Etiologic pattern of genital ulcers in Lusaka, Zambia: has chancroid been eliminated?

BACKGROUND: Genital ulcers are a public health problem in developing countries. The World Health Organization recommends the use of syndromic guidelines for sexually transmitted infection treatment in resource-constrained countries. Monitoring local etiologies provides information that may aid policy for sexually transmitted infection treatment. We investigated the etiology of genital ulcer disease among outpatients in Lusaka, Zambia. METHODOLOGY: Swabs from genital ulcers of 200 patients were tested using polymerase chain reaction for Treponema pallidum, herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), Haemophilus ducreyi, and Chlamydia trachomatis. RESULTS: The prevalence of the detected pathogens was as follows; HSV-2, 28%; T. pallidum, 11.5%; C. trachomatis, 3%; HSV-1, 0.5%; and H. ducreyi, 0%. Coinfection with HSV-2 and T. pallidum was 1.5%, and coinfection of HSV-2 and C. trachomatis was 1%. In 55% of the patients, no etiologic diagnosis could be established. CONCLUSIONS: H. ducreyi was not detected, whereas HSV-2 and T. pallidum were the commonest pathogens. Nondetection of H. ducreyi requires further studies. If the present findings are validated, treatment guidelines would require to be revised in Zambia.

Trends in the relative prevalence of genital ulcer disease pathogens and association with HIV infection in Johannesburg, South Africa, 2007-2015.

BACKGROUND: In South Africa, treatment of genital ulcer disease (GUD) occurs in the context of syndromic management. GUD aetiological studies have been conducted in Johannesburg since 2007. We report on GUD pathogen prevalence, sero-prevalence of STI co-infections and aetiological trends among GUD patients presenting to a community-based primary healthcare facility in Johannesburg over a 9-year period. METHODS AND FINDINGS: GUD surveys were conducted from January to April each year. Consecutive genital ulcers were sampled from consenting adults. Swab-extracted DNA was tested by multiplex real-time PCR assays for herpes simplex virus (HSV), Treponema pallidum (TP), Haemophilus ducreyi (HD) and Chlamydia trachomatis (CT). HSV-positive DNA extracts were further subtyped into HSV-1 and HSV-2 using a commercial PCR assay; CT-positive extracts were tested with an in-house PCR assay specific for serovars L1-L3 (lymphogranuloma venereum). Sera were tested for HIV, HSV-2, and syphilis co-infections. Giemsa-stained ulcer smears were screened for Klebsiella granulomatis by microscopy. Data were analysed with STATATM version 14. Of 771 GUD specimens, 503 (65.2%) had a detectable pathogen: HSV 468 (60.7%); TP 30 (3.9%); CT L1-3 7 (0.9%); HD 4 (0.5%). No aetiological agents were detected in 270 (34.8%) ulcer specimens. Seroprevalence rates were as follows: HIV 61.7%; HSV-2 80.2% and syphilis 5.8%. There was a strong association between GUD pathogen detection and HIV seropositivity (p < 0.001); 68% of cases caused by HSV were co-infected with HIV. There was a significant decline in the relative prevalence of ulcer-derived HSV over time, predominantly from 2013-2015 (p-value for trend = 0.023); and a trend towards a decrease in the HIV seropositivity rate (p-value for trend = 0.209). CONCLUSIONS: HSV remains the leading cause of pathogen-detectable GUD in South Africa. The prevalence of HIV co-infection among GUD patients is high, underlining the importance of linkage to universal HIV testing and treatment in primary healthcare settings.

Sexually Transmitted Infections.

Sexually transmitted infections (STIs) remain a significant burden on public health in the United States. Primary prevention counseling with early diagnosis and treatment remain the best methods to decrease the incidence of STIs. Through significant public heath interventions, the incidence of gonorrhea, Chlamydia, and trichomoniasis is decreasing; however, the incidence of primary and secondary syphilis is increasing. Human papilloma virus remains the most common STI, but new vaccinations have the possibility of having a significant impact on this virus's disease potential. This review discusses the most common STIs in the United States, focusing on clinical presentation, diagnosis, and treatment.

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.

HIV-2 infection among prostitutes working in The Gambia: association with serological evidence of genital ulcer diseases and with generalized lymphadenopathy.

Three hundred and fifty-five prostitutes working in The Gambia were enrolled in a study of retroviral infections. Eight-seven (24.6%) were infected with HIV-2 only, two (0.6%) with HIV-1 only, four (1.1%) had sera showing double HIV-1/HIV-2 reactivity, and 37 (10.4%) were seropositive for HTLV-I. After allowing for socioeconomic and serological variables in a multivariate analysis, HIV-2 infection was associated with serological evidence of a previous episode of syphilis [a rapid plasma reagin (RPR) positive/Treponema pallidum haemagglutination assay (TPHA) positive; odds ratio (OR) = 2.18, 95% confidence interval (CI) = 1.19-3.98], with having antibodies against Haemophilus ducreyi (OR = 2.05, 95% CI = 0.89-4.70) or against HTLV-I (OR = 2.17, 95% CI = 0.91-5.19). HIV-2-seropositive prostitutes were three times more likely [17 out of 78 (22%) versus 15 out of 219 (7%), P less than 0.001] to have generalized lymphadenopathy than those who were seronegative. These data suggest that genital ulcer diseases may facilitate the transmission of HIV-2, and that HIV-2 rapidly induces the appearance of generalized lymphadenopathy in a substantial proportion of infected individuals.

Fleroxacin in the treatment of chancroid: an open study in men seropositive or seronegative for the human immunodeficiency virus type 1.

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.

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.

Sexually transmitted diseases in HIV-infected persons.

It appears incontestable that there is a link between genital ulcer disease and HIV infection. On the one hand the natural history and response to therapy of syphilis, HSV-2, and chancroid are all modified by the immunosuppressive effects of HIV infection. On the other hand, HIV transmission is probably facilitated by the disruption of the normal epithelial barriers of the genital organs caused by these ulcerative infections. Information is somewhat less convincing that a similar association exists between the nonulcerative STDs (trichomonas, gonorrhea, chlamydial infections) and HIV. Conceptually, the mucosal inflammation associated with these infections might serve as a focus for HIV transmission. The available data, though suggestive, do not strongly support this contention. Theoretically though, even a small risk might potentially result in significant HIV transmission given the prevalence of nonulcerative STDs. These infectious processes do not appear to be markedly altered by HIV induced immunosuppression. The ability of HPV to cause dysplastic changes in cervical and anal tissue did not require the AIDS epidemic to come to light. In HIV infection, disruptions of immunoregulatory processes, which might ordinarily control the progression of potentially malignant cell lines, have created fertile ground for an increasing incidence of premalignant and malignant cytologic changes. The mutual impact these processes have or may have on one another requires that clinicians who care for patients with either HIV infection or with STDs should be thoroughly familiar with both and not consider them somehow exclusive of one another. Efforts toward the prevention and control of STDs should be considered important in the control and prevention of HIV transmission.

Chancroid and the role of genital ulcer disease in the spread of human retroviruses.

Chancroid is the most prevalent form of genital ulcer disease in developing countries and is undergoing a resurgence in industrialized countries. As a result of a nonspecificity of the clinical findings, the etiologic diagnosis of genital ulcer disease requires laboratory support. Genital ulcer disease is a risk factor for the transmission of human retroviral infections. An understanding of this interaction is emerging and will impact on the treatment and control programs for the agents causing genital ulcer disease.

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.

Isolation of anaerobes from clinical chancroid associated with fluctuant bubo in men.

Microbial flora especially anaerobes were studied in 67 patients with genital ulcers due to chancroid (diagnosed clinically) and 53 controls with genital ulcers due to other causes. The aerobic flora was similar in patients of chancroid with or without associated bubo and in controls. Anaerobes were however, isolated with higher frequency from chancroid ulcers associated with fluctuant bubo compared to those without bubo (P less than 0.01) and with non-fluctuant bubo (P less than 0.05). Anaerobic bacteria like Bacteroides melaninogenicus, B. fragilis and anaerobic cocci may play a role in the perpetuation of genital ulcers and development of bubo in chancroid.

PIP: The microbial isolates in 67 men with genital ulcers due to chancroid and 53 controls with genital ulcers due to other causes were investigated. The study subjects comprised 14% of men presenting to a sexually transmitted disease facility in India in 1986. Bubo was present in 37 of the chancroid patients and was fluctuant in 20. At least 1 organism was isolated in both subjects and controls. Monomicrobial growth was observed in 20 chancroid patients and 20 controls; the remainder were polymicrobial. Anaerobic cocci were isolated in 44 (66%) of men with chancroid and 25 (47%) of those with ulcers of miscellaneous etiology, while aerobes were present in 52 (77%) men with chancroid and 39 (73%) controls. Finally, anaerobes were isolated in 17 (57%) of ulcers without bubo, 11 (65%) of ulcers with nonfluctuant bubo, and 18 (90%) of chancroid ulcers associated with fluctuant bubo. There was a significant difference in the anaerobe isolation rate in men with fluctuant bubo and those without bubo (pp0.01) and between patients with fluctuant non nonfluctuant bubo (p0.05). The finding that anaerobes were isolated more frequently, but not at a statistically significant level, from chancroid ulcers than ulcers of other etiology fails to support the hypothesis that anaerobes are a major cause of chancroid. On the other hand, the data do support the view that anaerobes such as anaerobic cocci and Bacteroides melaninogenicus are significant in the perpetuation of chancroid ulcers and the development of fluctuant bubo.

Update on chancroid: an important cause of genital ulcer disease.

Chancroid is a major cause of genital ulcer disease worldwide, and occurred at epidemic rates in the United States in the late 1980s. Though the recent epidemic in the U.S. appears to be waning, a number of areas continue to report significant numbers of cases. Chancroid is a particular concern, because, like other diseases that cause genital ulceration, it is associated with an increased risk for transmission or acquisition of human immunodeficiency virus (HIV). Recent studies have advanced the understanding of chancroid epidemiology, and new diagnostic tests may improve the ability to recognize and appropriately treat chancroid. Increased awareness of chancroid, with appropriate treatment for suspected lesions, along with public health efforts to implement prevention in high-risk populations, will be critical to prevent ongoing transmission of chancroid, and potentially ongoing transmission of HIV.

The African AIDS epidemic.

In parts of sub-Saharan Africa, nearly 25 percent of the population is HIV-positive as a result of heterosexual transmission of the virus. Could lack of circumcision make men in this region particularly susceptible?

Genital ulcer disease in patients attending a public sexually transmitted disease clinic in Singapore: an epidemiologic study.

Genital ulcer disease forms about 10% of all sexually transmitted diseases (STDs) in Singapore. In this retrospective study of 531 cases of genital ulcer disease presenting at the Department of STD Control, 91.6% were due to venereal causes and 8.4% were due to non-venereal causes. The venereal causes of genital ulcers were found to be genital herpes (71.5%), chancroid (15.8%), primary syphilis (3.4%) and lymphogranuloma venereum (1%). The non-venereal causes were mainly trauma, drug eruptions or were non-specific in nature. The peak incidence in both sexes occurred in the 20-39 year age group. Males outnumbered females by a ratio of 5.8:1. The ethnic distribution showed an under-representation of Malays relative to the racial makeup of the general population, reflecting perhaps a protective effect conferred by circumcision from genital ulcer diseases or a lower health-risk sexual behaviour in this ethnic group. The accuracy of initial clinical diagnosis was low indicating the need for laboratory investigations to establish accurate aetiologic diagnosis. Commercial sex workers were the main source of infection in males, highlighting the continued need to educate, screen and effectively treat this high risk group.

Low dose erythromycin regimen for the treatment of chancroid.

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.

[Diagnosis and therapy of ulcus molle]. / Diagnose und Therapie des Ulcus molle.

In developing countries of tropical Africa and South-East Asia chancroid is the most important cause of genital ulzerations. In the last decade also in industrial countries of the western hemisphere sporadic epidemics of this sexually transmitted disease were observed. This surprising revival of a disease already thought to have died out induced advances in cultivation and characterization of the etiologic agent as well as new therapeutic approaches. Treatment regimens based on erythromycin, cephalosporins of the third generation or a combination of amoxillin with the beta-lactamase inhibitor clavulanic acid can be recommended. Penicillins and tetracyclines are mostly ineffective because of plasmid-mediated resistance in Haemophilus ducreyi. As in other sexually transmitted diseases simultaneous infections with other pathogens have to be taken into consideration. The sexual partners of the patients should likewise be examined and if need, be treated.

Genital ulcers disease among sexually transmitted disease clinic attendees in Ibadan, Nigeria.

Genital ulcer disease (GUD) is a risk factor in the transmission of human immuno deficiency virus (HIV). The goal of this study is to estimate proportion, identify risk factors, and improve prevention and control of GUD. This is a retrospective study of 211 cases of GUD seen between 1993 and 1997 in an urban public sexually transmitted disease (STD) clinic. Genital ulcers form 7.6% of all STDs seen. Overall, genital herpes was commonest (89 or 42.25%). It was the predominant infection (84 or 44.7%) in the males, while lymphogranuloma venereum (52 or 24.7%) was in females. The peak incidence in both sexes occurred in the 20-29 age group. Males out numbered females by a ratio of 8:1. Most of the patients were single 114 (68.3%) and most 70 or 33.3% were students. Risk markers identified were: casual sex (103 or 53.5%) and multiple sexual partners (77 or 36.5%). Both were significantly higher (P < 0.05) in single patients. Self-treatment, use of multiple drugs and incomplete course of antibiotics were also common. The need to intensify STDS education programmes to all occupational groups and to students in particular is highlighted. Commercial sex workers require periodic education, screening and treatment.