Studying dynamics of the HIV epidemic: population-based data compared with sentinel surveillance in Zambia.

OBJECTIVES: To establish population-based HIV survey data in selected populations, and to assess the validity of extrapolation from HIV sentinel surveillance amongst antenatal clinic attenders (ANC) to the general population. METHODS: In a population survey, adults aged > or = 15 years were selected by stratified random cluster sampling (n = 4195). The survey was carried out in catchment populations of clinics used for national HIV surveillance. The methodology allows detailed comparisons of HIV infection patterns to be made in two areas (urban and rural). Whereas the sentinel surveillance used serum-based HIV testing, the population survey used saliva (93.5% consented to provide a saliva sample). RESULTS: Surveillance of ANC tended to underestimate the overall HIV prevalence of the general population, but differences were not statistically significant. In the urban area, the adjusted overall HIV prevalence rate of ANC (aged 15-39 years) was 24.4% [95% confidence interval (CI), 20.9-28.0] compared with 26.0% (95% CI, 23.4-28.6) in the general population. The respective rural estimates were 12.5% (95% CI, 9.3-15.6) versus 16.4% (95% CI, 12.1-20.6). Age-specific prevalence rates showed ANC to overestimate infection in teenagers (aged 15-19 years), whereas in the reverse direction of those aged > or = 30 years. Teenagers analysed by single year of age revealed both ANC and women in the general population with about the same steep increase in prevalence by age, but the former at consistently higher rates. Extrapolations might be biased substantially due to the higher pregnancy rates amongst uninfected individuals. CONCLUSIONS: ANC-based data might draw a rather distorted picture of current dynamics of the HIV epidemic. Even though representing an obvious oversimplification, extrapolations of overall prevalence rates may correlate with that of the general population.

PIP: Assessments of the dynamics of the HIV/AIDS epidemic in Africa are based largely on sentinel surveillance of antenatal clinic (ANC) attenders. The validity of use of this key sentinel group in terms of HIV prevalence estimation was evaluated in a population-based survey of 4195 Zambian adults recruited through stratified random cluster sampling in urban Lusaka and rural Mposhi district in 1995-96. The survey was carried out in catchment populations of clinics used for national HIV surveillance. Overall, ANC surveillance tended to underestimate HIV prevalence in the general population, but differences were not statistically significant in either the urban or the rural area. In Lusaka, the adjusted overall HIV prevalence among ANC attenders was 24.4% compared with 26.0% in the population-based survey. The rural estimates were 12.5% and 16.4%, respectively. Comparison of age-specific prevalences indicated ANC overestimated infection in teenagers and underestimated HIV in those aged 30 years and over. Prevalence rates increased steeply by age, at comparable increment levels among women in both samples, while men had stable prevalence rates by age. These findings suggest that extrapolations from surveillance data may indeed produce a distorted picture of the current dynamics of the HIV epidemic in the population at large. Women with higher educational attainment are underrepresented in the ANC surveys. The higher pregnancy and birth rates among HIV-negative compared to HIV-positive women is another potential source of bias, as is the high rate of ANC clients aged 18-19 years (66%, compared with 34% in the general population of women). Information on single year of age, educational level, and residence should be collected in sentinel surveillance systems to allow appropriate stratification. Since HIV prevalence in young people may be the most reliable marker of changes in incidence, sample size increases in the 15-19 year age group should be considered.

Declining HIV prevalence and risk behaviours in Zambia: evidence from surveillance and population-based surveys.

OBJECTIVE: To examine trends in HIV prevalence and behaviours in Zambia during the 1990s. METHODS: The core Zambian system for epidemiological surveillance and research has two major components: (i) HIV sentinel surveillance at selected antenatal clinics (ANC) in all provinces; and (ii) population-based HIV surveys in selected sentinel populations (1996 and 1999). The former was refined in 1994 to improve the monitoring of prevalence trends, whereas the latter was designed to validate ANC-based data, to study change in prevalence and behaviour concomitantly and to assess demographic impacts. RESULTS: The ANC-based data showed a dominant trend of significant declines in HIV prevalence in the 15--19 years age-group, and for urban sites also in age-group 20--24 years and overall when rates were adjusted for over-representation of women with low education. In the general population prevalence declined significantly in urban women aged 15--29 years whereas it showed a tendency to decline among rural women aged 15-24 years. Prominent decline in prevalence was associated with higher education, stable or rising prevalence with low education. There was evidence in urban populations of increased condom use, decline in multiple sexual partners and, among younger women, delayed age at first birth. CONCLUSIONS: The results suggested a dominant declining trend in HIV prevalence that corresponds to declines in incidence since the early 1990s attributable to behavioural changes. Efforts to sustain the ongoing process of change in the well-educated segments of the population should not be undervalued, but the modest change in behaviour identified among the most deprived groups represents the major preventive challenge.

The HIV epidemic in Zambia: socio-demographic prevalence patterns and indications of trends among childbearing women.

OBJECTIVE: To examine socio-demographic HIV prevalence patterns and trends among childbearing women in Zambia. DESIGN: Repeated cross-sectional surveys. METHODS: Personal interviews and unlinked anonymous testing of blood samples of women attending antenatal care in selected areas. RESULTS: The 1994 data includes information from 27 areas and a total of 11,517 women. The HIV prevalence among urban residents appeared with moderate variation at a very high level (range 25-32%, comparing provinces). The geographical variation was more prominent in rural populations (range 8-16%) and was approximately half the prevalence level of the urban populations. With the exception of the 15-19 years age-group, HIV infection was found to rise sharply with increasing educational attainment (odds ratio, 3.1; confidence interval, 2.6-3.8) when contrasting extreme educational levels. Although the assessment of trends is somewhat restricted, the available information indicates stable prevalence levels in most populations over the last 2-4 years. CONCLUSIONS: The data showed extremely high HIV prevalence levels among childbearing women. Longer time-intervals between surveys are needed, however, in order to verify the stability in prevalence identified by this study. The tendency to changing differentials by social status is suggested as a possible sign of an ongoing process of significant behavioural change.

PIP: A series of cross-sectional surveys conducted in Zambia revealed extremely high HIV prevalence among childbearing women. The analysis was based on data derived from an HIV sentinel surveillance system established among childbearing-age women in Zambia in 1990 and expanded in 1994 to improve geographic coverage and obtain data on socio-demographic characteristics. In 1994, when complete data on HIV status was obtained on 11,517 women from 27 areas, overall HIV prevalence was 19.8%. This rate ranged from 22% to 35% in Lusaka and provincial headquarters, from 25% to 32% in urban areas, and from 8% to 16% in rural areas. In both urban and rural areas, HIV prevalence was highest in the 25-29 year age group (34% and 17%, respectively). With the exception of the 15-19 year group, seroprevalence also rose significantly with increasing educational attainment; the odds ratio was 3.13 for the most educated compared to the least educated women. The lack of HIV prevalence socioeconomic differentials among 15-19 year olds, who became sexually active at a time when information about AIDS prevention was available, may be indicative of a process of behavioral change. Only 1 area (Kalabo) showed a trend of increase in the past 2-3 years; in other areas, HIV infection rates appear to have stabilized.

Micronutrient supplementation in the AIDS diarrhoea-wasting syndrome in Zambia: a randomized controlled trial.

OBJECTIVE: As HIV has spread through sub-Saharan Africa, persistent diarrhoea has emerged as a major problem in hospitals and in the community in severely affected areas. We have previously demonstrated that antiprotozoal therapy with albendazole reduces diarrhoea in AIDS patients in urban Zambia. This trial was designed to test the hypothesis that the clinical response to albendazole might be improved by oral micronutrient supplementation. DESIGN: Randomized, placebo-controlled trial. SETTING: Home care service of Ndola Central Hospital, Zambia. PATIENTS: HIV-seropositive patients with persistent diarrhoea. INTERVENTION: Patients were randomized to albendazole plus vitamins A, C and E, selenium and zinc orally or albendazole plus placebo, for 2 weeks. MAIN OUTCOME MEASURES: Time with diarrhoea following completion of treatment; mortality; adverse events. RESULTS: Serum vitamin A and E concentrations before treatment were powerful predictors of early mortality, but supplementation did not reduce time with diarrhoea or mortality during the first month, even after taking into account initial vitamin A or E concentrations, CD4 cell count or clinical markers of illness severity. Serum concentrations of vitamins A and E did not increase significantly in supplemented patients compared with those given placebo, and there were no changes in CD4 cell count or haematological parameters. No adverse events were detected except those attributable to underlying disease. CONCLUSIONS: Although micronutrient deficiency is predictive of early death in Zambian patients with the diarrhoea-wasting syndrome, short-term oral supplementation does not overcome it nor influence morbidity or mortality.

Factors influencing the difference in HIV prevalence between antenatal clinic and general population in sub-Saharan Africa.

OBJECTIVE: To compare HIV prevalence in antenatal clinics (ANC) and the general population, and to identify factors determining the differences that were found. DESIGN: Cross-sectional surveys in the general population and in ANC in three cities. METHODS: HIV prevalence measured in adults in the community was compared with that measured by sentinel surveillance in ANC in Yaoundé, Cameroon, Kisumu, Kenya, and Ndola, Zambia. RESULTS: In Yaoundé and Ndola, the HIV prevalence in ANC attenders was lower than that in women in the population overall, and for age groups over 20 years. In Kisumu, the HIV prevalence in ANC attenders was similar to that in women in the population at all ages. The only factors identified that influenced the results were age, marital status, parity, schooling, and contraceptive use. The HIV prevalence in women in ANC was similar to that in the combined male and female population aged 15-40 years in Yaoundé and Ndola, but overestimated it in Kisumu. In Yaoundé and Ndola, the overall HIV prevalence in men was approximated by using the age of the father of the child reported by ANC attenders, but this method overestimated the HIV prevalence in Kisumu, and did not give good age-specific estimates. CONCLUSION: Few factors influenced the difference in HIV prevalence between ANC and the population, which could aid the development of adjustment procedures to estimate population HIV prevalence. However, the differences between cities were considerable, making standard adjustments difficult. The method of estimating male HIV prevalence should be tested in other sites.

'Behind walls': a study of HIV risk behaviours and seroprevalence in prisons in Zambia.

Inmate populations include a large number of individuals at risk of HIV infection. However, there is insufficient data about HIV/AIDS epidemiology in prisons. Our study, conducted in Zambia, a sub-Saharan African nation with an estimated HIV prevalence of 19% in adults, was designed to address this shortfall.

Educational level is associated with condom use within non-spousal partnerships in four cities of sub-Saharan Africa.

BACKGROUND: Rates of condom use in sub-Saharan Africa have remained too low to curb HIV/sexually transmitted disease (STD) epidemics. A better understanding of the main determinants of condom use would aid promotion. METHODS: Cross-sectional population surveys were conducted in four cities in sub-Saharan Africa: Yaoundé, Cameroon; Cotonou, Benin; Ndola, Zambia; and Kisumu, Kenya. In each city, the aim was to interview a random sample of 1000 men and 1000 women aged 15--49 years, including questions on characteristics of non-spousal partnerships in the past 12 months. RESULTS: Data on condom use were available for 4624 non-spousal partnerships. In the four cities, the proportion of partnerships in which condoms were used always or most of the time ranged from 23.8 to 33.5% when reported by men and from 10.7 to 25.9% when reported by women. Based on the reports from men, condom use was associated with higher educational level of the male partner in Yaoundé [adjusted odds ratio (aOR) = 1.76] and Ndola (aOR = 2.94) and with higher educational level of the female partner in Cotonou (aOR = 2.36) and Kisumu (aOR = 2.76). Based on the reports from women, condom use was associated with higher educational level of the female partner in Kisumu (aOR = 2.60) and Ndola (aOR = 4.50) and with higher educational level of the male partner in Yaoundé (aOR = 3.32). Associations with other determinants varied across cities and for men and women. CONCLUSIONS: Education was found to be a key determinant of condom use in all four cities. This suggests that educational level increases response to condom promotion and highlights the need for special efforts to reach men and women with low educational attainment.

Male circumcision and HIV infection in four cities in sub-Saharan Africa.

OBJECTIVES: To explore the role of male circumcision in the spread of HIV infection in four urban populations in sub-Saharan Africa. DESIGN AND METHODS: A cross-sectional population based study was conducted in four cities in sub-Saharan Africa with different levels of HIV infection. HIV prevalence among adults was relatively low in Cotonou (Benin) and in Yaoundé (Cameroon), and exceeded 25% in Kisumu (Kenya) and in Ndola (Zambia). In each city, a random sample was taken of men and women aged 15-49 years from the general population. Consenting study participants were interviewed about their sociodemographic characteristics and their sexual behaviour, and were tested for HIV, herpes simplex virus type 2, syphilis, gonorrhoea and chlamydial infection. Men underwent a genital examination. RESULTS: In Cotonou and in Yaoundé, the two low HIV prevalence cities, 99% of men were circumcised. In Kisumu 27.5% of men were circumcised, and in Ndola this proportion was 9%. In Kisumu, the prevalence of HIV infection was 9.9% among circumcised men and 26.6% among uncircumcised men. After controlling for socio-demographic characteristics, sexual behaviour and other sexually transmitted infections, the protective effect of male circumcision remained with an adjusted odds ratio of 0.26 (95% confidence interval = 0.12-0.56). In Ndola, the prevalence of HIV infection was 25.0% in circumcised men and 26.0% in uncircumcised men. The power was insufficient to adjust for any differences in sexual behaviour. CONCLUSIONS: The differences in epidemic spread of HIV are likely to be due to differences in the probability of transmission of HIV during sexual exposure as well as differences in sexual behaviour. Male circumcision is one of the factors influencing the transmission of HIV during sexual intercourse, and this study confirms the population level association between HIV and lack of male circumcision, as well as a strong individual level association in Kisumu, the only city with sufficient power to analyze this association.

Why do young women have a much higher prevalence of HIV than young men? A study in Kisumu, Kenya and Ndola, Zambia.

OBJECTIVE: To examine the factors responsible for the disparity in HIV prevalence between young men and women in two urban populations in Africa with high HIV prevalence. DESIGN: Cross-sectional survey, aiming to include 1000 men and 1000 women aged 15-49 years in Kisumu, Kenya and Ndola, Zambia. METHODS: Participants were interviewed and tested for HIV and other sexually transmitted infections. Analyses compared the marital and non-marital partnership patterns in young men and women, and estimated the likelihood of having an HIV-infected partner. RESULTS: Overall, 26% of individuals in Kisumu and 28% in Ndola were HIV-positive. In both sites, HIV prevalence in women was six times that in men among sexually active 1 5-19 year olds, three times that in men among 20-24 year olds, and equal to that in men among 25-49 year olds. Age at sexual debut was similar in men and women, and men had more partners than women. Women married younger than men and marriage was a risk factor for HIV, but the disparity in HIV prevalence was present in both married and unmarried individuals. Women often had older partners, and men rarely had partners much older than themselves. Nevertheless, the estimated prevalence of HIV in the partners of unmarried men aged under 20 was as high as that for unmarried women. HIV prevalence was very high even among women reporting one lifetime partner and few episodes of sexual intercourse. CONCLUSIONS: Behavioural factors could not fully explain the discrepancy in HIV prevalence between men and women. Despite the tendency for women to have older partners, young men were at least as likely to encounter an HIV-infected partner as young women. It is likely that the greater susceptibility of women to HIV infection is an important factor both in explaining the male-female discrepancy in HIV prevalence and in driving the epidemic. Herpes simplex virus type 2 infection, which is more prevalent in young women than in young men, is probably one of the factors that increases women's susceptibility to HIV infection.

The epidemiology of gonorrhoea, chlamydial infection and syphilis in four African cities.

OBJECTIVES: To compare the epidemiology of gonorrhoea, chlamydial infection and syphilis in four cities in sub-Saharan Africa; two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low HIV prevalence (Cotonou, Benin and Yaoundé, Cameroon). DESIGN: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa. METHODS: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) Trichomonas vaginalis infection. Risk factor analyses were carried out for chlamydial infection and syphilis seroreactivity. RESULTS: The prevalence of gonorrhoea ranged between 0% in men in Kisumu and 2.7% in women in Yaoundé. Men and women in Yaoundé had the highest prevalence of chlamydial infection (5.9 and 9.4%, respectively). In the other cities, the prevalence of chlamydial infection ranged between 1.3% in women in Cotonou and 4.5% in women in Kisumu. In Ndola, the prevalence of syphilis seroreactivity was over 10% in both men and women; it was around 6% in Yaoundé, 3-4% in Kisumu, and 1-2% in Cotonou. Chlamydial infection was associated with rate of partner change for both men and women, and with young age for women. At the population level, the prevalence of chlamydial infection correlated well with reported rates of partner change. Positive syphilis serology was associated with rate of partner change and with HSV-2 infection. The latter association could be due to biological interaction between syphilis and HSV-2 or to residual confounding by sexual behaviour. At the population level, there was no correlation between prevalence of syphilis seroreactivity and reported rates of partner change. CONCLUSION: Differences in prevalence of chlamydial infection could be explained by differences in reported sexual behaviour, but the variations in prevalence of syphilis seroreactivity remained unexplained. More research is needed to better understand the epidemiology of sexually transmitted infections in Africa.

The epidemiology of trichomoniasis in women in four African cities.

OBJECTIVES: To describe the epidemiology of Trichomonas vaginalis infection and its association with HIV infection, in women in four African cities with different levels of HIV infection. DESIGN: Cross-sectional study, using standardized methods, including a standardized questionnaire and standardized laboratory tests, in four cities in sub-Saharan Africa: two with a high prevalence of HIV infection (Kisumu, Kenya and Ndola, Zambia), and two with a relatively low prevalence of HIV (Cotonou, Benin and Yaoundé, Cameroon). METHODS: In each city, a random sample of about 2000 adults aged 15-49 years was taken. Consenting men and women were interviewed about their socio-demographic characteristics and their sexual behaviour, and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection, and (women only) T. vaginalis infection. Risk factor analyses were carried out for trichomoniasis for each city separately. Multivariate analysis, however, was only possible for Yaoundé, Kisumu and Ndola. RESULTS: The prevalence of trichomoniasis was significantly higher in the high HIV prevalence cities (29.3% in Kisumu and 34.3% in Ndola) than in Cotonou (3.2%) and Yaoundé (17.6%). Risk of trichomoniasis was increased in women who reported more lifetime sex partners. HIV infection was an independent risk factor for trichomonas infection in Yaoundé [adjusted odds ratio (OR) = 1.8, 95% confidence interval (CI) = 0.9-3.7] and Kisumu (adjusted OR = 1.7, 95% CI = 1.1-2.7), but not in Ndola. A striking finding was the high prevalence (40%) of trichomonas infection in women in Ndola who denied that they had ever had sex. CONCLUSION: Trichomoniasis may have played a role in the spread of HIV in sub-Saharan Africa and may be one of the factors explaining the differences in levels of HIV infection between different regions in Africa. The differences in prevalence of trichomoniasis between the four cities remain unexplained, but we lack data on the epidemiology of trichomoniasis in men. More research is required on the interaction between trichomoniasis and HIV infection, the epidemiology of trichomoniasis in men, and trichomonas infections in women who deny sexual activity.

HIV-1 subtypes and the HIV epidemics in four cities in sub-Saharan Africa.

OBJECTIVE: To describe the distribution of HIV-1 subtypes in two cities with high HIV prevalence (Kisumu, Kenya and Ndola, Zambia) and two with relatively low prevalence (Cotonou, Benin and Yaoundé, Cameroon), and to examine whether the differences in prevalence of HIV infection could be due to the predominance within the infected populations of subtypes with differing efficiency of heterosexual transmission. METHODS: For around 100 randomly selected HIV-positive sera from the general population and 60 from sex workers in each city, the HIV-1 subtype was determined in the envfragment. For between 19 and 52 of the sera from the general population and 20-32 sera from sex workers, the subtype was also determined in the gag fragment. RESULTS: Over 70% of infections in Cotonou, Yaoundé and Kisumu were with subtype A (by env). However, around one-half of subtype A infections in Cotonou and Yaoundé were found to be the circulating recombinant form CRF02_AG when the gag fragment was also examined. A large number of different HIV strains were found in Yaoundé, including some belonging to group O. Over 20% of infections in Kisumu and around 10% in Yaoundé were with isolated intersubtype recombinant forms. All but a few infections in Ndola were with subtype C and no recombinants were found. CONCLUSIONS: The pattern of distribution of subtypes that we found does not suggest that differences in circulating subtypes play a major role in explaining the differences in prevalence of HIV-1 infection between the four cities. The emergence and spread of recombinants requires close surveillance to adapt testing strategies if needed, to inform vaccine development and to ascertain their role in the future spread of HIV.

Ecological and individual level analysis of risk factors for HIV infection in four urban populations in sub-Saharan Africa with different levels of HIV infection.

OBJECTIVE: To identify factors that could explain differences in rate of spread of HIV between different regions in sub-Saharan Africa. DESIGN: Cross-sectional study. METHODS: The study took place in two cities with a relatively low HIV prevalence (Cotonou, Benin and Yaoundé, Cameroon), and two cities with a high HIV prevalence (Kisumu, Kenya and Ndola, Zambia). In each of these cities, a representative sample was taken of about 1000 men and 1000 women aged 15-49 years. Consenting men and women were interviewed about their socio-demographic background and sexual behaviour; and were tested for HIV, herpes simplex virus type 2 (HSV-2), syphilis, Chlamydia trachomatis and Neisseria gonorrhoea infection, and (women only) Trichomonas vaginalis. Analysis of risk factors for HIV infection was carried out for each city and each sex separately. Adjusted odds ratios (aOR) were obtained by multivariate logistic regression. RESULTS: The prevalence of HIV infection in sexually active men was 3.9% in Cotonou, 4.4% in Yaoundé, 21.1% in Kisumu, and 25.4% in Ndola. For women, the corresponding figures were 4.0, 8.4, 31.6 and 35.1%. High-risk sexual behaviour was not more common in the high HIV prevalence cities than in the low HIV prevalence cities, but HSV-2 infection and lack of circumcision were consistently more prevalent in the high HIV prevalence cities than in the low HIV prevalence cities. In multivariate analysis, the association between HIV infection and sexual behavioural factors was variable across the four cities. Syphilis was associated with HIV infection in Ndola in men [aOR = 2.7, 95% confidence interval (CI) = 1.5-4.91 and in women (aOR = 1.7, 95% CI = 1.1-2.6). HSV-2 infection was strongly associated with HIV infection in all four cities and in both sexes (aOR ranging between 4.4 and 8.0). Circumcision had a strong protective effect against the acquisition of HIV by men in Kisumu (aOR = 0.25, 95% CI = 0.12-0.52). In Ndola, no association was found between circumcision and HIV infection but sample sizes were too small to fully adjust for confounding. CONCLUSION: The strong association between HIV and HSV-2 and male circumcision, and the distribution of the risk factors, led us to conclude that differences in efficiency of HIV transmission as mediated by biological factors outweigh differences in sexual behaviour in explaining the variation in rate of spread of HIV between the four cities.

The epidemiology of HSV-2 infection and its association with HIV infection in four urban African populations.

OBJECTIVES: To estimate age- and sex-specific herpes simplex virus type-2 (HSV-2) prevalence in urban African adult populations and to identify factors associated with infection. DESIGN AND METHODS: Cross-sectional, population-based samples of about 2000 adults interviewed in each of the following cities: Cotonou, Benin; Yaoundé, Cameroon; Kisumu, Kenya and Ndola, Zambia. Consenting study participants were tested for HIV, HSV-2 and other sexually transmitted infections. RESULTS: HSV-2 prevalence was over 50% among women and over 25% among men in Yaoundé, Kisumu and Ndola, with notably high rates of infection among young women in Kisumu and Ndola (39% and 23%, respectively, among women aged 15-19 years). The prevalence in Cotonou was lower (30% in women and 12% in men). Multivariate analysis showed that HSV-2 prevalence was significantly associated with older age, ever being married, and number of lifetime sexual partners, in almost all cities and both sexes. There was also a strong, consistent association with HIV infection. Among women, the adjusted odds ratios for the association between HSV-2 and HIV infections ranged from 4.0 [95% confidence interval (CI) = 2.0-8.0] in Kisumu to 5.5 (95% CI = 1.7-18) in Yaoundé, and those among men ranged from 4.6 (95% CI = 2.7-7.7) in Ndola to 7.9 (95% CI = 4.1-15) in Kisumu. CONCLUSIONS: HSV-2 infection is highly prevalent in these populations, even at young ages, and is strongly associated with HIV at an individual level. At a population level, HSV-2 prevalence was highest in Kisumu and Ndola, the cities with the highest HIV rates, although rates were also high among women in Yaoundé, where there are high rates of partner change but relatively little HIV infection. The high prevalence of both infections among young people underlines the need for education and counselling among adolescents.

Multicentre study on factors determining differences in rate of spread of HIV in sub-Saharan Africa: methods and prevalence of HIV infection.

OBJECTIVE: The objective of this study was to explore whether the differences in rate of spread of HIV in different regions in sub-Saharan Africa could be explained by differences in sexual behaviour and/or factors influencing the probability of HIV transmission during sexual intercourse. METHODS: A cross-sectional, population-based study was conducted in two cities with a high HIV prevalence (Kisumu in Kenya and Ndola in Zambia) and two cities with a relatively low HIV prevalence (Cotonou in Benin and Yaoundé in Cameroon). In each of these cities, approximately 1000 men and 1000 women, aged 15-49 years, were randomly selected from the general population. Consenting men and women were interviewed and were tested for HIV, syphilis, herpes simplex virus type 2 (HSV-2), gonorrhoea, chlamydial infection and trichomoniasis (the latter for women only). In addition, a survey was conducted on a random sample of 300 sex workers in each city. The research instruments, including the questionnaires and the laboratory procedures, were standardized to permit comparison of results. RESULTS: The numbers of men interviewed were 1021 in Cotonou, 973 in Yaoundé, 829 in Kisumu, and 720 in Ndola. The corresponding figures for women were 1095, 1116, 1060 and 1130. In Yaoundé, Kisumu and Ndola, the response rates for men were lower than for women due to failure to make contact with eligible men. The proportion of eligible women who were interviewed was 86% in Yaoundé, and 89% in Kisumu and Ndola. In Yaoundé, 76% of eligible men were interviewed, along with 82% in Kisumu and 75% in Ndola. The prevalence of HIV infection in men was 3.3% in Cotonou, 4.1% in Yaoundé, 19.8% in Kisumu and 23.2% in Ndola. For women, the respective figures were 3.4, 7.8, 30.1 and 31.9%. The prevalence of HIV infection among women aged 15-19 years was 23.0% in Kisumu and 15.4% in Ndola. Among women in Kisumu who had their sexual debut 5 years before the interview, the prevalence of HIV infection was 46%; in Ndola, it was 59%. Among sex workers, the prevalence of HIV infection was 57.5% in Cotonou, 34.4% in Yaoundé, 74.7% in Kisumu and 68.7% in Ndola. CONCLUSIONS: The HIV prevalence rates in the general population confirmed our preliminary assessment of the level of HIV infection in the four cities, which was based on estimates of HIV prevalence from sentinel surveillance among pregnant women. The very high prevalence of HIV infection among young women in Kisumu and Ndola calls for urgent intervention.

Comparative analysis of commercial assays for the detection and quantification of Human Immunodeficiency Virus Type 1 (HIV-1) RNA in plasma from patients infected with HIV-1 subtype C.

The commercial assays commonly used to quantify plasma human immunodeficiency virus type 1 (HIV-1) RNA in clinical settings were designed to assess HIV-1 subtype B. We compared the performance of 4 commercial assays (Amplicor versions 1.0 and 1.5 [Roche]; Quantiplex [Chiron]; and NASBA HIV-1 RNA QT [Organon Teknika]) in detecting and quantifying HIV-1 RNA in plasma from HIV-infected persons from Zambia, an area where HIV-1 subtype C is predominant. Each assay detected plasma HIV-1 RNA, but they do not all measure statistically similar quantities of plasma HIV-1 RNA.

Severe linear growth retardation in rural Zambian children: the influence of biological variables.

BACKGROUND: The prevalence of stunting in preschool children in Zambia is high; stunting has detrimental effects on concurrent psychomotor development and later working capacity. OBJECTIVE: Our objective was to investigate biological variables that may contribute to linear growth retardation in preschool children in Samfya District, Zambia. DESIGN: Children aged 6-9 mo (n = 108) and 14-20 mo (n = 102) attending mother-and-child health clinics were included. With a mixed-longitudinal design, they were followed up 9 and 21 mo later. Height and weight of children and their mothers were measured. Biochemical measures (eg, serum zinc, retinol, thyrotropin, iron, and acute phase protein concentrations), malaria parasitemia, and intestinal parasitosis were assessed. RESULTS: Height-for-age z scores (HAZ) were low, indicating a high prevalence of stunting (36-79%). Ninety percent of the children were anemic, 53-71% had elevated acute phase proteins, and 80% had malaria parasitemia. Regression analyses showed that maternal height predicted the children's height at 6-9 mo (regression coefficient = 0.05; 95% CI: 0.02, 0.08). The children's height at an early age (6-9 and 14-20 mo) showed a strong relation with their height at later ages (22-30 and 34-41 mo). Serum micronutrient status did not show a significant relation with later HAZ. CONCLUSION: Unlike other studies, we did not identify specific biological factors, such as health and micronutrient status, which contribute to the retardation of linear growth. The normal zinc and iodine statuses of the children suggest that at least these factors are not causal.

TAPI polymorphisms in several human ethnic groups: characteristics, evolution, and genotyping strategies.

Genetic variations in the locus encoding the transporter associated with antigen processing, subunit 1 (TAP1), were systematically studied using samples from Caucasians, Africans, Brazilians, and compared with data from chimpanzees. PCR-amplified genomic sequences corresponding to the 11 exons were analyzed by single-strand conformation polymorphism (SSCP) and sequencing. Six nonsynonymous and 2 synonymous single nucleotide polymorphisms (SNPs) were found to be common in one ethnic group or another, and they involved codons 254 (Gly-GGC/Gly-GGT) in exon 3, 333 (Ile-ATC/Val-GTC) in exon 4, 370 (Ala-GCT/Val-GTT) in exon 5, 458 (Val-GTG/Leu-TTG) in exon 6, 518 (Val-GTC/Ile-ATC) in exon 7, 637 (Asp-GAC/Gly-GGC), 648 (Arg-CGA/Gln-CAA) and 661 (Pro-CCG/Pro-CCA) in exon 10. At each SNP site the sequence listed first was predominant in all ethnic groups. Several SNPs segregated on the same chromosome regardless of populations and species. Together, the SNPs produced 5 major human TAP1 alleles, 4 of which matched the officially recognized alleles *0101, *02011, *0301, and *0401; the 5th allele differed from each of those by at least 4 SNPs. Overall, TAP1*0101 was the predominant allele in all ethnic groups, with frequencies ranging from 0.667 in Zambians to 0.808 in US Caucasians. The TAP1*0401 frequency showed the greatest difference between Africans (0.221-0.254) and Caucasians (0.033), with Brazilians (0.058) fitting in the middle. Consistent with earlier work based on Caucasians and gorillas, *0101 appeared to be the newest human TAP1 allele, suggesting a dramatic spread of *0101 into all human populations examined. Characterization of TAP1 polymorphisms allowed the design of a PCR-based genotyping scheme that targeted 7 SNP sites and required 2 separate genotyping techniques.

Novel alleles at the lymphotoxin alpha (LTalpha) locus mark extended HLA haplotypes in native Africans.

Genetic variations at the closely related tumor necrosis factor alpha (TNFalpha or TNF) and lymphotoxin alpha (LTalpha, formerly TNFbeta) loci have been well documented in various human populations, and several haplotypes spanning the MHC class I and class II loci are known to carry specific TNF alleles. Genotyping of the TNFc microsatellite within the first intron of LTalpha in 285 Rwandans and 319 Zambians revealed two predominant alleles, c1 at frequencies of 0.598 and 0.683 and c2 at 0.384 and 0.307, respectively. Overall, the distribution of TNFc genotypes containing the major alleles conformed well to the Hardy-Weinberg equilibrium in both cohorts. Two previously unrecognized minor TNFc alleles were also detected: the first, designated c0, was found in 10 native Africans and was the only allele present in 10 chimpanzees; the second, designated c3, was seen in 6 other African patients. Further genotyping at loci for HLA class I, class II, and for transporters associated with antigen processing, subunit 1 (TAP1) in those 16 individuals suggested a tight, stable extended haplotype involving c0 and 26Asn (LTalpha)-TNF3 (TNF promoter -238A and -308G)-DRB1*1503-DQB1*0602-TAP1.2 (333Val)-TAP1.4 (637Gly). The c3 allele was observed on another extended haplotype with 26Thr (LTalpha)-TNF1 (TNF promoter -238G and -308G)-DQB1*0102-DQB1*0501-TAP1*0101 (333Ile and 637Asp). The c3-tagged haplotype further extended to Cw*15 at the HLA class I C locus, but no specific A or B alleles could be unambiguously assigned. Positive associations between c2 homozygosity and HIV-1 seronegative status in both Rwandans and Zambians (odds ratio = 2.03 and 2.00, p = 0.04 and 0.07, respectively) had little effect on the haplotype assignments. These findings suggest a preferential expansion of the human TNFc dinucleotide (CT/AG) repeat sequence and further imply the existence of two extended MHC lineages that have not been disrupted by recombinations.

Virologic and immunologic determinants of heterosexual transmission of human immunodeficiency virus type 1 in Africa.

More than 80% of the world's HIV-infected adults live in sub-Saharan Africa, where heterosexual transmission is the predominant mode of spread. The virologic and immunologic correlates of female-to-male (FTM) and male-to-female (MTF) transmission are not well understood. A total of 1022 heterosexual couples with discordant HIV-1 serology results (one partner HIV infected, the other HIV uninfected) were enrolled in a prospective study in Lusaka, Zambia and monitored at 3-month intervals. A nested case-control design was used to compare 109 transmitters and 208 nontransmitting controls with respect to plasma HIV-1 RNA (viral load, VL), virus isolation, and CD4(+) cell levels. Median plasma VL was significantly higher in transmitters than nontransmitters (123,507 vs. 51,310 copies/ml, p < 0.001). In stratified multivariate Cox regression analyses, the risk ratio (RR) for FTM transmission was 7.6 (95% CI: 2.3, 25.5) for VL > or = 100,000 copies/ml and 4.1 (95% CI: 1.2, 14.1) for VL between 10,000 and 100,000 copies/ml compared with the reference group of <10,000 copies/ml. Corresponding RRs for MTF transmission were 2.1 and 1.2, respectively, with 95% CI both bounding 1. Only 3 of 41 (7%) female transmitters had VL < 10,000 copies/ml compared with 32 of 93 (34%) of female nontransmitters (p < 0.001). The transmission rate within couples was 7.7/100 person-years and did not differ from FTM (61/862 person-years) and MTF (81/978 person-years) transmission. We conclude that the association between increasing plasma viral load was strong for female to male transmission, but was only weakly predictive of male to female transmission in Zambian heterosexual couples. FTM and MTF transmission rates were similar. These data suggest gender-specific differences in the biology of heterosexual transmission.