Tuberculose: principais fatores associados ao abandono do tratamento / Tuberculosis: main factors associated with treatment abandonment / Tuberculosis: principales factores asociados al abandono del tratamiento

O abandono do tratamento de tuberculose é uma questão relevante e preocu- pante na saúde pública mundial. Mediante uma revisão integrativa, esse estudo busca identificar os possíveis fatores que levam ao abandono do tratamento. Foi realizada pes- quisa em estudos indexados nas bases de dados: Biblioteca Virtual em Saúde (BVS) e Scientific Eletronic Library Online (SciELO), no período de 2017 a 2021, utilizando-se os seguintes descritores (DeCS): tuberculose, agente antituberculose e tuberculose pul- monar. Ao fim, foram selecionados onze estudos, publicados nos idiomas português, es- panhol e inglês. Os resultados mostraram que o abandono está relacionado a fatores de diversas esferas, com destaque para as esferas social, da saúde e a do próprio tratamento. Como perfil das pessoas dos casos de abandono, em geral, observou-se que elas são eco- nomicamente ativas, com faixa etária entre 15 e 49 anos, possuem baixa escolaridade, baixa renda e é comum que os usos abusivos de álcool e drogas sejam apresentados como comorbidades relevantes. Portanto, o trabalho evidenciou os principais fatores associados ao abandono do tratamento de tuberculose e a importância da participação de diferentes atores como forças que somarão para diminuir a ocorrência do problema em questão.

The abandonment of tuberculosis treatment is a relevant and worrisome issue in public health worldwide. Through an integrative review, this study seeks to iden- tify the possible factors that lead to treatment dropout. A search was carried out in studies indexed in the databases: Virtual Health Library (BVS) and Scientific Electronic Library Online (SciELO), from 2017 to 2021, using the following descriptors (DeCS): tuberculo- sis, antitubercular agentes and pulmonary tuberculosis. Finally, eleven studies, published in Portuguese, Spanish and English, were selected. The results showed that abandonment is related to factors from different spheres, with emphasis on the social, health and treat- ment spheres. As for the profile of people in cases of abandonment, in general, it was observed that they are economically active, aged between 15 and 49 years old, have low education, low income and it is common for alcohol and drug abuse to be presented as relevant comorbidities. Therefore, the work highlighted the main factors associated with the abandonment of tuberculosis treatment and the importance of the participation of dif- ferent actors as forces that will add to reduce the occurrence of the problem in question. KEYWORDS: Tuberculosis; Antitubercular Agents; Pulmonary Tuberculosis.

El abandono del tratamiento de la tuberculosis es un tema relevante y pre- ocupante en la salud pública mundial. A través de una revisión integradora, este estudio busca identificar los posibles factores que conducen al abandono del tratamiento. Se rea- lizó una búsqueda en estudios indexados en las bases de datos: Biblioteca Virtual en Salud (BVS) y Scientific Electronic Library Online (SciELO), de 2017 a 2021, utilizando los siguientes descriptores (DeCS): tuberculosis, agente antituberculoso y tuberculosis pul- monar. Al final, fueron seleccionados once estudios, publicados en portugués, español e inglés. Los resultados mostraron que el abandono está relacionado con factores en dife- rentes esferas, con énfasis en las esferas social, de salud y de tratamiento. Como perfil de las personas en casos de abandono, en general, se observó que son económicamente acti- vas, con edades entre 15 y 49 años, baja escolaridad, bajos ingresos y es común que el abuso de alcohol y drogas se presenten como comorbilidades relevantes. Por lo tanto, el trabajo destacó los principales factores asociados al abandono del tratamiento de la tuber- culosis y la importancia de la participación de diferentes actores como fuerzas que se sumarán para disminuir la ocurrencia del problema en cuestión.

Factors of abandonment of tuberculosis treatment in the public health network / Factores de abandono al tratamiento de la tuberculosis en la red pública de salud

ABSTRACT This study determines the factors of abandonment of tuberculosis treatment in the public health network of Cali, Colombia, during years 2016 to 2018. We conducted an operational case-control investigation including 224 patients with tuberculosis (112 abandoned treatment and 112 completed it). We found that treatment abandonment for tuberculosis is driven by factors related to the individuals and health services that facilitate non-adherence and drive them away from the care provided in medical institutions.

RESUMEN Este estudio determina los factores de abandono al tratamiento de la tuberculosis en la red pública de salud de Cali, Colombia, durante los años 2016 a 2018. Se realizó una investigación operativa de casos y controles en la que se incluyeron 224 pacientes con tuberculosis (112 abandonaron el tratamiento y 112 lograron completarlo). Se encuentra que el abandono del tratamiento para la tuberculosis está impulsado por factores relacionados con el individuo y los servicios de salud que facilitan la no adherencia y los alejan de la atención brindada en las instituciones médicas.

Incidence, Diagnosis and Treatment of Otorhinolaryngologicl, Head and Neck Tuberculosis: A Prospective Clinical Study

Abstract Introduction Tuberculosis is a disease of diversified presentation. It affects almost all organs in the body, and otorhinolaryngological, head and neck involvement is not an exception. Objective To increase awareness about the different clinical presentations of otorhinolaryngological, head and neck tuberculosis, the techniques employed to diagnose it, and to assess the response to the treatment. Methods We conducted a prospective study of 114 patients who presented primarily with otorhinolaryngological, head and neck tuberculosis. Routine blood investigations, chest radiographs, the tuberculin test, and sputum examination for the presence of acid-fast bacilli were performed in all cases. Site-specific investigations were performed in relevant cases only. The patients were treated according to the antitubercular treatment (ATT) regimen recommended by the Indian Ministry of Health and Family Welfare's National Tuberculosis Elimination Program (NTEP), and they were followed up clinically two and six months after starting the ATT. Results Tubercular cervical lymphadenopathy was the most common clinical presentation (85.96%), followed by deep neck abscess (5.27%). Fine-needle aspiration cytology proved to be a reliable tool for the diagnosis of tubercular lymphadenopathy. Improvement at the end of 2 and 6 months of the ATT was observed in 90.35% and 96.50% of the cases respectively. Conclusion The diagnosis of otorhinolaryngological, head and neck tuberculosis requires a high index of clinical suspicion, and the ATT proved to be very effective in reducing the severity of the disease.

Factors affecting successful antituberculosis treatment: a single-center experience

SUMMARY OBJECTIVE: The identification of factors that influence a favorable antituberculosis treatment outcome could be of great use for the promotion of specific health actions to increase the success rate. Thus, the objective of this study was to investigate the factors affecting successful antituberculosis treatment in patients seen at a reference service in the Western region of São Paulo State/Brazil. METHODS: A retrospective study was carried out from 2010 to 2016 based on the data obtained from the Notification Disease Information System of TB patients treated at a reference service in Brazil. The study included patients with treatment outcomes and excluded those from the penitentiary system or with resistant or multidrug-resistant TB. Patients were categorized as having a successful (cured) or unsuccessful (treatment default and death) treatment outcome. The association between TB treatment outcomes and social and clinical factors was analyzed. RESULTS: A total of 356 cases of TB were treated between 2010 and 2016. Among the cases, the majority were cured and the overall treatment success rate was 85.96%, with a range between 80.33% (2010) and 97.65% (2016). After the exclusion of resistant/multidrug-resistant TB, 348 patients were analyzed. In the final logistic regression model analysis, education less than 8 years (OR 1.66; p<0.0001) and people living with human immunodeficiency virus/acquired immunodeficiency syndrome (OR 0.23; p<0.0046) were found to be significantly related to an unfavorable treatment outcome. CONCLUSION: Low education and being a person living with human immunodeficiency virus/acquired immunodeficiency syndrome are vulnerability factors that can affect the successful outcome of antituberculosis treatment.

Reviewing the Compounding Risks for Tuberculosis DrugInduced Liver Injury in a Patient with Transfusion Dependent Thalassaemia

@#A patient presents with jaundice three weeks into commencement of anti-tuberculosis therapy (ATT). Tuberculosis drug-induced liver injury (TB-DILI) is a main concern in patients commencing ATT. Studies have reported various risk factors associated with TB-DILI, urging vigilance in monitoring liver enzymes in these patients. We aim to review the causes of jaundice in a patient with transfusion dependent thalassaemia commenced on ATT and highlight the risk factors associated with TB-DILI.

Hepatotoxicidad por antituberculosos en pacientes con tuberculosis multidrogorresistente / Hepatotoxicity due to antitubercular drugs in multidrug-resistant tuberculosis patients

RESUMEN Objetivo: Describir las características clínicas de la injuria hepática inducida por antituberculosos (IHIA) en pacientes con tuberculosis multirresistente (MDR-TB). Materiales y métodos: Estudio retrospectivo de pacientes hospitalizados con TB-MDR e IHIA. Se utilizó los criterios de la DILI-Expert Working Group, y el instrumento de análisis de causalidad fue el RUCAM (Roussel Uclaf Causality Assessment Method). La asociación específica de la IHIA con un antituberculoso fue por un proceso de reexposición o suspensión y recuperación. Resultados: Reportamos 7 casos de MDR-TB e IHIA; la edad media (desviación estándar) fue de 39,1 (3,3) años. La media de la IHIA apareció después de 30,4 (27,70) días de iniciar el tratamiento. Tres (43,00 %) pacientes presentaron ictericia. En cuanto al patrón, en 4 (57,00 %) fue hepatocelular y en 3 (43,00 %), colestásico. En 4 pacientes, la IHIA fue leve, y moderada en 3. En todos los casos estuvo involucrada la pirazinamida (pirazinamida sola, 4; pirazinamida y etionamida, 1; pirazinamida, rifampicina e isoniazida, 1; pirazinamida y rifampicina, 1). La estancia hospitalaria media fue de 48,10 (48,70) días. Los promedios de fosfatasa alcalina (FA), alanina aminotransferasa (ALT) y gamma-glutamiltranspeptidasa (GGT) sérica fueron 2,40 (1,10), 7,9 (7,10) y 5,60 (3,70) veces el límite superior normal (NUL), respectivamente. La bilirrubina total media fue 2,30 (2,10), rango de 0,50 a 6,40 mg/dl. Como parte del esquema de alta del paciente, se administraron quinolonas a 7 pacientes (levofloxacino, 6; ofloxacino, 1), y en un paciente se agregó ácido amoxicilina/ácido clavulánico. Conclusiones: La IHIA en pacientes con TB-MDR puede aparecer después del primer mes de tratamiento. El patrón de lesión común fue hepatocelular, y la pirazinamida fue el antimicobacteriano involucrado con mayor frecuencia.

ABSTRACT Objective: To describe the clinical characteristics of drug-induced liver injury (DILI) in multidrug-resistant tuberculosis (MDR-TB) patients. Materials and methods: A retrospective study conducted in hospitalized patients with MDR-TB and DILI. The criteria of the DILI Expert Working Group were used for the diagnosis of DILI, and the RUCAM (Roussel Uclaf Causality Assessment Method) for the causality analysis. The specific association between DILI and antitubercular drugs was established by drug rechallenge or discontinuation and recovery. Results: Seven cases of MDR-TB and DILI are described in this research. The mean age (standard deviation) was 39.10 (3.30) years. Mean DILI occurred 30.40 (27.70) days after starting the treatment. Three (43.00 %) patients presented jaundice. Regarding the type of injury, four (57.00 %) had hepatocellular injury and three (43.00 %) cholestatic injury. Four patients showed mild DILI and three moderate DILI. All the patients had taken pyrazinamide (pyrazinamide alone: four patients; pyrazinamide and ethionamide: one patient; pyrazinamide, rifampin and isoniazid: one patient; pyrazinamide and rifampicin: one patient). The mean hospital stay was 48.10 (48.70) days. The mean serum alkaline phosphatase (AP), alanine aminotransferase (ALT) and gamma-glutamyl- transpeptidase (GGT) were 2.40 (1.10), 7.90 (7.10) and 5.60 (3.70) times the upper limit of normal (ULN), respectively. The mean total bilirubin was 2.30 (2.00), with a range of 0.50 to 6.40 mg/dl. As part of the discharge plan, quinolones were given to seven patients (levofloxacin: six patients; ofloxacin: one patient) and amoxicillin/clavulanic acid was added to one patient. Conclusions: MDR-TB patients may develop DILI after the first month of treatment. Hepatocellular injury was the most common type of liver injury, and pyrazinamide was the most frequently used antimycobacterial.

Risk factors for anti-tuberculosis drug-induced liver injury in treatment-naive tuberculosis patients / 中华传染病杂志

Objective:To investigate the risk factors for anti-tuberculosis drug-induced liver injury (ATB-DILI) in treatment-naive tuberculosis patients, and to provide evidence to avoid the occurrence of ATB-DILI in treatment-naive tuberculosis patients receiving anti-tuberculosis drug treatment.Methods:A retrospective case-control study was carried out in 177 treatment-naive tuberculosis patients admitted to the Third Hospital of Hebei Medical University from January 2014 to December 2019. According to whether developed ATB-DILI during anti-tuberculosis treatment, the patients were divided into non-ATB-DILI group and ATB-DILI group. General basic data of sex, age and body mass index, hepatic biological parameters, prothrombin time, serum ferritin level, basic liver condition and the number of first line hepatotoxic anti-tuberculosis drugs were collected. Mann-Whitney U test and chi-square test were used for statistical analysis, and multi-factor logistic regression analysis was adopted to analyze risk factors for ATB-DILI in treatment-naive tuberculosis patients. Results:The incidence of ATB-DILI was 20.3%(36/177) in the 177 treatment-naive tuberculosis patients. Alanine aminotransferase (ALT), aspartate aminotransferase, incidence of high serum ferritin and the number of first line hepatotoxic anti-tuberculosis drugs were significantly different between non-ATB-DILI group and ATB-DILI group ( Z=-2.13, Z=-2.08, χ2=9.08 and Z=-2.79, respectively, all P<0.050). Multivariate logistic regression analysis showed that chronic viral liver disease (odds ratio ( OR)=9.675, P<0.001), the number of first line hepatotoxic anti-tuberculosis drugs ( OR=4.863, P=0.001), baseline ALT level ( OR=1.016, P=0.011) and high serum ferritin level ( OR=3.336, P=0.018) were the independent risk factors for ATB-DILI. The number of first line hepatotoxic anti-tuberculosis drugs (regression coefficient was 1.582) and baseline ALT level (regression coefficient was 0.016) were both positively correlated with the occurrence of ATB-DILI. Conclusions:Chronic viral liver disease, the number of first line hepatotoxic anti-tuberculosis drugs, higher baseline ALT level and high serum ferritin level are the independent risk factors for ATB-DILI.

Current status of antimicrobial therapy for tuberculosis / 中国基层医药

Multidrug-resistant tuberculosis has a long treatment course and a low sputum-negative conversion rate, which have always been the treatment challenges. New drugs for multidrug-resistant tuberculosis have been constantly explored by scholars worldwide. Multiple antibacterial drugs have been found to have the therapeutic effects on multidrug-resistant tuberculosis. Treatment options that can shorten the duration of tuberculosis are also being explored. Addition of certain antibacterial drugs has been found to shorten the duration of tuberculosis. This paper reviews the effects of antibacterial drugs against tuberculosis.

Assessment of factors associated with potential drug-drug interactions in patients with tuberculosis and HIV/AIDS

Abstract INTRODUCTION: The concomitant use of antituberculosis and antiretroviral drugs, as well as drugs to treat other diseases, can cause drug-drug interactions. This study aimed to describe potential drug-drug interactions (pDDI) in patients with TB and HIV/AIDS co-infection, as well as to analyze possible associated factors. METHODS: This study was performed in a reference hospital for infectious and contagious diseases in the southeastern region of Brazil and evaluated adult patients co-infected with tuberculosis and HIV/AIDS. A cross-sectional study was conducted in which sociodemographic, clinical, and pharmacotherapeutic characteristics were assessed. The pDDI were identified using the Drug-Reax software. Association analysis was performed using either a chi-squared test or a Fisher's exact test. Correlation analysis was performed using the Spearman's coefficient. RESULTS: The study included 81 patients, of whom 77 (95.1%) were exposed to pDDI. The most frequent interactions were between antituberculosis and antiretroviral drugs, which can cause therapeutic ineffectiveness and major adverse reactions. A positive correlation was established between the number of associated diseases, the number of drugs used, and the number of pDDI. An association was identified between contraindicated and moderate pDDI with excessive polypharmacy and hospitalization. CONCLUSIONS: We found a high frequency of pDDI, especially among those hospitalized and those with excessive polypharmacy. These findings highlight the importance of pharmacists in the pharmacotherapeutic monitoring in these patients.

Analysis of Mycobacterium tuberculosis drug susceptibility test results and its spatial distribution characteristics in Dali Bai Autonomous Prefecture from 2017 to 2019 / 中华检验医学杂志

Objective:Analyze the drug resistance of Mycobacterium tuberculosis (MTB) to commonly used anti-tuberculosis drugs and its spatial distribution in Dali Bai Autonomous Prefecture from 2017 to 2019, which would provid a reference for the treatment of tuberculosis and the prevention and control of drug-resistant tuberculosis. Methods:A total of 1 013 Mycobacterial strains were isolated from sputum samples in the tuberculosis laboratories of the designated People′s hospital of 12 counties (cities) of Dali Bai Autonomous Prefecture from January 2017 to December 2019. Proportional method was used to conduct drug susceptibility tests and strain identification of 6 anti-tuberculosis drugs. Further used ArcMap10.2 and GeoDa1.14 software to visualize the map display and spatial autocorrelation analysis of the drug resistance of MTB.Results:From 2017 to 2019, the drug resistance rates of MTB in Dali Prefecture were 10.33%(28/271), 10.35%(55/531) and 30.00%(51/170), respectively, showing an rising trend ( χ2=26.62, P<0.05). Among 1 030 samples, 972 strains (95.95%) was MTB and 41 strains (4.05%) was non-tuberculous Mycobacterium (NTM). The total resistance rate of 972 strains of MTB was 13.79% (134/972), of which the single resistance rate was 6.59% (64/972), the multi-drug resistance rate was 4.84% (47/972), and the poly-drug resistance rate was 2.06% (20/972), the rate of extensive drug resistance is 0.31% (3/972). There are 25 combinations of drug resistance patterns. The detection rate of NTM was 4% (41/1 013), among which Midu County had the highest detection rate (0.89%, 9/1 013). The spatial distribution showed that the number of MTB resistant strains among counties and cities had a negative spatial correlation (Moran′s I value was -0.367, P<0.05). It shows that there is no clustering of drug resistance among counties and cities, and the resistance is serious in individual counties and cities. Yongping County and Nanjian Yi Autonomous County had low and high aggregation, and Yunlong County had high and low aggregation. Conclusions:The drug resistance of MTB showed an rising trend in Dali Bai Autonomous Prefecture from 2017 to 2019. The number of drug-resistant strains among regions was not randomly distributed, the regional difference was large, and spatial autocorrelation analysis provided theoretical clues and basis for the formulation of drug resistance prevention and control measures for tuberculosis in the whole state.

Application evaluation of whole-genome sequencing technology in predicting drug resistance of second-line injectable of anti-tuberculosis drugs / 中华检验医学杂志

Objective:To evaluate the clinical-application values of whole genome sequencing (WGS) technology to detect the drug resistance feature of second-line injectable drugs (SLIDs) for multidrug-resistant tuberculosis treatment.Methods:The proportional-method drug sensitivity test and the whole gene sequencing technology were used to simultaneously examine the resistance of three SLIDs: kanamycin (Km) and Amikacin(Am) and capreomycin (Cm) in 172 multidrug-resistant tuberculosis (MDR) strains preserved in the strain bank of the Tuberculosis Laboratory of Shenzhen Chronic Disease Prevention and Control Center from 2013 to 2017. The proportional-susceptibility tests were considered as the gold standard to evaluate the sensitivity, specificity and consistency of WGS results. The samples with differences between the two methods were compared with the minimum inhibitory concentration detection method. The McNemar test was used to statistically analyze the detection rates of the two methods, and a P value<0.05 indicated the significant difference between two groups. Results:A total of 172 MDR strains were included in this study. Two mutated genes were identified by the WGS examination: rrs and eis. Among these genes, rrs-A1401G mutation occurred in 58.3% in Am resistant strains, 14/18 in Km resistant strains or 14/14 in Cm resistant strains, respectively. The sensitivity, specificity and consistency of WGS predicted Am were 14/15, 93.6%, and 68.0%, 15/15, 98.1%, and 90.0% in Km, or 14/15, 100%, and 96.0% in Cm. There were 13 strains with inconsistent results by the two methods. One strain was retested by MIC as a drug-resistant strain and other 12 strains were sensitive. There were 11 strains with inconsistent Am test results, and WGS test results showed that 8 strains had rrs-514-A/C mutations, while DST and MIC tests were sensitive. Conclusion:WGS is enough is sensitive and specific for diagnosing SLIDs resistance.

Clinical features of liver injury induced by anti-tuberculosis drugs and related risk factors / 临床肝胆病杂志

Objective To investigate the clinical features of liver injury induced by anti-tuberculosis drugs and related risk factors. Methods A total of 129 patients who were diagnosed with liver injury induced by anti-tuberculosis drugs in Shenzhen Third People's Hospital from January 2017 to December 2018 were enrolled and divided into abnormal liver function group with 51 patients (39.53%) and drug-induced liver injury (DILI) group with 78 patients (60.47%), and among these 129 patients, 13 (10.08%) had liver failure. A retrospective analysis was performed for their laboratory markers as well as treatment and prognosis data. The chi-square test was used for comparison of categorical data between two groups; the independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The multivariable logistic regression model was used to investigate the risk factors for DILI and liver failure. Results There were significant differences between the DILI group and the abnormal liver function group in chronic HBV co-infection ( χ 2 =5.616, P =0.018), asymptomatic liver injury ( χ 2 =9.451, P =0.002), liver failure ( χ 2 =9.453, P =0.002), need to adjust anti-tuberculosis regimen ( χ 2 =16.787, P 8 weeks (odds ratio [ OR ]=3.94, 95% confidence interval [ CI ]: 1.02-15.25, P =0.047) and asymptomatic liver injury ( OR =7.64, 95% CI : 1.63-35.86, P =0.010) were independent risk factors for DILI; chronic HBV co-infection ( OR =14.42, 95% CI : 2.66-78.09, P =0.002) and time to identification of liver injury > 8 weeks ( OR =11.97, 95% CI : 2.03-70.50, P =0.006) were independent risk factors for liver failure, while albumin ≥35 g/L ( OR =0.07, 95% CI : 0.01-0.51, P =0.010) was a protective factor. Conclusion Anti-tuberculosis drugs may induce severe liver injury, and HBV co-infection, asymptomatic liver injury, long time to identification of liver injury, and low albumin level may increase the risk of severe liver injury. Regular follow-up, liver function monitoring, appropriate nutritional support, and HBV screening are important for reducing the risk of liver injury during anti-tuberculosis therapy.

Clinical features of liver injury induced by anti-tuberculosis drugs and related risk factors / 临床肝胆病杂志

Objective To investigate the clinical features of liver injury induced by anti-tuberculosis drugs and related risk factors. Methods A total of 129 patients who were diagnosed with liver injury induced by anti-tuberculosis drugs in Shenzhen Third People's Hospital from January 2017 to December 2018 were enrolled and divided into abnormal liver function group with 51 patients (39.53%) and drug-induced liver injury (DILI) group with 78 patients (60.47%), and among these 129 patients, 13 (10.08%) had liver failure. A retrospective analysis was performed for their laboratory markers as well as treatment and prognosis data. The chi-square test was used for comparison of categorical data between two groups; the independent samples t -test was used for comparison of normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The multivariable logistic regression model was used to investigate the risk factors for DILI and liver failure. Results There were significant differences between the DILI group and the abnormal liver function group in chronic HBV co-infection ( χ 2 =5.616, P =0.018), asymptomatic liver injury ( χ 2 =9.451, P =0.002), liver failure ( χ 2 =9.453, P =0.002), need to adjust anti-tuberculosis regimen ( χ 2 =16.787, P 8 weeks (odds ratio [ OR ]=3.94, 95% confidence interval [ CI ]: 1.02-15.25, P =0.047) and asymptomatic liver injury ( OR =7.64, 95% CI : 1.63-35.86, P =0.010) were independent risk factors for DILI; chronic HBV co-infection ( OR =14.42, 95% CI : 2.66-78.09, P =0.002) and time to identification of liver injury > 8 weeks ( OR =11.97, 95% CI : 2.03-70.50, P =0.006) were independent risk factors for liver failure, while albumin ≥35 g/L ( OR =0.07, 95% CI : 0.01-0.51, P =0.010) was a protective factor. Conclusion Anti-tuberculosis drugs may induce severe liver injury, and HBV co-infection, asymptomatic liver injury, long time to identification of liver injury, and low albumin level may increase the risk of severe liver injury. Regular follow-up, liver function monitoring, appropriate nutritional support, and HBV screening are important for reducing the risk of liver injury during anti-tuberculosis therapy.

Efeitos adversos às drogas antituberculose: hepatotoxicidade / Adverse effects to antituberculosis drugs: hepatotoxicity

Objetivo: Verificar a frequência de efeitos adversos em pacientes em uso de drogas antituberculose de primeira linha, além dos fatores de risco associados aos efeitos adversos e à hepatotoxicidade. Métodos: Estudo transversal, envolvendo 196 pacientes portadores de tuberculose em Maceió (AL), de agosto de 2017 a junho de 2018. Os efeitos adversos foram classificados de acordo com o Manual de Recomendações para Controle da Tuberculose de 2011, do Ministério da Saúde, em efeitos menores (queixas gastrintestinais, cutâneos, articulares e neurológicos) e maiores (psicose e hepatotoxicidade). Os fatores de risco avaliados foram: idade superior a 40 anos, etilismo, sexo feminino, anemia, doença hepática anterior, diabetes e infecção por HIV. Resultados: Foram observados efeitos adversos às drogas antituberculose em 85 pacientes (43,4%); destes, 40,8% eram menores e 8,2%, maiores. Os mais frequentes foram distúrbios gastrintestinais (25,5%) e cutâneos (15,3%). Identificaram-se como fatores de risco anemia, diabetes e doença hepática anterior. Hepatotoxicidade foi diagnosticada em 15 pacientes (10,6%), dos quais 80% eram sintomáticos, sendo fatores de risco doença hepática anterior e diabetes. Houve suspensão da terapia em todos os casos de hepatotoxicidade com modificação do esquema em 80% dos casos. Conclusão: Demonstrou-se frequência elevada de efeitos adversos às drogas antituberculose, associada à doença hepática anterior e ao diabetes. A hepatotoxicidade representou o efeito adverso mais grave, responsável pela suspensão e pela adequação do esquema terapêutico.

Objective: To determine the adverse effects frequency in patients on first-line antituberculosis drugs, as well as the risk factors associated with adverse effects and hepatotoxicity. Methods: Cross-sectional study, involving 196 tuberculosis patients in Maceió (AL), from August 2017 to June 2018. Adverse effects were classified according to the Manual de Recomendações para Controle da Tuberculose, of the Brazilian Health Ministry, in minor effects (gastrointestinal, cutaneous, articular, neurologic complaints) and major effects (psychosis and hepatotoxicity). The risk factors evaluated were age over 40 years, alcoholism, female sex, anemia, previous hepatic disease, diabetes, and infection by HIV. Results: Adverse effects to the antituberculosis drugs were observed in 85 patients (43.4%) and, among those, 40.8% were minor and 8.2% were major effects. The most frequent were gastrointestinal (25.5%) and skin (15.3%) disorders. Risk factors were identified as anemia, diabetes, and previous hepatic disease. Hepatotoxicity was diagnosed in 15 patients (10.6%), from which 80% were symptomatic, with previous hepatic disease and diabetes being the risk factors. Therapy was discontinued in all cases of hepatotoxicity with regimen modification in 80% of cases. Conclusion: An elevated frequency of adverse effects to antituberculosis drugs was demonstrated. Hepatotoxicity represented the most severe adverse effect, being responsible for the discontinuation and adaptation of the therapeutic regimen.

Tuberculosis multidrogorresistente / Multidrug-resistant tuberculosis / Tuberculose multirresistente

La tuberculosis (TB) es la enfermedad bacteriana infecciosa que más muertes causa en el mundo, panorama que puede empeorar debido a la drogorresistencia. La tuberculosis multidrogoresistente (TB-MDR), es decir la que presenta resistencia simultánea a isoniazida y rifampicina (principales fármacos antituberculosos), tiene una relevancia particular: de los 10 millones de personas que desarrollan TB anualmente, 458.000 presentan TB-MDR con un pronóstico mucho peor que el de los infectados por cepas sensibles. En el presente artículo se exploran los principales aspectos de la TB-MDR, haciendo énfasis en su tratamiento

Tuberculosis (TB) is the worldwide leading infectious cause of death and, the emergence of drug-resistant tuberculosis can only worsen the scenario. Multidrug-Resistant Tuberculosis (TB-MDR) has proven resistant to both isoniazid and rifampin, the main antituberculous drugs. Out of 10 million people developing TB annually, 458 000 exhibit TB-MDR, having worse prognosis than those infected by sensitive strains. Recently, new drug-resistant TB treatment guidelines were issued both by the World Health Organization and health authorities in Colombia. The present paper explores the main aspects of TB-MDR emphasizing s sanitary authorities also, new guidelines were published by Colombian minister of health and social protection. In this paper, the main aspects of TB-MDR are explored, especially those related to its treatment.

Vigilancia por el laboratorio de la tuberculosis resistente en menores de 15 años, Colombia, 2010 a 2015 / Resistant tuberculosis in children under 15 years of age, Colombia 2010-2015

Resumen Introducción. La tuberculosis en los niños es un reflejo de transmisión reciente en la comunidad. Se estima que en el mundo cada año un millón de niños enferma por esta causa; en Colombia se notificaron 291 casos en el 2015. Objetivo. Actualizar la información obtenida de las actividades de vigilancia por el laboratorio de la farmacorresistencia del bacilo Mycobacterium tuberculosis en menores de 15 años en Colombia entre el 2010 y el 2015. Materiales y métodos. Se llevó a cabo un estudio retrospectivo de corte transversal. Se estudiaron las variables de procedencia, sexo, edad, tipo de tuberculosis y estado de HIV en los casos sensibles y resistentes. Estos se clasificaron como caso nuevo sin tratamiento o caso previamente tratado para analizar el perfil de resistencia a fármacos de primera y segunda línea. Resultados. De los 3.440 casos notificados, en el 16,4 % se practicó la prueba de sensibilidad. El 50,6 % eran mujeres, la forma pulmonar se presentó en el 70,6 % y el 1,4 % presentó coinfección de tuberculosis y HIV. Se estudiaron 565 casos, de los cuales 503 (89,0 %) eran nuevos: el 3,9 % con tuberculosis multirresistente y el 9,5 % con resistencia global. Los previamente tratados fueron 62 (10,9 %), 4,8 % con multirresistencia y 19,3 % con resistencia global. No se evidenciaron diferencias estadísticamente significativas en los años estudiados. La proporción de tuberculosis extremadamente resistente en los casos nuevos evaluados fue de 9,0 %. Conclusiones. Es necesario que el Ministerio de Salud y Protección Social y el Instituto Nacional de Salud promuevan el uso de pruebas diagnósticas rápidas y muy sensibles, como las moleculares recomendadas por la Organización Mundial de la Salud.

Abstract Introduction: Tuberculosis in children is a recent transmission reflection in the community. It is estimated that every year one million children get sick in the world because of this. In Colombia, 291 cases were notified in 2015. Objective: To update the information obtained from the surveillance activities of the drug-resistance laboratory in children younger than 15 years of age in Colombia between 2010 and 2015. Materials and methods: This was a cross-sectional retrospective study. We studied the variables of origin, gender, age, type of tuberculosis, and HIV status in sensitive and resistant cases. We classified them according to their treatment background between new and previously treated to analyze their first and second line drug resistance profile. Results: From the notified cases, 16.4 % had a sensitivity test. 50.6 % were women, the pulmonary form was present in 70.6% cases, and 1.4 % presented with tuberculosis/HIV coinfection. We studied 565 cases, from which 503 (89.1 %) were new, presenting with multidrug-resistant tuberculosis, and a global resistance of 3.9 % and 9.5 %, respectively. From them, 62 had been previously treated (10.9 %), with 4.8 % and 19.3 % multidrug resistance and global resistance, respectively. There was no evidence of statistically significant differences during the studied years. Extremely resistant tuberculosis in new cases was 9.0 %. Conclusions: It is necessary for the Ministerio de Salud y Protección Social and the Instituto Nacional de Salud to promote the use of faster and more sensitive diagnostic tests such as the molecular ones recommended by the World Health Organization.

Notified Incidence of Tuberculosis in Foreign-born Individuals in Jeju Province, Republic of Korea / 예방의학회지

OBJECTIVES: In the Republic of Korea (ROK), the notified incidence of tuberculosis in foreign-born individuals (NITFBI) has increased recently, as has the rate of multidrug-resistant (MDR) and rifampicin-resistant (RR) tuberculosis in foreigners staying in the ROK. As Jeju Province in ROK has a no-visa entry policy, control programs for NITFBI should be consolidated. The aim was to evaluate the status of NITFBI, with a focus on the distribution of MDR/RR tuberculosis by nationality. METHODS: Data on tuberculosis incidence in individuals born in Jeju Province and in foreign-born individuals were extracted from the Korean Statistical Information Service of Statistics Korea, and the Infectious Disease Surveillance Web Statistics of the Korea Centers for Disease Control and Prevention, respectively. RESULTS: Among all notified incident cases of tuberculosis, the proportion of NITFBI increased from 1.46% in 2011 to 6.84% in 2017. China- and Vietnam-born individuals accounted for the greatest proportion of the 95 cases of NITFBI. Seven cases of MDR/RR tuberculosis were found, all involving patients born in China. CONCLUSIONS: In Jeju Province, ROK, NITFBI might become more common in the near future. Countermeasures for controlling active tuberculosis in immigrants born in high-risk nations for tuberculosis should be prepared in Jeju Province, since it is a popular tourist destination.

Effect of linezolid on inflammatory factors and T lymphocyte levels in patients with severe tuberculosis / 中国基层医药

Objective@#To observe the effects of linezolid on the levels of inflammatory factors and T lymphocytes in patients with severe tuberculosis.@*Methods@#Sixty patients with severe tuberculosis treated in Jinhua Guangfu Hospital from April 2016 to November 2017 were selected and divided into control group(n=30) and observation group(n=30) according to different treatment options.The control group was treated with personalized anti-tuberculosis regimen.The observation group was treated with linezolid on the basis of the control group, and both two groups were treated for 9 months.The changes of interleukin-1(IL-1), tumor necrosis factor alpha(TNF-α), IL-6, IL-10 and CD3+, CD4+, CD8+ and CD4+/CD8+ were observed before and after treatment.The incidence of liver injury, thrombocytopenia, myelosuppression, nausea and vomiting, diarrhea were observed.@*Results@#Before treatment, there were no statistically significant differences in IL-1, TNF-α, IL-6, IL-10, CD3+, CD4+, CD8+, CD4+/CD8+ between the two groups(all P>0.05). At 9 months after treatment, the levels of IL-1, TNF-α, IL-6 and IL-10 in the control group were (10.94±1.31)ng/L, (3.03±0.49)ng/L, (183.43±13.24)ng/L, (134.93±34.51)ng/L, respectively, which in the observation group were (6.89±1.29)ng/L, (2.49±0.45)ng/L, (129.48±10.74)ng/L, (189.35±43.27)ng/L, respectively, the differences between the two groups were statistically significant(t=12.195, 11.214, 8.414, 11.291, all P<0.05). The CD3+, CD4+, CD8+, CD4+/CD8+ in the control group were (47.61±7.16)%, (15.49±6.64)%, (20.58±5.61)%, (0.79±0.19) , respectively, which in the observation group were (65.46±8.31)%, (30.23±7.85)%, (34.59±7.41)%, (0.87±0.24) , respectively, the differences between the two groups were statistically significant(t=10.497, 7.865, 12.128, 10.291, all P<0.05). There were no statistically significant differences in the incidence of liver function impairment, thrombocytopenia, myelosuppression, nausea and vomiting, and diarrhea between the two groups(all P>0.05).@*Conclusion@#Linezolid in the treatment of severe tuberculosis can reduce the level of inflammatory factors, improve the cellular immune level of patients, and has a lower incidence of adverse effects.

Clinical effect of acupoint application combined with conventional anti-tuberculosis treatment on pulmonary tuberculosis and its influence on the immune function / 中国基层医药

Objective@#To explore the effect of acupoint application combined with conventional anti-tuberculosis treatment on pulmonary tuberculosis and its effect on the immune function of patients.@*Methods@#A total of 64 patients with pulmonary tuberculosis who visited Hangzhou Red Cross Hospital from March 2016 to September 2017 were selected in the study.The patients were randomly divided into control group (n=30) and observation group (n=34) according to the digital table.The clinical curative effect (obvious absorption, absorption, no change and deterioration), lung function (FVC, FEV1 and FVC/FEV1), immune function(CD3+, CD4+, CD8+, CD4+/CD8+, IgC, IgA, IgM) were compared between the two groups.@*Results@#The absorptive rate of the control group was 46.67%, which was significantly lower than that of the observation group(76.47%, χ2=6.04, P<0.05). After treatment, the levels of FVC, FEV1 and FVC/FEV1 of the two groups were significantly increased compared with before treatment..After treatment, the levels of FVC, FEV1 and FVC/FEV1 in the observation group were (2.20±0.48)L, (2.50±0.34)L, (87.44±13.60)%, respectively, which were significantly higher than those in the control group [(1.63±0.32)L, (2.02±0.44)L, (80.28±12.66)%] (t=6.607, 5.687, 2.558, all P<0.05). After treatment, the CD3+, CD4+, CD8+, CD4+/CD8+, IgC, IgA, IgM levles in the observation group were significantly increased compared with before treatment (all P<0.05). After treatment, the CD3+, CD4+, CD8+, CD4+/CD8+, IgC, IgA, IgM levles in the observation group were (73.25±6.17)%, (38.65±5.75)%, (36.58±3.17)%, (1.52±0.65), (15.49±1.49)g/L, (3.07±1.30)g/L, (1.94±0.50)g/L, respectively, which were significantly higher than those in the control group[(68.43±6.4)%, (34.72±5.68)%, (35.02±3.08)%, (1.16±0.78), (12.61±1.64)g/L, (2.23±0.90)g/L, (1.68±0.35)g/L] (t=3.590, 3.223, 2.340, 2.340, 8.594, 3.550, 2.846, all P<0.05).@*Conclusion@#Conventional anti-tuberculosis chemotherapy drugs combined with acupuncture has better effect than conventional anti-tuberculosis chemotherapy drugs.It can significantly improve the immune function of patients, improve the success rate of treatment, and speed up the improvement of the patients' condition.

Effect of linezolid on inflammatory factors and T lymphocyte levels in patients with severe tuberculosis / 中国基层医药

Objective To observe the effects of linezolid on the levels of inflammatory factors and T lymphocytes in patients with severe tuberculosis.Methods Sixty patients with severe tuberculosis treated in Jinhua Guangfu Hospital from April 2016 to November 2017 were selected and divided into control group(n =30) and observation group(n =30) according to different treatment options.The control group was treated with personalized anti-tuberculosis regimen.The observation group was treated with linezolid on the basis of the control group,and both two groups were treated for 9 months.The changes of interleukin-1 (IL-1),tumor necrosis factor alpha (TNF-α),IL-6,IL-10 and CD3+,CD4+,CD8+ and CD4+/CD8+ were observed before and after treatment.The incidence of liver injury,thrombocytopenia,myelosuppression,nausea and vomiting,diarrhea were observed.Results Before treatment,there were no statistically significant differences in IL-1,TNF-α,IL-6,IL-10,CD4+,CD8+,CD8+,CD4+/CD8+ between the two groups(all P＞0.05).At 9 months after treatment,the levels of IL-1,TNF-α,IL-6 and IL-10 in the control group were (10.94 ± 1.31) ng/L,(3.03 ± 0.49) ng/L,(183.43 ± 13.24) ng/L,(134.93 ± 34.51) ng/L,respectively,which in the observation group were (6.89 ± 1.29) ng/L,(2.49 ± 0.45) ng/L,(129.48 ± 10.74) ng/L,(189.35 ± 43.27)ng/L,respectively,the differences between the two groups were statistically significant(t =12.195,11.214,8.414,11.291,all P ＜ 0.05).The CD3+,CD4+,CD8+,CD4+/CD8+ in the control group were (47.61 ± 7.16) ％,(15.49 ± 6.64) ％,(20.58 ± 5.61) ％,(0.79 ± 0.19),respectively,which in the observation group were (65.46 ± 8.31) ％,(30.23 ± 7.85) ％,(34.59 ± 7.41) ％,(0.87 ± 0.24),respectively,the differences between the two groups were statistically significant (t =10.497,7.865,12.128,10.291,all P ＜ 0.05).There were no statistically significant differences in the incidence of liver function impairment,thrombocytopenia,myelosuppression,nausea and vomiting,and diarrhea between the two groups(all P ＞ 0.05).Conclusion Linezolid in the treatment of severe tuberculosis can reduce the level of inflammatory factors,improve the cellular immune level of patients,and has a lower incidence of adverse effects.