Abstract
This study aims to explore the MDR-TB spreading in an outbreak area of Thailand. A crossectional study is carried out to determine bacteria and host genetic factors relate to MDR-TB infection in patients and their contacts, epidemic process, and treatment outcomes. The sample population including MDR-TB patients who were registered at Makarak hospital between 2014 to 2019. A total of 205 MDR-TB isolates were sequenced and a total of 352 MDR-TB contacts from 152 MDR-TB patients were enrolled in this study. A total of 205 MDR-TB isolates were sequenced, 88.8 % of these were MDR-TB cases, while the other 4.4 % and 6.8% were pre-XDR-TB and XDR-TB respectively. The result of whole genome sequencing and SNPs analysis showed 4 lineages(L) of the MDR-TB genotype in this study, including L1, L2, L3, and L4. L2 of Beijing strains (L2-Beijing) was the most common genotype and 77% of the L2-Beijing genotype belonged to the sub-lineage of Asia African3 (AAF3). When we considered the number of SNPs different among AAF3 genotype, found that 34.1 % of those were clonal. And found that, patient with DM is more likely to be in a group of clonal MDR-TB than without DM. Of 352 MDR-TB contacts, 71.3% were household contacts, 64.1% were working for the age group. There were 31.5% of contact had the comorbid disease, included DM, HT, and other disease were 8.8, 16.2, and 10.5% respectively. A latent tuberculosis infection (LTBI) among contacts of clonal and non-clonal MDR-TB were 27.8% and 30.2% respectively. However, there was no statistically significant difference between these 2 groups (p-value = 0.697). To identify host genetic factors associated with MDR-TB infection, GWAS was used to an identified specific genes associated with MDR-TB infection. We considered contact with IGRA positive as a case and contact with IGRA negative was control. The most common significant SNPs and genes were located on chromosome 6 and HLA gene, including HLA-DRA and HLA-DRB1 which had been reported in previous studies. Other significant SNPs were also found to be associated with TB infection, the SLC1A2 gene on chromosome 11. In summary, a high proportion and homogeneous gentic of AAF3 strain among MDR-TB patients may reflect the adaptation of the strain to spread more readily in thai population, and the increasing of this pathogenic strain may impact the tuberculosis control program. Early diagnosis and contact tracing will be essential to inhibit the spread of these strains. Furthermore, it will be important to ensure that future vaccines protect against these strains.
