Case report: Hansen's disease in an active duty soldier presenting with type 1 reversal reaction.

Leprosy, or Hansen's disease (HD), is caused by the bacterium Mycobacterium leprae and is a significant cause of morbidity worldwide. Clinical manifestations range from isolated skin rash to severe peripheral neuropathy. Treatment involves a prolonged course of multiple antimicrobials. Although rare in the U.S., with only 168 new cases reported in 2016, HD remains a prevalent disease throughout the world, with 214,783 new cases worldwide that same year.1 It remains clinically relevant for service members born in and deployed to endemic regions. This report describes a case of HD diagnosed in an active duty soldier born and raised in Micronesia, a highly endemic region.

Phenotypic, molecular and antimicrobial susceptibility assessment in isolates from chronic ulcers of cured leprosy patients: a case study in Southern Brazil.

BACKGROUND: One of the most stigmatizing physical sequelae of leprosy in cured patients is the development of chronic lower extremity ulcers. The bacterial diversity present in ulcers is considered one of the factors that can delay the healing process, as well as serve as a focus for severe secondary infections. OBJECTIVE: To identify the microbiota and antimicrobial resistance profile of bacteria isolated from skin ulcers in patients cured of leprosy. METHODS: After obtaining informed consent, material was collected from ulcers of 16 patients treated at the Outpatient Public Health Dermatology Clinic of Rio Grande do Sul and Hospital Colônia Itapuã. Samples were collected during dressing, and the material sent to the Microbiology Laboratory of the Federal University of Health Sciences of Porto Alegre for microbiological culture. Methicillin-resistant Staphylococcus aureus (MRSA) was characterized by two molecular methods, including detection of the mecA gene by PCR and SCCmecgene typing. RESULTS: Cultures revealed microorganisms in all ulcers: Gram-negative bacilli in 80%, Gram-positive cocci in 63%, and mixed microflora in 36%. Staphylococcus aureus and Pseudomonas aeruginosa were the most prevalent bacteria. Assessment of the antimicrobial resistance profile was notable for the presence of MRSA. Molecular analysis of this isolate revealed presence of the mecA gene contained in a type IV staphylococcal cassette chromosome mec (SCCmec). CONCLUSIONS: In patients with leprosy, laboratory culture of skin ulcers is essential for correct antibiotic selection and to control emerging pathogens, such as MRSA carrying SCCmec type IV.

Phenotypic, molecular and antimicrobial susceptibility assessment in isolates from chronic ulcers of cured leprosy patients: a case study in Southern Brazil

BACKGROUND: One of the most stigmatizing physical sequelaeof leprosy in cured patients is the development of chronic lower extremity ulcers. The bacterial diversity present in ulcers is considered one of the factors that can delay the healing process, as well as serve as a focus for severe secondary infections. OBJECTIVE: To identify the microbiota and antimicrobial resistance profile of bacteria isolated from skin ulcers in patients cured of leprosy. METHODS: After obtaining informed consent, material was collected from ulcers of 16 patients treated at the Outpatient Public Health Dermatology Clinic of Rio Grande do Sul and Hospital Colônia Itapuã. Sampleswere collected during dressing, and the material sent to the Microbiology Laboratory of the Federal University of Health Sciences of Porto Alegre for microbiological culture. Methicillin-resistant Staphylococcus aureus (MRSA) was characterized by two molecular methods, including detection of the mecA gene by PCR and SCCmecgene typing. RESULTS: Cultures revealed microorganisms in all ulcers: Gram-negative bacilli in 80%, Gram-positive cocci in 63%, and mixed microflora in 36%. Staphylococcus aureus and Pseudomonas aeruginosa were the most prevalent bacteria. Assessment of the antimicrobial resistance profile was notable for the presence of MRSA. Molecular analysis of this isolate revealed presence of the mecA gene contained in a type IV staphylococcal cassette chromosome mec (SCCmec). CONCLUSIONS: In patients with leprosy, laboratory culture of skin ulcers is essential for correct antibiotic selection and to control emerging pathogens, such as MRSA carrying SCCmec type IV. .

Ulcerated and nonulcerated nontuberculous cutaneous mycobacterial granulomas in cats and dogs.

BACKGROUND: Mycobacterial granulomas of the skin and subcutis can be caused by one of a number of pathogens. This review concentrates on noncultivable species that cause diseases characterized by focal granuloma(s), namely leproid granuloma (in dogs) and feline leprosy (in cats). Clinically indistinguishable lesions can be caused by tuberculous organisms (Mycobacterium bovis and Mycobacterium microti) and members of the Mycobacterium avium complex. Rapidly growing mycobacterial species that cause infection of the subcutaneous panniculus associated with draining tracts are not discussed. Disease caused by Mycobacterium ulcerans is an important emerging differential diagnosis for ulcerated cutaneous nodules in certain localized regions. CLINICAL LESIONS: Lesions comprise one or multiple nodules in the skin/subcutis. These are generally firm and well circumscribed, and typically become denuded of hair. They may or may not ulcerate, depending on the virulence of the causal organisms and the immune response of the host. DIAGNOSIS: The most inexpensive, noninvasive means of diagnosis is by submission of methanol-fixed, Romanowsky-stained smears to a Mycobacterium Reference Laboratory after detecting negatively stained or acid-fast bacilli on cytological smears. Scrapings of material from slides usually provide sufficient mycobacterial DNA to enable identification of the causal organism using sequence analysis of amplicons after PCR using specific mycobacterial primers. THERAPY: Therapy relies upon a combination of marginal resection of easily accessible lesions and treatment using two or three drugs effective against slowly growing mycobacteria, choosing amongst rifampicin, clarithromycin, clofazimine and pradofloxacin/moxifloxacin.

A fatal case of Lucio phenomenon from India.

A 65-year-old man presented with cutaneous ulcerations involving the legs, hands, abdomen, buttocks, and pinna, along with fever, arthralgia, and anorexia for the prior 10 days. On cutaneous examination, dark, irregular-shaped bizarre erythematous purpuric spots and angulated ulcers were seen over bilateral, upper extremities and trunk including dorsum of hands, finger tips and the pinnae of both ears. Most striking were the presence of multiple deep ulcers covered with a blackish eschar and in some areas yellow slough eroding the subcutaneous tissue with ragged margins. These ulcers were distributed symmetrically over the thighs, lower legs and gluteal region. Slit-skin smear examination revealed a bacterial index (BI) of 6+ with globi from earlobes, ulcers 3+, eyebrows 3+ and normal skin 2+ and morphologically showed mainly solid (20-30%), fragmented (60-70%) and granular (5-10%) acid-fast bacilli. Biopsy from the ulcer margin revealed an ulcerated epidermis and dermis. The dermis had infiltrate of foamy macrophages, and evidence of ischemic necrotizing vasculitis, with fibrinoid necrosis and new vessel formation. There was presence of clumps of acid-fast bacilli (AFB) within macrophages, periadnexally, perivascularly, and also within endothelial cells. These clinical and histopathological features helped us to arrive at the diagnosis of Lucio phenomenon in an untreated case of Lucio leprosy which is rarely reported from areas other than Mexico.

[Mycobacterium shinshuense and Mycobacterium leprae infections: usefulness of genetical examinations].

Although Mycobacterium shinshuense and M. leprae infections are relatively rare in the fields of dermatology, an early diagnosis is one of the important prognostic factors of these infections. Applications of the genetical examinations such as PCR and 16S rDNA sequencing are helpful in early diagnosis with culture nagative cases. Short target PCR tests are available to detect DNA of M. shinshuense or M. leprae from clinical specimens including formalin fixed-paraffin embedded samples. A partial 16s rDNA sequencing is functional with enough intact bacterial DNA. A similarity search based on the partial 16S rDNA sequences using RIDOM database is an easy and powerful tool to estimate the species of mycobacteria, however, it is not enough for the identification in some cases. For instance, a clinical isolate of M. shinshuense is clearly discriminated from M. leprae (92.75% sequence identity), however, difficult to be identified from M. marinum and M. ulcerans (99.77% sequence identity). The phylogenetic tree based on 16S rDNA sequences is illustrating that both M. leprae (closely related to M. haemophilum) and M. shinshuense (closely related to M. marinum and M. ulcerans, and also M. tuberculosis) are relatively related species and distantly related to rapidly growing species among 30 species of pathogenic mycobacteria which have been isolated in Japan.

Use of the immunodominant 18-kiloDalton small heat shock protein as a serological marker for exposure to Mycobacterium ulcerans.

While it is well established that proximity to wetlands is a risk factor for contracting Buruli ulcer, it is not clear what proportion of a population living in an area where the etiologic agent, Mycobacterium ulcerans, is endemic is actually exposed to this disease. Immunological cross-reactivity among mycobacterial species complicates the development of a specific serological test. Among immunodominant proteins recognized by a panel of anti-M. ulcerans monoclonal antibodies, the M. ulcerans homologue of the M. leprae 18-kDa small heat shock protein (shsp) was identified. Since this shsp has no homologues in M. bovis and M. tuberculosis, we evaluated its use as a target antigen for a serological test. Anti-18-kDa shsp antibodies were frequently found in the sera of Buruli ulcer patients and of healthy household contacts but rarely found in controls from regions where the infection is not endemic. The results indicate that only a small proportion of M. ulcerans-infected individuals contract the clinical disease.

Mycobacterium ulcerans ulcers: a proposed surgical management algorithm.

Mycobacterium ulcerans (MU) is the third common mycobacterial infection after tuberculosis and leprosy. In endemic areas, MU ulcers should be considered in the differential diagnosis of any unusual or nonhealing lesion or ulcer. Diagnosis and treatment should be instigated promptly. Delay may lead to disfiguring or disabling scars. Surgical management, therefore, should aim towards early excision, with clear margins of the ulcer. We present 4 consecutive patients treated by our department within a 6-month period for MU ulcers. The presentation, diagnosis and surgical management are described. Based on our experience and after reviewing the literature, we have developed a surgical algorithm for the management of MU ulcers.

Immunogenicity of Mycobacterium ulcerans Hsp65 and protective efficacy of a Mycobacterium leprae Hsp65-based DNA vaccine against Buruli ulcer.

Buruli ulcer, a disease caused by Mycobacterium ulcerans, is emerging as an increasingly important cause of morbidity throughout the world, for which surgery is the only efficient treatment to date. The aim of this work was to identify potential vaccine candidates in an experimental model of mouse infection. In BALB/c mice infected with M. ulcerans subcutaneously, Hsp65 appeared to be an immunodominant antigen eliciting both humoral and cellular responses. However, vaccination of mice with a DNA vector encoding Mycobacterium leprae Hsp65 only poorly limited the progression of M. ulcerans infection. In contrast, a substantial degree of protection was conferred by subcutaneous vaccination with BCG, suggesting that BCG antigens that are conserved in M. ulcerans, such as TB10.4, the 19 kDa antigen, PstS3 and Hsp70, may be interesting to consider as subunit vaccines in future prospects.

Nerve damage in Mycobacterium ulcerans-infected mice: probable cause of painlessness in buruli ulcer.

Buruli ulcer is an emerging chronic painless skin disease found in the tropics and caused by Mycobacterium ulcerans; however, it remains unknown why the large and deep ulcers associated with this disease remain painless. To answer this question, we examined the pathology of BALB/c mice inoculated in the footpads with M. ulcerans African strain 97-107. On days 54 to 70 after inoculation, extensive dermal ulcers, subcutaneous edema, and numerous acid-fast bacilli were noted at the inoculate region. Nerve invasion occurred in the perineurium and extended to the endoneurium, and some nerve bundles were swollen and massively invaded by acid-fast bacilli. However, Schwann cell invasion, a characteristic of leprosy, was not observed. Vacuolar degeneration of myelin-forming Schwann cells was noted in some nerves which may be induced by mycolactone, a toxic lipid produced by M. ulcerans. Polymerase chain reaction analysis of microdissected nerve tissue sections showed positive amplification of M. ulcerans-specific genomic sequences but not of Mycobacterium leprae-specific sequences. Behavioral tests showed decrease of pain until edematous stage, but markedly ulcerated animals showed ordinary response against stimulation. Our study suggests that the painlessness of the disease may be partly due to intraneural invasion of bacilli. Further studies of nerve invasion in clinical samples are urgently needed.