Hepatitis G and hepatitis C RNA viruses coexisting in cryoglobulinemia.

OBJECTIVE: Hepatitis G virus (HGV) has been identified as a new member of the Flaviridae family, which includes the hepatitis C virus (HCV). There is a well established association between HCV and cryoglobulinemia; however, to date HGV has not been linked with various types of cryoglobulinemia. We investigated the association of HGV with cryoglobulinemia. METHODS: We studied 10 patients with cryoglobulinemia. The cryoglobulins were purified and identified by immunofixation electrophoresis. HGV and HCV RNA were studied in the serum and in purified cryoglobulins by reverse transcriptase polymerase chain reaction. RESULTS: Nine of 10 patients were women, aged 37-74 years. These patients had combinations of hepatitis C (6), vasculitis (7), lymphoproliferative (3), and autoimmune and connective tissue diseases (3). Of the 10 patients, 3 were positive for both HGV RNA and HCV RNA. Two of three patients with dual infection of HGV and HCV had malignancies (Waldenstrom's macroglobulinemia, B cell lymphoma). In one of these 3 patients HGV RNA was positive in the cryoglobulin fraction, but not in serum. Three other patients were positive for HCV RNA alone. CONCLUSION: HGV may be associated with cryoglobulins. Our three patients were co-infected with HCV. Since our series is small, the pathogenetic role of hepatitis G and its relationship to malignancy remain to be elucidated.

Human immunodeficiency virus type 1 seroconversion in women with genital ulcers.

Genital ulcers are implicated as a risk factor enhancing susceptibility to human immunodeficiency virus type 1 (HIV-1) infection. A prospective study to determine the incidence of and risk factors associated with acquisition of HIV-1 in women with genital ulcers was done. HIV-1-seronegative women with genital ulcers attending a clinic for sexually transmitted diseases in Nairobi were followed to HIV-1 seroconversion over a 6-month period. Of 81 women, 10 seroconverted to HIV-1. The crude 6-month incidence of HIV-1 infection was 12%. Risk factors associated with seroconversion included cervical ectopy (rate ratio [RR], 4.9; 95% confidence interval [CI], 1.5-15.6) and pelvic inflammatory disease (RR, 6.3; 95% CI, 1.9-20.4). Thus, cervical ectopy and pelvic inflammatory disease may increase susceptibility to HIV-1 in women with genital ulcers.

Single-dose cefixime versus single-dose ceftriaxone in the treatment of antimicrobial-resistant Neisseria gonorrhoeae infection.

Sexually transmitted diseases (STDs) have a significant adverse effect on reproductive and child health worldwide. The control of STDs such as gonorrhea is therefore an absolute priority. Cefixime, an oral third-generation cephalosporin with in vitro activity similar to that of ceftriaxone, may be an effective candidate for the treatment of gonorrhea. The efficacy of a single oral 400-mg dose of cefixime was compared with that of a single intramuscular 250-mg dose of ceftriaxone for the treatment of Neisseria gonorrhoeae urethritis in 190 men and cervicitis in 46 women in Nairobi, Kenya. A bacteriologic cure was recorded in 100% of 63 evaluatable patients treated with ceftriaxone and 118 (98%) of 121 evaluatable patients treated with cefixime. Cefixime, as a single oral dose, is an effective alternative for the treatment of uncomplicated gonococcal urethritis in men and cervicitis in women.

Human immunodeficiency virus type 1 infection in women attending a sexually transmitted diseases clinic in Kenya.

A cross-sectional study was conducted among women attending a sexually transmitted diseases clinic in Nairobi, kenya, to determine the prevalence of and associated risk factors for human immunodeficiency virus (HIV) type 1 infection. HIV-1 antibody was detected in 13.8% of 600 women. This virus was found most frequently in prostitutes (odds ratio [OR], 7.2), in women reporting a history of genital ulcers (OR, 2.3), and in those with a current diagnosis of genital ulcers (OR, 5.1). Lifetime duration of oral contraceptive use was significantly greater in HIV-1-positive women. Multivariate analysis revealed an association between genital ulcers and HIV-1 infection (OR, 3.8). The strongest association for HIV-1 infection, however, occurred with genital ulcers in combination with the use of oral contraceptives (OR, 25.7).

A randomized, double-blind study of the efficacy of fleroxacin versus trimethoprim-sulfamethoxazole in men with culture-proven chancroid.

Chancroid is linked to the spread of human immunodeficiency virus type 1 (HIV-1) in East Africa. Effective, easily administered therapy is a priority for the control of Haemophilus ducreyi. The efficacy of a single oral dose of fleroxacin, 400 mg, was compared to a 3-day oral course of trimethoprim-sulfamethoxazole (TMP-SMZ), 160/800 mg, twice daily for the treatment of chancroid in 98 HIV-1-seronegative men in Nairobi, Kenya. No differences were noted between the two groups with respect to demographic characteristics, sexual behavior, and clinical characteristics. Culture-proven failure occurred in 1 (3%) of 36 fleroxacin-treated patients and in 11 (30%) of 37 TMP-SMZ-treated patients (P = .005). Fleroxacin, as a single oral dose, is an effective treatment for culture-proven chancroid in patients who are HIV-1 seronegative. TMP-SMZ is no longer predictably effective due to the recent emergence of resistance to both sulfonamides and to trimethoprim.

Association of cervical ectopy with heterosexual transmission of human immunodeficiency virus: results of a study of couples in Nairobi, Kenya.

To identify risk factors involved in heterosexual transmission of human immunodeficiency virus (HIV), a cross-sectional study of HIV-seropositive men and their spouses was conducted in Nairobi, Kenya. Of 70 spouses, 40 (57%) were seropositive and 30 (43%) were seronegative for HIV. In univariate analysis, the presence of cervical ectopy (odds ratio, 4.7; P = .006) was the only statistically significant variable associated with HIV infection in women. After controlling for possible confounding variables using multivariate logistic regression analysis, the presence of cervical ectopy (odds ratio, 5.0; P = .007) remained the only independent predictor of HIV seropositivity. These findings suggest that cervical ectopy may be a newly identified risk factor for heterosexual transmission of HIV.

Treatment of acute pelvic inflammatory disease in the ambulatory setting: trial of cefoxitin and doxycycline versus ampicillin-sulbactam.

Ampicillin-sulbactam (750 mg) given orally twice daily for 10 days was evaluated for the treatment of acute pelvic inflammatory disease (PID) in an ambulatory setting in Nairobi, Kenya. The first 26 women received ampicillin-sulbactam in an open-label fashion, and the remaining 75 women were randomly selected to receive either ampicillin-sulbactam (n = 38) or cefoxitin (2 g) intramuscularly and probenecid (1 g) orally, followed by doxycycline (100 mg) orally twice daily for 10 days (n = 37). Women were enrolled in a sexually transmitted disease clinic and were followed for clinical and microbiologic responses at 1 to 2 weeks and 4 to 6 weeks posttreatment. Women had a later follow-up visit to note interim pregnancy or underwent hysterosalpingography for fertility outcome assessment. The short-term clinical response rates were 70% for ampicillin-sulbactam and 72% for cefoxitin-doxycycline (P = 0.47). Among Chlamydia trachomatis-infected women treated with ampicillin-sulbactam, three had microbiologic relapse. The post-PID tubal obstruction rates were similar in the two groups: 18% for ampicillin-sulbactam and 33% for cefoxitin-doxycycline (P = 0.31). Neither regimen was highly effective as a therapy for acute PID. These data strongly argue that primary prevention must be the goal for a reduction of PID morbidity and show that improved therapy for the treatment of PID in the ambulatory setting is needed.

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.

Human immunodeficiency virus, genital ulcers and the male foreskin: synergism in HIV-1 transmission.

Epidemiologic studies in Nairobi and elsewhere in Africa, have shown that men infected with HIV-1 more commonly have a history of genital ulcer disease compared to uninfected men. In one study, HIV infected men were three times as likely to have a recent history of genital ulcers. In a prospective study of seronegative men, those presenting with chancroid had a five-fold risk of seroconversion during follow-up compared to men presenting with urethritis. Uncircumcised men had an increased risk of seroconversion which was independent of their risk of genital ulcer disease. Over 95% of attributable risk in men with STD was either genital ulceration or the presence of a foreskin. Genital ulcers are a major risk factor for HIV infection among prostitutes. The increased risk is about 10-fold among prostitutes with ulcers compared to a cohort who did not. We hypothesize from these studies that genital ulcers are the major portals of entry for HIV infection and also increased shedding of virus infected cells into the vaginal secretions. HIV seropositive prostitutes are more susceptible to chancroid with a two-fold increase in the prevalence of genital ulcers as compared to HIV negative women. The use of condoms by their clients prevents both genital ulcer disease and HIV acquisition among prostitutes. Chancroid is more difficult to treat in HIV infected men with one-third of patients failing single dose treatment regimens as compared to less than five percent of men without HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Evaluation of fleroxacin (RO 23-6240) as single-oral-dose therapy of culture-proven chancroid in Nairobi, Kenya.

Chancroid is gaining importance as a sexually transmitted disease because of its association with transmission of human immunodeficiency virus type 1 (HIV-1). Effective, simply administered therapy for chancroid is necessary. Fleroxacin is effective against Haemophilus ducreyi in vitro. We performed an initial randomized clinical trial to assess the efficacy of fleroxacin for treatment of chancroid in Nairobi, Kenya. Fifty-three men with culture-positive chancroid were randomly assigned to receive either 200 mg (group 1) or 400 mg (group 2) of fleroxacin as a single oral dose. Groups 1 and 2 were similar with regard to severity of disease, bubo formation, and HIV-1 status. A satisfactory clinical response to therapy was noted in 23 of 26 patients (88%) in group 1 and 18 of 23 patients (78%) in group 2. Bacteriological failure occurred in 1 of 26 evaluable patients (4%) in group 1 and 4 of 23 evaluable patients (17%) in group 2. Two of 37 HIV-1-seronegative men (5%) and 3 of 11 HIV-1-infected men (27%) were bacteriological failures. Fleroxacin, 200 or 400 mg as a single oral dose, is efficacious therapy for microbiologically proven chancroid in patients who do not have concurrent HIV-1 infection. Among HIV-1-infected men, a single dose of 200 or 400 mg of fleroxacin is inadequate therapy for chancroid.

PIP: In Kenya, researchers enrolled 53, men aged 18-60 years with chancroid who enrolled at the Nairobi City Council Special Treatment Clinic in a clinical trial to test the efficacy of fleroxacin in clinical Haemophilus ducreyi infections. They randomly allocated the men the group receiving 200 mg of oral fleroxacin or the group receiving 400 mg of oral fleroxacin. 88% of the men receiving 200 mg oral fleroxacin (group 1) experienced either improvement in their clinical status or healing compared to 78% of the men receiving 400 mg oral fleroxacin. 2 of 7 (29%) patients who experienced delayed healing tested positive for HIV-1. 2 of 22 patients (9%) who healed right away were HIV-1 positive. The size of the genital ulcer had the most significant effect on healing time. The mean widest ulcer diameter was 9.5 mm in men who healed quickly while it was 18.5 mm in men who experienced a delay in healing (p .005). Microbiological cure occurred in 92% of men from group 1 and in 83% of those in group 2. The difference in microbiological failure rates of HIV-1 seropositive men and HIV-1 seronegative men approached significance (27% vs. 5%; p = .07). These results showed that a 200 or 400 mg single dose of oral fleroxacin is an efficacious treatment for men with microbiologically confirmed chancroid who are not HIV-1 infected. On the other hand, a single dose of neither 200 or 400 mg of oral fleroxacin adequately treats chancroid in HIV-1 infected men. Further study of chancroid treatment in HIV infected patients is needed, especially since chancroid may facilitate HIV transmission.

Comparison of Sheffield media with standard media for the isolation of Haemophilus ducreyi.

Isolation of Haemophilus ducreyi is the only method for the definitive diagnosis of chancroid. Culture on supplemented gonococcal base (GCHgs) or on supplemented Muller-Hinton agar (MHHb) has yielded the best isolation rates. Sheffield media is an alternative to standard media. We compared the isolation rate of H. ducreyi on GCHgs and MHHb to that on the Sheffield media with and without 5% horse blood. Vancomycin (3 mg/L) was added to all media. Of the 87 specimens cultured from patients with genital ulcer disease, 57 (66%) were positive on either GCHgs or MHHb or on both. Twenty six (30%) were positive on GCHgs only, 15 (17%) on MHHb only, and 15 (17%) on both. One culture was positive on Sheffield medium with 5% horse blood; none were positive on Sheffield medium without horse blood. Stock strains showed good growth at 48 hr on GCHgs and MHHb, but no growth at 48 hr and only minimally detectable growth at 72 hr on Sheffield media with horse blood. No growth was detected on Sheffield media without horseblood. Thus optimal culture of H. ducreyi in Kenya requires two media, supplemented gonococcal base and Muller-Hinton agar. Sheffield media is not useful for the primary isolation of H. ducreyi.

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.

Treating chancroid with enoxacin.

Increasing resistance of Haemophilus ducreyi to antimicrobials necessitates further trials of new antimicrobial agents for treating chancroid. Enoxacin has excellent in vitro activity against H ducreyi, and a randomised clinical trial of three doses of enoxacin 400 mg at intervals of 12 hours compared with a single dose of trimethoprim/sulphametrole (TMP/SMT) 640/3200 mg was therefore conducted. Of 169 men enrolled in the study, 86 received enoxacin and 83 received TMP/SMT. Ulcers were improved or cured in 65/73 men treated with enoxacin and 57/70 men treated with TMP/SMT. This difference was not significant. At 72 hours after treatment, H ducreyi was eradicated from ulcers of 72/77 men treated with enoxacin and of 67/74 of those treated with TMP/SMT. Patients with buboes responded equally well to both treatments. Of 100 H ducreyi strains tested, all were susceptible to both 0.25 mg/l enoxacin and the combination of 0.25 mg/l TMP and 5 mg/l SMT. Although most men treated with either regimen were cured, neither regimen appeared to be the optimum treatment for chancroid. This study shows the efficacy of enoxacin for a soft tissue infection caused by Gram negative organisms.

Genital ulceration as a risk factor for human immunodeficiency virus infection.

Among 115 heterosexual men who presented with genital ulcers to a sexually transmitted disease clinic in Nairobi, Kenya, the prevalence of serum antibody to HIV was 16.5%. A past history of genital ulcers was reported by 12 (63%) of 19 men with antibody to HIV versus 30 (31%) of 96 without antibody (P = 0.008). HIV infection was also positively associated with lack of circumcision, but was not associated with the etiology of the current genital ulcer. Logistic regression analysis (adjusted for age, number of recent sex partners, recent prostitute contact, circumcision, tribal ethnic identity, past history of urethritis, and current diagnoses) confirmed only the association between prior history of genital ulcer disease and HIV infection; (P = 0.04, odds ratio 2.35, 95% confidence limits, 1.01-5.47). The incidence of genital ulcers, particularly chancroid, is much higher in parts of Africa than in Europe or North America. This may contribute to the increased risk of heterosexual transmission of HIV in Africa. Aggressive control of chancroid and syphilis may offer one very feasible approach to reducing transmission of HIV in this region.

Urethral infection with Haemophilus ducreyi in men.

Carriage of Haemophilus ducreyi has not been adequately investigated in men, and its role in urethritis is unknown. In this study 456 men with H. ducreyi-culture positive genital ulcers were investigated. Among these men, 16 (3.5%) had urethritis. H. ducreyi was isolated from the urethra of nine men (1.9%). Of 57 men who had chancroid but not urethritis, none had H. ducreyi isolated from the urethra. Of 106 patients presenting with only acute urethritis, H. ducreyi was found in one. We conclude that H. ducreyi is responsible for acute urethritis in men, but that it rarely, if ever, can be cultured from the urethra of men with chancroid who do not have symptomatic urethritis.

Retrospective seroepidemiology of AIDS virus infection in Nairobi populations.

Among 446 sera from prostitutes in Nairobi, the prevalence of antibody to human immunodeficiency virus (HIV) rose from 4% in 1981 to 61% in 1985. None of 118 men with chancroid seen in 1980 had antibody to HIV compared with 15% of 107 such men in 1985. Among pregnant women, 2.0% were seropositive in 1985 versus none of 111 in 1981. Seropositive prostitutes and women with sexually transmitted diseases (STDs) tended to have more sex partners and had a higher prevalence of gonorrhoea, and in women with STDs, significantly more seropositive women practiced prostitution. Pregnant women and men with STDs who were born in the most-western region of Kenya were more likely to have antibody to HIV than were such groups from other geographic areas. Our results indicate that the AIDS virus was recently introduced into Kenya, that HIV can rapidly disseminate in a high-risk group of heterosexuals, and that prostitutes may have significantly contributed to the spread of the virus.