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Sexually transmitted diseases in children.

Fifty eight (16%) of the 362 patients, who reported to Dermatology and STD Department with symptoms pertaining to their genitourinary system were below 14 years of age. Fifty four (93.1%) of these children belonged to families of lower socio-economic strata. All the children were slum dwellers and none of them had studied beyond the third class. Syphilis was seen in 27.6%, gonorrhea in 24.1%, chancroid in 22.4%, candidiasis in 10.3%, condylomata acuminata in 6.9% and herpes genitalis in 6.9% of these children. The probable reasons for the increased prevalence of sexually transmitted diseases in children as ascertained by this study were sexual promiscuity and probably sexual assault.

Adolescent↗

Epidemiology of sexually transmitted diseases in Singapore, 1977 to 1993.

The pattern and prevalence of sexually transmitted diseases (STDs) have changed over the past decades. There is a decline in the prevalence of STDs in many countries. The prevalence of bacterial STDs including gonorrhoea, syphilis and chancroid have declined because of the availability of effective antibiotics whereas the prevalence of viral STDs, including herpes simplex and viral warts, have increased as no effective antiviral drugs are available for these infections at present. The highest proportion of patients with STDs are still those below 30 years old. Most of the patients acquire STDs from commercial sex workers. Health education and prevention remain the most important ways to control STDs until effective antiviral agents and vaccines against STDs become available. Constant monitoring of the trends of STDs will help the authorities to implement relevant and cost-effective preventive programmes.

Adolescent↗

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.

Adolescent↗

Antimicrobial therapy of non-viral sexually transmitted diseases--an update.

Azithromycin is an azalide antibiotic with important properties which allow it to be used as a single-dose treatment for genital Chlamydia trachomatic infections. A single 1 g dose is as effective as a standard seven-day course of doxycycline. Ofloxacin 400 mg bid for seven days is also effective against Chlamydia trachomatis. Both azithromycin 2 g and ofloxacin are also effective against uncomplicated gonorrhoea. Neisseria gonorrhoeae continues to be sensitive to third generation cephalosporins, e.g. ceftriaxone 125 mg. Oral single dose cephalosporins offer ease of administration and safety, e.g. cefixime (400 mg), cefuroxime axetil (1 g) and cefpodoxime proxetil (200 mg). The fluoroquinolones, e.g. ciprofloxacin (500 mg) and ofloxacin (400 mg), are being increasingly used as first-line medications, however, caution is recommended as the development of resistance is anticipated and already being detected in many areas. Syphilis continues to be sensitive to penicillin. This should be administered parenterally. Coexistent human immunodeficiency virus infection may make standard therapy inadequate, and closer follow-up is recommended. Therapy with non-penicillin antibiotics is still inadequately studied. Chancroid is treated with ceftriaxone, ciprofloxacin, azithromycin, or erythromycin. In some areas, resistance to tetracyclines and TMP-SMX has made these drugs ineffective as first-line treatments. Bacterial vaginosis is effectively treated with a single dose of metronidazole 1 g or 500 mg bid over seven days. Similar regimens are also effective against trichomoniasis. Vulvovaginal candidiasis can be treated with topical imidazole preparations or oral antifungal medications.

Chancroid↗

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.

Chancroid↗

Evidence of Haemophilus ducreyi adherence to and cytotoxin destruction of human epithelial cells.

The adherence of ten different Haemophilus ducreyi strains to cultured human epithelial cells and the subsequent destruction of these cells was investigated in vitro using HEp-2 and HeLa cells. Bacterial adherence was measured with two assays, one employing viable bacteria and the other radiolabeled bacteria. In addition, the capacity of H. ducreyi to invade/penetrate the HEp-2 cells was examined. Differential interference contrast and transmission electron microscopy techniques were also used. In both cell lines, all ten strains of H. ducreyi manifested substantial adherence (the rates being 4-20% of the inoculum), irrespective of whether the bacteria were cultivated on solid or liquid media. Bacterial adherence reached a peak after about 2-3 h of incubation, though it was already manifest after only 15 min, a finding suggesting constitutive rather than inducible properties of H. ducreyi adhesins to be involved. The adherence capacity was diminished, but not totally abolished, when bacteria were heat-treated at 100 degrees C for 30 min, indicating the adhesins to be fairly stable. On the other hand, treatment of HEp-2 cells with methanol, glutaraldehyde and emetine dichloride significantly reduced the adherence, indicating viable eukaryotic cells with native surface structures to be involved in bacterial adherence. This capacity of H. ducreyi to adhere to HEp-2 cells was confirmed both by electron microscopy and by differential interference microscopy. Some adherent bacteria were also capable of penetrating epithelial cells, as observed with an invasion assay and confirmed by transmission electron microscopy. Further incubation of the cell monolayers with the ten strains resulted in the cell-death and total damage of monolayers for seven cytotoxin-producing strains, indicating cytotoxin action to be responsible for the destruction of the monolayer. All strains manifested capacity to survive and multiply on the cell monolayer. We propose the first step in the pathogenesis of chancroid to be the adherence of bacteria to epithelial cells, followed by the action of cytotoxin and further bacterial proliferation. This sequence of events is suggested to result in the production of genital ulcers by H. ducreyi organisms.

Bacterial Adhesion↗

Haemophilus ducreyi adheres to human keratinocytes.

Haemophilus ducreyi, Moraxella catarrhalis and a non-piliated Escherichia coli K-12 strain were studied for their ability to bind to human keratinocytes in vitro. Epidermal cells isolated from neonatal foreskins were grown to confluence in serum-free keratinocyte media. Probing of the monolayers with anti-cytokeratin antibody showed that 97% of cells were keratinocytes. Bacteria were grown to mid-log phase and seeded onto the monolayers. At various time-points monolayers were washed with PBS to remove non-adherent bacteria, and the monolayers were quantitatively cultured. After 120 min, 15 to 23% of the H. ducreyi inocula bound to the monolayer, while less than 1% of the M. catarrhalis or E. coli controls bound. Wet mounts of fixed monolayers observed with differential interference contrast microscopy confirmed the quantitative data. We conclude that H. ducreyi binds to keratinocytes and that this process may play a role in the initiation of chancroid.

Bacterial Adhesion↗

The impact of Haemophilus ducreyi cytolethal distending toxin on cells involved in immune response.

The Haemophilus ducreyi cytolethal distending toxin (HdCDT) induces cell cycle arrest and thereby inhibits cell proliferation of many cultured mammalian cell-lines. We investigated the effect of HdCDT on circulating human hematopoietic cells, including T- and B-cells, monocytes and polymorphonuclear cells (PMN). Lymphocytes were stimulated with T- and B-cell specific mitogens, whereas monocytes and PMN with endotoxin. HdCDT inhibited the mitogen-induced proliferation of T-cells in a dose-dependent manner as assayed by [(3)H]-thymidine incorporation and MTT assays. Similarly to T-cells, HdCDT also inhibited the proliferation of B-cells and consequently the immunoglobulin production, measured by ELISPOT and ELISA assays. In contrast, the HdCDT did not affect monocytes or PMN, as measured by MTT assay. The TNF-alpha production by monocytes and the phagocytic ability of PMN were neither affected. The monocytic cell line THP-1 was, however, sensitive to the toxin, seen as a reduction of proliferation and viability after exposure to HdCDT. In conclusion, exposure to HdCDT significantly affects the proliferation and other biological activities of stimulated human T- and B-cells, while circulating monocytes and PMN are not sensitive to HdCDT. The sensitivity of cells of the acquired immune system to HdCDT may hamper specific host response to H. ducreyi and contribute to persistence of chancroid lesions.

B-Lymphocytes↗

Quinolone antibacterial agents for the treatment of genitourinary tract infections.

The fluoroquinolones have expanded the therapeutic options available for the treatment of genitourinary tract infections. Their ease of oral administration, favourable pharmacokinetics, low incidence of adverse reactions, and broad spectrum of in vitro activity against aerobic and facultative organisms make them especially suitable for treating bacteriuria, particularly when pathogens are resistant to other available oral agents. Their efficacy has also been established in the treatment of prostatis, gonorrhea and chancroid. They have lower in vitro activity against chlamydia, ureaplasma and anaerobes, and their role in the treatment of non-gonococcal urethritis, vaginitis and acute pelvic inflammatory disease is less well established.

4-Quinolones↗

[European Association of Urology guidelines on urinary and male genital tract infections].

Today, the classical bacteria that cause venereal diseases, e.g. gonorrhea, syphilis, chancroid and inguinal granuloma, only account for a small proportion of all known sexually transmitted diseases (STDs). Other bacteria and viruses as well as yeasts, protozoa and epizoa must also be regarded as causative organisms of STD. Taken together, all sexually transmitted infections comprise more than 30 relevant STD pathogens. However, not all pathogens that can be sexually transmitted manifest diseases in the genitals and not all infections of the genitals are exclusively sexually transmitted. Concise information and tables summarising the diagnostic and therapeutic management of STDs in the field of urology allow a synoptic overview, and are in agreement with the recent international guidelines of other specialist areas. Special considerations (i.e. HIV infection, pregnancy, infants, allergy) and recommended regimens are presented.

Disease Notification↗

Mouse subcutaneous chamber model for in vivo growth of Haemophilus ducreyi.

The ability of Haemophilus ducreyi, the causative agent of chancroid, to grow in subcutaneous chambers implanted in mice was studied. All seven H. ducreyi strains tested were able to maintain a long-term infection in ICR mice; one mouse remained infected with strain Hd175 for more than 4 months. Growth curves obtained following the removal of chamber fluid at various time points from infected mice demonstrated that H. ducreyi was growing during the course of the infection. In addition, all three mouse strains tested (ICR, CBA and BALB/c) were able to maintain long-term H. ducreyi infections. This model will be valuable in studying the effects of in vivo growth on the antigenic composition of H. ducreyi as well as for the identification of virulence factors.

Animals↗

Interactions of Haemophilus ducreyi and purified cytolethal distending toxin with human monocyte-derived dendritic cells, macrophages and CD4+ T cells.

To evaluate the early stages of the host response to chancroid bacterium Haemophilus ducreyi, we investigated the in vitro responses of monocyte-derived dendritic cells (DCs) and macrophages (MQs) to this pathogen and Haemophilus influenzae. The phagocytic activities and pro-inflammatory cytokine secretion profiles of the antigen-presenting cells (APCs) were analyzed after exposure to gentamycin-killed bacteria, H. ducreyi lipooligosaccharide (LOS), and purified cytolethal distending toxin (HdCDT). T-cell proliferation and cytokine release were examined after co-culturing isolated autologous CD4+ T cells with antigen-pulsed APCs. Both the DCs and MQs phagocytosed H. ducreyi and H. influenzae, as estimated by flow cytometry. All of the strains induced APC secretion of TNF-alpha, IL-6, IL-8, and IL-12, as measured by ELISA. Other human cells, particularly endothelial cells and fibroblasts, also produced cytokines when stimulated with these bacteria. Purified LOS at concentration 1 microg/ml induced two to threefold lower levels of cytokines than the whole bacteria, which indicates that other components are involved in immune activation. HdCDT inhibited partially the production of the aforementioned cytokines. High levels of IFN-gamma, but not of IL-4 and IL-13, were secreted by T cells after activation by either DCs or MQs that were pre-exposed to bacteria, indicating the Th1 nature of the immune response. The levels of T-cell proliferation induced by H. ducreyi were lower than those induced by H. influenzae. HdCDT-treated APCs did not display cytokine responses or T-cell proliferation. These results indicate that HdCDT intoxication, which results in progressive apoptosis of APCs, may hamper early stage immune responses.

Apoptosis↗

Induction of apoptosis/necrosis in various human cell lineages by Haemophilus ducreyi cytolethal distending toxin.

We investigated the impact of highly purified Haemophilus ducreyi cytolethal distending toxin (HdCDT) on the apoptosis and necrosis of various human cells; including myeloid cells, epithelial cells, keratinocytes, and primary fibroblasts. The levels of apoptosis and necrosis induced in these cells were compared to those induced by HdCDT in human T cells and in the Jurkat T cell line. Levels of caspase-3 activity were measured, and membrane changes like phosphatidylserine (PS) translocation was evaluated after double-staining with the fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI) using flow cytometry. HdCDT induced various degrees of apoptosis and necrosis in dose- and time-dependent manners in cells of various lineages. Early and late apoptosis (annexin V-stained cells) were induced in more than 90% of T cells and monocytes after treatment with 100 ng/ml HdCDT for 24 and 48 h, respectively. The corresponding numbers for epithelial cells, keratinocytes, and fibroblasts were 26-32% after treatment with 100 ng/ml HdCDT for 48 h. HdCDT appears to eliminate effectively by inducing apoptosis those cells that are involved in immune responses. Epithelial cells, keratinocytes and fibroblasts, which are important for the healing of chancroid ulcers, are eliminated by apoptosis or necrosis after contact with HdCDT, albeit slower and to a lesser extent than T cells.

Annexin A5↗

Cutaneous manifestations of sexually transmitted diseases.

Sexually transmitted diseases remain a prevalent problem in the United States and throughout the world, despite efforts in prevention and education. This review highlights the cutaneous manifestations of the following sexually transmitted diseases: syphilis, chancroid, lymphogranuloma venereum, granuloma inguinale, genital herpes, genital warts, scabies, and pediculosis pubis. Emphasis is placed on the clinical findings, diagnostic methodology, and recommended treatment for each disease.

Humans↗

Sexually transmitted diseases and travelers.

Sexually active travelers are at risk for a variety of STDs, including traditional venereal infections such as gonorrhea, chlamydial urethritis, syphilis, chancroid, and herpes simplex infection. More recently, hepatitis B, hepatitis C, and HIV-1 have also been described. Risk varies depending on the geographic area of travel and the type of sexual contact. Physicians should be aware of the prevalence of antimicrobial resistance of N. gonorrhoeae and H. ducreyi because this will affect empiric antibiotic therapy. Prevention should focus on proper and consistent usage of barrier contraceptives.

Humans↗

Amebiasis of the penis.

Penile amebiasis is rarely a recognized entity because the penis is not the usual site of presentation for amebiasis. Homosexual men have a higher risk of acquiring the lesion. Amebic ulcers resemble cutaneous lesions arising from squamous cell carcinoma, chancroid, primary syphilis, granuloma inguinale, and many other causes. An amebic ulcer should be suspected in a patient with balanoposthitis that resists antibiotic therapy. Biopsy is fundamental to isolate the trophozoites to confirm the diagnosis. Metronidazole and hydrochloric emetine are still the treatment of choice. This diagnosis should especially be considered in cases of lesions detected in patients who practice anogenital sex or who are immunocompromised.

Adolescent↗