Antibody to Rmp (outer membrane protein 3) increases susceptibility to gonococcal infection.

The severe adverse effects of gonococcal infection on human fertility suggests that Neisseria gonorrhoeae would exert powerful selection for the development of a protective immune response in humans. N. gonorrhoeae is an obligate human pathogen and must persist in humans to survive. Since it is an ecologically successful organism, it must have evolved strategies to evade any human immune response it elicits. In a longitudinal study among 243 women working as prostitutes and experiencing frequent gonococcal infection, younger women, women with HIV infection, and women with antibody to the gonococcal outer membrane protein 3 (Rmp) were at increased risk of infection (adjusted odds ratio 3.4, CI95% 1.1-10.4, P < 0.05). Rmp is highly conserved in N. gonorrhoeae and the blocking of mucosal defences may be one of its functions. As similar proteins occur in many gram negative mucosal pathogens, the enhancing effect of such proteins may be a general strategy whereby bacteria evade human immune responses.

PIP: Between March 1985 and July 1986 researchers enrolled 243 female prostitutes in Pumwani community of Nairobi, Kenya, in a longitudinal study to examine the relationship between the antibody to the gonococcal outer membrane protein 3 (Rmp Ab) and gonococcal mucosal infection. Few women used condoms. 69% were HIV-1 seropositive. Just 9.5% (23) of the women had not had any gonococcal infections, despite probable exposure to them, indicating the possibility of some acquired protective immunity to Neisseria gonorrhoea. 90.5% had had at least 1 gonococcal infection. Women with Rmp Ab faced a greater risk of gonococcal infection than those who were Rmp Ab negative (OR = 3.4;l p .05), denoting that Rmp Ab increases susceptibility to gonococcal mucosal infections. Women older than 29 years were at lower risk of gonococcal infection than those younger than 29 years (odds ratio [OR] = 0.3; p .03). Women who used oral contraceptives (OCs) were also likely to be infected with N. gonorrhoea (OR = 3; p = .062). Further, 31% of OC users had cervical ectopy compared to just 14% of nonusers (OR = 2.8; p .005), suggesting that the effect of OCs on the cervix make it more susceptible to gonococcal infection. Rmp Ab also exists in many other gram-negative mucosal pathogens, often playing the same role as it does in N. gonorrhoea infection. Thus, Rmp Ab may be a common scheme bacteria used to elude human immune responses. These findings provide more understanding as to why N. gonorrhoea is an ecologically successful human pathogen.

Epidemiologic evidence for the development of serovar-specific immunity after gonococcal infection.

We tested the hypothesis that strain-specific immunity occurs after gonococcal infection in a longitudinal study of 227 prostitutes resident in one small community who experienced frequent gonococcal infections. Women were examined and cultured for Neisseria gonorrhoeae at 2-wk intervals. Gonococcal isolates were typed according to protein 1 serovar, auxotype, and beta-lactamase plasmid type, and classified as to serovar and strain. The hypothesis was tested by comparing the predictions of the hypothesis with the observations of the study. Over the 14-mo period of the study, major changes in the prevalence of specific serovars were observed in the gonococcal population infecting these women. Women with HIV infection experienced a higher rate of gonococcal infection (0.56 +/- 0.03 vs. 0.46 +/- 0.04, P less than 0.05, t test) compared with HIV-negative women and were more likely to experience multiple infections with the same strain. The duration of prostitution was inversely related to the frequency of gonococcal infection. Women experiencing an infection with a specific gonococcal serovar were at a 2- to 10-fold reduced risk of reinfection with the same serovar, except for the 1B-1 serovar. The results of the study were consistent with all four predictions of the hypothesis. Infection with a specific gonococcal serovar results in specific but incomplete protection against subsequent infection with the homologous serovar. The mechanism of this protection remains to be determined.

Antibodies to opacity proteins (Opa) correlate with a reduced risk of gonococcal salpingitis.

Acute salpingitis complicating cervical gonococcal infection is a significant cause of infertility. Relatively little data are available concerning the pathophysiologic mechanisms of this disease. A cohort of 243 prostitutes residing in Nairobi were followed between March 1985 and April 1988. Gonococcal cultures were performed at each visit, and acute salpingitis was diagnosed clinically. Serum at enrollment was tested by immunoblot for antibody to gonococcal outer membrane proteins. 8.6% (146/1689) of gonococcal infections were complicated by salpingitis. Increased risk of salpingitis was associated with younger age, shorter duration of prostitution, HIV infection, number of gonococcal infections, and episodes of nongonococcal salpingitis. Rmp antibody increased the risk of salpingitis. Antibody to Opa decreased the risk of salpingitis. By logistic regression analysis, antibody to Opa was independently associated with decreased risk of gonococcal salpingitis (adjusted odds ratio [OR], 0.35; 95% confidence interval [95%CI], 0.17-0.76); HIV infection (adjusted OR, 3.5; 95% CI, 0.96-12.8) and episodes of nongonococcal salpingitis (adjusted OR, 3.4; 95% CI, 1.8-6.4) were independently associated with an increased risk of salpingitis. Antibody to Opa appears to protect against ascending gonococcal infection, perhaps by interfering with Opa mediated adherence and endocytosis. The demonstration of natural immunity that protects against upper genital tract infection in women suggests that a vaccine to prevent gonococcal salpingitis is possible.

HIV pathogenesis: mechanisms of susceptibility and disease progression.

The understanding of the factors associated with HIV-1 acquisition and disease progression has been significantly advanced in the past few years. These factors can be broadly defined as intrinsic or acquired and are operative at the levels of disease acquisition and progression or both. Much recent attention has focused on the identification of allelic variants at specific genetic loci that alter either susceptibility to infection or the natural history of disease progression. In addition, a more detailed understanding of the immunologic responses to HIV-1 and factors that perturb these responses has greatly enhanced our understanding of the immunologic control of HIV-1 and the roles of cofactors in HIV-1 acquisition and disease progression.

HIV infection among lower socioeconomic strata prostitutes in Nairobi.

A cohort of 418 lower socioeconomic strata prostitutes were enrolled in a study of the epidemiology of sexually transmitted diseases (STDs) between January and April 1985. Sixty-two per cent of the women were seropositive for HIV infection at enrollment. Significant associations were found between HIV seropositivity and Tanzanian origin (OR = 2.12, CI 95% = 1.18-3.81, P less than 0.03), younger age, a shorter duration of prostitution, reduced fecundity, use of oral contraceptives (OR = 1.8, CI 95% = 1.1-2.9, P less than 0.05) and genital ulcer disease (OR = 3.32, P less than 0.00001). No associations were noted with other STD. Stepwise logistic regression analysis confirmed independent associations between HIV infection and Tanzanian origin (OR = 2.27, CI 95% = 1.25-4.14, P less than 0.007), reduced fecundity (OR = 0.83, CI 95% = 0.74-0.94, P less than 0.003), oral contraceptive use (OR = 2.02, CI 95% = 1.22-3.35, P less than 0.006) and duration of prostitution (OR = 0.39, CI 95% = 0.23-0.65, P less than 0.004). Oral contraceptives may increase susceptibility to HIV or may be a marker for other factors which increase risk of acquisition. Further studies are necessary to confirm this association.

Genetic analysis of human DNA recovered from minute amounts of serum or plasma.

A rapid and inexpensive method is described where a small amount of serum or plasma was used as the source of DNA for genetic analysis. Using a silica gel matrix DNA was isolated from 50 microliters of archived serum or plasma. The specimens were collected from 13 individuals at two separate time points 3-6 years apart. The polymorphic region of second exon of the MHC class II gene HLA DQA1 was amplified using the polymerase chain reaction (PCR) to sufficient quantities to permit genetic analysis using allele-specific oligonucleotides (ASO). Allelic typing of each specimen was performed and the reproducibility of the method was demonstrated in that in all 13 cases the two independently isolated specimens produced the identical ASO binding patterns. No qualitative difference was noted in the amplified product generated from plasma or serum. This study demonstrates (a) that minute amounts of serum or plasma are able to provide sufficient quantity and quality of DNA to permit genetic analyses (b) and that the source of serum can be archived for many years.

HIV type 1 resistance in Kenyan sex workers is not associated with altered cellular susceptibility to HIV type 1 infection or enhanced beta-chemokine production.

A small group of women (n = 80) within the Nairobi-based Pumwani Sex Workers Cohort demonstrates epidemiologic resistance to HIV-1 infection. Chemokine receptor polymorphisms and beta-chemokine overproduction have been among the mechanisms suggested to be responsible for resistance to HIV-1 infection. This study attempts to determine if any of those mechanisms are protecting the HIV-1-resistant women. Genetic analysis of CCR5 and CCR3 from the resistant women demonstrated no polymorphisms associated with resistance. Expression levels of CCR5 among the resistant women were shown to be equivalent to that found in low-risk seronegative (negative) controls, while CXCR4 expression was greater among some of the resistant women. In vitro infection experiments showed that phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from resistant women were as susceptible to infection to T cell- and macrophage-tropic North American and Kenyan HIV-1 isolates as were the PBMCs from negative controls. No significant difference in circulating plasma levels of MIP-1alpha and MIP-1beta were found between the resistant women and negative or HIV-1-infected controls. In vitro cultures of media and PHA-stimulated PBMCs indicated that the resistant women produced significantly less MIP-1alpha and MIP-1beta than did negative controls and no significant difference in RANTES levels were observed. In contrast to studies in Caucasian cohorts, these data indicate that CCR5 polymorphisms, altered CCR5 and CXCR4 expression levels, cellular resistance to in vitro HIV-1 infection, and increased levels of beta-chemokine production do not account for the resistance to HIV-1 infection observed among the women of the Pumwani Sex Workers Cohort.

Molecular cloning and sequence analysis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from the human parasite Schistosoma mansoni.

cDNA clones encoding the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase [(S)-mevalonate:NADP+ oxidoreductase (CoA-acylating), EC 1.1.1.34] from the human parasite Schistosoma mansoni have been isolated and characterized. The composite 3459 base pairs of cDNA sequence contains a 2844-base-pair open reading frame corresponding to a protein of 948 amino acids. The predicted S. mansoni HMG-CoA reductase protein contains a hydrophobic amino terminus consisting of seven potential transmembrane domains that are structurally conservative but are not identical in amino acid sequence with HMG-CoA reductases from other species. The hydrophilic carboxyl terminus of the S. mansoni HMG-CoA reductase protein, however, shares 48-52% sequence identity with the carboxyl termini of other HMG-CoA reductases in a region that contains the catalytic domain. When expressed as a fusion protein in Escherichia coli, the carboxyl-terminal domain of the schistosome protein exhibits HMG-CoA reductase enzyme activity.

A spliced leader is present on a subset of mRNAs from the human parasite Schistosoma mansoni.

We present evidence that a subset of mRNAs in the human parasitic trematode Schistosoma mansoni contain an identical 36-nucleotide spliced leader (SL) sequence at their 5' termini. The SL is derived from a 90-nucleotide nonpolyadenylylated RNA (SL RNA), presumably by trans-splicing. Neither the SL nor the SL RNA share significant sequence identity with previously described trans-spliced leaders and SL RNAs in trypanosomatid protozoans or nematodes. However, several features, such as predicted secondary structure, trimethylguanosine cap, and potential Sm binding site, suggest similarities among SL RNAs in widely divergent organisms. Our evidence also indicates that the exon 3 acceptor site of the 3-hydroxy-3-methylglutaryl-CoA reductase gene can be spliced either to the SL by trans-splicing or to an upstream exon, 2, by cis-splicing. The presence of a SL sequence in S. mansoni, a member of the phylum Platyhelminthes, suggests that transplicing may be a common feature of other lower invertebrates.

Biosynthesis of chloramphenicol. Studies on the origin of the dichloroacetyl moiety.

Chloramphenicol produced by cultures of Streptomyces species 3022a supplemented with sodium [1,2-13C]acetate was labelled with 13C exclusively in the dichloromethine (2.6 +/- 0.1%) and carbonyl (0.59 +/- 0.05% carbon atoms. Satellite signals from 13C-13C coupling between covalently bonded 13C-enriched carbon atoms were too intense to be attributed to random combination of labelled atoms at the average enrichments measured, but their intensity relative to those of the signals for uncoupled 13C atoms indicated that most of the precursor had been incorporated after 13C-13C bond fission. Since [2,3-13c]succinic acid enriched only the carbonyl carbon atom of chloramphenicol, these results suggest that neither acetate nor a Krebs cycle intermediate is a direct precursor of the dichloroacetyl group. Cultures supplemented with [2-3h]-or [2h2]-dichloroacetic acid incorporated negligible amounts of isotope into the antibiotic; on this evidence, the free acid is not an intermediate in chloramphenicol biosynthesis and the acylation step may precede chlorination.

Acute sexually transmitted infections increase human immunodeficiency virus type 1 plasma viremia, increase plasma type 2 cytokines, and decrease CD4 cell counts.

In Kenya, the median incubation time to AIDS in seroconverting sex workers is 4 years; this incubation time is specific to female sex workers. We studied the influence of acute sexually transmitted infections (STIs) on several immunologic parameters in 32 human immunodeficiency virus type 1 (HIV-1)-positive and 10 HIV-1-negative women sex workers who were followed for 1-5 months. Plasma cytokines, soluble cytokine receptors, CD4 and CD8 T cell counts, and HIV-1 plasma viremia were quantitated before, during, and after episodes of STI. Increases in interleukin (IL)-4, IL-6, IL-10, soluble tumor necrosis factor (TNF)-alpha, and viremia and a decline in CD4(+) T cell counts occurred during gonococcal cervicitis and returned to baseline after treatment. Increases in viremia correlated with increased IL-4 and decreased IL-6 concentrations. Similar changes were seen among women with acute pelvic inflammatory disease. Acute bacterial STI resulted in increased HIV-1 viremia. This may be mediated through increased inflammatory cytokines or through modulation of immune responses that control HIV-1 viremia.

A review of HIV-1 in Africa.

PIP: As the AIDS epidemic reaches a dramatic stage of development, the time for African countries to establish effective control programs has come. The history of AIDS in Africa is different from that other regions of the world. The disease developed among heterosexual communities. By 1987, over 8,000 cases of AIDS had been reported from 37 of the 47 nations of Africa. Over 2,000 of these cases were found in Uganda. However, under-reporting and under-representation of the number of actual cases is still a problem. In many cases, there has been a failure to recognize the disease. The demographic and geographic distribution of seroprevalence is discussed. Because of the inaccuracies in AIDS reporting in Africa, epidemic forecasting is difficult. If 5 million are currently infected, a potential 50 million Africans may be infected by 1993. A further discussion of the risk factors for HIV-1 holds that promiscuity is the major problem. Cures and inexpensive treatments for the infection are years away. Energy, resources, and national committees in Africa and the world must be coordinated to combat the ultimate crisis of this century.^ieng

Prevention of transmission of human immunodeficiency virus in Africa: effectiveness of condom promotion and health education among prostitutes.

Condom use was assessed after a programme of education about the acquired immunodeficiency syndrome and a condom distribution programme in a well-characterised prostitute population in Nairobi. Women received their education at group meetings (barazas) and at individual counselling sessions during which they were given the results of serological tests for the human immunodeficiency virus (group 1) or at barazas only (group 2), or through very little of either (group 3). During the counselling sessions free condoms were distributed. Before either of the programmes started, 10%, 9%, and 7% of groups 1, 2, and 3 women, respectively, reported occasional use of condoms. By November 1986, 80%, 70%, and 58% of groups 1, 2, and 3 women, respectively, reported at least some condom use. The mean frequency of condom use was 38.7 (SD 31.8)%, 34.6 (34.5)%, and 25.6 (29.5)% of sexual encounters in groups 1, 2, and 3 women. 20 of 28 women who were non-condom-users seroconverted compared with 23 of 50 women who reported some use of condoms.

PIP: In some parts of Africa, prostitutes and their clients represent the groups at greatest risk of human immunodeficiency virus (HIV) infection and the major disseminators of the virus. As part of a cohort study of the epidemiology of sexually transmitted diseases in Nairobi, 595 prostitutes have been followed since 1985. At the start of the study, 61% of these prostitutes were infected with HIV. Health education, initially about conventional sexually transmitted diseases and subsequently about acquired immunodeficiency syndrome (AIDS), was a major component of this project. Health education was provided at barazas (general community meetings including lectures, skits, role playing, and discussion) and individual counseling sessions. To evaluate the effectiveness of such health promotion efforts on the prevention of HIV infection, specifically on adoption of condom use, the prostitutes were divided into 3 groups: 1) those who received their health education through both barazas and individual sessions at which the results of serological tests for HIV infection were discussed; 2) those who attended barazas only; and 3) prostitutes who received neither intervention. Condoms were distributed free of charge to all prostitutes who requested them. At the start of the project, only 10%, 7%, and 7% of prostitutes in Groups 1, 2, and 3, respectively, reported some use of condoms. After 6 months in the program, this statistic had increased to 80%, 70%, and 58%, respectively. The mean frequency of condom use was 38.7%, 34.6%, and 25.6% of sexual encounters in Group 1, 2, and 3 women. Any condom use resulted in a 3-fold reduction in risk of seroconversion. 20 of 28 women who were not condom users seroconverted compared with 23 of 50 condom users. Stepwise logistic regression confirmed that group discussion was the factor most significantly associated with condom use.

Genetic diversity and mosaicism at the por locus of Neisseria gonorrhoeae.

The por genes of the predominant serovars of Neisseria gonorrhoeae circulating in a high-frequency transmitter core group located in Nairobi, Kenya, were examined for nucleotide sequence polymorphism. The level of por gene diversity did not differ significantly between core group-derived gonococcal strains and gonococcal strains originating elsewhere. However, por mosaicism appeared to be more frequent among core group-derived strains, suggesting that recombination of different por sequences may be a important strategy by which N. gonorrhoeae generates por gene diversity within core group populations. Despite extensive sequence variability, por expressed by gonococcal isolates of different geographic origin exhibited conserved patterns of nucleotide change, suggesting that diversity among por alleles may also be finite.

HIV-1-specific cellular immune responses among HIV-1-resistant sex workers.

The goal of the present study was to determine whether there were HIV-1 specific cellular immune responses among a subgroup of women within a cohort of Nairobi prostitutes (n = 1800) who, despite their intense sexual exposure to HIV-1, are epidemiologically resistant to HIV-1 infection. Of the 80 women defined to be resistant, 24 were recruited for immunological evaluation. The HIV-1-specific T-helper responses were determined by IL-2 production following stimulation with HIV-1 envelope peptides and soluble gp120. Cytotoxic T lymphocyte responses were determined by lysis of autologous EBV-transformed B cell lines infected with control vaccinia virus or recombinant vaccinia viruses containing the HIV-1 structural genes env, gag and pol. Resistant women had significantly increased HIV-1 specific T-helper responses, as determined by in vitro IL-2 production to HIV-1 envelope peptides and soluble glycoprotein 120, compared with low-risk seronegative and HIV-1-infected controls (P < or = 0.01, Student's t-test). Seven of the 17 (41%) resistant women showed IL-2 stimulation indices > or = 2.0. HIV-1-specific CTL responses were detected among 15/22 (68.2%) resistant women compared with 0/12 low-risk controls (Chi-squared test, P < 0.001). In the two resistant individuals tested, the CTL activity was mediated by CD8+ effectors. Many HIV-1-resistant women show evidence of HIV-1-specific T-helper and cytotoxic responses. These data support the suggestion that HIV-1-specific T-cell responses contribute to protection against HIV-1 infection.

Condom use prevents genital ulcers in women working as prostitutes. Influence of human immunodeficiency virus infection.

Control of genital ulcer disease (GUD) is a proposed intervention to slow the dissemination of human immunodeficiency virus (HIV) infection. Programs for the control of sexually transmitted diseases (STD) should focus on groups of high-frequency transmitters, such as prostitutes and their clientele. This study illustrates the interaction between the prevalence of chancroid, use of barrier prophylaxis against STDs, and HIV infection in a population of female prostitutes in Nairobi. Four hundred and twenty three women were evaluated. Despite the increased use of condoms, the prevalence of genital ulcers remained constant between 1986-87 and 1987-88. Genital ulcer disease was simultaneously associated with HIV infection (adjusted odds ratio: 3.7, P less than .01) whereas it was independently and inversely associated with more consistent condom use (P less than .01). The authors conclude that genital ulcer disease can be controlled in these populations but concurrent HIV infection increases the difficulty of this intervention.

PIP: Counselors at a Nairobi City Commission Maternal/Child Health Clinic interviewed prostitutes in a certain residential area every 6 months between 1986-1988 about sexual practices and condom use. In addition, every 6 months, health workers examined the women on a demand basis free of charge, promoted condom use, provided condoms, informed then about sexually transmitted diseases (STDs) and HIV infection, and took samples to test for STD and HIV status. Prostitutes were 3 times more likely to use condoms in 1987-1988 than 1986-1987, but the prevalence of genital ulcers remained basically the same (34% in 1986-1987 and 32% in 1987-1988). Hemophilus ducreyi was responsible for at least 80% of the genital ulcers. In 1987-1988, 35% of HIV-1 seropositive women had genital ulcers while only 14% of HIV-1 seronegative women did (p.01). In fact, genital ulcer prevalence increased significantly in HIV-1 seropositive women as the disease stage of HIV-1 advanced (27% of asymptomatic healthy women, 35% of women with generalized lymphadenopathy, and 46% of women with clinical HIV related disease; p.05). Thus this study suggested that the immunosuppressive traits of preexisting HIV infection negate any protective effect that condoms normally have against genital ulcers. Indeed the researchers proposed that a complex bidirectional epidemiologic and biologic interaction of HIV and H. ducreyi infection to be the basis of the HIV-1 epidemic in these women. In conclusion, strategies to curtail the transmission of HIV among heterosexuals should consists of programs which understand and change sexual behavior resulting in a decline in the contribution of prostitutes or other core groups to the HIV epidemic, condom use to prevent STD and HIV transmission, and control of genital ulcers in high frequency transmitters including prostitutes and clients.

Cofactors in male-female sexual transmission of human immunodeficiency virus type 1.

In a study of human immunodeficiency virus type 1 (HIV-1)-uninfected African prostitutes, 83 (67%) of 124 seroconverted to HIV-1. Oral contraceptive use (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.1-8.6; P less than .03), genital ulcers (mean annual episodes, 1.32 +/- 0.55 in seroconverting women vs. 0.48 +/- 0.21 in seronegative women; P less than .02) and Chlamydia trachomatis infections (OR, 3.6; CI, 1.3-11.0; P less than .02) were associated with increased risk of HIV-1 infection. Condom use reduced the risk of HIV-1 infection (OR, 0.11; CI, 0.05-0.27; P less than .0001). Stepwise logistic regression analysis confirmed independent associations between HIV-1 infection and oral contraceptive use, condom use, genital ulcers, and C. trachomatis. The presence of other sexually transmitted diseases may in part explain the heterosexual HIV-1 epidemic in Africa and may represent important targets for intervention to control HIV-1 infection.

Human immunodeficiency virus infection among men with sexually transmitted diseases. Experience from a center in Africa.

Heterosexual transmission of the human immunodeficiency virus (HIV) appears to occur readily in Africa but less commonly in North America and Europe. We conducted a case-control study among men attending a clinic for sexually transmitted diseases in Nairobi to determine the prevalence of HIV infection and the risk factors involved. HIV antibody was detected in 11.2 percent of 340 men who enrolled in the study. Reports of nonvaginal heterosexual intercourse and homosexuality were notably rare. Recent injections and blood transfusions were not associated with HIV infection. Travel and frequent contact with prostitutes were associated with HIV seropositivity. Men who were uncircumcised were more likely to have HIV infection (odds ratio, 2.7; P = 0.003), as were those who reported a history of genital ulcers (odds ratio, 7.2; P less than 0.001). A current diagnosis of genital ulcers was also associated with HIV seropositivity (odds ratio, 2.0; P = 0.028). Multivariate analysis revealed an independent association of genital ulcers with HIV infection in both circumcised and uncircumcised men. Uncircumcised men were more frequently infected with HIV, regardless of a history of genital ulcers. Our study finds that genital ulcers and an intact foreskin are associated with HIV infection in men with a sexually transmitted disease. Genital ulcers may increase men's susceptibility to HIV, or they may increase the infectivity of women infected with HIV. The intact foreskin may operate to increase the susceptibility to HIV.

Female to male transmission of human immunodeficiency virus type 1: risk factors for seroconversion in men.

To determine the frequency and risk factors for female to male sexual transmission of human immunodeficiency virus type 1 (HIV-1), a prospective study was carried out in 422 men who had acquired a sexually transmitted disease (STD) from a group of prostitutes with a prevalence of HIV-1 infection of 85%. The initial seroprevalence of HIV among the men was 12%. 24 of 293 (8.2%) initially seronegative men seroconverted to HIV-1. Newly acquired infection was independently associated with frequent prostitute contact (risk ratio 3.2, 95% confidence interval 1.2-8.1), with the acquisition of genital ulcer disease (risk ratio 4.7, 95% confidence interval 1.3-17.0), and with being uncircumcised (risk ratio 8.2, 95% confidence interval 3.0-23.0). 96% of documented seroconversions occurred in men with one or both of the latter two risk factors. In a subgroup of 73 seronegative men who reported a single prostitute sexual contact, the frequency of HIV-1 infection was 8.2% during 12 weeks of observation. No man without a genital ulcer seroconverted. A cumulative 43% of uncircumcised men who acquired an ulcer seroconverted to HIV-1 after a single sexual exposure. These data indicate an extremely high rate of female to male transmission of HIV-1 in the presence of STD and confirm a causal relation between lack of male circumcision, genital ulcer disease, and susceptibility to HIV-1 infection.