Mycobacterium tuberculosis Isolates of Beijing Genotype in Thailand

To the Editor: Anh and colleagues recently reported that in new tuberculosis (TB) cases from Vietnam, Mycobacterium tuberculosis isolates of the Beijing genotype are associated with younger age and, in isolates from Ho Chi Minh City, with resistance against isoniazid and streptomycin (1). However, occurrence of Beijing genotype M. tuberculosis strains may be different in other Southeast Asian countries such as Thailand.

From May 1999 to June 2000, we obtained 244 M. tuberculosis isolates from TB patients at Ramathibodi Hospital, Bangkok, Thailand (the hospital treats approximately 625 TB patients annually). The isolates have been prospectively analyzed by DNA-fingerprinting with the spoligotyping method (2). Drug-resistance testing and recording of patients´ data (sex, age, geographic origin) were completed for 204 of 244 patients. The 204 patients originated from all six regions of Thailand, although the central region (comprising the Bangkok area) and the northeast region predominated (59% and 23.5%, respectively). Altogether 111 male and 93 female patients with a median age of 34 years (1 to 89 years) were included. Status of BCG vaccination or HIV infection were not assessed.

The Beijing genotype was found in 90 (44.1%) of the 204 isolates analyzed in detail, without significant differences regarding the respective patients´ geographic origin or sex. Thus in Thailand, the frequency of the Beijing type is somewhere between the frequency in Vietnam (53%) (1) and in peninsular Malaysia (estimated at 24%) (3). Using the same age groups as Anh and colleagues, we did not find an association of Beijing genotype with young age (p = 0.41; chi-square test for trend). Although Beijing type isolates were more frequent among patients <25 years (18 [56%] of 32) than among those >25 years (69 [43%] of 161), this was not significant (p = 0.13). This association remained not significant, if only isolates from the central or the northeast region were analyzed.

Of 204 isolates, 62 (30%) showed resistance to >1 of 4 drugs tested (isoniazid, 8.8%; rifampicin, 6.4%; streptomycin, 19.6%; ethambutol, 4.9%). However, overall drug resistance, resistance to single drugs, and multidrug resistance were not associated with the Beijing genotype. The frequency of resistance was similar in distribution but overall lower than reported for the Ho Chi Minh City isolates (isoniazid, 24%; rifampicin, 2%; streptomycin, 31%; ethambutol, 2%) (1).

In both studies, the highest percentage of drug resistance was found for streptomycin. In our sample, this was not associated with particular spoligotypes or with geographic origin of the patient. Furthermore, streptomycin-resistant isolates were not more frequent in older age groups, although there was a nonsignificant trend (p = 0.12; chi-square_trend). Streptomycin is still used for standard quadritherapy in Thailand, and occurrence of resistant strains can reflect selection or transmission recently or in the past. This differs from occurrence of streptomycin resistance in countries where streptomycin is no longer used in standard therapy (4).

In the original description of the Beijing family of strains in 1995, Beijing genotype isolates were found in 7 (37%) of 19 Thai isolates (5). In a subsequent IS6110 restriction fragment length polymorphism analysis, 80 (38%) of 211 isolates from central Thailand collected in 1994 to 1995 belonged to the Beijing family (6). Whether 90 (44%) of 204 among our recent isolates reflect a reliable increase in Beijing type transmission over the last 5 years, is difficult to state. However, the fact that no correlation of Beijing type with (young) age of the patient was observed in the previous analysis (6) supports the notion that increasing incidence of the Beijing strain in Thai cases is not due to recent transmission.

The M. tuberculosis population appears to be considerably more heterogeneous in Thailand than in the large urban areas of Vietnam. In our study, the three most common spoligopatterns besides Beijing, S156, S153, and S22 (according to the nomenclature of Soini et al. [7]), together comprised 20% of 244 isolates. However, the second most frequent spoligopattern, the "Vietnam genotype" (S10 according to Soini), reportedly shared by 27% of the Vietnamese isolates, was not found in our sample of Thai isolates. Only 20 different spoligopatterns were found among 499 isolates in the Vietnam study, compared to 60 among 244 isolates in our study.

Although the Beijing genotype of M. tuberculosis has been recognized in settings of emerging drug resistance around the world, the situation in Southeast Asian countries with a high frequency of Beijing type isolates appears to be nonuniform.

Wolfgang M. Prodinger,* Porntip Bunyaratvej,† Roongnapa Prachaktam,† and Marion Pavlic*
^*University of Innsbruck, Innsbruck, Austria; and †Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand

References

1. Anh DD, Borgdorff MW, Van LN, Lan NTN, van Gorkom T, Kremer K, et al. Mycobacterium tuberculosis genotype Beijing emerging in Vietnam. Emerg Infect Dis 2000;6:302-5.
2. Dale JW, Nor RM, Ramayah S, Tang TH, Zainuddin ZF. Molecular epidemiology of tuberculosis in Malaysia. J Clin Microbiol 1999;37:1265-8.
3. Kamerbeek J, Schouls L, Kolk A, van Agterveld M, van Soolingen D, Kuijper S, et al. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol 1997;35:907-14.
4. Niemann S, Richter E, Rusch-Gerdes S, Thielen H, Heykes-Uden H. Outbreak of rifampin and streptomycin-resistant tuberculosis among homeless in Germany. Int J Tuberc Lung Dis 1999;3:1146-7.
5. van Soolingen D, Qian L, de Haas PE, Douglas JT, Traore H, Portaels F, et al. Predominance of a single genotype of Mycobacterium tuberculosis in countries of east Asia. J Clin Microbiol 1995;33:3234-8.
6. Palittapongarnpim P, Luangsook P, Tansuphaswadikul S, Chuchottaworn C, Prachaktam R, Sathapatayavongs B. Restriction fragment length polymorphism study of Mycobacterium tuberculosis in Thailand using IS6110 as probe. Int J Tuberc Lung Dis 1997;1:370-6.
7. Soini H, Pan X, Amin A, Graviss EA, Siddiqui A, Musser JM. Characterization of Mycobacterium tuberculosis isolates from patients in Houston, Texas, by spoligotyping. J Clin Microbiol 2000;38:669-76.

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