The changing epidemiology of genital ulcer disease in South Africa: has donovanosis been eliminated?

OBJECTIVES: We used an in-house molecular assay for the detection of Klebsiella granulomatis in ulcer specimens collected over a 12-year surveillance period in order to determine whether a diagnosis of donovanosis could be ascribed to genital ulcer disease (GUD) of unknown aetiology in our setting. METHODS: Between 2007 and 2018, a total of 974 genital ulcer specimens with no previously identified sexually transmitted (STI) pathogens were selected from STI aetiological surveys conducted in all nine provinces of South Africa. Giemsa-stained ulcer smears from the same participants had previously been routinely analysed for the presence of typical Donovan bodies within large mononuclear cells. A Klebsiella screening assay targeting the phoE (phosphate porin) gene was used in combination with restriction digest analysis and sequencing to confirm the presence of K. granulomatis. RESULTS: The Klebsiella screening assay tested positive in 19/974 (2.0%) genital ulcer specimens. Restriction digest analysis and nucleotide sequencing of the phoE gene confirmed that none of these specimens was positive for K. granulomatis DNA. Similarly, Donovan bodies were not identified in the Giemsa stained ulcer smears of these specimens. CONCLUSIONS: This is the first study to assess K. granulomatis as a cause of genital ulceration in South Africa over a 12-year surveillance period using molecular methods. The results demonstrate that K. granulomatis is no longer a prevalent cause of GUD in our population.

Donovanosis: [review]

Donovanosis is a chronic bacterial illness frequently associated with sexually transmitted infections (STI) and is under diagnosed both in endemic areas as well as in countries in which doctors have little experience with tropical diseases. The utilization of syndromic diagnosis and treatment of STIs in various parts of the world and the previous use of antibiotics make it difficult to find Donovan bodies in the cytodiagnostic and hystopathological exams, requiring the utilization of technology that is neither routine nor often accessible to confirm the hypothesized diagnosis. Therefore, it is necessary to bring medical professionals up to date about this infectious disease.

Donovanosis.

Donovanosis is a chronic bacterial illness frequently associated with sexually transmitted infections (STI) and is under diagnosed both in endemic areas as well as in countries in which doctors have little experience with tropical diseases. The utilization of syndromic diagnosis and treatment of STIs in various parts of the world and the previous use of antibiotics make it difficult to find Donovan bodies in the cytodiagnostic and hystopathological exams, requiring the utilization of technology that is neither routine nor often accessible to confirm the hypothesized diagnosis. Therefore, it is necessary to bring medical professionals up to date about this infectious disease.

Donovanosis in Australia: going, going...

In the 1990s donovanosis (or granuloma inguinale) had disappeared from most parts of the developed world. However, any practitioner working in the Northern Territory, far north Queensland, or the northern part of Western Australia would have been aware of the spectrum of morbidity associated with the condition in the Aboriginal and Torres Strait Islander population--ranging from mild genital ulceration to severe, disfiguring disease and disseminated, life threatening infection.

Selected sexually transmitted diseases and their relationship to HIV.

Although sexually transmitted diseases (STDs) are underreported and underrecognized, they are a major source of morbidity, mortality, and represent a major socioeconomic cost in developing and industrialized nations. Individuals who develop STDs are often coinfected with human immunodeficiency virus (HIV). Coinfection with HIV both facilitates the natural history of STDs and worsens the clinical picture. The objective of this article is to provide a review to the practicing clinician on the epidemiology, clinical manifestations, methods of diagnosis, and treatment for four cutaneous STDs--chancroid, genital herpes, granuloma inguinale, and lymphogranuloma venereum--in coinfected HIV patients.

Donovanosis.

Donovanosis, a chronic cause of genital ulceration, has recently been the subject of renewed interest after a long period of relative obscurity. The causative organism, Calymmatobacterium granulomatis, has been cultured for the first time in many years and a polymerase chain reaction diagnostic using a colorimetric detection system has been developed. Phylogenetic analysis confirms close similarities with the genus Klebsiella and a proposal made that C granulomatis be reclassified as Klebsiella granulomatis comb nov. Azithromycin has emerged as the drug of choice and should be used if the diagnosis is confirmed or suspected. In donovanosis endemic areas, syndromic management protocols for genital ulceration may need to be adapted locally. A significant donovanosis epidemic was reported in Durban from 1988-97 but the current status of this epidemic is unclear. The donovanosis elimination programme among Aboriginals in Australia appears successful and is a model that could be adopted in other donovanosis endemic areas. Overall, the incidence of donovanosis seems to be decreasing. Increased attention would undoubtedly be paid to donovanosis if policy makers recognised more readily the importance of genital ulcers in fuelling the HIV epidemic.

Donovanosis: an update.

Donovanosis has been ignored for many years until recently. The condition still has a limited geographical distribution. A significant epidemic of donovanosis has been identified in KwaZulu/Natal, South Africa where it may be a risk factor for acquiring HIV in men. After a gap of more than 30 years, the organism was cultured by researchers in Durban, South Africa and Darwin, Australia. Polymerase chain reaction (PCR) techniques for donovanosis were developed soon after, most recently using a colorimetric detection system. Similarities between the causative organism, Calymmatobacterium granulomatis and Klebsiella spp. were confirmed. A proposal that the organism be reclassified under the genus Klebsiella has been put forward. Azithromycin has been confirmed as the drug of choice but is yet to be accepted universally because of cost issues. Treatment in patients with significant HIV induced immune deficiency may need to be prolonged. A donovanosis eradication programme is underway amongst the aboriginal community in Australia. Elsewhere, management through current syndromic guidelines for genital ulcers are yet to be validated in areas where donovanosis is endemic. PCR testing should enable further recognition of donovanosis and lead to more concerted efforts in disease control and possible eradication.

Ulcera genital crónica e infección por VIH / Chronic genitalis ulcer and HIV infections

En el Centro de Referencia de Enfermedades de Transmisión Sexual A. Barton, Callao, Perú, entre Enero de 1996 y Junio de 1997, se reportaron 11 casos de Ulcera Genital Crónica (UGC), los cuales por criterios clínico, epidemiológico y de respuesta terapéutica tuvieron el diagnóstico probable de Donovanosis. Seis de los pacientes eran hombres que tenían sexo con hombres y la localización más frecuente fue en el ano. En diez pacientes hubo una respuesta al tratamiento con Doxicilina y Trimetoprin/Sulfametoxazol. Diez pacientes aceptaron realizarse la prueba de ELISA para VIH, resultando seis de ellos positivos con Western Blot confirmatorio. La alta pevalencia de infección por VIH en este grupo nos permite asumir que la UGC es un importante facilitador de la infección por VIH.

Clinico-epidemiologic features of granuloma inguinale in the era of acquired immune deficiency syndrome.

BACKGROUND AND OBJECTIVES: Granuloma Inguinale (GI) is an endemic sexually transmitted disease (STD) in India. With increasing prevalence of human immunodeficiency virus (HIV) among patients with STD at a clinic in Mumbai, a study was conducted to determine clinico-epidemiologic features of GI and HIV. GOAL: To determine possible interaction between GI and HIV. STUDY DESIGN: Prospective follow-up of 21 consecutive cases (GI in HIV-seropositive individuals) and 29 controls (GI in HIV-seronegative individuals) to determine time to heal. All cases and controls received a standard treatment regimen of erythromycin, 2 g po daily, under supervision until healing occurred. RESULTS: Although GI ulcers at recruitment were not significantly larger among HIV-seropositive individuals as compared with those seen among HIV-seronegative individuals (mean size 4.4 cm2 vs. 3.6 sq2; odds ratio [OR] 1.22, confidence interval [CI] .95, 0.63, 2.40; p = 0.52), the former took longer time to heal completely (mean 25.7 days vs. 16.8 days; OR 1.82, CI .95, 0.99, 3.36; p = 0.03) and tended to produce greater tissue destruction (as included in results). CONCLUSION: These findings are important because slow-healing GI ulcers with underlying HIV infection, which may be caused by their interaction, will lead to increased transmission of both the infections.

PIP: Infection with genital ulcer disease (GUD) facilitates the transmission of HIV. However, granuloma inguinale (GI), an endemic sexually transmitted disease (STD) in India, has been ignored as a cause of GUD. In the context of increasing prevalence of HIV infection among patients with STD at a clinic in Mumbai, a study was conducted to determine the clinico-epidemiologic features of GI and HIV, with the goal of identifying any possible interaction between the two. 21 consecutive cases of GI in HIV-seropositive individuals and 29 controls, HIV-seronegative individuals with GI, participated in the prospective follow-up study to determine how long it takes for GUD to heal. Healing was considered complete when total re-epithelization of the ulcer(s) was observed. All cases and controls received a standard treatment regimen of erythromycin under supervision until healing occurred. While the GI ulcers at recruitment were not significantly larger among HIV-seropositive individuals compared with those among HIV-seronegative individuals, the former took longer to heal completely; an average of 25.7 days compared to 16.8 days, respectively. The former ulcers also tended to produce greater tissue destruction. Slow-healing GI ulcers with underlying HIV infection can lead to the increased transmission of both infections.

A comparison of prevalence rates of genital ulcers among persons attending a sexually transmitted disease clinic in Jamaica.

Two cross-sectional surveys were undertaken, from December 1982 to August 1983 and from November 1990 to January 1991, to estimate the prevalence rates of genital ulcer disease (GUD) in all patients presenting with a new sexually transmitted disease (STD) complaint to the STD clinic at the Comprehensive Health Centre in Kingston, Jamaica. Diagnosis of syphilis and human immunodeficiency virus (HIV) infection was based on results of laboratory tests, but diagnosis of the other STDs was based on clinical features. Data from these two surveys were compared, and reported national annual incidence data for GUD reviewed. In 1982/83 6.8% of 23,050 patients had GUD, men (9.3%) more often than women (4.2%; p < 0.001). In 1990/91 the prevalence rate was 12.8%, with increased rates for both men (18.2%) and women (6.8%; p < 0.001). In patients with GUD, a clinical diagnosis of genital herpes was made, in 1982/83 and 1990/91, respectively, in 16.8% and 7.8% of the patients; syphilis, in 12.9% and 18.8%; chancroid, in 12.4% and 13.3%; viral warts, in 5.7% and 6.3%; lymphogranuloma venereum, in 4.1% and 3.9%; and granuloma inguinale, in 3.6% and 2.3%. In men the rate for syphilis was 19% in 1990/91 and 8% in 1982/83 (p = 0.001); and for genital herpes it was 7% in 1990/91 and 17% in 1982/83 (p = 0.025). These reversals were attributed to intense media coverage of herpes in 1982/83. There was no difference in prevalence rates between the two surveys for these diseases in women, or for lymphogranuloma venereum, granuloma inguinale and genital warts in men and women. A clinical diagnosis could not be made in 44.4% of cases in 1982/83 (particularly in men), and in 47.6% of cases in 1990/91. GUDs facilitate transmission and adversely affect the prognosis of HIV. The increase in their prevalence has implications for the evolution of the local HIV epidemic, and should be addressed effectively by strengthening the STD/HIV control programme.

PIP: The prevalence of genital ulcer disease (GUD) was investigated in two cross-sectional studies of patients presenting to the sexually transmitted disease (STD) clinic at the Comprehensive Health Center in Kingston, Jamaica, between December 1982 and August 1983 (n = 23,050) and between November 1990 and January 1991 (n = 1001). The median age of participants was 26 years for men and 25 years for women; most were low-income inner-city residents. The prevalence of GUD rose from 6.8% (9.3% in men and 4.2% in women) in the 1982-83 survey to 12.8% (18.2% in men and 6.8% in women) in 1990-91. In 1982-83 and 1990-91, respectively, genital herpes was diagnosed in 16.8% and 7.8% of patients, syphilis in 12.9% and 18.8%, chancroid in 12.4% and 13.3%, viral warts in 5.7% and 6.3%, lymphogranuloma venereum in 4.1% and 3.9%, and granuloma inguinale in 3.6% and 2.3%. A clinical diagnosis could not be made in 44.4% of cases in 1982-83 and in 47.6% in 1990-91. Since GUDs facilitate the transmission of HIV, HIV prevention efforts must include the strengthening of STD control programs. All cases of GUD should be screened for both syphilis and HIV, with prompt treatment to reduce the period of GUD transmissibility. Jamaica has revised its national STD case management guidelines to include simplified algorithms for GUD management and strengthened STD surveillance and contact tracing. Changes in GUD prevalence over time may be a useful indicator for evaluating the impact of STD/HIV interventions.