Vigilancia de la resistencia a los medicamentos antituberculosos en Cuba, 2010-2011

Introduction: Antituberculosis-drug resistance surveillance is very important to identify multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis isolates.Objective: To determine the prevalence of resistance in M. tuberculosis strains isolated between 2010 and 2011, and to demonstrate the laboratory performance in the external quality control of drug susceptibility testing.Materials and methods: A prospective longitudinal study was carried out to determine antituberculosis-drug resistance in 657 M. tuberculosis isolates obtained throughout the country. The nitrate reductase assay was used to detect resistance to isoniazid and rifampin. The proportion method was performed to confirm resistance to these drugs and to further investigate in multidrug-resistant isolates their susceptibility to streptomycin, ethambutol, ofloxacin, kanamycin and capreomycin. Additionally, as part of external quality control, susceptibility was evaluated in two M. tuberculosis strain panels.Results: In 95.69% of the isolates recovered from new tuberculosis cases, and in 72.64% of isolates from previously treated patients we found susceptibility to isoniazid and rifampicin; multidrug resistance was 1,03 and 10.38%, respectively. We found two extensively resistant isolates. Except for ethambutol and capreomycin, the efficiency of all other drugs was 100% in the external quality control.Conclusion: The study confirmed the low prevalence of M. tuberculosis multidrug-resistant isolates in Cuba. This result was confirmed by the external quality control of drug susceptibility testing.Introducción. La vigilancia de la resistencia a medicamentos antituberculosos permite alertar sobre el hallazgo de aislamientos de Mycobacterium tuberculosis multirresistentes y extremadamente resistentes.Objetivo. Determinar los patrones de resistencia de los aislamientos de M. tuberculosis recuperados en Cuba entre los años 2010 y 2011 y demostrar el desempeño del Laboratorio Nacional de Referencia en la ejecución de las pruebas de sensibilidad.Materiales y métodos. Se realizó un estudio prospectivo longitudinal en el que se incluyeron 657 aislamientos de M. tuberculosis recibidos de todo el país. Se empleó el método de la nitrato reductasa para detectar resistencia a isoniacida y rifampicina, y el método de las proporciones para corroborar la resistencia a dichos medicamentos e investigar la sensibilidad a estreptomicina, etambutol, ofloxacina, kanamicina y capreomicina en aislamientos multirresistentes. Como parte del control de calidad externo de las pruebas de sensibilidad, se evaluaron dos paneles de cepas de M. tuberculosis.Resultados. En 95,69 % de los aislamientos recuperados de casos nuevos de tuberculosis y en 72,64 % de los recuperados de casos previamente tratados, se encontró sensibilidad a isoniacida y rifampicina, siendo la multirresistencia de 1,03 y 10,38 %, respectivamente. Se encontraron dos aislamientos extremadamente resistentes. Con la excepción del etambutol y la capreomicina, para todos los medicamentos la eficiencia fue de 100% en el control de calidad externo.Conclusiones. Se confirmó la baja prevalencia de aislamientos de M. tuberculosis multirresistentes en Cuba, resultado avalado por el excelente desempeño demostrado en el control de calidad externo de las pruebas de sensibilidad

Phenotypic and Genetic Characterization of Antimicrobial Profiles of Helicobacter pylori Strains in Cuba

The study evaluated the antibiotic resistance patterns of Helicobacter pylori strains against metronidazole and clarithromycin in a hospital in Havana, Cuba. Eighty-five percent, 22.5%, and 10% of 40 H. pylori strains investigated were resistant to metronidazole, ciprofloxacin, and clarithromycin respectively but all were susceptible to amoxicillin and tetracycline. RdxA truncation was found only in metronidazole-resistant strains. In such strains, reported are eight and two novel mutations in the rdxA and frxA genes respectively. Two-point mutations in the 23S rRNA genes of clarithromycin-resistant strains were detected. A high prevalence of metronidazole resistance was found in Cuban H. pylori strains. Mutations in the rdxA gene may contribute more significantly than frxA gene to the high level of resistance to metronidazole. This study supports the need to continue monitoring the antibiotic susceptibility in H. pylori in Cuba to guide the treatment of such infection

Phenotypic and Genetic Characterization of Antimicrobial Profiles of Helicobacter pylori Strains in Cuba

The study evaluated the antibiotic resistance patterns of Helicobacter pylori strains against metronidazole and clarithromycin in a hospital in Havana, Cuba. Eighty-five percent, 22.5%, and 10% of 40 H. pylori strains investigated were resistant to metronidazole, ciprofloxacin, and clarithromycin respectively but all were susceptible to amoxicillin and tetracycline. RdxA truncation was found only in metronidazole-resistant strains. In such strains, reported are eight and two novel mutations in the rdxA and frxA genes respectively. Two-point mutations in the 23S rRNA genes of clarithromycin-resistant strains were detected. A high prevalence of metronidazole resistance was found in Cuban H. pylori strains. Mutations in the rdxA gene may contribute more significantly than frxA gene to the high level of resistance to metronidazole. This study supports the need to continue monitoring the antibiotic susceptibility in H. pylori in Cuba to guide the treatment of such infection

West Nile Virus Infection in Humans and Horses, Cuba

A surveillance system to detect West Nile virus (WNV) was established in Cuba in 2002. WNV infection was confirmed by serologic assays in 4 asymptomatic horses and 3 humans with encephalitis in 2003 and 2004. These results are the first reported evidence of WNV activity in Cuba

Genetic association study of childhood aggression across raters, instruments, and age

Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association metaanalysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis AGGoverall was 3.31% (SE= 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P= 1.6E-06), PCDH7 (P= 2.0E-06), and IPO13 (P= 2.5E-06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations rg among rater-specific assessment of AGG ranged from rg= 0.46 between self- and teacher-assessment to rg= 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong rgs with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range |rg|: 0.19-1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (rg=∼-0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range |rg| : 0.46-0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.</p

Haemophilus influenzae susceptibilidad a los antimicrobianos y comportamiento frente a la vacuna en Cuba

Se presenta el resultado del Monitoreo/Vigilancia de la Resistencia de las cepas circulantes de Haemophilus influenzae en Cuba, aisladas de pacientes con procesos invasivos de meningoencefalitis bacteriana. Fueron estudiadas 1155 cepas colectadas recibidas de todo el pa&amp;iacute;&amp;shy;s, durante un per&amp;iacute;odo ininterrumpido de 17 a&amp;ntilde;os, desde enero del 1989 a diciembre de 2005. El trabajo se desarroll&amp;oacute; en el Laboratorio Nacional de Referencia de Microbiolog&amp;iacute;&amp;shy;a del Instituto de Medicina Tropical &amp;quot;Pedro Kour&amp;iacute;&amp;quot; MINSAP. Todas las cepas fueron caracterizadas microbiol&amp;oacute;gicamente y para su estudio, fueron divididas en dos grupos: un primer grupo (1097), correspondiente a la etapa prevacunal (1989-1999) y un segundo grupo de 58 cepas, de la etapa postvacunal (2000-2005). En ambos, se estudi&amp;oacute; la susceptibilidad a los antimicrobianos determin&amp;aacute;ndose la Concentraci&amp;oacute;n Inhibitoria M&amp;iacute;&amp;shy;nima, comprob&amp;aacute;ndose para el primer grupo, una elevada resistencia a: ampicilina (44.4%), cloranfenicol (40.9%), cotrimoxazol (48.3%) y tetraciclina (30.3%). En la etapa postvacunal, se evidenci&amp;oacute; una disminuci&amp;oacute;n relativa de la resistencia a ampicilina a 36.4%, cloranfenicol a 32.7%, cotrimoxazol a 36.4% y a la tetraciclina de 15.5%, &amp;eacute;sta &amp;uacute;ltima, con resultados estad&amp;iacute;&amp;shy;sticamente significativos. Todas las cepas resistentes a la ampicilina resultaron productoras de &amp;beta; lactamasa. La multirresistencia fue detectada en 40.6% de las cepas en la etapa prevacunal disminuyendo a 13.8% en la postvacunal. De una etapa a otra, los patrones de resistencia y multirresistencia disminuyeron significativamente. Se se&amp;ntilde;ala el impacto positivo de la vacunaci&amp;oacute;n sobre la morbilidad y la mortalidad de la meningoencefalitis bacteriana por Haemophilus influenzae b en Cuba, compar&amp;aacute;ndola con lo sucedido en otros pa&amp;iacute;&amp;shy;ses desarrollados y en desarrollo, as&amp;iacute;&amp;shy; como la potencialidad de que el pa&amp;iacute;&amp;shy;s haya logrado la &amp;uacute;nica vacuna conjugada conocida que hasta la fecha haya sido obtenida por s&amp;iacute;&amp;shy;ntesis qu&amp;iacute;&amp;shy;mica y aplicada masivamente en el 2005, con resultados positivos. Se ratifica la necesidad de mantener el Monitoreo/Vigilancia de las cepas de Haemophilus influenzae en el tiempo, su caracterizaci&amp;oacute;n microbiol&amp;oacute;gica y gen&amp;eacute;tica as&amp;iacute;&amp;shy; como el trabajo del Laboratorio Nacional de Referencia de Microbiolog&amp;iacute;&amp;shy;a, el que permiti&amp;oacute; sustentar la historicidad y comportamiento de las cepas de Haemophilus influenzae b invasivas en el pa&amp;iacute;&amp;shy;s base del presente trabajo