<p>Figure displays a stacked graph showing the temporal distribution of human adapted MTBC ... more <p>Figure displays a stacked graph showing the temporal distribution of human adapted MTBC (left y-axis) and a linear graph showing the prevalence of <i>Mycobacterium tuberculosis</i> sensu stricto (MTBss) and <i>Mycobacterium africanum</i> (Maf) (right y-axis) over the entire 8-year study period.</p
<p>This figure shows the; (A) Sum and case notification rate of all TB cases from September... more <p>This figure shows the; (A) Sum and case notification rate of all TB cases from September 2012 to December 2014, (B) Sum and normalized distribution of MTBss cases, (C) Sum and normalized distribution of Maf. The total number of cases per year was used as the denominator for normalization. Sampling from TamM did not meet our criteria for being included in analyses for case notification rate and so was excluded in all columns of panel A. Likewise we also recorded no cases in 2012 as such TamM was excluded from 2012 analysis (panel B and C). This figure was created using the ArcMap program in ArcGIS v. 10.0. Abbreviations: MTBss, <i>Mycobacterium tuberculosis</i> sensu stricto; Maf, <i>Mycobacterium africanum</i>; MamE, Mamprusi East district; TamM, Tamale Metropolis; AshK, Ashiedu Keteke; Ayaw, Ayawaso; Able, Ablekuma; OsuK, Osu Klottey; Okai, Okaikoi; Kpes, Kpeshie.</p
<p>Sputum samples were obtained from fifteen sampling sites (health facilities) all located... more <p>Sputum samples were obtained from fifteen sampling sites (health facilities) all located within three regions in Ghana; Greater Accra, Central and Northern regions. During the period September 2012 –December 2014, samples were obtained mainly from all the 13 diagnostic centres within the Accra metropolis, (serving more than 46% of the Greater Accra region populace) and the two health facilities located in the northern region (Tamale Teaching Hospital and BMC Nalerigu). The ArcMap program in ArcGIS v. 10.0 was used to create the map.</p
<p>The figure shows the (A) Sum and normalized distribution of lineage 4 cases, (B) Sum and... more <p>The figure shows the (A) Sum and normalized distribution of lineage 4 cases, (B) Sum and normalized distribution of Ghana sub-lineages cases, (C) Sum and normalized distribution of Cameroon sub-lineage cases. The total number of cases per year was used as the denominator for normalization. This study recorded no TB cases for TamM in 2012, consequently TamM was excluded from all analysis carried out using 2012 data. This figure was created using the ArcMap program in ArcGIS v. 10.0. Abbreviations: L4, Lineage 4; Ghana, Ghana genotypes (Ghana sub-lineage); Cam, Cameroon sub-lineage; MamE, Mamprusi East district; TamM, Tamale Metropolis; AshK, Ashiedu Keteke; Ayaw, Ayawaso; Able, Ablekuma; OsuK, Osu Klottey; Okai, Okaikoi; Kpes, Kpeshie.</p
<p>Diagram shows the spatial distribution of (A) 2551 <i>Mycobacterium tuberculosis&l... more <p>Diagram shows the spatial distribution of (A) 2551 <i>Mycobacterium tuberculosis</i> complex (MTBC) strains; (B) 2535 human adapted MTBC; (C) regional prevalence of 1883 Lineage 4 sub lineages; (D) regional prevalence of 516 <i>Mycobacterium africanum</i> (Maf) isolates from the geographical regions served by the health facility where sampling was carried out in Ghana. Animal strains were found to be associated with the North (p = 0.0389). Similarly, Lineage 2 was found to be associated with the North (p = 0.0006). The most dominant Lineage 4 sub-lineage in the North is Ghana (p = 0.0000) whereas in the South is Cameroon, even though the association is not statistically significant. The unknown sub-type of Lineage 4 is associated with South (p = 0.0001).</p
<p>The figure shows the distribution of MTBC species/lineages/sub-lineages within the 13 di... more <p>The figure shows the distribution of MTBC species/lineages/sub-lineages within the 13 districts where participants resided. The blue coloured panel shows the distribution of all the tuberculosis cases recruited with well-defined residential status. The red, brown and green coloured panels show the distribution of lineage 4, lineage 5 and lineage 6 respectively. All other sub-lineages/species have been indicated in the respective legends. This figure was created using the ArcMap program in ArcGIS v. 10.0. Abbreviations: MTBC, <i>Mycobacterium tuberculosis</i> complex; MTBss, <i>Mycobacterium tuberculosis</i> sensu stricto; Maf, <i>Mycobacterium africanum</i>; L4, Lineage 4; L5, Lineage 5; L6, Lineage 6; Ghana, Ghana genotypes (Ghana sub-lineage); Cam, Cameroon sub-lineage; MamE, Mamprusi East district; TamM, Tamale Metropolis; AgWM, Agona West Municipal; GomE, Gomoa East; AwuS, Awutu Senya; GaSM, Ga South Municipal; GaWM, Ga West Municipal; GaCM, Ga Central Municipal; GaEM, Ga East Municipal; AMA, Accra Metropolis; LaNM, La-Nkwantanang Madina Municipal; AdeM, Adenta Municipal; Kpes, Kpeshie Municipal.</p
Human tuberculosis is caused by members of the Mycobacterium tuberculosis Complex (MTBC). The MTB... more Human tuberculosis is caused by members of the Mycobacterium tuberculosis Complex (MTBC). The MTBC comprises several human-adapted lineages known as M. tuberculosis sensu stricto as well as two lineages (L5 and L6) traditionally referred to as M. africanum. Strains of L5 and L6 are largely limited to West Africa for reasons unknown, and little is known on their genomic diversity, phylogeography and evolution. Here, we analyzed the genomes of 365 L5 and 326 L6 strains, plus five related genomes that had not been classified into any of the known MTBC lineages, isolated from patients from 21 African countries.Our population genomic and phylogeographical analyses show that the unclassified genomes belonged to a new group that we propose to name MTBC Lineage 9 (L9). While the most likely ancestral distribution of L9 was predicted to be East Africa, the most likely ancestral distribution for both L5 and L6 was the Eastern part of West Africa. Moreover, we found important differences betwe...
Background Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in bo... more Background Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in both livestock and humans. The association of some M. bovis strains with hyper-virulence, MDR-TB and disseminated disease makes it imperative to understand the biology of the pathogen. Methods Mycobacterium bovis (15) among 1755 M. tuberculosis complex (MTBC) isolated between 2012 and 2014 were characterized and analyzed for associated patient demography and other risk factors. Five of the M. bovis were whole-genome sequenced and comparatively analyzed against a global collection of published M. bovis genomes. Results Mycobacterium bovis was isolated from 3/560(0.5%) females and 12/1195(1.0%) males with pulmonary TB. The average age of M. bovis infected cases was 46.8 years (7-72years). TB patients from the Northern region of Ghana (1.9%;4/212) had a higher rate of infection with M. bovis (OR=2.7,p=0.0968) compared to those from the Greater Accra region (0.7%;11/1543). Among TB patients wi...
Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some count... more Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some countries of West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including N = 175 Lineage 5 (L5) and N = 78 Lineage 6 (L6). We found that the genomic diversity of L6 was higher than in L5 despite the smaller sample size. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Even though over 90% of the human T cell epitopes were conserved in both lineages, L6 showed a higher ratio of non-synonymous to synonymous single nucleotide variation in these epitopes overall compared to L5. Of the 10% human T cell epitopes that were variable, most carried mutations that were lineage-specific. Our findings indicate that Maf L5 and L6 differ in some of their population genomic characteristics, possibly reflecting different selection pressures linked to distinct ecological niches.
Generalist and specialist species differ in the breadth of their ecological niches. Little is kno... more Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.
For cultivation of Mycobacterium ulcerans from clinical specimens, we optimized the release of ba... more For cultivation of Mycobacterium ulcerans from clinical specimens, we optimized the release of bacteria from swabs, as well as decontamination and cultivation on supplemented medium. Nevertheless, the proportions of positive cultures, 41.7% (5/12) for fine-needle-aspiration (FNA) samples and 43.8% (49/112) for swab samples, were lower than those we have previously observed for excised tissue specimens.
<p>Figure displays a stacked graph showing the temporal distribution of human adapted MTBC ... more <p>Figure displays a stacked graph showing the temporal distribution of human adapted MTBC (left y-axis) and a linear graph showing the prevalence of <i>Mycobacterium tuberculosis</i> sensu stricto (MTBss) and <i>Mycobacterium africanum</i> (Maf) (right y-axis) over the entire 8-year study period.</p
<p>This figure shows the; (A) Sum and case notification rate of all TB cases from September... more <p>This figure shows the; (A) Sum and case notification rate of all TB cases from September 2012 to December 2014, (B) Sum and normalized distribution of MTBss cases, (C) Sum and normalized distribution of Maf. The total number of cases per year was used as the denominator for normalization. Sampling from TamM did not meet our criteria for being included in analyses for case notification rate and so was excluded in all columns of panel A. Likewise we also recorded no cases in 2012 as such TamM was excluded from 2012 analysis (panel B and C). This figure was created using the ArcMap program in ArcGIS v. 10.0. Abbreviations: MTBss, <i>Mycobacterium tuberculosis</i> sensu stricto; Maf, <i>Mycobacterium africanum</i>; MamE, Mamprusi East district; TamM, Tamale Metropolis; AshK, Ashiedu Keteke; Ayaw, Ayawaso; Able, Ablekuma; OsuK, Osu Klottey; Okai, Okaikoi; Kpes, Kpeshie.</p
<p>Sputum samples were obtained from fifteen sampling sites (health facilities) all located... more <p>Sputum samples were obtained from fifteen sampling sites (health facilities) all located within three regions in Ghana; Greater Accra, Central and Northern regions. During the period September 2012 –December 2014, samples were obtained mainly from all the 13 diagnostic centres within the Accra metropolis, (serving more than 46% of the Greater Accra region populace) and the two health facilities located in the northern region (Tamale Teaching Hospital and BMC Nalerigu). The ArcMap program in ArcGIS v. 10.0 was used to create the map.</p
<p>The figure shows the (A) Sum and normalized distribution of lineage 4 cases, (B) Sum and... more <p>The figure shows the (A) Sum and normalized distribution of lineage 4 cases, (B) Sum and normalized distribution of Ghana sub-lineages cases, (C) Sum and normalized distribution of Cameroon sub-lineage cases. The total number of cases per year was used as the denominator for normalization. This study recorded no TB cases for TamM in 2012, consequently TamM was excluded from all analysis carried out using 2012 data. This figure was created using the ArcMap program in ArcGIS v. 10.0. Abbreviations: L4, Lineage 4; Ghana, Ghana genotypes (Ghana sub-lineage); Cam, Cameroon sub-lineage; MamE, Mamprusi East district; TamM, Tamale Metropolis; AshK, Ashiedu Keteke; Ayaw, Ayawaso; Able, Ablekuma; OsuK, Osu Klottey; Okai, Okaikoi; Kpes, Kpeshie.</p
<p>Diagram shows the spatial distribution of (A) 2551 <i>Mycobacterium tuberculosis&l... more <p>Diagram shows the spatial distribution of (A) 2551 <i>Mycobacterium tuberculosis</i> complex (MTBC) strains; (B) 2535 human adapted MTBC; (C) regional prevalence of 1883 Lineage 4 sub lineages; (D) regional prevalence of 516 <i>Mycobacterium africanum</i> (Maf) isolates from the geographical regions served by the health facility where sampling was carried out in Ghana. Animal strains were found to be associated with the North (p = 0.0389). Similarly, Lineage 2 was found to be associated with the North (p = 0.0006). The most dominant Lineage 4 sub-lineage in the North is Ghana (p = 0.0000) whereas in the South is Cameroon, even though the association is not statistically significant. The unknown sub-type of Lineage 4 is associated with South (p = 0.0001).</p
<p>The figure shows the distribution of MTBC species/lineages/sub-lineages within the 13 di... more <p>The figure shows the distribution of MTBC species/lineages/sub-lineages within the 13 districts where participants resided. The blue coloured panel shows the distribution of all the tuberculosis cases recruited with well-defined residential status. The red, brown and green coloured panels show the distribution of lineage 4, lineage 5 and lineage 6 respectively. All other sub-lineages/species have been indicated in the respective legends. This figure was created using the ArcMap program in ArcGIS v. 10.0. Abbreviations: MTBC, <i>Mycobacterium tuberculosis</i> complex; MTBss, <i>Mycobacterium tuberculosis</i> sensu stricto; Maf, <i>Mycobacterium africanum</i>; L4, Lineage 4; L5, Lineage 5; L6, Lineage 6; Ghana, Ghana genotypes (Ghana sub-lineage); Cam, Cameroon sub-lineage; MamE, Mamprusi East district; TamM, Tamale Metropolis; AgWM, Agona West Municipal; GomE, Gomoa East; AwuS, Awutu Senya; GaSM, Ga South Municipal; GaWM, Ga West Municipal; GaCM, Ga Central Municipal; GaEM, Ga East Municipal; AMA, Accra Metropolis; LaNM, La-Nkwantanang Madina Municipal; AdeM, Adenta Municipal; Kpes, Kpeshie Municipal.</p
Human tuberculosis is caused by members of the Mycobacterium tuberculosis Complex (MTBC). The MTB... more Human tuberculosis is caused by members of the Mycobacterium tuberculosis Complex (MTBC). The MTBC comprises several human-adapted lineages known as M. tuberculosis sensu stricto as well as two lineages (L5 and L6) traditionally referred to as M. africanum. Strains of L5 and L6 are largely limited to West Africa for reasons unknown, and little is known on their genomic diversity, phylogeography and evolution. Here, we analyzed the genomes of 365 L5 and 326 L6 strains, plus five related genomes that had not been classified into any of the known MTBC lineages, isolated from patients from 21 African countries.Our population genomic and phylogeographical analyses show that the unclassified genomes belonged to a new group that we propose to name MTBC Lineage 9 (L9). While the most likely ancestral distribution of L9 was predicted to be East Africa, the most likely ancestral distribution for both L5 and L6 was the Eastern part of West Africa. Moreover, we found important differences betwe...
Background Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in bo... more Background Bovine tuberculosis (bTB) caused by Mycobacterium bovis is a re-emerging problem in both livestock and humans. The association of some M. bovis strains with hyper-virulence, MDR-TB and disseminated disease makes it imperative to understand the biology of the pathogen. Methods Mycobacterium bovis (15) among 1755 M. tuberculosis complex (MTBC) isolated between 2012 and 2014 were characterized and analyzed for associated patient demography and other risk factors. Five of the M. bovis were whole-genome sequenced and comparatively analyzed against a global collection of published M. bovis genomes. Results Mycobacterium bovis was isolated from 3/560(0.5%) females and 12/1195(1.0%) males with pulmonary TB. The average age of M. bovis infected cases was 46.8 years (7-72years). TB patients from the Northern region of Ghana (1.9%;4/212) had a higher rate of infection with M. bovis (OR=2.7,p=0.0968) compared to those from the Greater Accra region (0.7%;11/1543). Among TB patients wi...
Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some count... more Mycobacterium africanum (Maf) causes a substantial proportion of human tuberculosis in some countries of West Africa, but little is known on this pathogen. We compared the genomes of 253 Maf clinical isolates from Ghana, including N = 175 Lineage 5 (L5) and N = 78 Lineage 6 (L6). We found that the genomic diversity of L6 was higher than in L5 despite the smaller sample size. Regulatory proteins appeared to evolve neutrally in L5 but under purifying selection in L6. Even though over 90% of the human T cell epitopes were conserved in both lineages, L6 showed a higher ratio of non-synonymous to synonymous single nucleotide variation in these epitopes overall compared to L5. Of the 10% human T cell epitopes that were variable, most carried mutations that were lineage-specific. Our findings indicate that Maf L5 and L6 differ in some of their population genomic characteristics, possibly reflecting different selection pressures linked to distinct ecological niches.
Generalist and specialist species differ in the breadth of their ecological niches. Little is kno... more Generalist and specialist species differ in the breadth of their ecological niches. Little is known about the niche width of obligate human pathogens. Here we analyzed a global collection of Mycobacterium tuberculosis lineage 4 clinical isolates, the most geographically widespread cause of human tuberculosis. We show that lineage 4 comprises globally distributed and geographically restricted sublineages, suggesting a distinction between generalists and specialists. Population genomic analyses showed that, whereas the majority of human T cell epitopes were conserved in all sublineages, the proportion of variable epitopes was higher in generalists. Our data further support a European origin for the most common generalist sublineage. Hence, the global success of lineage 4 reflects distinct strategies adopted by different sublineages and the influence of human migration.
For cultivation of Mycobacterium ulcerans from clinical specimens, we optimized the release of ba... more For cultivation of Mycobacterium ulcerans from clinical specimens, we optimized the release of bacteria from swabs, as well as decontamination and cultivation on supplemented medium. Nevertheless, the proportions of positive cultures, 41.7% (5/12) for fine-needle-aspiration (FNA) samples and 43.8% (49/112) for swab samples, were lower than those we have previously observed for excised tissue specimens.
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