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.

Chancroid and granuloma inguinale.

Haemophilus ducreyi is a fastidious pathogen that can be routinely cultured with the appropriate media and incubation environment. Prostituted women appear to be the usual reservoir. In Africa, chancroid is emerging as the major risk factor for acquisition of HIV-1 following heterosexual intercourse. Despite the emergence of resistance to a number of antimicrobial agents, H. ducreyi remains susceptible to ceftriaxone, erythromycin, and ciprofloxacin. Control and eradication of outbreaks of chancroid have been successful on several occasions in Western societies; strategies to control epidemic genital ulcer disease are required in developing countries. Granuloma inguinale is caused by a small, gram-negative rod, which has never been well-characterized. The presence of Donovan bodies is a specific and sensitive diagnostic characteristic. Very little is known about the epidemiology of the disease. Specific treatment programs using trimethoprim-sulfamethoxazole or erythromycin seem to be quite effective. Control strategies have not been adequately investigated.

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: 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.

Granuloma inguinale in association with pregnancy and HIV infection.

OBJECTIVES: A retrospective study to confirm the clinical impression of an increasing prevalence of granuloma inguinale (GI) in women, and to evaluate its association with pregnancy and HIV infection. METHODS: Clinical records of all patients with a definitive diagnosis of GI attending the gynecology and antenatal clinics at King Edward VIII Hospital, Durban, South Africa, over a period of 36 months (January 1991-December 1993). RESULTS: A total of 123 women were diagnosed with GI. The diagnosis was made by tissue smear alone in 21% (n = 26), histology 43% (n = 53) and by a combination of smear and histology in the rest. Forty-two percent (n = 52) were pregnant. The only difference between pregnant and non-pregnant women were the presence of rectal and pelvic lesions in the latter. Sixty-nine percent (n = 36) delivered vaginally while the remaining (n = 16) were delivered by cesarean section. The indications for cesarean section were obstetric except for a patient in labor with extensive untreated vulval granuloma. In the majority (85%) GI had no influence on pregnancy outcome. There was no evidence of congenital GI in the neonates. Twenty-seven percent (30/113) had positive syphilis serology and 16% (18/110) had antibody to HIV. There were no differences in the clinical features and outcome of HIV positive and negative women. CONCLUSION: This study shows that GI is increasing in pregnancy in Durban, South Africa. Despite the concern that pregnancy promotes dissemination of GI, such an effect could not be established as the clinical response to treatment and outcome were similar in both pregnant and non-pregnant women. Infection with HIV also did not alter the clinical presentation and outcome of the disease in the patients studied.

[Donovanosis in Pará]. / Donovanose no Pará.

From 1954 to 1990 granuloma inguinale was diagnosed in 259 patients al the dermatology service of the Universidade Federal do Pará in Belém, Brazil. Among them, 56 cases had occurred in the twenty-year period 1954-1974 and as many as 133 cases were seen during the last five years only. Greater sexual liberty, poor social and economic conditions, and especially increasing homosexual behavior were implicated by the authors as chief determinants for this augmented incidence of the disease.

Sexually transmitted diseases in Australia: a decade of change. Epidemiology and surveillance.

Survival data in the last decade for sexually transmitted diseases (STDs) other than human immunodeficiency virus (HIV) are uneven across the states/territories. The incidence of gonorrhoea decreased by more than 80%, but at different times in different patient groups, different states, and different anatomical sites. There was a resurgence of rectal gonorrhoea in homosexual men in 1989-1991. Resistance to penicillin steadily increased, and partial resistance to quinolones has emerged. There was a marked decline in syphilis in most states. Lymphogranuloma venereum is rare, and chancroid seen mostly in returning travellers from Southeast Asia; however, hundreds of cases of donovanosis are seen annually among rural Aborigines. The prevalence of genital infections with Chlamydia trachomatis remained stable at 2.5%-14% in STD clinics, and 5% in family planning clinics. The numbers of cases of clinical genital herpes and warts are mostly unavailable. However, specific serology for herpes simplex virus type 2 (HSV-2) indicates that 14% of antenatal clinic patients, and 40%-60% of STD patients have been exposed. Pap smears have detected the presence of human papilloma virus (HPV) in 14%-40% of various clinic populations. Exposure to hepatitis B in the non-Aboriginal population decreased markedly. Hepatitis C infection occurred in a high percentage of injecting drug users; the evidence for sexual transmission is not strong. An epidemic of hepatitis A infection occurred in male homosexuals in 1989-1991. Changes in the Australian sex industry resulted in marked improvements in the sexual health of local (but not international) sex workers. The high levels of STDs in Aboriginal communities continues to cause concern.

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.

Status of granuloma inguinale in Papua New Guinea.

Granuloma inguinale has been endemic in Papua New Guinea for at least eighty years and recently appears to be increasing, particularly in the urban centres. Most patients were found to be recent migrants to the Port Moresby area with low socioeconomic status and poor personal hygiene. The disease was found more frequently in males. A possible association between carcinoma of the penis and granuloma inguinale was observed. Lesions were chronic, progressive and located mainly in the genital region. Attempts to culture the causative agent were unsuccessful.

Donovanosis in Dutch South New Guinea: history, evolution of the epidemic and control.

PIP: The focus on donovanosis (venereal granuloma) in Dutch South New Guinea is relevant because the epidemic number of sexually transmitted disease cases (10,000) occurring between 1922-52 affected a small population (15,000) of the Marind-anim people. The history, evolution, and control are discussed as well as the relationship between medical and social factors and depopulation. Sections are devoted to identification of sources, the ethnographic background of the Marind-amin, evolution of the epidemic, the systematic campaign to eradicate the disease, and a final report on the relationship between the illness, depopulation, the original culture, and the effects of contact. The principle data sources were the Kooyman's SPC report of 1954, the medical report of 1913, the medical literature of Thierfelder and others, memoranda of government officers from the Resident Office at Merauke, and the logbook of the Roman Catholic mission begun in 1905. The 1954 report concluded that the coastal Marind-amin population dropped from 10,000 to 5,000 between 1900-20 due to a lowered birth rate and influenza mortality, and occurred before the spread of donovanosis. Sexual practices account for the low birthrate before 1923. When sexual practices were intensified upon the arrival of foreigners, donovanosis was spread more rapidly. The ritual was to avert sickness by having 1 woman have intercourse with many men. Government intervention in 1923 stabilized the birth rate. The population remained static due to the lack of young people, a high infant mortality rate, and a 1938/9 influenza epidemic. Nutrition was found not to be a factor. In the ethnographic literature, the belief in otiv--bombari is described. This emphasis on sexual activity (promiscuous sex with a religious base and semen as a curative power) was responsible for the spread of the disease. It is surmised that the disease appeared at a festival in 1905 and the spread was apparent by 1908. Model villages were established which were free of donovanosis and compulsory treatment enforced. The present culture may reflect the government and religious intervention of the 1920's.^ieng

Prevalence of concomitant sexually transmitted infections in Goroka.

During 18 months all 339 patients attending a sexually transmitted disease clinic in Goroka, Papua New Guinea had serological tests for syphilis carried out. The clinical diagnosis of syphilis made in 60 patients by the paramedical staff of the clinic was confirmed by both VDRL and TPHA tests in 52%. Concomitant syphilis was diagnosed on serological grounds in 16% with ulcerative lesions, 4% with a urethral discharge and 6% of subjects with other conditions. A total of 7% of patients subsequently diagnosed serologically to have syphilis, left the clinic untreated, and because of logistical reasons, few could later be traced.