Two tales: Worldwide distribution of Central Asian (CAS) versus ancestral East-African Indian (EAI) lineages of Mycobacterium tuberculosis underlines a remarkable cleavage for phylogeographical, epidemiological and demographical characteristics

The East African Indian (EAI) and Central Asian (CAS) lineages of Mycobacterium tuberculosis complex (MTBC) mainly infect tuberculosis (TB) patients in the eastern hemisphere which contains many of the 22 high TB burden countries including China and India. We investigated if phylogeographical, epidemiological and demographical characteristics for these 2 lineages differed in SITVIT2 database. Genotyping results and associated data (age, sex, HIV serology, drug resistance) on EAI and CAS lineages (n = 10,974 strains) were extracted. Phylogenetic and Bayesian, and other statistical analyses were used to compare isolates. The male/female sex ratio was 907/433 (2.09) for the EAI group vs. 881/544 (1.62) for CAS (p-value<0.002). The proportion of younger patients aged 0-20 yrs. with CAS lineage was significantly higher than for EAI lineage (18.07% vs. 10.85%, p-value<0.0001). The proportion of multidrug resistant and extensively drug resistant TB among CAS group (30.63% and 1.03%, respectively) was significantly higher than in the EAI group (12.14% and 0.29%, respectively; p-value<0.0001). Lastly, the proportion of HIV+ patients was 20.34% among the EAI group vs. 3.46% in the CAS group (p-value<0.0001). This remarkable split observed between various parameters for these 2 lineages was further corroborated by their geographic distribution profile (EAI being predominantly found in Eastern-Coast of Africa, South-India and Southeast Asia, while CAS was predominantly found in Afghanistan, Pakistan, North India, Nepal, Middle-east, Libya, Sudan, Ethiopia, Kenya and Tanzania). Some geo-specificities were highlighted. This study demonstrated a remarkable cleavage for aforementioned characteristics of EAI and CAS lineages, showing a North-South divide along the tropic of cancer in Eastern hemisphere-mainly in Asia, and partly prolonged along the horn of Africa. Such studies would be helpful to better comprehend prevailing TB epidemic in context of its historical spread and evolutionary features, and provide clues to better treatment and patient-care in countries and regions concerned by these lineages.

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S1 Fig. MST based on 12-loci MIRU-VNTRs of CAS lineage strains, according to country of origin of patients.
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S2 Fig. MST based on 12-loci MIRU-VNTRs of EAI lineage strains, according to country of origin of patients.
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S3 Fig. Neighbor joining tree based on 338 CAS lineage strains containing information on both spoligotyping patterns and 12-loci MIRU having a 12-MIT number. Each leaf represents a SIT/12-MIT couple.
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S4 Fig. Neighbor joining tree based on 513 EAI lineage strains containing information on both spoligotyping patterns and 12-loci MIRU having a 12-MIT number. Each leaf represents a SIT/12-MIT couple.
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S5 Fig. Main genotypes of CAS and EAI lineage strains with information on spoligotypes (SIT), 12 and 15-loci MIRU-VNTRs, as well as mean age, male/female sex ratio, and HIV+/HIV- status ratio of patie
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S6 Fig. Spoligoforest tree on CAS dataset drawn using by SpolTools software (available through http://spoltools.emi.unsw.edu.au/; [21–22], and shown as a Hierarchical Layout.
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S7 Fig. Spoligoforest tree on EAI dataset drawn using SpolTools software (available through http://spoltools.emi.unsw.edu.au/; [21–22], and shown as a Hierarchical Layout.
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S8 Fig. Maps representing potential geo-specificities of SITs 22, 25, 292 and 1340.
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S9 Fig. PCA based on CAS lineage strains showing distribution of CAS sublineages in function of spoligotyping patterns.
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S10 Fig. PCA based on CAS lineage strains showing country of origin of patients in function of spoligotyping patterns.
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S11 Fig. PCA based on EAI lineage strains showing distribution of EAI sublineages in function of spoligotyping patterns.
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S12 Fig. PCA based on EAI lineage strains showing country of origin of patients in function of spoligotyping patterns.
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S13 Fig. Distribution (percentage) of drug resistance information for CAS and EAI lineages in function of year of isolation.
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S1 Table. Global dataset used in this study for the CAS isolates.
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S2 Table. Global dataset used in this study for the EAI isolates.
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S3 Table. Distribution of age-groups of patients in function of lineages and UN subregions.
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How to cite
Couvin David, Reynaud Yann, Rastogi Nalin (2019). Two tales: Worldwide distribution of Central Asian (CAS) versus ancestral East-African Indian (EAI) lineages of Mycobacterium tuberculosis underlines a remarkable cleavage for phylogeographical, epidemiological and demographical characteristics. Plos One. 14 (7). e0219706 (20p.). https://doi.org/10.1371/journal.pone.0219706, https://archimer.ifremer.fr/doc/00771/88279/

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