T-cell recognition of mycobacterial GroES peptides in Thai leprosy patients and contacts.

We report here the mapping of T-cell-stimulatory determinants of the GroES 10-kDa heat shock protein homologues from Mycobacterium leprae and Mycobacterium tuberculosis, which are known as major immunogens in mycobacterial infections. Peripheral blood mononuclear cells (PBMC) from treated tuberculoid leprosy or lepromatous leprosy patients and from healthy household or hospital staff contacts of the patients were cultured with 20 16-mer peptides covering the entire sequences of both M. leprae and M. tuberculosis GroES. The total number of recognized peptides was found to be the largest in family contacts, while responder frequencies to the individual tested peptides varied (5 to 80%) with specificity between the patient and contact groups. Proliferative responses to some peptides showed positive or negative associations of low statistical significance with DR and DQ alleles, though responses to most GroES peptides were genetically permissive. Notably, the sequence of the 25-40 peptide of M. leprae, but not that of M. tuberculosis, was more frequently stimulatory in tuberculoid leprosy patients than in either group of sensitized healthy contacts. This peptide bound to a number of HLA-DR molecules, of which HLA-DRB5*0101 had the strongest affinity. The epitope core binding to this allele was localized to the 29-to-37 sequence, and its key residue was localized to the M. leprae-specific glutamic acid at position 32. This epitope may be of interest for the development of a blood test- or skin test-based diagnostic reagent for tuberculoid leprosy, subject to further clinical evaluation in untreated patients.

A study on the effectiveness and safety of the WHO/MDT regimen in the northeast of Thailand; a prospective study, 1984-1996.

The aim of this prospective study was to determine the effectiveness and safety of the multidrug therapy as recommended by the World Health Organization (WHO/MDT) in 1982. One-hundred-eighty-eight newly diagnosed leprosy patients [130 paucibacillary (PB) and 58 multibacillary (MB) patients] from three provinces in northeastern Thailand were recruited into a study from April 1984 to March 1985. The study lasted until May 1996. The results showed that 182 patients finished their course of WHO/MDT, representing a treatment completion rate of 95%; 167 (122 PB and 45 MB) were released from surveillance (RFS); 82 PB patients were still available for follow up by the end of 1994 and 31 MB patients by May 1996. Two PB patients were diagnosed with a relapse, showing a relapse rate of 0.2 per 100 person-years at risk. After an average of 8 years of follow up, no MB relapses have been diagnosed. The proportion of patients with a WHO grade 2 disability among PB and MB patients increased from 4% and 8% at the start of treatment to 7% and 13% at last examination, respectively. It is concluded that the fixed-duration, 6-month WHO/MDT regimen for PB leprosy and the 24-month regimen for MB leprosy are effective, acceptable and safe, and that clinical activity, histopathological activity and/or a positive skin smear at release from treatment (RFT) have no bearing on the efficacy of the WHO/MDT regimens. The relapse rates are low and in accordance with most published data available to date. The importance of skin-smear services for a reliable classification (WHO PB/MB classification for control programs) is stressed.