title: Detecting Mutations in the Mycobacterium tuberculosis Pyrazinamidase Gene pncA to Improve Infection Control and Decrease Drug Resistance Rates in Human Immunodeficiency Virus Coinfection.
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.
authors.affiliation: Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Matthew Z
authors.initials: MZ
authors.lastname: Dudley
authors.affiliation: Laboratorio de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.|Laboratorio de Investigación en Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Patricia
authors.initials: P
authors.lastname: Sheen
authors.affiliation: Asociación Benéfica Proyectos en Informatica, Salud, Medicina, y Agricultura (PRISMA), Lima, Peru.|Laboratorio de Investigación en Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.|Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gilman
authors.affiliation: Facultad de Medicina, Universidad Nacional Mayor de San Marcos, Lima, Peru.|Hospital Nacional Dos de Mayo, Lima, Peru.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ticona
authors.affiliation: Infectious Diseases and Immunity, Wellcome Trust Centre for Global Health Research, Imperial College London, London, United Kingdom.
authors.forename: Jon S
authors.initials: JS
authors.lastname: Friedland
authors.affiliation: Infections Diseases and Immunity, Imperial College London, London, United Kingdom.|Department of Medical Microbiology, St. George's Hospital, London, United Kingdom.
authors.forename: Daniela E
authors.initials: DE
authors.lastname: Kirwan
authors.affiliation: Laboratorio de Investigación en Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Luz
authors.initials: L
authors.lastname: Caviedes
authors.affiliation: Hospital de Apoyo Maria Auxiliadora, Lima, Peru.
authors.forename: Richard
authors.initials: R
authors.lastname: Rodriguez
authors.affiliation: Asociación Benéfica Proyectos en Informatica, Salud, Medicina, y Agricultura (PRISMA), Lima, Peru.
authors.forename: Lilia Z
authors.initials: LZ
authors.lastname: Cabrera
authors.affiliation: Laboratorio de Investigación en Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Jorge
authors.initials: J
authors.lastname: Coronel
authors.affiliation: Infectious Diseases and Immunity, Wellcome Trust Centre for Global Health Research, Imperial College London, London, United Kingdom.|Laboratorio de Investigación en Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Louis
authors.initials: L
authors.lastname: Grandjean
authors.affiliation: TB Centre, London School of Hygiene and Tropical Medicine, London, United Kingdom.|Asociación Benéfica Proyectos en Informatica, Salud, Medicina, y Agricultura (PRISMA), Lima, Peru.|Laboratorio de Investigación en Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: David A J
authors.initials: DAJ
authors.lastname: Moore
authors.affiliation: Innovation For Health and Development (IFHAD), Laboratory of Research and Development, Universidad Peruana Cayetano Heredia, Lima, Peru.|Infectious Diseases and Immunity, Wellcome Trust Centre for Global Health Research, Imperial College London, London, United Kingdom.
authors.forename: Carlton A
authors.initials: CA
authors.lastname: Evans
authors.affiliation: Universidad Nacional Mayor de San Marcos, Lima, Peru.|Hospital Nacional Dos de Mayo, Lima, Peru.
authors.forename: Luz
authors.initials: L
authors.lastname: Huaroto
authors.affiliation: Universidad Nacional Mayor de San Marcos, Lima, Peru.|Hospital Nacional Dos de Mayo, Lima, Peru.
authors.forename: Víctor
authors.initials: V
authors.lastname: Chávez-Pérez
authors.affiliation: Laboratorio de Investigación en Enfermedades Infecciosas, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.|Laboratorio de Bioinformática y Biología Molecular, Laboratorios de Investigación y Desarrollo, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Peru.
authors.forename: Mirko
authors.initials: M
authors.lastname: Zimic
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000995:Antitubercular Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016022:Case-Control Studies; D024881:Drug Resistance, Bacterial; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D014376:Tuberculosis / Q000150:complications* / Q000382:microbiology / Q000517:prevention & control*; D055815:Young Adult
chemical_list: D000995:Antitubercular Agents; D000581:Amidohydrolases; C487496:PncA protein, Mycobacterium tuberculosis