Biomedical subjects
Publications and source records attributed to A R Ronald.
Waning interest in urinary tract infection (UTI) research has limited clinical advances during the past two decades. Although care has improved for some specific UTI syndromes, there is limited evidence for most of the decisions made each day in the management of these infections. Additional clinical research is necessary to improve UTI prevention and care strategies.
Our objectives were to describe the baseline findings of a trial of antibiotic prophylaxis to prevent sexually transmitted infections (STIs) and HIV-1 in a cohort of Nairobi female sex workers (FSWs). A questionnaire was administered and a medical examination was performed. HIV-negative women were randomly assigned to either one gram azithromycin or placebo monthly. Mean age of the 318 women was 32 years, mean duration of sex work 7 years and mean number of clients was 4 per day. High-risk behaviour was frequent: 14% practised anal intercourse, 23% sex during menses, and 3% used intravenous drugs. While 20% reported condom use with all clients, 37% never use condoms. However, STI prevalence was relatively low: HIV-1 27%, bacterial vaginosis 46%, Trichomonas vaginalis 13%, Neisseria gonorrhoeae 8%, Chlamydia trachomatis 7%, syphilis 6% and cervical intraepithelial neoplasia (CIN) 3%. It appears feasible to access a population of high-risk FSWs in Nairobi with prevention programmes, including a proposed trial of HIV prevention through STI chemoprophylaxis.
A randomized, double-blind, placebo-controlled clinical trial was conducted in Nairobi, Kenya, to compare single-dose ciprofloxacin with a 7-day course of erythromycin for the treatment of chancroid. In all, 208 men and 37 women presenting with genital ulcers clinically compatible with chancroid were enrolled. Ulcer etiology was determined using culture techniques for chancroid, serology for syphilis, and a multiplex polymerase chain reaction for chancroid, syphilis, and herpes simplex virus (HSV). Ulcer etiology was 31% unmixed chancroid, 23% unmixed syphilis, 16% unmixed HSV, 15% mixed etiology, and 15% unknown. For 111 participants with chancroid, cure rates were 92% with ciprofloxacin and 91% with erythromycin. For all study participants, the treatment failure rate was 15%, mostly related to ulcer etiologies of HSV infection or syphilis, and treatment failure was 3 times more frequent in human immunodeficiency virus-infected subjects than in others, mostly owing to HSV infection. Ciprofloxacin is an effective single-dose treatment for chancroid, but current recommendations for empiric therapy of genital ulcers may result in high treatment failure due to HSV infection.
OBJECTIVE: To evaluate the accuracy and costs of newer rapid human immunodeficiency virus (HIV) antibody tests in primary health care settings in rural Zambia. METHODS: Three rural hospitals participated in this study. During a baseline assessment period, HIV testing practices were recorded on 250 consecutive clients at each hospital. Baseline evaluation was compared with 250 subsequent consecutive clients tested using a testing algorithm consisting of an initial screening HIV Dipstick test (McDonald Scientific [PVT] Limited, Harare, Zimbabwe) followed by confirmatory testing of all reactive specimens using the HIV Capillus test (Cambridge Diagnostics, Galway, Ireland), in conformity with World Health Organization HIV testing recommendations. Quality control was performed at a national university teaching hospital laboratory. RESULTS: A total of 1,500 clients was entered, with an HIV seropositivity rate of 53.2%. Most HIV testing was performed on patients with signs and symptoms suggestive of HIV infection. Same-day results were provided for only 16%. The HIV Dipstick testing algorithm sensitivity was 96.9%, and specificity was 98.0%. Counselor dissatisfaction was greater with the Dipstick algorithm as a result of 5.3% discordant results. Use of the HIV Dipstick testing algorithm cost between US $3.00 and US $3.80 per client tested. CONCLUSIONS: The accuracy of HIV testing in unsophisticated rural laboratories in Zambia is acceptable. Although HIV Dipstick testing algorithm costs were relatively high for a developing country, this HIV testing procedure is currently the most economical method available in Zambia. Accurate, less costly HIV testing algorithms are still needed.
OBJECTIVES: Globally approximately 25% of men are circumcised for religious, cultural, medical, or parental choice reasons. However, controversy surrounds the procedure, and its benefits and risks to health. We review current knowledge of the health benefits and risks associated with male circumcision. METHODS: We have used, where available, previously conducted reviews of the relation between male circumcision and specific outcomes as "benchmarks", and updated them by searching the Medline database for more recent information. RESULTS: There is substantial evidence that circumcision protects males from HIV infection, penile carcinoma, urinary tract infections, and ulcerative sexually transmitted diseases. We could find little scientific evidence of adverse effects on sexual, psychological, or emotional health. Surgical risks associated with circumcision, particularly bleeding, penile injury, and local infection, as well as the consequences of the pain experienced with neonatal circumcision, are valid concerns that require appropriate responses. CONCLUSION: Further analyses of the utility and cost effectiveness of male circumcision as a preventive health measure should, in the light of this information, be research and policy priorities. A decision as to whether to recommend male circumcision in a given society should be based upon an assessment of the risk for and occurrence of the diseases which are associated with the presence of the foreskin, versus the risk of the complications of the procedure. In order for individuals and their families to make an informed decision, they should be provided with the best available evidence regarding the known benefits and risks.
We aimed to determine if the clinical and histological features of chancroid are altered by HIV infection. Male patients presenting to the Nairobi special treatment clinic with a clinical diagnosis of chancroid were eligible for the study. A detailed history, physical examination, swabs for Haemophilus ducreyi culture and blood for HIV serology, syphilis serology and CD4 counts were obtained from all patients. Punch biopsies from an ulcer were obtained from 10 patients and either fixed in 10% formalin or snap frozen in Optimum Cutting Temperature (OCT) medium compound at -70 degrees C. Patients were treated with erythromycin and followed for 3 weeks. Chi-square and Student's t-test were used to determine if the clinical and laboratory features of chancroid differed between HIV-seropositive and seronegative individuals. Cox regression survival analysis was used to determine if HIV infection altered cure rates of chancroid at 21 days. Immunohistochemical staining was performed using lymphocytic and macrophage markers and tissue sections were analysed by 2 pathologists in a blinded manner. Between February and November 1994, 109 HIV-seropositive and 211 HIV-seronegative individuals were enrolled in the study. HIV patients had ulcers of longer duration than HIV-seronegative patients (P=0.03). Although cure rates were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% v 54%, P=0.002). A dense interstitial and perivascular inflammatory infiltrate extending from the reticular to deep dermis was present in all biopsies. This consisted of equal amounts of CD4 and CD8 T-lymphocytes as well as macrophages. The histological and immunohistochemical picture was identical for HIV-positive and negative patients. HIV infection slows the healing rates of chancroid ulcers despite appropriate antibiotic therapy. This clinical difference cannot be attributed to an altered histopathological response to HIV infection. Additional studies are needed to elucidate the mechanisms responsible for this finding.
Urinary infections complicated by structural anomalies, metabolic alterations, abnormalities of host response, or unusual or difficult-to-treat pathogens commonly occur in our practices. Therapeutic regimens for most of these patient populations are empiric and unproven. Our understanding of specific microbial virulence factors is inadequate. Until well-designed interventions are proven, management strategies will depend on clinical biases and "trial and error" therapeutic attempts. Presumably, over the course of the next decade, better answers will emerge that will improve our ability to prevent and more adequately manage our patients with complicated UTIs.
The factors responsible for the explosive spread of human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa continue to be identified and debated. One of the most controversial factors has been male circumcision. This cross-sectional study was conducted to measure the association between circumcision status and infection with HIV-1 among men with genital ulcer disease. Eight hundred and ten men participated in the study, of whom 190 (23%) were HIV-1-positive. A logistic regression model adjusted for behavioral and historical showed that HIV-1 positivity was independently associated with being uncircumcised (adjusted odds ratio [OR], 4.8; 95% confidence interval [CI], 3.3-7.2) and with a history of urethral discharge (adjusted OR, 2.0; 95% CI, 1.4-2.8). This association could not be explained by measures of sexual exposure to HIV-1 among this population. Male circumcision should be considered as an intervention strategy for AIDS control.
We conducted a prospective observational study to determine the clinical features, the degree of immunosuppression, and the prevalence of human immunodeficiency virus type 1 (HIV-1) infection associated with herpes zoster in Kenya. The study included 196 HIV-1 positive individuals and 34 HIV-1 negative individuals between the ages of 16 and 50 years who presented to a referral clinic in Nairobi. Comparison of the clinical characteristics in the two groups found that the duration of illness in the HIV-1-positive group was longer (32 vs. 22 days; P < .001) and that the HIV-1-positive group was more likely to have generalized lymphadenopathy (74% vs. 3%; OR: 12.2; 95% CI: 1.6, 91.7), severe pain (69% vs. 39%; OR: 3.6; 95% CI; 1.7, 7.6), bacterial superinfection (15% vs. 6%; OR: 5.7; 95% CI: 1.3, 25.0), and more than one affected dermatome (38% vs. 18%; OR: 2.8; 95% CI: 1.1, 8.0). Dermatomal distribution of the lesions was similar in the two groups, except for cranial lesions, which occurred exclusively in the HIV-1-positive group. The mean CD4 T lymphocyte count at presentation was 333/mm(3) in the HIV-1-positive group and 777/mm(3) in the HIV-1-negative group (P < .001). Herpes zoster is often recognized as the initial HIV-1-related illness in Kenya despite the fact that patients have moderate to severe depression of CD4 cell counts at presentation. Although the clinical features of herpes zoster may be more severe in HIV-1-positive individuals, recovery is generally complete and uncomplicated.
HIV-1 is spreading rapidly through heterosexual intercourse in many societies. Slowing the transmission of this virus is the most urgent global public health priority. Our understanding of the biologic differences between societies that account for most vacancies in heterosexual HIV transmission are now understood. Effective interventions to slow transmission must be designed, implemented, and evaluated. Human and fiscal resources must be provided through a shared global effort. The consequences of failing to do so will lead to a world catastrophe of unprecedented magnitude.
Haemophilus ducreyi is the commonest cause of genital ulcer disease in Africa and is associated with heterosexual transmission of human immunodeficiency virus(HIV). The World Health Organization currently recommends erythromycin 500 mg three times a day for seven days as the treatment of choice for Haemophilus ducreyi infection. We studied the effectiveness of a lower dose erythromycin treatment regime, 250 mg three times a day for seven days in the treatment of chancroid. Patients with genital ulcer disease presenting at Nairobi City council clinic between January and March, 1992 were recruited into the study. Swabs were taken from the ulcers for Haemophilus ducreyi and venous blood was screened for syphilis and HIV antibodies. A total of 219 patients were enrolled for the study and were reviewed on days seven and fourteen for side effects, bacteriological and clinical cure rates. 26.4% of the study population were HIV-1 seropositive. The treatment regime was well tolerated and effective in both HIV seropositive and seronegative patients. Complete bacteriological cure rate was achieved in Haemophilus ducreyi culture positives by day seven irrespective of the HIV serostatus. However, the clinical cure rate for HIV seropositive patients was 88% compared to 99% for seronegative patients (p<.001). It is concluded that a low dose erythromycin is an inexpensive and effective treatment for chancroid with complete bacteriological cure rate, although the healing process takes longer in HIV seropositive patients.
The sexual transmission of human immunodeficiency virus type 1 (HIV-1) continues at an alarming rate in sub-Saharan Africa despite the fact that awareness of AIDS is high. One explanation for this alarming rate may be that individuals do not believe that they are personally at risk for AIDS and are not sufficiently motivated to make changes in their behavior. We conducted a cross-sectional study of men with genital ulcer disease to assess their sexual behavior and their perceived risk of AIDS. We studied 787 men between the ages of 17 and 54 years who presented to a referral clinic for sexually transmitted diseases (STDs) in Nairobi, Kenya. Of these 787 men, 188 (24%) were infected with HIV-1. Awareness of AIDS was essentially universal in this population; however, only 64 men (8%) thought that they were personally at risk of developing AIDS. A logistic regression analysis found that men who believed they were personally at risk knew someone with AIDS (odds ratio [OR], 8.9; 95% confidence interval [CI], 4.0-19.7), received information about AIDS from television or video (OR, 3.0; 95% CI, 1.7-5.5), or had previously had an STD (OR, 2.2; 95% CI, 1.2-4.1). Except for a modest increase in condom use, there was no significant difference in sexual behavior between the group who considered themselves to be at risk for AIDS and the group who did not consider themselves to be at risk. The results of this study challenge the current strategies on HIV/AIDS education and prevention for urban men in Kenya.
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.
Fleroxacin was prescribed to treat both HIV-negative and HIV-positive men with proven chancroid in an open study. HIV-negative men were treated with a single 400-mg dose of fleroxacin, and HIV-positive men were treated with 400 mg daily for 5 days. Three of the 58 evaluable HIV-negative men were clinical and microbiologic failures, and two of the 22 evaluable HIV-positive men had persisting infection with Haemophilus ducreyi. Both regimens were well tolerated. Fleroxacin is an acceptable alternative to existing treatment regimens for chancroid in men.
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Ceftriaxone in a dose of 250 mg given intramuscularly is currently recommended for the treatment of chancroid. Among 133 men in Nairobi, Kenya, with culture-proven chancroid, who were treated with ceftriaxone, treatment failed in 35%. Poor outcome was associated with human immunodeficiency virus type 1 seropositivity. Thus, treatment recommendations for chancroid should be reevaluated.
The humoral immune response to purified lipooligosaccharide (LOS) and outer membrane proteins (OMP) of Haemophilus ducreyi was evaluated. Sera from chancroid-endemic (Uganda, Kenya) and -nonendemic (Canada) countries were tested by an ELISA. The response to OMPs was cross-reactive with other Haemophilus species, and elevated levels of antibody were detected in patients that did not have chancroid. The LOS component stimulated an H. ducreyi-specific immune response that was detected only in patients with chancroid. The sensitivity of the LOS ELISA was 96% (95% confidence interval, 89.9%-100%) and the specificity was 97% (95% confidence interval, 95.8%-98.2%). Thus, the anti-H. ducreyi LOS immune response is a significant diagnostic and epidemiologic indicator.
Therapeutic standards have not been well defined for many forms of bacterial urinary tract infection. In women with uncomplicated infections, these exist for bacterial cystitis and for acute pyelonephritis. For most other categories of illness, among patients with complicated infections, no treatment regimens have been determined. As a result, well-designed clinical trials for these patient populations should be a priority.