors (KIR) interact with Human Leukocyte Antigen (HLA) to modify natural killer- and T-cell function. KIR are implicated in HIV acquisition by small studies that have not been widely replicated. A role for KIR in HIV disease progression is more widely replicated and supported by functional studies. METHODS: To assess the role of KIR and KIR ligands in HIV acquisition and disease course, we studied at-risk women in South Africa between 2004-2010. Logistic regression was used for nested case-control analysis of 154 women who acquired vs. 155 who did not acquire HIV, despite high exposure. Linear mixed-effects models were used for cohort analysis of 139 women followed prospectively for a median of 54 months (IQR 31-69) until 2014. RESULTS: Neither KIR repertoires nor HLA alleles were associated with HIV acquisition. However, KIR haplotype BB was associated with lower viral loads (-0.44 log10 copies/ml; SE = 0.18; p = 0.03) and higher CD4+ T-cell counts (+80 cells/µl; SE = 42; p = 0.04). This was largely explained by the protective effect of KIR2DL2/KIR2DS2 on the B haplotype and reciprocal detrimental effect of KIR2DL3 on the A haplotype. CONCLUSIONS: Although neither KIR nor HLA appear to have a role in HIV acquisition, our data are consistent with involvement of KIR2DL2 in HIV control. Additional studies to replicate these findings are indicated.

Screening for 'window-period' acute HIV infection among pregnant women in rural South Africa.

OBJECTIVES: The aim of this study was to evaluate the HIV-1 RNA pooled nucleic acid amplification testing (NAAT) strategy to screen pregnant women in the 'window period' of acute HIV infection (AHI) in rural South Africa. METHODS: In 2007 and 2008, 750 consecutive pregnant women on their first antenatal care visit to a primary health care clinic were tested anonymously for HIV infection. HIV-1 RNA pooled NAAT was performed on HIV antibody-negative samples. All positive pools were tested individually and positive samples were classified as incident cases to calculate HIV incidence. RESULTS: The overall HIV prevalence was 37.3% [95% confidence interval (CI) 34.3­41.3]. Of the 467 HIV antibody-negative samples, four (0.9%) were HIV-1 RNA-positive. The mean viral load in the four samples was 386 260 HIV-1 RNA copies/mL (range 64 200­1 228130). The HIV incidence was 11.2%per year (95% CI 0.3­22.1) and all women with AHI were 21 years of age. CONCLUSIONS: Identifying AHI in pregnancy is important for health interventions to reduce perinatal and heterosexual transmission of HIV, and to estimate HIV incidence for epidemiological surveillance.

TB treatment outcomes following directly-observed treatment at an urban outpatient specialist TB facility in South Africa.

The treatment of 450 consecutive new patients with pulmonary TB was evaluated to determine outcome following directly-observed treatment. In all, 176 (39.1%) patients were cured, 23 (5.1%) completed treatment, 80 (17.8%) defaulted treatment, 24 (5.3%) died, 54 (12.0%) were lost to follow-up and 93 (20.7%) were transferred out. Increasing age was significant for death. Males were more likely to default and those with negative pretreatment sputum smears and those who were unemployed were more likely to be lost to follow-up. The overall treatment success rate remains low. Our data suggests that greater emphasis is needed to improve TB treatment success.

Seroprevalence of HIV infection in rural South Africa.

OBJECTIVES: To establish the prevalence of HIV infection in rural South Africa and to investigate demographic factors that influence this prevalence. DESIGN: An anonymous HIV seroprevalence survey was performed in conjunction with a population-based malaria surveillance programme. SETTING: The rural area of northern Natal/KwaZulu, South Africa. PARTICIPANTS: A total of 5023 black African participants were recruited by malaria surveillance agents during house-to-house visits; each house in an endemic malaria area is visited approximately once every 6 weeks. Participants included 4044 healthy and 979 febrile individuals (i.e., suspected of having malaria). MAIN OUTCOME MEASURES: HIV-1 and HIV-2 serological status, degree of mobility, age and sex. RESULTS: Sixty of the 5023 blood specimens were confirmed to be HIV-1-antibody-positive by Western blot, an overall prevalence of 1.2% (95% confidence interval, 0.9-1.5). None of the specimens was positive for HIV-2 antibodies. After adjusting for age, presence of fever and migrancy, women had a 3.2-fold higher prevalence of HIV-1 infection than men. HIV-1 infection was approximately three times more common among subjects who had changed their place of residence recently (2.9 versus 1.0%, P < 0.01). CONCLUSIONS: The prevalence of HIV-1 infection is higher among women than men resident in rural Natal/KwaZulu, South Africa. This is at least in part the result of oscillatory migration, particularly of men who work in urban areas but have families and homes in rural areas. Migration is associated with a higher prevalence of HIV-1 infection, suggesting that improving social conditions so that families are not separated and become settled in their communities is one way to help reduce the spread of HIV-1.

PIP: As part of a population-based malaria surveillance program in late 1990, surveillance agents took blood samples from 979 people who had had a fever within the last 2 weeks and from 4044 healthy people during regular house-to-house visits in rural northern Natal/KwaZulu, South Africa, to determine HIV seroprevalence and risk factors of HIV infection. 60 (1.2%) people were HIV-1 seropositive. No one had HIV-2 infection. Febrile people had a 30% higher sex-adjusted relative risk (RR) of HIV-1 infection than healthy individuals, but this increase was insignificant. Women were at greater risk of HIV-1 infection than men (1.6% vs. 0.4%; age-adjusted RR = 3.8). In fact, this risk still existed when the researchers controlled for fever (RR = 3.75) and migrancy (RR = 3.2). The fall in the RR for women from 3.8 to 3.2 when controlled for migrancy suggested an underrepresentation of migrant male workers in the study sample. 2.3% of the women in their childbearing years (15-44) were HIV-1 seropositive, indicating an increased likelihood of transmission of HIV-1 to newborns. The youngest person afflicted with HIV-1 was a 12-year-old female and the oldest was a 66-year-old woman. No 10-to-19-year-old males tested HIV-1 positive, while 1.7% of the 10-to-19-year-old females did, suggesting that the young females had sex with older men. This may have indicated teenage prostitution and sexual abuse. 2.9% of the people who changed their place of residence within the last year (migrancy) had HIV-1 infection. For women it was linked to a 2.4 times higher RR (age-adjusted) of HIV-1 infection. For men, the age-adjusted RR was even greater (7.3). Even though HIV-1 seroprevalence was about 45% greater in areas crossed by the main national road than it was in other areas (1.3% vs. 0.9%), the difference was not significant. Since migrants were a key source of HIV-1 infection, improvement in social conditions, allowing families to live together and to settle in their communities, may reduce HIV-1 transmission.

Phase 1 trial of nonoxynol-9 film among sex workers in South Africa.

OBJECTIVES: To assess the acceptability and safety of a vaginal nonoxynol-9 film in a group of sex workers at a truck stop in South Africa. DESIGN: A randomized double-blinded crossover trial was conducted between April 1995 and July 1995. INTERVENTION: Seventy-two mg nonoxynol-9 film and an identical glycerine placebo film. METHODS: Following informed consent, each study participant was randomly assigned the designated pre-coded film for 1 month. The second month was a film-free washout period and the participants used the alternate film in the third month. Besides measuring behavioural and clinical outcomes, colposcopy examination for genital lesions, serology and microbiology investigations for sexually transmitted diseases and semi-quantitative PCR for vaginal HIV load estimates were performed. RESULTS: Twenty women participated in the study. The women reported, on average, 19 sexual encounters per week. Vaginal intercourse was protected 25% of the time by condoms. On average, 11 vaginal films, either nonoxynol-9 or placebos were inserted per week. There were no statistically significant differences between the two treatment groups for genital lesions (P = 0.29), reported side effects (P = 0.73), and viral load (P = 0.9). However, the proportions of clinically detected genital lesions (six out of eight versus two out of eight) and self-reported side-effects (five out of eight versus three out of eight) were higher in the nonoxynol-9 group when compared with the placebo group. Incident sexually transmitted diseases occurred more frequently in the placebo group. An increased viral load was associated with the development of a genital lesion (relative risk, 6.0; 95% confidence interval, 0.81-44.4). CONCLUSIONS: The 72 mg film formulation of nonoxynol-9 was an acceptable product for use in this population of sex workers. Although no statistically significant differences in adverse outcomes were detected, clinically there appeared to be an increase in minor lesions and self-reported side-effects with nonoxynol-9 and less protection against sexually transmitted diseases with the placebo. Furthermore, HIV shedding was correlated with the presence of incident vaginal or cervical lesions. This brings into question the potential narrow margin of safety for this product; additional Phase 2 studies are therefore required.

Household clustering and intra-household transmission patterns of hepatitis B virus infection in South Africa.

The objective of this study was to investigate household clustering of hepatitis B virus (HBV) infection in South Africa in order to understand intra-household patterns of virus transmission that would provide information on potential risk factors of HBV infection. Subjects were the household contacts of 28 hepatitis B surface antigen (HBsAg) positive children (index-carrier), 22 hepatitis B surface antibody positive children (index-past-infection) and 35 children with no serological evidence of HBV infection (index-negative). Evidence of HBV infection (at least one positive HBV marker) was present in 73.7%, 48.7% and 38.2% and HBsAg was present in 19.9%, 8.7% and 2.9% of household contacts of index-carrier (N = 186), index-past-infection (N = 150) and index-negative (N = 207) children respectively. The clustering of HBV infection and HBsAg was present in all subgroups of household contacts regardless of the degree of relatedness to the index child. As age increased, the cumulative prevalence of HBV infection increased while the likelihood of being HBsAg positive decreased. Regardless of age, males were more likely (p less than 0.01) than females to be HBsAg positive. We conclude that HBV infection clusters in households; that there is an increased susceptibility, which is probably not genetically mediated, of becoming an HBV carrier in certain households and that males are at greater risk of being HBV carriers. Intra-household horizontal person-to-person transmission, the precise mechanisms of which are not known, is important in South African blacks.

The prevalence and transmission of hepatitis B virus infection in urban, rural and institutionalized black children of Natal/KwaZulu, South Africa.

The sera of statistically selected urban (805), rural (238) and institutionalized (127) black children were tested for markers of hepatitis B virus (HBV) infection. The age-standardized (6-14 years) prevalence rates of HBs antigenaemia for comparison between urban, rural and institutionalized children were 10%, 18.5% and 25.1% and the HBV exposure rates were 31.4%, 62.1% and 72.0% respectively. In the newborn to six years age group the prevalence rates of HBsAg and HBV exposure were 2.5% and 7.1% for urban children and 53.1% and 70.3% for institutionalized children. Peak prevalences of HBsAg occurred in the 6-8 year age group and were 14.4% and 22.6% in urban and rural children respectively. Hepatitis Be Antigen (HBeAg) was detected in 46.5% and antibodies to hepatitis Be antigen (HBeAb) in 10.0% of all HBsAg positive children. Multiple mechanisms involving horizontal rather than vertical transmission appeared to be important in urban children, with HBV exposure in females being significantly associated with ear-piercing (p less than 0.001) and scarification (p less than 0.05). In addition, HBsAg was detected in 25 of 29 pools of bloodfed mosquitoes caught at the children's institution and was negative in all four pools of unfed mosquitoes, suggesting that these arthropods may also be one factor in the horizontal spread of HBV infection. Familial clustering of HBV infection was suggested by a significantly higher (p less than 0.01) prevalence of HBsAg amongst family contacts of HBsAg positive urban children (17.7%) than in the control groups of family contacts of HBsAb positive children (8%) and children who were negative for all HBV markers (2.4%). The significance and implications of these findings are discussed.

A retrospective study of human immunodeficiency virus infection and drug-resistant tuberculosis in Durban, South Africa.

SETTING: King George V hospital, a specialist referral hospital for tuberculosis (TB) patients in Durban, South Africa. OBJECTIVE: To investigate the relationship between drug-resistant TB and human immunodeficiency virus (HIV) infection. DESIGN: Retrospective descriptive study of 295 patient records, for the period January 1991 to April 1994, which were reviewed to collect data on HIV status, drug susceptibility and outcome as well as age, race, gender and previous TB treatment. RESULTS: Overall, 42 patients (14.2%) were HIV-seropositive while the rate of multidrug-resistant TB (MDR-TB) was 10.2%. Of those previously treated, 6.1% were HIV-seropositive while of those with no known history of previous TB, 5.4% were HIV-seropositive. A history of previous antituberculosis treatment was the strongest predictor for the presence of organisms resistant (Odds Ratio = 3.1; P = 0.0016) to one or more of the antituberculosis drugs. The prevalence of HIV infection was 13.1% in patients with drug-resistant TB and 14.9% in patients with drug-sensitive TB. CONCLUSION: The HIV epidemic has not exacerbated the occurrence of drug-resistant TB. History of previous TB treatment, and not HIV infection, was the principal factor associated with TB which is resistant to at least one primary anti-TB drug. However, as the HIV epidemic progresses in a milieu of high TB prevalence, the link with drug-resistant TB warrants constant monitoring and investigation.

HIV infection and asymptomatic sexually transmitted infections in a rural South African community.

The objective was to determine the prevalence of HIV and other sexually transmitted infections (STIs) in a rural community. A population-based survey of adults in 110 homesteads was conducted in 1995. A questionnaire on demographics, sexual practices and history of STDs was administered. Neisseria gonorrhoeae and Chlamydia trachomatis infections were detected using ligase chain reaction (LCR) assay of urine. The seroprevalence of syphilis rapid plasma reagin (RPR) and Treponema pallidum haemagglutination assay (TPHA) and HIV infection (ELISA) was determined. Among 259 subjects the prevalence of HIV was 10.5%, N. gonorrhoeae 4.5%, C. trachomatis 6.1% and active syphilis 8.8%. All infections were asymptomatic. Forty per cent of sexually active men had more than one concurrent sexual partner. Only 14% of subjects had ever used condoms. The STI epidemic is being promoted by high levels of asymptomatic infections, high partner concurrency and low condom use.

PIP: This study determined the prevalence of HIV and other sexually transmitted infections (STIs) in a rural South African community. A population-based survey of adults in 110 homesteads was conducted in 1995. A questionnaire on demographics, sexual practices and histories of STIs was administered. Neisseria gonorrhea and Chlamydia trachomatis infections were detected using ligase chain reaction assay of urine. The seroprevalence of syphilis rapid plasma reagin and Treponema pallidum hemagglutination assay and HIV infection (ELISA) was determined. Among 259 subjects, the prevalence of HIV was 10.5%; N. gonorrhea, 4.5%; C. trachomatis, 6.1%; active syphilis, 8.8%. All infections were asymptomatic. About 40% of sexually active men had more than one concurrent sexual partner. Only 14% of subjects had ever used condoms. In general, these findings indicate that high levels of asymptomatic infections, high partner concurrence, and low condom use are promoting the STI epidemic in this community.

Socio-medical indicators of health in South Africa.

Socio-medical indicators developed by WHO for monitoring progress towards Health-for-All have been adapted to reveal, clearly and objectively, the devastating impact of state planning based on an outmoded immoral and unscientific philosophy of race superiority in South Africa on the health of the disenfranchised majority within the context of social and economic discrimination; Health policy indicators confirm that the government is committed to three options (Bantustans, A New Constitution, and A Health Services Facilities Plan) all of which are inconsistent with the attainment of Health-for-All; Social and economic indicators reveal gross disparities between African, Coloured, Indian, and White living and working conditions; Provision of health care indicators show the overwhelming dominance of high technology curative medical care consuming about 97 percent of the health budget with only minor shifts towards community-based comprehensive care; and Health status indicators illustrate the close nexus between privilege, dispossession and disease with Whites falling prey to health problems related to affluence and lifestyle, while Africans, Coloureds, and Indians suffer from disease due to poverty. All four categories of the indicator system reveal discrepancies which exist between Black and White, rich and poor, urban and rural. To achieve the social goal of Health-for-All requires a greater measure of political commitment from the state. We conclude that it is debatable whether a system which maintains race discrimination and exploitation can in fact be adapted to provide Health-for-All.

PIP: This report evaluates the effects of race discrimination on the health status of South Africa using a socio-medical indicator system derived by WHO. The indicator system consists of 4 categories: health policy indicators, social and economic indicators related to health, indicators of provision of health care, and health status indicators. Political commitment is essential for the attainment of health for the population; the government of South Africa is committed to 3 different options influencing health, all described in detail. Budget allocation is an objective measure of commitment; 3.2% of the GNP was spent on health in 1981, and only 2.2% of the total health budget is devoted to preventive medicine. Absence of democratic structures for all to express needs and demands results in racially biased allocation and distribution of health services. Social and economic indicators relating to health include rate of population increase, gross national product, income distribution, work conditions, literacy rates, housing needs, and food availability. Indicators of basic health status include nutritional status, child mortality rates (15.6/1000 for Africans, 1.1 for whites) and life expectancy at birth (for black males 45.0 yrs and for black females 47.3, for white males 65.5 and white females 71.9). In order to achieve health for all, action is needed at the political level to eliminate apartheid, and at policy and decision making levels, to improve living and health conditions.

Improved survival in multidrug-resistant tuberculosis patients receiving integrated tuberculosis and antiretroviral treatment in the SAPiT Trial.

BACKGROUND: The therapeutic effects of antiretroviral treatment (ART) in patients with multidrug-resistant tuberculosis (MDR-TB) and human immunodeficiency virus (HIV) infection have not been established. OBJECTIVE: To assess therapeutic outcomes of integrating ART with treatment for MDR-TB. DESIGN: A subgroup of MDR-TB patients from a randomised controlled trial, the SAPiT (Starting Antiretroviral Therapy at Three Points in Tuberculosis) study, conducted in an out-patient clinic in Durban, South Africa, from 2008 to 2012. METHODS: Clinical outcomes at 18 months were compared in patients randomised to receive ART within 12 weeks of initiating standard first-line anti-tuberculosis treatment with those who commenced ART after completing anti-tuberculosis treatment. RESULTS: Mycobacterium tuberculosis drug susceptibility results were available in 489 (76%) of 642 SAPiT patients: 23 had MDR-TB, 14 in the integrated treatment arm and 9 in the sequential treatment arm. At 18 months, the mortality rate was 11.9/100 person-years (py; 95%CI 1.4-42.8) in the combined integrated treatment arm and 56.0/100 py (95%CI 18.2-130.8) in the sequential treatment arm (hazard ratio adjusted for baseline CD4 count and whether MDR-TB treatment was initiated: 0.14; 95%CI 0.02-0.94, P = 0.04). CONCLUSION: Despite the small sample size, the 86% reduction in mortality due to early initiation of ART in MDR-TB patients was statistically significant.

Phase I safety and immunogenicity evaluations of an alphavirus replicon HIV-1 subtype C gag vaccine in healthy HIV-1-uninfected adults.

On the basis of positive preclinical data, we evaluated the safety and immunogenicity of an alphavirus replicon HIV-1 subtype C gag vaccine (AVX101), expressing a nonmyristoylated form of Gag, in two double-blind, randomized, placebo-controlled clinical trials in healthy HIV-1-uninfected adults. Escalating doses of AVX101 or placebo were administered subcutaneously to participants in the United States and Southern Africa. Because of vaccine stability issues, the first trial was halted prior to completion of all dose levels and a second trial was implemented. The second trial was also stopped prematurely due to documentation issues with the contract manufacturer. Safety and immunogenicity were evaluated through assessments of reactogenicity, reports of adverse events, and assessment of replication-competent and Venezuelan equine encephalitis (VEE) viremia. Immunogenicity was measured using the following assays: enzyme-linked immunosorbent assay (ELISA), chromium 51 ((51)Cr)-release cytotoxic T lymphocyte (CTL), gamma interferon (IFN-γ) ELISpot, intracellular cytokine staining (ICS), and lymphoproliferation assay (LPA). Anti-vector antibodies were also measured. AVX101 was well tolerated and exhibited only modest local reactogenicity. There were 5 serious adverse events reported during the trials; none were considered related to the study vaccine. In contrast to the preclinical data, immune responses in humans were limited. Only low levels of binding antibodies and T-cell responses were seen at the highest doses. This trial also highlighted the difficulties in developing a novel vector for HIV.

Opportunities for treating sexually transmitted infections and reducing HIV risk in rural South Africa.

AIM: This paper is a report of a study to determine the aetiological distribution of sexually transmitted infections and prevalence of human immunodeficiency virus infection in selected primary health care clinic attendees. BACKGROUND: South Africa has a high prevalence of human immunodeficiency virus and other sexually transmitted infections. Sexually transmitted infections are managed syndromically in the public sector as part of the essential nurse-driven primary care services provided at no cost to the client. METHOD: This cross-sectional study was conducted in a rural community in South Africa between September and November 2002. A total of 277 consenting women were recruited. Vulvo-vaginal swabs were collected for screening for Neisseriae gonorrheae, Chlamydia trachomatis and Trichomonas vaginalis using DNA amplification methods and Gram stain with Nugent's score for the diagnosis of bacterial vaginosis. Seroprevalence of syphilis and human immunodeficiency virus infection were determined. FINDINGS: The overall prevalence of human immunodeficiency virus in the study was 43.7% (95% confidence interval 37.6-50.0) with the prevalence in family planning clinic attendees 45.5% (95% confidence interval 38.9-52.3) and antenatal clinic attendees 33.3% (95% confidence interval 19.6-50.3). The prevalence of sexually transmitted infections amongst both the antenatal clinic and family planning attendees accounted for at least 70% of cases. Fifty per cent of women had one recognized sexually transmitted infection with 17.9% of the family planning and 14.5% of the antenatal clinic attendees having infections from two recognized pathogens. All infections were asymptomatic. CONCLUSION: Nurse-driven antenatal and family planning services provide a useful opportunity for integrating reproductive health services, human immunodeficiency virus voluntary counselling and testing and treatment of sexually transmitted infections.

Traditional healers and AIDS prevention.

A qualitative case study of the views and experiences of an isangoma was undertaken to explore potential preventive health roles that traditional healers could play with regard to the AIDS epidemic. The isangoma's knowledge of the transmission mechanisms, risk groups and prevention strategies for AIDS was accurate. Her questionable beliefs included a Nazi conspiracy as the source of AIDS, a string ritual to prevent promiscuity and a conviction that she could treat AIDS. Notwithstanding the latter beliefs, her generally factual knowledge of AIDS indicated that she could be an important source of AIDS information in the community; she was, in fact, already providing some AIDS counselling. Considering their large clientele, established preventive health ethic, extensive distribution in rural areas and potential ability to influence the contextual factors that affect risk-reducing behaviours (e.g. condom use), it is recommended that traditional healers be incorporated into AIDS prevention programmes where they can play a role in community-based AIDS education and condom promotion.

Impact of the political violence in Natal on emergency surgical services of a tertiary hospital.

In order to investigate the impact of the political violence in Natal on a tertiary hospital's emergency surgical services, 5 days in February 1990 (based on newspaper reports of political violence) were identified and matched for the day of week and time of month to obtain comparable control days in February 1989. Data for each of the 10 days were obtained from casualty department attendance registers and a 40% random sample of emergency outpatients' charts. Comparing violence to control days, the total number of patients treated in casualty increased by 9.6% (1,915 v. 1,747), first visits to casualty by black patients increased by 34.4% (1,741 v. 1,295) and emergency patients treated in the casualty department increased by 29.6% (206 v. 159). Gunshot injuries accounted for 21.4% and 3.1% of surgical emergencies on violence and control days, respectively (relative risk 6.79; 95% confidence interval 2.76-16,73; P less than 0.001). Men comprised 76.2% and 65.4% of surgical emergencies on violence and control days, respectively (P less than 0.05). The mean age of surgical emergency patients with gunshot injuries was 26.4 years on violence days and 31.4 years on control days. Among surgical emergencies, gunshot injuries accounted for 19.2% of ward admissions on violence days compared with 5% on control days. Political violence in Natal increased the utilisation of tertiary hospital emergency surgical services, particularly for young black men with gunshot injuries requiring inpatient care. Until there is peace in this region, tertiary hospital emergency surgical services need to be strengthened and prepared to cope with the trauma resulting from the political violence.

Sero-epidemiology of hepatitis A in black South African children.

A community-based sero-epidemiological survey was undertaken to determine the age-specific prevalence rates of hepatitis A virus (HAV) infection in a representative sample of 782 urban black children aged from newborn to 13 years. Among children aged 0-5 months, the prevalence of anti-HAV was 68.8% (95% confidence interval (CI) 60.6-77.0%); this fell to a low of 2.5% (CI 0.1-4.9%) in those aged 6-11 months, implying the presence of maternal antibody in the first few months of life. By the age of 2 years, 51.2% (CI 45.7-56.7%) had anti-HAV, by age 4 the prevalence had risen to 81.4% (CI 75.5-87.3%) and by age 6, the prevalence of anti-HAV was almost 100% (CI 90.5-96.7%), reflecting the poor socio-economic and environmental conditions these children live in. The lowest prevalence of HAV infection among urban black South African children was during infancy, before the age at which the incidence rate rose sharply; e.g. 1 out of 5 children was already infected with HAV by its 2nd birthday. Vaccination in infancy will therefore have the biggest impact on the spread of HAV. However, before HAV vaccination in infancy is advocated, vaccine immunogenicity in infancy and the possible detrimental effect of maternal antibodies on the immunogenicity of the vaccine need clarification.