RESUMEN
The "Harlingen" IS6110 restriction fragment length polymorphism (RFLP) cluster has linked over 100 tuberculosis cases in The Netherlands since 1993. Four Mycobacterium tuberculosis isolates that were epidemiologically linked to this cluster had different spoligotype patterns, as well as slightly divergent IS6110 profiles, compared to the majority of the isolates. Sequencing of the direct repeat (DR) locus revealed sequence polymorphisms at the putative deletion sites. These deletion footprints provided evidence for independent deletions of the central region of the DR locus in three isolates, while the different genotype of the fourth isolate was explained by transmission. Our finding suggests that convergent deletions in the DR locus occur frequently. However, deletion footprints are not suitable to detect convergent deletions in the DR because they seem to be exceptional. Deletion footprints in the DR were not described previously, and we did not observe them in any public M. tuberculosis complex sequences. We conclude that preferential deletions in the DR loci of closely related strains are usually an unnoted event that interferes with clustering of closely related strains.
Asunto(s)
ADN Bacteriano/genética , Mycobacterium tuberculosis/genética , Secuencias Repetitivas de Ácidos Nucleicos , Eliminación de Secuencia , Tuberculosis/epidemiología , Técnicas de Tipificación Bacteriana , Elementos Transponibles de ADN , Genotipo , Humanos , Epidemiología Molecular , Tipificación Molecular , Países Bajos/epidemiología , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Análisis de Secuencia de ADN , Tuberculosis/microbiologíaRESUMEN
To investigate whether genome sequencing yields more useful markers than those currently used to study the epidemiology of tuberculosis, it was applied to three Mycobacterium tuberculosis isolates of the Harlingen outbreak. Our findings suggest that single nucleotide polymorphisms can be used to identify transmission chains in restriction fragment length polymorphism clusters.
Asunto(s)
Técnicas de Tipificación Bacteriana , ADN Bacteriano/genética , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/genética , Tuberculosis/microbiología , Análisis por Conglomerados , ADN Bacteriano/química , Genoma Bacteriano , Humanos , Epidemiología Molecular/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido SimpleRESUMEN
BACKGROUND: Knowledge of the HIV status in patients with tuberculosis (TB) and vice versa is crucial for proper individual patient management, while knowledge of the prevalence of co-infection guides preventive and therapeutic strategies. The aim of the study was to assess if national disease databases on TB and HIV are adequate sources to provide this information. METHODS: A two way capture-recapture analysis to assess the completeness of the registers, and to obtain the prevalence of TB-HIV co-infection in the Netherlands in the years 2002-2012. RESULTS: HIV testing was performed in less than 50% of the patients with TB. Of the 932 TB-HIV infected patients, just 293 (31.4%) were registered in both registers. Under-reporting of TB-HIV co-infection ranged from 50% to 70% in the national TB register, and from 31% to 37% in the HIV database. Prevalence of TB-HIV co-infection in the Netherlands in 2012 was 7.1% (95% CI 6.0% to 8.3%), which was more than double of the prevalence estimated from the national TB database. CONCLUSIONS: TB-HIV co-infection is markedly under-reported in national disease databases. There is an urgent need for improved registration and preferably a routine data exchange between the two surveillance systems.
Asunto(s)
Coinfección/epidemiología , Notificación de Enfermedades/estadística & datos numéricos , Infecciones por VIH/epidemiología , Informática en Salud Pública/estadística & datos numéricos , Tuberculosis/epidemiología , Adolescente , Adulto , Notificación de Enfermedades/normas , Femenino , Humanos , Masculino , Tamizaje Masivo/estadística & datos numéricos , Persona de Mediana Edad , Países Bajos/epidemiología , Vigilancia de la Población , Prevalencia , Informática en Salud Pública/normas , Sistema de RegistrosRESUMEN
A total of six polymorphisms were identified by comparing the genomes of the first and the last isolate of a well-characterized transmission chain of Mycobacterium tuberculosis involving five patients over a 12 and a half year period. The six polymorphisms consisted of four single nucleotide changes (SNPs), a tandem repeat polymorphism (TRP) and a previously identified IS6110 transposition event. These polymorphic sites were surveyed in each of the isolates from the five patients in the transmission chain. Surprisingly, five of the six polymorphisms accumulated in a single patient in the transmission chain; this patient had been non-compliant to tuberculosis treatment. This first insight into the tempo and mode of molecular evolution in M. tuberculosis at the patient-to-patient level suggests that the molecular evolution of the pathogen in vivo is characterized by periods of relative genomic stability followed by bursts of mutation. Whatever the mechanism for the accumulation of mutations, this observation may have profound consequences for the application of vaccines and therapeutic drugs, the management and treatment of disease outbreaks of M. tuberculosis, the most important bacterial pathogen of humans.