Vitamin A and risk of HIV-1 seroconversion among Kenyan men with genital ulcers.

BACKGROUND: Vitamin A is involved in normal immune function and the maintenance of mucosal integrity through complex effects on cellular differentiation. OBJECTIVE: We sought to determine whether serum vitamin A levels were associated with altered susceptibility to primary infection with HIV-1 in men with high-risk sexual behaviour and genital ulcers who presented for treatment at an STD clinic in Nairobi, Kenya. METHODS: HIV-1 seronegative men were prospectively followed. Vitamin A levels at study entry were compared among 38 men who HIV-1 seroconverted versus 94 controls who remained HIV seronegative. RESULTS: Vitamin A deficiency (retinol less than 20 microg/dl) was very common and was present in 50% of HIV-1 seroconverters versus 76% of persistent seronegatives. Seroconversion was independently associated with a retinol level greater than 20 microg/dl (HR 2.43, 95% CI 1.25-4.70, P = 0.009), and a genital ulcer aetiology caused by Haemophilus ducreyi (HR 3.49, 95% CI 1.03-11.67, P = 0.04). Circumcision was independently associated with protection (HR 0.46, 95% CI 0.23-0.93, P = 0.03). CONCLUSION: Vitamin A deficiency was not associated with an increased risk of HIV-1 infection among men with concurrent STD. A decreased risk of HIV-1 seroconversion was independently associated with lower retinol levels. The effects of vitamin A on macrophage and lymphoid cell differentiation may paradoxically increase mucosal susceptibility to HIV-1 in some vulnerable individuals, such as men with genital ulcers. Lack of circumcision and chancroid are confirmed as important co-factors for heterosexual HIV-1 transmission. The role of vitamin A in heterosexual HIV-1 transmission requires further study.

Clinical and in situ cellular responses to Haemophilus ducreyi in the presence or absence of HIV infection.

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.

PIP: Chancroid is caused by infection with Hemophilus ducreyi, and is associated with an increased risk for the sexual transmission of HIV-1. The authors assessed whether the clinical and histological features of chancroid are changed by HIV infection, using 320 male patients who presented during February-November 1994 to the City of Nairobi Special Treatment Clinic with a clinical diagnosis of chancroid. 109 subjects were HIV seropositive and 211 were HIV seronegative. A detailed history, physical examination, swabs for Hemophilus 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 Celsius. Patients were treated with erythromycin and followed for 3 weeks. HIV patients had ulcers of longer duration than did HIV-seronegative patients. Although cure rates were similar at 3 weeks, HIV patients had lower cure rates at 1 week (23% vs. 54%). A dense interstitial and perivascular inflammatory infiltrate extending from the reticular to deep dermis was present in all biopsies. The infiltrate 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 HIV-negative patients. Study findings therefore indicate that HIV infection slows the healing rates of chancroid ulcers despite appropriate antibiotic therapy. The clinical difference cannot be attributed to an altered histopathological response to HIV infection.

Genital ulcer disease among STD clinic attenders in Nairobi: association with HIV-1 and circumcision status.

In previous studies, genital ulcers in men have been found to be associated with increased risk of HIV-1 seroconversion. To further explore this association male patients attending a sexually transmitted disease (STD) clinic in Nairobi for either urethritis (controls, n = 276) or a genital ulcer (cases, n = 607) were compared with respect to sexual behaviour, presence of HIV-1 antibody and circumcision status. Patients were followed to study risk factors for incident genital ulcers and HIV-1 seroconversion. At entry, being married was associated with higher prevalence of HIV-1 (OR = 1.76) and genital ulcers (OR = 1.42). Lack of circumcision was associated with both HIV-1 infection (OR = 4.67) and the presence of a genital ulcer (OR = 2.23). Genital ulcers were also associated with HIV-1 infection (OR = 1.87) independent of circumcision status. On follow-up, HIV-1 seropositivity was associated with incident genital ulcers. It is argued that the association between genital ulcers and HIV-1 infection may be more complex than ulcers simply being a risk factor for HIV-1 infection, and that HIV-1 infection may either increase the risk of acquiring a genital ulcer, or HIV-1 infection and genital ulcers may have some unknown risk factor in common.

PIP: Male patients (mean age, 28 years) attending a sexually transmitted disease clinic in Nairobi, Kenya, for either urethritis (276 controls) or a genital ulcer (607 cases) were compared with respect to sexual behavior, presence of HIV-1 antibody, and circumcision status. Only 164 men were not circumcised. Circumcised men reported more life-time sex partners than uncircumcised men (19 vs. 10, p 0.01). Patients were followed up for 196 days to explore the risk factors for incident genital ulcers and HIV-1 seroconversion. On average, 2.66 follow-up visits per patient were recorded. 28 men seroconverted to HIV-1 during follow-up. 61% of the ulcer patients reported sex workers as the likely source of their infection, whereas 58% of the urethritis patients did so. Multiple logistic regression variables of marital status, age, and genital ulcer in the past were used to examine the relationship among these variables. Ulcer in the past was a significant predictor of a current ulcer (p 0.01) and higher age was significantly associated with HIV-1 seropositivity (p 0.01). At entry, being married was associated with higher prevalence of HIV-1 (odds ratio [OR] = 1.76) and genital ulcers (OR = 1.42). Lack of circumcision was associated with both HIV-1 infection (OR = 4.67) and the presence of a genital ulcer (OR = 2.3). 68 men acquired a new ulcer during follow-up. HIV-1 seropositivity at enrolment was significantly associated with genital ulcer reinfection (relative risk = 3.63 by Cox's regression). Genital ulcers were also associated with HIV-1 infection (OR = 1.87) independent of circumcision status. On follow-up, HIV-1 seropositivity was associated with incident genital ulcers. The association between genital ulcers and HIV-1 infection may be more complex than ulcers' simply being a risk factor for HIV-1 infection: either HIV-1 infection may increase the risk of acquiring a genital ulcer or HIV-1 infection and genital ulcers may have some unknown risk factor in common.

A morphological study of penile chancroid lesions in human immunodeficiency virus (HIV)-positive and -negative African men with a hypothesis concerning the role of chancroid in HIV transmission.

Chancroid, the most common cause of genital ulceration in Africa, is known to be associated epidemiologically with heterosexual transmission of human immunodeficiency virus (HIV). The pathophysiological mechanisms by which chancroid might facilitate the spread of HIV are obscure. To investigate the role of chancroid in HIV transmission, the authors studied the histological features of biopsies from 11 men with penile chancroid lesions including five who were serologically positive for HIV. The histomorphologic and immunophenotypic nature of the inflammatory infiltrates suggests that there is a significant role for cell-mediated immunity in the host response to Hemophilus ducreyi infection. This response may be critical to the role of chancroid in HIV transmission.

An immunohistochemical analysis of naturally occurring chancroid.

Haemophilus ducreyi is a major cause of genital ulcer disease in many developing countries and is associated with augmented transmission of human immunodeficiency virus (HIV). However, the mechanisms through which H. ducreyi produces ulceration are poorly understood. The characteristics of the host response to H. ducreyi and the pathobiology of its potential contribution to increased HIV susceptibility are not known. Chancroid ulcer biopsies from 8 patients were analyzed histologically and immunohistochemically. All biopsies had perivascular and interstitial mononuclear cell infiltrates that extended deep into the dermis. The infiltrate, which contained macrophages and CD4 and CD8 lymphocytes, was consistent with a delayed hypersensitivity type cell-mediated immune response. The recruitment of CD4 T lymphocytes and macrophages may in part explain the facilitation of HIV transmission in patients with chancroid.

Lesions of primary and secondary syphilis contain activated cytolytic T cells.

This study demonstrates that CD8+ cytotoxic lymphocytes (CTL) are found in both primary and secondary syphilis lesions. CD8+ T cells were detected by immunohistology, and mRNAs for granzyme B and perforin were detected by reverse transcription and PCR, suggesting that CD8+ cytotoxic lymphocytes are activated.

Primary and secondary syphilis lesions contain mRNA for Th1 cytokines.

Phagocytosis of Treponema pallidum by cytokine-activated macrophages aids bacterial clearance and lesion resolution in early syphilis. To investigate the cytokine profiles of cells infiltrating primary and secondary syphilis lesions, reverse transcription and polymerase chain reaction (RT-PCR) were used to detect cytokine mRNA in 13 lesion biopsies. Both primary and secondary lesions contained mRNA encoding interleukin (IL)-2, interferon-gamma (IFN-gamma), IL-12p40, and IL-10. In contrast to a lesion from a patient with recurrent herpes simplex virus type 2, no message for IL-4 could be detected in any of the syphilis lesions, and 10 of 13 had no mRNA for IL-5 or IL-13. These findings are consistent with a Th1-predominant local cellular response activating macrophages and support the hypothesis that IFN-gamma-activated macrophages are primary effectors in treponeme clearance.

Herpes zoster as the initial presentation of human immunodeficiency virus type 1 infection in Kenya.

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.

Leukocyte esterase urine strips for the screening of men with urethritis--use in developing countries.

BACKGROUND AND OBJECTIVES: The leukocyte esterase (LE) strip is a useful tool for the screening of men with urethritis. In developing countries, where laboratory facilities are limited, and sexually transmitted diseases endemic, simple and inexpensive diagnostic tests which perform well, would be of great value. METHODS: Men presenting with urethritis to a referral clinic for sexually transmitted diseases in Nairobi, Kenya participated in this cohort analytical study. First-void urine was collected for LE dipstick testing as part of the diagnostic work-up. The results of the dipstick measurement were compared with the laboratory detection of Chlamydia trachomatis and Neisseria gonorrhoeae. RESULTS: Of 200 men with symptoms of urethritis, 33 (17%) had a pathogen detected from the urethra or the urine. Chlamydia was detected in urine by PCR in 22 (11%), and gonorrhoea was cultured from the urethra in 11 (6%). Esterase activity (trace or greater) had a sensitivity of 76%, a specificity of 80%, a positive predictive value of 42% and a negative predictive value of 94% for the presence of chlamydia or gonorrhoea. CONCLUSIONS: The use of the LE dipstick for the screening of men with symptomatic urethritis can improve diagnostic accuracy and reduce the amount of empiric antimicrobial therapy. The low detection rate of chlamydia in these men with a clinical diagnosis of nongonococcal urethritis needs further study.