Recent transmission of drug-resistant Mycobacterium tuberculosis in a prison population in southern Brazil / Transmissão recente de Mycobacterium tuberculosis resistentes aos antimicrobianos em população carcerária no sul do Brasil

ABSTRACT We conducted a cross-sectional, retrospective study, characterized by classical and molecular epidemiology, involving M. tuberculosis isolates from a regional prison in southern Brazil. Between January of 2011 and August of 2014, 379 prisoners underwent sputum smear microscopy and culture; 53 (13.9%) were diagnosed with active tuberculosis. Of those, 8 (22.9%) presented with isoniazid-resistant tuberculosis. Strain genotyping was carried out by 15-locus mycobacterial interspersed repetitive unit-variable-number tandem-repeat analysis; 68.6% of the patients were distributed into five clusters, and 87.5% of the resistant cases were in the same cluster. The frequency of drug-resistant tuberculosis cases and the rate of recent transmission were high. Our data suggest the need to implement an effective tuberculosis control program within the prison system.

RESUMO Estudo transversal, retrospectivo, com isolados de M. tuberculosis de pacientes de um presídio regional no sul do Brasil, caracterizado através de epidemiologia clássica e molecular. Entre janeiro de 2011 e agosto de 2014, 379 detentos foram submetidos a baciloscopia e cultura, sendo 53 (13,9%) diagnosticados com tuberculose ativa. Desses, 8 (22,9%) apresentavam tuberculose resistente a isoniazida. A genotipagem das cepas foi realizada por 15-locus mycobacterial interspersed repetitive units-variable number of tandem repeat analysis; 68,6% dos pacientes estavam distribuídos em cinco clusters, e 87,5% dos casos resistentes estavam em um mesmo cluster. Verificou-se uma frequência elevada de casos de resistência e alta taxa de transmissão recente. Estes dados sugerem a necessidade da implantação de um programa efetivo de controle da tuberculose no sistema prisional.

Active case detection among household contacts of multi drug resistant tuberculosis patients in a tertiary care setting

Close contacts of multi drug resistant tuberculosis patients are expected to be at increased risk of developing the disease and therefore need screening on priority basis to have an effective TB control program. Active household contact screening is an effective and cheaper way to detect and treat MDR-TB at its early stages. To determine active TB cases among household contacts of MDR-TB patients in a tertiary care setting. Descriptive study, conducted at PMRC TB Research Centre in collaboration with Institute of Chest Medicine, King Edward Medical University/Mayo Hospital, Lahore from November 2012 to December 2013. Patients suffering from MDR-TB and seeking treatment from Institute of Chest Medicine were selected as index patients. Their contacts [spouses, children, parents, siblings and other relatives] underwent sputum smear microscopy. Those found positive for AFB were subjected for MTB RIF assay by GeneXpert to determine rifampicin resistance. Data was analysed using IBM Statistics SPSS version 20.0. A total of 692 contacts of 112 MDR-TB patients were studied. Among them, 374[54%] were males and 318[46%] female. Seventeen contacts were found smear positive and of these 15[88%] were also confirmed as MTB by GeneXpert. Four [23%] contacts were rifampicin resistant. Of the affected contacts, majority were sisters [23.5%]. Active TB was detected in contacts of patients having MDR-TB with few also showing rifampicin resistance. TB screening should be done in all contacts of TB patients, especially those having drug resistance

Caracterização da tuberculose multidroga resistente durante a gravidez, em Campinas, Estado de São Paulo, Brasil, no período de 1995 a 2007 / Characterization of multidrug-resistant tuberculosis during pregnancy in Campinas, State of São Paulo, Brazil, from 1995 to 2007

INTRODUÇÃO: Foi feito um acompanhamento das gestantes tratadas para tuberculose multidroga resistente (TB-MDR) durante a gravidez, em Campinas, Estado de São Paulo, no período de 1995 a 2007. MÉTODOS: No estudo retrospectivo, foram incluídas pacientes com cepa resistente, pelo menos à isoniazida e à rifampicina e gravidez em qualquer momento, durante o tratamento. Os casos receberam esquema individualizado baseado nos padrões de resistência medicamentosa e nos antecedentes de tratamento de cada paciente. RESULTADOS: Sete gestantes apresentaram resistência a duas ou mais drogas. Três já estavam grávidas, antes do início do tratamento e quatro engravidaram depois. Duas estavam com Aids, uma foi a óbito e em outra ocorreu falência de tratamento. Todas apresentaram tuberculose avançada com achados radiológicos graves e para cinco pacientes o tempo médio da conversão do escarro foi de quatro meses. Duas gestantes foram curadas. Dois recém-nascidos foram infectados com o HIV por suas progenitoras. CONCLUSÕES: O resultado do tratamento foi insatisfatório e a supervisão direta é imperativa na TB-MDR durante a gestação. O planejamento familiar deve ser fortemente recomendado.

INTRODUCTION: There was a follow-up of pregnant women treated for multidrug-resistance tuberculosis (MDR-TB) during pregnancy in Campinas, State of São Paulo, Brazil, from 1995 to 2007. METHODS: In a retrospective study, patients with tuberculosis who were resistant to at least isoniazid and rifampicin and had pregnancy at any time during the treatment were included. The cases were individually treated, considering drug susceptibility test results and patients' prior treatments. RESULTS: Seven cases presented resistance to two or more drugs. Three were already pregnant before the beginning of the treatment, and four conceived after. Two were with AIDS; one died, and the therapeutic program in the other one failed. All showed advanced tuberculosis with acute radiological findings, and the median sputum conversion time for five patients was four months. Two patients were cured. Two newborn babies were infected with HIV by their mothers. CONCLUSIONS: The outcome was unsatisfactory, and direct supervision is imperative in MDR-TB during pregnancy. The family planning program should be strongly recommended.

Tuberculosis transmission across the United States-Mexico border / Transmisión transfronteriza de la tuberculosis entre México y los Estados Unidos

In this era of increasing drug resistance among infectious diseases such as tuberculosis (TB), the complex population dynamics of border areas must be monitored more extensively. TB remains a major public health threat; its antimicrobial treatment is long; and the only vaccine licensed in the world, live-attenuated Mycobacterium bovis Bacille Calmette-Guérin (BCG), exhibits varying efficacy. In addition to epidemiological surveillance, the underlying determinants contributing to the health and wellbeing of populations are of key importance. Although it received heightened attention in the past, tuberculosis transmission in the United States-Mexico border area demands renewed interest. Lessons learned should be applied to similar areas around the globe.

En esta época en la que cada vez es mayor la farmacorresistencia de enfermedades infecciosas como la tuberculosis, es preciso vigilar más ampliamente la compleja dinámica de la población de las zonas fronterizas. La tuberculosis sigue siendo un problema muy importante de salud pública, el tratamiento antimicrobiano es prolongado y la vacuna BCG (Bacilo de Calmette-Guérin) -la única autorizada en el mundo, elaborada con bacilos atenuados de Mycobacterium bovis- tiene eficacia variable. Además de la vigilancia epidemiológica, revisten suma importancia los determinantes fundamentales que inciden en la salud y el bienestar de las poblaciones. Si bien la transmisión transfronteriza de la tuberculosis entre México y los Estados Unidos recibió gran atención en el pasado, la situación actual exige renovar el interés por este tema. Es necesario aplicar las lecciones aprendidas en zonas similares del resto del mundo.

Tuberculosis pediátrica, MDR-TB y XDR-TB en la provincia de Buenos Aires durante el período 2002-2007 / Paediatric tuberculosis, MDR-TB and XDR-TB in Buenos Aires province during the period 2002-2007

Los objetivos de este estudio fueron: describir la incidencia de tuberculosis (TB), MDR-TB Y XDR-TB en niños y adultos, y analizar la transmisión entre contactos comprobados. Fue realizado un análisis retrospectivo de los casos notificados al Programa de Control de Tuberculosis de Buenos Aires (PCTB). Durante este lapso se notificaron 30784 casos nuevos de TB, 4276 (14.0%) niños y 26508 adultos. El 4.9% (14/284) y el 71 % (146/ 2042) de los niños y adultos tenían MDR-TB, 5.1 % (13/256) de los niños y 5.3% (86/ 1616) de los adultos eran vírgenes de tratamiento. Se registraron 12 casos de XDR-TB en adultos, 3 sin tratamiento previo. Además 25.0% (40/160) de los casos MDR pertenecían a 9 familias o eran trabajadores de salud. La transmisión en estos casos fue verificada por pruebas moleculares. La evaluación del tratamiento para casos con MDR-TB o XDR-TB pudo realizarse en 47.5% de los casos ya que de 76 adultos y 6 niños no se obtuvo información. Asimismo, se pone de manifiesto la necesidad de contar con una notificación exhaustiva y un riguroso estudio de cohortes que permitan conocer y evaluar la situación real de la TB en la provincia. Debería asimismo recomendarse el incremento en la realización de cultivos y pruebas de sensibilidad que permitan determinar el perfil de resistencia bacteriana para tratar apropiadamente la TBP y la MDR- TB, indicadores de transmisión activa y del impacto de las actividades del PCTB en la comunidad.

The aims of the study were to describe the incidence of tuberculosis (TB), multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) in children and adults and to analyze the transmission of infection among proved contacts. The method was a retrospective analysis of notified cases to the TB Control Programme of Buenos Aires province. During the period 2002-2007, 30784 TB cases were notified; 4276 (14.0%) were children and 26508 adults. The prevalence of MDR-TB was 4.9% (14/ 284) among children and 7.1 % (146/2042) among adults. The proportions of MDR-TB cases who had not had any previous TB treatment were 5.1 % (13/256) in children and 5.3% (86/1616) in adults. A total of 12 XDR-TB cases were notified in adults; 3 of them without any previous TB treatment. Among the 160 MDR-TB cases, 40 belonged to 9 families or were health workers. Transmission in these cases was traced by molecular epidemiology tests. Data on evaluation of treatment outcomes were only available for 47.5% of MDR-TB cases; no information was registered in 76 adults and 6 children. Intensive notification and strict follow-up of cohort of cases are needed in arder to know and assess the actual TB situation in the province. It is also recommended to increase the use of cultures and drug susceptibility tests to have better estimates of the prevalence of drug-resistant TB, prescribe more effective treatment of TB and MDR- TB, improve indicators of infection transmission and better assess the impact of the TB control activities in the community.

Tuberculosis transmission of predominant genotypes of Mycobacterium tuberculosis in Northern suburbs of Buenos Aires city region / Transmisión de la tuberculosis por genotipos predominantes de Mycobacterium tuberculosis en la región Gran Buenos Aires Norte

In 2003, the incidence of tuberculosis in Argentina showed an increase compared to 2002. The severe national crisis at the end of the 90s has probably strongly contributed to this situation. The goal of this work was to estimate the extent of the spread of the most predominant Mycobacterium tuberculosis strains and to assess the spread of predominant M. tuberculosis clusters as determined by spoligotyping and IS6110 RFLP. The study involved 590 pulmonary, smear-positive TB cases receiving medical attention at health centers and hospitals in Northern Buenos Aires (NBA) suburbs, from October 2001 to December 2002. From a total of 208 clinical isolates belonging to 6 major clusters, 63 (30.2%) isolates had identical spoligotyping and IS6110 RFLP pattern. Only 22.2% were shown to have epidemiological connections with another member of their respective cluster. In these major clusters, 30.2% of the 208 TB cases studied by both molecular techniques and contact tracing could be convincingly attributable to a recently acquired infection. This knowledge may be useful to assess the clonal distribution of predominant M. tuberculosis clusters in Argentina, which may make an impact on TB control strategies.

La incidencia de la tuberculosis en Argentina mostró en 2003 un incremento en comparación con 2002. La grave crisis nacional a fines de los 90 ha probablemente contribuido en gran medida a esta situación. El objetivo del presente trabajo fue determinar la diversidad genética de aislamientos de Mycobacterium tuberculosis y el grado de dispersión de algunas cepas mayoritarias genéticamente relacionadas. El estudio involucró 590 aislamientos clínicos provenientes de muestras respiratorias con examen directo positivo, de pacientes atendidos en los hospitales y centros de salud que conforman la región Gran Buenos Aires Norte (NBA), de octubre de 2001 a diciembre de 2002. De 208 aislamientos que se encontraron en los 6 mayores clusters, 63 (30,2%) tenían patrones idénticos de spoligotyping y de IS6110 RFLP. En el 22,2% de los casos fue posible verificar la conexión epidemiológica con otro miembro del respectivo cluster. Concluimos que el 30,2% de estos agrupamientos principales pueden ser atribuidos a una infección reciente. Estos resultados pueden ser útiles para determinar la distribución clonal de los grupos predominantes de M. tuberculosis en Argentina, lo que puede impactar en las estrategias de control de la tuberculosis.

Ocorrência de tuberculose doença entre contatos de tuberculose sensível e multirresistente / Occurrence of active tuberculosis in households inhabited by patients with susceptible and multidrug-resistant tuberculosis

INTRODUÇAO: Desde os primeiros anos da quimioterapia anti-tuberculose, existe polêmica a respeito da transmissibilidade, infectividade, virulência e patogenicidade de bacilos sensíveis e resistentes à quimioterapia. OBJETIVO: Determinar a ocorrência de casos de tuberculose doença entre contatos intra-domiciliares de tuberculose multirresistente e tuberculose sensível. MÉTODO: Foi realizado um estudo caso-controle, sendo considerado tuberculose multirresistente o caso de portador de bacilo resistente a pelo menos rifampicina e isoniazida, e tuberculose sensível o caso que tivesse feito o primeiro tratamento num período semelhante ao primeiro tratamento do caso de tuberculose multirresistente, estando o paciente curado no momento da entrevista. Contato foi definido como o residente no domicílio do caso índice. Os casos foram selecionados a partir dos resultados dos testes de sensibilidade obtidos pelo método das proporções no Laboratório Central do Estado do Ceará, e os controles constituídos por pacientes bacilíferos registrados no Programa de Controle da Tuberculose, entre 1.990 e 1.999. RESULTADOS: Foram avaliados 126 portadores de tuberculose multirresistente e 176 de tuberculose sensível. O número de contatos foi de 557 no grupo dos casos, 752 no grupo controle e a média de contatos por caso índice foi de 4,42 e 4,27 respectivamente. Entre os casos, 4,49 por cento dos contatos (25/557) fizeram tratamento para tuberculose após os casos índices. Esse percentual foi de 5,45 por cento (41/752) entre os controles (p = 0,4468). Ocorreu micro-epidemia de tuberculose multirresistente confirmada por teste de sensibilidade em oito famílias. CONCLUSAO: Os resultados deste estudo sugerem que a ocorrência de tratamentos de tuberculose gerados entre contatos intra-domiciliares de tuberculose sensível e tuberculose multirresistente é semelhante.

Molecular fingerprinting of multidrug-resistant mycobacterium tuberculosis strains in Beirut reveals genetic diversity and father to daughter transmission

The typing of six consecutive multidrug-resistant Mycobacterium tuberculosis strains isolated from patients with tuberculosis [TB] at the American University of Beirut Medical Center, was performed by touchdown double-repetitive-element [DRE]-PCR. The isolates exhibited four distinct patterns in DRE-PCR with three isolates exhibiting unique patterns and three isolates yielded similar DNA fragment patterns [cluster pattern]. Only two of the three cluster isolates exhibited identical patterns as revealed by restriction fragment length polymorphism [RFLP] targeting specific mutations in the rpoB and katG genes that confer resistance to rifampin and isoniazid, respectively. A direct epidemiological linkage for the two isolates exhibiting genotypic relatedness was also established as the isolates were recovered from a 33-year-old man and his 8-year-old daughter. The data show that transmission of multidrug-resistant M. tuberculosis strains is contributing to the emergence of drug-resistant TB in Beirut. Combining DRE-PCR with RFLP at the rpo B and katG genes could provide a powerful means for investigating the spread of multidrug-resistant M. tuberculosis strains in Lebanon

Hospital transmission of multidrug-resistant Mycobacterium tuberculosis in Rosario, Argentina

Multidrug-resistant tuberculosis has emerged over the last two years at Carrasco Hospital, located in Rosario city. Nosocomial transmission among 7 AIDS patients admitted into the same ward between June and December/94 was supported by temporal clustering of cases, matching drug susceptibility, and identical lS6llO fingerprints. Among 8 non-HIV chronic cases without evidence of reciprocal contact outside the hospital, two additional clusters of 2 and 4 cases, respectively, were identified. The latter was found to be generated by a strain genetically related to the one that infected AIDS patients. lt is hypothesized that an ancestor strain, common to both, might have been brought into the hospital long before the outbreak was first suspected.