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Background: Together with Treponema pallidum subspecies pertenue, Haemophilus ducreyi is a major cause of exudative cutaneous ulcers (CUs) in children. For H. ducreyi, both class I and class II strains, asymptomatic colonization, and environmental reservoirs have been found in endemic regions, but the epidemiology of this infection is unknown., Methods: Based on published whole-genome sequences of H. ducreyi CU strains, a single-locus typing system was developed and applied to H. ducreyi-positive CU samples obtained prior to, 1 year after, and 2 years after the initiation of a mass drug administration campaign to eradicate CU on Lihir Island in Papua New Guinea. DNA from the CU samples was amplified with class I and class II dsrA-specific primers and sequenced; the samples were classified into dsrA types, which were geospatially mapped. Selection pressure analysis was performed on the dsrA sequences., Results: Thirty-seven samples contained class I sequences, 27 contained class II sequences, and 13 contained both. There were 5 class I and 4 class II types circulating on the island; 3 types accounted for approximately 87% of the strains. The composition and geospatial distribution of the types varied little over time and there was no evidence of selection pressure., Conclusions: Multiple strains of H. ducreyi cause CU on an endemic island and coinfections are common. In contrast to recent findings with T. pallidum pertenue, strain composition is not affected by antibiotic pressure, consistent with environmental reservoirs of H. ducreyi. Such reservoirs must be addressed to achieve eradication of H. ducreyi.

Background: Yaws-like chronic ulcers can be caused by Treponema pallidum subspecies pertenue, Haemophilus ducreyi, or other, still-undefined bacteria. To permit accurate evaluation of yaws elimination efforts, programmatic use of molecular diagnostics is required. The accuracy and sensitivity of current tools remain unclear because our understanding of T. pallidum diversity is limited by the low number of sequenced genomes., Methods: We tested samples from patients with suspected yaws collected in the Solomon Islands and Ghana. All samples were from patients whose lesions had previously tested negative using the Centers for Disease Control and Prevention (CDC) diagnostic assay in widespread use. However, some of these patients had positive serological assays for yaws on blood. We used direct whole-genome sequencing to identify T. pallidum subsp pertenue strains missed by the current assay., Results: From 45 Solomon Islands and 27 Ghanaian samples, 11 were positive for T. pallidum DNA using the species-wide quantitative polymerase chain reaction (PCR) assay, from which we obtained 6 previously undetected T. pallidum subsp pertenue whole-genome sequences. These show that Solomon Islands sequences represent distinct T. pallidum subsp pertenue clades. These isolates were invisible to the CDC diagnostic PCR assay, due to sequence variation in the primer binding site., Conclusions: Our data double the number of published T. pallidum subsp pertenue genomes. We show that Solomon Islands strains are undetectable by the PCR used in many studies and by health ministries. This assay is therefore not adequate for the eradication program. Next-generation genome sequence data are essential for these efforts., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Haemophilus ducreyi (HD) and Treponema pallidum subspecies pertenue (TP) are major causative agents of cutaneous ulcer (CU) in the tropics. Azithromycin is recommended to treat sexually transmitted HD infections and has good in vitro activity against HD strains from both genital and skin ulcers. We investigated the efficacy of oral single-dose azithromycin on HD-CU., Methods: We conducted a community-based cohort study in Lihir Island, Papua New Guinea, from October 2014 through May 2016. Consenting patients with skin ulcers >1 cm in diameter were eligible for this study and had collected a lesional swab for polymerase chain reaction (PCR). All participants were treated with single-dose azithromycin (30 mg/kg) and were followed up for assessment of clinical resolution. We retrospectively classified patients according to PCR results into HD, TP, and PCR-negative groups. The primary endpoint was healing rates of HD-CU at 14 days after treatment., Results: We obtained full outcome data from 246 patients; 131 (53.3%) were HD PCR positive, 37 (15.0%) were TP positive, and 78 (31.7%) were negative for all tests. Healing rates were 88.5% (95% confidence interval [CI], .82-.93) in the HD group, 78.4% [95% CI, .63-.89] in the TP group, and 74.4% (95% CI, .64-.83) in the PCR-negative group. If we included the participants with improved ulcers, the healing rates increased to 94.7%, 97.3%, and 89.7% respectively. HD cases classified as not healed all converted to HD-negative PCR., Conclusions: Based upon clinical resolution and PCR conversion to HD negative, a single oral dose of azithromycin is efficacious for the treatment of HD-CU. These results have implications for the treatment of individual patients and for the use of antibiotics in public health strategies to control CU in the tropics., (© The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Four spotted fever group rickettsiae (SFGR) are known to infect humans in the United States. A member of the SFGR designated 364D and detected in Dermacentor occidentalis ticks has not previously been identified as a human pathogen., Methods: An 80-year-old man from a rural northern California community presented with an eschar on his forearm. A skin punch biopsy of the lesion was evaluated by immunohistochemistry and molecular analysis. Serum specimens obtained from the patient and 3 other area residents with similar illnesses were tested by immunofluorescence and Western immunoblot for antibodies to SFGR. Ticks were collected near the patient's residence and tested for SFGR., Results: Abundant intracellular rickettsiae and fragmented rickettsial antigens were observed in the mononuclear inflammatory infiltrates of the biopsy. Nucleotide sequences of DNA fragments amplified from the biopsy were identical to those of 364D. Convalescent sera from all four patients exhibited high immunoglobulin G titers to Rickettsia rickettsii, Rickettsia rhipicephali, and 364D antigens. Three adult D. occidentalis were positive for 364D, R. rhipicephali, and an unidentified Rickettsia species., Conclusions: This is the first confirmation of human disease associated with the SFGR 364D, which was likely transmitted by D. occidentalis. Although the patients described here presented with a single cutaneous eschar as the principal manifestation, the full spectrum of illness associated with 364D has yet to be determined. Possible infection with 364D or other SFGR should be confirmed through molecular techniques in patients who present with "spotless" Rocky Mountain spotted fever or have serum antibodies to R. rickettsii with group-specific assays.

Chancroid is a sexually transmitted infection associated with genital ulceration and lymphadenopathy caused by Haemophilus ducreyi. Localized skin infections, in the absence of genital lesions, have not been previously reported. We report 3 cases of lower limb ulceration in children caused by H. ducreyi and postulate that H. ducreyi may be a previously unrecognized cause of chronic skin ulceration.

Background: Morbidity due to Buruli ulcer disease (BUD), a cutaneous infection caused by Mycobacterium ulcerans, has been increasingly recognized in rural West Africa. The source and mode of transmission remain unknown., Methods: To identify BUD risk factors, we conducted a case-control study in 3 BUD-endemic districts in Ghana. We enrolled case patients with clinically diagnosed BUD and obtained skin biopsy specimens. M. ulcerans infection was confirmed by at least 1 of the following diagnostic methods: histopathologic analysis, culture, polymerase chain reaction, and Ziehl-Neelsen staining of a lesion smear. We compared characteristics of case patients with confirmed BUD with those of age- and community-matched control subjects using conditional logistic regression analysis., Results: Among 121 case patients with confirmed BUD, leg lesions (49%) or arm lesions (36%) were common. Male case patients were significantly more likely than female case patients to have lesions on the trunk (25% vs. 6%; P = .009). Multivariable modeling among 116 matched case-control pairs identified wading in a river as a risk factor for BUD (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.27-5.68; P = .0096). Wearing a shirt while farming (OR, 0.27; 95% CI, 0.11-0.70; P = .0071), sharing indoor living space with livestock (OR, 0.36; 95% CI, 0.15-0.86; P = .022), and bathing with toilet soap (OR, 0.41; 95% CI, 0.19-0.90; P = .026) appeared to be protective. BUD was not significantly associated with penetrating injuries (P = .14), insect bites near water bodies (P = .84), bacille Calmette-Guerin vaccination (P = .33), or human immunodeficiency virus infection (P = .99)., Conclusions: BUD is an environmentally acquired infection strongly associated with exposure to river areas. Exposed skin may facilitate transmission. Until transmission is better defined, control strategies in BUD-endemic areas could include covering exposed skin.

Extrapharyngeal infections caused by Corynebacterium ulcerans have rarely been reported previously, and diphtheria toxin production has usually not been addressed. This case demonstrates that strains of C. ulcerans that produce diphtheria toxin can cause infections of the skin that completely mimic typical cutaneous diphtheria, thereby potentially providing a source of bacteria capable of causing life-threatening diseases in the patient's environment. Therefore, it is recommended to screen wound swabs for coryneform bacteria, identify all isolates, carefully assess possible toxin production, and send questionable strains to a specialist or a reference laboratory.

Clinical, microbiological, and immunologic responses were evaluated in volunteers vaccinated intradermally with bacille Calmette-Guérin (BCG). Most volunteers (98%) developed ulcerative lesions that drained for a mean +/- SE of 4.3 +/- 0.29 weeks. Mycobacterial DNA was detected by a polymerase chain reaction-based amplification technique in biopsy specimens from BCG ulcers 2 weeks after vaccination and in blood specimens 3 days after vaccination. Mycobacteria were cultured from ulcer drainage 2 months after vaccination, demonstrating a prolonged potential risk of contact spread of the vaccine strain. The duration of ulcer drainage was inversely correlated with prevaccination lymphoproliferative (r = -0.515; P < .002) and interferon gamma (r = -0.841; P < .002) responses specific to mycobacteria and directly correlated with postvaccination increases in lymphoproliferative (r = 0.498; P < .002) and interferon gamma (r = 0.688; P < .02) responses specific to mycobacteria. These results demonstrate the clinical reactogenicity of BCG and the potential risk of contact spread of the vaccine strain and suggest that clinical reactogenicity is a trade-off for the induction of protective mycobacterial immunity.

The factors responsible for the explosive spread of human immunodeficiency virus type 1 (HIV-1) in sub-Saharan Africa continue to be identified and debated. One of the most controversial factors has been male circumcision. This cross-sectional study was conducted to measure the association between circumcision status and infection with HIV-1 among men with genital ulcer disease. Eight hundred and ten men participated in the study, of whom 190 (23%) were HIV-1-positive. A logistic regression model adjusted for behavioral and historical showed that HIV-1 positivity was independently associated with being uncircumcised (adjusted odds ratio [OR], 4.8; 95% confidence interval [CI], 3.3-7.2) and with a history of urethral discharge (adjusted OR, 2.0; 95% CI, 1.4-2.8). This association could not be explained by measures of sexual exposure to HIV-1 among this population. Male circumcision should be considered as an intervention strategy for AIDS control.

Disseminated Mycobacterium scrofulaceum infection has rarely been reported (only 8 cases to date), and no case of infection associated with AIDS has been reported in detail. We report a case of disseminated M. scrofulaceum infection in an AIDS patient that presented as chronic ulcerative and nodular skin lesions with probable cavitary lung involvement. We discuss reported cases of dissminated M. scrofulaceum infection and features of human immunodeficiency virus (HIV)-associated disease due to mycobacteria other than tuberculosis. Although our patient died before susceptibility testing could be completed, the M. scrofulaceum isolate was found to be susceptible to clarithromycin, ethambutol, and clofazimine. Physicians who evaluate skin lesions in HIV-infected persons should perform appropriate mycobacterial studies and search for disseminated disease. Drug susceptibility testing for mycobacteria other than tuberculosis is not yet standardized, but the broth dilution method, currently being studied in clinical trials of treatment for Mycobacterium avium complex, may be superior to older methods. After the possibility of Mycobacterium tuberculosis infection has been excluded, physicians should consider administering initial empirical therapy with two or more drugs, including a newer macrolide, to AIDS patients with disseminated mycobacterial disease.