ABSTRACT
Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients' skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.
Subject(s)
Anti-Infective Agents/pharmacology , Drug Resistance, Bacterial/genetics , Mycobacterium leprae/drug effects , Phylogeny , Codon, Nonsense , DNA, Bacterial/chemistry , Genome, Bacterial , Humans , Microbial Sensitivity Tests , Mycobacterium leprae/genetics , Mycobacterium leprae/isolation & purificationABSTRACT
Leprosy is a chronic human disease caused by the yet-uncultured pathogen Mycobacterium leprae. Although readily curable with multidrug therapy (MDT), over 200,000 new cases are still reported annually. Here, we obtain M. leprae genome sequences from DNA extracted directly from patients' skin biopsies using a customized protocol. Comparative and phylogenetic analysis of 154 genomes from 25 countries provides insight into evolution and antimicrobial resistance, uncovering lineages and phylogeographic trends, with the most ancestral strains linked to the Far East. In addition to known MDT-resistance mutations, we detect other mutations associated with antibiotic resistance, and retrace a potential stepwise emergence of extensive drug resistance in the pre-MDT era. Some of the previously undescribed mutations occur in genes that are apparently subject to positive selection, and two of these (ribD, fadD9) are restricted to drug-resistant strains. Finally, nonsense mutations in the nth excision repair gene are associated with greater sequence diversity and drug resistance.
Subject(s)
Humans , Phylogeny , DNA, Bacterial/chemistry , Microbial Sensitivity Tests , Genome, Bacterial , Codon, Nonsense , Drug Resistance, Bacterial/genetics , Anti-Infective Agents/pharmacology , Mycobacterium leprae/isolation & purification , Mycobacterium leprae/drug effects , Mycobacterium leprae/geneticsABSTRACT
Although the prevalence rate of leprosy in the Republic of Yemen has dropped below the WHO elimination level of less than one case per 10,000 of the population, it is still regarded as a serious public health problem calling for continued vigilance, notably in the detection and treatment of hidden and undiagnosed cases. In the past, religious misinterpretation has generated adverse behaviour patterns towards people affected by leprosy, characterized by aggression, negligence and isolation. Until about 1982, following a visit of a leprologist (Dr S. K. Noordeen) from the World Health Organization, there was no leprosy control programme and attempts to establish one remained ineffective until in 1989, when an agreement was signed between the Ministry of Public Health and Population and the German Leprosy Relief Association. This led to the development of a leprosy control programme in four governorates, later extended to the rest of the country. This paper describes the progress made in the control of leprosy in the Yemen, 1989-2003, by the Ministry of Health and Population and the GLRA, in association with two local societies.
Subject(s)
Health Promotion , Interinstitutional Relations , Leprosy/prevention & control , Outcome Assessment, Health Care , Female , Government Programs , Humans , Leprosy/epidemiology , Male , Prevalence , Yemen/epidemiologySubject(s)
Communicable Disease Control/organization & administration , Leprostatic Agents/therapeutic use , Leprosy/drug therapy , Leprosy/prevention & control , Developing Countries , Female , Health Promotion/organization & administration , Humans , Incidence , Leprosy/mortality , Male , Outcome Assessment, Health Care , Program Development , Program Evaluation , Risk Assessment , Severity of Illness Index , Survival Analysis , Yemen/epidemiologyABSTRACT
Leprosy control activities in Yemen are reviewed historically and up to the present time. Since 1983 the World Health Organization's multidrug therapy has been used in the National Leprosy Control Programme. Current activities are carried out in 63 leprosy clinics distributed all over the country and staffed by trained primary health care workers and medical assistants. In Yemen leprosy prevalence has declined from 1400 per 10,000 population in 1990 to 647 in 1997. Over the same period, new case detection rates per 10,000 population increased from 185 to 517. A backlog of leprosy cases continues to transmit the disease in Yemen.