ML Flow serological test: complementary tool in leprosy

Abstract Background The evaluation of household contacts of leprosy cases allows the early diagnosis of new cases. Objective To associate the results of the ML Flow test with the clinical characteristics of leprosy cases and to verify their positivity in household contacts, in addition to describing the epidemiological profile of both. Methods Prospective study with patients diagnosed over the course of one year (n = 26), without prior treatment, and their household contacts (n = 44) in six municipalities in northwestern São Paulo, Brazil. Results There was a predominance of men among the leprosy cases, of 61.5% (16/26); 77% (20/26) were over 35 years old; 86.4% (22/26) were multibacillary; 61.5% (16/26) had a positive bacilloscopy; and 65.4% (17/26) had no physical disability. The ML Flow test was positive in 53.8% (14/26) of the leprosy cases and was associated with those who had a positive bacilloscopy and were diagnosed as multibacillary (p-value <0.05). Among the household contacts, 52.3% (23/44) were women and aged over 35 years; 81.8% (36/44) had been vaccinated with BCG ‒ Bacillus Calmette-Guérin. The ML Flow test was positive in 27.3% (12/44) of household contacts, all of whom lived with multibacillary cases; seven lived with positive bacilloscopy cases and six with consanguineous cases. Study limitations Difficulty in convincing the contacts to undergo the evaluation and collection of the clinical sample. Conclusion The ML Flow test, when positive in household contacts, can help the identification of cases that require more attention by the health team, as it indicates a predisposition to disease development, especially when they are household contacts of multibacillary cases, with positive bacilloscopy and consanguineous. The ML Flow test also helps in the correct clinical classification of the leprosy cases.

ML Flow serological test: complementary tool in leprosy.

BACKGROUND: The evaluation of household contacts of leprosy cases allows the early diagnosis of new cases. OBJECTIVE: To associate the results of the ML Flow test with the clinical characteristics of leprosy cases and to verify their positivity in household contacts, in addition to describing the epidemiological profile of both. METHODS: Prospective study with patients diagnosed over the course of one year (n = 26), without prior treatment, and their household contacts (n = 44) in six municipalities in northwestern São Paulo, Brazil. RESULTS: There was a predominance of men among the leprosy cases, of 61.5% (16/26); 77% (20/26) were over 35 years old; 86.4% (22/26) were multibacillary; 61.5% (16/26) had a positive bacilloscopy; and 65.4% (17/26) had no physical disability. The ML Flow test was positive in 53.8% (14/26) of the leprosy cases and was associated with those who had a positive bacilloscopy and were diagnosed as multibacillary (p-value <0.05). Among the household contacts, 52.3% (23/44) were women and aged over 35 years; 81.8% (36/44) had been vaccinated with BCG ‒ Bacillus Calmette-Guérin. The ML Flow test was positive in 27.3% (12/44) of household contacts, all of whom lived with multibacillary cases; seven lived with positive bacilloscopy cases and six with consanguineous cases. STUDY LIMITATIONS: Difficulty in convincing the contacts to undergo the evaluation and collection of the clinical sample. CONCLUSION: The ML Flow test, when positive in household contacts, can help the identification of cases that require more attention by the health team, as it indicates a predisposition to disease development, especially when they are household contacts of multibacillary cases, with positive bacilloscopy and consanguineous. The ML Flow test also helps in the correct clinical classification of the leprosy cases.

Epidemiological profile and follow-up of patients with pulmonary disease by non-tuberculous mycobacteria in Baixada Santista area, São Paulo.

OBJECTIVE: To present the frequency and species diversity of non-tuberculous mycobacteria, estimate the prevalence of non-tuberculous mycobacterial pulmonary disease, describe the epidemiological profile, and determine the follow-up of patients with non-tuberculous mycobacterial pulmonary disease living in a region with a high burden of tuberculosis. METHODS: This a retrospective cohort observational study using data records obtained from the Instituto Adolfo Lutz - Santos and from the São Paulo Sistema de Vigilância de Tuberculose do Estado de São Paulo in the period between 2000 and 2009. The studied variables were: socio-demographic characteristics, current and past history of tuberculosis, aspects related to diagnosis, and treatment and associated diseases. RESULTS: We included 319 non-tuberculous mycobacteria isolates in the study, corresponding to 257 patients. The species Mycobacterium kansasii (28.5%) and Mycobacterium fortuitum (16.6%) presented the higher occurrence. In 10.9% (24) of the patients, there was a criterion for confirming a case of pulmonary disease due to non-tuberculous mycobacteria. In relation to gender and age, male and individuals over 50 years old were the most frequent. Considering the confirmed cases, 47.8% had a past history of tuberculosis. CONCLUSION: The lack of information about the cases is evident, since pulmonary disease due to non-tuberculous mycobacteria is not mandatory. The therapeutic regimen according to the identified species is fundamental for success in combating the infections caused by non-tuberculous mycobacteria. Besides that, information about the regional epidemiology of pulmonary disease caused by non-tuberculous mycobacteria and the search for associations with other comorbidities are important to establish the correct treatment. In order to improve surveillance of pulmonary diseases by non-tuberculous mycobacteria, we suggest the implantation of a sentinel surveillance and of population-based studies.

Epidemiological profile and follow-up of patients with pulmonary disease by non-tuberculous mycobacteria in Baixada Santista area, São Paulo

ABSTRACT Objective To present the frequency and species diversity of non-tuberculous mycobacteria, estimate the prevalence of non-tuberculous mycobacterial pulmonary disease, describe the epidemiological profile, and determine the follow-up of patients with non-tuberculous mycobacterial pulmonary disease living in a region with a high burden of tuberculosis. Methods This a retrospective cohort observational study using data records obtained from the Instituto Adolfo Lutz - Santos and from the São Paulo Sistema de Vigilância de Tuberculose do Estado de São Paulo in the period between 2000 and 2009. The studied variables were: socio-demographic characteristics, current and past history of tuberculosis, aspects related to diagnosis, and treatment and associated diseases. Results We included 319 non-tuberculous mycobacteria isolates in the study, corresponding to 257 patients. The species Mycobacterium kansasii (28.5%) and Mycobacterium fortuitum (16.6%) presented the higher occurrence. In 10.9% (24) of the patients, there was a criterion for confirming a case of pulmonary disease due to non-tuberculous mycobacteria. In relation to gender and age, male and individuals over 50 years old were the most frequent. Considering the confirmed cases, 47.8% had a past history of tuberculosis. Conclusion The lack of information about the cases is evident, since pulmonary disease due to non-tuberculous mycobacteria is not mandatory. The therapeutic regimen according to the identified species is fundamental for success in combating the infections caused by non-tuberculous mycobacteria. Besides that, information about the regional epidemiology of pulmonary disease caused by non-tuberculous mycobacteria and the search for associations with other comorbidities are important to establish the correct treatment. In order to improve surveillance of pulmonary diseases by non-tuberculous mycobacteria, we suggest the implantation of a sentinel surveillance and of population-based studies.

Mycobacterium leprae: aspectos da resistência aos fármacos na poliquimioterapia / Drug resistance in multidrug therapy for Mycobacterium leprae

Introdução: O diagnóstico da hanseníase possui números significativos que causam preocupação à saúde pública. Os casos de resistência medicamentosa nessa doença se iniciaram em meados dos anos 60 e diante do problema, a Organização Mundial da Saúde instituiu em 1981 a poliquimioterapia, associação dos antibióticos rifampicina, dapsona e clofazimina, tratamento atual de escolha. A resistência aos fármacos na hanseníase é reportada pela literatura, desvelando um obstáculo à sua eliminação. Apresentamos nessa revisão os principais aspectos da resistência medicamentosa no tratamento para hanseníase e seus impactos. Metodologia: Revisão sistemática sobre os aspectos da resistência medicamentosa utilizando a pesquisa exploratória como metodologia de abordagem. Foram pesquisados os termos resistência medicamentosa, hanseníase, recidiva, alterações genéticas e os operadores booleanos "and" e "or" na busca. Resultados e discussão: A dificuldade de tomar a medicação corretamente foi um dos principais fatores que acarretaram resistência do bacilo Mycobacterium leprae aos fármacos. Homens de países norte e sul-americanos e asiáticos foram os mais atingidos por episódios de resistência. A resistência medicamentosa é uma das principais causas de recidivas em hanseníase. O principal fármaco causador de resistência medicamentosa descrito nos trabalhos foi a dapsona (46,6%) e a maioria das alterações genéticas encontradas estão no gene rpoB; 23,2% dos registros relatados foram de resistência secundária aos fármacos e, também, sete casos de resistência múltipla a esses medicamentos. Conclusão: Os principais aspectos da resistência medicamentosa na hanseníase são os equívocos ao ingerir os medicamentos e as alterações genéticas na bactéria. Os impactos causados estão na dificuldade de refazer o tratamento, a possibilidade de nova transmissão e o aparecimento de sintomas mais graves.

Introduction: The diagnosis of leprosy has significant numbers causing public health concern. Reports of drug resistance in this disease begun in the mid-1960s and due to this problem, the World Health Organization instituted a multidrug therapy with rifampicin, dapsone, and clofazimine antibiotic association in 1981, which is currently the first-choice treatment for leprosy. Cases of drug resistance have been reported in literature, revealing an obstacle to the eradication of the disease. This paper has the purpose of presenting the key aspects and impacts of drug resistance in the treatment for leprosy. Methods: Systematic review of the drug resistance aspects using exploratory research as an approach methodology. The authors searched the terms drug resistance, leprosy, recurrence, genetic alterations, and the Boolean operators "and" and "or" between them. Results and discussion: The difficulty in taking the medication correctly was one of the key factors that led to drug resistance for Mycobacterium leprae. Men from North and South American, as well as from Asian countries, were the most affected by episodes of resistance. Drug resistance is one of the main causes of leprosy recurrences. Dapsone was the most frequently identified drug resistance in the studies (46.6%), while most of the genetic alterations were found in the rpoB gene; 23.2% of the cases were from secondary resistance episodes, and seven cases of multiple resistance were reported. Conclusion: The misconceptions when taking the treatment and the Mycobacterium leprae genetic alterations have been described as the key aspects of drugs resistance in leprosy and the impacts caused are the difficulty in redoing the treatment, the possibility of new transmission, and the appearance of more severe symptoms.

Diagnosis of the leprosy laboratory care network in Regional Health Department XV, São José do Rio Preto, São Paulo, Brazil. / Diagnóstico da rede de atendimento laboratorial de hanseníase no Departamento Regional de Saúde XV, São José do Rio Preto, São Paulo.

OBJECTIVE: To present the situational diagnosis of the leprosy laboratory reference network in the region of São José do Rio Preto, SP, Brazil. METHODS: This was an evaluation study with a descriptive design. The data were collected by means of an online form filled in by those in charge of the leprosy program in 2018. RESULTS: All 102 municipalities that make up the region provided the requested data, 82.4% (84/102) requested slit-skin smear microscopy and of these 68 received training. Of the total, 11.7% sent slit-skin smears to other laboratories outside the reference network. Only 57.8% (59/102) requested a biopsy, of these 47 had a doctor responsible for taking the biopsy sample and 31 did not send biopsy samples for analysis in the reference network. Lack of an adequate room, few trained professionals, absence of material for transportation and absence of printed test requisitions were described as aspects that hinder leprosy case diagnosis in the region. CONCLUSION: The laboratory network is fragile and needs to be restructured.

Diagnosis of the Hansen's disease laboratory care network at the Regional Health Department XV, São José do Rio Preto, São Paulo, Brazil / Diagnóstico de la red de atención de laboratorio de la enfermedad de Hansen en el Departamento Regional de Salud XV, São José do Rio Preto, São Paulo, Brasil / Diagnóstico da rede de atendimento laboratorial de hanseníase no Departamento Regional de Saúde XV, São José do Rio Preto, São Paulo

Objective. To present the situational diagnosis of the laboratory reference network for leprosy in the region of São José do Rio Preto, SP, Brazil. Methods. An online form was sent to each person responsible for the leprosy program. Results. All 102 municipalities that make up the region sent the requested data, 82.4% (84/102) requested slit skin smear microscopy and of these 68 received training. Of the total, 11.7% send slit skin smear to other laboratories without respecting the reference network. Only 57.8% (59/102) requested a biopsy, of these 47 had a doctor responsible for the collection and 31 didn´t respect the reference network for forwarding the biopsies. Aspects that make it difficult to diagnose leprosy cases in the region have been described as the lack of an adequate room, trained professionals, the absence of material for transportation and the request for printed exams. Conclusion. The laboratory network is fragile and needs to be respected in its initial composition or reorganized.

Objetivo. Apresentar o diagnóstico situacional da rede laboratorial para hanseníase na região de São José do Rio Preto, SP, Brasil. Métodos. Pesquisa de avaliação com desenho descritivo. Os dados foram coletados por meio de formulário online preenchido pelos responsáveis do programa de hanseníase, em 2018. Resultados. Todos os 102 municípios que compõem a região enviaram os dados solicitados, 84 (82,4%) solicitavam a baciloscopia e destes, 68 receberam capacitação. Do total, 11,7% enviavam baciloscopia para outros laboratórios sem respeitar a rede de referência. Apenas 59 (57,8%) solicitavam a biópsia e destes, 47 tinham médico responsável pela coleta e 31 não respeitavam a rede de referência para encaminhamento das biópsias. Foram descritos, como aspectos que dificultavam o diagnóstico dos casos de hanseníase na região, a falta de sala adequada, poucos profissionais capacitados, ausência de material para transporte e de requisição de exames impressa. Conclusão. A rede laboratorial se encontra fragilizada, necessitando reestruturação.

Diagnóstico da rede de atendimento laboratorial de hanseníase no Departamento Regional de Saúde XV, São José do Rio Preto, São Paulo / Diagnóstico de la red de atención de laboratorio de lepra en el Departamento Regional de Salud XV, São José do Rio Preto, São Paulo, Brasil / Diagnosis of the leprosy laboratory care network in Regional Health Department XV, São José do Rio Preto, São Paulo, Brazil

Objetivo: Apresentar o diagnóstico situacional da rede laboratorial para hanseníase na região de São José do Rio Preto, SP, Brasil. Métodos: Pesquisa de avaliação com desenho descritivo. Os dados foram coletados por meio de formulário online preenchido pelos responsáveis pelo programa de hanseníase, em 2018. Resultados: Todos os 102 municípios que compõem a região enviaram os dados solicitados, 84 (82,4%) solicitavam a baciloscopia; e destes, 68 receberam capacitação. Do total, 11,7% enviavam baciloscopia para outros laboratórios sem respeitar a rede de referência. Apenas 59 (57,8%) solicitavam a biópsia, e destes, 47 tinham médico responsável pela coleta e 31 não respeitavam a rede de referência para encaminhamento das biópsias. Foram descritos, como aspectos que dificultavam o diagnóstico dos casos de hanseníase na região, a falta de sala adequada, poucos profissionais capacitados, ausência de material para transporte e de requisição de exames impressa. Conclusão: A rede laboratorial se encontra fragilizada, necessitando reestruturação.

Objetivo: Presentar el diagnóstico de la situación de la red de laboratorios para lepra en la región de São José do Rio Preto, SP, Brasil. Métodos: Estudio de evaluación con diseño descriptivo. Los datos fueron recolectados a través de un formulario en línea por cada persona responsable del programa de lepra en 2018. Resultados: Los 102 municipios que conforman la región enviaron los datos solicitados, el 82,4% (84/102) solicitaba la baciloscopia y de estos 68 recibieron capacitación. Del total, el 11.7% enviaba la baciloscopia a otros laboratorios sin respetar la red de referencia. Solo el 57,8% (59/102) solicitó una biopsia, y de estos, 47 tenía un médico responsable de la recolección y 31 no respetaron la red de referencia para enviar las biopsias. Los aspectos que dificultan el diagnóstico de casos de lepra en la región SJRP se describieron como la falta de una sala adecuada, profesionales capacitados, ausencia de material para el transporte y de solicitudes de exámenes impresos. Conclusión: La red de laboratorios está fragilizada y debe ser respetada en su composición inicial o reexaminada y reorganizada.

Objective: To present the situational diagnosis of the leprosy laboratory reference network in the region of São José do Rio Preto, SP, Brazil. Methods: This was an evaluation study with a descriptive design. The data were collected by means of an online form filled in by those in charge of the leprosy program in 2018. Results: All 102 municipalities that make up the region provided the requested data, 82.4% (84/102) requested slit-skin smear microscopy and of these 68 received training. Of the total, 11.7% sent slit-skin smears to other laboratories outside the reference network. Only 57.8% (59/102) requested a biopsy, of these 47 had a doctor responsible for taking the biopsy sample and 31 did not send biopsy samples for analysis in the reference network. Lack of an adequate room, few trained professionals, absence of material for transportation and absence of printed test requisitions were described as aspects that hinder leprosy case diagnosis in the region. Conclusion: The laboratory network is fragile and needs to be restructured.

Epidemiologia global de pacientes com tuberculose multidrogarresistente (MDR-TB) e extensivamente resistente (XDR-TB) / Global epidemiology of patients with multidrugresistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB)

A tuberculose multidrogarresistente (MDR-TB) e a tuberculose extensivamente resistente (XDR-TB), levantam preocupações pelo grande número de casos, especialmente na África, Ásia e Europa, e pela taxa de sucesso ainda baixa no tratamento, atingindo 54% para MDR-TB e 30% para XDR-TB. O objetivo do presente estudo é relatar as diferentes realidades epidemiológicas dos doentes com MDR-TB e XDR-TB em diferentes partes do mundo. Foram revisados artigos da última década nas bases científicas disponíveis. Os estudos mostraram que a maioria das pessoas afetadas pela MDR-TB são do sexo masculino, migrantes ou imigrantes, que já haviam sido tratados anteriormente. Descrevemos que o tratamento da tuberculose (TB) usualmente resulta em cura, mas também pode levar à seleção dos bacilos mais resistentes. Mostramos que o surgimento de cepas resistentes na TB se deve ao tratamento inadequado de formas mais simples de TB, com cepas resultantes de manejo difícil e que as populações vulneráveis são as mais afetadas. Salientamos que o abandono do tratamento é fator que comumente origina esse problema complexo da doença e elencamos os genes de resistência mais estudados. (AU)

Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) raise concerns for their great number of cases, especially in Africa, Asia and Europe, and for their still low treatment success rate, reaching 54% for MDR-TB and 30% for XDR-TB. The objective of this study is to report the epidemiological situation of patients with MDR-TB and XDR-TB in different parts of the world. Articles published in the last decade were collected from available scientific databases and reviewed. The studies showed that most of those affected by MDR-TB are male, migrants or immigrants, and had been previously treated for tuberculosis (TB). We report that TB treatment usually ends in cure, but may also lead to selection of the most resistant bacilli. We show that the emergence of resistant strains in TB is due to inappropriate treatment of simpler forms of TB, resulting in strains of difficult management, and that the most vulnerable populations are the most affected. We emphasize that treatment dropout is the factor most commonly associated with this complicated issue, and also list the most studied multidrug resistance genes. (AU)

Mycobacterium tuberculosis e micobactérias não tuberculose em paciente com síndrome da imunodeficiência adquirida e câncer: relato de caso / Mycobacterium tuberculosis and non-tuberculous mycobacteria in a patient with acquired immunodeficiency syndrome and cancer: case report

O presente estudo relata o caso de um paciente de difícil tratamento com infecção mista por tuberculose (TB) e micobactérias não tuberculosas (MNT). O paciente é portador de HIV, câncer e outras doenças associadas. A TB foi elucidada em internação devido a quadro de hemoptise. No período da TB/MNT, a carga viral manteve-se indetectável e o Linfócito T CD4+ variou de 117 a 622 cél/mm3. Os principais sintomas foram febre, tosse, emagrecimento e sudorese. O exame de Raio-X mostrou suspeita de TB bilateral cavitária, a baciloscopia foi negativa e várias culturas apresentaram resultado positivo. As identificações dos isolados foram: Complexo Mycobacterium tuberculosis, Mycobacterium intracelullare/chimaera e M. fortuitum, isolados de amostras pulmonares. Iniciado tratamento para TB em outubro de 2015, atualmente tratando de MNT e mantendo cultura positiva com identificação de M. intracelullare. Os Testes de suscetibilidade aos fármacos para M. intracelullare mostraram resistência a Isoniazida, Rifampicina, Ciprofloxacina, Etambutol e Rifabutina. A terapia para a síndrome da imunodeficiência adquirida (AIDS) aumentou a sobrevida do paciente, trazendo novos desafios para o diagnóstico, controle de tratamento e cuidados da atenção básica para os pacientes com TB/micobacterioses/HIV. Este caso exemplifica que a decisão por um tratamento empírico pode ser uma escolha acertada em casos com clínica e imagem compatíveis e baciloscopia ou TRM negativos.

The present study is a case report of a difficult-to-treat patient with mixed tuberculosis (TB) and non-tuberculous mycobacteria (NTM) infection. The patient has HIV, cancer and other associated diseases. TB was elucidated upon hospitalization due to hemoptysis. In the TB/NTM period, the viral load remained undetectable and CD4 ranged from 622 to 117 cells/mm3. The main symptoms were fever, cough, weight loss and sweating. The X-ray examination showed suspicion of bilateral cavitary TB; the bacilloscopy was negative and several cultures presented positive results. The following isolates were identified: Mycobacterium tuberculosis complex, Mycobacterium intracelullare/chimaera and M. fortuitum, isolated from lung samples. The TB treatment was initiated in October 2015, currently treating NTM and maintaining positive culture with identification of M. intracelullare. Antimicrobial sensitivity tests for M. intracelullare showed resistance to Isoniazid, Rifampicin, Ciprofloxacin, Ethambutol and Rifabutin. Acquired Immune Deficiency Syndrome (AIDS) therapy has increased patient survival, bringing new challenges for diagnosis, treatment control, and basic care for TB/mycobacterial/HIV patients. This case exemplifies that the decision of an empirical treatment may be the correct choice in cases with compatible clinical and imaging tests and negative smear microscopy or molecular tests.

Desempenho da cultura líquida MGIT após implementação em uma rede de laboratórios públicos do estado de São Paulo / Performance of liquid culture MGIT after implementation in a network of public laboratories of Sao Paulo state

A OMS, em 2007, recomendou a implementação da cultura líquida para o diagnóstico da tuberculose (TB) e teste de sensibilidade para países de baixa e média renda. Neste estudo foi avaliado odesempenho da cultura líquida MGIT em condição de rotina após dois anos de implantação em uma rede de laboratórios públicos. Foi efetuada análise retrospectiva de dados da cultura líquida,realizadas em dez laboratórios regionais do Instituto Adolfo Lutz, de janeiro a março de 2010. Foram incluídas amostras submetidas a baciloscopia, cultura líquida MGIT automatizada ou manual eidentificação presuntiva do complexo Mycobacterium tuberculosis (CMTB). Foram detectadas 1.159 culturas positivas. Destas, 113 (9,7%) contaminaram, e 1.046 foram analisadas, sendo 850 (81,3%) CMTB, 116 (11,1%) micobactérias não tuberculosas e 6 (0,6%) Nocardia sp. A taxa de contaminação foi de 2,2% e o acréscimo da cultura para o diagnóstico da TB foi de 29,9%. A média do tempo de detecção da cultura foi de 14,7 dias (DP+/- 11,7 dias). A acurácia da identificação presuntiva foide 91,3%. A cultura líquida MGIT demonstrou ser excelente alternativa para efetuar diagnóstico da TB e das micobacterioses, em razão da rapidez possibilitando uma intervenção rápida e eficaz no tratamento.

In 2007, WHO recommended the implementation of liquid culture for tuberculosis (TB) diagnosis anddrug-susceptibility test in low and middle-income countries. This study evaluated the performanceof MGIT culture in routine condition after two years of its implementation in a public laboratoriesnetwork. This is a retrospective study, which analyzed the data on the liquid culture performed in ten regional laboratories of the Institute Adolfo Lutz, from January to March 2010. The data included clinical samples submitted to microscopy, automated or manual MGIT culture and presumptive M. tuberculosis complex (MTBC) identification by analyzing the cord formation. Culture waspositive in 1,159 samples. Of these, 113 (9.7%) contaminated, and 1,046 were analyzed, of which 850 (81.3%) were identified as MTBC, 116 (11.1%) as non-tuberculous mycobacteria and 6 (0.6%)as Nocardia sp. Contamination rate was 2.2% and the contribution of culture to the TB diagnosis was 29.9%. The detection mean time was 14.7 days (SD+/-11.7 days). The accuracy of the presumptive identification of MTBC was 91.3%. MGIT liquid culture demonstrated to be an excellent alternative for diagnosing TB and mycobacterioses, because of the rapidity of diagnosis, thus allowing an immediate and effective treatment.

Tuberculosis associated factors caused by Mycobacterium tuberculosis of the RDrio genotype

BACKGROUND: Tuberculosis (TB) continues to be a disease that affects many countries around the world, including Brazil. Recently, a subtype of Latin American-Mediterranean family strain was identified and characterised by RDRio. The strain has been associated with different characteristics of the disease. OBJECTIVES: In the present study we investigated the association of epidemiological, clinical, radiological and bacteriological variables with pulmonary tuberculosis caused by RDRioMycobacterium tuberculosis strain in large regions of São Paulo. METHODS: We conducted a cross-sectional study in 530 patients with pulmonary tuberculosis, diagnosed using sputum culture, from two regions of the São Paulo state in Brazil. The samples were brought to São Paulo reference laboratories for epidemiological, clinical, radiological and bacteriological analyses, and the data were obtained from a TB notification system. RDRio genotyping and Spoligotyping of the samples were performed. For the analysis of the categorical variables we used the chi-square test or the Fisher's exact test, and for the continuous variables, the Mann-Whitney test. In addition, a logistic regression was used for multivariate analysis. Differences with p < 0.05 were considered significant. FINDINGS THE RDRIO: deletion was identified in 152 (28.7%) samples. In the univariate analysis, both the age groups above 25 years and alcohol consumption were associated with the RDRio deletion. The multivariate analysis confirmed the association of the RDRio deletion with the age groups: 25-35 years old [OR: 2.28 (1.02-5.07; p = 0.04)] and 36-60 years old (OR: 2.36 (1.11-5.05); p = 0.03], and also with alcohol consumption [OR: 1.63 (1.05-2.54); p = 0,03]. MAIN CONCLUSIONS: In this study, we identified new factors associated with the M. tuberculosis of the RDRio deletion strains infection.

Desempenho da cultura líquida MGIT após implementação em uma rede de laboratórios públicos do estado de São Paulo / Performance of liquid culture MGIT after implementation in a network of public laboratories of Sao Paulo state

A OMS, em 2007, recomendou a implementação da cultura líquida para o diagnóstico da tuberculose (TB) e teste de sensibilidade para países de baixa e média renda. Neste estudo foi avaliado o desempenho da cultura líquida MGIT em condição de rotina após dois anosde implantação em uma rede de laboratórios públicos. Foi efetuada análise retrospectiva de dados da cultura líquida, realizadas em dez laboratórios regionais do Instituto Adolfo Lutz, de janeiro a março de 2010. Foram incluídas amostras submetidas a baciloscopia, cultura líquida MGIT automatizada ou manual e identificação presuntiva do complexo Mycobacterium tuberculosis (CMTB). Foram detectadas 1.159 culturas positivas. Destas, 113 (9,7%) contaminaram, e 1.046 foram analisadas, sendo 850 (81,3%) CMTB, 116 (11,1%) micobactérias não tuberculosas e 6 (0,6%) Nocardia sp A taxa de contaminação foi de 2,2% e o acréscimo da cultura para o diagnóstico da TB foi de 29,9%. A média do tempo de detecção da cultura foi de 14,7 dias (DP+/- 11,7 dias). A acurácia da identificação presuntiva foi de 91,3%. A cultura líquida MGIT demonstrou ser excelente alternativa para efetuar diagnóstico da TB e das micobacterioses, em razão da rapidez possibilitando uma intervenção rápida e eficaz no tratamento.

In 2007, WHO recommended the implementation of liquid culture for tuberculosis (TB) diagnosis and drug-susceptibility test in low and middle-income countries. This study evaluated the performance of MGIT culture in routine condition after two years of its implementation in a public laboratories network.This is a retrospective study, which analyzed the data on the liquid culture performed in ten regional laboratories of the Institute Adolfo Lutz, from January to March 2010. The data included clinical samples submitted to microscopy, automated or manual MGIT culture and presumptive M. tuberculosis complex (MTBC) identification by analyzing the cord formation. Culture was positive in 1,159 samples. Of these, 113 (9.7%) contaminated, and 1,046 were analyzed, of which 850 (81.3%) were identified as MTBC, 116 (11.1%) as non-tuberculous mycobacteria and 6 (0.6%) as Nocardia sp. Contamination rate was 2.2% and the contribution of culture to the TB diagnosis was 29.9%. The detection mean time was 14.7 days (SD+/-11.7 days). The accuracy of the presumptive identification of MTBC was 91.3%. MGIT liquid culture demonstrated to be an excellent alternative for diagnosing TB and mycobacterioses, because of the rapidity of diagnosis, thus allowing an immediate and effective treatment.

Virtual network: to analyze the knowledge about leprosy of MORHAN volunteers

O objetivo do estudo foi revelar o conhecimento sobre hanseníase dos voluntários participantes da Rede virtual de Mobilização (REMOB) do Movimento de Reintegração das pessoas Atingidas pela Hanseníase (MORHAN) em relação a aspectos gerais, diagnóstico, transmissão e tratamento. Os voluntários da REMOB foram convidados a responder um formulário on line contendo 35 afirmativas sobre hanseníase e perguntas específicas sobre o voluntariado. Participaram do estudo 105 voluntários, representando 20 estados brasileiros, a média de idade foi de 38,9 (dp14,14), 72,4% eram atuantes na área da saúde, 73,3% tinham nível superior e/ou pós-graduação, para 63,8% as atividades voluntárias não iniciaram por conhecer alguém com a doença. O percentual médio de acertos sobre diagnóstico foi de 84,2%, aspectos gerais 83,2%, transmissão 71,6% e tratamento 61,9%. O conhecimento sobre hanseníase foi maior nas questões referentes ao diagnóstico e menor sobre tratamento que embora sejam bastante específicas, devem ser alvo de investimento para capacitação permanente.

The objective of this study was to investigate knowledge about leprosy of volunteers participating in the Virtual Mobilization Network (REMOB) for the Reintegration Movement of People Affected by Leprosy (MORHAN) in relation to general aspects, diagnosis, transmission and treatment of the disease. REMOB volunteers were asked to answer an online questionnaire containing 35 questions about leprosy and specific questions about volunteering. The study included 105 volunteers in 20 Brazilian states with a mean age of 38.9 (sd=14.14) years. A total of 72.4% were healthcare professionals, 73.3% had college diplomas or were postgraduates, and for 63.8% volunteering did not begin because they knew someone with the disease. Respondents correctly answered, on average, 84.2% of the questions about diagnosis, 83.2% about general aspects, 71.6% about transmission and 61.9% on treatment. The knowledge of leprosy was better in respect to the diagnosis and worse in relation to treatment and should be the target for investment in ongoing training.

Clinical and epidemiological profiles of individuals with drug-resistant tuberculosis.

Drug-resistant tuberculosis (TB) is a growing global threat. Approximately 450,000 people developed multidrug-resistant TB worldwide in 2012 and an estimated 170,000 people died from the disease. This paper describes the sociodemographic, clinical-epidemiological and bacteriological aspects of TB and correlates these features with the distribution of anti-TB drug resistance. Mycobacterium tuberculosis (MT) cultures and drug susceptibility testing were performed according to the BACTEC MGIT 960 method. The results demonstrated that MT strains from individuals who received treatment for TB and people who were infected with human immunodeficiency virus were more resistant to TB drugs compared to other individuals (p < 0.05). Approximately half of the individuals received supervised treatment, but most drug-resistant cases were positive for pulmonary TB and exhibited positive acid-fast bacilli smears, which are complicating factors for TB control programs. Primary healthcare is the ideal level for early disease detection, but tertiary healthcare is the most common entry point for patients into the system. These factors require special attention from healthcare managers and professionals to effectively control and monitor the spread of TB drug-resistant cases.

Clinical and epidemiological profiles of individuals with drug-resistant tuberculosis

Drug-resistant tuberculosis (TB) is a growing global threat. Approximately 450,000 people developed multidrug-resistant TB worldwide in 2012 and an estimated 170,000 people died from the disease. This paper describes the sociodemographic, clinical-epidemiological and bacteriological aspects of TB and correlates these features with the distribution of anti-TB drug resistance. Mycobacterium tuberculosis (MT) cultures and drug susceptibility testing were performed according to the BACTEC MGIT 960 method. The results demonstrated that MT strains from individuals who received treatment for TB and people who were infected with human immunodeficiency virus were more resistant to TB drugs compared to other individuals (p < 0.05). Approximately half of the individuals received supervised treatment, but most drug-resistant cases were positive for pulmonary TB and exhibited positive acid-fast bacilli smears, which are complicating factors for TB control programs. Primary healthcare is the ideal level for early disease detection, but tertiary healthcare is the most common entry point for patients into the system. These factors require special attention from healthcare managers and professionals to effectively control and monitor the spread of TB drug-resistant cases.

Controle de qualidade externo nos laboratórios de tuberculose do estado de São Paulo, Brasil / External quality control of the tuberculosis laboratory network of São Paulo state, Brazil

Os objetivos deste estudo foram de avaliar a qualidade técnica de laboratórios públicos e conveniados ao Sistema Único de Saúde(SUS) que fazem baciloscopia da tuberculose (TB) e de apresentar os dados do Controle de Qualidade Externo (CQE) realizado na rede de laboratórios de TB do estado de São Paulo, Brasil. Neste contexto, foi realizado o estudo descritivo retrospectivo do CQE de 198 laboratórios supervisionados no biênio 2009-2010. A concordância entre os resultados das baciloscopias executadas nos laboratórios supervisionados e de supervisores foi de 99,4 %; e as porcentagens relativas de resultados falso-positivos e falsonegativos foram, respectivamente, de 1,9 % e 0,4 %. A comparação entre a qualidade dos esfregaços realizados por laboratórios públicos e conveniados mostrou que os públicos apresentaram qualidade superior (valor-p<0,05). Este estudo mostrou que 74,2 % dos laboratórios foram aprovados no CQE; e o desempenho dos laboratórios conveniados foi inferior ao dos públicos. Estes dados reforçam a importância de manter programa de CQE de baciloscopia e de capacitação dos profissionais, considerando-se ser este um exame diagnóstico muito utilizado e relevante no país...

Cenário atual da tuberculose / Current scenario of tuberculosis

Mesmo após 133 anos desde a descoberta do Mycobacterium tuberculosis, a tuberculose continua ser uma das principais causas de morte por doenças infecciosas no mundo, principalmente em países em desenvolvimento.O objetivo deste estudo foi mostrar aspectos relevantes da doença visando uma atualização literária e a busca de um olhar mais atento à problemática da tuberculose no contexto atual. Foram utilizados 130 artigos advindos das bases LILACS, MEDLINE/PUBMED, SCielo, Paho, Biblioteca Cochrane, WHOLIS, IBECS e Scopus, com as principais palavras-chaves selecionadas em terminologia em saúde encontradas no DECS. As espécies pertencentes ao Complexo M. tuberculosis compartilham cerca de 99% de identidade do DNA,com sequências altamente conservadas, mas diferem na distribuição geográfica, patogenicidade e hospedeiros. O mecanismo de resistência clinicamente significativo para rifampicina é uma mutação do gene rpoB, que codifica o alvo desse antibiótico. Há grandes avanços no diagnóstico da TB, com novos instrumentos de biologia molecular e testes rápidos, mas ainda não substituem os métodos clássicos bacteriológicos, apesar de suas conhecidas limitações. Atualmente, a associação de métodos moleculares, principalmente aqueles baseados em reações da PCR tem proporcionado grande impulso nos estudos da epidemiologia molecular do MT. Embora haja uma diminuição do número de casos no mundo, dentre os desafios da doença estão a necessidade de pesquisas na área, envolvimento político para solucionar as questões sociais atribuídas à TB, treinamento permanente dos profissionais e monitoramento de vigilância dos casos para eliminar a doença no cenário mundial.

Even 133 years after the discovery of Mycobacterium tuberculosis, tuberculosis continues to be one of the main causes of death due to infectious diseases worldwide, especially in developing countries. The objective of this study was, after a survey of recent publications, to show issues relevant to the disease and to takea closer look at the tuberculosis problem in the current context. A total of 130 articles were found in the LILACS, MEDLINE/PubMed, SciELO, Paho, Cochrane Library, WHOLIS, IBECS and Scopus databases using the main keywords selected from health terminology of MeSH. Species belonging to the M. tuberculosis complex have highly conserved sequences and share about 99% DNA identity, but differ in their geographic distribution, pathogenicityand host. The clinically significant mechanismof rifampicin resistance is due to a mutation of the rpoB gene which encodes the target of the antibiotic. Great advances in the diagnosis of tuberculosis have occurred, with new molecular biology tools and rapid tests, but without replacing classical bacteriological methods, despite their known limitations. Recently, the association of molecular methods, especially based on PCR, has provided great impetus in molecular epidemiology studies of M. tuberculosis. Although the number of cases in the world has decreased, among the challenges are the need for further research, political involvement to solve social issues linked to tuberculosis, permanent training and the surveillance of cases in order to eliminate the disease on the world stage.

Detection of Mycobacterium tuberculosis complex by nested polymerase chain reaction in pulmonary and extrapulmonary specimens / Detecção do complexo Mycobacterium tuberculosis por nested polymerase chain reaction em espécimes pulmonares e extrapulmonares

OBJECTIVE: To compare the performance of nested polymerase chain reaction (NPCR) with that of cultures in the detection of the Mycobacterium tuberculosis complex in pulmonary and extrapulmonary specimens. METHODS: We analyzed 20 and 78 pulmonary and extrapulmonary specimens, respectively, of 67 hospitalized patients suspected of having tuberculosis. An automated microbial system was used for the identification of Mycobacterium spp. cultures, and M. tuberculosis IS6110 was used as the target sequence in the NPCR. The kappa statistic was used in order to assess the level of agreement among the results. RESULTS: Among the 67 patients, 6 and 5, respectively, were diagnosed with pulmonary and extrapulmonary tuberculosis, and the NPCR was positive in all of the cases. Among the 98 clinical specimens, smear microscopy, culture, and NPCR were positive in 6.00%, 8.16%, and 13.26%, respectively. Comparing the results of NPCR with those of cultures (the gold standard), we found that NPCR had a sensitivity and specificity of 100% and 83%, respectively, in pulmonary specimens, compared with 83% and 96%, respectively, in extrapulmonary specimens, with good concordance between the tests (kappa, 0.50 and 0.6867, respectively). CONCLUSIONS: Although NPCR proved to be a very useful tool for the detection of M. tuberculosis complex, clinical, epidemiological, and other laboratory data should also be considered in the diagnosis and treatment of pulmonary and extrapulmonary tuberculosis. .

OBJETIVO: Comparar o desempenho da técnica nested polymerase chain reaction (NPCR) com aquele de culturas na detecção do complexo Mycobacterium tuberculosis em espécimes pulmonares e extrapulmonares. MÉTODOS: Analisamos 20 e 78 espécimes pulmonares e extrapulmonares, respectivamente, de 67 pacientes hospitalizados com suspeita de tuberculose. Um sistema automatizado foi utilizado na identificação de culturas de Mycobacterium spp., e M. tuberculosis IS6110 foi utilizada como sequência alvo na NPCR. A estatística kappa foi utilizada para verificar a concordância entre os resultados. RESULTADOS: Entre os 67 pacientes, 6 e 5, respectivamente foram diagnosticados com tuberculose pulmonar e extrapulmonar, e a NPCR foi positiva em todos os casos. Entre os 98 espécimes clínicos, a baciloscopia, cultura e NPCR foram positivas em 6,00%, 8,16% e 13,26%, respectivamente. Comparando-se os resultados da NPCR com aqueles da cultura (padrão ouro) nos espécimes pulmonares, a sensibilidade e a especificidade foram 100% e 83%, respectivamente, enquanto essas nos espécimes extrapulmonares foram 83% e 96% respectivamente, com boa concordância entre os testes (kappa, 0,50 e 0,6867, respectivamente). CONCLUSÕES: Embora a NPCR tenha se mostrado uma ferramenta muito útil na detecção do complexo M. tuberculosis, No entanto, os resultados positivos da NPCR devem ser associados à clínica, dados clínicos, epidemiológicos e outros dados laboratoriais devem também ser considerados no diagnóstico e tratamento da tuberculose pulmonar e extrapulmonar. .

Detection of Mycobacterium tuberculosis complex by nested polymerase chain reaction in pulmonary and extrapulmonary specimens.

OBJECTIVE: To compare the performance of nested polymerase chain reaction (NPCR) with that of cultures in the detection of the Mycobacterium tuberculosis complex in pulmonary and extrapulmonary specimens. METHODS: We analyzed 20 and 78 pulmonary and extrapulmonary specimens, respectively, of 67 hospitalized patients suspected of having tuberculosis. An automated microbial system was used for the identification of Mycobacterium spp. cultures, and M. tuberculosis IS6110 was used as the target sequence in the NPCR. The kappa statistic was used in order to assess the level of agreement among the results. RESULTS: Among the 67 patients, 6 and 5, respectively, were diagnosed with pulmonary and extrapulmonary tuberculosis, and the NPCR was positive in all of the cases. Among the 98 clinical specimens, smear microscopy, culture, and NPCR were positive in 6.00%, 8.16%, and 13.26%, respectively. Comparing the results of NPCR with those of cultures (the gold standard), we found that NPCR had a sensitivity and specificity of 100% and 83%, respectively, in pulmonary specimens, compared with 83% and 96%, respectively, in extrapulmonary specimens, with good concordance between the tests (kappa, 0.50 and 0.6867, respectively). CONCLUSIONS: Although NPCR proved to be a very useful tool for the detection of M. tuberculosis complex, clinical, epidemiological, and other laboratory data should also be considered in the diagnosis and treatment of pulmonary and extrapulmonary tuberculosis.