Universidad Peruana Cayetano Heredia

Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection

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dc.contributor.author Dudley, Matthew Z.
dc.contributor.author Sheen Cortavarria, Patricia
dc.contributor.author Gilman, Robert Hugh
dc.contributor.author Ticona, Eduardo
dc.contributor.author Friedland, Jon S.
dc.contributor.author Kirwan, Daniela E.
dc.contributor.author Caviedes, Luz
dc.contributor.author Rodriguez, Richard
dc.contributor.author Cabrera, Lilia Z.
dc.contributor.author Coronel, Jorge
dc.contributor.author Grandjean, Louis
dc.contributor.author Moore, David Alexander James
dc.contributor.author Evans, Carlton Anthony William
dc.contributor.author Huaroto, Luz
dc.contributor.author Chavez-Perez, Victor
dc.contributor.author Zimic-Peralta, Mirko Juan
dc.date.accessioned 2019-02-06T14:45:12Z
dc.date.available 2019-02-06T14:45:12Z
dc.date.issued 2016
dc.identifier.uri https://hdl.handle.net/20.500.12866/5056
dc.description.abstract Hospital infection control measures are crucial to tuberculosis (TB) control strategies within settings caring for human immunodeficiency virus (HIV)–positive patients, as these patients are at heightened risk of developing TB. Pyrazinamide (PZA) is a potent drug that effectively sterilizes persistent Mycobacterium tuberculosis bacilli. However, PZA resistance associated with mutations in the nicotinamidase/pyrazinamidase coding gene, pncA, is increasing. A total of 794 patient isolates obtained from four sites in Lima, Peru, underwent spoligotyping and drug resistance testing. In one of these sites, the HIV unit of Hospital Dos de Mayo (HDM), an isolation ward for HIV/TB coinfected patients opened during the study as an infection control intervention: circulating genotypes and drug resistance pre- and postintervention were compared. All other sites cared for HIV-negative outpatients: genotypes and drug resistance rates from these sites were compared with those from HDM. HDM patients showed high concordance between multidrug resistance, PZA resistance according to the Wayne method, the two most common genotypes (spoligotype international type [SIT] 42 of the Latino American-Mediterranean (LAM)-9 clade and SIT 53 of the T1 clade), and the two most common pncA mutations (G145A and A403C). These associations were absent among community isolates. The infection control intervention was associated with 58–92% reductions in TB caused by SIT 42 or SIT 53 genotypes (odds ratio [OR] = 0.420, P = 0.003); multidrug-resistant TB (OR = 0.349, P < 0.001); and PZA-resistant TB (OR = 0.076, P < 0.001). In conclusion, pncA mutation typing, with resistance testing and spoligotyping, was useful in identifying a nosocomial TB outbreak and demonstrating its resolution after implementation of infection control measures. en_US
dc.language.iso eng
dc.publisher American Society of Tropical Medicine and Hygiene
dc.relation.ispartofseries American Journal of Tropical Medicine and Hygiene (ASTMH Journal)
dc.rights info:eu-repo/semantics/restrictedAccess
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject Adolescent en_US
dc.subject Adult en_US
dc.subject Aged en_US
dc.subject Amidohydrolases/genetics/metabolism en_US
dc.subject Antitubercular Agents/pharmacology/therapeutic use en_US
dc.subject Case-Control Studies en_US
dc.subject Drug Resistance, Bacterial en_US
dc.subject Female en_US
dc.subject Gene Expression Regulation, Bacterial en_US
dc.subject Gene Expression Regulation, Enzymologic en_US
dc.subject Genotype en_US
dc.subject HIV Infections/complications en_US
dc.subject Humans en_US
dc.subject Male en_US
dc.subject Middle Aged en_US
dc.subject Mutation en_US
dc.subject Mycobacterium tuberculosis/enzymology/genetics/metabolism en_US
dc.subject Tuberculosis/complications/microbiology/prevention & control en_US
dc.subject Young Adult en_US
dc.title Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection en_US
dc.type info:eu-repo/semantics/article
dc.identifier.doi https://doi.org/10.4269/ajtmh.15-0711
dc.subject.ocde https://purl.org/pe-repo/ocde/ford#3.03.06
dc.relation.issn 1476-1645


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