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.

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.

Treatment of chancroid with ciprofloxacin. A prospective, randomized clinical trial.

Chancroid is a major sexually transmitted disease in many developing countries. Although single-dose and short-course treatment of chancroid have been described, the increasing resistance of Hemophilus ducreyi to antimicrobial agents requires continuing evaluation of new therapies. Ciprofloxacin is a new quinolone antimicrobial agent with excellent in vitro efficacy against H. ducreyi. A double-blind, randomized clinical trial was conducted comparing a single-dose ciprofloxacin regimen (500 mg) and a three-day regimen of ciprofloxacin (500 mg twice daily) with a three-day regimen of trimethoprim-sulfamethoxazole (160 and 800 mg, respectively, twice daily) for the treatment of chancroid. The three-day ciprofloxacin regimen successfully eradicated H. ducreyi, and resulted in rapid clinical improvement in all 40 patients followed, with no failures. The other two regimens were also effective, but bacteriologic and clinical failure occurred in two and three patients following treatment with single-dose ciprofloxacin and three days of trimethoprim-sulfamethoxazole, respectively. All patients with buboes had resolution of lesions. There were no significant adverse effects associated with ciprofloxacin or trimethoprim-sulfamethoxazole. All three regimens are effective therapy for chancroid and H. ducreyi infections. If resistance to trimethoprim-sulfamethoxazole becomes widespread, ciprofloxacin may become a first-line therapy for chancroid. This study also demonstrates the efficacy of ciprofloxacin in soft tissue infection.

Isolation and identification of Haemophilus ducreyi in a clinical laboratory.

Routine procedures used to isolate Haemophilus ducreyi in a busy laboratory are reported. Identification was based on colony morphology and nutritional and biochemical properties of 120 fresh isolates of H. ducreyi. These isolates grew very well on Gonococcal Agar and Mueller-Hinton Agar incubated at 34 degrees C in candle extinction jars containing moistened filter paper. Colonies varied in size, giving a polymorphic appearance. They were smooth, dome-shaped, and buff-yellow to grey in colour, and measured 2 mm in diameter. They could be pushed intact across the agar surface. By microscopic examination of gram-stained smears the isolates were gram-negative coccobacilli arranged in short chains, clumps or whorls and occasionally in typical "rail track" arrangements. Individual bacteria showed bipolar staining. Colonies autoagglutinated in saline. All strains were catalase-negative and did not produce indole or H2S. They were oxidase- and beta-lactamase positive and required X but not V factor for growth. Now that reliable techniques have been developed and characteristics established it is possible for most clinical laboratories to isolate and identify this organism from most patients with chancroid.

Gonococcal drug resistance and treatment of gonorrhoea in Nairobi.

PIP: The in vitro antibiotic sensitivities of 108 isolates of Neisseria gonorrhoeae from a Nairobi clinic were determined by the agar dilution method. The results indicate that the majority of gonococci were relatively resistant to penicillin (86%) and to tetracycline (85%). By using the relationship between the in vitro antibiotic sensitivity of gonococci and treatment failure of gonorrhea in US patients, we predict that the minimum treatment failure rate for the gonorrhea treatment schemes used in the US would be 5.6% for aqueous procaine penicillin G, 4.8 megaunits intramuscularly together with 1.0 g probenecid by mouth; 6.9% for oral tetracycline HC1, given 500 mg 4 times daily for 5 days; 10.4% for a single oral dose of ampicillin, 3.5 g together with 1.0 g of oral probenecid; and 6.2% for a single dose of spectinomycin, 2.0 g intramuscularly. Gonococcal drug resistance and morbidity will likely continue to increase in Kenya in the absence of a gonorrhea control program.^ieng

Treatment of gonorrhea with single-dose thiamphenicol in Kenya.

The efficacy of a single 2.5-g dose of thiamphenicol against infection with penicillinase-producing strains of Neisseria gonorrhoeae (PPNG) or non-penicillinase-producing strains (non-PPNG) was studied in a two-phase clinical trial in Nairobi. The first phase included men who had had a urethral discharge for less than seven days, were infected with either PPNG or non-PPNG, and had not received previous treatment. The second phase included men with PPNG infections that had not responded to treatment with penicillin. The overall cure rate (determined by follow-up examinations and cultures three and ten days after treatment) was 90.6% in the first phase of the study and 92.1% in the second phase. A second 2.5-g dose of thiamphenicol was administered to four of the six patients in the second phase whose cultures yielded gonococci after the initial dose; the infections of all four patients were cured. The results of disk diffusion tests of gonococcal isolates did not correlate well with the outcome of treatment.

Parents of infants with ophthalmia neonatorum: a high-risk group for sexually transmitted diseases.

One hundred forty-nine mothers and 74 fathers of infants who presented at the Special Treatment Clinic (Nairobi) with ophthalmia neonatorum were evaluated. Neisseria gonorrhoeae was isolated from 60 (40%) of 149 mothers and Chlamydia trachomatis was isolated from 31 (21%). Twenty-six mothers (17.5%) had clinical evidence of endometritis or pelvic inflammatory disease. Mothers with endometritis and/or pelvic inflammatory disease were more often infected with N. gonorrhoeae (65%) than were mothers without these conditions (24%) (P less than or equal to .001). N. gonorrhoeae was isolated from ten (14%) and C. trachomatis from three (9%) of 32 fathers, and nongonococcal urethritis was diagnosed in an additional 21 fathers (28%). Seven of ten men with gonococcal urethritis and 18 of 21 with nongonococcal urethritis had no symptoms. These data confirm that the presence of ophthalmia neonatorum in a neonate should be considered as a strong indicator of sexually transmitted disease in the parents. Although most infections in fathers were asymptomatic, the mothers were at high risk for complications.

Single-dose therapy with trimethoprim-sulfametrole for chancroid in females.

Women with genital ulcer disease who were culture-positive for Haemophilus ducreyi were treated with a single dose of the drug combination trimethoprim-sulfametrole; the dosage was 640 mg of trimethoprim and 3,200 mg of sulfametrole. All 27 women who were treated with this regimen and adequately followed were cured. Thus a single dose of trimethoprim-sulfametrole appears to be an effective treatment regimen for women with chancroid in Kenya.

Microbiology of vaginal discharge in Nairobi, Kenya.

Among women attending a sexually transmitted disease (STD) clinic in Nairobi with vaginal discharge, Neisseria gonorrhoeae and Chlamydia trachomatis were isolated from the cervix in 32 (26%) of 122 and four (7%) of 58 women respectively. Infection with Trichomonas vaginalis, Candida albicans, Gardnerella vaginalis, and Mycoplasma spp were diagnosed in 42 of 122 (34%), 26 of 110 (24%), 75 of 100 (75%), and 42 of 89 (47%) women respectively. Mixed infections with at least two pathogens were found in 23 (26%) of 89 women examined for all microorganisms. Infection with N gonorrhoeae was significantly associated with abdominal pain.

Single-dose ceftriaxone for chancroid.

Men with genital ulcers that were culture positive for Haemophilus ducreyi were treated with intramuscular ceftriaxone and randomized to three different dose regimens. All but 1 of 50 men treated with 1 g of intramuscular ceftriaxone were cured. Similarly, 0.5 and 0.25 g cured 43 of 44 men and 37 of 38 men, respectively. A single dose of 250 mg of intramuscular ceftriaxone is an effective treatment for chancroid.

Genital ulcers in Kenya. Clinical and laboratory study.

Of 97 patients with genital ulcers attending a special treatment clinic in Nairobi, Kenya, 60 harboured Haemophilus ducreyi, four herpes simplex virus, and five Neisseria gonorrhoeae. Eleven patients had serological evidence of syphilis; of these one case was confirmed by darkfield microscopy. In the remaining cases no aetiological agent was identified. An enriched chocolate agar with vancomycin and serum was a useful medium for primary isolation of H ducreyi. Tetracycline was generally ineffective in the treatment of ulcers, but sulfadimidine was successful in almost 80% of cases.

Epidemiology of chancroid and Haemophilus ducreyi in Nairobi, Kenya.

Of 300 men in Nairobi, Kenya, with culture-proven chancroid, 57% had acquired infection from prostitutes. The majority of infections were acquired in the city of Nairobi. All 10 female source contacts examined had genital ulcers. 13 of 29 female secondary contacts were culture-positive for Haemophilus ducreyi and 10 of these infected women had clinical chancroid. Of 122 prostitutes from the middle and lower social strata, 12 had genital ulcers, 5 of which were culture-positive for H ducreyi, and a further 5 had symptomless genital carriage of H ducreyi. Prostitutes are a major reservoir of H ducreyi in Nairobi. No evidence of transmission of H ducreyi by women without clinical chancroid was detected.

Prostitutes are a major reservoir of sexually transmitted diseases in Nairobi, Kenya.

Prostitutes are a major reservoir of sexually transmitted diseases in many developing nations. In Nairobi we found that 16%, 28%, and 46%, respectively, of upper-, middle-, and lower-social strata prostitutes were infected with Neisseria gonorrhoeae. Genital ulcers and infections with Haemophilus ducreyi were more prevalent among prostitutes of the middle and lower social strata. A group of 97 prostitutes of the lower social strata were followed longitudinally to determine the rate of reinfection with N. gonorrhoeae. The mean time to acquisition of a new infection was 12.0 +/- 9.2 days. These results show that in Nairobi prostitutes are a readily identifiable group of high-frequency transmitters of gonococcal infection. Strategies based on intervention in the prostitute reservoir could prove to be an effective means of control of gonococcal infections in developing nations.

Treatment of chancroid. A comparison of sulphamethoxazole and trimethoprim-sulphamethoxazole.

Since sulphonamides are no longer predictably effective in the treatment of chancroid the combination of trimethoprim-sulphamethoxazole (TMP-SMX) was evaluated to identify other effective regimens. One hundred and nine patients with genital ulcers (75 men and 34 women) seen at the Special Treatment Clinic in Nairobi, Kenya, were randomly assigned to treatment with a seven day course of either sulphamethoxazole 1000 mg twice daily or trimethoprim (160 mg)-sulphamethoxazole (800 mg) (TMP-SMX) twice daily. Haemophilus ducreyi was isolated from the ulcer in 57 patients (33 men and 24 women). 16 patients were subsequently diagnosed serologically as having syphilis. No aetiological diagnosis was made in 40 patients. Treatment with sulphamethoxazole failed in five of 21 (24%) culture positive patients who were available for evaluation after seven days, whereas all 19 of such patients who were treated with TMP-SMX responded to treatment. Of the 21 isolates available for susceptibility testing, all were susceptible to trimethoprim alone (MIC less than 0.5 mg/l) and three were resistant to sulphonamides, all three containing a 4.9 megadalton (Mdal) plasmid. Two of the three patients from whom these isolates had been obtained were treated with sulphamethoxazole and both were clinical and bacteriological failures. Five of six patients with sulphonamide-susceptible H ducreyi responded to treatment with sulphamethoxazole. Failure of sulphonamides to eradicate H ducreyi in some patients with chancroid is associated with the presence of a sulphonamide resistant plasmid. In regions where this plasmid is present in H ducreyi TMP-SMX is the preferred treatment for chancroid.

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.

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.

The clinical diagnosis of genital ulcer disease in men in the tropics.

Since the clinical diagnosis of genital ulcers without laboratory confirmation is not reliable in developed countries, we postulated that clinical diagnosis alone would be no more reliable in developing countries. A presumptive clinical diagnosis of chancroid, genital herpes, syphilis, or lymphogranuloma venereum was made for 100 male patients at the Special Treatment Clinic in Nairobi, Kenya. This diagnosis was then compared to the final diagnosis determined by laboratory identification of the pathogen, by culture, or by serologic response. In 64 patients, a final diagnosis of either chancroid, syphilis, or genital herpes was established. The diagnostic accuracy varied from 75% for chancroid to 42% for syphilis and 43% for herpes. The overall diagnostic accuracy was 66%. The predictive values of positive clinical diagnoses were 84% for chancroid, 60% for syphilis, and 75% for herpes. Thus, clinical diagnosis of genital ulcer disease was not sufficiently reliable in this study.

Antimicrobial therapy of chancroid: an evaluation of five treatment regimens correlated with in vitro sensitivity.

One hundred fifty-one men with genital ulcer disease were assigned randomly to treatment with one of five oral antimicrobial regimens: (1) sulfadimidine (1 g four times daily for seven days); (2) tetracycline (500 mg four times daily for seven days); (3) trimethoprim-sulfamethoxazole (TMP-SMZ; 160 mg of TMP and 800 mg of SMZ twice daily for seven days); (4) doxycycline (300 mg as a single dose); or (5) TMP-sulfametrole (640 mg of TMP and 3,200 mg of sulfametrole once as a single dose). Haemophilus ducreyi was isolated from 81 (54%) of the men, and 35 strains were available for testing of antimicrobial susceptibility. The TMP-SMZ and TMP-sulfametrole regimens were more effective than sulfadimidine, tetracycline, or single-dose doxycycline in curing ulcers. Only one of 35 strains tested was susceptible to tetracycline (less than or equal to 8 mg/liter), and only ten of 35 strains were susceptible to doxycycline (less than or equal to 4 mg/liter), whereas all were susceptible to trimethoprim (less than or equal to 2 mg/liter). The correlation between in vitro susceptibility and bacteriologic response to the antimicrobial agents requires further investigation. In particular, sulfonamide resistance did not always identify failure to respond to sulfadimidine.

Clinical and microbiologic studies of genital ulcers in Kenyan women.

The etiology of genital ulcers in women in tropical regions is poorly understood. Eighty-nine women, presenting to a sexually transmitted disease clinic in Nairobi (Kenya) with a primary complaint of genital ulcers, were evaluated prospectively in a clinical and laboratory study. A final etiologic diagnosis was possible for 60 (67%) of the women. Culture for Haemophilus ducreyi was positive for 43 women, eight had secondary syphilis with ulcerated condyloma latum, three had primary syphilis, one had both chancroid and syphilis, two had moniliasis, two had herpetic ulceration, and one had a traumatic ulcer. The clinical characteristics that best distinguished chancroid from secondary syphilis were ulcer excavation and a rough ulcer base. No etiologic diagnosis was established for 29 patients. However, the clinical and epidemiologic features of these patients suggested that they were similar if not identical to the patients with H. ducreyi culture-positive chancroid. Further studies are necessary to determine the etiology of ulcers in females in whom no pathogen was identified.