Title : Active tuberculosis in household contacts: Whole genome sequencing based genomic diversity, transmission dynamics and drug resistance pattern analysis
Abstract:
Background:
MTBC genotyping improved the understanding of transmission dynamics and is used to support or refute transmission assumptions between epidemiologically linked cases. This study aimed to investigate genomic diversity, transmission dynamics and drug resistance mutation in epidemiologically linked pulmonary TB cases and their household contact of central Ethiopia.
Methods:
The study was conducted from January 2023 to December 2023 at randomly selected public health facilities in central part of Ethiopia. A total of 50 genomes form Pulmonary TB case and their HHC were considered for WGS analysis using the MTBSeq pipeline and Ridom SeqSphere software for drug resistance and genotypic analysis(SNP distance cut-of 12 ) .
Result:
Through the analysis of successful WGS data from 48 isolates, we discovered that most of the isolates were part of lineages L4 (Euro-American, 33/48; 68.75%) and L3 (Delhi-CAS, 12/48; 25.0%), with the Euro-American (L.4.2.2) being the most prevalent sub-lineage (16/48; 33.33%). Tuberculosis caused by M. bovis represented 4.17% (2/48). Among the 48 isolates approximately one-fifth of isolates were found to be at least MDR?TB (10/48; 20.83%). The transmission analysis revealed 4 related events resulting in an overall clustering rate of 17.02% (8 out of 47) .Almost 75% (3 out of 4) of the clustered strains came from the same household, while 25% were from non-index household contacts. Out of the 10 index-HHC pairs who had valid WGS analysis, three share the exactly matched genome. We have also identified previously unreported mutations linked to resistance Amikacin, and Ethioniamid.
Conclusion:
Individuals residing in areas with a high burden of tuberculosis are at risk of contracting the disease from sources beyond their homes. Genomic sequencing gives insights into the epidemiological patterns of TB, leading to better strategies for target groups at high risk of unnoted TB transmission.
Key word:
Household contact, Index case, WGS.