Increased vaginal pH in Ugandan women: what does it indicate?

Abnormal vaginal flora (AVF), indicative of bacterial vaginosis (BV) and/or aerobic vaginitis (AV), amongst other abnormalities, is a risk factor for multiple complications in pregnant as well as non-pregnant women. Screening for such conditions could help prevent these complications. Can self-testing for increased vaginal pH reliably detect BV and other high-risk microflora types, and is this more accurate than performing Gram stain-based Nugent score when screening for high-risk microflora? A total of 344 women presenting at different outpatient clinics in Mulago Hospital and Mbuikwe Outpatient clinics in Kampala, Uganda, were asked to test themselves by introducing a gloved finger into the vagina and smearing it on a microscopy slide, on which a pH strip was attached. Self-assessed categories of normal (pH 3.6-4.4), intermediate (4.5-4.7) or high pH (>4.7) were compared with demographic and with centralised microscopic data, both in air-dried rehydrated wet mounts (Femicare), as well as in Gram-stained specimens (Nugent). AVF was present in 38 %, BV in 25 % and AV in 11 % of patients. High pH and AVF is correlated with human immunodeficiency virus (HIV), infertility, frequent sex, but not vaginal douching. Screening for raised pH detects 90 % of AVF cases, but would require testing over half of the population. As AV and non-infectious conditions are frequent in women with AVF and high pH, Nugent score alone is an insufficient technique to screen women for a high-risk vaginal microflora, especially in infertile and HIV-infected women.

Acceptance of self-testing for increased vaginal pH in different subsets of Ugandan women.

We assessed the acceptance of self-testing for vaginal pH in 344 Ugandan women in different clinical settings. Women tested themselves by insertion of a gloved finger into the vagina to test vaginal pH and provide a smear on a glass slide. None of the tested women found the test very difficult: 8% found it somewhat difficult, 16% rather easy and 76% very easy to do. Of the 20% who found it difficult to read the test result, more women were attending a family planning clinic or had a higher diploma (P = 0.001). Pregnant women were least likely to understand of the meaning of the test, while those visiting family planning clinics had the opposite experience. HIV-infected women were most motivated to accept: 95% would be happy to use the test more often if requested, and another 3.5% felt they might be better motivated to do repeat testing after extra explanation. Self-sampling of vaginal pH is well accepted by Ugandan women. Our new method also allows diagnostic work-up by formal microscopy. Before commencing large-scale population screening, unexpected reactions of different subpopulations should be taken into account.

Aetiology of diarrhoea among persons with HIV and their family members in rural Uganda: a community-based study.

OBJECTIVES: To identify pathogens associated with diarrhoea in HIV-infected persons and their HIV-uninfected family members. DESIGN: Prospective cohort study. SETTING: Rural community in eastern Uganda. SUBJECTS: Eight hundred and seventy nine HIV-infected adults (74% females and median age 35 years (IQR, 29-41) and 2771 HIV-uninfected family members (51% females and median age 11 years (IQR 6-16) were included. MAIN OUTCOME MEASURES: Using microscopy and culture, stools were tested for parasites, bacteria and bacterial-antimicrobial-susceptibility. Logistic regression models, adjusting for age, CD4 cells, season, household clustering and use of safe-water system were used for relationships between pathogens, diarrhoea and HIV. RESULTS: Persons with HIV had similar pathogens in diarrhoeal (69%) and nondiarrhoeal stools (57%). Most diarrhoea was not associated with identifiable aetiology; the population attributable risk of diarrhoea for known diarrhoea pathogens was 32%. Enteric bacteria (19%), enteropathogenic or enterotoxigenic E. coli (8%), Aeromonas species (7%), Strongyloides stercoralis (8%) and Cryptosporidium parvum (5%). HIV-infected, stools had more Cryptosporidium parvum than HIV-uninfected (OR 2.64, 95% CI 1.43-4.87). Most bacteria were resistant to commonly used antimicrobials irrespective of HIV status. CONCLUSIONS: Irrespective of HIV-status, aetiologies of majority of their diarrhoea in Uganda cannot be identified by microscopy and culture. Bacterial pathogens isolated have high resistance to common antimicrobials. Empiric treatment should be tailored to local bacterial-resistance patterns.

Maternal morbidity following emergency caesarean section in asymptomatic HIV-1 infected patients in Mulago Hospital Kampala, Uganda.

Sepsis following caesarean section remains an important cause of morbidity in Uganda's Mulago Hospital. This study was designed to assess whether asymptomatic HIV infection could be contributing to this form of morbidity. A total of 500 patients who had undergone emergency CS had their blood tested for HIV-1 on the 1st postoperative day. They were followed-up for wound sepsis, genital tract infection and duration of stay in the hospital after the operation. There were 98 (20.5%) HIV-1 seropositives. The incidence of postoperative wound sepsis (p = 0.948, 95% CI 0.56-1.86), genital tract infection (p = 0.339, 95% CI = 0.74-2.39) and hospital stay > 8 days (p = 0.327, 0.78-2.09) were not statistically significantly different between the cases and controls. Significant predisposing factors to postoperative morbidity were poor general condition on admission, dehydration, preoperative clinical anaemia, and ruptured membranes prior to the operation. Postoperative morbidity following emergency caesarean section was not statistically associated with retrospective asymptomatic HIV-1 infection.

Understanding the barriers to clubfoot treatment adherence in Uganda: a rapid ethnographic study.

PURPOSE: The Ponseti method has been demonstrated to be an effective, low-technology method of correcting congenital clubfoot. The purpose of this paper is to identify barriers to adherence to the Ponseti method of clubfoot treatment in Uganda. Understanding of barriers underlies successful and culturally appropriate approaches to program implementation. METHOD: A qualitative study (rapid ethnographic study), using semi-structured interviews, focus groups and observation, was conducted. Interviews were conducted with parents of children with clubfoot (42), adults with clubfoot (2), community leaders (40), traditional healers (39) and practitioners treating clubfoot (38). Some 48 focus groups (24 male, 24 female) were conducted with general community members to ascertain their opinions on the potential barriers. The data was collected by a team of researchers in 8 districts of Uganda over the period of one month. It was then coded manually by the researchers and sorted into themes. RESULTS: The barriers to adherence were classified into 6 themes: (i) problems with programmatic resource availability and regional differences, (ii) distance to treatment site, (iii) poverty, (iv) lack of paternal support, (v) caregiver's other responsibilities, and (vi) challenges of the treatment process. A number of factors that were helpful for encouraging adherence were also identified: (i) outreach and follow-up services, (ii) counselling/caregiver-practitioner partnership, (iii) family harmony and solidarity, and (iv) receiving quality care. CONCLUSIONS: Our study highlights the barriers to adherence in the treatment of clubfoot, as well as factors that could be helpful for overcoming these barriers. This information provides health planners with knowledge to assist them in meeting the needs of the population and implementing effective and appropriate awareness and treatment programs for clubfoot in Uganda.

Early undergraduate research experience at Makerere University Faculty of Medicine: a tool for promoting medical research.

BACKGROUND: Research is one of the key distinguishing features of an academic institution. The way an institution grooms its future researchers determines its long term survival. The ability to do and communicate ones research findings is so important that it is now an internationally recognized minimum competency for graduate of any medical school. To remain relevant the Faculty of Medicine Makerere University needs to identify research enhancing opportunities like undergraduate research experiences. METHODS: This was a cross sectional study involving 424 graduate and undergraduate students of Makerere University Medical School on the traditional curriculum. A self administered questionnaire was used to capture reported details of individual research experiences. RESULTS: There were 424 student respondents, 88% of whom were undergraduates (372/424). About 41% (176/424) of these respondents reported having had a previous research experience. Among the postgraduates 74% (37/50) reported having had a previous research experience compared with 68% (139/342) of the undergraduates [OR=4.16, 2.07-8.57]. The sum of individual undergraduate experiences had the strongest positive correlation with the total number of studies done by an individual [R=0.801]. CONCLUSION: Early, guided undergraduate research experience can be used to promote research within the Faculty of Medicine Makerere University. Running Head: Research Undergraduates Makerere.

Nutritional status and food consumption patterns of young children living in Western Uganda.

OBJECTIVES: The aim of this pilot study was to compare the nutritional status and food consumption patterns of children under five years. DESIGN: Quantitative, exploratory, cross sectional study. SETTING: Kabarole district, western Uganda. Kabarole district is a rural district with subsistence farming as the main income. SUBJECTS: Two hundred and five children between 12 and 72 months of age living in AIDS affected homes versus children living in non-AIDS affected homes were examined. RESULTS: Fifty-five percent of all children were stunted and 20.5% were underweight. There was no difference in the prevalence of malnutrition between children living in AIDS affected homes versus non-AIDS affected homes. Only children between 12-35 months suffered from a daily deficit in caloric intake. The older children consumed the basic recommended daily intake (RDI) for protein, fat, iron and vitamin A. Due to frequent disease episodes and limitations in the estimations of individual total energy expenditure, the results are likely underestimations of the children's true nutritional requirements. The type of foods given to children in AIDS affected homes and controls were quite similar. CONCLUSION: Young children in Kabarole district suffer from severe chronic malnutrition rates, but rates and feeding patterns are not different in AIDS affected versus non AIDS affected homes.

Social marketing of pre-packaged treatment for men with urethral discharge (Clear Seven) in Uganda.

We implemented social marketing of pre-packaged treatment for men with urethral discharge (Clear Seven) in Uganda, and studied its feasibility, acceptability and effectiveness as a possible means to treat STDs and thereby prevent HIV. Clear Seven was distributed at private health care outlets in three rural districts and two divisions of the capital. Comparisons were made with a pre-intervention period in the same sites plus one additional rural district. There were almost universally positive attitudes to Clear Seven. Cure rate (84% versus 47%), treatment compliance (93% versus 87%), and condom use during treatment (36% versus 18%) were significantly higher among Clear Seven users (n=422) than controls (n=405). Partner referral was similar but fewer Clear Seven partners were symptomatic when seeking treatment. Distribution of socially marketed pre-packaged treatment for male urethritis should be expanded in sub-Saharan Africa. Consideration should be given to developing similar kits for women.

Age, temperature, and parasitaemia predict chloroquine treatment failure and anaemia in children with uncomplicated Plasmodium falciparum malaria.

The prevalence of chloroquine-resistant Plasmodium falciparum malaria has been increasing in sub-Saharan Africa and parts of South America over the last 2 decades, and has been associated with increased anaemia-associated morbidity and higher mortality rates. Prospectively collected clinical and parasitological data from a multicentre study of 788 children aged 6-59 months with uncomplicated P. falciparum malaria were analysed in order to identify risk factors for chloroquine treatment failure and to assess its impact on anaemia after therapy. The proportion of chloroquine treatment failures (combined early and late treatment failures) was higher in the central-eastern African countries (Tanzania, 53%; Uganda, 80%; Zambia, 57%) and Ecuador (54%) than in Ghana (36%). Using logistic regression, predictors of early treatment failure included younger age, higher baseline temperature, and greater levels of parasitaemia. We conclude that younger age, higher initial temperature, and higher baseline parasitaemia predict early treatment failure and a higher probability of worsening anaemia between admission and days 7 or 14 post-treatment.

HIV counselling and testing in rural Uganda: communities' attitudes and perceptions towards an HIV counselling and testing programme.

Study results on the assessment of a community-wide HIV counselling and testing programme are presented. The aim of this qualitative study was to elucidate whether HIV counselling and testing (HIV CT) was acceptable to a rural community and whether they expressed a need for it. From a total of 2,267 persons of Kigoyera Parish, western Uganda, who were HIV tested and counselled, 171 persons participated in 17 focus group discussions. Most participants expressed a strong need for HIV counselling and testing services. The counsellors were seen as competent and confidential. Community health workers were favoured as the preferred provider of HIV CT services. However, participants stressed that they should not come from the same community. Most participants felt that a HIV CT programme available only once is not enough and did not induce a change in sexual behaviour, e.g. increased condom use. They requested counselling services that are continuously offered. The study results also showed that there is a demand for HIV counselling services without being HIV tested.

IE1-pp65 recombinant protein from human CMV combined with a nanoparticulate carrier, SMBV, as a potential source for the development of anti-human CMV adoptive immunotherapy.

BACKGROUND: Human cytomegalovirus (HCMV) infection and reactivation following allogeneic bone marrow transplantation is a major source of complications in grafted patients including pneumonitis, graft rejection and even death. Adoptive immunotherapy consisting in transfer of CD4(+) and CD8(+) T cells directed against HCMV has proved its worth. Nevertheless, established procedures have to be improved in terms of safety and waiting period required to obtain specific T cells. METHODS: As an alternative to infectious virus used in current strategies, we purified a recombinant protein IE1-pp65 resulting from the fusion of the regulatory IE1 and matrix pp65 proteins, both known as the major targets of the overall anti-HCMV T cell response. Based on our previous data demonstrating its use for in vitro stimulation and expansion of anti-HCMV CD4(+) and CD8(+) T cells (Vaz-Santiago et al, 2001, J.Virol, 75:7840-47) from peripheral blood mononuclear cells (PBMC) of seropositive donors, we planned to improve its in vitro immunogenicity through association with a nanoparticulate carrier, SMBV. RESULTS: We demonstrated that using of SMBV/IE1-pp65 formulation allowed to potentiate in vitro activation of T cells and to expand more CD8(+) T cells than with soluble IE1-pp65, following stimulation of PBMC. DISCUSSION: These data suggest the use of SMBV/IE1-pp65 formulation as a potential source of antigen for efficient T cells expansion in the development of safe anti-HCMV immunotherapy.

Purification of Ag-specific T lymphocytes after direct peripheral blood mononuclear cell stimulation followed by CD25 selection. I. Application to CD4(+) or CD8(+) cytomegalovirus phosphoprotein pp65 epitope determination.

The two main constraints that currently limit a broader usage of T cell therapy against viruses are the delay required to obtain specific T cells and the safety of the selection procedure. In the present work we developed a generally applicable strategy that eliminates the need for APC for timing reasons, and the need for infectious viral strains for safety concerns. As a model, we used the selection of T lymphocytes specific for the immunodominant CMV phosphoprotein pp65. PBMC from healthy seropositive donors were first depleted of IL-2R alpha-chain CD25(+) cells and were then stimulated for 24-96 h with previously defined peptide Ags or with autologous PBMC infected with a canarypox viral vector encoding the total pp65 protein (ALVAC-pp65). Subsequent immunomagnetic purification of newly CD25-expressing cells allowed efficient recovery of T lymphocytes specific for the initial stimuli, i.e., for the already known immunodominant epitope corresponding to the peptides used as a model or for newly defined epitopes corresponding to peptides encoded by the transfected pp65 protein. Importantly, we demonstrated that direct PBMC stimulation allowed recovery not only of CD8(+) memory T lymphocytes, but also of the CD4(+) memory T cells, which are known to be crucial to ensure persistence of adoptively transferred immune memory. Finally, our analysis of pp65-specific T cells led to the identification of several new helper and cytotoxic epitopes. This work thus demonstrates the feasibility of isolating memory T lymphocytes specific for a clinically relevant protein without the need to prepare APC, to use infectious viral strains, or to identify immunodominant epitopes.

Ex vivo stimulation and expansion of both CD4(+) and CD8(+) T cells from peripheral blood mononuclear cells of human cytomegalovirus-seropositive blood donors by using a soluble recombinant chimeric protein, IE1-pp65.

The transfer of anti-human cytomegalovirus (HCMV) effector T cells to allogeneic bone marrow recipients results in protection from HCMV disease associated with transplantation, suggesting the direct control of CMV replication by T cells. IE1 and pp65 proteins, both targets of CD4(+) and CD8(+) T cells, are considered the best candidates for immunotherapy and vaccine design against HCMV. In this report, we describe the purification of a 165-kDa chimeric protein, IE1-pp65, and its use for in vitro stimulation and expansion of anti-HCMV CD4(+) and CD8(+) T cells from peripheral blood mononuclear cells (PBMC) of HCMV-seropositive donors. We demonstrate that an important proportion of anti-HCMV CD4(+) T cells was directed against IE1-pp65 in HCMV-seropositive donors and that the protein induced activation of HLA-DR3-restricted anti-IE1 CD4(+) T-cell clones, as assessed by gamma interferon (IFN-gamma) secretion and cytotoxicity. Moreover, soluble IE1-pp65 stimulated and expanded anti-pp65 CD8(+) T cells from PBMC of HLA-A2, HLA-B35, and HLA-B7 HCMV-seropositive blood donors, as demonstrated by cytotoxicity, intracellular IFN-gamma labeling, and quantitation of peptide-specific CD8(+) cells using an HLA-A2-peptide tetramer and staining of intracellular IFN-gamma. These results suggest that soluble IE1-pp65 may provide an alternative to infectious viruses used in current adoptive strategies of immunotherapy.

Low impact of a community-wide HIV testing and counseling program on sexual behavior in rural Uganda.

Study results on the assessment of a community-wide HIV counseling and testing program are presented. The aim of this study was to elucidate whether HIV counseling and testing was effective in reducing high risk sexual behavior of a rural population in Uganda. From a total of 2,267 persons of Kigoyera Parish, western Uganda, who were HIV tested and counseled, 495 persons were selected and interviewed about their sexual behavior. Persons who were HIV tested showed no difference in sexual behavior compared to those who were not tested (condom use 4.3% vs. 5.5%, mean number of sexual partner in the past three months 1.8 vs. 2.0). The conclusion is that only knowing the HIV serostatus is not enough to reduce high risk behavior. The study results also showed that there is a demand for HIV counseling services without being HIV tested.

Knowledge, attitude and practice about sexually transmitted diseases among university students in Kampala.

BACKGROUND: Sexually transmitted diseases (STDs) remain an important cause of morbidity and mortality among women in the child-bearing age. In order to institute appropriate preventive measures there is need to establish the profile of knowledge of the predisposing factors and causation of STDs, attitude to sexual practice and sexual patterns among the susceptible young people, such as university students. STUDY POPULATION: Non medical university students, Makerere University. DESIGN: Descriptive cross sectional study. METHODS: A detailed questionnaire identifying socio-demographic characteristics, sexual patterns, knowledge of STDs as well as attitudes towards prevention of STDs was administered to 400 non medical university students of Makerere University. RESULTS: Knowledge of the clinical features of gonorrhoea and AIDS was high; most knew the predisposing factors for STDs (multiple sexual partners 90%; unprotected sexual intercourse 93%; rape 81%; sex outside marriage 78%, and sex under the influence of alcohol 73%) but not so for syphilis. Males were three times more likely to contract STDs (27%) than their female (9%) counterparts. Whereas knowledge on methods of prevention was high (>90%) it was not followed by appropriate behavioural patterns. More female (33.5%) students had heard about Trichomonas vaginalis than males (23%); (((2) = 17.1; < 0.0001). This study has shown that more female than male students got information from their parents (((2) = 25.3; p < 0.001) while more male students had their source of information from previous sexual intercourse (((2) = 12.9; p = 0.001). CONCLUSION: The level of knowledge about STDs and their prevention is not matched by sexual behavioural patterns, and male students undertake more risky sexual behaviour. Sexual education should be introduced at the university as a means of increasing students' awareness about the problem and prevention of sexually transmitted diseases including HIV/AIDS.

Incoming human cytomegalovirus pp65 (UL83) contained in apoptotic infected fibroblasts is cross-presented to CD8(+) T cells by dendritic cells.

Human cytomegalovirus (HCMV) infection is well controlled mainly by cytotoxic CD8(+) T lymphocytes (CTL) directed against the matrix protein pp65 despite the numerous immune escape mechanisms developed by the virus. Dendritic cells (DCs) are key antigen-presenting cells for the generation of an immune response which have the capacity to acquire antigens via endocytosis of apoptotic cells and thus present peptides to major histocompatibility complex class I-restricted T cells. We examined whether this mechanism could contribute to the activation of anti-pp65 CTL. In this study, we show that infection by HCMV AD169 induced sensitization of MRC5 fibroblasts to tumor necrosis factor alpha-mediated apoptosis very early after virus inoculation and that pp65 contained in apoptotic cells came from the delivery of the matrix protein into the cell. We observed that immature DCs derived from peripheral monocytes were not permissive to HCMV AD169 infection but were able to internalize pp65-positive apoptotic infected MRC5 cells. We then demonstrated that following exposure to these apoptotic bodies, DCs could activate HLA-A2- or HLA-B35-restricted anti-pp65 CTL, suggesting that they acquired and processed properly fibroblast-derived pp65. Together, our data suggest that cross-presentation of incoming pp65 contained in apoptotic cells may provide a quick and efficient way to prime anti-HCMV CD8(+) T cells.

N-linked oligosaccharides can protect target cells from the lysis mediated by NK cells but not by cytotoxic T lymphocytes: role of NKG2-A.

We have previously shown that glycophorin A (GPA), inserted by electropulsation into the membrane of K562 cells, protected them from natural killer (NK) cell-mediated cytotoxicity and the unique N-linked oligosaccharide of GPA was essential for resistance to occur. The present study demonstrates that the protection level conferred by GPA is similar to the resistance induced by HLA-Cw3 expressed by transfected K562 cells. A monoclonal antibody against NKG2-A, an NK inhibitory receptor interacting with HLA class I antigens and belonging to the C-type lectin receptor, was able to restore the ability of NK cells to lyse K562 cells expressing HLA-Cw3 at the cell membrane but not electroinserted-GPA, suggesting that the N-linked oligosaccharide of GPA cannot be a ligand for NKG2-A. GPA was then electroinserted into the membrane of two lymphoblastoid B-cell lines: one was sensitive to NK cell-mediated lysis, the other was susceptible to cytotoxic CD8+ T-lymphocyte (CTL)-mediated cytotoxicity. The electroinserted GPA protected the target cells from NK-mediated cytotoxicity, whereas it did not modify the cell susceptibility to lysis by CTL. Endoglycosidase F treatment abolished the resistance towards NK cell-mediated lysis, suggesting that N-linked glycans could inhibit mechanisms used by NK cells to exert their cytotoxic function in agreement with our previous results.

Education attainment as a predictor of HIV risk in rural Uganda: results from a population-based study.

We examined the association between education and prevalent HIV-1 infection in the Rakai district, rural Uganda based on a cross-sectional analysis of a population-based cohort. In 1990, 1397 men and 1705 women aged 13 years and older, were enrolled in 31 randomly selected communities. Strata were comprised of main road trading centres, secondary road trading villages and rural villages. Sociodemographic and behavioural data were obtained by interview and serum for HIV serostatus were obtained in the home. The analysis examines the association between sex-specific prevalent HIV infection and educational attainment, categorized as secondary, primary or none. The odds ratios (ORs) and 95% confidence intervals (95% CIs) of HIV infection were estimated, using no education as the referent group. Higher levels of education were associated with a higher HIV seroprevalence in bivariate analyses (OR 2.7 for primary and 4.1 for secondary education, relative to no education). The strength of the association was diminished but remained statistically significant after multivariate adjustment for sociodemographic and behavioural variables (adjusted OR of HIV infection 1.6 (95% CI: 1.2-2.1)) for primary education and 1.5 (95% CI: 1.0-2.2) for secondary education. Stratified multivariate analyses by place of residence indicated that the association between education and HIV prevalence was statistically significant in the rural villages, but not in the main road trading centres and intermediate trading villages. Educational attainment is a significant predictor of HIV risk in rural Uganda, in part because of risk behaviours and other characteristics among better educated individuals. Preventive interventions need to focus on better educated adults and on school-aged populations.

PIP: This is a cross-sectional analysis of a population-based cohort study conducted to examine both the associations between educational attainment and HIV-1 serostatus as well as the relationship between education and other HIV risk factors in Rakai district, Uganda. A total of 3102 respondents (1397 men and 1705 women aged 13 years and older) completed a questionnaire and provided blood samples. The samples of community clusters was stratified into three strata: trading centers on main roads, intermediate trading villages on secondary roads, and rural agricultural villages with no roads or only minor road connection. Analysis has shown a consistent association between higher level of educational attainment and HIV-1 prevalence among the residents. The strength of the association was decreased but remained statistically relevant after multivariate adjustment for sociodemographic and behavioral variables [adjusted OR for HIV infection, 1.6 (95% CI, 1.2-2.1) for primary education and 1.5 (95% CI, 1.0-2.2) for secondary education]. Stratified multivariate analyses by place of residence showed that the relationship between education and HIV prevalence was markedly higher in the rural villages compared to the other two strata. Education provides greater economic resources, which facilitate behaviors that put individuals at greater risk. Analysis of findings suggests that HIV prevention strategies should focus on the more educated individuals, particularly in rural settings and among younger women.

Age of male circumcision and risk of prevalent HIV infection in rural Uganda.

OBJECTIVE: To assess whether circumcision performed on postpubertal men affords the same level of protection from HIV-1 acquisition as circumcisions earlier in childhood. DESIGN: Cross-sectional study of a population-based cohort. SETTING: Rakai district, rural Uganda. METHODS: A total of 6821 men aged 15-59 years were surveyed and venous blood samples were tested for HIV-1 and syphilis. Age at circumcision was dichotomized into men who were circumcised before or at age 12 years (prepubertal) and men circumcised after age 12 years (postpubertal). Postpubertal circumcised men were also subdivided into those reporting circumcision at ages 13-20 years and > or = 21 years. RESULTS: HIV-1 prevalence was 14.1% in uncircumcised men, compared with 16.2% for men circumcised at age > or = 21 years, 10.0% for men circumcised at age 13-20 years, and 6.9% in men circumcised at age < or = 12 years. On bivariate analysis, lower prevalence of HIV-1 associated with prepubertal circumcision was observed in all age, education, ethnic and religious groups. Multivariate adjusted odds ratio of prevalent HIV-1 infection associated with prepubertal circumcision was 0.39 [95% confidence interval (CI), 0.29-0.53]. In the postpubertal group, the adjusted odds ratio for men circumcised at ages 13-20 years was 0.46 (95% CI, 0.28-0.77), and 0.78 (95% CI, 0.43-1.43) for men circumcised after age 20 years. CONCLUSIONS: Prepubertal circumcision is associated with reduced HIV risk, whereas circumcision after age 20 years is not significantly protective against HIV-1 infection. Age at circumcision and reasons for circumcision need to be considered in future studies of circumcision and HIV risk.