Hotspots, Households and Hospitals: Enhanced Drug-resistant Tuberculosis Case Finding in Namibia

Poor case management, pharmacokinetic variability and on-going transmission have fostered the drug-resistant tuberculosis (DR-TB) epidemic leading to a global estimated number of \>500,000 new multidrug resistant (MDR) TB cases per year, of which roughly 10% are extensively drug resistant (XDR). Namibia is a high TB burden country with an incidence rate of 446/100,000 in 2016; about 11,000 new cases per year. 3.9% of new cases and 8.7% of previously treated cases have MDR-TB. Whole genome sequencing (WGS) has recently been applied to interrogate the complete genetic code of Mycobacterium tuberculosis (Mtb) strains. WGS can be used to infer relationships between identified strains as well as determine genomic variations involved in resistance development. The specific aims of the H3TB study are to: (i) characterise the DR-TB epidemic, in terms of clinical, epidemiological, geospatial, social network and laboratory data, to identify transmission hotspots in three regions of Namibia, (ii) evaluate the feasibility of targeted case finding intervention strategies to improve DR-TB control in highly affected populations and (iii) develop a transmission model to investigate the potential impact of the case finding intervention strategies on DR-TB incidence in Namibia. A prospective surveillance study started in January 2020, which includes all DR-TB cases in Namibia, and which will nest H3TB. Data collection tools and other study implementation tools have been designed and implemented. The study team is working in close collaboration with the National Institute of Pathology, where all DR-TB cases from the country are registered, to ensure all possible cases are captured. This is important for the identification of transmission hotspots. After HREC and MOHSS approval, individuals with GeneXpert® MTB/RIF rifampicin-resistant samples and a positive Mtb culture from three regions in Namibia will be included in a transmission hotspot identification study. Preliminary data have shown that DR-TB clusters exist in these regions. Clinical, epidemiological, geospatial, social network and laboratory data (GeneXpert® MTB/RIF, culture, drug sensitivity tests) will be collected. WGS capacity has been established at the UNAM research laboratory, where WGS will be performed on the samples of H3TB participants; results will be validated at the Research Center Borstel in Germany. These study results in conjunction with a systematic review and meta-analysis will inform the design of case finding interventions which will be evaluated through a mixed-methods feasibility study conducted at high transmission areas (hotspots, households and hospitals). Data from these studies and the TB programme will be used to develop the model which will include a health economics component. The study will strengthen DR-TB diagnosis, surveillance and control, inform DR-TB case finding policy in Namibia and regionally, inform resource allocation by identifying high transmission areas and create preliminary data to design a large scale DR-TB case finding intervention.