Nineteen cases of Buruli ulcer diagnosed in Japan from 1980 to 2010

Abstract

The etiology, clinical manifestations, and treatment of 19 sporadic cases of Buruli ulcer (BU) in Japan are described. The cases originated in different regions of Honshu Island, with no evidence of patient contact with an aquatic environment. The majority (73.7%) of cases occurred in females, with an average age of 39.1 years for females and 56.8 years for males. All patients developed ulcers on exposed areas of the skin (e.g., face, extremities). Most ulcers were <5 cm in diameter (category I), except in one severe progressive case (category II). Pain was absent in 10 of the 19 cases. Fourteen ulcers were surgically excised, and nine patients needed skin grafting. All cases were treated with various antibiotic regimens, with no reported recurrences as of March 2011. Mycobacterium ulcerans-specific IS2404 was detected in all cases. Ten isolates had identical 16S rRNA gene sequences, which were similar to those of M. ulcerans. However, the rpoB gene showed a closer resemblance to Mycobacterium marinum or Mycobacterium pseudoshottsii. PCR identified pMUM001 in all isolates but failed to detect one marker. DNA-DNA hybridization misidentified all isolates as M. marinum. The drug susceptibility profile of the isolates also differed from that of M. ulcerans. Sequence analysis revealed "Mycobacterium ulcerans subsp. shinshuense" as the etiologic agent of BU in Japan. Clinical manifestations were comparable to those of M. ulcerans but differed as follows: (i) cases were not concentrated in a particular area; (ii) there was no suspected connection to an aquatic environment; (iii) drug susceptibility was different; and (iv) bacteriological features were different.

Fig. 1.

Distribution of BU patients in Japan. Most of the patients lived in a typical temperate region, and all lived on the island of Honshu. The two plus signs on the map indicate 38°N, 140°E, and 31°N, 130°60′E, placing most of the island in the temperate zone.

Fig. 2.

Ages and genders of BU patients in Japan.

Fig. 3.

(A) Buruli ulcer case 8: a category I ulcer on the right forearm. (B) Buruli ulcer case 3: a category II ulcer on the right elbow extensor surface.

Fig. 4.

Localization, pain, and surgical treatment of ulcer lesions by age and gender.

Fig. 5.

Phylogenetic analyses of M. ulcerans subsp. shinshuense based on the 16S rRNA gene (A), the hsp65 gene (B), the 16S–23S intergenic spacer region (C), and the rpoB gene (D).