The Emergence of Novel Spoligotypes of Highly Drug-Resistant Mycobacterium tuberculosis Isolates in Fujian, China

Abstract

Shufang Lin,1 Shuzhen Wei,1 Yong Zhao,1 Zhisong Dai,1 Jian Lin,1 Yu Pang2 1Fujian Provincial Key Laboratory of Zoonosis Research, Fujian Center for Disease Control and Prevention, Fuzhou, People’s Republic of China; 2Department of Bacteriology and Immunology, Beijing Key Laboratory for Drug-Resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People’s Republic of ChinaCorrespondence: Shuzhen Wei, Fujian Center for Disease Control and Prevention, No. 386, Chong’an Road, Jin’an District, Fuzhou, Fujian, 350012, People’s Republic of China, Tel/Fax [phone], Email [email protected] Yu Pang, Beijing Chest Hospital, Capital Medical University, No. 97, Machang, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel/Fax [phone], Email [email protected]: Here, we aimed to determine the population structure of Mycobacterium tuberculosis (MTB) genotypes in Fujian and explore risk factors associated with infection with the Beijing genotype. We also explored the association between Beijing genotype and drug resistance.Methods: Representative MTB isolates obtained during provincial-level routine anti-tuberculosis drug resistance surveillance conducted since 2013 in 11 Fujian counties were analyzed using McSpoligotyping. In vitro drug susceptibilities to anti-tuberculosis drugs were determined using the standard Löwenstein–Jensen proportion method.Results: Overall, 477 MTB isolates were included in the study, of which 245 isolates belonged to the Beijing genotype family and 232 possessed non-Beijing genotypes. Ultimately, a total of 204 spoligotypes were identified that included 58 spoligotype international types (SITs) from the SITVITWEB database and 146 novel spoligotypes. As compared to patients < 25 years of age (control group), elderly patients (≥ 65 years of age) were more likely to be infected with non-Beijing genotypes [aOR 18.69, 95% CI (5.80– 60.26)], with risk of infection with non-Beijing genotypes increasing with age [aOR 3.73, 95% CI (1.67– 8.30) for patients 45– 64 years of age]. Additionally, as compared to isolates with Beijing and other non-Beijing genotypes, significantly greater proportions of isolates with novel spoligotypes exhibited PTO- and PAS-resistance. Moreover, a markedly higher proportion of isolates with novel spoligotypes exhibited OFX-resistance as compared to isolates with other non-Beijing genotypes.Conclusion: Our data demonstrated that the Beijing genotype is the predominant MTB sublineage in Fujian and that the prevalence rate of infection with this MTB genotype decreases with advancing patient age. Notably, the prevalence rate of this genotype in Fujian TB patients is relatively lower than in other regions of China. In addition, the emergence of novel spoligotypes of highly drug-resistant MTB isolates highlights the urgent need for ongoing molecular genotyping surveillance in Fujian.Keywords: Mycobacterium tuberculosis, genotype, spoligotype, drug resistant

Keywords

• mycobacteriumtuberculosis
• genotype
• spoligotype
• drug resistant;