Journal Article > ResearchFull Text
Nat Genet. 31 October 2016; Volume 48 (Issue 12); 1535-1543.; DOI: 10.1038/ng.3704
Stucki D, Brites D, Jeljeli L, Coscolla M, Liu Q, et al.
Nat Genet. 31 October 2016; Volume 48 (Issue 12); 1535-1543.; DOI: 10.1038/ng.3704
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.
Journal Article > ResearchFull Text
Trop Med Int Health. 1 February 2007; Volume 12 (Issue 2); DOI:10.1111/j.1365-3156.2007.01813.x
Mugittu K, Priotto G, Guthmann JP, Kiguli J, Adjuik M, et al.
Trop Med Int Health. 1 February 2007; Volume 12 (Issue 2); DOI:10.1111/j.1365-3156.2007.01813.x
Polymerase chain reaction (PCR) genotyping of malaria parasites in drug efficacy trials helps differentiate reinfections from recrudescences. A combination therapy trial of one (n = 115) or three (n = 117) days artesunate (1AS, 3AS 4 mg/kg/day) plus sulphadoxine-pyrimethamine (SP) vs. SP alone (n = 153) was conducted in Mbarara, a mesoendemic area of western Uganda. All paired recurrent Plasmodium falciparum parasitaemias on days 7, 14, 21 and 28 post-treatment were genotyped by PCR amplification and analysis of glutamate-rich protein (glurp) and merozoite surface proteins (msp) 1 and 2 genes to distinguish recrudescent from new infections. A total of 156 (1AS = 61, 3AS = 35, SP alone = 60) of 199 paired recurrent samples were successfully analysed and were resolved as 79 recrudescences (1AS = 32, 3AS = 8, SP = 39) and 77 as new infections (1AS = 29, 3AS = 27, SP = 21). The ratios of proportions of new to recrudescent infections were 0.2, 0.9, 1.4 and 1.9 on days 7, 14, 21 and 28, respectively (P < 0.001, chi(2) test for linear trend). Unexpected high new infection rates were observed early in follow-up on days 7 [5/26 (19.2%)] and 14 [24/51 (47.1%)]. These results impact significantly on resistance monitoring and point to the value of genotyping all recurrent infections in antimalarial trials.
Journal Article > ResearchAbstract
Nat Genet. 19 January 2015; Volume 47 (Issue 3); DOI:10.1038/ng.3195
Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S, et al.
Nat Genet. 19 January 2015; Volume 47 (Issue 3); DOI:10.1038/ng.3195
Mycobacterium tuberculosis strains of the Beijing lineage are globally distributed and are associated with the massive spread of multidrug-resistant (MDR) tuberculosis in Eurasia. Here we reconstructed the biogeographical structure and evolutionary history of this lineage by genetic analysis of 4,987 isolates from 99 countries and whole-genome sequencing of 110 representative isolates. We show that this lineage initially originated in the Far East, from where it radiated worldwide in several waves. We detected successive increases in population size for this pathogen over the last 200 years, practically coinciding with the Industrial Revolution, the First World War and HIV epidemics. Two MDR clones of this lineage started to spread throughout central Asia and Russia concomitantly with the collapse of the public health system in the former Soviet Union. Mutations identified in genes putatively under positive selection and associated with virulence might have favored the expansion of the most successful branches of the lineage.