Geospatial distribution of Mycobacterium tuberculosis genotypes in Africa

ObjectiveTo investigate the distribution of Mycobacterium tuberculosis genotypes across Africa.MethodsThe SITVIT2 global repository and PUBMED were searched for spoligotype and published genotype data respectively, of M. tuberculosis from Africa. M. tuberculosis lineages in Africa were described and compared across regions and with those from 7 European and 6 South-Asian countries. Further analysis of the major lineages and sub-lineages using Principal Component analysis (PCA) and hierarchical cluster analysis were done to describe clustering by geographical regions. Evolutionary relationships were assessed using phylogenetic tree analysis.ResultsA total of 14727 isolates from 35 African countries were included in the analysis and of these 13607 were assigned to one of 10 major lineages, whilst 1120 were unknown. There were differences in geographical distribution of major lineages and their sub-lineages with regional clustering. Southern African countries were grouped based on high prevalence of LAM11-ZWE strains; strains which have an origin in Portugal. The grouping of North African countries was due to the high percentage of LAM9 strains, which have an origin in the Eastern Mediterranean region. East African countries were grouped based on Central Asian (CAS) and East-African Indian (EAI) strain lineage possibly reflecting historic sea trade with Asia, while West African Countries were grouped based on Cameroon lineage of unknown origin. A high percentage of the Haarlem lineage isolates were observed in the Central African Republic, Guinea, Gambia and Tunisia, however, a mixed distribution prevented close clustering.ConclusionsThis study highlighted that the TB epidemic in Africa is driven by regional epidemics characterized by genetically distinct lineages of M. tuberculosis. M. tuberculosis in these regions may have been introduced from either Europe or Asia and has spread through pastoralism, mining and war. The vast array of genotypes and their associated phenotypes should be considered when designing future vaccines, diagnostics and anti-TB drugs.研究目的：探究非洲结核分枝杆菌（Mycobacterium tuberculosis）基因型的分布特征。 研究方法：分别检索SITVIT2全球数据库与PubMed文献库，获取非洲来源结核分枝杆菌的间隔区寡核苷酸分型（spoligotype）数据与已发表的基因型数据。对非洲的结核分枝杆菌谱系进行描述，并跨区域与7个欧洲国家、6个南亚国家的结核分枝杆菌谱系开展对比分析；进一步采用主成分分析（Principal Component Analysis, PCA）与层次聚类分析（hierarchical cluster analysis）对主要谱系及亚谱系进行分析，以阐明其地理区域聚集特征；同时采用系统发育树分析评估其进化关系。 研究结果：本研究共纳入35个非洲国家的14727株分离株，其中13607株被划分为10个主要谱系之一，剩余1120株无法确定谱系。主要谱系及其亚谱系的地理分布存在差异，且呈现区域聚集性：南非国家的聚集特征源于LAM11-ZWE菌株的高流行率，该菌株起源于葡萄牙；北非国家的聚集特征则与LAM9菌株的高占比相关，该菌株起源于东地中海区域；东非国家的聚集特征以中亚（Central Asian, CAS）与东非印度（East-African Indian, EAI）菌株谱系为主，这可能反映了其与亚洲的历史海上贸易往来；而西非国家的聚集特征则基于起源未知的喀麦隆谱系。在中非共和国、几内亚、冈比亚与突尼斯，可观察到高占比的哈勒姆（Haarlem）谱系分离株，但因分布混杂，未能形成明显的聚集特征。 研究结论：本研究表明，非洲的结核病流行由以基因多样性结核分枝杆菌谱系为特征的区域流行所驱动。该区域的结核分枝杆菌可能源自欧洲或亚洲，并通过畜牧业、采矿活动与战争传播扩散。在未来研发结核疫苗、诊断试剂与抗结核药物时，应考虑到丰富多样的基因型及其对应的表型特征。