SNP genotypes of Mycobacterium leprae isolates in Thailand and their combination with rpoT and TTC genotyping for analysis of leprosy distribution and transmission.

Based on the discovery of three single nucleotide polymorphisms (SNPs) in Mycobacterium leprae, it has been previously reported that there are four major SNP types associated with different geographic regions around the world. Another typing system for global differentiation of M. leprae is the analysis of the variable number of short tandem repeats within the rpoT gene. To expand the analysis of geographic distribution of M. leprae, classified by SNP and rpoT gene polymorphisms, we studied 85 clinical isolates from Thai patients and compared the findings with those reported from Asian isolates. SNP genotyping by PCR amplification and sequencing revealed that all strains like those in Myanmar were SNP type 1 and 3, with the former being predominant, while in Japan, Korea, and Indonesia, the SNP type 3 was found to be more frequent. The pattern of M. leprae distribution in Thailand and Myanmar is quite similar, except that SNP type 2 was not found in Thailand. In addition, the 3-copy hexamer genotype in the rpoT gene is shared among the isolates from these two neighboring countries. On the basis of these two markers, we postulate that M. leprae in leprosy patients from Myanmar and Thailand has a common historical origin. Further differentiation among Thai isolates was possible by assessing copy numbers of the TTC sequence, a more polymorphic microsatellite locus.

TLR2 Arg677rp polymorphism in leprosy: revisited

We investigated the Toll-like receptor 2 (TLR2) Arg677Trp polymorphism, associated with lepromatous leprosy in the Korean population and shown to abrogaet TLR2-mediated signalling in response to mycobacterial ligands, in 286 Indian leprosy patients and 183 ethnically matched controls. The case-control comparison also involved investigation of possible variation(s) in the promoter region of the TLR2 gene. Genotyping results after direct PCR sequencing showed that the TLR2 Arg677Trp polymorphism associated with lepromatous leprosy in the Korean population is not a true polymorphism of the TLR2 gene and has resulted from the variation present in the 93% homologous duplicated region of TLR2 exon 3 present approximately 23 kb upstream

Typing of clinical isolates of Mycobacterium leprae and their distribution in Korea.

Although there is no genetic diversity in isolates of Mycobacterium leprae, the variance of tandem repeats in the rpoT gene was recently demonstrated. We have typed clinical isolates of M. leprae in Korea using difference of the tandem repeats in the rpoT gene. Among 69 patients, 65 Korean isolates (94.2%) demonstrated four copies of the 6 bp tandem repeat (GACATC) in the rpoT gene, and incidences of three copies were found in only two Koreans and two foreigners (2.9%, respectively).

Progression of eye disease in "cured" leprosy patients: implications for understanding the pathophysiology of ocular disease and for addressing eyecare needs.

BACKGROUND: Ocular damage in leprosy is due either to nerve damage or infiltration by mycobacteria. There is currently little information about the magnitude and nature of incident ocular pathology in cured leprosy patients. This information would increase our understanding of the pathophysiology of ocular involvement in leprosy and help in developing programmes to address the eyecare needs of leprosy patients who have been released from treatment. The cumulative incidence of leprosy related ocular pathology and cataract was measured during an 11 year follow up period in cured leprosy patients released from treatment in Korea. METHODS: In 1988 standardised eye examinations were performed on 501 patients in eight resettlement villages in central South Korea. In May 1999 standardised eye examinations were repeated in this population. RESULTS: Among the patients in whom there was no sight threatening leprosy related ocular disease (lagophthalmos, posterior synechia, or keratitis) in 1988, 14.7% developed one or more of these conditions. Overall, among those with no vision reducing cataract in 1988, 26.4% had developed a vision reducing lens opacity in at least one eye. Among patients examined in both 1988 and 1999, 14.3% developed visual impairment and 5.7% developed blindness. CONCLUSION: This study demonstrates that leprosy related ocular pathology progresses in some patients even after they are cured mycobiologically. The progressive leprosy related lesions are the result of chronic nerve damage; ocular lesions due to infiltration by Mycobacterium leprae did not develop. Based on the factors found to be associated with development of the most visually significant findings (posterior synechia, keratitis, and cataract) certain patients should be targeted at discharge for active follow up eye care. We suggest that patients with lagophthalmos (even in gentle closure), trichiasis, small pupils, and posterior synechiae should be screened regularly for the development of lagophthalmos in forced closure, keratitis, and cataract.

Prevalence of IgM antibodies to phenolic glycolipid I among household contacts and controls in Korea and the Philippines.

Phenolic glycolipid I (PGL-I) is a Mycobacterium leprae-specific antigen and the antibodies to the antigen may suggest an M. leprae infection. To compare the M. leprae transmission among the populations, we compared the prevalence of anti-PGL-I IgM antibodies among household contacts and controls between Korea and the Philippines. In Korea (prevalence of leprosy--0.04: 1000), the prevalence of anti-PGL-I antibodies were 4.8% among controls and 8.0% among contacts, respectively. On the other hand, the seroprevalence rate was 10.8% among controls and 13.4% among contacts in the Philippines (prevalence of leprosy--0.70: 1000). Interestingly, a marked difference was noted in the prevalance of anti-PGL-I antibodies among children between the countries; 10-14% among children under 10 years old and 15-18% among those aged between 10 and 19 in the Philippines compared to 0% and 2.9-6.4% in Korea, respectively. This study, therefore suggests that a high prevalance of anti-PGL-I IgM antibodies among children may indicate an active transmission of M. leprae, resulting in a higher incidence of leprosy in the population.

Comparison of the old and new W.H.O. leprosy disability grading scheme for ocular disabilities.

We compared the old (1970) and new (1988) World Health Organization schemes for classifying the ocular disabilities in leprosy patients. 509 leprosy patients from eight resettlement villages in central South Korea were examined and graded by eye according to both of the schemes. A more liberal definition of severely disabled in 1988 resulted in a 119% increase in eyes graded as severely disabled in this population. 59 eyes were graded as severely disabled by the old scheme and 129 eyes were so graded according to the new scheme. Keratitis, one of three measures of moderate disability in the old scheme, was replaced by corneal anaesthesia in the new scheme, but this change did not make a substantial difference in the number of patients in the moderately impaired category. In the absence of longitudinal studies documenting the significance of keratitis, it is unclear whether the change in an improvement. The new disability scheme improved upon the old by removing the criteria for mild impairment.