RESUMEN
BACKGROUND: Papua New Guinea (PNG) is a high tuberculosis (TB) burden country of the WHO Western Pacific Region, but so far research on drug resistance (DR) and genotypes of Mycobacterium tuberculosis (M. tuberculosis) was only conducted in few provinces in the country. The aim of the present study was to obtain baseline data on the level of drug resistance and the genotypic diversity of circulating M. tuberculosis in additional provinces and to investigate the differences between three selected sites across PNG. RESULTS: Genotyping of 147 M. tuberculosis clinical isolates collected in Goroka, Eastern Highlands Province, in Alotau, Milne Bay Province and in Madang, Madang Province revealed three main lineages of M. tuberculosis: Lineage 4 (European-American lineage), Lineage 2 (East-Asian lineage) and Lineage 1 (Indo-Oceanic lineage). All three lineages were detected in all three sites, but the individual lineage compositions varied significantly between sites. In Madang Lineage 4 was the most prevalent lineage (76.6%), whereas in Goroka and Alotau Lineage 2 was dominating (60.5% and 84.4%, respectively) (p < 0.001). Overall, phenotypic drug susceptibility testing showed 10.8% resistance to at least one of the first-line drugs tested. Of all resistant strains (23/212) 30.4% were Streptomycin mono-resistant, 17.4% were Isoniazid mono-resistant and 13% were Rifampicin mono-resistant. Multi-drug resistant (MDR) TB was found in 2.8% of all tested cases (6/212). The highest amount of MDR TB was found in Alotau in Milne Bay Province (4.6%). CONCLUSION: A large number of drug resistant TB infections are present in the country and MDR TB has already been detected in all three surveyed regions of PNG, highlighting the importance of monitoring drug resistance and making it a high priority for the National Control Program. Due to the high prevalence of Lineage 2 in Milne Bay Province and given the frequent association of this lineage with drug resistance, monitoring of the latter should especially be scaled up in that province.
Asunto(s)
Farmacorresistencia Bacteriana , Variación Genética , Mycobacterium tuberculosis/clasificación , Mycobacterium tuberculosis/efectos de los fármacos , Tuberculosis/microbiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antituberculosos/farmacología , Femenino , Genotipo , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Tipificación Molecular , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/aislamiento & purificación , Papúa Nueva Guinea/epidemiología , Tuberculosis/epidemiología , Adulto JovenRESUMEN
BACKGROUND: The incidence and characteristics of tuberculosis (TB) in remote areas of Papua New Guinea (PNG) are largely unknown. The purpose of our study was to determine the incidence of TB in the Gulf Province of PNG and describe disease characteristics, co-morbidities and drug resistance profiles that could impact on disease outcomes and transmission. METHODS: Between March 2012 and June 2012, we prospectively collected data on 274 patients presenting to Kikori Hospital with a presumptive diagnosis of TB, and on hospital inpatients receiving TB treatment during the study period. Sputum was collected for microscopy, GeneXpert analysis, culture and genotyping of isolates. RESULTS: We estimate the incidence of TB in Kikori to be 1290 per 100,000 people (95% CI 1140 to 1460) in 2012. The proportion of TB patients co-infected with HIV was 1.9%. Three of 32 TB cases tested were rifampicin resistant. Typing of nine isolates demonstrated allelic diversity and most were related to Beijing strains. CONCLUSIONS: The incidence of TB in Kikori is one of the highest in the world and it is not driven by HIV co-infection. The high incidence and the presence of rifampicin resistant warrant urgent attention to mitigate substantial morbidity in the region.
Asunto(s)
Tuberculosis/tratamiento farmacológico , Tuberculosis/epidemiología , Tuberculosis/microbiología , Adolescente , Adulto , Alelos , Antituberculosos/uso terapéutico , Niño , Preescolar , Coinfección , Femenino , Genotipo , Infecciones por VIH/complicaciones , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Papúa Nueva Guinea/epidemiología , Estudios Prospectivos , Rifampin/uso terapéutico , Factores de Riesgo , Esputo , Tuberculosis Resistente a Múltiples Medicamentos/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Monitoring drug resistance in Mycobacterium tuberculosis is essential to curb the spread of tuberculosis (TB). Unfortunately, drug susceptibility testing is currently not available in Papua New Guinea (PNG) and that impairs TB control in this country. We report for the first time M. tuberculosis mutations associated with resistance to first and second-line anti-TB drugs in Madang, PNG. A molecular cluster analysis was performed to identify M. tuberculosis transmission in that region. RESULTS: Phenotypic drug susceptibility tests showed 15.7% resistance to at least one drug and 5.2% multidrug resistant (MDR) TB. Rifampicin resistant strains had the rpoB mutations D516F, D516Y or S531L; Isoniazid resistant strains had the mutations katG S315T or inhA promoter C15T; Streptomycin resistant strains had the mutations rpsL K43R, K88Q, K88R), rrs A514C or gidB V77G. The molecular cluster analysis indicated evidence for transmission of resistant strain. CONCLUSIONS: We observed a substantial rate of MDR-TB in the Madang area of PNG associated with mutations in specific genes. A close monitoring of drug resistance is therefore urgently required, particularly in the presence of drug-resistant M. tuberculosis transmission. In the absence of phenotypic drug susceptibility testing in PNG, molecular assays for drug resistance monitoring would be of advantage.
Asunto(s)
Antituberculosos/farmacología , Farmacorresistencia Bacteriana , Mutación Missense , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Tuberculosis/microbiología , Proteínas Bacterianas/genética , Pruebas de Sensibilidad Microbiana , Mycobacterium tuberculosis/aislamiento & purificación , Papúa Nueva Guinea , Proyectos PilotoRESUMEN
Recent figures show that tuberculosis (TB) is advancing and killing more than two million people annually, yet no breakthrough in rapid diagnostics is in sight. Volatile metabolites of Mycobacterium tuberculosis (MTB) may provide just that. It is well established that MTB produces nicotinic acid in vitro. We have converted the free acid into methyl nicotinate and detected statistically significant differences in the breath of smear positive patients compared with healthy (smear negative) subjects.