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.
Figure S1: Frequency of M. tuberculosis Lineages/sub-lineages in Africa, January 2007-December 2018: Frequency of Indo-oceanic lineage/sub-lineages (A); Beijing sublineage (B); CAS-sublineage (C), Euro-American lineage/sub-lineages (D); M. africanum West Africa I & II (E); M. tuberculosis Eth lineage 7 and sub-lineages (F); and proportion of each M. tuberculosis lineage in Africa (G).
Table S1: Distribution of M. tuberculosis complex strains, specimen source/s, genotyping method/s, molecular anti-TB drug resistance rate and resistance mechanisms in M. tb across African countries, January 2007 to December 2018
Table S2: Resistance mechanisms, molecular diagnosis method/s used, frequency and proportion of gene mutation per total resistant M. tuberculosis complex isolates across African countries, January 2007- December 2018
Table S3: Molecular antibiotics resistance rates and resistance mechanisms in M. tuberculosis complex across African countries, January 2007-December 2018.
Table S4: Frequency of gene mutation(s) and specific amino acid/nucleotide changes conferring antitubercular drug resistances across African countries January 2007- December 2018
Table S5: Distribution of specimen source/s, phenotypic DST method/s used, total number of isolates, and phenotypic antibiotics monoresistance rate, MDR and XDR rate of M. tb complex across African countries, January 2007- December 2018
Table S6: Distribution of genotypes/lineages/sub-lineages, frequency and patterns of antibiotics resistance-conferring mutations across African countries, January 2007- December 2018
Supplementary dataset 1: Metadata of M. tuberculosis isolates included in phylogenomic analyses.
Supplementary dataset 2: Country-by-country frequency of lineage and sub-lineage of M. tuberculosis in Africa: January 2007-December 2018