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CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking.

The chemokine receptors (CCRs) CCR4 and CCR10, and the cutaneous lymphocyte antigen (CLA), have each been proposed as critical mediators of skin-specific TH lymphocyte homing in mice and humans. CLA initiates skin homing by mediating E-selectin-dependent tethering and rolling within cutaneous venules, but the specific roles of CCR4 and CCR10 are unclear. We have generated an antihuman CCR10 monoclonal antibody (mAb; 1B5) to illuminate the individual contributions of these molecules. This mAb allows us to compare CCR10, CCR4, and CLA expression within human TH populations. The mAb 1B5 recognizes functional CCR10 expression, as chemotactic responsiveness to cutaneous T-cell-attracting chemokine (CTACK)/CCL27 (a CCR10 ligand) parallels the staining of TH subsets. We find CCR10 expressed by only a minority (approximately 30%) of blood-borne, skin-homing (CLA+/CCR4+) TH cells. However, essentially all members of the relatively small "effector" (CLA+/CCR4+/CD27-/CCR7-) skin-homing TH population express CCR10. Most skin-infiltrating lymphocytes in allergic delayed-type hypersensitivity (DTH) and bacterial chancroid skin lesions express both CCR4 and CLA, but only about 10% express CCR10. This suggests for the 2 models of TH skin homing studied here that CCR10+ TH cells have no advantage over other CLA+/CCR4+ TH cells in homing to cutaneous sites. We conclude that the skin-homing TH compartment is itself divided into distinct subpopulations, the smaller of which expresses both CCR4 and CCR10, and the larger of which expresses only CCR4. Thus, CCR10 is unlikely to be necessary for cutaneous homing of TH cells in the models studied here. CCR10 may instead play a role in the movement of specialized "effector" cutaneous TH cells to and/or within epidermal microenvironments.

Animals↗

Development of a heminested polymerase chain reaction assay for the detection of Haemophilus ducreyi in clinical specimens.

Detection of Haemophilus ducreyi in genital ulcer specimens by culture lacks sensitivity. To enhance detection, a heminested polymerase chain reaction (PCR) assay was developed targeting the nucleotide sequence of a gene, designated p27, which encodes for a 27 kDa H. ducreyi-specific protein. The p27 PCR assay detected all (37/37) H. ducreyi strains tested and gave no amplified product from DNA extracts of any of 31 other microorganisms, from 30 non-genital ulcer specimens, or from 29 urethral and vaginal swab specimens collected from non-chancroid STD patients. In genital ulcer disease specimens, compared to combined positive results obtained by culture and a previously described PCR assay, the p27 PCR assay showed a sensitivity of 91% (48/53). The p27 PCR assay provides a specific and a sensitive detection of H. ducreyi in clinical specimens.

Bacterial Proteins↗

Sexually transmitted diseases: a survey of case management in Malawi.

A national survey of sexually transmitted disease (STD) case management was carried out at 39 health care facilities in Malawi in 1994. Fifty-four health care providers were observed managing 150 patients presenting with selected STD syndromes and 103 providers were interviewed. STD case management was assessed by calculation of WHO/GPA prevention indicators (PIs) from observation data. The overall rate for PI-6, which measures correct assessment and treatment of STD patients was 11% (81% for history taking, 46% in physical examination, and 13% correct antibiotic treatment according to national guidelines). The score for PI-7, which measures overall patient counselling was 29% (65% for partner notification and 40% for condom advice). Although Haemophilus ducreyi is at least as common as Treponema pallidum as the causative agent for genital ulcers, only 16% of patients with genital ulcers were treated effectively for chancroid vs 56% for syphilis. Female patients received less comprehensive care than male STD patients. Only 20% of STD patients were offered condoms. Overall, the survey results support the policy decision to adopt syndromic management of STDs, and provide baseline information for planning and evaluation of a national control programme.

Africa↗

Evolution of the cutaneous immune response to experimental Haemophilus ducreyi infection and its relevance to HIV-1 acquisition.

Haemophilus ducreyi causes the sexually transmitted disease chancroid, which facilitates HIV-1 transmission. Skin biopsies were obtained from subjects experimentally infected with H. ducreyi to study the evolution of the immune response and immunophenotypes relevant to transmission of HIV-1. Compared with peripheral blood, there was an enrichment of T cells and macrophages after 48 h of infection in the skin. Neutrophils became the predominant cell type by 7-9 days. By immunohistochemistry, macrophage-inflammatory protein-1alpha was not present early in infection, but was abundant at later stages. RANTES was present throughout the papular and pustular stages of experimental infection, but not present in uninfected control skin. Stromal cell-derived factor-1 was present at low levels in all samples examined. Macrophages in lesions had significantly increased expression of CCR5 and CXCR4 compared with peripheral blood cells, and CD4 T cells had significant up-regulation of CCR5. The magnitude of increased expression of these receptors was not replicated when PBMCs were incubated with H. ducreyi or H. ducreyi lipooligosaccharide in vitro. Together with the disruption of mucosal and skin barriers, the presence of cells with up-regulated HIV-1 coreceptors in H. ducreyi-infected lesions may provide an environment that facilitates the acquisition of R5 (CCR5), X4 (CXCR4), and dual-tropic HIV-1 strains.

Chancroid↗

Sexually transmitted diseases: testing and treating.

Adolescents remain a group at particular risk for STD acquisition due to a combination of biological and psychosocial factors. Access to care can be an obstacle to seeking appropriate screening and treatment for many adolescents; undetected infection may lead to unwanted sequelae, including pelvic inflammatory disease, chronic abdominal pain, tubal scarring, and increased risk of ectopic pregnancy. With respect to gonorrhea, chlamydia, syphilis, and chancroid, the hope is that improved detection will decrease sequelae by prompting earlier recognition and treatment. In all cases of suspected sexual abuse cultures remain of utmost importance because of the negative consequences associated with a possible false-positive test result. Urine screening in certain settings, such as school-based health centers and juvenile detention centers, remains positive; however, adolescents with a positive test may still require further evaluation to identify HPV and abnormal Pap smear findings, syphilis, and other STDs currently not recognizable with a simple urine screen.

Adolescent↗

An overview of sexually transmitted diseases. Part I.

Sexually transmitted diseases are a persistent problem in the United States and throughout the world. Many of these infections involve the skin and may be encountered in the field of dermatology. This 3-part review highlights the cutaneous features, diagnosis, and treatment of 11 of the most commonly encountered sexually transmitted diseases, other than AIDS. However, this review does not cover sexually transmitted diseases such as chlamydia, which do not regularly have cutaneous manifestations. Part 1 focuses on syphilis, disseminated gonococcal infection, chancroid, lymphogranuloma venereum, granuloma inguinale, and genital herpes. Additional features, such as epidemiology and transmission of the organism, are discussed when applicable.

Chancroid↗

HIV/STDs in minority women: educational and medical interventions to alter the spread.

HIV is but one form of sexually transmitted disease (STD). Many of the other STDs, especially those that produce ulcerating lesions, such as herpes simplex, syphilis, and chancroid, are associated with increased shedding of HIV if the individual is seropositive, and with increased risk of infection if a seronegative individual with that type of STD has unprotected intercourse with an HIV-positive partner. Thus, control and treatment of other STDs is very important in the management and prevention of the spread of HIV/AIDS.

Chancroid↗

Characterization of skin lesions in mice following intradermal inoculation of Haemophilus ducreyi.

Twelve strains of H. ducreyi, which included two reference strains, were each inoculated intradermally into the flanks of CBA mice. All strains produced self-limited lesions which were macroscopically and microscopically typical of those seen in chancroid. Pustular nodules, about 5mm in diameter, developed at all inoculation sites by the second day when 10(7) organisms were inoculated. Approximately half of these lesions ulcerated and all had regressed by 2 weeks. Smaller nodules developed at about half the sites from the second to the fifth day when 10(6) or 10(5) organisms were given, but these did not ulcerate. No lesions were seen when 10(3) organisms were inoculated. Organisms were recovered from the lesions up to 11 days after inoculation. Specific H. ducreyi antigen, sought by a monoclonal antibody test, was detected in lesions up to 15 days following inoculation. Heat-killed organisms of H. ducreyi also produced nodules and ulcers although these were slightly smaller than those which developed after inoculation of viable bacteria. Similar lesions to those caused by H. ducreyi were produced after intradermal inoculation of about 10(8) viable or killed Neisseria gonorrhoeae organisms. Treatment of mice with ceftriaxone had little or no effect on the subsequent development of H. ducreyi-induced lesions. These findings indicated that the lesions were not produced specifically by viable H. ducreyi organisms. Ulcers were also produced following intradermal inoculation of purified lipopolysaccharide (LPS) from H. ducreyi or N. gonorrhoeae, but not by cell-free filtrates prepared from H. ducreyi cultures indicating a possible role for LPS in the pathogenesis of ulcerative skin lesions.

Animals↗

Quinolones in the treatment of sexually transmitted diseases.

Many of the new quinolone-carboxylic acids possess in vitro activity against a variety of sexually transmitted pathogens. Neisseria gonorrhoeae and Hemophilus ducreyi are particularly susceptible to those antimicrobial agents while the in vitro sensitivities of Chlamydia trachomatis and genital mycoplasmas vary widely amongst the quinolones and range from poor to modest. Clinically, single dose therapy with many of the quinolones has been highly effective in curing gonorrhea and appears to be promising in the management of chancroid. In contrast, however, the quinolones (even when used in multiple dose, 7 to 10 day regimens) have been disappointing to date in the treatment of chlamydial and nongonococcal infections. Currently there is little data available with regard to other sexually transmitted diseases but it appears that the quinolones will not be useful in the therapy of syphilis or bacterial vaginosis.

4-Quinolones↗

[Diagnosis and therapy of ulcus molle today. Case report and review of the literature].

Chancroid, an ulcerous disease of the genitalia caused by Haemophilus ducreyi, occurs rarely but regularly in Germany. Exact diagnosis is based on the clinical features and a direct smear, and in particular on cultivation of the organism, showing its unique macromorphological characteristics. The sensitivity of cultivation has increased due to the development of selective media for primary isolation. Resistance problems during the last decade meant that a change to new therapeutic strategies was unavoidable. The work presented here includes a case report and a review of the recent literature, it illustrates modern methods of diagnosis and treatment of Haemophilus ducreyi infections 100 years after the first description of the organism.

Administration, Topical↗

[Diagnosis and therapy of ulcus molle].

In developing countries of tropical Africa and South-East Asia chancroid is the most important cause of genital ulzerations. In the last decade also in industrial countries of the western hemisphere sporadic epidemics of this sexually transmitted disease were observed. This surprising revival of a disease already thought to have died out induced advances in cultivation and characterization of the etiologic agent as well as new therapeutic approaches. Treatment regimens based on erythromycin, cephalosporins of the third generation or a combination of amoxillin with the beta-lactamase inhibitor clavulanic acid can be recommended. Penicillins and tetracyclines are mostly ineffective because of plasmid-mediated resistance in Haemophilus ducreyi. As in other sexually transmitted diseases simultaneous infections with other pathogens have to be taken into consideration. The sexual partners of the patients should likewise be examined and if need, be treated.

Anti-Bacterial Agents↗

Problems in the treatment of bacterial sexually transmitted diseases.

Although most bacterial sexually transmitted diseases (STDs) can be effectively treated, currently available regimens are far from ideal. Increasingly widespread plasmid-mediated resistance to the penicillins limits the use of these agents in the treatment of Neisseria gonorrhoeae and Hemophilus ducreyi infections. Chromosomally mediated antimicrobial resistance to the tetracyclines, penicillins, erythromycins, and sulfonamides further limits therapeutic options in the treatment of gonorrhea, and plasmid-mediated resistance to sulfonamides and tetracyclines is frequent in H. ducreyi infections. In patients with Chlamydia trachomatis infections, effective regimens that can more easily be complied with (shorter duration, less frequent dosing) are needed, as are effective alternative regimens for use in pregnancy and in infants. In selected STDs that are polymicrobial (pelvic inflammatory disease and bacterial vaginosis, for example) or that often present simultaneously (gonorrhea-chlamydia, gonorrhea-syphilis, chancroid-syphilis), single-drug regimens that are effective against several genital pathogens would be ideal. Only limited therapeutic alternatives are available for some STDs, especially in pregnant women or in patients with penicillin allergy. Thus, antimicrobial resistance, drug toxicity, poor compliance, limited alternatives in pregnancy or allergy, and the lack of single agents possessing a broad spectrum of activity against multiple genital pathogens limit currently available therapy.

Anti-Bacterial Agents↗

Sexually transmitted diseases.

This article summarizes the major sexually transmitted diseases with an emphasis on diagnosis, therapy, and follow-up. Topics included are syphilis, gonorrhea, herpes genitalis, nongonococcal urethritis, lymphogranuloma venereum, granuloma inguinale, chancroid, condyloma acuminatum, molluscum contagiosum, and venereally transmitted gastrointestinal disease.

Adolescent↗

Nonsexual transmission of sexually transmitted diseases: an infrequent occurrence.

Sexually transmitted diseases occur in epidemic numbers in the United States today. Nonsexual transmission of these diseases is rarely an issue in adults. However, when the same diseases are found in children, the tendency of pediatricians and other health care practitioners has been to believe the mode of transmission is asexual. A review of gonorrhea, Chlamydia trachomatis, herpes genitalis, condyloma acuminata, Trichomonas vaginalis, syphilis, chancroid, and granuloma inguinale infections has been made to address the issue of nonsexual transmission of sexually transmitted diseases. Nonsexual transmission of these infections is an infrequent occurrence and when they affect the prepubertal child, sexual abuse must be highly suspected.

Adolescent↗

Genital ulcer disease.

There are five major sexually transmitted diseases producing genital ulcerations. Their prevalence varies among geographic regions. Whereas genital herpes is the most frequent cause of genital ulcer in western Europe and North America, the most common cause of genital ulcer disease in developing countries appears to be chancroid. Owing to frequently atypical presentation and mixed infections, an accurate clinical diagnosis is very difficult. Successful management of genital ulcer disease depends on accurate diagnosis corroborated by performance of appropriate laboratory tests when possible.

Chancroid↗

The 1993 sexually transmitted disease treatment guidelines.

This article will review the 1993 STD Treatment Guidelines of particular importance to dermatologic clinical practice. Topics include STD/HIV prevention, management of sexual partners, STD in persons with HIV co-infection, genital ulcer disease (GUD) including syphilis, herpes simplex virus (HSV) infection, lymphogranuloma venereum (LGV) and chancroid, therapy of nongonococcal (NGU) and chlamydial urethritis and cervicitis, gonococcal (GC) infections, HPV infection, hepatitis B virus (HBV) infection, pediculosis pubis, and scabies.

Chancroid↗

Sexually transmitted diseases in HIV-infected persons.

It appears incontestable that there is a link between genital ulcer disease and HIV infection. On the one hand the natural history and response to therapy of syphilis, HSV-2, and chancroid are all modified by the immunosuppressive effects of HIV infection. On the other hand, HIV transmission is probably facilitated by the disruption of the normal epithelial barriers of the genital organs caused by these ulcerative infections. Information is somewhat less convincing that a similar association exists between the nonulcerative STDs (trichomonas, gonorrhea, chlamydial infections) and HIV. Conceptually, the mucosal inflammation associated with these infections might serve as a focus for HIV transmission. The available data, though suggestive, do not strongly support this contention. Theoretically though, even a small risk might potentially result in significant HIV transmission given the prevalence of nonulcerative STDs. These infectious processes do not appear to be markedly altered by HIV induced immunosuppression. The ability of HPV to cause dysplastic changes in cervical and anal tissue did not require the AIDS epidemic to come to light. In HIV infection, disruptions of immunoregulatory processes, which might ordinarily control the progression of potentially malignant cell lines, have created fertile ground for an increasing incidence of premalignant and malignant cytologic changes. The mutual impact these processes have or may have on one another requires that clinicians who care for patients with either HIV infection or with STDs should be thoroughly familiar with both and not consider them somehow exclusive of one another. Efforts toward the prevention and control of STDs should be considered important in the control and prevention of HIV transmission.

Chancroid↗

In vitro susceptibility of Haemophilus ducreyi to several antibiotics.

Haemophilus ducreyi was isolated from 59 (52%) of 113 men with a clinical diagnosis of chancroid. The following MIC50 (MIC90) values for H. ducreyi were obtained: erythromycin 0.14 (0.5) micrograms/ml, trimethoprim 0.25 (8.0) micrograms/ml, ceftriaxone 0.009 (0.14) micrograms/ml, and ciprofloxacin 0.007 (0.04) micrograms/ml. These data indicate that all isolates appear to be fully susceptible to erythromycin and the other antimicrobial agents tested, although ciprofloxacin was the most effective antibiotic.

Anti-Bacterial Agents↗