Antibiotic resistance of Mycobacterium tuberculosis complex in Africa : a systematic review of current reports of molecular epidemiology, mechanisms and diagnostics

Abstract

BACKGROUND : Tuberculosis (TB) remains a main global public health problem. However, a systematic review of TB resistance epidemiology in Africa is wanting. METHODS : A comprehensive systematic search of PubMed, Web of Science and ScienceDirect for English research articles reporting on the molecular epidemiology of Mycobacterium tuberculosis complex resistance in Africa from January 2007 to December 2018 was undertaken. RESULTS AND CONCLUSION : Qualitative and quantitative synthesis were, respectively, undertaken with 232 and 186 included articles, representing 32 countries. TB monoresistance rate was highest for isoniazid (59%) and rifampicin (27%), particularly in Zimbabwe (100%), Swaziland (100%), and Sudan (67.9%) whilst multidrug resistance (MDR) rate was substantial in Zimbabwe (100%), Sudan (34.6%), Ivory Coast (24.5%) and Ethiopia (23.9%). Resistance-conferring mutations were commonly found in katG (n = 3694), rpoB (n = 3591), rrs (n = 1272), inhA (n = 1065), pncA (n = 1063) and embB (n = 705) in almost all included countries: S315G/I/N/R/T, V473D/F/G/I, Q471H/Q/R/Y, S303C/L etc. in katG; S531A/F/S/G, H526A/C/D/G, D516A/E/G etc. in rpoB; A1401G, A513C etc. in rrs; -15C→T, -17G→A/T, -16A→G etc. in inhA; Ins456C, Ins 172 G, L172P, C14R, Ins515G etc. in pncA. Commonest lineages and families such as T (n = 8139), LAM (n = 5243), Beijing (n = 5471), Cameroon (n = 3315), CAS (n = 2021), H (n = 1773) etc., with the exception of T, were not fairly distributed; Beijing, Cameroon and CAS were prevalent in South Africa (n = 4964), Ghana (n = 2306), and Ethiopia/Tanzania (n = 799/635), respectively. Resistance mutations were not lineage-specific and sputum (96.2%) were mainly used for diagnosing TB resistance using the LPA (38.5%), GeneXpert (17.2%), whole-genome sequencing (12.3%) and PCR/amplicon sequencing (9%/23%). Intercountry spread of strains was limited while intra-country dissemination was common. TB resistance and its diagnosis remain a major threat in Africa, necessitating urgent action to contain this global menace.