Management Of Genital Ulcer Disease Research Articles

Genital ulcer disease: A review.

Genital ulcer disease (GUD) continues to be an important cause of morbidity and mortality worldwide. It is an important risk factor for the acquisition of HIV. GUD is mainly caused by five sexually transmitted infections. Three pathogens most frequently associated with GUD are herpes simplex virus 2 (HSV-2), Treponema pallidum, and Haemophilus ducreyi. Although their prevalence varies among different geographical regions, HSV-2 is the leading cause of this syndrome globally. In recent years, there has been an epidemiological transition of HSV-1 with a growing role of this virus as a causative agent of GUD. GUD may present with unique features depending on the etiological agent that can help clinicians identify the etiology and start treatment. However, owing to atypical presentations and co-infections, an accurate clinical diagnosis is often a challenge without confirmatory laboratory tests. Standard methods used to detect the causative pathogens of GUD have limitations. Molecular methods can provide a more sensitive and rapid microbiological diagnosis, with detection of the pathogen from the clinical sample directly. In situations where no laboratory support is available, the syndromic approach for management should be followed. The current scenario, clinical presentation (typical and atypical), laboratory diagnosis, and management of GUD will be discussed in this review. We searched PubMed literature and Google search engine using the terms "genital ulcer disease," "epidemiology of genital ulcer disease," and "clinical features of genital ulcer disease and atypical presentations" and relevant literature was selected to provide current perspectives of GUD.

Estimating syphilis seroprevalence among patients in a sexually transmitted infections clinic in Lilongwe, Malawi.

The syndromic management of genital ulcer disease (GUD) misses asymptomatic syphilis cases but is widely utilized in resource-limited settings without diagnostic capabilities to ensure treatment for the most common etiologies of GUD. We used rapid serology tests for syphilis screening at a Malawian sexually transmitted infections clinic. The estimated seroprevalence was 9% and was highest among patients with genital ulcers (26%) and newly diagnosed HIV infection (19%). Rapid syphilis screening has the potential to increase syphilis detection, but accurate patient histories regarding syphilis diagnosis and prior treatment are needed.

Etiology of Genital Ulcer Disease in Male Patients Attending a Sexually Transmitted Diseases Clinic: First Assessment in Cuba.

Sexually transmitted diseases (STDs) and in particular genital ulcer disease (GUD) have a major impact on morbidity and mortality in developing countries. The World Health Organization recommends the use of syndromic guidelines for the treatment of sexually transmitted infections (STIs) in resource-constrained countries. Surveillance of autochthonous etiologies provides epidemiological information contributing to the prevention and treatment of STIs. We investigated the etiology and factors associated with GUD among male patients attending a STD clinic in Havana, Cuba. Swabs from genital ulcers of 113 male patients, collected from May 2012 to June 2015, were analyzed using PCR for herpes simplex virus types 1 and 2, Treponema pallidum, Haemophilus ducreyi, and Chlamydia trachomatis. We also investigated the clinical and epidemiological characteristics associated with the presence of these pathogens in GUD. At least one of the pathogens was detected in 70% of patients. The occurrence of the pathogens was herpes simplex virus type 2 (HSV-2) (51.3%), T. pallidum (29.2%), and C. trachomatis (1.8%). Co-infections occurred as follows: T. pallidum-HSV-2 (10.6%), C. trachomatis-HSV-2 (0.9%) and C. trachomatis-T. pallidum (0.9%). Herpes simplex virus type 1 and H. ducreyi were not detected. Ages 15 to 40 years, HIV-positive serostatus, and no condom use were significant risk factors for the presence of HSV-2 in genital ulcers. Our preliminary results highlight the predominance of HSV-2 and T. pallidum as the leading GUD etiologies in the study population and identified risk factors associated with HSV-2. This information should help to inform guidelines for better management of GUD in Havana, Cuba.

006.6 High prevalence of chlamydia and gonorrhoea among patients with genital ulcer disease in zimbabwe: potential implications for syndromic management

Background Syndromic management of genital ulcer disease (GUD) as recommended by the Zimbabwe Ministry of Health and Child Care, includes antibiotics against Treponema pallidum (TP: benzathine penicillin), Haemophilus ducreyi (HD: erythromycin), and herpes simplex virus (HSV: acyclovir). However, these medications are not recommended to treat co-infections with Neisseria gonorrhoeae (NG: ceftriaxone or kanamycin) and Chlamydia trachomatis (CT: doxycycline or azithromycin) and, unless a person with GUD is simultaneously diagnosed with genital discharge syndromes (GDS), NG and CT co-infections will not be treated according to guidelines. Methods In an ongoing study, we enrolled men and women with GDS or GUD syndromes in 6 clinics with high STI prevalence in Zimbabwe. In addition to testing ulcer secretions for TP, HD, and HSV by multiplex polymerase chain reaction (National Institute of Communicable Diseases, Johanneburg), all patients had urine (males) or vaginal swabs (females) tested for NG and CT by nucleic acid amplification (GeneXpert ® ). Results To date, 302 patients have been enrolled for whom testing is complete, including 106 GUD and 196 GDS patients. NG and/or CT infections were present in 19/52 (36.5%) female GUD patients and 13/54 (24.1%) male GUD patients, compared to 26/96 (27.1%) female GDS patients and 68/100 (68.0%) male GDS patients. Of 32 GUD patients infected with NG (N = 24) and/or CT (N = 17), including 9 dual infections, only 4/18 (22%) of women and 4/14 (29%) of men met objective criteria for simultaneous GDS syndromic management. Conclusion In our study, urethral or vaginal GC and/or CT infections were present in 30% of patients with GUD, of whom three quarters would not have been treated according to recommended syndromic treatment guidelines for sexually transmitted infections. Our study methods and findings should be relevant for Zimbabwe and other countries that are using a syndromic approach to STI control.

Genital Ulcer Disease in India

In India, genital ulcer disease (GUD) syndrome is clinically classified as herpetic or nonherpetic and managed accordingly; laboratory support is unavailable at most health facilities. We undertook a study to determine the etiology of GUDs in men presenting to sexually transmitted infection (STI) clinics and assess the performance of the national algorithm for syndromic management of herpetic and nonherpetic GUDs in India. A cross-sectional study was conducted among men with complaints of genital ulcers attending 8 STI clinics in 4 states. Ulcer swabs were collected and tested by the multiplex polymerase chain reaction method to determine the etiology of GUD. Of the 194 men recruited, etiology was confirmed in 121 GUD cases (62%). Herpes simplex virus (48%) was the most common etiological agent identified, followed by Treponema pallidum (23%) and mixed infections (9%). One case of Haemophilus ducreyi was confirmed in this series. The overall sensitivity and specificity of the national syndromic management algorithm for GUD were 68% and 52%, respectively. Using the national algorithm, 52 (42%) cases clinically misclassified as either herpetic (18 cases) or nonherpetic (34 cases) GUD resulting in incorrect treatment. Our findings suggest a revision of existing national STI treatment guidelines in India to include treatment of syphilis infections of all GUD patients. Periodic studies are required to monitor changing spectrum of GUD etiologies in India.

Microbial Diversity of Genital Ulcer Disease in Men Enrolled in a Randomized Trial of Male Circumcision in Kisumu, Kenya

BackgroundMedical male circumcision (MMC) reduces the risk of genital ulcer disease (GUD) in men by 50%. In Ugandan and Kenyan trials, a sexually transmissible agent was not identified in 50–60% of GUD specimens by polymerase chain reaction (PCR) assay. We sought to better define the etiology of GUD in men participating in the Kenyan trial and examine how MMC affects GUD etiology.MethodsWe defined GUD of unknown etiology as negative for HSV (type 1 and type 2), T. pallidum, and H. ducreyi by PCR, and negative for HSV-2 and T. pallidum by serology. We identified bacterial microbiota in a subset of 59 GUD specimens using multitag pyrosequencing of the 16S rRNA gene, and compared results by unknown vs. STI-associated etiology. Statistical analysis employed Bray-Curtis similarity measure of bacterial community by etiology, hierarchical clustering and logistic regression.ResultsIn 59 GUD specimens from 59 men, 23 (39%) had unknown etiology. Bacterial diversity was greater in GUD of unknown than STI etiology (p = 0.01). Fusobacteria (Fusobacterium spp. and Sneathia spp.) were more commonly detected in men with GUD of unknown etiology [adjusted OR = 5.67; 95% CI: 1.63–19.8] as were Oxobacter spp. and Anaerovorax spp. [adjusted OR = 3.12; 95% CI: 0.83–11.7]. Sequences from these four anaerobic bacterial taxa were more often detected in uncircumcised men than circumcised men (p<0.05).ConclusionsAnaerobic bacteria are more common in genital ulcers of uncircumcised men. The specific anaerobic bacteria associated with GUD of unknown etiology have cytotoxic properties that can exacerbate epithelial disruptions leading to ulcer-like appearance. MMC may reduce GUD through a reduction in these anaerobic bacteria.

P3-S5.01 Microbial diversity of genital ulcer disease in men enrolled in a randomised trial of male circumcision in Kisumu, Kenya

BackgroundMedical male circumcision (MMC) reduces the risk of HIV acquisition by ∼60%, in part by reducing genital ulcer disease (GUD) and HSV-2. In the Ugandan and Kenyan trials, PCR did...

Impact of aciclovir on ulcer healing, lesional, genital and plasma HIV-1 RNA among patients with genital ulcer disease in Malawi

By a randomised, double-blind, placebo-controlled trial of aciclovir 800 mg twice daily for 5 days added to the syndromic management of genital ulcer disease (GUD) to determine the impact on ulcer healing and HIV outcomes. Patients presenting with GUD in Malawi were evaluated for HIV and herpes simplex virus type-2 (HSV-2) serologies, ulcer aetiology, lesional, genital and plasma HIV-1 RNA and CD4+ count. Patients were followed up at days 2, 4, 7, 14 and 28. The primary study outcome was ulcer healing at day 14, with secondary outcomes being lesional and genital HIV-1 shedding at day 14 and HIV-1 plasma viral load at day 28 among HIV-1/HSV-2 co-infected individuals. Four hundred and twenty-two patients (74% male) were randomised (208 to aciclovir, 214 to placebo), of whom 61% were HIV-1 seropositive and 72% HSV-2 seropositive; 67% (267/398) had HSV-2 ulcers. 85% of ulcers were healed at day 14 with no difference between treatment arms (risk ratio (RR)=1.02, 95% CI 0.93 to 1.11). Among 244 HIV-1/HSV-2 co-infected individuals, aciclovir reduced lesional HIV-1 RNA (adjusted RR=0.64, 95% CI 0.41 to 0.99) and seminal HIV-1 RNA (adjusted RR=0.59, 95% CI 0.40 to 0.88), but not cervical HIV-1 RNA or plasma HIV-1 RNA. Episodic HSV treatment with aciclovir added to syndromic management did not produce a significant clinical benefit in this African population.

Recent advances in management of genital ulcer disease and anogenital warts

Genital ulcer disease (GUD) constitutes a major public health problem. Most of them are the result of sexually transmitted diseases. Genital herpes, syphilis, lymphogranuloma venereum, granuloma venereum, or chancroid are the commonly encountered GUD. The treatment modalities for these disorders have changed with advent and use of drugs such as azithromycin. The treatment modalities differ in patients with HIV disease. Further vaccines for herpes genitalis and human papilloma virus has opened new avenues in management of these diseases. In regions where there are no diagnostic facilities or where the costs of diagnostic tests are prohibitive, syndromic management of GUD is preferred.

Herpes Simplex Virus Infection and Genital Ulcer Disease Among Patients with Sexually Transmitted Infections in Dar es Salaam, Tanzania

The relative importance of Haemophilus ducreyi and Treponema pallidum in genital ulcer disease in Africa has decreased recently, whereas that of herpes simplex virus (HSV) type 2 has increased. We analysed 301 lesional specimens from Tanzanian patients with genital ulcer disease for the presence of H. ducreyi, T. pallidum and HSV-1/HSV-2 by performing a separate PCR for each pathogen. Infectious agents were detected in 211 (70%) of the cases. A single pathogen was found in 191 samples and two or more pathogens in the remaining 20. HSV-2 represented 83% of all identified pathogens, HSV-1 8%, T. pallidum 4% and H. ducreyi 5%. HSV-1 was identified as a single pathogen in four samples, in combination with others in an additional 14 samples. Thus, HSV-1 can also be the cause of genital ulcer disease in Africa. Regular surveillance of genital ulcer disease aetiology is important in programs for management of genital ulcer disease and HIV in Africa.

Changes in the Etiology of Sexually Transmitted Diseases in Botswana between 1993 and 2002: Implications for the Clinical Management of Genital Ulcer Disease

In recent years, increasing evidence has accumulated that suggests the majority of cases of genital ulcer disease in sub-Saharan Africa are due to viral and not bacterial infections. Although many cross-sectional studies support such a trend, few serial cross-sectional data are available to show the evolution of genital ulcer disease over time. We surveyed the prevalence of sexually transmitted diseases (STDs) among patients with STD symptoms and women recruited from family planning clinics in 3 cities in Botswana in 2002 and compared our findings with those from a survey of a similar population conducted in 1993. The observed proportion of cases of genital ulcer disease due to chancroid decreased from 25% in 1993 to 1% in 2002, whereas the proportion of ulcers due to herpes simplex virus increased from 23% in 1993 to 58% in 2002. Although the proportion of ulcers due to syphilis was similar for both surveys, the rate of positive serologic test results for syphilis among patients with genital ulcer disease decreased from 52% in 1993 to 5% in 2002. During this period, decreases in the prevalence of gonorrhea, syphilis-reactive serologic findings, chlamydial infection, and trichomoniasis were also detected among patients with STDs and women from family planning clinics. These changes remained significant after estimates were adjusted for the sensitivity and specificity of diagnostic tests. Our findings suggest a decrease in the prevalence of bacterial STDs and trichomoniasis, a reduction in the proportion of ulcers due to bacterial causes, and an increase in the proportion of ulcers due to herpes simplex virus during the period 1993-2002. These changes should be taken into consideration when defining new guidelines for the syndromic management of genital ulcer disease.

Genital herpes and human immunodeficiency virus: double trouble.

The synergistic relationship between herpes simplex virus type 2 (HSV-2) and transmission of human immunodeficiency virus (HIV) can be substantial in developing countries that have high prevalences of both viral infections. Genital herpes, most frequently caused by HSV-2, has become the leading cause of genital ulcer disease worldwide. This review of recent research on genital herpes and enhanced susceptibility to, and transmission of, HIV is part of the "Advances in HIV/AIDS research series" which endeavours to form a bridge between the research into HIV and acquired immunodeficiency syndrome (AIDS) and the practice of HIV/AIDS prevention, care and support in developing countries. Research findings have shown that being seropositive for HSV-2 can increase the risk of HIV acquisition among high-risk HIV-negative people exposed to HIV and, likewise, the infectiousness of individuals co-infected with HIV-1 and HSV-2 can increase during periods of HSV-2 reactivation. These observations have led to the initiation of several intervention trials and could ultimately lead to the setting of new priorities in public health and clinical practice. WHO has recently issued new guidelines for the syndromic management of genital ulcer disease that include antiviral treatment for lesions consistent with genital herpes. The United States Centers for Disease Control and Prevention issued updated Sexually Transmitted Diseases Treatment Guidelines in 2002 that recommended the use of type-specific serological tests for diagnosing HSV-2. Recently launched proof-of-concept, HSV-2 intervention trials in several countries will help to determine the proportion of new HIV infections that could be prevented by suppression of HSV-2, and the findings from these studies will inform those involved in setting prevention and treatment priorities and strategies in developing countries.

Increasing relative prevalence of HSV-2 infection among men with genital ulcers from a mining community in South Africa

Objectives: To determine the aetiology of genital ulcer disease (GUD) and its association with HIV infection in the mining community of Carletonville, South Africa, from two cross sectional surveys of...

Coexistence of urethritis with genital ulcer disease in South Africa: influence on provision of syndromic management

Objective: To assess whether syndromic management of genital ulcer disease was sound, if based on the premise that men with genital ulcers rarely have a concomitant urethral infection. Methods: Specimens...

Modification of syphilitic genital ulcer manifestations by coexistent HIV infection.

Conflicting data exist regarding whether HIV infection leads to changes in the clinical manifestations and severity of genital ulcer disease (GUD). To determine the impact of HIV on the etiology and clinical severity of GUD. From July 1990 to July 1992, consecutive patients presenting to the two Baltimore City Health Department (BCHD) Sexually Transmitted Diseases clinics were approached as candidates for enrollment in a prospective study to determine factors associated with the transmission and acquisition of sexually transmitted diseases (STDs). Of the 1368 patients who presented to the BCHD, 214 (16%) had genital ulcerations: 160 (21%) of 757 men and 54 (9%) of 611 women. Among the patients with GUD who had undergone HIV testing, 28 (14%) of 204 were infected with HIV: 25 (17%) of 151 men and 3 (6%) of 53 women. Although both groups-those infected with HIV and those not infected with HIV--presented with GUD of similar duration (10 versus 11 days; P = 0.17), multiple lesions were found more frequently in men with HIV infection than in uninfected men: 87% versus 62% (P = 0.02). Although not statistically significant, GUD in men with HIV infection more often were deep (64% versus 44%, respectively) rather than superficial (36% versus 57%, respectively; P = 0.08), and larger (505 mm(2) versus 109 mm 2; P = 0.06). Primary syphilis caused more GUD among men with HIV infection than among uninfected men: 9 (36%) of 25 versus 24 (19%) of 126, respectively (P < 0.01). Secondary syphilis was diagnosed with concomitant GUD more frequently among men with HIV infection than among uninfected men: 3 (13%) of 25 versus 3 (2%) of 123, respectively (P < 0.01). In this study, patients who presented with GUD were more likely to be infected with HIV. A higher proportion of men with HIV infection had multiple lesions, and the lesions were more likely to be caused by syphilis.

How effective is syndromic management of STDs?: A review of current studies.

Studies of the accuracy of syndromic management have demonstrated widely varying results depending upon gender, location of infection, risk group, organisms, among other factors. To review current knowledge about syndromic management of sexually transmitted diseases (STDs) and to make recommendations about the strengths and weaknesses of different syndromic management algorithms. The authors identified articles and abstracts about the syndromic management of STDs. Evaluation of the effectiveness of algorithms for urethral discharge, genital ulcer disease, and vaginal discharge was based primarily on published sensitivity and specificity data. Overall, algorithms for the diagnosis and treatment of urethral discharge and genital ulcer disease in men had high sensitivities or cure rates (urethral discharge, 87-99%; genital ulcer disease, 68-98%). The sensitivities for the algorithms for vaginal discharge ranged from 73% to 93% among women presenting with symptoms of vaginal discharge, and from 29% to 86% among women not presenting with symptoms. Vaginal discharge was not found to be an effective indicator of cervical infection and, therefore, is not an independently effective screening tool to detect women with cervical infection, especially in low-risk or asymptomatic populations. Incorporating risk scores can improve the accuracy of algorithms to detect cervical infection. Algorithms for urethral discharge and genital ulcer disease can be effective in STDs. The current algorithms for vaginal discharge are not highly effective in detecting gonorrhea and chlamydia in women; risk scores can improve their efficacy, but must be tailored to reflect community risks. Without attention to the qualitative aspects of STD syndromic management, these methods will likely have even less accuracy than the studies reviewed above. There remains an urgent need for the development of an affordable, rapid, and effective diagnostic technique that will improve STD detection in resource-poor settings.

The clinical diagnosis of genital ulcer disease in men.

We report the sensitivity and specificity of physical examination findings for diagnosing primary syphilis, chancroid, and genital herpes. The physical features of genital ulcers in 446 men were measured in accordance with a quantitative scale. Two hundred-twenty of these men had an established, single microbiological diagnosis. Forty-five (20%) had primary syphilis, 118 (54%) had chancroid, and 57 (26%) had genital herpes. There was considerable overlap in the clinical presentation of these three diseases. The classic clinical sign complex attributed to primary syphilis (painless, indurated, clean-based ulcers) was only 31% sensitive but 98% specific. The classic presentation of a chancroid ulcer (a deep, undermined, purulent ulcer) was only 34% sensitive but 94% specific. The classic description of genital herpes ulcers (multiple, shallow, tender ulcers) was only 35% sensitive but 94% specific. Inguinal lymph node findings did not contribute significantly to clinical diagnostic accuracy. These data indicate that the clinical diagnosis of genital ulcer disease can be made with reasonable certainty only for a minority of patients. Rapid, sensitive, and specific diagnostic tests for syphilis, chancroid, and genital herpes are needed.

Syndromic management of genital ulcer disease--a critical appraisal.

Syndromic management of genital ulcer disease--a critical appraisal.

Syndromic management of genital ulcer disease--a reply.

Syndromic management of genital ulcer disease--a reply.

Syndromic management of genital ulcer disease--a response

Syndromic management of genital ulcer disease--a response