Spoligotyping based genetic diversity of Mycobacterium tuberculosis in Ethiopia: a systematic review

Abstract

Background: Understanding the types of strains and lineages of Mycobacterium tuberculosis (M. tuberculosis) circulating in a country is of paramount importance for tuberculosis (TB) control program of that country. The main aim of this study was to review and compile the results of studies conducted on strains and lineages of M. tuberculosis in Ethiopia.

Methods: A systematic search and review of articles published on M. tuberculosis strains and lineages in Ethiopia were made. PubMed and Google Scholar databases were considered for the search while the keywords used were M. tuberculosis, molecular epidemiology, molecular typing spoligotyping and Ethiopia.

Result: Twenty-one studies were considered in this review and a total of 3071 M. tuberculosis isolates and 3067 strains were included. These studies used spoligotyping and identified five lineages including Indo-Ocean, East Asian/Beijing, East African-Indian, Euro-American and Ethiopian in a proportion of 7.1%, 0.2%, 23.0%, 64.8%, and 4.1%, respectively. Thus, Euro-American was the most frequently (64.8%) occurring Lineage while East Asian was the least (0.2%) frequently occurring Lineage in the country. Surprisingly, the Ethiopian Lineage seemed to be localized to northeastern Ethiopia. In addition, the top five clades identified by this review were T, CAS, H, Manu and Ethiopian comprising of 48.0%, 23.0%, 11.0%, 6.0% and 4.1% of the strains, respectively. Furthermore, predominant shared types (spoligotype patterns) identified were SIT149, SIT53, SIT25, SIT37, and SIT21, each consisting of 420, 343, 266, 162 and 102 isolates, respectively, while, on the other hand, 15% of the strains were orphan.

Conclusion: According to the summary of the results of this review, diversified strains and lineages of M. tuberculosis were found in Ethiopia, and the frequencies of occurrence of these strains and lineages were variable in different regions of the country. This systematic review is registered in the PRISMA with the registration number of 42017059263.

Keywords: Diversity; Ethiopia; Genotyping; Molecular epidemiology; Mycobacterium tuberculosis.

Fig. 1

PRISMA flow diagram of study selection and literature search. A total of 21 studies involving 3067 clinical strains were identified for inclusion in the review. A total of 133 citations were identified from PubMed and Google Scholar databases. Of these, 30 studies were selected which used genotyping analysis by Spoligotyping after reviewing the title and abstracts. Additional screening was conducted in the full text and journal quality was considered and additionally, 9 studies were excluded because of repeated publication and data were not available

Fig. 2

Proportions of shared strains of M. tuberculosis reported from Ethiopia

Fig. 3

Distribution of M. tuberculosis lineages using spoligotyping across regions of Ethiopia. The lineages identified were: Lineage 1 (L-1) or Indo-Oceanic (IO), L-2 or East Asian (EA), L-3 or East African India (EAI) and L-4 or Euro-American (EUA), L-7 or Ethiopian and Unknown (U). The predominant lineages identified from almost all regions of the country were L-4. The Ethiopian L-7 was mainly identified from Amhara region and there was no data from Gambella region and very few strains (four) belongs to L-3 from Tigray region and one strain each belongs to L-4 from Dire Dawa city and Harari region. AA: Addis Ababa, AM: Amhara, AF: Afar, BG: Benishangul-Gumz, DD: Dire Dawa, HR: Harari, OR: Oromia, SNNPR: South Nation and Nationalities Peoples’, SM: Somali and TG: Tigray. Proportions of total lineages identified in Ethiopia namely; L-1 (7.1%), L-2 (0.2%), L-3 (23.0%), L-4 (64.8%) and L-7 (4.1%)

Fig. 4

Distribution of clades of M. tuberculosis identified in different regions of Ethiopia. Clade designations according to STVIT2 and TBinsight database: Beijing clade in East Asian lineage; CAS clade in East African-Indian (EAI) lineage; Haarlem (H) clade, Latin American-Mediterranean (LAM) clade, the ancestral “Manu” family, an ill-defined T clade and the IS6110-low-binding X clade in Euro American; ETH belongs to the newly identified Ethiopian lineage 7