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Haemophilus ducreyi.

Genital ulcer disease as a risk factor for HIV transmission has become apparent in the fight against AIDS. In poor communities in developing countries with people living under low hygienic conditions chancroid is often reported to be the most common form of genital ulcer. It is caused by Haemophilus ducreyi; a fastidious bacterium, notoriously difficult to grow in the laboratory. Apart from a few small micro-epidemics from time to time the disease, which has interesting immunological aspects, is now rare and almost forgotten in most industrialized countries. This may be part of the reason why there is no simple and inexpensive diagnostic test available yet that would be useful in the low-resource settings where chancroid is prevalent. The present review focuses on the diagnosis and pathogenesis of chancroid.

Chancroid↗

Comparison of clinically directed, disease specific, and syndromic protocols for the management of genital ulcer disease in Lesotho.

OBJECTIVE: To evaluate two protocols for the syndromic management of genital ulcer disease (GUD) in Lesotho, southern Africa and to compare the performance of these protocols with that of a conventional disease specific approach. METHODS: A cross sectional study was conducted among consecutive patients with GUD attending an STD clinic in Maseru, Lesotho. The clinical diagnoses were made by using predefined criteria at the initial visit before the performance of laboratory tests. Attempts were made to detect the specific aetiology of the genital ulcers using PCR assays and syphilis serology. The results of PCR assays and syphilis serology were used as the gold standard against which the performance of the management approaches were applied. RESULTS: Of 100 patients initially recruited into the study, Haemophilus ducreyi infection was detected in 56%, herpes simplex virus in 26%, Treponema pallidum in 23%, and lymphogranuloma venereum in 7%. No pathogens were detected in 6% of patients. 17% of patients had mixed infections. Sensitivity, specificity, positive and negative predictive values of the three management protocols for GUD were compared after applying each to the study population. Theoretically, the lowest correct treatment rate would have been obtained by using the disease specific protocol (62%) compared with more than 90% in both syndromic management protocols. Considerable overtreatment for primary syphilis would occur following application of both syndromic protocols. This would be the result of the overdiagnosis of chancroid, in particular the misdiagnosis of genital herpes as chancroid, which would receive treatment for syphilis unnecessarily. The HIV seroprevalence among these patients was 36%. A significantly higher rate of HIV seropositivity was detected among the patients with herpes simplex virus infection when compared with those patients having other causes of genital ulcer disease (58% v 27%; odds ratio 3.73; 95% CI 1.26-11.26; p = 0.01). CONCLUSIONS: Poor sensitivity, specificity, and predictive values were recorded when the disease specific protocol was applied to the study population. In contrast, the syndromic management protocols provided adequate treatment for more than 90% of patients with GUD. Protocol C, which identified a minority of cases of genital herpes, was found to have an advantage when compared with protocol B (all patients with genital ulcer disease treated for both syphilis and chancroid) in that 29% of genital herpes cases would receive appropriate counselling.

Chancroid↗

[Chronic genital ulcerations and HIV infection: 29 cases].

Genital ulcers are common manifestations of infectious disease. The incidence of genital ulcers featuring a chronic course has increased since the beginning of the AIDS epidemic. The purpose of this 18-month cross-sectional study was to determine the main infectious causes of chronic genital ulcers (CGU) and their correlation with HIV infection. A total of 29 patients with CGU defined as an ulcer showing no sign of healing after more than one month were studied. Mean age ranged from 24 to 54 years. The male-to-female sex ratio was 1:5. The etiology was herpes in 19 cases (65.5 p. 100), chancroid in 6 cases (20.6 p. 100), streptococcal infection in 2 cases (6.8 p. 100), Pseudomonas aeruginosa infection in 1 case (3.4 p. 100) and cutaneous amibiasis in 1 case (3.4 p. 100). Twenty-two patients (75.8 p. 100) presented HIV infection including 16 with HIV1 and 6 with HIV1 and HIV2. All patients with herpes were HIV-positive. Eighteen of these patients were in stage C3 of HIV infection. Genital herpes was the main etiology of UGC in patients with HIV infection (p < 0.001). Conversely chancroid was the main etiology in patients without HIV infection (p < 0.05). This finding suggests that herpetic CGU is highly suggestive of AIDS whereas chancroid CGU is not. Although syphilis is widespread in Africa, it was not a cause of CGU in this study. Search for herpes simplex virus or Haemophilus ducreyi in patients with CGU is an important criteria for presumptive diagnosis of AIDS in Africa.

Adult↗

Genital ulcers in women.

Women who are in a low socioeconomic status are most vulnerable to genital ulcer disease (GUD). GUD is recognized as an important co-factor for acquisition of HIV. GUD etiology has been elucidated in the past decade, with the availability of multiplex polymerase chain reaction. Worldwide, herpes simplex virus-2 (HSV-2) is the leading cause of GUD. However, mainly in women in developed countries, the incidence of GUD causation by HSV-1 is rising, owing to adolescents who are HSV-1 naïve and to increased oral sex practices. Especially in some African countries, the still high prevalence of chancroid should decrease in the next decade, because chancroid can easily be avoided and treated. Syphilitic ulcers seemed to be almost extinct, but recently there has been a resurgence of syphilis worldwide with the availability of effective HIV treatment. Development of herpes and chancroid vaccines, condom use, and the provision of education and accessible treatment facilities should help those women who now suffer from recurrent GUD infections.

Adolescent↗

Human immunodeficiency virus, genital ulcers and the male foreskin: synergism in HIV-1 transmission.

Epidemiologic studies in Nairobi and elsewhere in Africa, have shown that men infected with HIV-1 more commonly have a history of genital ulcer disease compared to uninfected men. In one study, HIV infected men were three times as likely to have a recent history of genital ulcers. In a prospective study of seronegative men, those presenting with chancroid had a five-fold risk of seroconversion during follow-up compared to men presenting with urethritis. Uncircumcised men had an increased risk of seroconversion which was independent of their risk of genital ulcer disease. Over 95% of attributable risk in men with STD was either genital ulceration or the presence of a foreskin. Genital ulcers are a major risk factor for HIV infection among prostitutes. The increased risk is about 10-fold among prostitutes with ulcers compared to a cohort who did not. We hypothesize from these studies that genital ulcers are the major portals of entry for HIV infection and also increased shedding of virus infected cells into the vaginal secretions. HIV seropositive prostitutes are more susceptible to chancroid with a two-fold increase in the prevalence of genital ulcers as compared to HIV negative women. The use of condoms by their clients prevents both genital ulcer disease and HIV acquisition among prostitutes. Chancroid is more difficult to treat in HIV infected men with one-third of patients failing single dose treatment regimens as compared to less than five percent of men without HIV infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗

[The etiopathogenesis of ulcus molle: current status of knowledge--approaches to future research].

Chancroid is a sexually transmitted disease characterized by genital ulceration. Although the pathology of chancroid lesions has been well described, we still know relatively little about the mechanism by which the causative agent, the bacterium Haemophilus ducreyi, produces disease. It is hoped that a better understanding of both the pathogenicity of H. ducreyi and the pathogenesis of chancroid will provide a rational basis for the development of improved strategies for the control of this disease.

Animals↗

[Sexually transmissible diseases following travel in tropical countries].

Travel to tropical countries is an important factor in the spread of sexually transmitted diseases. In spite of intensive anti-AIDS campaigns, some 30% of Swiss tourists have casual sexual contacts abroad. The prevalence of sexually transmitted diseases is higher in tropical countries than in western industrialized countries. More than 25% of cases of gonorrhea treated in Switzerland from 1989-1991 were imported from abroad. The penicillin producing Neisseria gonorrhoeae strains (PPNG) isolated in Switzerland from 1989-1991 are mainly imported from abroad (60%). The typical "imported sexually transmitted diseases" in Switzerland are chancroid, lymphogranuloma venereum and donovanosis. The clinical manifestations, laboratory and special examinations, and treatment of these diseases are described. The most frequent sexually transmitted disease from the so-called "imported tropical STD's" is chancroid. Chancroid is also a major risk factor for HIV infection.

Chancroid↗

Approach to the patient with genital ulcer disease.

The three major diseases characterized by genital ulcers--genital herpes, syphilis, and chancroid--are common, with genital herpes being most common in industrialized countries and chancroid being most common in developing countries. One fourth to one half of patients with genital ulcers have no diagnosed cause for their illness despite diagnostic efforts. The bulk of these cases is probably constituted by one of the three diseases for which diagnostic tests are falsely negative. There is accumulating evidence that genital ulcers facilitate the transmission of human immunodeficiency virus (HIV), and they may also be markers of high-risk behavior for acquisition of HIV. Appropriate therapy of patients with genital ulcers (as well as their sexual partners) depends on accurate diagnosis. Patients with genital ulcers, particularly those with syphilis or chancroid, should be encouraged to undergo testing for HIV infection.

Diagnosis, Differential↗

Iron and virulence of Haemophilus ducreyi in a primate model.

BACKGROUND AND OBJECTIVES: The pathogenesis of chancroid is currently unclear. There are discrepancies between the virulence of Haemophilus ducreyi in the human and animal experiments. Iron availability influences the virulence of many pathogens. The objective of this study was to investigate the role of iron in virulence of H. ducreyi. STUDY DESIGN: Intradermal inoculation of the primate Macaca mulatta was studied as an animal model for pathogenesis of chancroid. This model then was used to study the influence of iron availability on virulence of H. ducreyi. Eleven strains of H. ducreyi with proven avirulence in the rabbit intradermal test and one virulent control strain were used. Two of the strains had been shown to cause ulcers in a human inoculation experiment. Strains were suspended in fluid with different iron compounds before intradermal injection. Other monkeys were treated with injectable iron before inoculation with bacteria suspended. RESULTS: All but one of the test strains produced a chancroid-like ulcer from which H. ducreyi could be isolated. The minimal ulcerative dose was 10(5) cfu. Iron in the injection fluid decreased this dose 10-fold. In animals pretreated with intramuscular iron, the minimal ulcerative dose decreased to 10(4) cfu and all eleven strains became ulcerative. CONCLUSIONS: The availability of iron increases virulence of H. ducreyi. The iron pretreated primate model is useful for the study of virulence factors of H. ducreyi because of its ability to produce lesions with strains that avirulent in other animal models but pathogenic to humans.

Animals↗

Antimicrobial susceptibility of Haemophilus ducreyi.

The susceptibility of 19 isolates of Haemophilus ducreyi from a recent chancroid outbreak and four reference strains was determined in vitro to 13 antimicrobial agents. The rabbit intradermal test for virulence was positive for all of the local isolates, but not for the reference strains. The "nonvirulent" reference strains were inhibited by lower minimum inhibitory concentrations (MICs) of most agents tested. For the virulent isolates, the range of MICs (in micrograms per milliliter) of the following were: of vancomycin, 8 to 128; of polymyxin, 32 to 128; of cloxacillin, 32 to 64; of tetracycline, 0.5 to 32; of cephalothin, 4 to 8; of doxycycline, 0.25 to 8; and of kanamycin, 1 to 8. Three strains were resistant to penicillin and ampicillin (MIC >/= 128 mug/ml), and these three strains produced beta-lactamase. The remainder were susceptible to 4 mug/ml. All strains were susceptible to rifampin (MIC </= 1 mug/ml), chloramphenicol (MIC </= 4 mug/ml), sulfisoxazole (MIC </= 8 mug/ml), and nalidixic acid (MIC </= 8 mug/ml). These susceptibilities of H. ducreyi indicate several antimicrobial agents that may be effective for chancroid treatment and support the use of vancomycin in a selective medium for the culture of chancroid genital ulcers.

Animals↗

Clinical and microbiological evaluation of 46 episodes of genital ulceration.

In 44 consecutive patients 46 episodes of genital ulceration were studied. The presumptive clinical diagnosis was evaluated by extensive microbiological investigations. In 15 (33%) episodes the clinical diagnosis did not accord with the microbiological one. Chancroidal lesions were most commonly found to have other microbiological aetiology. Secondary invasion of treponemal or viral lesions by other bacterial species (mostly anaerobes or pyogenic cocci) or genital pyodermia were the cause of confusion in six of nine cases of chancroid. In the other three a ducreyilike bacterium was found. Direct Gram staining of ulcer material did not help the diagnosis of chancroid. The implications of the results of this study for clinical practice are discussed.

Adult↗

HIV-1 seroconversion in patients with and without genital ulcer disease. A prospective study.

OBJECTIVE: To determine the relative risk for human immunodeficiency virus (HIV-1) seroconversion in patients with and without genital ulcers caused by chancroid, syphilis, and herpes. DESIGN: A prospective cohort study. SETTING: An inner-city, sexually transmitted disease clinic. PATIENTS: Patients seronegative for HIV-1 with and without genital ulcers who were followed for a minimum of 3 months. INTERVENTIONS: Questionnaire to obtain data on demographics, sexual behavior, and illicit drug use; testing for HIV-1 at entry and at a minimum of 3 months after entry; medical examination for the presence or absence of genital ulcer disease. RESULTS: Overall, 758 heterosexual men with no history of injection drug use completed the study; HIV-1 seroconversion occurred in 10 of 344 (2.9%; 95% CI, 1.4% to 5.3%) men with a genital ulcer and in 4 of 414 (1%; CI, 0.2% to 2.5%) without a genital ulcer (relative risk, 3.0; P = 0.05). In a multiple logistic regression analysis, those men with chancroid and a new sexually transmitted disease during follow-up each had about three times the risk for HIV-1 seroconversion (P < or = 0.04). CONCLUSIONS: In this group of heterosexual men, chancroid and repeated acquisition of sexually transmitted diseases appeared to facilitate the sexual transmission of HIV-1.

Adult↗

Genital ulceration in males at Ga-Rankuwa Hospital, Pretoria.

One hundred previously untreated Black male patients presenting with genital ulceration were seen as outpatients at Ga-Rankuwa Hospital, Pretoria. Syphilis was the commonest cause of ulceration, being present alone in 33% of patients. Chancroid occurred almost as frequently, being found alone in 28% of cases. A double infection with both syphilis and chancroid occurred in a further 16%. Herpes genitalis was found alone in 4% and together with chancroid in 1%. One patient was found to have granuloma inguinale and another had lymphogranuloma venereum. In 16% of the patients no cause for the ulcerations could be found.

Adolescent↗

Sexually transmitted diseases in the tropics.

Several sexually transmitted diseases are endemic in the tropics. The morbidity and mortality from the human immunodeficiency viruses (HIV-1 and HIV-2) alone now rival that caused by Plasmodium falciparum malaria in several African and Asian nations. The genital ulcers of chancroid and syphilis facilitate the sexual transmission of HIV. Within the last two decades, the bacteria causing chancroid and gonorrhoea throughout the world have acquired plasmids that mediate bacterial resistance to penicillins and other antibiotics. This has significantly increased the costs of treatment. There is little prospect that the prevalence of gonorrhoea, chancroid, syphilis and HIV will decrease in the tropics in the near future without a global change in sexual behaviours and practices.

Female↗

Antibodies directed against Haemophilus ducreyi heat shock proteins.

The response to heat shock in Haemophilus ducreyi has been investigated by labelling newly synthesized proteins with a pulse of 35S-methionine at a range of temperatures between 30-40 degrees C. Proteins were then separated by SDS-PAGE and analysed by autoradiography of the resultant profiles. Four heat shock proteins (HSP) were identified of apparent molecular weight < 14, 58.5, 74 and 78 kDa. The three larger proteins appeared to be independently controlled and inducible in a range of H. ducreyi strains. The protein profiles were also probed by Western blot with serum from an immunized rabbit, serum from a rabbit infected intradermally with H. ducreyi, mouse monoclonal antibodies (MAb) and a pool of human sera from patients with chancroid. The rabbit sera, the human serum pool and MAb (BB11) reacted with epitopes on the HSP of 58.5 kDa, whereas only the immunized rabbit serum and another MAb (CC11) reacted with epitopes on the HSP of 78 kDa. The HSP of 58.5 kDa appears to be immunogenic and may play a part in the host response to H. ducreyi and the pathogenesis of chancroid.

Animals↗

Attachment of Haemophilus ducreyi to human foreskin fibroblasts involves LOS and fibronectin.

Haemophilus ducreyi is the causative agent of the genital ulcer disease Chancroid. Chancroid has been shown to increase the risk of heterosexual transmission of HIV. Little is known regarding the attachment or localization of this organism to human cells in either the dermal or epidermal layer. In this study the attachment of H. ducreyi to human foreskin fibroblast (HFF) cells was further characterized. Attachment was mediated by more than one mechanism. Proteinase K treatment but not trypsinization of H. ducreyi significantly reduced attachment suggesting protein involvement. In addition, purified lipooligosaccharide (LOS) was able to inhibit attachment in a dose dependent manner. It appeared that the organism binds to fibronectin in the extracellular matrix of HFF cells, since competition studies using fibronectin showed that it was able to significantly reduce attachment in a dose dependent manner whereas collagen did not. We hypothesize that the attachment of H. ducreyi involves both a protein mediator of attachment (likely pili) as well as LOS and that one or both of these bacterial components interacts with fibronectin in the extracellular matrix to mediate attachment to HFF cells.

Antibodies, Monoclonal↗

Beta-lactams in sexually transmitted diseases: rationale for selection and dosing regimens.

A review is given of the selection and rational of optimal treatment regimens for patients with sexually transmitted pathogens, e.g. in cases of gonorrhea, chlamydial infections, chancroid, syphilis, pelvic inflammatory diseases and ophthalmia neonatorum. The scientific basis for the selection of a beta-lactam agent is discussed, including dose, MIC, the critical serum level and maintenance interval, and the duration of therapy. Except in the case of penicillinase-producing Neiserria gonorrhoeae, penicillin remained until recently the most effective agent available against many sexually transmitted diseases. However, ceftriaxone, a new third-generation cephalosporin, has been shown to have a long half-life (8 h) and excellent in vitro efficacy against Neiserria gonorrhoeae (including penicillinase-producing strains) and Haemophilis ducreyi. In view of its exceptional clinical efficacy against both gonorrhea and chancroid, clinical studies of its efficacy against other sexually transmitted diseases appear warranted.

Anti-Bacterial Agents↗

Laboratory diagnosis of Haemophilus ducreyi: sensitivity of culture media.

Laboratory confirmation of the clinical diagnosis of chancroid requires the isolation of Haemophilus ducreyi. Enriched gonococcal (GcHbS) and Mueller-Hinton agar (MHHb) both support the growth of most strains of H. ducreyi. In this study we compared the isolation rate of H. ducreyi on GcHbs and MHHb media in 111 men with genital ulcer disease. A second culture was obtained in 84 men at 48 hr in order to determine the reproducibility of H. ducreyi culture. The sensitivity of a single and a sequential pair of cultures on GcHbS was 67% and 74%, respectively, on men with presumed chancroid. The sensitivity of the MHHb as a single culture was 53%. Using both media for the initial culture of genital ulcers, and repeating the culture on GcHbs at 48 hr, increased the sensitivity of the isolation of H. ducreyi to 92% in men who had no prior antimicrobial use and who had no laboratory evidence of primary syphilis.

Chancroid↗