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Conclusions and Recommendations
WGS analysis uncovered the presence of diversified Mtb genotypes circulating in the Tigray Region with the highest proportion of L4. The high proportion of MDR-TB among new and previously treated patients and the association of L4 with drug-resistance is very alarming, which calls for an urgent need for locally adapted intervention. The high proportion of MDR-TB among newly diagnosed cases and the high level of RTI indicate an ongoing transmission, which suggests the need for an enhanced TB control program performance to interrupt transmission. The increased proportion of MDR-TB among previously treated cases indicates a need for better patient management to help prevent the evolution of drug resistance.
The study highlighted the usefulness of mutations at rpoB, katG, embB, rpsL, pncA, ethA, gyrA and rrs genes as a molecular marker for the rapid detection of resistance to RIF, INH, ETB, SM, PZA, ETH, FLQs and injectable 2nd-line anti-TB drugs, respectively. Hence, rapid detection and treatment of DR-TB can significantly improve the TB control program to halt transmission. WGS analysis showed numerous mutations that cause resistance to all 1st-and 2nd-line anti-TB drugs that are not included in the WHO and nationally recommended molecular assays. A significant proportion of disputed rpoB mutations were reported.
Overall, the findings underlined the importance of urgently strengthening the regional TB control program to detect and provide appropriate early treatment and follow-up for TB cases. There should be an optimal implementation of the five WHO-recommended priority actions to manage DR-TB to reduce the current high MDR-TB burden in the study region. Additionally, our findings suggest the need for conducting periodic surveillance of drug-resistance conferring mutations, early diagnosis and treatment of TB. Scale-up of rapid testing and detection of MDR/RR-TB cases in the region is crucial. Besides, given the limitations of the currently recommended molecular techniques (LPA) for detecting drug resistance, the NTCP should consider establishing WGS at regional levelsso that 1st- and 2nd-line DR mutations can periodically be monitored to prevent and control the transmission of DR-TB in the community.
Future works
Our study indicates a high proportion of MDR-TB among new cases, which shows the active transmission of DR-TB in the community. This suggests the need for further study on household contacts to assess the transmission dynamics of DR-TB in the community.Understanding the drug
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susceptibility patterns and associated factors of Mtb among extrapulmonary patients is an area for future studies. This has not yet been done and necessitates future work in this study area to have full information on DR-TB's magnitude in the study area.
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