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 > ReviewFull Text
Lancet Infect Dis. 24 March 2013; Volume 13 (Issue 5); DOI:10.1016/S1473-3099(13)70030-6
Abubakar I, Zignol M, Falzon D, Raviglione M, Ditui L, et al.
Lancet Infect Dis. 24 March 2013; Volume 13 (Issue 5); DOI:10.1016/S1473-3099(13)70030-6
Journal Article > ReviewAbstract
J Infect Dis. 3 April 2012; Volume 205 (Issue suppl_2); DOI:10.1093/infdis/jir858
Zumla A, Abubakar I, Raviglione M, Hoelscher M, Ditui L, et al.
J Infect Dis. 3 April 2012; Volume 205 (Issue suppl_2); DOI:10.1093/infdis/jir858
Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis-specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed.
Journal Article > ReviewAbstract
J Infect Dis. 10 April 2012; Volume 205 (Issue suppl_2); DOI:10.1093/infdis/jir860
McNerney R, Maeurer M, Abubakar I, Marais BJ, McHugh TD, et al.
J Infect Dis. 10 April 2012; Volume 205 (Issue suppl_2); DOI:10.1093/infdis/jir860
Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics.
Journal Article > CommentaryFull Text
Nat Rev Drug Discov. 17 July 2015; Volume 14 (Issue 8); DOI:10.1038/nrd4696
Zumla A, Chakaya JM, Hoelscher M, Ntoumi F, Rustomjee R, et al.
Nat Rev Drug Discov. 17 July 2015; Volume 14 (Issue 8); DOI:10.1038/nrd4696