Chancroid: from clinical practice to basic science.

PubMed

Lewis, D A

2000-01-01

Chancroid is a sexually transmitted disease caused by the bacterium Haemophilus ducreyi. It usually presents as a genital ulcer and may be associated with regional lymphadenopathy and bubo formation. H. ducreyi infection is predominantly seen in tropical resource-poor regions of the world where it is frequently the most common etiological cause of genital ulceration. Genital ulcer disease has been shown to be an extremely important co-factor in HIV transmission. With the advent of the AIDS epidemic, there has been increased research effort to elucidate those factors involved in the pathogenesis of chancroid. Several putative virulence factors have now been identified and isogenic H. ducreyi mutants constructed by mutagenesis of their encoding genes. This approach has facilitated investigations into the role each of these putative virulence factors may play in H. ducreyi pathogenesis through the use of in vitro and in vivo model systems. One major goal of current chancroid research is to identify antigens which are immunogenic and could form the basis of a vaccine against H. ducreyi infection. Such a vaccine, if shown to be effective in decreasing the prevalence of chancroid, could have the added benefit of slowing down the HIV incidence rates in those populations where chancroid is a major co-factor for HIV transmission.

Rising incidence of chancroid in Rotterdam. Epidemiological, clinical, diagnostic, and therapeutic aspects.

PubMed Central

Nayyar, K C; Stolz, E; Michel, M F

1979-01-01

The incidence of chancroid in Rotterdam has increased by more than five-fold during 1977-78. In a retrospective study of 53 patients with chancroid seen at this clinic during this period, the results of smears were positive in 82% and of cultures in 84% (of those for whom cultures had been performed). Symptoms were generally mild. Treatment with co-trimoxazole was highly effective clinically, as confirmed by in-vitro sensitivity studies. PMID:526847

2017 European guideline for the management of chancroid.

PubMed

Lautenschlager, Stephan; Kemp, Michael; Christensen, Jens Jørgen; Mayans, Marti Vall; Moi, Harald

2017-03-01

Chancroid is a sexually acquired infection caused by Haemophilus ducreyi. The infection is characterized by one or more genital ulcers, which are soft and painful, and regional lymphadenitis, which may develop into buboes. The infection may easily be misidentified due to its rare occurrence in Europe and difficulties in detecting the causative pathogen. H. ducreyi is difficult to culture. Nucleic acid amplification tests can demonstrate the bacterium in suspected cases. Antibiotics are usually effective in curing chancroid.

European guideline for the management of chancroid, 2011.

PubMed

Kemp, M; Christensen, J J; Lautenschlager, S; Vall-Mayans, M; Moi, H

2011-05-01

Chancroid is a sexually acquired disease caused by Haemophilus ducreyi. The infection is characterized by one or more genital ulcers, which are soft and painful, and regional lymphadenitis which may develop into buboes. The infection may easily be misidentified due to its rare occurrence in Europe and difficulties in detecting the causative pathogen. H. ducreyi is difficult to culture. Polymerase chain reaction (PCR) can demonstrate the bacterium in suspected cases. Antibiotics will usually be efficient for curing chancroid.

Immunization with the Haemophilus ducreyi hemoglobin receptor HgbA protects against infection in the swine model of chancroid.

PubMed

Afonina, Galyna; Leduc, Isabelle; Nepluev, Igor; Jeter, Chrystina; Routh, Patty; Almond, Glen; Orndorff, Paul E; Hobbs, Marcia; Elkins, Christopher

2006-04-01

The etiologic agent of chancroid is Haemophilus ducreyi. To fulfill its obligate requirement for heme, H. ducreyi uses two TonB-dependent receptors: the hemoglobin receptor (HgbA) and a receptor for free heme (TdhA). Expression of HgbA is necessary for H. ducreyi to survive and initiate disease in a human model of chancroid. In this study, we used a swine model of H. ducreyi infection to demonstrate that an experimental HgbA vaccine efficiently prevents chancroid, as determined by several parameters. Histological sections of immunized animals lacked typical microscopic features of chancroid. All inoculated sites from mock-immunized pigs yielded viable H. ducreyi cells, whereas no viable H. ducreyi cells were recovered from inoculated sites of HgbA-immunized pigs. Antibodies from sera of HgbA-immunized animals bound to and initiated antibody-dependent bactericidal activity against homologous H. ducreyi strain 35000HP and heterologous strain CIP542 ATCC; however, an isogenic hgbA mutant of 35000HP was not killed, proving specificity. Anti-HgbA immunoglobulin G blocked hemoglobin binding to the HgbA receptor, suggesting a novel mechanism of protection through the limitation of heme/iron acquisition by H. ducreyi. Such a vaccine strategy might be applied to other bacterial pathogens with strict heme/iron requirements. Taken together, these data suggest continuing the development of an HgbA subunit vaccine to prevent chancroid.

Cutaneous chancroid in a visitor from Vanuatu.

PubMed

McBride, William J H; Hannah, Rory C S; Le Cornec, Genevera M; Bletchly, Cheryl

2008-05-01

A 23-year-old woman from Vanuatu presented to an Australian hospital with a 3-week history of a non-healing ulcer on the lower leg. A swab was submitted for a multiplex polymerase chain reaction designed to investigate genital ulcerative conditions. Haemophilus ducreyi was detected and the gene product was subsequently sequenced, confirming the diagnosis of cutaneous chancroid. The lesion responded to intramuscular benzathine penicillin. This report adds further evidence that cutaneous chancroid should be considered in the evaluation of skin ulcers in the south Pacific.

Immune Cells Are Required for Cutaneous Ulceration in a Swine Model of Chancroid

PubMed Central

San Mateo, Lani R.; Toffer, Kristen L.; Orndorff, Paul E.; Kawula, Thomas H.

1999-01-01

Cutaneous lesions of the human sexually transmitted genital ulcer disease chancroid are characterized by the presence of intraepidermal pustules, keratinocyte cytopathology, and epidermal and dermal erosion. These lesions are replete with neutrophils, macrophages, and CD4+ T cells and contain very low numbers of cells of Haemophilus ducreyi, the bacterial agent of chancroid. We examined lesion formation by H. ducreyi in a pig model by using cyclophosphamide (CPA)-induced immune cell deficiency to distinguish between host and bacterial contributions to chancroid ulcer formation. Histologic presentation of H. ducreyi-induced lesions in CPA-treated pigs differed from ulcers that developed in immune-competent animals in that pustules did not form and surface epithelia remained intact. However, these lesions had significant suprabasal keratinocyte cytotoxicity. These results demonstrate that the host immune response was required for chancroid ulceration, while bacterial products were at least partially responsible for the keratinocyte cytopathology associated with chancroid lesions in the pig. The low numbers of H. ducreyi present in lesions in humans and immune-competent pigs have prevented localization of these organisms within skin. However, H. ducreyi organisms were readily visualized in lesion biopsies from infected CPA-treated pigs by immunoelectron microscopy. These bacteria were extracellular and associated with necrotic host cells in the epidermis and dermis. The relative abundance of H. ducreyi in inoculated CPA-treated pig skin suggests control of bacterial replication by host immune cells during natural human infection. PMID:10456960

Immunization with the Haemophilus ducreyi Hemoglobin Receptor HgbA Protects against Infection in the Swine Model of Chancroid

PubMed Central

Afonina, Galyna; Leduc, Isabelle; Nepluev, Igor; Jeter, Chrystina; Routh, Patty; Almond, Glen; Orndorff, Paul E.; Hobbs, Marcia; Elkins, Christopher

2006-01-01

The etiologic agent of chancroid is Haemophilus ducreyi. To fulfill its obligate requirement for heme, H. ducreyi uses two TonB-dependent receptors: the hemoglobin receptor (HgbA) and a receptor for free heme (TdhA). Expression of HgbA is necessary for H. ducreyi to survive and initiate disease in a human model of chancroid. In this study, we used a swine model of H. ducreyi infection to demonstrate that an experimental HgbA vaccine efficiently prevents chancroid, as determined by several parameters. Histological sections of immunized animals lacked typical microscopic features of chancroid. All inoculated sites from mock-immunized pigs yielded viable H. ducreyi cells, whereas no viable H. ducreyi cells were recovered from inoculated sites of HgbA-immunized pigs. Antibodies from sera of HgbA-immunized animals bound to and initiated antibody-dependent bactericidal activity against homologous H. ducreyi strain 35000HP and heterologous strain CIP542 ATCC; however, an isogenic hgbA mutant of 35000HP was not killed, proving specificity. Anti-HgbA immunoglobulin G blocked hemoglobin binding to the HgbA receptor, suggesting a novel mechanism of protection through the limitation of heme/iron acquisition by H. ducreyi. Such a vaccine strategy might be applied to other bacterial pathogens with strict heme/iron requirements. Taken together, these data suggest continuing the development of an HgbA subunit vaccine to prevent chancroid. PMID:16552053

Immune cells are required for cutaneous ulceration in a swine model of chancroid.

PubMed

San Mateo, L R; Toffer, K L; Orndorff, P E; Kawula, T H

1999-09-01

Cutaneous lesions of the human sexually transmitted genital ulcer disease chancroid are characterized by the presence of intraepidermal pustules, keratinocyte cytopathology, and epidermal and dermal erosion. These lesions are replete with neutrophils, macrophages, and CD4(+) T cells and contain very low numbers of cells of Haemophilus ducreyi, the bacterial agent of chancroid. We examined lesion formation by H. ducreyi in a pig model by using cyclophosphamide (CPA)-induced immune cell deficiency to distinguish between host and bacterial contributions to chancroid ulcer formation. Histologic presentation of H. ducreyi-induced lesions in CPA-treated pigs differed from ulcers that developed in immune-competent animals in that pustules did not form and surface epithelia remained intact. However, these lesions had significant suprabasal keratinocyte cytotoxicity. These results demonstrate that the host immune response was required for chancroid ulceration, while bacterial products were at least partially responsible for the keratinocyte cytopathology associated with chancroid lesions in the pig. The low numbers of H. ducreyi present in lesions in humans and immune-competent pigs have prevented localization of these organisms within skin. However, H. ducreyi organisms were readily visualized in lesion biopsies from infected CPA-treated pigs by immunoelectron microscopy. These bacteria were extracellular and associated with necrotic host cells in the epidermis and dermis. The relative abundance of H. ducreyi in inoculated CPA-treated pig skin suggests control of bacterial replication by host immune cells during natural human infection.

First reported case of chancroid in the Czech Republic.

PubMed

Rob, Filip; Jilich, David; Lásiková, Šárka; Křížková, Veronika; Hercogová, Jana

2018-01-01

We describe the first case of chancroid seen in the Czech Republic, diagnosed in a 40-year-old heterosexual HIV-positive man. Despite genital localization of the ulcer, the transmission of Haemophilus ducreyi infection in our patient remains unclear, as he denied having sexual intercourse and he did not travel outside the Czech Republic for several months before the ulcer appeared. The correct diagnosis has been revealed by a multiplex nucleic acid amplification test. Physicians in countries in the eastern and central Europe region should be aware that chancroid can occur in their patients.

Chancroid - desperate patient makes own diagnosis.

PubMed

Barnes, P; Chauhan, M

2014-09-01

We report a case of chancroid in a white heterosexual man in the United Kingdom. This patient was seen by four separate health services over a period of five weeks with excruciatingly painful penile ulcers. Despite several negative herpes simplex virus polymerase chain reaction tests and a self-diagnosis of chancroid, he was repeatedly offered multiple courses of aciclovir. This case highlights the need for awareness of alternative diagnoses in persistent cases of genital ulcer disease. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

A comparative study of therapeutic response of patients with clinical chancroid to ciprofloxacin, erythromycin, and cotrimoxazole.

PubMed

D'Souza, P; Pandhi, R K; Khanna, N; Rattan, A; Misra, R S

1998-07-01

Cotrimoxazole has traditionally been used as first drug for treatment of chancroid in India. With reports of increasing resistance to the drug, this study was conducted to compare treatment response of clinical chancroid between ciprofloxacin, 500 mg twice daily for 3 days, erythromycin, 500 mg four times daily for 7 days, and double-strength cotrimoxazole (trimethoprim 160 mg + sulfamethoxazole 800 mg), twice daily for 7 days. Forty-six patients with a clinical diagnosis of chancroid were randomly divided into 3 groups. Sixteen patients received ciprofloxacin, whereas 15 each received erythromycin and cotrimoxazole. Patients were seen on day 7, 14, and if needed day 21. Clinical response was noted in terms of cure, improvement, or failure. Excellent response was observed to both ciprofloxacin and erythromycin therapy with cure rates of 93.7% and 93.3%, respectively. Improvement was observed in 6.7% cases in both groups. There were no failures with either ciprofloxacin or erythromycin. Poor response to cotrimoxazole therapy was observed with 53.3% cure rates and a high failure rate of 46.7%. Ciprofloxacin and erythromycin are equally effective in chancroid. Ciprofloxacin is better in terms of dosage schedule, duration of treatment, and low cost. Cotrimoxazole should be discontinued as drug of choice because of high failure rates.

Oral immunization using HgbA in a recombinant chancroid vaccine delivered by attenuated Salmonella typhimurium SL3261 in the temperature-dependent rabbit model.

PubMed

Breau, Cathy; Cameron, D William; Desjardins, Marc; Lee, B Craig

2012-01-31

Chancroid, a sexually transmitted genital ulcer disease caused by the Gram-negative bacterium Haemophilus ducreyi, facilitates the acquisition and transmission of HIV. An effective vaccine against chancroid has not been developed. In this preliminary study, the gene encoding the H. ducreyi outer membrane hemoglobin receptor HgbA was cloned into the plasmid pTETnir15. The recombinant construct was introduced into the attenuated Salmonella typhimurium SL3261 strain and stable expression was induced in vitro under anaerobic conditions. The vaccine strain was delivered into the temperature-dependent rabbit model of chancroid by intragastric immunization as a single dose, or as three doses administered at two-weekly intervals. No specific antibody to HgbA was elicited after either dose schedule. Although the plasmid vector survived in vivo passage for up to 15 days following single oral challenge, HgbA expression was restricted to plasmid isolates recovered one day after immunization. Rabbits inoculated with the 3-dose booster regimen achieved no protective immunity from homologous challenge. These results emphasize that refinements in plasmid design to enhance a durable heterologous protein expression are necessary for the development of a live oral vaccine against chancroid. Copyright © 2011 Elsevier B.V. All rights reserved.

Chancroid, primary syphilis, genital herpes, and lymphogranuloma venereum in Antananarivo, Madagascar.

PubMed

Behets, F M; Andriamiadana, J; Randrianasolo, D; Randriamanga, R; Rasamilalao, D; Chen, C Y; Weiss, J B; Morse, S A; Dallabetta, G; Cohen, M S

1999-10-01

Ulcer material from consecutive patients attending clinics in Antananarivo, Madagascar, was tested using multiplex polymerase chain reaction (M-PCR) to detect Treponema pallidum, Haemophilus ducreyi, and herpes simplex virus. Sera were tested for syphilis and for IgG and IgM antibodies to Chlamydia trachomatis by microimmunofluorescence testing (MIF). By M-PCR, 33% of 196 patients had chancroid, 29% had syphilitic ulcers, and 10% had genital herpes; 32% of the ulcer specimens were M-PCR negative. Compared with M-PCR, syphilis serology was 72% sensitive and 83% specific. The sensitivity of clinical diagnosis of syphilis, chancroid, and genital herpes was 93%, 53%, and 0% and specificity was 20%, 52%, and 99%, respectively. Less schooling was associated with increased prevalence of syphilitic ulcers (P=.001). Sixteen patients (8%) were clinically diagnosed with lymphogranuloma venereum (LGV); 1 plausible case of LGV was found by MIF. In Madagascar, primary care of genital ulcers should include syndromic treatment for syphilis and chancroid.

Chancroid in Sheffield. A report of 22 cases diagnosed by isolating Haemophilus ducreyi in a modified medium.

PubMed Central

Hafiz, S; Kinghorn, G R; McEntegart, M G

1981-01-01

The causative organism of chancroid, Haemophilus ducreyi, is generally considered to be very fastidious and its isolation, maintenance, and detailed study very demanding. In this study a modified medium was developed, which allowed the organism to be isolated more frequently than previously would have been expected. Twenty-two cases of chancroid were confirmed by the isolation of H ducreyi in 160 patients with genital ulceration examined over a one-year period. The cases were apparently unrelated, and in only five was there a history of recent sexual contact abroad. Concurrent infection with other sexually transmitted diseases was present in 18 (81.8%) patients, and in 14 (63.6%) both H ducreyi and herpes simplex virus were isolated form the same genital ulcers. Thus, these findings indicate that chancroid is underdiagnosed in England and that H ducreyi may frequently occur as a secondary invader of damaged genital skin and mucosa. PMID:6976815

Evaluation of 500- and 1,000-mg doses of ciprofloxacin for the treatment of chancroid.

PubMed Central

Bodhidatta, L; Taylor, D N; Chitwarakorn, A; Kuvanont, K; Echeverria, P

1988-01-01

A randomized, double-blind study was performed comparing ciprofloxacin in a 500-mg single dose with 1,000 mg (500-mg doses given 12 h apart) for the treatment of chancroid in Thailand. Haemophilus ducreyi was isolated from 87 (48%) of 180 men with a clinical diagnosis of chancroid. For men with ulcers that were culture positive for H. ducreyi, rates of cure were 100% in the 500-mg group and 98% in the 1,000-mg group. For men with ulcers that were culture negative for H. ducreyi, rates of cure were 93% in the 500-mg group and 96% in the 1,000-mg group. The MIC of ciprofloxacin for 50% of isolates among 85 isolates of H. ducreyi was 0.007 micrograms/ml (range, 0.002 to 0.03 micrograms/ml). No significant adverse effects were detected in either group. These data indicate that both of these treatment regimens are equally effective therapies for chancroid in Thailand. PMID:3293526

Passive immunization with a polyclonal antiserum to the hemoglobin receptor of Haemophilus ducreyi confers protection against a homologous challenge in the experimental swine model of chancroid.

PubMed

Leduc, Isabelle; Fusco, William G; Choudhary, Neelima; Routh, Patty A; Cholon, Deborah M; Hobbs, Marcia M; Almond, Glen W; Orndorff, Paul E; Elkins, Christopher

2011-08-01

Haemophilus ducreyi, the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired by H. ducreyi from its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome of H. ducreyi, only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface of H. ducreyi and partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against an H. ducreyi infection, possibly by preventing acquisition of the essential nutrient heme.

Imported pedal chancroid: case report.

PubMed Central

Marckmann, P; Højbjerg, T; von Eyben, F E; Christensen, I

1989-01-01

A man aged 22 who had returned from the Fiji Islands to Denmark had chancroid on the left foot, but no history or sign of primary genital infection. The pedal location only is an unusual presentation of the disease, which was diagnosed only microbiologically. Chronic tropical ulcers therefore demand special microbiological attention. Images PMID:2753511

Thiamphenicol in the treatment of chancroid. A study of 1,128 cases.

PubMed

Belda Junior, W; Siqueira, L F; Fagundes, L J

2000-01-01

Thiamphenicol, an aminic derivate of hydrocarbilsulfonil propandiol, was used for the treatment of 1,171 chancroid bearing patients. Each patient was medicated with 5.0 g of granulated thiamphenicol, orally, in a single dose, and was reevaluated 3, 7 and 10 days after the treatment. Ten patients (0.89%) did not respond to the proposed treatment. 133 patients presented healed ulcers after 3 days of treatment, 976 patients healed chancres on the seventh day after the treatment, and 39 patients took 10 days to present healed chancres. The results of this study indicate that the rate of patients that were cured, the low incidence of side effects, and the practicality of administration make of thiamphenicol an excellent choice for the treatment of chancroid.

Localization of Haemophilus ducreyi in naturally acquired chancroidal ulcers.

PubMed

Bauer, Margaret E; Townsend, Carisa A; Ronald, Allan R; Spinola, Stanley M

2006-08-01

Haemophilus ducreyi causes the sexually transmitted genital ulcer disease chancroid. In human inoculation experiments, bacteria colocalize with neutrophils and macrophages but remain extracellular. The organism also colocalizes with collagen and fibrin but not with keratinocytes, fibroblasts, laminin, or fibronectin. These relationships are established by 48 h postinoculation and persist through the pustular stage of disease. To extend these observations to the ulcerative stage of disease, and to compare results in the human model with those of natural disease, we obtained biopsies from patients with naturally acquired chancroid. All ulcers were culture positive for H. ducreyi and histologically very similar to pustules from the human model. Staining with H. ducreyi-specific monoclonal antibodies demonstrated H. ducreyi within 5 biopsies. The organism was chiefly found within the granulocytic infiltrate of the ulcer. Dual staining for H. ducreyi and eukaryotic tissue components showed that H. ducreyi colocalized with neutrophils and fibrin at the ulcerative stage of disease. No bacteria were associated with keratinocytes, fibroblasts, or collagen. Overall, these findings are consistent with results from the human model. This is the first reported study to localize bacteria specifically identified as H. ducreyi within naturally acquired chancroid.

An immunohistochemical analysis of naturally occurring chancroid.

PubMed

King, R; Gough, J; Ronald, A; Nasio, J; Ndinya-Achola, J O; Plummer, F; Wilkins, J A

1996-08-01

Haemophilus ducreyi is a major cause of genital ulcer disease in many developing countries and is associated with augmented transmission of human immunodeficiency virus (HIV). However, the mechanisms through which H. ducreyi produces ulceration are poorly understood. The characteristics of the host response to H. ducreyi and the pathobiology of its potential contribution to increased HIV susceptibility are not known. Chancroid ulcer biopsies from 8 patients were analyzed histologically and immunohistochemically. All biopsies had perivascular and interstitial mononuclear cell infiltrates that extended deep into the dermis. The infiltrate, which contained macrophages and CD4 and CD8 lymphocytes, was consistent with a delayed hypersensitivity type cell-mediated immune response. The recruitment of CD4 T lymphocytes and macrophages may in part explain the facilitation of HIV transmission in patients with chancroid.

Chancroid: a review for the family practitioner.

PubMed Central

Jordan, W. C.

1991-01-01

Chancroid, as the name implies, is like a chancre. Unlike the painless chancre of syphilis, it is painful, darkfield negative, and does not respond to penicillin therapy. The number of cases have continued to rise in recent years. Because it can cause irreversible anatomical destruction, making the correct diagnosis is important and can prevent chronic morbidity. Images Figure 1 Figure 2 Figure 3 PMID:1956085

Presumptive specific clinical diagnosis of genital ulcer disease (GUD) in a primary health care setting in Nairobi.

PubMed

Ndinya-Achola, J O; Kihara, A N; Fisher, L D; Krone, M R; Plummer, F A; Ronald, A; Holmes, K K

1996-01-01

Of 22,274 patients 12 years of age or older attending a primary health care clinic in Nairobi, 1076 (4.8%) complained of symptoms suggesting a sexually transmitted disease (STD). Of these, 518 females and 462 males underwent complete clinical evaluation, and 78% had objective microbiologic or clinical evidence of STD, including 168 (17.1%) with genital ulcer disease (GUD). Presumptive specific clinical diagnoses on initial physical examination in cases of GUD were chancroid (131 patients), syphilis (25), genital herpes (15) and lymphogranuloma venereum (LGV) (1). Clinical diagnoses correlated only weakly with microbiological and serological diagnoses. Haemophilus ducreyi was isolated from 51 (41%) of the 125 with a clinical diagnosis of chancroid, and 4 (22%) of 18 with a diagnosis of syphilis, herpes, or LGV (P = 0.13). The rapid plasma reagin (RPR) test was reactive in 6 (24%) of 25 with a clinical diagnosis of syphilis, 18 (12.3%) of 146 with a diagnosis of chancroid or herpes, and 37 (4.7%) of 786 without a genital ulcer (P < 0.001, GUD vs no GUD). Sensitivity, specificity, and positive predictive value for presumptive clinical diagnosis of chancroid, relative to H. ducreyi isolation, were 93%, 16%, and 41%; and for diagnosis of syphilis, relative to reactive RPR, were 25%, 88% and 25%. Specific treatment based on presumptive specific clinical diagnosis frequently was inadequate for syphilis among patients with GUD and reactive RPR test. Syndromic treatment of GUD with antimicrobial combinations active against both chancroid and syphilis would be preferable to treatment with single drugs based on presumptive specific clinical diagnoses for this population.

Single-dose ceftriaxone for chancroid.

PubMed Central

Bowmer, M I; Nsanze, H; D'Costa, L J; Dylewski, J; Fransen, L; Piot, P; Ronald, A R

1987-01-01

Men with genital ulcers that were culture positive for Haemophilus ducreyi were treated with intramuscular ceftriaxone and randomized to three different dose regimens. All but 1 of 50 men treated with 1 g of intramuscular ceftriaxone were cured. Similarly, 0.5 and 0.25 g cured 43 of 44 men and 37 of 38 men, respectively. A single dose of 250 mg of intramuscular ceftriaxone is an effective treatment for chancroid. PMID:3566241

Chancroid: clinical manifestations, diagnosis, and management

PubMed Central

Lewis, D

2003-01-01

Chancroid is a sexually transmitted disease (STD) caused by the Gram negative bacterium Haemophilus ducreyi and is characterised by necrotising genital ulceration which may be accompanied by inguinal lymphadenitis or bubo formation. H ducreyi is a fastidious organism which is difficult to culture from genital ulcer material. DNA amplification techniques have shown improved diagnostic sensitivity but are only performed in a few laboratories. The management of chancroid in the tropics tends to be undertaken in the context of syndromic management of genital ulcer disease and treatment is usually with erythromycin. A number of single dose regimens are also available to treat H ducreyi infection. Genital ulceration as a syndrome has been associated with increased transmission of human immunodeficiency virus (HIV) infection in several cross sectional and longitudinal studies. Effective and early treatment of genital ulceration is therefore an important part of any strategy to control the spread of HIV infection in tropical countries. PMID:12576620

Chancroid: clinical manifestations, diagnosis, and management.

PubMed

Lewis, D A

2003-02-01

Chancroid is a sexually transmitted disease (STD) caused by the Gram negative bacterium Haemophilus ducreyi and is characterised by necrotising genital ulceration which may be accompanied by inguinal lymphadenitis or bubo formation. H ducreyi is a fastidious organism which is difficult to culture from genital ulcer material. DNA amplification techniques have shown improved diagnostic sensitivity but are only performed in a few laboratories. The management of chancroid in the tropics tends to be undertaken in the context of syndromic management of genital ulcer disease and treatment is usually with erythromycin. A number of single dose regimens are also available to treat H ducreyi infection. Genital ulceration as a syndrome has been associated with increased transmission of human immunodeficiency virus (HIV) infection in several cross sectional and longitudinal studies. Effective and early treatment of genital ulceration is therefore an important part of any strategy to control the spread of HIV infection in tropical countries.

[Chancroid in Algeria: the status of this sexually transmitted disease in 1995].

PubMed

Boudghène-Stambouli, O; Merad-Boudia, A

1997-01-01

Absent for several decades, the chancroid reappeared in Algeria in 1988. In the unique department of Dermatology and Venereology of the University Hospital of the country of Tlemcen (more than 700,000 inhabitants), we wanted to know the state of this STD seven years after the report of the first cases. The file of the consulting patients were examined. We looked for the principal characteristics of this STD: age, sex, incubation period, place infection contact, type of relation, clinical presentation, evolution without and with treatment, other associated STD (syphilis, HIV). From August 1988 (1st case) to December 1995, 144 cases of chancroid were collected = 1988: 6, 1989: 5, 1990: 7, 1991: 18, 1992: 11, 1993: 33, 1994: 48, 1995: 16. The presentation is quite stereotyped; it concerns males only, singles in must cases, having had sexual relations with prostitutes. The incubation period is short (less than 10 days), the characteristic ulceration presents, very often, some adenopathies. The treatment by cotrimoxazole is efficient. They are no concomitant syphilis or HIV infection. The chancroid is the first cause of genital ulceration in the world. Since 1991, it is the principal STD in our department. It spreads within a male population, young singles associated with prostitutes. It is well installed in Algeria, and its role, although minor, in the transmission of the HIV infection, should not be neglected.

Passive Immunization with a Polyclonal Antiserum to the Hemoglobin Receptor of Haemophilus ducreyi Confers Protection against a Homologous Challenge in the Experimental Swine Model of Chancroid▿

PubMed Central

Leduc, Isabelle; Fusco, William G.; Choudhary, Neelima; Routh, Patty A.; Cholon, Deborah M.; Hobbs, Marcia M.; Almond, Glen W.; Orndorff, Paul E.; Elkins, Christopher

2011-01-01

Haemophilus ducreyi, the etiologic agent of chancroid, has an obligate requirement for heme. Heme is acquired by H. ducreyi from its human host via TonB-dependent transporters expressed at its bacterial surface. Of 3 TonB-dependent transporters encoded in the genome of H. ducreyi, only the hemoglobin receptor, HgbA, is required to establish infection during the early stages of the experimental human model of chancroid. Active immunization with a native preparation of HgbA (nHgbA) confers complete protection in the experimental swine model of chancroid, using either Freund's or monophosphoryl lipid A as adjuvants. To determine if transfer of anti-nHgbA serum is sufficient to confer protection, a passive immunization experiment using pooled nHgbA antiserum was conducted in the experimental swine model of chancroid. Pigs receiving this pooled nHgbA antiserum were protected from a homologous, but not a heterologous, challenge. Passively transferred polyclonal antibodies elicited to nHgbA bound the surface of H. ducreyi and partially blocked hemoglobin binding by nHgbA, but were not bactericidal. Taken together, these data suggest that the humoral immune response to the HgbA vaccine is protective against an H. ducreyi infection, possibly by preventing acquisition of the essential nutrient heme. PMID:21646451

Virtual screening of phytochemicals to novel targets in Haemophilus ducreyi towards the treatment of Chancroid.

PubMed

Tripathi, Pranav; Chaudhary, Ritu; Singh, Ajeet

2014-01-01

Conventionally, drugs are discovered by testing chemically synthesized compounds against a battery of in vivo biological screens. Information technology and Omic science enabled us for high throughput screening of compound libraries against biological targets and hits are then tested for efficacy in cells or animals. Chancroid, caused by Haemophilus ducreyi is a public health problem and has been recognized as a cofactor for Human Immunodeficiency Virus (HIV) transmission. It facilitates HIV transmission by providing an accessible portal entry, promoting viral shedding, and recruiting macrophages as well as CD4 cells to the skin. So, there is a requirement to develop an efficient drug to combat Chancroid that can also diminish HIV infection. In-silico screening of potential inhibitors against the target may facilitate in detection of the novel lead compounds for developing an effective chemo preventive strategy against Haemophilus ducreyi. The present study has investigated the effects of approximately 1100 natural compounds that inhibit three vital enzymes viz. Phosphoenolpyruvate phosphotransferase, Acetyl-coenzyme A carboxylase and Fructose 1, 6-bisphosphatase of Haemophilus ducreyi in reference to a commercial drug Rifabutin. Results reveal that the lead compound uses less energy to bind to target. The lead compound parillin has also been predicted as less immunogenic in comparison to Rifabutin. Further, better molecular dynamics, pharmacokinetics, pharmacodynamics and ADME-T properties establish it as an efficient chancroid preventer.

First case of chancroid in 14 years at the largest STI clinic in Paris, France.

PubMed

Fouéré, Sébastien; Lassau, François; Rousseau, Clotilde; Bagot, Martine; Janier, Michel

2016-08-01

We report the first case of chancroid seen at our clinic in 14 years. It was diagnosed by nuclear acid amplification test in a male patient returning from Madagascar. Although the disease is considered on the verge of disappearance even in tropical countries, its real potential for reemergence - due to new strains of Haemophilus ducreyi, underreporting and a lack of widespread use of molecular testing - could be underestimated. © The Author(s) 2016.

[Chancroid].

PubMed

Holst, Helle; Hartmann-Petersen, Susanna; Dargis, Rimtas; Andresen, Keld; Christensen, Jens Jørgen; Kemp, Michael

2007-05-28

Chancroid is caused by the bacterium Haemophilus ducreyi. It is a sexually transmitted disease causing a soft chancre with a necrotic base and purulent exudate. The incidence of this illness is very low in Denmark and is probably underestimated. The bacterium is very fragile in transport, and culture is often negative. The chance of demonstrating the bacterium is greatly enhanced by the use of molecular techniques. In this case, we report on a specific PCR test for H. ducreyi that was used to establish the diagnosis in a 40-year-old male.

Chancroid and Haemophilus ducreyi.

PubMed Central

Morse, S A

1989-01-01

Haemophilus ducreyi is the causative agent of chancroid, one of the genital ulcerative diseases. H. ducreyi is the major cause of genital ulcer disease in Africa and Southeast Asia and is of increasing concern in the United States. Definitive diagnosis of chancroid requires the isolation and identification of H. ducreyi, but isolation of this organism is difficult and the available medium is not optimal for all strains. Fluorescent antibody and serologic tests are of limited value. In general, our knowledge of this organism is rather limited, and indeed, recent studies have questioned the placement of H. ducreyi in the genus Haemophilus. H. ducreyi has relatively few biochemical activities, and epidemiologic studies are limited because there are limited phenotypic markers available for strain typing. Specific virulence factors of H. ducreyi have yet to be identified. Antimicrobial resistance in H. ducreyi is of special concern, as this organism has acquired both gram-negative and gram-positive resistance determinants. In addition, some of these determinants can be mobilized and transferred to other Haemophilus species or to Neisseria gonorrhoeae. Images PMID:2650859

Comparison of enzyme immunoassays for antibodies to Haemophilus ducreyi in a community outbreak of chancroid in the United States.

PubMed

Chen, C Y; Mertz, K J; Spinola, S M; Morse, S A

1997-06-01

The performance of two EIAs (adsorption EIA and lipooligosaccharide [LOS] EIA) that detect antibodies to Haemophilus ducreyi was evaluated with serum specimens obtained from 163 patients (96 with genital ulcer disease [GUD]). Paired serum specimens (initial and follow-up) were obtained from 52 of the GUD patients. By use of initial serum specimens from 82 GUD patients whose etiologic agents for their ulcers had been identified, the adsorption EIA had a sensitivity and specificity for chancroid of 53% and 71%, while the LOS EIA had a sensitivity and specificity of 48% and 89%, respectively. Sensitivity and specificity of the adsorption EIA increased to 78% and 84%, respectively, when the results of follow-up serum specimens were used to calculate optimal performance. The proportion of patients testing positive for H. ducreyi who had anti-H. ducreyi IgG antibodies, as determined by adsorption EIA, increased with the duration of infection, thus limiting the role of EIAs in the diagnosis of chancroid.

Simplified PCR for detection of Haemophilus ducreyi and diagnosis of chancroid.

PubMed Central

West, B; Wilson, S M; Changalucha, J; Patel, S; Mayaud, P; Ballard, R C; Mabey, D

1995-01-01

A simplified PCR was developed for detection of Haemophilus ducreyi in samples from chancroid patients. The strategy included a straightforward chloroform extraction sample preparation method, a one-tube nested PCR to minimize contamination risks, and a colorimetric method for detection of products. Primers were designed from published nucleotide sequences of the 16S rRNA gene of H. ducreyi, with longer outer primers for annealing at a higher temperature and shorter inner primers labelled with biotin and digoxigenin for binding with avidin and colorimetric detection. The PCR technique detected all 35 strains of H. ducreyi tested, from four different geographical regions, and was negative for other, related strains of bacteria and for the common contaminating bacteria tested. Of 25 samples from H. ducreyi culture-positive chancroid patients, 24 were PCR positive and 1 produced a weak reaction. Of 83 samples from clinical cases of chancroid in the Republic of South Africa, 69 were PCR positive. The sensitivity of PCR compared with that of clinical diagnosis was 83%. All 50 negative control samples were negative. Encouraging results were also obtained with a consecutive series of 25 genital ulcer patients in Tanzania, of whom 9 were PCR positive. The adaptations of this simplified PCR strategy, at the sensitivity and specificity levels obtained, mean it will be useful for detection of H. ducreyi in areas where the organism is endemic, particularly where testing by culture is difficult or impossible. PMID:7540625

Treating chancroid: summary of studies in southern Africa.

PubMed Central

Ballard, R C; Duncan, M O; Fehler, H G; Dangor, Y; Exposto, F L; Latif, A S

1989-01-01

Recent studies undertaken in southern Africa and elsewhere indicate that many short or single dose treatments are available to treat chancroid. Erythromycin 500 mg three times a day for five days, ciprofloxacin 500 mg, sulphamethopyrazine 800 mg and trimethoprim 1000 mg or sulphametrole 3200 mg and trimethoprim 640 mg as single oral doses, or ceftriaxone 250 mg as a single intramuscular injection are all effective in treating the disease. The widespread use of these regimens largely depends on the accuracy of diagnosis, susceptibilities of local Haemophilus ducreyi isolates to antimicrobials, and financial considerations. PMID:2629710

Three day oral course of Augmentin to treat chancroid.

PubMed Central

Ndinya-Achola, J O; Nsanze, H; Karasira, P; Fransen, L; D'Costa, L J; Piot, P; Ronald, A R

1986-01-01

Amoxycillin and clavulanic acid (Augmentin; Beecham Research Laboratories) was used to treat patients with bacteriologically proved chancroid in three different dose regimens. A single dose of Augmentin (amoxycillin 3 g, clavulanic acid 350 mg) was found to be ineffective. A similar dose repeated after 24 hours was equally ineffective, but a dose (amoxycillin 500 mg, clavulanic acid 250 mg) given every 8 hours for three days was found to be effective. The drug was well tolerated and no side effects were noted in any of the patients treated. PMID:3733082

Treatment of chancroid. A comparison of sulphamethoxazole and trimethoprim-sulphamethoxazole.

PubMed Central

Fast, M V; Nsanze, H; Plummer, F A; D'Costa, L J; MacLean, I W; Ronald, A R

1983-01-01

Since sulphonamides are no longer predictably effective in the treatment of chancroid the combination of trimethoprim-sulphamethoxazole (TMP-SMX) was evaluated to identify other effective regimens. One hundred and nine patients with genital ulcers (75 men and 34 women) seen at the Special Treatment Clinic in Nairobi, Kenya, were randomly assigned to treatment with a seven day course of either sulphamethoxazole 1000 mg twice daily or trimethoprim (160 mg)-sulphamethoxazole (800 mg) (TMP-SMX) twice daily. Haemophilus ducreyi was isolated from the ulcer in 57 patients (33 men and 24 women). 16 patients were subsequently diagnosed serologically as having syphilis. No aetiological diagnosis was made in 40 patients. Treatment with sulphamethoxazole failed in five of 21 (24%) culture positive patients who were available for evaluation after seven days, whereas all 19 of such patients who were treated with TMP-SMX responded to treatment. Of the 21 isolates available for susceptibility testing, all were susceptible to trimethoprim alone (MIC less than 0.5 mg/l) and three were resistant to sulphonamides, all three containing a 4.9 megadalton (Mdal) plasmid. Two of the three patients from whom these isolates had been obtained were treated with sulphamethoxazole and both were clinical and bacteriological failures. Five of six patients with sulphonamide-susceptible H ducreyi responded to treatment with sulphamethoxazole. Failure of sulphonamides to eradicate H ducreyi in some patients with chancroid is associated with the presence of a sulphonamide resistant plasmid. In regions where this plasmid is present in H ducreyi TMP-SMX is the preferred treatment for chancroid. PMID:6351957

Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta-analysis.

PubMed

Weiss, H A; Thomas, S L; Munabi, S K; Hayes, R J

2006-04-01

Male circumcision is associated with reduced risk of HIV infection. This may be partly because of a protective effect of circumcision on other sexually transmitted infections (STI), especially those causing genital ulcers, but evidence for such protection is unclear. Our objective was to conduct a systematic review and meta-analyses of the associations between male circumcision and infection with herpes simplex virus type 2 (HSV-2), Treponema pallidum, or Haemophilus ducreyi. Electronic databases (1950-2004) were searched using keywords and text terms for herpes simplex, syphilis, chancroid, ulcerative sexually transmitted diseases, or their causative agents, in conjunction with terms to identify epidemiological studies. References of key articles were hand searched, and data were extracted using standardised forms. Random effects models were used to summarise relative risk (RR) where appropriate. 26 articles met the inclusion criteria. Most syphilis studies reported a substantially reduced risk among circumcised men (summary RR = 0.67, 95% confidence interval (CI) 0.54 to 0.83), although there was significant between study heterogeneity (p = 0.01). The reduced risk of HSV-2 infection was of borderline statistical significance (summary RR = 0.88, 95% CI 0.77 to 1.01). Circumcised men were at lower risk of chancroid in six of seven studies (individual study RRs: 0.12 to 1.11). This first systematic review of male circumcision and ulcerative STI strongly indicates that circumcised men are at lower risk of chancroid and syphilis. There is less association with HSV-2. Potential male circumcision interventions to reduce HIV in high risk populations may provide additional benefit by protecting against other STI.

Reportable diseases

MedlinePlus

... western equine encephalitis Botulism Brucellosis Chancroid Chickenpox Chlamydia Cholera Coccidioidomycosis Cryptosporidiosis Cyclosporiasis Diphtheria Giardiasis Gonorrhea Haemophilus influenza, ...

Thiamphenicol in the treatment of chancroid in men.

PubMed Central

Latif, A S

1982-01-01

Thiamphenicol was used to treat 547 men with chancroid. An oral dose of 2.5g was given on the first day and a further dose of 1.25g a week later if the lesions had not healed. Eighty-seven (15.9%) patients defaulted from follow up and 23 (4.2%) had positive serological test results for syphilis. Of the remaining 437 patients, 27 (6.2%) failed to respond to treatment, 258 (59%) were cured after the single dose, and 152 (34.8%) required a second dose. The overall cure rate was 93.8%. PMID:7034860

Male circumcision and risk of syphilis, chancroid, and genital herpes: a systematic review and meta‐analysis

PubMed Central

Weiss, H A; Thomas, S L; Munabi, S K; Hayes, R J

2006-01-01

Objectives Male circumcision is associated with reduced risk of HIV infection. This may be partly because of a protective effect of circumcision on other sexually transmitted infections (STI), especially those causing genital ulcers, but evidence for such protection is unclear. Our objective was to conduct a systematic review and meta‐analyses of the associations between male circumcision and infection with herpes simplex virus type 2 (HSV‐2), Treponema pallidum, or Haemophilus ducreyi. Methods Electronic databases (1950–2004) were searched using keywords and text terms for herpes simplex, syphilis, chancroid, ulcerative sexually transmitted diseases, or their causative agents, in conjunction with terms to identify epidemiological studies. References of key articles were hand searched, and data were extracted using standardised forms. Random effects models were used to summarise relative risk (RR) where appropriate. Results 26 articles met the inclusion criteria. Most syphilis studies reported a substantially reduced risk among circumcised men (summary RR = 0.67, 95% confidence interval (CI) 0.54 to 0.83), although there was significant between study heterogeneity (p = 0.01). The reduced risk of HSV‐2 infection was of borderline statistical significance (summary RR = 0.88, 95% CI 0.77 to 1.01). Circumcised men were at lower risk of chancroid in six of seven studies (individual study RRs: 0.12 to 1.11). Conclusions This first systematic review of male circumcision and ulcerative STI strongly indicates that circumcised men are at lower risk of chancroid and syphilis. There is less association with HSV‐2. Potential male circumcision interventions to reduce HIV in high risk populations may provide additional benefit by protecting against other STI. PMID:16581731

Development of a Serological Test for Haemophilus ducreyi for Seroprevalence Studies

PubMed Central

Elkins, Christopher; Yi, Kyungcheol; Olsen, Bonnie; Thomas, Christopher; Thomas, Kevin; Morse, Stephen

2000-01-01

We developed a new enzyme immunoassay (rpEIA) for use in determining the seroprevalence of chancroid. Three highly conserved outer membrane proteins from Haemophilus ducreyi strain 35000 were cloned, overexpressed, and purified from Escherichia coli for use as antigens in the rpEIA. Serum specimens from patients with and without chancroid were assayed to determine optimum sensitivity and specificity and to establish cutoff values. On the basis of these data, rpEIA was found to be both sensitive and specific when used to test a variety of serum specimens from patients with genital ulcers and urethritis and from healthy blood donors. PMID:10747137

Treating chancroid with enoxacin.

PubMed Central

Naamara, W; Kunimoto, D Y; D'Costa, L J; Ndinya-Achola, J O; Nsanze, H; Ronald, A R; Plummer, F A

1988-01-01

Increasing resistance of Haemophilus ducreyi to antimicrobials necessitates further trials of new antimicrobial agents for treating chancroid. Enoxacin has excellent in vitro activity against H ducreyi, and a randomised clinical trial of three doses of enoxacin 400 mg at intervals of 12 hours compared with a single dose of trimethoprim/sulphametrole (TMP/SMT) 640/3200 mg was therefore conducted. Of 169 men enrolled in the study, 86 received enoxacin and 83 received TMP/SMT. Ulcers were improved or cured in 65/73 men treated with enoxacin and 57/70 men treated with TMP/SMT. This difference was not significant. At 72 hours after treatment, H ducreyi was eradicated from ulcers of 72/77 men treated with enoxacin and of 67/74 of those treated with TMP/SMT. Patients with buboes responded equally well to both treatments. Of 100 H ducreyi strains tested, all were susceptible to both 0.25 mg/l enoxacin and the combination of 0.25 mg/l TMP and 5 mg/l SMT. Although most men treated with either regimen were cured, neither regimen appeared to be the optimum treatment for chancroid. This study shows the efficacy of enoxacin for a soft tissue infection caused by Gram negative organisms. PMID:3044978

Clinical evaluation of rosoxacin for the treatment of chancroid.

PubMed Central

Haase, D A; Ndinya-Achola, J O; Nash, R A; D'Costa, L J; Hazlett, D; Lubwama, S; Nsanze, H; Ronald, A R

1986-01-01

One hundred seven men with Haemophilus ducreyi-positive chancroid were assigned to receive 300 mg of rosoxacin as a single dose or 150 mg twice daily for 3 days. Ulcers and buboes were followed clinically and bacteriologically for 1 month. Of 40 evaluable males on the 3-day regimen, 38 (95%) were cured, while only 14 of 23 (61%) males on the single-dose regimen were cured; this regimen was discontinued. There was one ulcer relapse at day 21 in both groups; the one relapse in the single-dose group had a persistent culture-positive bubo. Eight of nine (89%) buboes followed to the endpoint on the 3-day rosoxacin regimen were cured, versus three of six (50%) on the single-dose regimen. Adverse effects were mainly related to the central nervous system but were minor and did not require intervention. None of the treatment failures was due to organisms resistant to rosoxacin, and failure of the single-dose regimen presumably was related to duration of tissue levels rather than to drug resistance. Administration of 150 mg of rosoxacin twice daily for 3 days is an effective regimen for the therapy of chancroid and is a reasonable alternative to other short-course regimens. PMID:3489439

Haemophilus ducreyi: from sexually transmitted infection to skin ulcer pathogen.

PubMed

Lewis, David A; Mitjà, Oriol

2016-02-01

This article provides an overview of the biology, epidemiology, clinical features, diagnostic tests, and treatment of Haemophilus ducreyi infection, with special reference to the decline of chancroid and the recent emergence of H. ducreyi as a pathogen responsible for chronic limb ulceration clinically similar to yaws. Chancroid has declined in importance as a sexually transmitted infection in most countries where it was previously endemic. Chancroid may be caused by either class I or class II H. ducreyi isolates; these two classes diverged from each other approximately 1.95 million years ago. H. ducreyi has recently emerged as a cause of chronic skin ulceration in the Pacific region and Africa. Based on sequencing of whole genomes and defined genetic loci, it appears that the cutaneous H. ducreyi strains diverged from the class I genital strains relatively recently. H. ducreyi should be considered as a major cause of chronic limb ulceration in both adults and children and appropriate molecular diagnostic assays are required to determine ulcer aetiology. The high prevalence of H. ducreyi-related cutaneous ulceration in yaws-endemic countries has challenged the validity of observational surveys to monitor the effectiveness of the WHO's yaws eradication campaign.

Rapid control of a chancroid outbreak: implications for Canada.

PubMed Central

Jessamine, P G; Brunham, R C

1990-01-01

From June to November 1987 an outbreak of chancroid occurred in Winnipeg, the first in more than 10 years; 14 people (9 men, 5 women) were involved. Nine of the cases were confirmed through culture. A control strategy was implemented in November 1987 that included presumptive treatment of genital ulcer disease with single-dose antimicrobial therapy, intensive tracing of contacts and treatment of asymptomatic sexual contacts. The origin of the outbreak was not determined, and an epidemiologic link between all the patients could not be demonstrated. The isolates were found to contain the same plasmid; this suggested that a single clone of Haemophilus ducreyi was responsible for the outbreak. Images Fig. 2 PMID:2337844

The cytolethal distending toxin from the chancroid bacterium Haemophilus ducreyi induces cell-cycle arrest in the G2 phase.

PubMed

Cortes-Bratti, X; Chaves-Olarte, E; Lagergård, T; Thelestam, M

1999-01-01

The potent cytolethal distending toxin produced by Haemophilus ducreyi is a putative virulence factor in the pathogenesis of chancroid. We studied its action on eukaryotic cells, with the long-term goal of understanding the pathophysiology of the disease. Intoxication of cultured human epithelial-like cells, human keratinocytes, and hamster fibroblasts was irreversible, and appeared as a gradual distention of three- to fivefold the size of control cells. Organized actin assemblies appeared concomitantly with cell enlargement, promoted by a mechanism that probably does not involve small GTPases of the Rho protein family. Intoxicated cells did not proliferate. Similar to cells treated with other cytolethal distending toxins, these cells accumulated in the G2 phase of the cell cycle, demonstrating an increased level of the tyrosine phosphorylated (inactive) form of the cyclin-dependent kinase p34(cdc2). DNA synthesis was not affected until several hours after this increase, suggesting that the toxin acts directly on some kinase/phosphatase in the signaling network controlling the p34(cdc2) activity. We propose that this toxin has an important role both in the generation of chancroid ulcers and in their slow healing. The toxin may also be an interesting new tool for molecular studies of the eukaryotic cell- cycle machinery.

The cytolethal distending toxin from the chancroid bacterium Haemophilus ducreyi induces cell-cycle arrest in the G2 phase

PubMed Central

Cortes-Bratti, Ximena; Chaves-Olarte, Esteban; Lagergård, Teresa; Thelestam, Monica

1999-01-01

The potent cytolethal distending toxin produced by Haemophilus ducreyi is a putative virulence factor in the pathogenesis of chancroid. We studied its action on eukaryotic cells, with the long-term goal of understanding the pathophysiology of the disease. Intoxication of cultured human epithelial-like cells, human keratinocytes, and hamster fibroblasts was irreversible, and appeared as a gradual distention of three- to fivefold the size of control cells. Organized actin assemblies appeared concomitantly with cell enlargement, promoted by a mechanism that probably does not involve small GTPases of the Rho protein family. Intoxicated cells did not proliferate. Similar to cells treated with other cytolethal distending toxins, these cells accumulated in the G2 phase of the cell cycle, demonstrating an increased level of the tyrosine phosphorylated (inactive) form of the cyclin-dependent kinase p34cdc2. DNA synthesis was not affected until several hours after this increase, suggesting that the toxin acts directly on some kinase/phosphatase in the signaling network controlling the p34cdc2 activity. We propose that this toxin has an important role both in the generation of chancroid ulcers and in their slow healing. The toxin may also be an interesting new tool for molecular studies of the eukaryotic cell- cycle machinery. PMID:9884340

A humoral immune response confers protection against Haemophilus ducreyi infection.

PubMed

Cole, Leah E; Toffer, Kristen L; Fulcher, Robert A; San Mateo, Lani R; Orndorff, Paul E; Kawula, Thomas H

2003-12-01

Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. Neither naturally occurring chancroid nor experimental infection with H. ducreyi results in protective immunity. Likewise, a single inoculation of H. ducreyi does not protect pigs against subsequent infection. Accordingly, we used the swine model of chancroid infection to examine the impact of multiple inoculations on a host's immune response. After three successive inoculations with H. ducreyi, pigs developed a modestly protective immune response evidenced by the decreased recovery of viable bacteria from lesions. All lesions biopsied 2 days after the first and second inoculations contained viable H. ducreyi cells, yet only 55% of the lesions biopsied 2 days after the third inoculation did. Nearly 90% of the lesions biopsied 7 days after the first inoculation contained viable H. ducreyi cells, but this percentage dropped to only 16% after the third inoculation. Between the first and third inoculations, the average recovery of CFU from lesions decreased approximately 100-fold. The reduced recovery of bacteria corresponded directly with a fivefold increase in H. ducreyi-specific antibody titers and the emergence of bactericidal activity. These immune sera were protective when administered to naïve pigs prior to challenge with H. ducreyi. These data suggest that pigs mount an effective humoral immune response to H. ducreyi after multiple exposures to the organism.

Chancroid

MedlinePlus

... one half of infected men have only a single ulcer. Women often have 4 or more ulcers. ... MD, PhD, Assistant Professor in Medicine, Harvard Medical School; Assistant in Medicine, Division of Infectious Disease, Department ...

Epidemiology, clinical features, diagnosis and treatment of Haemophilus ducreyi - a disappearing pathogen?

PubMed

Lewis, David A

2014-06-01

Chancroid, caused by Haemophilus ducreyi, has declined in importance as a sexually transmitted pathogen in most countries where it was previously endemic. The global prevalence of chancroid is unknown as most countries lack the required laboratory diagnostic capacity and surveillance systems to determine this. H. ducreyi has recently emerged as a cause of chronic skin ulceration in some South Pacific islands. Although no antimicrobial susceptibility data for H. ducreyi have been published for two decades, it is still assumed that the infection will respond successfully to treatment with recommended cephalosporin, macrolide or fluoroquinolone-based regimens. HIV-1-infected patients require careful follow-up due to reports of treatment failure with single dose regimens. Buboes may need additional treatment with either aspiration or excision and drainage.

Health education for STD patients in a New Delhi hospital.

PubMed

Hiramani, A B; Srivastava, U; Misra, R S

1985-09-01

The impact of sexually transmitted disease (STD) education on patients who presented for treatment of syphillis, gonorrhea, chancroid, or gonorrhea and chancroid at the STD clinic of a hospital in New Delhi, India, was assessed. 1st a pilot study of 31 patients was undertaken to determine their level of knowledge about syphilis, gonorrhea, and chancroid. This information was then used to design appropriate educational materials, including folders, photographs, flip-charts, and posters. The impact of these materials on the knowledge level of a group of patients with 1 or more of the 3 diseases was then assessed. 107 patients who presented at the clinic for treatment were interviewed in order to obtain baseline information on their STD knowledge levels. Individual education sessions were held with 80 of the 107 patients. Some of the educational materials were used during the education sessions and the patients were instructed to read the remaining materials on their own. Approximately 18 days following the education sessions, 56 of the 80 patients were retested on their knowledge of STDs. The remaining patients were lost to followup. Analysis of the data indicated that the majority of the 107 respondents were unmarried, between 20-25 years of age, and earning less than Rs.600. The baseline test indicated that most of the patients had some knowledge about their own diseases, but little knowledge about the other 2 diseases. Many of the respondents had misconceptions about the causes and effects of the diseases. The results of the retests following the educational sessions indicated that the patients with syphilis or gonorrhea tripled their knowledge level of the 3 STDs and that patients with chancroid more than doubled their STD knowledge level. 2/3 of the 56 patients said that the program increased their understanding of STDs. The educational method preferred by the largest proportion of respondents (64%) was the individual educational sessions. The folders and photographs were ranked as 2nd and 3rd in preference. Many of the patients had delayed seeking treatment for their condition. The major reason for the delay was that the patient did not understand the seriousness of the disease.

Development of the polymerase chain reaction for diagnosis of chancroid.

PubMed Central

Chui, L; Albritton, W; Paster, B; Maclean, I; Marusyk, R

1993-01-01

The published nucleotide sequences of the 16S rRNA gene of Haemophilus ducreyi were used to develop primer sets and probes for the diagnosis of chancroid by polymerase chain reaction (PCR) DNA amplification. One set of broad specificity primers yielded a 303-bp PCR product from all bacteria tested. Two 16-base probes internal to this sequence were species specific for H. ducreyi when tested with 12 species of the families Pasteurellaceae and Enterobacteriaceae. The two probes in combination with the broad specificity primers were 100% sensitive with 51 strains of H. ducreyi isolated from six continents over a 15-year period. The direct detection of H. ducreyi from 100 clinical specimens by PCR showed a sensitivity of 83 to 98% and a specificity of 51 to 67%, depending on the number of amplification cycles. Images PMID:8458959

The cytolethal distending toxin of Haemophilus ducreyi aggravates dermal lesions in a rabbit model of chancroid.

PubMed

Wising, Catharina; Mölne, Lena; Jonsson, Ing-Marie; Ahlman, Karin; Lagergård, Teresa

2005-05-01

Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, produces a cytolethal distending toxin (HdCDT) that inhibits cultured cell proliferation, leading to cell death. A rabbit model of dermal infection was used to investigate the roles of H. ducreyi bacteria and HdCDT in the development, clinical appearance, and persistence of infection. A non-toxin producing H. ducreyi strain, and for comparison purposes a non-capsulated Haemophilus influenzae strain, were inoculated intradermally, with and without co-administration of purified HdCDT. Co-administration of HdCDT resulted in significant aggravation of H. ducreyi-induced inflammatory lesions, and development of ulcers in rabbit skin. Less pronounced inflammatory lesions and lack of epithelial eruption were observed after inoculation with H. influenzae. Histopathological sections of the H. ducreyi-induced lesions, in both the presence and absence of HdCDT, showed dense infiltrates of the same type inflammatory cells, with the exception of a prominent endothelial cell proliferation noted in sections from lesions caused by H. ducreyi and toxin. Signs of chronic inflammation with involvement of T cells, macrophages, eosinophils, and granuloma formation were observed after H. ducreyi inoculation both with and without toxin. In conclusion, H. ducreyi causes a pronounced, chronic inflammation with involvement of T cells and macrophages, and in combination with HdCDT production of ulcers in the rabbit model. These pathogenic mechanisms may promote the development and persistence of chancroid ulcers.

Expression of Haemophilus ducreyi Collagen Binding Outer Membrane Protein NcaA Is Required for Virulence in Swine and Human Challenge Models of Chancroid

PubMed Central

Fulcher, Robert A.; Cole, Leah E.; Janowicz, Diane M.; Toffer, Kristen L.; Fortney, Kate R.; Katz, Barry P.; Orndorff, Paul E.; Spinola, Stanley M.; Kawula, Thomas H.

2006-01-01

Haemophilus ducreyi, the etiologic agent of the sexually transmitted genital ulcer disease chancroid, has been shown to associate with dermal collagen fibers within infected skin lesions. Here we describe NcaA, a previously uncharacterized outer membrane protein that is important for H. ducreyi collagen binding and host colonization. An H. ducreyi strain lacking the ncaA gene was impaired in adherence to type I collagen but not fibronectin (plasma or cellular form) or heparin. The mutation had no effect on serum resistance or binding to HaCaT keratinocytes or human foreskin fibroblasts in vitro. Escherichia coli expressing H. ducreyi NcaA bound to type I collagen, demonstrating that NcaA is sufficient to confer collagen attachment. The importance of NcaA in H. ducreyi pathogenesis was assessed using both swine and human experimental models of chancroid. In the swine model, 20% of lesions from sites inoculated with the ncaA mutant were culture positive for H. ducreyi 7 days after inoculation, compared to 73% of wild-type-inoculated sites. The average number of CFU recovered from mutant-inoculated lesions was also significantly reduced compared to that recovered from wild-type-inoculated sites at both 2 and 7 days after inoculation. In the human challenge model, 8 of 30 sites inoculated with wild-type H. ducreyi progressed to the pustular stage, compared to 0 of 30 sites inoculated with the ncaA mutant. Together these results demonstrate that the collagen binding protein NcaA is required for H. ducreyi infection. PMID:16622201

Expression of Haemophilus ducreyi collagen binding outer membrane protein NcaA is required for virulence in swine and human challenge models of chancroid.

PubMed

Fulcher, Robert A; Cole, Leah E; Janowicz, Diane M; Toffer, Kristen L; Fortney, Kate R; Katz, Barry P; Orndorff, Paul E; Spinola, Stanley M; Kawula, Thomas H

2006-05-01

Haemophilus ducreyi, the etiologic agent of the sexually transmitted genital ulcer disease chancroid, has been shown to associate with dermal collagen fibers within infected skin lesions. Here we describe NcaA, a previously uncharacterized outer membrane protein that is important for H. ducreyi collagen binding and host colonization. An H. ducreyi strain lacking the ncaA gene was impaired in adherence to type I collagen but not fibronectin (plasma or cellular form) or heparin. The mutation had no effect on serum resistance or binding to HaCaT keratinocytes or human foreskin fibroblasts in vitro. Escherichia coli expressing H. ducreyi NcaA bound to type I collagen, demonstrating that NcaA is sufficient to confer collagen attachment. The importance of NcaA in H. ducreyi pathogenesis was assessed using both swine and human experimental models of chancroid. In the swine model, 20% of lesions from sites inoculated with the ncaA mutant were culture positive for H. ducreyi 7 days after inoculation, compared to 73% of wild-type-inoculated sites. The average number of CFU recovered from mutant-inoculated lesions was also significantly reduced compared to that recovered from wild-type-inoculated sites at both 2 and 7 days after inoculation. In the human challenge model, 8 of 30 sites inoculated with wild-type H. ducreyi progressed to the pustular stage, compared to 0 of 30 sites inoculated with the ncaA mutant. Together these results demonstrate that the collagen binding protein NcaA is required for H. ducreyi infection.

Ulcerative Vaginitis Due to Torulopsis Glabrata: A Case Report

PubMed Central

Clark, John F. J.; Faggett, Timothy; Peters, Barbara; Sampson, Calvin C.

1978-01-01

A patient with ulcerative vaginitis is presented. The differential diagnosis included malignant ulcer, chancroid, and granuloma venereum. Torulopsis glabrata vaginitis, which was subsequently proven, responded successfully to clotrimazole suppositories. Predisposing and related factors and isolation and identification procedures are discussed. PMID:569709

Evaluation of humoral and cell-mediated inducible immunity to Haemophilus ducreyi in an animal model of chancroid.

PubMed Central

Desjardins, M; Filion, L G; Robertson, S; Kobylinski, L; Cameron, D W

1996-01-01

To study the mechanisms of inducible immunity to Haemophilus ducreyi infection in the temperature-dependent rabbit model of chancroid, we conducted passive immunization experiments and characterized the inflammatory infiltrate of chancroidal lesions. Polyclonal immunoglobulin G was purified from immune sera raised against H. ducreyi 35000 whole-cell lysate or a pilus preparation and from naive control rabbits. Rabbits were passively immunized with 24 or 48 mg of purified polyclonal immunoglobulin G intravenously, followed 24 h after infusion by homologous titered infectious challenge. Despite titratable antibody, no significant difference in infection or disease was observed. We then evaluated the immunohistology of lesions produced by homologous-strain challenge in sham-immunized rabbits and those protectively vaccinated by pilus preparation immunization. Immunohistochemical stains for CD5 and CD4 T-lymphocyte markers were performed on lesion sections 4, 10, 15, and 21 days from infection. Lesions of pilus preparation vaccinees compared with those of controls had earlier infiltration with significantly more T lymphocytes (CD5+) and with a greater proportion of CD4+ T lymphocytes at day 4 (33% +/- 55% versus 9.7% +/- 2%; P = 0.002), corroborating earlier sterilization (5.0 +/- 2 versus 13.7 +/- 0.71 days; P < 0.001) and lesion resolution. Intraepithelial challenge of pilus-vaccinated rabbits with 100 micrograms of the pilus preparation alone produced indurated lesions within 48 h with lymphoid and plasmacytoid infiltration, edema, and extravasation of erythrocytes. We conclude that passive immunization may not confer a vaccine effect in this model and that active vaccination with a pilus preparation induces a delayed-type hypersensitivity skin test response and confers protection through cell-mediated immunity seen as an amplified lymphocytic infiltrate and accelerated maturation of the T-lymphocyte response. PMID:8613391

Medical Surveillance Monthly Report (MSMR). Volume 2, Number 10, December 1996

DTIC Science & Technology

1996-12-01

satellite clinics. Not all sites reporting. Date of Report: 7-Dec-96 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma ... Venereum (d) Syphilis unspec. (e) Syph, tertiary (f) Syph, congenital MSMRVol. 02 / No. 10 7 Acute Respiratory Disease (ARD) Surveillance Among Army

Medical Surveillance Monthly Report (MSMR). Volume 3, Number 1, January 1997

DTIC Science & Technology

1997-01-01

all sites reporting. Date of Report: 7-Jan-97 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis...Listeriosis - - - - - - - 1 - - - 1 2 Lyme disease 1 - - 1 - 7 5 1 3 1 - - 19 Lymphogranuloma Vnrm - - 1 1 1 1 - - 3 2 - - 9 (Continued) MSMRVol. 03 / No

Medical Surveillance Monthly Report (MSMR). Volume , Number 4, July 1995

DTIC Science & Technology

1995-07-01

Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis unspec. (e) Syph, tertiary (f) Syph, congenital...disease 1 1 1 1 1 1 6 Lymphogranuloma Vnrm 1 2 1 1 4 - 9 (Continued) MSMRVol. 01 / No. 04 11 TABLE S1. Notifiable conditions reported through Medical

Using the Estimating Supplies Program to Develop Material Solutions for the U.S. Air Force Medical Gynecological Treatment Team (FFGYN)

DTIC Science & Technology

2007-12-10

ADENOPATHY, CHANCROID, GENITAL HERPES SIMPLEX, LYMPHOGRANULOMA VENEREUEM, SYPHILLIS, HPV 5 5 271 SEXUALLY TRANSMITTED DISEASE, GONORRHEA...INCISION 3 1 4 269 SEXUALLY TRANSMITTED DISEASE, NSU, MUCUPURULENT, CERVICITIS, TRICOMONAS 3 3 270 SEXUALLY TRANSMITTED DISEASE, GENITAL ULCERS

Chronic cutaneous ulcers secondary to Haemophilus ducreyi infection.

PubMed

Peel, Trisha N; Bhatti, Deepak; De Boer, Jim C; Stratov, Ivan; Spelman, Denis W

2010-03-15

Haemophilus ducreyi is a well recognised causative agent of genital ulcers and chancroid. We report two unusual cases of non-sexually transmitted H. ducreyi infection leading to chronic lower limb ulcers. Both patients were Australian expatriates visiting Australia from the Pacific Islands--one from Papua New Guinea and the other from Vanuatu.

A mixed infection of syphilis and chancroid.

PubMed

Lundquist, C D

1984-02-01

The clinical differentiation between a hard chancre and a soft chancre is well known to dermatologists. We present a patient with both a hard and a soft chancre developing on the penis. Thorough investigational studies should be made of all patients with venereal disease to determine whether more than one venereal disease is present.

An investigation of genital ulcers in Jackson, Mississippi, with use of a multiplex polymerase chain reaction assay: high prevalence of chancroid and human immunodeficiency virus infection.

PubMed

Mertz, K J; Weiss, J B; Webb, R M; Levine, W C; Lewis, J S; Orle, K A; Totten, P A; Overbaugh, J; Morse, S A; Currier, M M; Fishbein, M; St Louis, M E

1998-10-01

In 1994, an apparent outbreak of atypical genital ulcers was noted by clinicians at the sexually transmitted disease clinic in Jackson, Mississippi. Of 143 patients with ulcers tested with a multiplex polymerase chain reaction (PCR) assay, 56 (39%) were positive for Haemophilus ducreyi, 44 (31%) for herpes simplex virus, and 27 (19%) for Treponema pallidum; 12 (8%) were positive for > 1 organism. Of 136 patients tested for human immunodeficiency virus (HIV) by serology, 14 (10%) were HIV-seropositive, compared with none of 200 patients without ulcers (P < .001). HIV-1 DNA was detected by PCR in ulcers of 6 (50%) of 12 HIV-positive patients. Multivariate analysis indicated that men with chancroid were significantly more likely than male patients without ulcers to report sex with a crack cocaine user, exchange of money or drugs for sex, and multiple sex partners. The strong association between genital ulcers and HIV infection in this population highlights the urgency of preventing genital ulcers in the southern United States.

Medical Surveillance Monthly Report (MSMR). Volume 4, Number 3, April 1998

DTIC Science & Technology

1998-04-01

satellite clinics. Not all sites reporting. Date of Report: 7-Apr-98 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum ...5 41 Varicella,adult only 63 34 25 21 143 Lymphogranuloma Vnrm 12 14 1 2 29 Yellow fever 0 0 0 0 0 Total 2338 2395 2877 2397 10007 * Based on

Medical Surveillance Monthly Report (MSMR). Volume 4, Number 5, July/August 1998

DTIC Science & Technology

1998-08-01

98 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis unspec. (e) Syph, tertiary (f) Syph, congenital...Listeriosis 0 0 0 Vaccine advrs event 0 1 1 Lyme disease 4 9 13 Varicella,adult only 74 33 107 Lymphogranuloma Vnrm 0 0 0 Yellow fever 0 0 0 Total

Medical Surveillance Monthly Report MSMR). Volume 4, Number 7, October/November 1998

DTIC Science & Technology

1998-11-01

from main and satellite clinics. Not all sites reporting. ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d...Vaccine advrs event 0 4 5 9 Lyme disease 4 10 18 32 Varicella,adult only 73 30 1 104 Lymphogranuloma Vnrm 0 0 0 0 Yellow fever 0 0 0 0 Total

Medical Surveillance Monthly Report (MSMR). Volume 3, Number 5, July/August 1997

DTIC Science & Technology

1997-08-01

sites reporting. Date of Report: 7-Aug-97 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis unspec. (e...Listeriosis 0 0 0 Vaccine advrs event 0 0 0 Lyme disease 4 4 8 Varicella,adult only 68 38 106 Lymphogranuloma Vnrm 12 14 26 Yellow fever 0 0 0 Total

Medical Surveillance Monthly Report (MSMR). Volume 2, Number 4, April 1996

DTIC Science & Technology

1996-04-01

Report: 7-Apr-96 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis unspec. (e) Syph, tertiary (f...Lyme disease 1 1 1 1 1 3 3 1 - 1 - - 13 Lymphogranuloma Vnrm 1 2 1 1 4 1 - - 1 - - - 11 (Continued) MSMRVol. 02 / No. 04 21 TABLE S5. Notifiable

Direct Whole-Genome Sequencing of Cutaneous Strains of Haemophilus ducreyi

PubMed Central

Fookes, Maria; Wagner, Josef; Ghinai, Rosanna; Sokana, Oliver; Sarkodie, Yaw-Adu; Solomon, Anthony W.; Mabey, David C.W.; Thomson, Nicholas R.

2018-01-01

Haemophilus ducreyi, which causes chancroid, has emerged as a cause of pediatric skin disease. Isolation of H. ducreyi in low-income settings is challenging, limiting phylogenetic investigation. Next-generation sequencing demonstrates that cutaneous strains arise from class I and II H. ducreyi clades and that class II may represent a distinct subspecies. PMID:29553314

Assessing the antibiotic potential of essential oils against Haemophilus ducreyi.

PubMed

Lindeman, Zachary; Waggoner, Molly; Batdorff, Audra; Humphreys, Tricia L

2014-05-27

Haemophilus ducreyi is the bacterium responsible for the genital ulcer disease chancroid, a cofactor for the transmission of HIV, and it is resistant to many antibiotics. With the goal of exploring possible alternative treatments, we tested essential oils (EOs) for their efficacy as antimicrobial agents against H. ducreyi. We determine the minimum inhibitory concentration (MIC) of Cinnamomum verum (cinnamon), Eugenia caryophyllus (clove) and Thymus satureioides (thyme) oil against 9 strains of H. ducreyi using the agar dilution method. We also determined the minimum lethal concentration for each oil by subculturing from the MIC plates onto fresh agar without essential oil. For both tests, we used a 2-way ANOVA to evaluate whether antibiotic-resistant strains had a different sensitivity to the oils relative to non-resistant strains. All 3 oils demonstrated excellent activity against H. ducreyi, with MICs of 0.05 to 0.52 mg/mL and MLCs of 0.1-0.5 mg/mL. Antibiotic-resistant strains of H. ducreyi were equally susceptible to these 3 essential oils relative to non-resistant strains (p=0.409). E. caryophyllus, C. verum and T. satureioides oils are promising alternatives to antibiotic treatment for chancroid.

Chancroid and granuloma inguinale.

PubMed

Schwarz, R H

1983-03-01

Chancroid, also known as soft chancre, is seen infrequently and is manifested locally rather than systemically. The causative organism, Hemophilus ducreyi, is a short nonmotile bacillus, non-acid-fast, and usually gram-negative. Culture of the organism is difficult because contamination by other organisms inhibits the growth of H. ducreyi. Chancroid is relatively rare in the US but is more common in developing countries. It is a disease of the sexually promiscuous and is associated with poor hygiene. The lesions are usually obvious in the male but may be undetected in women. The incubation period is 3-5 days and the typical lesion is a soft nonindurated ulcer with a dirty exudate at the base, which is painful and exquisitely tender to palpation. Bubo formation is common and about half suppurate. Diagnosis depends on differentiation from other genital ulcers. The characteristics of the lesions and the nature of lymph node involvement are diagnostic features; smears and cultures are also involved but the organism may be difficult to isolate and the diagnosis must often be established on clinical grounds alone. In many instances no specific therapy other than cleansing with soap and water may be required. The sulfonamides, tetracycline, or a combination may be utilized. Prevention is usually a function of hygiene; condoms offer good protection. Granuloma inguinale, a disease of tropical and subtropical countries, is caused by the gram-negative, pleomorphic and microaerophilic bacterium Calymmatobacterium granulomatis. The mode of transmission is probably sexual but sexual transmission has been questioned on the basis that the disease is not very contagious. It is likely that a break in the skin or mucosa is necessary for the disease to become established. Lesions occur a few days to 3 months after inoculation in the form of 1 or more indurated papules which gradually break down to form ulcers. The ulceration may spread to the entire genitocrural area if untreated, but systemic disease is very rare. The diagnosis is usually suggested by the history and physical findings but confirmation can be obtained by smears of biopsy and histologic examination. The condition is responsive to a wide variety of antibiotics. Personal hygiene is the most effective means of prevention.

Medical Surveillance Monthly Report (MSMR). Volume 4, Number 4, May/June 1998

DTIC Science & Technology

1998-06-01

Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis unspec. (e) Syph, tertiary (f) Syph, congenital MSMRVol. 04 / No. 04 7...transmitted diseases, US Army medical treatment facilities* May, 1998 Reporting Chlamydia Urethritis non-spec. Gonorrhea Herpes Simplex Syphilis Prim/Sec... Syphilis Latent Other STDs** MTF/Post** Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Month 1998 Month 1998 Month 1998

Medical Surveillance Monthly Report (MSMR). Volume 3, Number 6, September 1997

DTIC Science & Technology

1997-09-01

1997 Prepared by the Medical Surveillance Activity, Directorate of Epidemiology and Disease Surveillance, United States Army Center for Health...Gonorrhea Herpes Simplex Syphilis Prim/Sec Syphilis Latent Other STDs** MTF/Post** Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur...clinics. Not all sites reporting. Date of Report: 7-Sep-97 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis

Chancroid, lymphogranuloma venereum, granuloma inguinale, genital herpes simplex infection, and molluscum contagiosum.

PubMed

Basta-Juzbašić, Aleksandra; Čeović, Romana

2014-01-01

Chancroid, lymphogranuloma venereum, and granuloma inguinale may be considered as tropical venereal diseases. These diseases were a major diagnostic and therapeutic challenge in past centuries. Currently, patients with these bacterial infections that are endemic to the tropics occasionally consult with dermatologists in temperate climates. Due to the increasing frequency of travel to the tropics for tourism and work, as well as the increasing number of immigrants from these areas, it is important for dermatologists practicing in temperate climates to be familiar with the dermatologic manifestations of such infections, to be prepared to diagnose these diseases, and to treat these patients. All three "tropical" infections respond well to prompt and appropriate antimicrobial treatment, although herpes progenitalis still cannot be cured, and the number of people infected keeps growing; moreover, genital herpes can be transmitted by viral shedding before and after the visual signs or symptoms. Acyclovir, valacyclovir, and famciclovir can shorten outbreaks and make them less severe or even stop them from happening. There is currently no etiologic treatment for molluscum contagiosum, and the majority of treatment options are mechanical, causing a certain degree of discomfort. The molluscum contagiosum virus, unlike the other infectious agents mentioned, does not invade the skin. © 2014 Elsevier Inc. All rights reserved.

Etiology of genital ulcer disease. A prospective study of 278 cases seen in an STD clinic in Paris.

PubMed

Hope-Rapp, Emilie; Anyfantakis, Vassili; Fouéré, Sebastien; Bonhomme, Philippe; Louison, Jean B; de Marsac, Thibault Tandeau; Chaine, Benedicte; Vallee, Pascale; Casin, Isabelle; Scieux, Catherine; Lassau, François; Janier, Michel

2010-03-01

The goal of this study was to identify the causes and factors associated with genital ulcer disease (GUD) among patients attending a sexually transmitted disease (STD) clinic in Paris. This study was a prospective investigation of GUD cases. Data were collected from 1995 to 2005. In each case, a Dark Field Examination (DFE), Gram stain, inoculation onto Thayer Martin agar, Columbia agar and chocolate agar with 1% isovitalex and 20% fetal calf serum, PCR Chlamydia trachomatis (Amplicor Roche), culture for herpes simplex virus (HSV) on MRC 5 cells and PCR HSV (Argene Biosoft) were obtained from the ulceration. First Catch Urine (FCU) PCR for Chlamydia trachomatis and syphilis, HIV, HSV, and HBV serologies were also performed. A total 278 cases of GUD were investigated, 244 (88%) in men and 34 (12%) in women. Primary syphilis accounted for 98 cases (35%), genital herpes for 74 (27%), chancroid for 8 (3%), other infections for 12 (5%). In 91 (32%) patients, no identifiable microorganism was documented. Primary syphilis was more prevalent in MSMs (P < 0.0001), while genital herpes and chancroid were significantly associated with heterosexuality (both P < 0.0001). A high level of HIV infection (27%) was found, particularly in patients with primary syphilis (33%). In the univariate analysis, no statistical difference was found between syphilis and herpes according to clinical presentation, pain being the only item slightly more frequent in herpes (P = 0.06). In the multivariable model syphilis was associated with being MSM (OR: 51.3 [95% CI: 14.7-178.7], P < 0.001) and with an ulceration diameter >10 mm (OR: 9.2 [95% CI: 2.9-30.7], P < 0.001). Genital herpes was associated with HIV infection in the subgroup of MSWs (OR: 24.4 [2.4-247.7], P = 0.007). We did not find significant differences in the clinical presentation of the ulcers according to HIV status. The profound changes of the epidemiology of GUD during the decade, due to disappearance of chancroid and reemergence of infectious syphilis have led to a new distribution of pathogens, genital herpes, primary syphilis and GUD from unknown origin, accounting each for one third of cases. No clinical characteristic is predictive of the etiology, underlining the importance of performing a thorough microbiologic evaluation. Close association with HIV is still a major public health problem.

Medical Surveillance Monthly Report (MSMR). Volume 3, Number 4, June 1997

DTIC Science & Technology

1997-06-01

STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma Venereum (d) Syphilis unspec. (e) Syph, tertiary (f) Syph, congenital MSMRVol. 03...Simplex Syphilis Prim/Sec Syphilis Latent Other STDs** MTF/Post** Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Cur. Cum. Month 1997...97 Chlamydia Gonorrhea Syphilis Jun-95 Sep-95 Dec-95 Mar-96 Jun-96 Sep-96 Dec-96 Mar-97 * Reports are included from main and satellite clinics. Not

Medical Surveillance Monthly Report (MSMR). Volume 3, Number 3, April 1997

DTIC Science & Technology

1997-04-01

and satellite clinics. Not all sites reporting. Date of Report: 7-Apr-97 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma ... Venereum (d) Syphilis unspec. (e) Syph, tertiary (f) Syph, congenital MSMRVol. 03 / No. 03 7 Active Duty Other FIGURE II. Reportable sexually...98 Lymphogranuloma Vnrm 1 3 3 5 12 Yellow fever 0 0 0 0 0 Total 2039 2044 1851 1539 7473 * Based on date of onset. Date of report: 7-Apr-97

Medical Surveillance Monthly Report (MSMR). Volume 3, Number 7, October 1997

DTIC Science & Technology

1997-10-01

main and satellite clinics. Not all sites reporting. Date of Report: 7-Oct-97 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma ... Venereum (d) Syphilis unspec. (e) Syph, tertiary (f) Syph, congenital § Includes participants in a large-scale ongoing chlamydia study (females only... Lymphogranuloma Vnrm 12 14 1 27 Yellow fever 0 0 0 0 Total 2320 2357 2468 7145 * Based on date of onset. Date of report: 7-Oct-97 MSMRVol. 03

Medical Surveillance Monthly Report (MSMR). Volume 4, Number 1, January 1998

DTIC Science & Technology

1998-01-01

and satellite clinics. Not all sites reporting. Date of Report: 7-Jan-98 ** Other STDs: (a) Chancroid (b) Granuloma Inguinale (c) Lymphogranuloma ... Venereum (d) Syphilis unspec. (e) Syph, tertiary (f) Syph, congenital § Includes participants in a large-scale ongoing chlamydia study (females only...only 63 34 25 12 134 Lymphogranuloma Vnrm 12 15 1 2 30 Yellow fever 0 0 0 0 0 Total 2342 2408 2864 1929 9543 * Based on date of onset. Date of

Antigen detection and immunological typing of Haemophilus ducreyi with a specific rabbit polyclonal serum.

PubMed Central

Roggen, E L; Pansaerts, R; Van Dyck, E; Piot, P

1993-01-01

A rabbit polyclonal serum was raised against the 29-kDa species-specific marker, as well as the 30- to 34-kDa immunotype-specific markers of Haemophilus ducreyi described elsewhere (E. Roggen, S. De Breucker, E. Van Dyck, and P. Piot, Infect. Immun. 60:590-595, 1992). These antigens were purified from a cocktail of H. ducreyi isolates by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The immune serum reacted in enzyme-linked immunosorbent assay (ELISA) preferentially with H. ducreyi, at a titer as high as 50,000. To make it specific to H. ducreyi, nonspecific antibodies were removed by adsorption on a mixture of Haemophilus spp., Escherichia coli, Candida albicans, and Corynebacterium spp. In the 29- to 34-kDa region of immunoblot profiles from H. ducreyi isolates (n = 450), the adsorbed serum revealed essentially the same antigens as did a pool of well-characterized human sera. Yet, eight different immunotypes were observed. With this rabbit polyclonal serum, an ELISA-based antigen detection test was developed. The adsorbed serum reacted specifically with all H. ducreyi isolates tested (n = 450), but not with other bacterial species (n = 15). This test was evaluated with a limited number of clinical specimens from African patients with culture-proven chancroid and no evidence for any other ulcerating etiology (n = 10) and a number of chancroid-negative control patients from Belgium (n = 20). Within this context, the test yielded a sensitivity and specificity of 100%. Images PMID:8349759

Neutropenia restores virulence to an attenuated Cu,Zn superoxide dismutase-deficient Haemophilus ducreyi strain in the swine model of chancroid.

PubMed

San Mateo, L R; Toffer, K L; Orndorff, P E; Kawula, T H

1999-10-01

Haemophilus ducreyi causes chancroid, a sexually transmitted cutaneous genital ulcer disease associated with increased heterosexual transmission of human immunodeficiency virus. H. ducreyi expresses a periplasmic copper-zinc superoxide dismutase (Cu, Zn SOD) that protects the bacterium from killing by exogenous superoxide in vitro. We hypothesized that the Cu,Zn SOD would protect H. ducreyi from immune cell killing, enhance survival, and affect ulcer development in vivo. In order to test this hypothesis and study the role of the Cu,Zn SOD in H. ducreyi pathogenesis, we compared a Cu,Zn SOD-deficient H. ducreyi strain to its isogenic wild-type parent with respect to survival and ulcer development in immunocompetent and immunosuppressed pigs. The Cu,Zn SOD-deficient strain was recovered from significantly fewer inoculated sites and in significantly lower numbers than the wild-type parent strain or a merodiploid (sodC+ sodC) strain after infection of immunocompetent pigs. In contrast, survival of the wild-type and Cu,Zn SOD-deficient strains was not significantly different in pigs that were rendered neutropenic by treatment with cyclophosphamide. Ulcer severity in pigs was not significantly different between sites inoculated with wild type and sites inoculated with Cu,Zn SOD-deficient H. ducreyi. Our data suggest that the periplasmic Cu,Zn SOD is an important virulence determinant in H. ducreyi, protecting the bacterium from host immune cell killing and contributing to survival and persistence in the host.

Neutropenia Restores Virulence to an Attenuated Cu,Zn Superoxide Dismutase-Deficient Haemophilus ducreyi Strain in the Swine Model of Chancroid

PubMed Central

San Mateo, Lani R.; Toffer, Kristen L.; Orndorff, Paul E.; Kawula, Thomas H.

1999-01-01

Haemophilus ducreyi causes chancroid, a sexually transmitted cutaneous genital ulcer disease associated with increased heterosexual transmission of human immunodeficiency virus. H. ducreyi expresses a periplasmic copper-zinc superoxide dismutase (Cu,Zn SOD) that protects the bacterium from killing by exogenous superoxide in vitro. We hypothesized that the Cu,Zn SOD would protect H. ducreyi from immune cell killing, enhance survival, and affect ulcer development in vivo. In order to test this hypothesis and study the role of the Cu,Zn SOD in H. ducreyi pathogenesis, we compared a Cu,Zn SOD-deficient H. ducreyi strain to its isogenic wild-type parent with respect to survival and ulcer development in immunocompetent and immunosuppressed pigs. The Cu,Zn SOD-deficient strain was recovered from significantly fewer inoculated sites and in significantly lower numbers than the wild-type parent strain or a merodiploid (sodC+ sodC) strain after infection of immunocompetent pigs. In contrast, survival of the wild-type and Cu,Zn SOD-deficient strains was not significantly different in pigs that were rendered neutropenic by treatment with cyclophosphamide. Ulcer severity in pigs was not significantly different between sites inoculated with wild type and sites inoculated with Cu,Zn SOD-deficient H. ducreyi. Our data suggest that the periplasmic Cu,Zn SOD is an important virulence determinant in H. ducreyi, protecting the bacterium from host immune cell killing and contributing to survival and persistence in the host. PMID:10496915

Comparison of culture media for the laboratory diagnosis of chancroid.

PubMed

Pillay, A; Hoosen, A A; Loykissoonlal, D; Glock, C; Odhav, B; Sturm, A W

1998-11-01

Seven different agar-based media were compared to determine the optimal set of culture media for primary isolation of Haemophilus ducreyi. Also, a new method for sampling genital ulcers -- with a disposable sterile plastic loop -- and processing specimens that provides a standardised inoculum for culture of H. ducreyi on various media is described. A total of 202 patients with genital ulcer disease was enrolled in this study. A sterile swab or plastic loop was used to sample the base of the ulcers and ulcer material was suspended in sterile phosphate-buffered saline. A 100-microl sample of this suspension was mixed with an equal volume of tryptic soy broth containing IsoVitaleX and centrifuged for 1 min. This suspension was used to inoculate the different media. Plates were incubated at 33 degrees C in micro-aerophilic conditions and examined for growth of H. ducreyi after 48 h. Of the 202 specimens, 77 (38.1%) were culture positive for H. ducreyi. None of the agar bases supported the growth of all H. ducreyi strains. Based on this observation, we recommend the universal use of Mueller-Hinton agar base supplemented with chocolate horse blood and IsovitaleX (MH-HBC) and Columbia agar base supplemented with bovine haemoglobin, activated charcoal, fetal calf serum and IsovitaleX (C-HgCh) to enable comparison of prevalence figures for chancroid. In addition, the novel sampling technique described in this study eliminates sampling bias normally associated with genital ulcer specimens.

[Import and local transmission of Haemophilus ducreyi].

PubMed

Knudsen, Troels Bygum; Sand, Carsten; Jensen, Jørgen Skov

2010-07-26

Chancroid is a sexually transmitted disease characterized by painful ulcers with a soft margin, necrotic base and purulent exudate. Previously, only sporadic, imported cases have been reported in Denmark. The bacterium is difficult to culture and novel polymerase chain reaction (PCR)-based methods for direct demonstration of bacterial DNA have facilitated rapid verification of the clinical diagnosis. We report two cases which demonstrate import and subsequent local transmission in Denmark. In both cases, the clinical diagnosis was rapidly verified by a combined PCR testing for multiple causes of venereal ulcers.

Sexually transmitted infections in Pakistan

PubMed Central

Maan, Muhammad Arif; Hussain, Fatma; Iqbal, Javed; Akhtar, Shahid Javed

2011-01-01

BACKGROUND AND OBJECTIVES: Sexually transmitted infections (STIs) represent a major global health problem leading to morbidity, mortality and stigma. Prior to this study there was no information on the prevalence and knowledge of STIs in Faisalabad, Pakistan. DESIGN AND SETTING: Prospective, cross-sectional study in patients attending STI clinics from July 2006 to September 2009. PATIENTS AND METHODS: After obtaining consent, patients completed structured questionnaires used for behavioral surveys. Blood and urethral swabs were collected and tested for syphilis, gonococcus, genital herpes, chlamydia and chancroid. RESULT: Mean (standard deviation) age of the 1532 participants was 38.9 (9.4) years, including 37.8 (10.2) years for males and 35.5 (6.3) years females. Male gender (n=1276, 83.3%), low socioeconomic class (n=1026, 67.0%) and residence in rural suburbs (n=970, 63.3%) were more common. Most (n=913, 59.6%) were aware of the modes of transmission of STIs and the associated complications, 20% (n=306) were condom users, and 21.2% (n=324) had knowledge of safe sex. Opposite-sex partners were preferred by 972 (63.4%) patients, while 29.9% (n=458) had both homosexual and heterosexual sex partners. Syphilis was present in 29.5% of patients (n=452); gonorrhea, in 13% (n=200), HSV-2, in 3.2% (n=49), chlamydia, in 4.7% (n=72) and chancroid, in 1.3% (n=20). CONCLUSION: This report establishes baseline local prevalence rates for STIs. Syphilis emerged as the most prevalent STI in Faisalabad. Population-based studies are required to study the epidemiology of STIs, along with initiation of national health-education campaign. PMID:21623055

Prevalence of, Antibody Response to, and Immunity Induced by Haemophilus ducreyi Hemolysin

PubMed Central

Dutro, Susan M.; Wood, Gwendolyn E.; Totten, Patricia A.

1999-01-01

Haemophilus ducreyi, the etiologic agent of chancroid, a genital ulcer disease, produces a cell-associated hemolysin whose role in virulence is not well defined. Hemolysin is encoded by two genes, hhdA and hhdB, which, based on their homology to Serratia marcescens shlA and shlB genes, are believed to encode the hemolysin structural protein and a protein required for secretion and modification of this protein, respectively. In this study, we determined the prevalence and expression of the hemolysin genes in 90 H. ducreyi isolates obtained from diverse geographic locations from 1952 to 1996 and found that all strains contained DNA homologous to the hhdB and hhdA genes. In addition, all strains expressed a hemolytic activity. We also determined that hemolysin is expressed in vivo and is immunogenic, as indicated by the induction of antibodies to hemolysin in both the primate and rabbit disease models as well as in human patients with naturally acquired chancroid. Wild-type strain 35000 and isogenic hemolysin-negative mutants showed no difference in lesion development in the temperature-dependent rabbit model. However, immunization of rabbits with the purified hemolysin protein reduced the recovery of wild-type H. ducreyi, but not hemolysin-negative mutants, from lesions. Our study indicates that hemolysin is a possible candidate for vaccine development due to its immunogenicity, expression in vitro and in vivo by most, if not all, strains, and the effect of immunization on reducing the recovery of viable H. ducreyi in experimental disease in rabbits. PMID:10377108

Trimeric autotransporter DsrA is a major mediator of fibrinogen binding in Haemophilus ducreyi.

PubMed

Fusco, William G; Elkins, Christopher; Leduc, Isabelle

2013-12-01

Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. In both natural and experimental chancroid, H. ducreyi colocalizes with fibrin at the base of the ulcer. Fibrin is obtained by cleavage of the serum glycoprotein fibrinogen (Fg) by thrombin to initiate formation of the blood clot. Fg binding proteins are critical virulence factors in medically important Gram-positive bacteria. H. ducreyi has previously been shown to bind Fg in an agglutination assay, and the H. ducreyi Fg binding protein FgbA was identified in ligand blotting with denatured proteins. To better characterize the interaction of H. ducreyi with Fg, we examined Fg binding to intact, viable H. ducreyi bacteria and identified a novel Fg binding protein. H. ducreyi bound unlabeled Fg in a dose-dependent manner, as measured by two different methods. In ligand blotting with total denatured cellular proteins, digoxigenin (DIG)-Fg bound only two H. ducreyi proteins, the trimeric autotransporter DsrA and the lectin DltA; however, only the isogenic dsrA mutant had significantly less cell-associated Fg than parental strains in Fg binding assays with intact bacteria. Furthermore, expression of DsrA, but not DltA or an empty vector, rendered the non-Fg-binding H. influenzae strain Rd capable of binding Fg. A 13-amino-acid sequence in the C-terminal section of the passenger domain of DsrA appears to be involved in Fg binding by H. ducreyi. Taken together, these data suggest that the trimeric autotransporter DsrA is a major determinant of Fg binding at the surface of H. ducreyi.

Macrolides for treatment of Haemophilus ducreyi infection in sexually active adults.

PubMed

Romero, Laura; Huerfano, Cesar; Grillo-Ardila, Carlos F

2017-12-11

Chancroid is a genital ulcerative disease caused by Haemophilus ducreyi. This microorganism is endemic in Africa, where it can cause up to 10% of genital ulcers. Macrolides may be an effective alternative to treat chancroid and, based on their oral administration and duration of therapy, could be considered as first line therapy. To assess the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults. We searched the Cochrane STI Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, WHO ICTRP, ClinicalTrials.gov and Web of Science to 30 October 2017. We also handsearched conference proceedings and reference lists of retrieved studies. Randomized controlled trials (RCTs) comparing macrolides in different regimens or with other therapeutic alternatives for chancroid. Two review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. We resolved disagreements through consensus. We used the GRADE approach to assess the quality of the evidence. Seven RCTs (875 participants) met our inclusion criteria, of which four were funded by industry. Five studies (664 participants) compared macrolides with ceftriaxone, ciprofloxacin, spectinomycin or thiamphenicol. Low quality evidence suggested there was no difference between the groups after treatment in terms of clinical cure (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.97 to 1.21; 2 studies, 340 participants with syndromic approach and RR 1.06, 95% CI 0.98 to 1.15; 5 studies, 348 participants with aetiological diagnosis) or improvement (RR 0.89, 95% CI 0.52 to 1.52; 2 studies, 340 participants with syndromic approach and RR 0.80, 95% CI 0.42 to 1.51; 3 studies, 187 participants with aetiological diagnosis). Based on low and very low quality evidence, there was no difference between macrolides and any other antibiotic treatments for microbiological cure (RR 0.93, 95% CI 0.74 to 1.16; 1 study, 45 participants) and minor adverse effects (RR 1.34, 95% CI 0.24 to 7.51; 3 studies, 412 participants).Two trials (269 participants) compared erythromycin with any other macrolide type. Low quality evidence suggested that, compared with azithromycin or rosaramicin, long courses of erythromycin did not increase clinical cure (RR 1.00, 95% CI 0.91 to 1.10; 2 studies, 269 participants with syndromic approach and RR 1.04, 95% CI 0.93 to 1.16; 2 studies, 211 participants with aetiological diagnosis), with a similar frequency of minor adverse effects between the groups (RR 1.14, 95% CI 0.63 to 2.06; 1 trial, 101 participants). For this comparison, subgroup analysis found no difference between HIV-positive participants (RR 1.02, 95% CI 0.73 to 1.43; 1 study, 38 participants) and HIV-negative participants (RR 1.04, 95% CI 0.94 to 1.14; 1 study, 89 participants). We downgraded the quality of evidence to low, because of imprecision, some limitations on risk of bias and heterogeneity.None of the trials reported serious adverse events, cost effectiveness and participant satisfaction. At present, the quality of the evidence on the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults is low, implying that we are uncertain about the estimated treatment effect. There is no statistically significant difference between the available therapeutic alternatives for the treatment of sexually active adults with genital ulcers compatible with chancroid. Low quality evidence suggests that azithromycin could be considered as the first therapeutic alternative, based on their mono-dose oral administration, with a similar safety and effectiveness profile, when it is compared with long-term erythromycin use.Due to sparse available evidence about the safety and effectiveness of macrolides to treat H ducreyi infection in people with HIV, these results should be taken with caution.

Trimeric Autotransporter DsrA Is a Major Mediator of Fibrinogen Binding in Haemophilus ducreyi

PubMed Central

Fusco, William G.; Elkins, Christopher

2013-01-01

Haemophilus ducreyi is the etiologic agent of the sexually transmitted genital ulcer disease chancroid. In both natural and experimental chancroid, H. ducreyi colocalizes with fibrin at the base of the ulcer. Fibrin is obtained by cleavage of the serum glycoprotein fibrinogen (Fg) by thrombin to initiate formation of the blood clot. Fg binding proteins are critical virulence factors in medically important Gram-positive bacteria. H. ducreyi has previously been shown to bind Fg in an agglutination assay, and the H. ducreyi Fg binding protein FgbA was identified in ligand blotting with denatured proteins. To better characterize the interaction of H. ducreyi with Fg, we examined Fg binding to intact, viable H. ducreyi bacteria and identified a novel Fg binding protein. H. ducreyi bound unlabeled Fg in a dose-dependent manner, as measured by two different methods. In ligand blotting with total denatured cellular proteins, digoxigenin (DIG)-Fg bound only two H. ducreyi proteins, the trimeric autotransporter DsrA and the lectin DltA; however, only the isogenic dsrA mutant had significantly less cell-associated Fg than parental strains in Fg binding assays with intact bacteria. Furthermore, expression of DsrA, but not DltA or an empty vector, rendered the non-Fg-binding H. influenzae strain Rd capable of binding Fg. A 13-amino-acid sequence in the C-terminal section of the passenger domain of DsrA appears to be involved in Fg binding by H. ducreyi. Taken together, these data suggest that the trimeric autotransporter DsrA is a major determinant of Fg binding at the surface of H. ducreyi. PMID:24042118

[Infectious pathology: vulvovaginitis, sexually transmitted diseases, pelvic inflammatory disease, tubo-ovarian abscesses].

PubMed

Ibarrola Vidaurre, M; Benito, J; Azcona, B; Zubeldía, N

2009-01-01

Sexually transmitted diseases are those where the principal path of infection is through intimate contact. Numerous patients attend Accidents and emergencies for this reason, both because of the clinical features and because of social implications. The most frequent symptoms are lower abdominal pain, vaginal bleeding or excessive or troubling vaginal flow. Vulvovaginites are one of the principal problems in the everyday clinical practice of gynaecology. A genital ulcer whose principal aetiology is herpes, followed by syphilis and chancroid, increases the risk of contracting HIV infection and alters the course of other sexually transmitted diseases. Inflammatory pelvic disease encompasses infections of the upper female genital tract. The importance of early diagnosis and suitable treatment is both due to the complications in its acute phase and to its sequels, which include chronic pain and sterility.

Use of signature-tagged mutagenesis to identify virulence determinants in Haemophilus ducreyi responsible for ulcer formation.

PubMed

Yeung, Angela; Cameron, D William; Desjardins, Marc; Lee, B Craig

2011-02-01

Elucidating the molecular mechanisms responsible for chancroid, a genital ulcer disease caused by Haemophilus ducreyi, has been hampered in part by the relative genetic intractability of the organism. A whole genome screen using signature-tagged mutagenesis in the temperature-dependent rabbit model (TDRM) of H. ducreyi infection uncovered 26 mutants with a presumptive attenuated phenotype. Insertions in two previously recognized virulence determinants, hgbA and lspA1, validated this genome scanning technique. Database interrogation allowed assignment of 24 mutants to several functional classes, including transport, metabolism, DNA repair, stress response and gene regulation. The attenuated virulence for a 3 strain with a mutation in hicB was confirmed by individual infection in the TDRM. The results from this preliminary study indicate that this high throughput strategy will further the understanding of the pathogenesis of H. ducreyi infection. Copyright © 2010 Elsevier B.V. All rights reserved.

Syphilis and human experimentation from World War II to the present: a historical perspective and reflections on ethics.

PubMed

Cuerda-Galindo, E; Sierra-Valenti, X; González-López, E; López-Muñoz, F

2014-11-01

Even after the Nuremberg code was published, research on syphilis often continued to fall far short of ethical standards. We review post-World War II research on this disease, focusing on the work carried out in Guatemala and Tuskegee. Over a thousand adults were deliberately inoculated with infectious material for syphilis, chancroid, and gonorrhea between 1946 and 1948 in Guatemala, and thousands of serologies were performed in individuals belonging to indigenous populations or sheltered in orphanages. The Tuskegee syphilis study, conducted by the US Public Health Service, took place between 1932 and 1972 with the aim of following the natural history of the disease when left untreated. The subjects belonged to a rural black population and the study was not halted when effective treatment for syphilis became available in 1945. Copyright © 2013 Elsevier España, S.L.U. and AEDV. All rights reserved.

On the evolution of the sexually transmitted bacteria Haemophilus ducreyi and Klebsiella granulomatis.

PubMed

Lagergård, Teresa; Bölin, Ingrid; Lindholm, Leif

2011-08-01

Haemophilus ducreyi and Klebsiella (Calymmatobacterium) granulomatis are sexually transmitted bacteria that cause characteristic, persisting ulceration on external genitals called chancroid and granuloma inguinale, respectively. Those ulcers are endemic in developing countries or exist, as does granuloma inguinale, only in some geographic "hot spots."H. ducreyi is placed in the genus Haemophilus (family Pasteurellacae); however, this phylogenetic position is not obvious. The multiple ways in which the bacterium may be adapted to its econiche through specialized nutrient acquisitions; defenses against the immune system; and virulence factors that increase attachment, fitness, and persistence within genital tissue are discussed below. The analysis of K. granulomatis phylogeny demonstrated a high degree of identity with other Klebsiella species, and the name K. granulomatis comb. nov. was proposed. Because of the difficulty in growing this bacterium on artificial media, its characteristics have not been sufficiently defined. More studies are needed to understand bacterial genetics related to the pathogenesis and evolution of K. granulomatis. © 2011 New York Academy of Sciences.

Treatment of chancroid, 1997.

PubMed

Schmid, G P

1999-01-01

Since the 1993 treatment guidelines for sexually transmitted diseases were published by the Centers for Disease Control and Prevention, experience has indicated that the regimens recommended then remain largely effective. The recommended therapies--with azithromycin (1 g orally, once), ceftriaxone (250 mg intramuscularly, once), or erythromycin (500 mg orally, four times a day for 7 days)--appear highly effective in the United States; limited data from Kenya suggest that the ceftriaxone regimen may not be as effective there as it once was. The alternative regimen of ciprofloxacin proposed in 1993 (500 mg orally, twice a day for 3 days) is as effective as the recommended therapies, but new information indicates that single-dose therapy with 500 mg orally is not as effective as the use of either larger single doses or more prolonged therapy. Persons who are infected with human immunodeficiency virus (HIV) do not respond as well as those who are not HIV-infected, and males who are uncircumcised appear not to respond as well as those who are circumcised.

Std trends in chengalpattu hospital.

PubMed

Krishnamurthy, V R; Ramachandran, V

1996-01-01

A retrospective data analysis was carried out to find the trends in frequency and distribution of different STDs at Chengalpattu during 1988-1994. Of the 4549 patients who attended the clinic 3621 (79.6%) were males and 928 (20.4%) were females. The commonest STD was Chancroid (24.4%) in men and Syphillis (29%) in women. Balanoposthitis (11.4%) ranked third among STDs in males. Though the STD attendance showed a declining trend, most diseases showed a constant distribution. The percentage composition of secondary and latent syphillis, Genital Warts, Genital Herpes and the Non-Venereal group showed an increased composition in recent years. Primary syphillis in females showed a definite declining trend. The HIV sero-positive detection rate was 2.06%. Of the 1116 patients screened for HIV antibody, 23 patients were detected sero-positive. Time Series Regression Analysis was used to predict the number of patients who would attend the STD clinic with various STDs in 1995 and 1996 to help in the understanding of the disease load and pattern in future, in resources management and in developing and evaluating preventive measures.

Sexually-transmitted diseases, AIDS and traditional healers in Mozambique.

PubMed

Green, E C; Jurg, A; Dgedge, A

1993-08-01

Qualitative research was conducted with traditional healers in Manica Province, Mozambique to develop an empirical, culturally-appropriate strategy for communication between government and traditional healers related to the prevention of STDs including AIDS. Most Manica healers regard AIDS as a new disease for which they lack medicines. However, when questioned on other sexually transmitted diseases, as defined by healers themselves, relatively complex disease taxonomies based on fine distinctions between symptoms emerged. Manica healers recognize two broad categories of STDs: siki and nyoka-related. The former seems to correspond with the more serious common STDs of Western biomedicine--syphilis, gonorrhea, chlamydia and chancroid--and is believed to be caused by a common invisible, microscopic agent, khoma. Nyoka-related illnesses are understood in terms of traditional ideas of pollution, and denote less serious, self-limiting genito-urinary conditions. Healers express great faith in the efficacy of traditional medicines. Based on the ethnomedical research findings, a culturally-sensitive and -specific AIDS/STD health education strategy for Manica indigenous healers was developed and began operating in a week-long workshop held in Chimoio, Mozambique in November 1991.

Inactivation of the Haemophilus ducreyi luxS gene affects the virulence of this pathogen in human subjects.

PubMed

Labandeira-Rey, Maria; Janowicz, Diane M; Blick, Robert J; Fortney, Kate R; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M; Hansen, Eric J

2009-08-01

Haemophilus ducreyi 35000HP contains a homologue of the luxS gene, which encodes an enzyme that synthesizes autoinducer 2 (AI-2) in other gram-negative bacteria. H. ducreyi 35000HP produced AI-2 that functioned in a Vibrio harveyi-based reporter system. A H. ducreyi luxS mutant was constructed by insertional inactivation of the luxS gene and lost the ability to produce AI-2. Provision of the H. ducreyi luxS gene in trans partially restored AI-2 production by the mutant. The luxS mutant was compared with its parent for virulence in the human challenge model of experimental chancroid. The pustule-formation rate in 5 volunteers was 93.3% (95% confidence interval, 81.7%-99.9%) at 15 parent sites and 60.0% (95% confidence interval, 48.3%-71.7%) at 15 mutant sites (1-tailed P < .001). Thus, the luxS mutant was partially attenuated for virulence. This is the first report of AI-2 production contributing to the pathogenesis of a genital ulcer disease.

Etiologic pattern of genital ulcers in Lusaka, Zambia: has chancroid been eliminated?

PubMed

Makasa, Mpundu; Buve, Anne; Sandøy, Ingvild Fossgard

2012-10-01

Genital ulcers are a public health problem in developing countries. The World Health Organization recommends the use of syndromic guidelines for sexually transmitted infection treatment in resource-constrained countries. Monitoring local etiologies provides information that may aid policy for sexually transmitted infection treatment. We investigated the etiology of genital ulcer disease among outpatients in Lusaka, Zambia. Swabs from genital ulcers of 200 patients were tested using polymerase chain reaction for Treponema pallidum, herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), Haemophilus ducreyi, and Chlamydia trachomatis. The prevalence of the detected pathogens was as follows; HSV-2, 28%; T. pallidum, 11.5%; C. trachomatis, 3%; HSV-1, 0.5%; and H. ducreyi, 0%. Coinfection with HSV-2 and T. pallidum was 1.5%, and coinfection of HSV-2 and C. trachomatis was 1%. In 55% of the patients, no etiologic diagnosis could be established. H. ducreyi was not detected, whereas HSV-2 and T. pallidum were the commonest pathogens. Nondetection of H. ducreyi requires further studies. If the present findings are validated, treatment guidelines would require to be revised in Zambia.

Experimental infection of human volunteers with Haemophilus ducreyi: fifteen years of clinical data and experience.

PubMed

Janowicz, Diane M; Ofner, Susan; Katz, Barry P; Spinola, Stanley M

2009-06-01

Haemophilus ducreyi causes chancroid, which facilitates transmission of human immunodeficiency virus type 1. To better understand the biology of H. ducreyi, we developed a human inoculation model. In the present article, we describe clinical outcomes for 267 volunteers who were infected with H. ducreyi. There was a relationship between papule formation and estimated delivered dose. The outcome (either pustule formation or resolution) of infected sites for a given subject was not independent; the most important determinants of pustule formation were sex and host effects. When 41 subjects were infected a second time, their outcomes segregated toward their initial outcome, confirming the host effect. Subjects with pustules developed local symptoms that required withdrawal from the study after a mean of 8.6 days. There were 191 volunteers who had tissue biopsy performed, 173 of whom were available for follow-up analysis; 28 (16.2%) of these developed hypertrophic scars, but the model was otherwise safe. Mutant-parent trials confirmed key features in H. ducreyi pathogenesis, and the model has provided an opportunity to study differential human susceptibility to a bacterial infection.

Sexually Transmitted Infections and Male Circumcision: A Systematic Review and Meta-Analysis

PubMed Central

Van Howe, Robert S.

2013-01-01

The claim that circumcision reduces the risk of sexually transmitted infections has been repeated so frequently that many believe it is true. A systematic review and meta-analyses were performed on studies of genital discharge syndrome versus genital ulcerative disease, genital discharge syndrome, nonspecific urethritis, gonorrhea, chlamydia, genital ulcerative disease, chancroid, syphilis, herpes simplex virus, human papillomavirus, and contracting a sexually transmitted infection of any type. Chlamydia, gonorrhea, genital herpes, and human papillomavirus are not significantly impacted by circumcision. Syphilis showed mixed results with studies of prevalence suggesting intact men were at great risk and studies of incidence suggesting the opposite. Intact men appear to be of greater risk for genital ulcerative disease while at lower risk for genital discharge syndrome, nonspecific urethritis, genital warts, and the overall risk of any sexually transmitted infection. In studies of general populations, there is no clear or consistent positive impact of circumcision on the risk of individual sexually transmitted infections. Consequently, the prevention of sexually transmitted infections cannot rationally be interpreted as a benefit of circumcision, and any policy of circumcision for the general population to prevent sexually transmitted infections is not supported by the evidence in the medical literature. PMID:23710368

Medical Examination of Aliens--Revisions to Medical Screening Process. Final rule.

PubMed

2016-01-26

The Centers for Disease Control and Prevention (CDC), within the Department of Health and Human Services (HHS), is issuing this final rule (FR) to amend its regulations governing medical examinations that aliens must undergo before they may be admitted to the United States. Based on public comment received, HHS/CDC did not make changes from the NPRM published on June 23, 2015. Accordingly, this FR will: Revise the definition of communicable disease of public health significance by removing chancroid, granuloma inguinale, and lymphogranuloma venereum as inadmissible health-related conditions for aliens seeking admission to the United States; update the notification of the health-related grounds of inadmissibility to include proof of vaccinations to align with existing requirements established by the Immigration and Nationality Act (INA); revise the definitions and evaluation criteria for mental disorders, drug abuse and drug addiction; clarify and revise the evaluation requirements for tuberculosis; clarify and revise the process for the HHS/CDC-appointed medical review board that convenes to reexamine the determination of a Class A medical condition based on an appeal; and update the titles and designations of federal agencies within the text of the regulation.

Experimental infection with Haemophilus ducreyi in persons who are infected with HIV does not cause local or augment systemic viral replication.

PubMed

Janowicz, Diane M; Tenner-Racz, Klara; Racz, Paul; Humphreys, Tricia L; Schnizlein-Bick, Carol; Fortney, Kate R; Zwickl, Beth; Katz, Barry P; Campbell, James J; Ho, David D; Spinola, Stanley M

2007-05-15

We infected 11 HIV-seropositive volunteers whose CD4(+) cell counts were >350 cells/ microL (7 of whom were receiving antiretrovirals) with Haemophilus ducreyi. The papule and pustule formation rates were similar to those observed in HIV-seronegative historical control subjects. No subject experienced a sustained change in CD4(+) cell count or HIV RNA level. The cellular infiltrate in biopsy samples obtained from the HIV-seropositive and HIV-seronegative subjects did not differ with respect to the percentage of leukocytes, neutrophils, macrophages, or T cells. The CD4(+):CD8(+) cell ratio in biopsy samples from the HIV-seropositive subjects was 1:3, the inverse of the ratio seen in the HIV-seronegative subjects (P<.0001). Although CD4(+) cells proliferated in lesions, in situ hybridization and reverse-transcription polymerase chain reaction for HIV RNA was negative. We conclude that experimental infection in HIV-seropositive persons is clinically similar to infection in HIV-seronegative persons and does not cause local or augment systemic viral replication. Thus, prompt treatment of chancroid may abrogate increases in viral replication associated with natural disease.

Sexual transmission of human T-cell lymphotropic virus type 1.

PubMed

Paiva, Arthur; Casseb, Jorge

2014-01-01

Human T-cell lymphotropic virus type 1 (HTLV-1) is endemic in many parts of the world and is primarily transmitted through sexual intercourse or from mother to child. Sexual transmission occurs more efficiently from men to women than women to men and might be enhanced by sexually transmitted diseases that cause ulcers and result in mucosal ruptures, such as syphilis, herpes simplex type 2 (HSV-2), and chancroid. Other sexually transmitted diseases might result in the recruitment of inflammatory cells and could increase the risk of HTLV-1 acquisition and transmission. Additionally, factors that are associated with higher transmission risks include the presence of antibodies against the viral oncoprotein Tax (anti-Tax), a higher proviral load in peripheral blood lymphocytes, and increased cervicovaginal or seminal secretions. Seminal fluid has been reported to increase HTLV replication and transmission, whereas male circumcision and neutralizing antibodies might have a protective effect. Recently, free virions were discovered in plasma, which reveals a possible new mode of HTLV replication. It is unclear how this discovery might affect the routes of HTLV transmission, particularly sexual transmission, because HTLV transmission rates are significantly higher from men to women than women to men.

Genital ulcer disease treatment for reducing sexual acquisition of HIV.

PubMed

Mutua, Florence M; M'imunya, James Machoki; Wiysonge, Charles Shey

2012-08-15

Genital ulcer disease by virtue of disruption of the mucosal surfaces may enhance HIV acquisition. Genital ulcer disease treatment with resolution of the ulcers may therefore contribute in reducing the sexual acquisition of HIV. To determine the effects of treatment of genital ulcer disease on sexual acquisition of HIV. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, LILACS, NLM Gateway, Web of Science, WHO International Clinical Trials Registry Platform, ClinicalTrials.gov, and reference lists of relevant publications for eligible studies published between 1980 and August 2011. Randomized controlled trials of any treatment intervention aimed at curing genital ulcer disease compared with an alternative treatment, placebo, or no treatment. We included only trials whose unit of randomization was the individual with confirmed genital ulcer. We independently selected studies and extracted data in duplicate; resolving discrepancies by discussion, consensus, and arbitration by third review author. We expressed study results as risk ratios (RR) with 95% confidence intervals (CI). There were three randomized controlled trials that met our inclusion criteria recruited HIV-negative participants with chancroid (two trials with 143 participants) and primary syphilis (one trial with 30 participants). The syphilis study, carried out in the US between 1995 and 1997, randomized participants to receive a single 2.0 g oral dose of azithromycin (11 participants); two 2.0 g oral doses of azithromycin administered six to eight days apart (eight participants); or benzathine penicillin G administered as either 2.4 million units intramuscular injection once or twice seven days apart (11 participants). No participant in the trial seroconverted during 12 months of follow-up. The chancroid trials, conducted in Kenya by 1990, found no significant differences in HIV seroconversion rates during four to 12 weeks of follow-up between 400 and 200 mg single oral doses of fleroxacin (one trial, 45 participants; RR 3.00; 95% CI 0.29 to 30.69), or between 400 mg fleroxacin and 800 mg sulfamethoxazole plus 160 mg trimethoprim (one trial, 98 participants; RR 0.33; 95% CI 0.04 to 3.09). Adverse events reported were mild to moderate in severity, and included Jarisch-Herxheimer reactions and gastrointestinal symptoms. The differences between the treatment arms in the incidence of adverse events were not significant. The quality of this evidence on the effectiveness of genital ulcer disease treatment in reducing sexual acquisition of HIV, according to GRADE methodology, is of very low quality. At present, there is insufficient evidence to determine whether curative treatment of genital ulcer disease would reduce the risk of HIV acquisition. The very low quality of the evidence implies that the true effect of genital ulcer disease treatment on sexual acquisition of HIV may be substantially different from the effect estimated from currently available data. However, genital ulcer diseases are public health problems in their own right and patients with these conditions should be treated appropriately; whether the treatment reduces the risk of HIV infection or not.

Gonorrhoea in Greenland, incidence and previous preventive measures: a review to improve future strategies

PubMed Central

Berntsen, Sine; Karlsen, Anders Peder Højer; Pedersen, Michael Lynge; Mulvad, Gert

2017-01-01

ABSTRACT Gonorrhoea continues to be a significant health challenge in Greenland. The aim of this study was to describe the development of gonorrhoea in Greenland through time including incidence rates and previous measures taken to address the challenge. A systematic literature search in PubMed, Embase and The Cochrane Library was conducted. Furthermore, local archives were searched in the Health Clinic in Nuuk for relevant literature. From the 1940s the incidence of gonorrhoea increased steadily with a steep incline around 1970, possibly as a consequence of changes in living conditions and urbanisation. Significant declines in the incidence were seen the late 1970s and again in the late 1980s, most likely in the wake of an outbreak of ulcus molle/chancroid in the 1970s and as a result of focused education in venereology for Greenlandic nurses in the late 1980s combined with the stop-AIDS campaign. Since the early 1990s the incidence of gonorrhoea in Greenland has not risen to previously high levels. However, the incidence remains high and with a gradually increasing trend. Prevention intervention strategies such as peer-to-peer sexual education, storytelling and involvement of parent/guardian in sexual education of the youth could be appropriate approaches to improve sexual health in Greenland. PMID:28745556

Gonorrhoea in Greenland, incidence and previous preventive measures: a review to improve future strategies.

PubMed

Berntsen, Sine; Karlsen, Anders Peder Højer; Pedersen, Michael Lynge; Mulvad, Gert

2017-01-01

Gonorrhoea continues to be a significant health challenge in Greenland. The aim of this study was to describe the development of gonorrhoea in Greenland through time including incidence rates and previous measures taken to address the challenge. A systematic literature search in PubMed, Embase and The Cochrane Library was conducted. Furthermore, local archives were searched in the Health Clinic in Nuuk for relevant literature. From the 1940s the incidence of gonorrhoea increased steadily with a steep incline around 1970, possibly as a consequence of changes in living conditions and urbanisation. Significant declines in the incidence were seen the late 1970s and again in the late 1980s, most likely in the wake of an outbreak of ulcus molle/chancroid in the 1970s and as a result of focused education in venereology for Greenlandic nurses in the late 1980s combined with the stop-AIDS campaign. Since the early 1990s the incidence of gonorrhoea in Greenland has not risen to previously high levels. However, the incidence remains high and with a gradually increasing trend. Prevention intervention strategies such as peer-to-peer sexual education, storytelling and involvement of parent/guardian in sexual education of the youth could be appropriate approaches to improve sexual health in Greenland.

Genital Ulcer Disease: How Worrisome Is It Today? A Status Report from New Delhi, India

PubMed Central

Muralidhar, Sumathi; Talwar, Richa; Anil Kumar, Deepa; Kumar, Joginder; Bala, Manju; Khan, Nilofar; Ramesh, V.

2013-01-01

Background and Objectives. Genital ulcer diseases represent a diagnostic dilemma, especially in India, where few STI clinics have access to reliable laboratory facility. The changing STI trends require that a correct diagnosis be made in order to institute appropriate treatment and formulate control policies. The objective of this study was to determine recent trends in aetiology of genital ulcers, by using accurate diagnostic tools. Methods. Specimens from 90 ulcer patients were processed for dark field microscopy, stained smears, culture for H. ducreyi, and real-time PCR. Blood samples were collected for serological tests. Results. Prevalence of GUD was 7.45 with mean age at initial sexual experience as 19.2 years. Use of condom with regular and nonregular partners was 19.5% and 42.1%, respectively. Sexual orientation was heterosexual (92.2%) or homosexual (2.2%). There were 8 cases positive for HIV (8.9%). Herpes simplex virus ulcers were the commonest, followed by syphilis and chancroid. There were no cases of donovanosis and LGV. Conclusions. A valuable contribution of this study was in validating clinical and syndromic diagnoses of genital ulcers with an accurate aetiological diagnosis. Such reliable data will aid treatment and better define control measures of common agents and help eliminate diseases amenable to elimination, like donovanosis. PMID:26316954

Host-pathogen interplay of Haemophilus ducreyi.

PubMed

Janowicz, Diane M; Li, Wei; Bauer, Margaret E

2010-02-01

Haemophilus ducreyi, the causative agent of the sexually transmitted infection chancroid, is primarily a pathogen of human skin. During infection, H. ducreyi thrives extracellularly in a milieu of professional phagocytes and other antibacterial components of the innate and adaptive immune responses. This review summarizes our understanding of the interplay between this pathogen and its host that leads to development and persistence of disease. H. ducreyi expresses key virulence mechanisms to resist host defenses. The secreted LspA proteins are tyrosine-phosphorylated by host kinases, which may contribute to their antiphagocytic effector function. The serum resistance and adherence functions of DsrA map to separate domains of this multifunctional virulence factor. An influx transporter protects H. ducreyi from killing by the antimicrobial peptide LL37. Regulatory genes have been identified that may coordinate virulence factor expression during disease. Dendritic cells and natural killer cells respond to H. ducreyi and may be involved in determining the differential outcomes of infection observed in humans. A human model of H. ducreyi infection has provided insights into virulence mechanisms that allow this human-specific pathogen to survive immune pressures. Components of the human innate immune system may also determine the ultimate fate of H. ducreyi infection by driving either clearance of the organism or an ineffective response that allows disease progression.

Sexually transmitted diseases: extract from the Annual Report of the Chief Medical Officer of the Department of Health and Social Security for the Year 1978.

PubMed

1980-06-01

In England, a comparison of the number of newly reported cases of sexually transmitted diseases for the years ending June 30, 1977 and 1978 indicated that during the latter year there was an increase in the incidence of early and late syphilis, genital candidosis, genital herpes, simplex, and nonspecific genital infection and a slight decline in the incidence of gonorrhea. During the year ending June 30, 1978, early syphilis increased 5.4% among men and 11.8% among women, and the number of cases/100,000 population was 10.18 for men and 1.91 for women. The reported number of new cases of late syphilis increased 15.8% during that same year, and the number of new cases/100,000 was 4.32 for men 1.90 for women. Gonorrhea cases decreased by 2.5% among men and by 3.3% among women, and the number of new cases/100,000 was 160.55 for men and 89.23 for women. The number of new cases of chancroid increased slightly, and there were 0.11 cases /100,000 population. Nonspecific genital infections increased for the total population by 2.2%; however, the rate among women declined by 2.1% and among men increased by 3.4%. The number of new cases of herpes simplex/100,000 population was 22.50 for men and 12.25 for women. 4 tables provided information on 1) the number of new reported cases for the years ending in June 30, 1977 and 1978 and the incidence rates for 1974-78 for syphilis, gonorrhea, and chancroid and 2) incidence rates for the years ending on June 1974-78 for other sexually transmitted diseases. During the year ending June 30, 1978, a total of 518,839 persons, representing a 2% increase over the previous year, presented at hospital clinics for venereal disease checkups. 5% of these individuals were noninfected. During 1978, progress was made in training more workers and expanding facilities for tracing individuals who had contact with persons known to have venereal disease. In addition, the genitourinary medical staff at facilities in England and Wales increased from 203-211 between 1977-78. 101 of these staff members were consultants. Consultants, according to the Special Advisory Committee in Genitourinary Medicine of the Royal College of Physicians should be members of the Royal College of Physicians and have 4 years of training at the senior registrar level. This requirement has been relaxed somewhat, however, due to recruitment difficulties. Requirement of male nurses is still inadedquate. In regard to progress in education and training personnel to work in the venereal disease area, a Department of Genitourinary Medicine is being established at the Middlesex Hospital Medical School of London University. British physicians played an active role in several international conferences on sexually transmitted diseases in 1978, and the Department of Health and Social Security continued to provide funds for health professionals to visit veneral disease centers in other countries in order to learn about new techniques for diagnosing and treating veneral disease.

Molecular phylogenetic analysis of non-sexually transmitted strains of Haemophilus ducreyi.

PubMed

Gaston, Jordan R; Roberts, Sally A; Humphreys, Tricia L

2015-01-01

Haemophilus ducreyi, the etiologic agent of chancroid, has been previously reported to show genetic variance in several key virulence factors, placing strains of the bacterium into two genetically distinct classes. Recent studies done in yaws-endemic areas of the South Pacific have shown that H. ducreyi is also a major cause of cutaneous limb ulcers (CLU) that are not sexually transmitted. To genetically assess CLU strains relative to the previously described class I, class II phylogenetic hierarchy, we examined nucleotide sequence diversity at 11 H. ducreyi loci, including virulence and housekeeping genes, which encompass approximately 1% of the H. ducreyi genome. Sequences for all 11 loci indicated that strains collected from leg ulcers exhibit DNA sequences homologous to class I strains of H. ducreyi. However, sequences for 3 loci, including a hemoglobin receptor (hgbA), serum resistance protein (dsrA), and a collagen adhesin (ncaA) contained informative amounts of variation. Phylogenetic analyses suggest that these non-sexually transmitted strains of H. ducreyi comprise a sub-clonal population within class I strains of H. ducreyi. Molecular dating suggests that CLU strains are the most recently developed, having diverged approximately 0.355 million years ago, fourteen times more recently than the class I/class II divergence. The CLU strains' divergence falls after the divergence of humans from chimpanzees, making it the first known H. ducreyi divergence event directly influenced by the selective pressures accompanying human hosts.

Carbon storage regulator A contributes to the virulence of Haemophilus ducreyi in humans by multiple mechanisms.

PubMed

Gangaiah, Dharanesh; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Ellinger, Sheila; Zwickl, Beth; Katz, Barry P; Spinola, Stanley M

2013-02-01

The carbon storage regulator A (CsrA) controls a wide variety of bacterial processes, including metabolism, adherence, stress responses, and virulence. Haemophilus ducreyi, the causative agent of chancroid, harbors a homolog of csrA. Here, we generated an unmarked, in-frame deletion mutant of csrA to assess its contribution to H. ducreyi pathogenesis. In human inoculation experiments, the csrA mutant was partially attenuated for pustule formation compared to its parent. Deletion of csrA resulted in decreased adherence of H. ducreyi to human foreskin fibroblasts (HFF); Flp1 and Flp2, the determinants of H. ducreyi adherence to HFF cells, were downregulated in the csrA mutant. Compared to its parent, the csrA mutant had a significantly reduced ability to tolerate oxidative stress and heat shock. The enhanced sensitivity of the mutant to oxidative stress was more pronounced in bacteria grown to stationary phase compared to that in bacteria grown to mid-log phase. The csrA mutant also had a significant survival defect within human macrophages when the bacteria were grown to stationary phase but not to mid-log phase. Complementation in trans partially or fully restored the mutant phenotypes. These data suggest that CsrA contributes to virulence by multiple mechanisms and that these contributions may be more profound in bacterial cell populations that are not rapidly dividing in the human host.

[Anorectal manifestations of sexually transmitted infections].

PubMed

Lautenschlager, Stephan

2013-07-01

The incidence of sexually transmitted infections is rising in Europe and in Switzerland since the beginning of the third millenium. Many organisms may affect the perianal skin and the anorectum. While some of these infections are a result of contigous spread from genital infection, most result from receptive anal intercourse affecting males who have sex with males but is seen increasingly in females as well since there is evidence of the increasing popularity of anal sex among heterosexuals. The symptoms of specific infections are largely dependent on the route and site of inoculation. Organisms that cause typical genital symptoms - such as syphilis, chancroid, herpes simplex or HPV-infection - result in similar symptoms when the perianal skin, the anoderm or the distal anal canal are the site of infection. Patients with proctitis may have unspecific signs in various degrees including mucous discharge, rectal bleeding, anorectal pain, superficial ulcers and sometimes generalized lymphadenopathy and fever. It is of utmost importance to include STIs (e. g. lymphogranuloma venereum, gonorrhea, non-LGV-chlamydia and herpes simplex) in the differential diagnosis in these patients. Unfortunately rectal infection with chlamydia and gonorrhea is asymptomatic in the majority of cases of men having sex with men and in high-risk females. A careful history and physical examination is essential in establishing a correct diagnosis, usually supported by proctoscopy, culture, PCR, serology and histology. Certain organisms, more commonly thought of as food- or water-borne disease may be sexually transmitted by direct or indirect fecal-oral contact from various sexual practices.

The Haemophilus ducreyi trimeric autotransporter adhesin DsrA protects against an experimental infection in the swine model of chancroid.

PubMed

Fusco, William G; Choudhary, Neelima R; Routh, Patty A; Ventevogel, Melissa S; Smith, Valerie A; Koch, Gary G; Almond, Glen W; Orndorff, Paul E; Sempowski, Gregory D; Leduc, Isabelle

2014-06-24

Adherence of pathogens to cellular targets is required to initiate most infections. Defining strategies that interfere with adhesion is therefore important for the development of preventative measures against infectious diseases. As an adhesin to host extracellular matrix proteins and human keratinocytes, the trimeric autotransporter adhesin DsrA, a proven virulence factor of the Gram-negative bacterium Haemophilus ducreyi, is a potential target for vaccine development. A recombinant form of the N-terminal passenger domain of DsrA from H. ducreyi class I strain 35000HP, termed rNT-DsrAI, was tested as a vaccine immunogen in the experimental swine model of H. ducreyi infection. Viable homologous H. ducreyi was not recovered from any animal receiving four doses of rNT-DsrAI administered with Freund's adjuvant at two-week intervals. Control pigs receiving adjuvant only were all infected. All animals receiving the rNT-DsrAI vaccine developed antibody endpoint titers between 3.5 and 5 logs. All rNT-DsrAI antisera bound the surface of the two H. ducreyi strains used to challenge immunized pigs. Purified anti-rNT-DsrAI IgG partially blocked binding of fibrinogen at the surface of viable H. ducreyi. Overall, immunization with the passenger domain of the trimeric autotransporter adhesin DsrA accelerated clearance of H. ducreyi in experimental lesions, possibly by interfering with fibrinogen binding. Copyright © 2014 Elsevier Ltd. All rights reserved.

Detection and discrimination of herpes simplex viruses, Haemophilus ducreyi, Treponema pallidum, and Calymmatobacterium (Klebsiella) granulomatis from genital ulcers.

PubMed

Mackay, Ian M; Harnett, Gerry; Jeoffreys, Neisha; Bastian, Ivan; Sriprakash, Kadaba S; Siebert, David; Sloots, Theo P

2006-05-15

Genital ulcer disease (GUD) is commonly caused by pathogens for which suitable therapies exist, but clinical and laboratory diagnoses may be problematic. This collaborative project was undertaken to address the need for a rapid, economical, and sensitive approach to the detection and diagnosis of GUD using noninvasive techniques to sample genital ulcers. The genital ulcer disease multiplex polymerase chain reaction (GUMP) was developed as an inhouse nucleic acid amplification technique targeting serious causes of GUD, namely, herpes simplex viruses (HSVs), H. ducreyi, Treponema pallidum, and Klebsiella species. In addition, the GUMP assay included an endogenous internal control. Amplification products from GUMP were detected by enzyme linked amplicon hybridization assay (ELAHA). GUMP-ELAHA was sensitive and specific in detecting a target microbe in 34.3% of specimens, including 1 detection of HSV-1, three detections of HSV-2, and 18 detections of T. pallidum. No H. ducreyi has been detected in Australia since 1998, and none was detected here. No Calymmatobacterium (Klebsiella) granulomatis was detected in the study, but there were 3 detections during ongoing diagnostic use of GUMP-ELAHA in 2004 and 2005. The presence of C. granulomatis was confirmed by restriction enzyme digestion and nucleotide sequencing of the 16S rRNA gene for phylogenetic analysis. GUMP-ELAHA permitted comprehensive detection of common and rare causes of GUD and incorporated noninvasive sampling techniques. Data obtained by using GUMP-ELAHA will aid specific treatment of GUD and better define the prevalence of each microbe among at-risk populations with a view to the eradication of chancroid and donovanosis in Australia.

Defining Potential Vaccine Targets of Haemophilus ducreyi Trimeric Autotransporter Adhesin DsrA

PubMed Central

Fusco, William G.; Choudhary, Neelima R.; Stewart, Shelley M.; Alam, S. Munir; Sempowski, Gregory D.; Elkins, Christopher

2015-01-01

Haemophilus ducreyi is the causative agent of the sexually transmitted genital ulcer disease chancroid. Strains of H. ducreyi are grouped in two classes (I and II) based on genotypic and phenotypic differences, including those found in DsrA, an outer membrane protein belonging to the family of multifunctional trimeric autotransporter adhesins. DsrA is a key serum resistance factor of H. ducreyi that prevents binding of natural IgM at the bacterial surface and functions as an adhesin to fibronectin, fibrinogen, vitronectin, and human keratinocytes. Monoclonal antibodies (MAbs) were developed to recombinant DsrA (DsrAI) from prototypical class I strain 35000HP to define targets for vaccine and/or therapeutics. Two anti-DsrAI MAbs bound monomers and multimers of DsrA from genital and non-genital/cutaneous H. ducreyi strains in a Western blot and reacted to the surface of the genital strains; however, these MAbs did not recognize denatured or native DsrA from class II strains. In a modified extracellular matrix protein binding assay using viable H. ducreyi, one of the MAbs partially inhibited binding of fibronectin, fibrinogen, and vitronectin to class I H. ducreyi strain 35000HP, suggesting a role for anti-DsrA antibodies in preventing binding of H. ducreyi to extracellular matrix proteins. Standard ELISA and surface plasmon resonance using a peptide library representing full-length, mature DsrAI revealed the smallest nominal epitope bound by one of the MAbs to be MEQNTHNINKLS. Taken together, our findings suggest that this epitope is a potential target for an H. ducreyi vaccine. PMID:25897604

Defining Potential Vaccine Targets of Haemophilus ducreyi Trimeric Autotransporter Adhesin DsrA.

PubMed

Fusco, William G; Choudhary, Neelima R; Stewart, Shelley M; Alam, S Munir; Sempowski, Gregory D; Elkins, Christopher; Leduc, Isabelle

2015-04-01

Haemophilus ducreyi is the causative agent of the sexually transmitted genital ulcer disease chancroid. Strains of H. ducreyi are grouped in two classes (I and II) based on genotypic and phenotypic differences, including those found in DsrA, an outer membrane protein belonging to the family of multifunctional trimeric autotransporter adhesins. DsrA is a key serum resistance factor of H. ducreyi that prevents binding of natural IgM at the bacterial surface and functions as an adhesin to fibronectin, fibrinogen, vitronectin, and human keratinocytes. Monoclonal antibodies (MAbs) were developed to recombinant DsrA (DsrA(I)) from prototypical class I strain 35000HP to define targets for vaccine and/or therapeutics. Two anti-DsrAI MAbs bound monomers and multimers of DsrA from genital and non-genital/cutaneous H. ducreyi strains in a Western blot and reacted to the surface of the genital strains; however, these MAbs did not recognize denatured or native DsrA from class II strains. In a modified extracellular matrix protein binding assay using viable H. ducreyi, one of the MAbs partially inhibited binding of fibronectin, fibrinogen, and vitronectin to class I H. ducreyi strain 35000HP, suggesting a role for anti-DsrA antibodies in preventing binding of H. ducreyi to extracellular matrix proteins. Standard ELISA and surface plasmon resonance using a peptide library representing full-length, mature DsrAI revealed the smallest nominal epitope bound by one of the MAbs to be MEQNTHNINKLS. Taken together, our findings suggest that this epitope is a potential target for an H. ducreyi vaccine.

A targetted intervention research on traditional healer perspectives of sexually transmitted illnesses in urban Zambia. Current research.

PubMed

Masauso Nzima, M; Romano, K; Anyangwe, S; Wiseman, J; Macwan'gi, M; Kendall, C; Green, E C

1996-07-01

Interviews with 81 traditional healers from 4 Copperbelt towns in Zambia (Chililabombwe, Chingola, Luanshya, and Mufulira) investigated healers' understanding of, attitudes toward, and management of sexually transmitted diseases (STDs). In general, Zambian traditional healers had detailed constructs of the physiology and infective processes underlying syphilis, gonorrhea, chancroid, and AIDS. STDs were considered to be caused by "dirt" or contamination residing in sperm or vaginal fluids and were closely linked to violations of moral codes. Healers shared complex nosologies based on distinctions between symptoms of different STD pathologies that were more inclusive than biomedical categories. Although condom use was not promoted, healers understood the importance of preventing an infective agent from passing from one person to another. Except for AIDS, STDs were considered curable by expelling the dirt through purgatives or emetics. Modern medicine was perceived as treating only STD symptoms, not curing. Most traditional healers insisted that the infected partner bring the other partner for consultation or treatment was withheld. Since these findings identified some areas of compatibility between indigenous and biomedical models of STDs, the Traditional Medicine Unit of the Ministry of Health and the HIV/AIDS Prevention Project of the Morehouse School of Medicine (Lusaka) established a program in which traditional healers receive AIDS training and learn to counsel clients on safer sex behaviors. Follow-up entails monthly meetings between health professionals and traditional healers. Since program initiation in June 1994, 800 traditional healers and 70 health professionals have participated. Traditional healers now sell condoms to their clients through a social marketing program.

Pattern of sexually transmitted diseases in patients presenting at Ayub teaching hospital, Abbottabad.

PubMed

Razvi, Syed Kamran Amir; Najeeb, Shahzad; Nazar, Hassan Shahzad

2014-01-01

Sexually transmitted diseases are present in all societies across the globe. Different cultures and societies show a different spectrum of these diseases. The last study conducted in Hazara division was back in 1995. We have conducted this study to see the recent trends and patterns of sexually transmitted diseases in the region. This cross-sectional study was conducted in Ayub Teaching Hospital, Abbottabad and included patients over a five year period from January 2010 till December 2014. Case sheets of 512 presenting with sexually transmitted diseases whose diagnosis was confirmed by related lab investigation were analysed retrospectively. Patients of all ages and both sexes were included. Out of these 512 patients only 47 were females and 465 were males. The age varied from 15-66 years. Gonorrhoea was the commonest disease with 231 cases. Genital warts were diagnosed in 60 cases. Non- gonococcal urethritis was seen in 57 patients. Genital Molluscum contagiosum was seen in 45 patients. Syphillis was diagnosed in 41 patients. Thirty-one cases of herpes genitalis, 25 cases of Chancroid, 13 cases of Lymphogranuloma venereum, were also seen. Five patients were found positive for HIV. Overwhelming majority of the patients were between the age of 19-35 years. 61% of the patients were married. The source of infection in male patients was mainly prostitutes (70%) but also included homosexual boys (21 %), married women (7.5%) and eunuchs (1.5%). The main source of infection in females was from husbands. The number of STD patients presenting in the region has increased significantly. The main factor is obviously the rise in population but also signifies the change in cultural and moral values.

Issues concerning women and AIDS: sexuality.

PubMed

Whipple, B

1992-01-01

In the US and globally women are contracting the human immunodeficiency virus (HIV) and developing the acquired immunodeficiency syndrome (AIDS) the fastest. Worldwide, HIV is transmitted primarily through heterosexual intercourse. In the US, the proportion of women who have contracted AIDS by heterosexual transmission has increased from 11% in 1984 to 34% in 1990. Women are at a greater risk than men for transmission by heterosexual intercourse as the ratio of women to men who acquire AIDS by heterosexual transmission is 3 to 1. Furthermore, 25% of AIDS cases caused by heterosexual transmission or iv drug use occurs in women. Although women often develop HIV-related serious gynecologic problems, including cervical cancer and refractory vaginal candidiasis, these conditions do not fall within the Centers for Disease Control definition of AIDS. Women who have gynecologic symptoms are not diagnosed as having AIDS, are not eligible for AIDS benefits, and live half as long as men do once they are diagnosed as being HIV infected. Little is known about the characteristics of HIV infection or AIDS in women. Sexually transmitted diseases (STDs) seem to act as cofactors for HIV infection. The human papilloma virus or genital warts, the herpes simplex virus, syphilis, chancroid, recurrent vaginal candidiasis, abnormal Pap smears, cervical neoplasias, and pelvic inflammatory disease have been associated with HIV infection in women. HIV infection should be considered in all women with symptoms of any of these disorders. Nurses must first become aware of the clinical manifestations of HIV infection specific to women. Nursing interventions should educate about safer-sex including condom use with nonoxynol 9, and the risks of sharing needles. Strategies must be developed that provide empowerment skills and are sensitive to the women's cultural, religious, and ethnic background, beliefs, and values.

Sialylation of lipooligosaccharides is dispensable for the virulence of Haemophilus ducreyi in humans.

PubMed

Spinola, Stanley M; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Zwickl, Beth; Katz, Barry P; Munson, Robert S

2012-02-01

Sialylated glycoconjugates on the surfaces of mammalian cells play important roles in intercellular communication and self-recognition. The sialic acid preferentially expressed in human tissues is N-acetylneuraminic acid (Neu5Ac). In a process called molecular mimicry, many bacterial pathogens decorate their cell surface glycolipids with Neu5Ac. Incorporation of Neu5Ac into bacterial glycolipids promotes bacterial interactions with host cell receptors called Siglecs. These interactions affect bacterial adherence, resistance to serum killing and phagocytosis, and innate immune responses. Haemophilus ducreyi, the etiologic agent of chancroid, expresses lipooligosaccharides (LOS) that are highly sialylated. However, an H. ducreyi sialyltransferase (lst) mutant, whose LOS contain reduced levels of Neu5Ac, is fully virulent in human volunteers. Recently, a second sialyltransferase gene (Hd0053) was discovered in H. ducreyi, raising the possibility that Hd0053 compensated for the loss of lst during human infection. CMP-Neu5Ac is the obligate nucleotide sugar donor for all bacterial sialyltransferases; LOS derived from an H. ducreyi CMP-Neu5Ac synthetase (neuA) mutant has no detectable Neu5Ac. Here, we compared an H. ducreyi neuA mutant to its wild-type parent in several models of pathogenesis. In human inoculation experiments, the neuA mutant formed papules and pustules at rates that were no different than those of its parent. When grown in media with and without Neu5Ac supplementation, the neuA mutant and its parent had similar phenotypes in bactericidal, macrophage uptake, and dendritic cell activation assays. Although we cannot preclude a contribution of LOS sialylation to ulcerative disease, these data strongly suggest that sialylation of LOS is dispensable for H. ducreyi pathogenesis in humans.

Haemophilus ducreyi infection induces activation of the NLRP3 inflammasome in nonpolarized but not in polarized human macrophages.

PubMed

Li, Wei; Katz, Barry P; Bauer, Margaret E; Spinola, Stanley M

2013-08-01

Recognition of microbial infection by certain intracellular pattern recognition receptors leads to the formation of a multiprotein complex termed the inflammasome. Inflammasome assembly activates caspase-1 and leads to cleavage and secretion of the proinflammatory cytokines interleukin-1 beta (IL-1β) and IL-18, which help control many bacterial pathogens. However, excessive inflammation mediated by inflammasome activation can also contribute to immunopathology. Here, we investigated whether Haemophilus ducreyi, a Gram-negative bacterium that causes the genital ulcer disease chancroid, activates inflammasomes in experimentally infected human skin and in monocyte-derived macrophages (MDM). Although H. ducreyi is predominantly extracellular during human infection, several inflammasome-related components were transcriptionally upregulated in H. ducreyi-infected skin. Infection of MDM with live, but not heat-killed, H. ducreyi induced caspase-1- and caspase-5-dependent processing and secretion of IL-1β. Blockage of H. ducreyi uptake by cytochalasin D significantly reduced the amount of secreted IL-1β. Knocking down the expression of the inflammasome components NLRP3 and ASC abolished IL-1β production. Consistent with NLRP3-dependent inflammasome activation, blocking ATP signaling, K(+) efflux, cathepsin B activity, and lysosomal acidification all inhibited IL-1β secretion. However, inhibition of the production and function of reactive oxygen species did not decrease IL-1β production. Polarization of macrophages to classically activated M1 or alternatively activated M2 cells abrogated IL-1β secretion elicited by H. ducreyi. Our study data indicate that H. ducreyi induces NLRP3 inflammasome activation via multiple mechanisms and suggest that the heterogeneity of macrophages within human lesions may modulate inflammasome activation during human infection.

Characterization of Haemophilus ducreyi cdtA, cdtB, and cdtC Mutants in In Vitro and In Vivo Systems

PubMed Central

Lewis, David A.; Stevens, Marla K.; Latimer, Jo L.; Ward, Christine K.; Deng, Kaiping; Blick, Robert; Lumbley, Sheryl R.; Ison, Catherine A.; Hansen, Eric J.

2001-01-01

Haemophilus ducreyi expresses a soluble cytolethal distending toxin (CDT) that is encoded by the cdtABC gene cluster and can be detected in culture supernatant fluid by its ability to kill HeLa cells. The cdtA, cdtB, and cdtC genes of H. ducreyi were cloned independently into plasmid vectors, and their encoded proteins expressed singly or in various combinations in an Escherichia coli background. All three gene products had to be expressed in order for E. coli-derived culture supernatant fluids to demonstrate cytotoxicity for HeLa cells. Isogenic H. ducreyi cdtA and cdtB mutants were constructed and used in combination with the wild-type parent strain and a previously described H. ducreyi cdtC mutant (M. K. Stevens, J. L. Latimer, S. R. Lumbley, C. K. Ward, L. D. Cope, T. Lagergard, and E. J. Hansen, Infect. Immun. 67:3900–3908, 1999) to determine the relative contributions of the CdtA, CdtB, and CdtC proteins to CDT activity. Expression of CdtA, CdtB, and CdtC appeared necessary for H. ducreyi-derived culture supernatant fluid to exhibit cytotoxicity for HeLa cells. Whole-cell sonicates and periplasmic extracts from the cdtB and cdtC mutants had no effect on HeLa cells, whereas these same fractions from a cdtA mutant had a very modest cytotoxic effect on these same human cells. CdtA appeared to be primarily associated with the H. ducreyi cell envelope, whereas both CdtB and CdtC were present primarily in the soluble fraction from sonicated cells. Both the cdtA mutant and the cdtB mutant were found to be fully virulent in the temperature-dependent rabbit model for experimental chancroid. PMID:11500438

Cloning and Characterization of the Lipooligosaccharide Galactosyltransferase II Gene of Haemophilus ducreyi

PubMed Central

Sun, Shuhua; Schilling, Birgit; Tarantino, Laurie; Tullius, Michael V.; Gibson, Bradford W.; Munson, Robert S.

2000-01-01

Haemophilus ducreyi is the etiologic agent of chancroid, a genital ulcer disease. The lipooligosaccharide (LOS) is considered to be a major virulence determinant and has been implicated in the adherence of H. ducreyi to keratinocytes. Strain A77, an isolate from the Paris collection, is serum sensitive, poorly adherent to fibroblasts, and deficient in microcolony formation. Structural analysis indicates that the LOS of strain A77 lacks the galactose residue found in the N-acetyllactosamine portion of the strain 35000HP LOS as well as the sialic acid substitution. From an H. ducreyi 35000HP genomic DNA library, a clone complementing the defect in A77 was identified by immunologic screening with monoclonal antibody (MAb) 3F11, a MAb which recognizes the N-acetyllactosamine portion of strain 35000HP LOS. The clone contained a 4-kb insert that was sequenced. One open reading frame which encodes a protein with a molecular weight of 33,400 was identified. This protein has homology to glycosyltransferases of Haemophilus influenzae, Haemophilus somnus, Neisseria species, and Pasteurella haemolytica. The putative H. ducreyi glycosyltransferase gene was insertionally inactivated, and an isogenic mutant of strain 35000HP was constructed. The most complex LOS glycoform produced by the mutant has a mobility on sodium dodecyl sulfate-polyacrylamide gel identical to that of the LOS of strain A77 and lacks the 3F11-binding epitope. Structural studies confirm that the most complex glycoform of the LOS isolated from the mutant lacks the galactose residue found in the N-acetyllactosamine portion of the strain 35000HP LOS. Although previously published data suggested that the serum-sensitive phenotype of A77 was due to the LOS mutation, we observed that the complemented A77 strain retained its serum-sensitive phenotype and that the galactosyltransferase mutant retained its serum-resistant phenotype. Thus, the serum sensitivity of strain A77 cannot be attributed to the galactosyltransferase mutation in strain A77. PMID:10735874

Pattern of sexually transmitted infections in males in interior Sindh: a 10-year-study.

PubMed

Bhutto, Abdul Manan; Shah, Aftab Hussain; Ahuja, Dileep Kumar; Solangi, Aijaz Hussain; Shah, Sharaf Ali

2011-01-01

Sexually transmitted infections (STIs) are widespread in Pakistan and have not been fully documented particularly in Sindh Province. The aim of this study is to determine the number and clinical pattern of various types of STIs in general population of Larkana division and its surrounding cities. A hospital based prospective study was carried out at Male-STD-Clinic in the Department of Dermatology, Shaheed Muhtarma Benazir Bhutto Medical University Hospital Larkana from January 2000 to December 2009. Among 4,288 patients, 3,947 (92.04%) had the history of extra marital sexual contact and simultaneously had developed the clinical signs of STIs; 341 (7.95%) had history of extra marital sexual contact but did not have the manifestation of STIs. Majority of the patients (3,860, 90.01%) had the history of heterosexual contact with different partners, but only few 171 (3.98%) of them had the history of homosexual contact. According the syndromic diagnosis 1930 (45.00%) patients had genital ulcer (including herpes genitals) with or without skin manifestations, 690 (16.09%) had urethral discharge, 431 (10.05%) had genital warts, 349 (8.14%) had lesions other than STIs related, 304 (7.08%) had more than one syndrome, 193 (4.50%) had scrotal swelling, 46 (1.07%) had inguinal bubo, 3 (0.06%) were human immunodeficiency virus (HIV) positive, and 1 (0.02%) had ophthalmia neonatorum. Based on the clinical and etiological grounds: 2560 (59.70%) had syphilis, 640 (14. 92%) had gonorrhoea, 399 (9.30%) had mixed infections, 40 (0.93%) had chancroid, 431 (10.05%) had genital warts, 40 (0.93%) had lymphogranuloma venerum (LGV) and granuloma inguinale (GI), 3 (0.06%) were HIV positive, 208 (4.85%) had genital herpes, 120 (2.79%) had orchitis, 56 (1.30%) had non gonococcal urethritis (chlamydia were 19), and 1 (0.02%) had ophthalmia neonatorum. Mode of transmission of STIs in this region is mainly by heterosexual contact and syphilis is the commonest followed by gonorrhoea.

Outer membrane protein P4 is not required for virulence in the human challenge model of Haemophilus ducreyi infection.

PubMed

Janowicz, Diane M; Zwickl, Beth W; Fortney, Kate R; Katz, Barry P; Bauer, Margaret E

2014-06-24

Bacterial lipoproteins often play important roles in pathogenesis and can stimulate protective immune responses. Such lipoproteins are viable vaccine candidates. Haemophilus ducreyi, which causes the sexually transmitted disease chancroid, expresses a number of lipoproteins during human infection. One such lipoprotein, OmpP4, is homologous to the outer membrane lipoprotein e (P4) of H. influenzae. In H. influenzae, e (P4) stimulates production of bactericidal and protective antibodies and contributes to pathogenesis by facilitating acquisition of the essential nutrients heme and nicotinamide adenine dinucleotide (NAD). Here, we tested the hypothesis that, like its homolog, H. ducreyi OmpP4 contributes to virulence and stimulates production of bactericidal antibodies. We determined that OmpP4 is broadly conserved among clinical isolates of H. ducreyi. We next constructed and characterized an isogenic ompP4 mutant, designated 35000HPompP4, in H. ducreyi strain 35000HP. To test whether OmpP4 was necessary for virulence in humans, eight healthy adults were experimentally infected. Each subject was inoculated with a fixed dose of 35000HP on one arm and three doses of 35000HPompP4 on the other arm. The overall parent and mutant pustule formation rates were 52.4% and 47.6%, respectively (P = 0.74). These results indicate that expression of OmpP4 in not necessary for H. ducreyi to initiate disease or progress to pustule formation in humans. Hyperimmune mouse serum raised against purified, recombinant OmpP4 did not promote bactericidal killing of 35000HP or phagocytosis by J774A.1 mouse macrophages in serum bactericidal and phagocytosis assays, respectively. Our data suggest that, unlike e (P4), H. ducreyi OmpP4 is not a suitable vaccine candidate. OmpP4 may be dispensable for virulence because of redundant mechanisms in H. ducreyi for heme acquisition and NAD utilization.

Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies.

PubMed

Gangaiah, Dharanesh; Spinola, Stanley M

2016-12-01

Haemophilus ducreyi has emerged as a major cause of cutaneous ulcers (CU) in yaws-endemic regions of the tropics in the South Pacific, South East Asia and Africa. H. ducreyi was once thought only to cause the genital ulcer (GU) disease chancroid; GU strains belong to 2 distinct classes, class I and class II. Using whole-genome sequencing of 4 CU strains from Samoa, 1 from Vanuatu and 1 from Papua New Guinea, we showed that CU strains diverged from the class I strain 35000HP and that one CU strain expressed β-lactamase. Recently, the Center for Disease Control and Prevention released the genomes of 11 additional CU strains from Vanuatu and Ghana; however, the evolutionary relationship of these CU strains to previously-characterized CU and GU strains is unknown. We performed phylogenetic analysis of 17 CU and 10 GU strains. Class I and class II GU strains formed two distinct clades. The class I strains formed two subclades, one containing 35000HP and HD183 and the other containing the remainder of the class I strains. Twelve of the CU strains formed a subclone under the class I 35000HP subclade, while 2 CU strains formed a subclone under the other class I subclade. Unexpectedly, 3 of the CU strains formed a subclone under the class II clade. Phylogenetic analysis of dsrA-hgbA-ncaA sequences yielded a tree similar to that of whole-genome phylogenetic tree. CU strains diverged from multiple lineages within both class I and class II GU strains. Multilocus sequence typing of dsrA-hgbA-ncaA could be reliably used for epidemiological investigation of CU and GU strains. As class II strains grow relatively poorly and are relatively more susceptible to vancomycin than class I strains, these findings have implications for methods to recover CU strains. Comparison of contemporary CU and GU isolates would help clarify the relationship between these entities.

The other STDs. Linked with HIV transmission, they are attracting new attention.

PubMed

Lande, R E

1992-12-01

Health officials began neglecting sexually transmitted diseases (STDs) (syphilis, gonorrhea, chlamydia, trichomoniasis, and chancroid) when the AIDS epidemic began. They now refocus efforts on STDs because data indicate that STDs facilitate HIV transmission. Even though the risk of HIV transmission is lower in people with nonulcerative STDs than those with genital ulcers (0-4 vs. 2-5 times), the link between nonulcerative STDs and HIV transmission is a greater problem since nonulcerative STD cases occur more often than genital ulcers. Many AIDS control programs execute STD control activities. Countries must improve existing STD control programs. They should strengthen STD surveillance. Viet Nam has established surveillance sites at STD clinics in 4 cities. Training different health providers in STD control would make STD services accessible to more people. These providers include nurses, midwives, pharmacists, and even traditional healers and should be based at pharmacies and primary health care, maternal and child health, and family planning clinics. Primary health care workers should use symptoms to diagnose and treat STDs rather than laboratory tests. 1 drawback of this syndromic approach is that about 50% of women do not exhibit STD symptoms. STD control programs must guarantee a steady reserve of drugs. In Zimbabwe, primary health clinics receive STD drugs from a decentralized drug distribution system (5-8 warehouses) rather than the older centralized system (1 warehouse). This has reduced the waiting time from 6 months to 4-6 weeks. Programs need to encourage individuals to seek early treatment of STDs via health education campaigns (e.g., mass media), outreach to high risk groups such as prostitutes and the patron, and contact tracing. STD counselors should promote condom use. An STD program in Nairobi, Kenya informs patients to use a condom during sex with any causal sex partner, shows patients how to put on and take off the condom, and tells them where they can obtain condoms.

Confronting the HIV epidemic in Asia and the Pacific: developing successful strategies to minimize the spread of HIV infection.

PubMed

Moodie, R; Aboagye-Kwarteng, T

1993-12-01

In Asia, the cumulative total of HIV-infected adults will reach 1.22 million by 1995, and, by 2000, the number is estimated to reach 11-45 million. The modes of transmission vary from country to country and include injecting drug users, commercial sex workers and their clients, commercial blood donors, hemophiliacs, and homosexuals. Social, cultural, and health factors also affect transmission, such as rites of passage to adulthood, lack of female autonomy, multiple sex partners, wars and civil unrest, and availability of drugs. The HIV epidemic has economic ramifications and causes, e.g., migrant worker camps, the sex industry, and rapid urbanization luring Burmese girls to Thailand. Governments must create an environment for behavior-change through financial, political, and legislative measures. Community organizations also play a role in prevention, as in programs initiated by a squatter settlement in Bangkok, where 36% of IV drug users were found to be HIV-positive. In Maharashtra State, India, peer-based prevention programs were developed for sex workers. Successful behavior change of individuals is based on redefinition of peer norms, understanding the danger and vulnerability to infection, and building confidence to change behavior. Successful programs require placing priority on HIV issues on the political agenda, negotiation and consensus-building skills, and competent program management. For instance, in Zimbabwe a project enlisted 380,000 people in 4500 education sessions within 2 years, and distributed 2.5 million condoms. Among sex workers, condom use increased from 5% to 50%. Implementation strategies include the provision of information and interpersonal education. In Zaire, mass media and social marketing efforts boosted condom sales from less than half a million in 1987 to over 20 million in 1991. The means to change behavior requires the availability of good quality condoms, disinfectants, and syringes. Furthermore, clinical management of gonorrhea, syphilis, human papillomavirus, and chancroid is vital to lowering the risk of HIV transmission. Continuous epidemiological research and the evaluation of prevention programs improve program effectiveness.

Haemophilus ducreyi Cutaneous Ulcer Strains Diverged from Both Class I and Class II Genital Ulcer Strains: Implications for Epidemiological Studies

PubMed Central

Gangaiah, Dharanesh

2016-01-01

Background Haemophilus ducreyi has emerged as a major cause of cutaneous ulcers (CU) in yaws-endemic regions of the tropics in the South Pacific, South East Asia and Africa. H. ducreyi was once thought only to cause the genital ulcer (GU) disease chancroid; GU strains belong to 2 distinct classes, class I and class II. Using whole-genome sequencing of 4 CU strains from Samoa, 1 from Vanuatu and 1 from Papua New Guinea, we showed that CU strains diverged from the class I strain 35000HP and that one CU strain expressed β-lactamase. Recently, the Center for Disease Control and Prevention released the genomes of 11 additional CU strains from Vanuatu and Ghana; however, the evolutionary relationship of these CU strains to previously-characterized CU and GU strains is unknown. Methodology/Principal Findings We performed phylogenetic analysis of 17 CU and 10 GU strains. Class I and class II GU strains formed two distinct clades. The class I strains formed two subclades, one containing 35000HP and HD183 and the other containing the remainder of the class I strains. Twelve of the CU strains formed a subclone under the class I 35000HP subclade, while 2 CU strains formed a subclone under the other class I subclade. Unexpectedly, 3 of the CU strains formed a subclone under the class II clade. Phylogenetic analysis of dsrA-hgbA-ncaA sequences yielded a tree similar to that of whole-genome phylogenetic tree. Conclusions/Significance CU strains diverged from multiple lineages within both class I and class II GU strains. Multilocus sequence typing of dsrA-hgbA-ncaA could be reliably used for epidemiological investigation of CU and GU strains. As class II strains grow relatively poorly and are relatively more susceptible to vancomycin than class I strains, these findings have implications for methods to recover CU strains. Comparison of contemporary CU and GU isolates would help clarify the relationship between these entities. PMID:28027326

Haemophilus ducreyi Seeks Alternative Carbon Sources and Adapts to Nutrient Stress and Anaerobiosis during Experimental Infection of Human Volunteers.

PubMed

Gangaiah, Dharanesh; Zhang, Xinjun; Baker, Beth; Fortney, Kate R; Gao, Hongyu; Holley, Concerta L; Munson, Robert S; Liu, Yunlong; Spinola, Stanley M

2016-05-01

Haemophilus ducreyi causes the sexually transmitted disease chancroid in adults and cutaneous ulcers in children. In humans, H. ducreyi resides in an abscess and must adapt to a variety of stresses. Previous studies (D. Gangaiah, M. Labandeira-Rey, X. Zhang, K. R. Fortney, S. Ellinger, B. Zwickl, B. Baker, Y. Liu, D. M. Janowicz, B. P. Katz, C. A. Brautigam, R. S. Munson, Jr., E. J. Hansen, and S. M. Spinola, mBio 5:e01081-13, 2014, http://dx.doi.org/10.1128/mBio.01081-13) suggested that H. ducreyi encounters growth conditions in human lesions resembling those found in stationary phase. However, how H. ducreyi transcriptionally responds to stress during human infection is unknown. Here, we determined the H. ducreyi transcriptome in biopsy specimens of human lesions and compared it to the transcriptomes of bacteria grown to mid-log, transition, and stationary phases. Multidimensional scaling showed that the in vivo transcriptome is distinct from those of in vitro growth. Compared to the inoculum (mid-log-phase bacteria), H. ducreyi harvested from pustules differentially expressed ∼93 genes, of which 62 were upregulated. The upregulated genes encode homologs of proteins involved in nutrient transport, alternative carbon pathways (l-ascorbate utilization and metabolism), growth arrest response, heat shock response, DNA recombination, and anaerobiosis. H. ducreyi upregulated few genes (hgbA, flp-tad, and lspB-lspA2) encoding virulence determinants required for human infection. Most genes regulated by CpxRA, RpoE, Hfq, (p)ppGpp, and DksA, which control the expression of virulence determinants and adaptation to a variety of stresses, were not differentially expressed in vivo, suggesting that these systems are cycling on and off during infection. Taken together, these data suggest that the in vivo transcriptome is distinct from those of in vitro growth and that adaptation to nutrient stress and anaerobiosis is crucial for H. ducreyi survival in humans. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Improving the National Board of Medical Examiners internal Medicine Subject Exam for use in clerkship evaluation.

PubMed

Elnicki, D Michael; Lescisin, Dianne A; Case, Susan

2002-06-01

To provide a consensus opinion on modifying the National Board of Medical Examiners (NBME) Medicine Subject Exam (Shelf) to: 1) reflect the internal medicine clerkship curriculum, developed by the Society of General Internal Medicine (SGIM) and the Clerkship Directors in Internal Medicine (CDIM); 2) emphasize knowledge important for a clerkship student; and 3) obtain feedback about students' performances on the Shelf. Two-round Delphi technique. The CDIM Research and Evaluation Committee and CDIM members on NBME Step 2 Committees. Using 1-5 Likert scales (5 = highest ratings), the group rated test question content for relevance to the SGIM-CDIM Curriculum Guide and importance for clerkship students' knowledge. The Shelf content is organized into 4 physician tasks and into 11 sections that are generally organ system based. Each iteration of the Shelf has 100 questions. Participants indicated a desired distribution of questions by physician task and section, topics critical for inclusion on each exam, and new topics to include. They specified the types of feedback clerkship directors desired on students' performances. Following the first round, participants viewed pooled results prior to submitting their second-round responses. Of 15 individuals contacted, 12 (80%) participated in each round. The desired distribution by physician task was: diagnosis (43), treatment (23), mechanism of disease (20), and health maintenance (15). The sections with the most questions requested were the cardiovascular (17), respiratory (15), and gastroenterology (12) sections. The fewest were requested in aging/ethics (4) and neurology, dermatology, and immunology (5 each). Examples of low-rated content were Wilson's Disease, chancroid and tracheal rupture (all <2.0). Health maintenance in type 2 diabetes, hypertension, and cardiovascular disease all received 5.0 ratings. Participants desired feedback by: section (4.6) and physician task (3.9), on performances of the entire class (4.0), and for individual students (3.8). Clerkship directors identified test content that was relevant to the curricular content and important for clerkship students to know, and they indicated a desired question distribution. They would most like feedback on their students' performance by organ system-based sections for the complete academic year. This collaborative effort could serve as a model for aligning national exams with course goals.

From in vivo to in vitro: How the Guatemala STD Experiments Transformed Bodies Into Biospecimens.

PubMed

Spector-Bagdady, Kayte; Lombardo, Paul A

2018-06-01

Policy Points: While most scholarship regarding the US Public Health Service's STD experiments in Guatemala during the 1940s has focused on the intentional exposure experiments, secondary research was also conducted on biospecimens collected from these subjects. These biospecimen experiments continued after the Guatemala grant ended, and the specimens were used in conjunction with those from the Tuskegee syphilis experiments for ongoing research. We argue there should be a public accounting of whether there are still biospecimens from the Guatemala and Tuskegee experiments held in US government biorepositories today. If such specimens exist, they should be retired from US government research archives because they were collected unethically as understood at the time. The US Public Health Service's Guatemala STD experiments (1946-1948) included intentional exposure to pathogens and testing of postexposure prophylaxis methods for syphilis, gonorrhea, and chancroid in over 1,300 soldiers, commercial sex workers, prison inmates, and psychiatric patients. Though the experiments had officially ended, the biospecimens collected from these subjects continued to be used for research at least into the 1950s. We analyzed historical documents-including clinical and laboratory records, correspondence, final reports, and medical records-for information relevant to these biospecimen experiments from the US National Archives. In addition, we researched material from past governmental investigations into the Guatemala STD experiments, including those of the US Presidential Commission for the Study of Bioethical Issues and the Guatemalan Comisión Presidencial para el Esclarecimiento de los Experimentos Practicados con Humanos en Guatemala. Identified spinal fluid, blood specimens, and tissue collected during the Guatemala diagnostic methodology and intentional exposure experiments were subsequently distributed to laboratories throughout the United States for use in ongoing research until at least 1957. Five psychiatric patient subjects involved in these biospecimen experiments died soon after experimental exposure to STDs. The same US government researchers working with the Guatemala biospecimens after the exposure experiments ended were also working with specimens taken from the Tuskegee syphilis study. There should be a complete public accounting of whether biospecimens from the Guatemala and Tuskegee experiments are held in US government biorepositories today. If they still exist, these specimens should be retired from such biorepositories and their future disposition determined by stakeholders, including representatives from the communities from which they were derived. © 2018 Milbank Memorial Fund.

Expression of the Flp proteins by Haemophilus ducreyi is necessary for virulence in human volunteers.

PubMed

Janowicz, Diane M; Cooney, Sean A; Walsh, Jessica; Baker, Beth; Katz, Barry P; Fortney, Kate R; Zwickl, Beth W; Ellinger, Sheila; Munson, Robert S

2011-09-22

Haemophilus ducreyi, the causative agent of the sexually transmitted disease chancroid, contains a flp (fimbria like protein) operon that encodes proteins predicted to contribute to adherence and pathogenesis. H. ducreyi mutants that lack expression of Flp1 and Flp2 or TadA, which has homology to NTPases of type IV secretion systems, have decreased abilities to attach to and form microcolonies on human foreskin fibroblasts (HFF). A tadA mutant is attenuated in its ability to cause disease in human volunteers and in the temperature dependent rabbit model, but a flp1flp2 mutant is virulent in rabbits. Whether a flp deletion mutant would cause disease in humans is not clear. We constructed 35000HPΔflp1-3, a deletion mutant that lacks expression of all three Flp proteins but has an intact tad secretion system. 35000HPΔflp1-3 was impaired in its ability to form microcolonies and to attach to HFF in vitro when compared to its parent (35000HP). Complementation of the mutant with flp1-3 in trans restored the parental phenotype. To test whether expression of Flp1-3 was necessary for virulence in humans, ten healthy adult volunteers were experimentally infected with a fixed dose of 35000HP (ranging from 54 to 67 CFU) on one arm and three doses of 35000HPΔflp1-3 (ranging from 63 to 961 CFU) on the other arm. The overall papule formation rate for the parent was 80% (95% confidence interval, CI, 55.2%-99.9%) and for the mutant was 70.0% (95% CI, 50.5%-89.5%) (P = 0.52). Mutant papules were significantly smaller (mean, 11.2 mm2) than were parent papules (21.8 mm2) 24 h after inoculation (P = 0.018). The overall pustule formation rates were 46.7% (95% CI 23.7-69.7%) at 30 parent sites and 6.7% (95% CI, 0.1-19.1%) at 30 mutant sites (P = 0.001). These data suggest that production and secretion of the Flp proteins contributes to microcolony formation and attachment to HFF cells in vitro. Expression of flp1-3 is also necessary for H. ducreyi to initiate disease and progress to pustule formation in humans. Future studies will focus on how Flp proteins contribute to microcolony formation and attachment in vivo. © 2011 Janowicz et al; licensee BioMed Central Ltd.

Haemophilus ducreyi Hfq contributes to virulence gene regulation as cells enter stationary phase.

PubMed

Gangaiah, Dharanesh; Labandeira-Rey, Maria; Zhang, Xinjun; Fortney, Kate R; Ellinger, Sheila; Zwickl, Beth; Baker, Beth; Liu, Yunlong; Janowicz, Diane M; Katz, Barry P; Brautigam, Chad A; Munson, Robert S; Hansen, Eric J; Spinola, Stanley M

2014-02-11

To adapt to stresses encountered in stationary phase, Gram-negative bacteria utilize the alternative sigma factor RpoS. However, some species lack RpoS; thus, it is unclear how stationary-phase adaptation is regulated in these organisms. Here we defined the growth-phase-dependent transcriptomes of Haemophilus ducreyi, which lacks an RpoS homolog. Compared to mid-log-phase organisms, cells harvested from the stationary phase upregulated genes encoding several virulence determinants and a homolog of hfq. Insertional inactivation of hfq altered the expression of ~16% of the H. ducreyi genes. Importantly, there were a significant overlap and an inverse correlation in the transcript levels of genes differentially expressed in the hfq inactivation mutant relative to its parent and the genes differentially expressed in stationary phase relative to mid-log phase in the parent. Inactivation of hfq downregulated genes in the flp-tad and lspB-lspA2 operons, which encode several virulence determinants. To comply with FDA guidelines for human inoculation experiments, an unmarked hfq deletion mutant was constructed and was fully attenuated for virulence in humans. Inactivation or deletion of hfq downregulated Flp1 and impaired the ability of H. ducreyi to form microcolonies, downregulated DsrA and rendered H. ducreyi serum susceptible, and downregulated LspB and LspA2, which allow H. ducreyi to resist phagocytosis. We propose that, in the absence of an RpoS homolog, Hfq serves as a major contributor of H. ducreyi stationary-phase and virulence gene regulation. The contribution of Hfq to stationary-phase gene regulation may have broad implications for other organisms that lack an RpoS homolog. Pathogenic bacteria encounter a wide range of stresses in their hosts, including nutrient limitation; the ability to sense and respond to such stresses is crucial for bacterial pathogens to successfully establish an infection. Gram-negative bacteria frequently utilize the alternative sigma factor RpoS to adapt to stresses and stationary phase. However, homologs of RpoS are absent in some bacterial pathogens, including Haemophilus ducreyi, which causes chancroid and facilitates the acquisition and transmission of HIV-1. Here, we provide evidence that, in the absence of an RpoS homolog, Hfq serves as a major contributor of stationary-phase gene regulation and that Hfq is required for H. ducreyi to infect humans. To our knowledge, this is the first study describing Hfq as a major contributor of stationary-phase gene regulation in bacteria and the requirement of Hfq for the virulence of a bacterial pathogen in humans.

The Haemophilus ducreyi LspA1 protein inhibits phagocytosis by using a new mechanism involving activation of C-terminal Src kinase.

PubMed

Dodd, Dana A; Worth, Randall G; Rosen, Michael K; Grinstein, Sergio; van Oers, Nicolai S C; Hansen, Eric J

2014-05-20

Haemophilus ducreyi causes chancroid, a sexually transmitted infection. A primary means by which this pathogen causes disease involves eluding phagocytosis; however, the molecular basis for this escape mechanism has been poorly understood. Here, we report that the LspA virulence factors of H. ducreyi inhibit phagocytosis by stimulating the catalytic activity of C-terminal Src kinase (Csk), which itself inhibits Src family protein tyrosine kinases (SFKs) that promote phagocytosis. Inhibitory activity could be localized to a 37-kDa domain (designated YL2) of the 456-kDa LspA1 protein. The YL2 domain impaired ingestion of IgG-opsonized targets and decreased levels of active SFKs when expressed in mammalian cells. YL2 contains tyrosine residues in two EPIYG motifs that are phosphorylated in mammalian cells. These tyrosine residues were essential for YL2-based inhibition of phagocytosis. Csk was identified as the predominant mammalian protein interacting with YL2, and a dominant-negative Csk rescued phagocytosis in the presence of YL2. Purified Csk phosphorylated the tyrosines in the YL2 EPIYG motifs. Phosphorylated YL2 increased Csk catalytic activity, resulting in positive feedback, such that YL2 can be phosphorylated by the same kinase that it activates. Finally, we found that the Helicobacter pylori CagA protein also inhibited phagocytosis in a Csk-dependent manner, raising the possibility that this may be a general mechanism among diverse bacteria. Harnessing Csk to subvert the Fcγ receptor (FcγR)-mediated phagocytic pathway represents a new bacterial mechanism for circumventing a crucial component of the innate immune response and may potentially affect other SFK-involved cellular pathways. Phagocytosis is a critical component of the immune system that enables pathogens to be contained and cleared. A number of bacterial pathogens have developed specific strategies to either physically evade phagocytosis or block the intracellular signaling required for phagocytic activity. Haemophilus ducreyi, a sexually transmitted pathogen, secretes a 4,153-amino-acid (aa) protein (LspA1) that effectively inhibits FcγR-mediated phagocytic activity. In this study, we show that a 294-aa domain within this bacterial protein binds to C-terminal Src kinase (Csk) and stimulates its catalytic activity, resulting in a significant attenuation of Src kinase activity and consequent inhibition of phagocytosis. The ability to inhibit phagocytosis via Csk is not unique to H. ducreyi, because we found that the Helicobacter pylori CagA protein also inhibits phagocytosis in a Csk-dependent manner. Harnessing Csk to subvert the FcγR-mediated phagocytic pathway represents a new bacterial effector mechanism for circumventing the innate immune response. Copyright © 2014 Dodd et al.

Sexually Transmitted Infections Among Hospitalized Patients With Human Immunodeficiency Virus Infection and Acquired Immune Deficiency Syndrome (HIV/AIDS) in Zahedan, Southeastern Iran.

PubMed

Hashemi-Shahri, Seyed Mohammad; Sharifi-Mood, Batool; Kouhpayeh, Hamid-Reza; Moazen, Javad; Farrokhian, Mohsen; Salehi, Masoud

2016-09-01

Studies show that nearly 40 million people are living with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) around the world and since the beginning of the epidemic, about 35 million have died from AIDS. Heterosexual intercourse is the most common route for transmission of HIV infection (85%). People with a sexually transmitted infection (STI), such as syphilis, genital herpes, chancroid, or bacterial vaginosis, are more likely to obtain HIV infection during sex. On the other hand, a patient with HIV can acquire other infections such as hepatitis C virus (HCV) and hepatitis B virus (HBV) and also STIs. Co-infections and co-morbidities can affect the treatment route of patients with HIV/AIDs. Sometimes, physicians should treat these infections before treating the HIV infection. Therefore, it is important to identify co-infection or comorbidity in patients with HIV/AIDS. This study was conducted in order to understand the prevalence of HIV/AIDS/STI co-infection. In this cross-sectional study, we evaluated all HIV/AIDS patients who were admitted to the infectious wards of Boo-Ali hospital (Southeastern Iran) between March 2000 and January 2015. All HIV/AIDS patients were studied for sexually transmitted infections (STI) such as syphilis, gonorrhea, hepatitis B virus (HBV) and genital herpes. A questionnaire including data on age, sex, job, history of vaccination against HBV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (anti-HBs), HCV-Ab, venereal disease research laboratory (VDRL) test, fluorescent treponemal antibody absorption (FTA-Abs) test, and urine culture was designed. Data was analyzed by the Chi square test and P values of < 0.05 were considered significant. Among the 41 patients with HIV/AIDS (11 females and 30 males; with age range of 18 to 69 years) five cases (12.1%) had a positive test (1:8 or more) for VDRL. The FTA-Abs was positive for all patients who were positive for VDRL. Gonorrhea was found in seven patients (17%) and three cases had genital herpes in clinical examinations. All patients who had positive test results for these STIs were male. Eleven patients (26.8%) had HBV infection (three females and eight males). hepatitis C virus (HCV) was found in 13 cases (31%). Eighty percent of patients were unemployed. Seventy-eight percent of patients with HIV/STI were aged between 18 and 38 years. There was a significant difference between sex and becoming infected with HIV and also STI (P < 0.05). Patients with HIV/AIDS are more likely to acquire other STIs, because the same behaviors that increase the risk of becoming HIV infected can also increase the risk of acquiring STIs. Having a sore on the skin due to an STI can make the transmission of HIV to the sex partner more likely than people who don't have such sore in their genital area.

Treatment of sexually transmitted bacterial diseases in pregnant women.

PubMed

Donders, G G

2000-03-01

Testing for and treating sexually transmitted diseases (STDs) in pregnant women deserves special attention. Treatment possibilities are limited because of potential risks for the developing fetus, and because effects can differ in pregnant compared with non-pregnant women, re-infection may be missed because of the intrinsic delicacy of contact-tracing during pregnancy and because pregnant women are more reluctant to take the prescribed medication in its full dose, if at all. However, the devastating effects of some of these genital infections far outweigh any potential adverse effects of treatment. Although active syphilis has become a rarity in most Western countries, it is still prevalent in South America, Africa and South-East Asia. Benzathine benzylpenicillin (2.4 million units once or, safer, twice 7 days apart) is the treatment of choice, although patients with syphilis of longer standing require 3 weekly injections as well as extensive investigation into whether there has been any damage due to tertiary syphilis. Despite declining rates of gonorrhea, the relative rate of penicillinase-producing strains is increasing, especially in South-East Asia. The recommended treatment is intramuscular ceftriaxone (125 or 250 mg) or oral cefixime 400 mg. Despite good safety records after accidental use, fluoroquinolones are contraindicated during pregnancy. An alternative to a fluoroquinolone in pregnant women with combined gonorrhea and chlamydial infection is oral azithromycin 1 or 2 g. Azithromycin as a single 1 g dose is also preferable to a 7 day course of erythromycin 500 mg 4 times a day for patients with chlamydial infection. Eradication of Haemophilus ducreyi in patients with chancroid can also be achieved with these regimens or intramuscular ceftriaxone 250 mg. Trichomonas vaginalis, which is often seen as a co-infection, has been linked to an increased risk of preterm birth. Patients infected with this parasite should therefore received metronidazole 500 mg twice daily for 7 days as earlier fears of teratogenesis in humans have not been confirmed by recent data. Bacterial vaginosis is also associated with preterm delivery in certain risk groups, such as women with a history of preterm birth or of low maternal weight. Such an association is yet to be convincingly proven in other women. The current advice is to treat only women diagnosed with bacterial vaginosis who also present other risk factors for preterm delivery. The treatment of choice is oral metronidazole 1 g/day for 5 days. The possible reduction of preterm birth by vaginally applied metronidazole or clindamycin is still under investigation. In general, both test of cure and re-testing after several weeks are advisable in most pregnant patients with STDs, because partner notification and treatment are likely to be less efficient than outside pregnancy and the impact of inadequately treated or recurrent disease is greater because of the added risk to the fetus. Every diagnosis of an STD warrants a full screen for concomitant genital disease. Most ulcerative genital infections, as well as abnormal vaginal flora and bacterial vaginosis, increase the sexual transmission efficiency of HIV, necessitating even more stringent screening for and treating of STD during pregnancy.