Obstacles in combating multidrug resistant tuberculosis in pediatric patients: a scope review / Obstáculos no combate à tuberculose multidroga resistente em pacientes pediátricos: uma revisão de escopo

Abstract Objectives: to identify the scientific evidence on excessively resistant and multidrug resistant tuberculosis in pediatric patients. Methods: this is a scope review of the literature, with a guiding question: "What is the scientific evidence on multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis in pediatric patients?". The research used the descriptors: "extensively drug-resistant tuberculosis" OR "multidrug-resistant tuberculosis" AND "pediatrics". The research was carried out in a double-blind manner in the following databases of the Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier and International Clinical Trials Registry Platform, with a temporal cut-off from 2011 to 2021, sending a final synthesized sample of 18 articles, which evaluated the methodological content through the level of evidence. Results: the results show the lack of research with a high level of evidence related to MDR-TB in children, the lack of adequate dosage of second-line drugs for the pediatric population and the importance of drug sensitivity testing for the cases of treatment Conclusions: it was identified that the obstacles to MDR-TB treatment were concentrated in the lack of detailed protocols, safe drug dosages with a low side effect, and mainly in the social health determinants and disease process involving MDR-TB.

Resumo Objetivos: identificar as evidências científicas sobre tuberculose excessivamente resistente e multidroga resistente em pacientes pediátricos. Métodos: trata-se de uma revisão de escopo da literatura, tendo como questão norteadora: "Quais as evidências científicas sobre tuberculose multidroga-resistente (TB-MDR) e tuberculose extensivamente resistente em pacientes pediátricos?" A pesquisa usou os descritores: "tuberculose extensivamente resistente a medicamentos" OR "tuberculose resistente a múltiplos medicamentos" AND "pediatria". A pesquisa foi realizada de modo duplo-cego nas bases de dados Medical Literature Analysis and Retrieval System Online, Regional Office for the Western Pacific's Institutional Repository for Information Sharing, Embase/Elsevier e International Clinical Trials Registry Platform, com um corte temporal de 2011 a 2021, sendo a amostra final sintetizada de 18 artigos, nos quais avaliou-se o conteúdo metodológico por meio do nível de evidência. Resultados: os resultados mostraram a escassez de pesquisas de alto nível de evidência relacionadas à TB-MDR em crianças, ausência de posologia adequada das drogas de segunda linha para o público pediátrico e a importância do teste de sensibilidade a drogas para o tratamento dos casos. Conclusões: identificou-se que os obstáculos do tratamento TB-MDR se concentraram na ausência de protocolos detalhados, de dosagens medicamentosas seguras e com menor efeito colateral, e, principalmente, nos determinantes sociais do processo saúde e doença que envolvem a TB-MDR.

Immune Regulatory Effect of Osteopontin Gene Therapy in a Murine Model of Multidrug Resistant Pulmonary Tuberculosis.

Tuberculosis (TB) has been for many years a major public health problem since treatment is long and sometimes ineffective favoring the increase of multidrug-resistant mycobacteria (MDR-TB). Gene therapy is a novel and effective tool to regulate immune responses. In this study we evaluated the therapeutic effect of an adenoviral vector codifying osteopontin (AdOPN), a molecule known for their roles to favor Th1 and Th17 type-cytokine expression which are crucial in TB containment. A single dose of AdOPN administration in BALB/c mice suffering late progressive pulmonary MDR-TB produced significant lower bacterial load and pneumonia, due to higher expression of IFN-γ, IL-12, and IL-17 in coexistence with increase of granulomas in number and size, resulting in higher survival, in contrast with mice treated with the control adenovirus that codify the green fluorescent protein (AdGFP). Combined therapy of AdOPN with a regimen of second line antibiotics produced a better control of bacterial load in lung during the first days of treatment, suggesting that AdOPN can shorten chemotherapy. Taken together, gene therapy with AdOPN leads to higher immune responses against TB infection, resulting in a new potential treatment against pulmonary TB that can co-adjuvant chemotherapy.

Palliative care needs among patients with advanced illnesses in Bhutan.

BACKGROUND: Palliative care improves the quality of lives of patients and families affected by advanced illnesses through the prevention and relief of suffering. While palliative care is well established in developed countries, it is inadequate or non-existent in most developing countries. Palliative care is an emerging concept in Bhutan, a tiny Himalayan Kingdom. A small community palliative care service is available in the national referral hospital with three dedicated inpatient palliative care beds. This study explored the needs for palliative care among patients diagnosed with advanced illnesses and is a component of a larger project aimed to inform a suitable palliative care model for the country. METHODS: This is a cross-sectional descriptive study. A survey, using a structured questionnaire including the EORTC QLQ-C30, was carried out among patients with advanced illness in hospitals, primary care units and communities across the country. Purposeful and snowball sampling strategies were used to recruit study participants. RESULTS: Seventy (76%), out of 93 eligible patients, agreed to participate in the survey. Participants reported low to moderate scores on physical, role, emotional, cognitive and social functioning, a moderate score for the global health/ quality of life scale and moderately high (worse) scores in symptoms including fatigue, pain, insomnia, loss of appetite and the financial impact from the disease. CONCLUSIONS: The symptom burden experienced by patients affected by advanced illnesses demonstrates the need for palliative care in Bhutan. These findings will help inform the development of a public health-focused palliative care model, modified to the Bhutanese context, as recommended by the World Health Organization.

Allogeneic Vγ9Vδ2 T-Cell Therapy Promotes Pulmonary Lesion Repair: An Open-Label, Single-Arm Pilot Study in Patients With Multidrug-Resistant Tuberculosis.

The WHO's "Global tuberculosis report 2020" lists tuberculosis (TB) as one of the leading causes of death globally. Existing anti-TB therapy strategies are far from adequate to meet the End TB Strategy goals set for 2035. Therefore, novel anti-TB therapy protocols are urgently needed. Here, we proposed an allogeneic Vγ9Vδ2 T-cell-based immunotherapy strategy and clinically evaluated its safety and efficacy in patients with multidrug-resistant TB (MDR-TB). Eight patients with MDR-TB were recruited in this open-label, single-arm pilot clinical study. Seven of these patients received allogeneic Vγ9Vδ2 T-cell therapy adjunct with anti-TB drugs in all therapy courses. Cells (1 × 108) were infused per treatment every 2 weeks, with 12 courses of cell therapy conducted for each patient, who were then followed up for 6 months to evaluate the safety and efficacy of cell therapy. The eighth patient initially received four courses of cell infusions, followed by eight courses of cell therapy plus anti-MDR-TB drugs. Clinical examinations, including clinical response, routine blood tests and biochemical indicators, chest CT imaging, immune cell surface markers, body weight, and sputum Mycobacterium tuberculosis testing, were conducted. Our study revealed that allogeneic Vγ9Vδ2 T cells are clinically safe for TB therapy. These cells exhibited clinical efficacy in multiple aspects, including promoting the repair of pulmonary lesions, partially improving host immunity, and alleviating M. tuberculosis load in vivo, regardless of their application in the presence or absence of anti-TB drugs. This pilot study opens a new avenue for anti-TB treatment and exhibits allogeneic Vγ9Vδ2 T cells as promising candidates for developing a novel cell drug for TB immunotherapy. Clinical Trial Registration: (https://clinicaltrials.gov/ct2/results?cond=&term=NCT03575299&cntry=&state=&city=&dist=) ( NCT03575299).

Patient- and provider-related factors in the success of multidrug-resistant tuberculosis treatment in Colombia / Factores de éxito del tratamiento de la tuberculosis multidrogorresistente relacionados con el paciente y el personal sanitario en Colombia / Fatores de êxito do tratamento da tuberculose multirresistente relacionados com o paciente e com a equipe de saúde na Colômbia

ABSTRACT Objective. To identify patient- and provider-related factors associated with the success of multidrug-resistant tuberculosis (MDR-TB) treatment in the six municipalities of Colombia with the highest number of MDR-TB cases. Methods. Bivariate and multivariate logistic regressions were used to analyze the association between treatment success (cure or treatment completion) and characteristics of the patients and physicians, nursing professionals, and psychologists involved in their treatment. The importance of knowledge in the management of MDR-TB cases was explored through focus groups with these providers. Results. Of 128 cases of TB-MDR, 63 (49.2%) experienced treatment success. Only 52.9% of the physicians and nursing professionals had satisfactory knowledge about MDR-TB. Logistic regression showed that being HIV negative, being affiliated with the contributory health insurance scheme, being cared for by a male physician, and being cared for by nursing professionals with sufficient knowledge were associated with a successful treatment outcome (p ≤ 0.05). Qualitative analysis showed the need for in-depth, systematic training of health personnel who care for patients with MDR-TB. Conclusions. Some characteristics of patients and healthcare providers influence treatment success in MDR-TB cases. Physicians' and nurses' knowledge about MDR-TB must be improved, and follow-up of MDR-TB patients who are living with HIV and of those affiliated with the subsidized health insurance scheme in Colombia must be strengthened, as these patients have a lower likelihood of a successful treatment outcome.

RESUMEN Objetivo. Identificar los factores asociados con el éxito del tratamiento de tuberculosis multidrogorresistente (TB-MDR) relacionados con los pacientes y el personal sanitario en seis municipios de Colombia con mayor número de casos. Métodos. Mediante regresiones logísticas bifactorial y multifactorial se analizó la asociación entre el tratamiento exitoso (curación o cumplimiento del tratamiento) y las características de los pacientes, y de los médicos, profesionales de enfermería y psicólogos vinculados al tratamiento. Se exploró la importancia del conocimiento en el manejo de los casos de TB-MDR mediante grupos focales con esos profesionales. Resultados. De los 128 casos con TB-MDR, 63 (49,2%) tuvieron un tratamiento exitoso. Solo 52,9% de los médicos y profesionales de enfermería tenía conocimientos satisfactorios sobre TB-MDR. La regresión logística mostró que ser negativo al VIH, estar afiliado al régimen de aseguramiento de salud contributivo, estar atendido por un médico del sexo masculino y por profesionales de enfermería con conocimientos suficientes se asociaron con un desenlace exitoso del tratamiento (p ≤ 0,05). El análisis cualitativo mostró la necesidad de profundizar y sistematizar la capacitación del personal sanitario que atiende los casos de TB-MDR. Conclusiones. En el éxito del tratamiento de los casos de TB-MDR influyen algunas características de los pacientes y el personal sanitario. Se requiere fortalecer los conocimientos sobre TB-MDR de médicos y enfermeros, y reforzar el seguimiento de los pacientes con TB-MDR positivos al VIH y de los que pertenecen al régimen subsidiado, dada su menor probabilidad de éxito al tratamiento.

RESUMO Objetivo. Identificar os fatores associados ao êxito do tratamento da tuberculose multirresistente (TBMR) relacionados ao paciente e à equipe de saúde nos seis municípios da Colômbia com o maior número de casos. Métodos. Mediante regressão logística bifatorial e multifatorial, analisou-se a associação entre o êxito do tratamento (cura ou completude do tratamento) e as características dos pacientes e dos médicos, profissionais de enfermagem e psicólogos envolvidos neste. Explorou-se a importância do conhecimento no manejo de casos de TBMR mediante grupos focais com os mesmos profissionais. Resultados. Dos 128 casos de TBMR, 63 (49.2%) lograram êxito no tratamento. Somente 52.9% dos médicos e profissionais de enfermagem tinham conhecimentos satisfatórios sobre TBMR. A regressão logística demonstrou que soronegatividade para o HIV, cobertura pelo sistema de saúde sob o regime de contribuinte, atendimento por um médico do sexo masculino e atendimento por profissionais de enfermagem com conhecimento suficiente foram fatores associados ao êxito do tratamento (p ≤ 0,05). A análise qualitativa demonstrou necessidade de aprofundar e sistematizar a capacitação do pessoal de saúde que atende casos de TBMR. Conclusões. Algumas características do paciente e da equipe de saúde influenciam no êxito do tratamento de casos de TBMR. É preciso fortalecer os conhecimentos dos médicos e profissionais de enfermagem sobre a TBMR e reforçar o seguimento dos pacientes com TBMR que vivem com HIV e os filiados ao sistema de saúde colombiano pelo regime subsidiado, os quais têm menor probabilidade de êxito do tratamento.

Factores de éxito del tratamiento de la tuberculosis multidrogorresistente relacionados con el paciente y el personal sanitario en Colombia / Patient- and provider-related factors in the success of multidrug tuberculosis treatment in Colombia / Fatores de êxito do tratamento da tuberculose multirresistente relacionados com o paciente e com a equipe de saúde na Colômbia

RESUMEN Objetivo. Identificar los factores asociados con el éxito del tratamiento de tuberculosis multidrogorresistente (TB-MDR) relacionados con los pacientes y el personal sanitario en seis municipios de Colombia con mayor número de casos. Métodos. Mediante regresiones logísticas bifactorial y multifactorial se analizó la asociación entre el tratamiento exitoso (curación o cumplimiento del tratamiento) y las características de los pacientes, y de los médicos, profesionales de enfermería y psicólogos vinculados al tratamiento. Se exploró la importancia del conocimiento en el manejo de los casos de TB-MDR mediante grupos focales con esos profesionales. Resultados. De los 128 casos con TB-MDR, 63 (49,2%) tuvieron un tratamiento exitoso. Solo 52,9% de los médicos y profesionales de enfermería tenía conocimientos satisfactorios sobre TB-MDR. La regresión logística mostró que ser negativo al VIH, estar afiliado al régimen de aseguramiento de salud contributivo, estar atendido por un médico del sexo masculino y por profesionales de enfermería con conocimientos suficientes se asociaron con un desenlace exitoso del tratamiento (p ≤ 0,05). El análisis cualitativo mostró la necesidad de profundizar y sistematizar la capacitación del personal sanitario que atiende los casos de TB-MDR. Conclusiones. En el éxito del tratamiento de los casos de TB-MDR influyen algunas características de los pacientes y el personal sanitario. Se requiere fortalecer los conocimientos sobre TB-MDR de médicos y enfermeros, y reforzar el seguimiento de los pacientes con TB-MDR positivos al VIH y de los que pertenecen al régimen subsidiado, dada su menor probabilidad de éxito al tratamiento.

ABSTRACT Objective. To identify patient- and provider-related factors associated with the success of multidrug-resistant tuberculosis (MDR-TB) treatment in the six municipalities of Colombia with the highest number of MDR-TB cases. Methods. Bivariate and multivariate logistic regressions were used to analyze the association between treatment success (cure or treatment completion) and characteristics of the patients and physicians, nursing professionals, and psychologists involved in their treatment. The importance of knowledge in the management of MDR-TB cases was explored through focus groups with these providers. Results. Of 128 cases of TB-MDR, 63 (49.2%) experienced treatment success. Only 52.9% of the physicians and nursing professionals had satisfactory knowledge about MDR-TB. Logistic regression showed that being HIV negative, being affiliated with the contributory health insurance scheme, being cared for by a male physician, and being cared for by nursing professionals with sufficient knowledge were associated with a successful treatment outcome (p ≤ 0.05). Qualitative analysis showed the need for in-depth, systematic training of health personnel who care for patients with MDR-TB. Conclusions. Some characteristics of patients and healthcare providers influence treatment success in MDR-TB cases. Physicians' and nurses' knowledge about MDR-TB must be improved, and follow-up of MDR-TB patients who are living with HIV and of those affiliated with the subsidized health insurance scheme in Colombia must be strengthened, as these patients have a lower likelihood of a successful treatment outcome.

RESUMO Objetivo. Identificar os fatores associados ao êxito do tratamento da tuberculose multirresistente (TBMR) relacionados ao paciente e à equipe de saúde nos seis municípios da Colômbia com o maior número de casos. Métodos. Mediante regressão logística bifatorial e multifatorial, analisou-se a associação entre o êxito do tratamento (cura ou completude do tratamento) e as características dos pacientes e dos médicos, profissionais de enfermagem e psicólogos envolvidos neste. Explorou-se a importância do conhecimento no manejo de casos de TBMR mediante grupos focais com os mesmos profissionais. Resultados. Dos 128 casos de TBMR, 63 (49.2%) lograram êxito no tratamento. Somente 52.9% dos médicos e profissionais de enfermagem tinham conhecimentos satisfatórios sobre TBMR. A regressão logística demonstrou que soronegatividade para o HIV, cobertura pelo sistema de saúde sob o regime de contribuinte, atendimento por um médico do sexo masculino e atendimento por profissionais de enfermagem com conhecimento suficiente foram fatores associados ao êxito do tratamento (p ≤ 0,05). A análise qualitativa demonstrou necessidade de aprofundar e sistematizar a capacitação do pessoal de saúde que atende casos de TBMR. Conclusões. Algumas características do paciente e da equipe de saúde influenciam no êxito do tratamento de casos de TBMR. É preciso fortalecer os conhecimentos dos médicos e profissionais de enfermagem sobre a TBMR e reforçar o seguimento dos pacientes com TBMR que vivem com HIV e os filiados ao sistema de saúde colombiano pelo regime subsidiado, os quais têm menor probabilidade de êxito do tratamento.

A case report of a child with probable drug resistant tuberculous pericarditis with a review of challenges involved in diagnosis, treatment and follow up of children with DR-TB pericarditis.

BACKGROUND: There are unique challenges in the diagnosis and management of multi drug resistant tuberculosis (MDR-TB) in children. It is difficult to obtain confirmatory microbiological diagnosis in TB pericarditis. It is essential to differentiate between drug sensitive and drug resistant forms of TB as it has a major bearing on the regimen used, and inappropriate TB treatment combined with steroid use for pericarditis can lead to deterioration. With lack of samples, the treatment decision relies on the drug resistance pattern of the close contact if available. Therapeutic challenges of MDR-TB management in a child involve use of toxic drugs that need to be judiciously handled. We report a 2 years 4 months old male child who was diagnosed with TB pericarditis and treated based on the resistance pattern of his mother who was on treatment for pulmonary MDR-TB. CASE PRESENTATION: This 2 years 4 months old male child was diagnosed with TB involving his pericardium. Getting him started on an appropriate regimen was delayed due to the difficulty in establishing microbiological confirmation and drug susceptibility. He was commenced on a regimen based on his mother's drug resistance pattern and required surgery due to cardiac failure during the course of his treatment. He successfully completed 2 years of therapy. CONCLUSIONS: This child's case demonstrates that despite unique challenges in diagnosis and management of drug resistant extra pulmonary tuberculosis in children, treatment of even complex forms can be successful. The need for high suspicion of MDR-TB, especially when there is close contact with pulmonary TB, careful design of an effective regimen that is tolerated by the child, indications for invasive surgical management of pericarditis, appropriate follow-up and management of adverse effects are emphasised.

Profile of osteoarticular tuberculosis in children.

OBJECTIVE: To determine clinical profile of osteoarticular tuberculosis (TB) in children. METHODS: Cross-sectional analysis from 2007 to 2013. All patients diagnosed with bone TB, spinal TB or TB abscesses were included. RESULTS: Out of 1318 children with TB, 39 (2.96%) had osteoarticular TB, of which 16 (42%) had osteomyelitis, 8 (20.5%) had spinal involvement, 7 (17.9%) had TB synovitis, 2 (5.1%) had psoas abscess and 6 (15.4%) had abscesses. The mean age of presentation was 7.1 ± 3.5 years (range 2-14 years). Of the 33 cases in which a culture was done, 25 (64%) showed a positive culture. Drug sensitivity tests were done in 21 patients of which 10 (47.6%) tested were drug resistant, of which 4 (36.4%) were multidrug resistant (MDR), 2 (18.2%) were extensively drug resistant (XDR), 3 were pre-XDR (27.3%) and 1 was polyresistant (9.1%). Nine (23.1%) patients had TB in the past with a treatment duration of 8.3 ± 5.3 months. Contact with a TB patient had occurred in 10 (25.6%) cases. Associated pulmonary TB were seen in 6 (15.39%) and TB meningitis were seen in 1 (2.6%) patients. Surgical intervention was needed in 11 (28.2%) patients of which 5 (45.5%) underwent curettage, drainage was done in 1 (9.1%), arthrotomy in 4 (36.4%) and spinal surgery in 1 (9.1%) patient. CONCLUSION: Drug resistant osteoarticular TB is an emerging problem in children.

New perspectives on difficult-to-treat tuberculosis based on old therapeutic approaches.

Tuberculosis (TB) is an important clinical and public health issue worldwide. Despite improved treatment success rates following the introduction of antibiotics in daily clinical practice, the expected decline in incidence has been hampered by HIV epidemics and multi- and extensively drug-resistant TB. During the pre-antibiotic era, TB therapies were mainly based on improving hygiene conditions, strengthening the immune system, and targeting the rest of the affected lungs with invasive techniques. Detailed knowledge of old non-pharmacological therapies might support physicians and researchers in the identification of new solutions for difficult-to-treat patients. We performed a narrative literature review on the main old therapeutic options prescribed for patients with TB. The main recommendations and contraindications of sanatorium therapies (i.e., bed rest, fresh air, sunlight) and pulmonary collapse techniques are reviewed, evaluating their physiological basis and their impact on patient outcomes. We report studies describing new interventional pulmonary and surgical techniques and assess new perspectives based on old medical and surgical treatments, whose potential implementation could help complicated patients.

Contribution of imaging in the management of resistant tuberculosis.

INTRODUCTION: Resistant tuberculosis is a topical subject given the difficulties of its management. OBJECTIVE: To evaluate the role of imaging in the diagnosis and follow-up of multidrug-resistant tuberculosis (MDR-TB). METHODS: Retrospective study of MDR-TB cases followed in Hall C of Abderrahmane Mami Hospital (2010 to 2016). RESULTS: Forty four patients included. The average age was 33 (15-58). The sex ratio was 1.7. Chest radiographs at the start of treatment showed lesions dominated by nodules (n = 39) and cavities (n = 36). The parenchymal lesions were bilateral (n = 32), associated pleural (n = 4) and mediastinal lesions (n = 7). During treatment, radiological improvement dominated during the first 7 months of treatment. Computed tomography was performed as part of the preoperative assessment of MDR-TB (n = 2), lung cancer extension assessment (n = 1) and etiological assessment of haemoptysis. It allowed to refute a suspected pulmonary embolism (n = 1) and to drain a pleural effusion. Parenchymal lesions on CT were dominated by nodules (n = 8) and cavities (n = 6). Mediastinal nodes (n = 4) and pleural effusions (n = 3) were noted. Ultrasonography showed pleural effusion with pleural thickening (n = 2) and permits its ponction. CONCLUSION: Imaging is a key element in the diagnostic approach to tuberculosis. It permits to evaluate tuberculous lesions and to detect tuberculous complications. It helps to guide the therapeutic management and evaluate its effectiveness.

Health-related quality of life of patients with multidrug-resistant tuberculosis in Yemen: prospective study.

BACKGROUND: Substantial efforts are currently focused on investigating and developing new multidrug-resistant tuberculosis (MDR-TB) drugs and diagnostic methods. In Yemen, however, the evaluation of health-related quality of life (HRQoL) and the effect of current MDR-TB treatment on the QoL are commonly ignored. This study evaluated the HRQoL during and after treatment and identified the risk factors that are predictive of HRQoL score differences. METHOD: A prospective cohort study was conducted in four of the five main MDR-TB centres in Yemen. The patients confirmed with MDR-TB completed the SF-36 V2 survey at the beginning of treatment, end of treatment (continous phase) and at the 1 year follow-up after completing treatment. A total normal base score (NBS) of < 47 reflects impairment of functions, whereas a mental component summary (MCS) score of < 43 indicates a risk of depression. RESULT: At the beginning of treatment, the mean scores for all health domains were < 47 NBS points (PF = 40.7, RP = 16.1, BP = 21.6, GH = 28.3, VT = 14.55, SF = 25.9, RE = 13.7, and MH = 14.7). At the completion of treatment, all eight health domains increase compare to beginning of treatment (PF = 59.3, RP = 31.1, BP = 40.9, GH = 48.5, VT = 30.5, SF = 46.6, RE =26.6 & MH = 27.7), but a follow-up duration of 1 year after completing treatment showed decreased NBS points in all domains (PF = 51.5, RP = 30.6, BP = 39.1, GH = 47.8, VT = 30.2, SF = 43.7, RE =26.4 & MH = 27.2). Age, history of streptomycin use, baseline lung cavity, marital status and length of sickness before MDR-TB diagnosis were predictive of in PCS score differences, whereas, age, smoking, baseline lung cavity, stigma, residence, marital status and length of sickness before MDR-TB diagnosis were predictive of MCS scores differences. CONCLUSION: The length of sickness before DR-TB diagnosis was found to be predictive of the trends in both PCS and MCS scores. Despite the positive outcome of MDR-TB treatment, the low HRQoL scores obtained for all heath domains and especially for mental health reflect a high depression status of patients even after 1 year of completing therapy. Moreover, the poor HRQoL, particularly regarding mental health, of study participants at the end of treatment demands the need for urgent attention from national tuberculosis control programme managers. Therefore, the Yemen Ministry of Health and the National Tuberculosis Control Programme should implement an intervention programme to enhance HRQoL at the end of treatment to avoid any further negative consequences of MDRTB in patients after treatment. Moreover, The HRQoL data of patients with MDR-TB must be collected at the different stages of MDR-TB treatment to provide an additional parameter for assessing the effectiveness of the treatment programme. TRIAL REGISTRATION: SNOYEM 1452. Registered 01 February 2013.

Abandono de tratamento anterior e caso de tuberculose multidroga resistente em uma instituição terciária na cidade do Rio de Janeiro / Abandonment of previous treatment and case of resistant multidrug tuberculosis in a tertiary institution in the city of Rio de Janeiro / Abandono de tratamiento anterior y caso de tuberculosis multidroga resistente en una institución terciaria en la ciudad de Río de Janeiro

Objetivos: Descrever as características dos casos de abandono do tratamento de tuberculose em pacientes que desenvolveram tuberculose multirresistente (TBMR). Métodos: Estudo descritivo de abordagem quantitativa, desenvolvido em uma instituição terciária de referência para tratamento de TBMR localizada na cidade do Rio de Janeiro. Foi utilizado instrumento estruturado com informações de quarenta prontuários entre os meses de agosto a dezembro de 2016. A análise dos dados foi realizada por meio do software SPSS. Resultados: Dos pacientes estudados, 35% abandonaram tratamento anterior de tuberculose. Conclusão e implicação para a prática: É necessária a identificação precoce de pacientes que apresentam maior risco para abandono do tratamento, bem como a criação de um modelo de assistência voltado ao perfil dos usuários que abandonam o tratamento, com uma prática participativa, com grupos educativos que promovam ações preventivas, identificando e estudando estratégias para a superação de barreiras ligadas à realidade de vida individual e coletiva

Objective: To describe the characteristics of cases of tuberculosis treatment abandonment in patients who developed MDR-TB. Methods: a descriptive study of a quantitative approach developed in a tertiary referral institution for the treatment of MDR-TB, located in the city of Rio de Janeiro. A structured instrument was used with information from forty medical records between August and December 2016. Data analysis was performed using SPSS software. Results: Of the patients studied, 35% abandoned previous treatment of tuberculosis. Conclusion and implication for the practice: early identification of patients who are at greater risk for treatment abandonment is required, as well as the creation of a model of assistance aimed at the profile of users who abandon treatment, with a participatory practice with educational groups That promote preventive actions, identifying, studying strategies for overcoming barriers linked to reality, individual and collective life

Objetivos: Describir las características de los casos de abandono del tratamiento de tuberculosis en pacientes que desarrollaron TBMR. Métodos: estudio descriptivo de abordaje cuantitativo, desarrollado en una institución terciaria de referencia para tratamiento de TBMR, ubicado en la ciudad de Río de Janeiro. Se utilizó instrumento estructurado con informaciones de cuarenta prontuarios entre los meses de agosto a diciembre de 2016. El análisis de los datos fue realizado a través del software SPSS. Resultados: de los pacientes estudiados, el 35% abandonó el tratamiento anterior de la tuberculosis.Conclusión e implicación para la práctica: es necesaria la identificación precoz de pacientes que presentan mayor riesgo para el abandono del tratamiento, así como la creación de un modelo de asistencia orientado al perfil de los usuarios que abandonan el tratamiento, con una práctica participativa, con grupos educativos Que promuevan acciones preventivas, identificando, estudiando estrategias para la superación de barreras ligadas a la realidad, de vida individual y colectiva

Managing severe tuberculosis and its sequelae: from intensive care to surgery and rehabilitation.

Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) continue to challenge physicians and public health specialists. Global treatment outcomes continue to be unsatisfactory, positive outcomes being achieved in only 54% of patients. Overall outcomes are even worse in patients infected with highly resistant strains. Treating MDR-/XDR-TB is difficult because of frequent adverse events, the long duration of drug regimens, the high costs of second-line drugs, chronic post-infectious sequelae, and loss of organ function. Ongoing research efforts (studies and trials) have various aims: increasing the rates of treatment success; understanding the potentialities of new and repurposed drugs; shortening the treatment duration; and reducing the rates of adverse events. It is hoped that better access to rapid diagnostics, increased awareness, and treatments that are more effective will reduce the rate of complications and of lung function impairment. This article aims to discuss the management of severe tuberculosis (defined as that which is potentially life threatening, requiring higher levels of care) and its sequelae, from intensive care to the postoperative period, rehabilitation, and recovery. We also discuss the nonpharmacological interventions available to manage chronic sequelae and improve patient quality of life. Because the majority of MDR-/XDR-TB cases evolve to lung function impairment (typically obstructive but occasionally restrictive), impaired quality of life, and low performance status (as measured by walk tests or other metrics), other interventions (e.g., smoking cessation, pulmonary rehabilitation, vaccination/prevention of secondary bacterial infections/exacerbations, complemented by psychological and nutritional support) are required.

Integrating tuberculosis and mental health services: global receptivity of national tuberculosis program directors.

A global survey of National Tuberculosis Program (NTP) directors. To assess the perceived mental health needs of persons with tuberculosis (TB), current practices, and receptivity to integrating evidence-based mental and substance use treatment into national TB guidelines. Semi-structured survey of NTP directors from 26 countries of all income levels using a standardized questionnaire. Of the 26 countries, 21 were classified as high incidence and/or burden countries for TB, TB and human immunodeficiency virus coinfection, and/or drug-resistant TB. Two NTPs included routine screening for any mental disorder, four assessed alcohol or drug use, and five had standard protocols for the co-management of disorders. If effective and low-cost integrated care models were available, 17 NTP directors felt that it was highly likely, and five somewhat likely, that their NTPs would integrate mental health treatment into national TB guidelines and services. The main perceived barriers to service integration were limited capacity, not recognizing mental health as a problem, insufficient resources, and TB-related social stigma. NTPs currently do not address mental disorders as part of routine practice. Nevertheless, receptivity is high, which creates a ripe opportunity to integrate the management of TB and mental disorders into the policies and guidelines of NTPs worldwide. .

Precision medicine in the clinical management of respiratory tract infections including multidrug-resistant tuberculosis: learning from innovations in immuno-oncology.

PURPOSE OF REVIEW: In the light of poor management outcomes of antibiotic-resistant respiratory tract infection (RTI)-associated sepsis syndrome and multidrug-resistant tuberculosis (MDR-TB), new management interventions based on host-directed therapies (HDTs) are warranted to improve morbidity, mortality and long-term functional outcomes. We review developments in potential HDTs based on precision cancer therapy concepts applicable to RTIs including MDR-TB. RECENT FINDINGS: Immune reactivity, tissue destruction and repair processes identified during studies of cancer immunotherapy share common pathogenetic mechanisms with RTI-associated sepsis syndrome and MDR-TB. T-cell receptors (TCRs) and chimeric antigen receptors targeting pathogen-specific or host-derived mutated molecules (major histocompatibility class-dependent/ major histocompatibility class-independent) can be engineered for recognition by TCR γδ and natural killer (NK) cells. T-cell subsets and, more recently, NK cells are shown to be host-protective. These cells can also be activated by immune checkpoint inhibitor (ICI) or derived from allogeneic sources and serve as potential for improving clinical outcomes in RTIs and MDR-TB. SUMMARY: Recent developments of immunotherapy in cancer reveal common pathways in immune reactivity, tissue destruction and repair. RTIs-related sepsis syndrome exhibits mixed immune reactions, making cytokine or ICI therapy guided by robust biomarker analyses, viable treatment options.

Pulmonary function and respiratory health after successful treatment of drug-resistant tuberculosis.

BACKGROUND: Post-treatment morbidity among subjects with drug-resistant tuberculosis (DR-TB) is unclear. METHODS: This was a cross-sectional study of patients from Tbilisi, Georgia with cavitary DR-TB and an outcome of cure. Participants had a chest X-ray (CXR), St. George Respiratory Quality (SGRQ) survey, and pulmonary function tests (PFTs) performed. Correlations between SGRQ and PFT results and factors associated with pulmonary impairment were examined. RESULTS: Among 58 subjects (median age 31 years), 40% used tobacco, 59% had prior TB, and 47% underwent adjunctive surgical resection. The median follow-up time was 41 months. Follow-up CXR revealed fibrosis in 30 subjects (52%) and bronchiectasis in seven (12%). The median forced expiratory volume (FEV1)/forced vital capacity (FVC) ratio was 0.72, with 24 subjects (41%) having a ratio of ≤0.70. Significant correlations existed between PFT measures and overall and component SGRQ scores. In linear regression, age, prior TB, and CXR fibrosis or bronchiectasis were significantly associated with decreased pulmonary function. Adjunctive surgery was significantly associated with a higher percent predicted FEV1 and FVC. CONCLUSIONS: A high proportion of DR-TB subjects had residual pulmonary impairment, particularly with recurrent TB and severe radiological disease. The association of surgical resection with improved lung function deserves further study. PFTs and SGRQ may both be useful to evaluate lung health.

Survival analysis of time to cure on multi-drug resistance tuberculosis patients in Amhara region, Ethiopia.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is caused by bacteria that are resistant to the most effective anti-tuberculosis drug. The MDR-TB is an increasing global problem and the spread of MDR-TB has different recovery time for different patients. Therefore, this study aimed to investigate the recovery time of MDR-TB patients in Amhara region, Ethiopia. METHOD: A retrospective study was carried out in seven hospitals having MDR-TB treatment center of Amhara region, Ethiopia from September 2015 to February 2018. An accelerated failure time and parametric shared frailty models were employed. RESULTS: The study revealed that the recovery time of MDR-TB patients in Amhara region was 21 months. Out of the total MDR-TB patients, 110 (35.4%) censored and 201 (64.6%) cured of MDR-TB. The clustering effect of frailty model was hospitals and the Weibull-gamma shared frailty model was selected among all and hence used for this study. The study showed that extra pulmonary MDR-TB patients had longer recovery time than that of seamier pulmonary MDR-TB patients in Amhara region, Ethiopia. According to this study, male MDR-TB patients, MDR-TB patients with co-morbidity and clinical complication were experiencing longer recovery time than that of the counter groups. This study also showed that MDR-TB patients with poor adherence had longer recovery time than those with good adherence MDR-TB patients. CONCLUSION: Among different factors considered in this study, MDR-TB type, clinical complication, adherence, co-morbidities, sex, and smoking status had a significant effect on recovery time of MDR-TB patients in Amhara region, Ethiopia. In conclusion, the Regional and Federal Government of Ethiopia should take immediate steps to address causes of recovery time of MDR-TB patients in Amhara region through encouraging adherence, early case detection, and proper handling of drug-susceptibility according to WHO guidelines.

Modern Collapse Therapy for Pulmonary Tuberculosis.

Multidrug-resistant tuberculosis (TB), extensively drug-resistant TB, and TB-human immunodeficiency virus (HIV) coinfection require a special approach in anti-TB treatment. Most patients cannot be successfully cured by conventional chemotherapy alone. They need a modern approach using minimally invasive therapeutic and surgical techniques. The novel approaches of collapse therapy techniques and minimally invasive osteoplastic thoracoplasty increase the effectiveness of complex anti-TB therapy. Achieving the required selective collapse of lung tissue in destructive pulmonary TB, especially in cases of drug resistance and/or HIV coinfection, leads to bacteriologic conversion, cavity closure, and successful cure.

Managing severe tuberculosis and its sequelae: from intensive care to surgery and rehabilitation / Tratamento da tuberculose grave e suas sequelas: da terapia intensiva à cirurgia e reabilitação

ABSTRACT Multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) continue to challenge physicians and public health specialists. Global treatment outcomes continue to be unsatisfactory, positive outcomes being achieved in only 54% of patients. Overall outcomes are even worse in patients infected with highly resistant strains. Treating MDR-/XDR-TB is difficult because of frequent adverse events, the long duration of drug regimens, the high costs of second-line drugs, chronic post-infectious sequelae, and loss of organ function. Ongoing research efforts (studies and trials) have various aims: increasing the rates of treatment success; understanding the potentialities of new and repurposed drugs; shortening the treatment duration; and reducing the rates of adverse events. It is hoped that better access to rapid diagnostics, increased awareness, and treatments that are more effective will reduce the rate of complications and of lung function impairment. This article aims to discuss the management of severe tuberculosis (defined as that which is potentially life threatening, requiring higher levels of care) and its sequelae, from intensive care to the postoperative period, rehabilitation, and recovery. We also discuss the nonpharmacological interventions available to manage chronic sequelae and improve patient quality of life. Because the majority of MDR-/XDR-TB cases evolve to lung function impairment (typically obstructive but occasionally restrictive), impaired quality of life, and low performance status (as measured by walk tests or other metrics), other interventions (e.g., smoking cessation, pulmonary rehabilitation, vaccination/prevention of secondary bacterial infections/exacerbations, complemented by psychological and nutritional support) are required.

RESUMO A tuberculose multirresistente e a tuberculose extensivamente resistente ainda são um desafio para médicos e especialistas em saúde pública. Os desfechos globais do tratamento ainda são insatisfatórios; apenas 54% dos pacientes têm um desfecho positivo. Os desfechos globais são ainda piores em pacientes infectados por cepas altamente resistentes. O tratamento da tuberculose multirresistente/extensivamente resistente é difícil em virtude dos eventos adversos frequentes, da longa duração dos esquemas terapêuticos, do alto custo dos medicamentos de segunda linha, das sequelas pós-infecciosas crônicas e da perda da função orgânica. Esforços de pesquisa (estudos e ensaios) estão em andamento e têm diversos objetivos: aumentar as taxas de sucesso do tratamento; compreender o potencial de medicamentos novos e reaproveitados; encurtar o tratamento e reduzir as taxas de eventos adversos. Espera-se que melhor acesso ao diagnóstico rápido, maior conhecimento e terapias mais eficazes reduzam as complicações e o comprometimento da função pulmonar. O objetivo deste artigo é discutir o tratamento da tuberculose grave (potencialmente fatal, que necessita de níveis maiores de atenção) e suas sequelas, desde a terapia intensiva até o pós-operatório, reabilitação e recuperação. São também discutidas as intervenções não farmacológicas disponíveis para tratar sequelas crônicas e melhorar a qualidade de vida dos pacientes. Como a maioria dos casos de tuberculose multirresistente/extensivamente resistente resulta em comprometimento da função pulmonar (obstrução principalmente, mas às vezes restrição), qualidade de vida prejudicada e desempenho reduzido (medido por meio de testes de caminhada ou outros), são necessárias outras intervenções (cessação do tabagismo, reabilitação pulmonar, vacinação e prevenção de infecções bacterianas secundárias/exacerbações, por exemplo, complementadas por apoio psicológico e nutricional).

Factores de riesgo que influyen en el fracaso al tratamiento individualizado de tuberculosis multidrogorresistente en la provincia de Ica. 2000-2014 / Risk factors that influence in the failure to the individualized treatment of multidrug-resistant tuberculosis in the province of ica. 2000-2014

Objetivo: Determinar los factores de riesgo que influyen en el fracaso al tratamiento individualizado de Tuberculosis Multidrogorresistente en la provincia de Ica. 2000-2014. Materiales y métodos: Estudio observacional, retrospectivo, tipo analítico, de casos y controles. La muestra estuvo conformada por 19 casos de fracaso al tratamiento individualizado, y por cada caso se tuvo dos controles de pacientes que curaron con tratamiento individualizado. Se realizó el análisis bivariado con un nivel de significancia del 5% se calculó del Odds Ratio (OR) con intervalo de confianza (IC) al 95%. Se realizó análisis de regresión logística. Resultados: En el análisis multivariado resultaron 4 factores de riesgo asociados a fracaso al tratamiento individualizado: resistencia a 5 o más drogas (OR=6,67, p=0,027), tener IMC menor de 18.5 al inicio del tratamiento (OR=7,61 p=0,023), presentar hemoptisis durante el tratamiento (OR= 19,89, P=0,001) y la presencia de cavernas en la radiografía de tórax inicial (OR=27,95, p=0,005). Conclusiones: Los pacientes con resistencia a 5 o más drogas antituberculosas, con IMC menor a 18.5, con hemoptisis durante el tratamiento y los que presentan caverna en la radiografía de tórax, tienen mayor riesgo de fracasar al tratamiento individualizado. (AU)

Objective: To determine the risk factors that influence the failure to individualized treatment of multidrug-resistant tuberculosis in the province of Ica. 2000-2014. Materials and methods:Observational, retrospective study, analytical type, of cases and controls. The sample consisted of 19 cases of failure to individualized treatment, and for each case there were two controls of patients who cured with individualized treatment. The bivariate analysis was performed with a level of significance of 5% was calculated from the Odds Ratio (OR) with 95% confidence interval (CI). Logistic regression analysis was performed. Results: In the multivariate analysis, there were 4 risk factors associated with failure to individualized treatment: resistance to 5 or more drugs (OR = 6.67, p = 0.027), having a BMI less than 18.5 at the beginning of treatment (OR = 7, 61 p = 0.023), presenting hemoptysis during treatment (OR = 19.89, P = 0.001) and the presence of caverns on the initial chest radiograph (OR = 27.95, p = 0.005). Conclusions: Patients with resistance to 5 or more antituberculous drugs, with a BMI less than 18.5, with hemoptysis during treatment and those who have a cavern on chest radiography, have a higher risk of failing individualized treatment. (AU)