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.

What matters most? A qualitative study exploring priorities for supportive interventions for people with tuberculosis in urban Viet Nam.

INTRODUCTION: The health and economic burden of tuberculosis (TB) in urban Viet Nam is high. Social protection and support interventions can improve treatment outcomes and reduce costs. However, evidence regarding optimal strategies in this context is lacking. This study aimed to increase understanding of what people with TB and healthcare providers (HCPs) perceive as important to improve TB treatment outcomes and reduce costs. METHODS: We conducted qualitative focus group discussions (seven groups, n=30) and key informant interviews (n=4) with people with drug-susceptible and multidrug-resistant TB and HCPs in Ha Noi and Ho Chi Minh City. Topic guides covered perspectives on and prioritisation of different forms of social protection and support. Data were analysed using reflexive thematic analysis and interpreted using a Framework for Transformative Social Protection. RESULTS: We identified three themes and seven subthemes. The first theme, 'Existing financial safety nets are essential, but could go further to support people affected by TB', highlights that support to meet the medical costs of TB treatment and flexible cash transfers are a priority for people with TB and HCPs. The second, 'It is important to promote "physical and spiritual health" during TB treatment', demonstrates that extended psychosocial and nutritional support would encourage people with TB during their treatment. The third, 'Accessibility and acceptability are critical in designing social support interventions for people with TB', shows the importance of ensuring that support is accessible and proportional to the needs of people with TB and their families. CONCLUSIONS: Accessible interventions that incorporate financial risk protection, nutritional and psychosocial support matter most to people with TB and HCPs in urban Viet Nam to improve their treatment outcomes and reduce catastrophic costs. This study can inform the design of stronger person-centred interventions to advance progress towards the goals of the WHO's End TB Strategy.

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.

Mental health interventions for rifampicin-resistant tuberculosis patients with alcohol use disorders, Zhytomyr, Ukraine.

INTRODUCTION: Despite concerted efforts, Ukraine is challenged by increasing rates of multidrug and rifampicin-resistant tuberculosis (MDR/RR-TB) comorbid with alcohol use disorder (AUD). This study describes a cohort of RR-TB patients with high alcohol consumption treated in MSF Zhytomyr Project, Ukraine. METHODOLOGY: We used programmatic data for 73 RR-TB patients screened with the AUD Identification Test March-July 2019 and followed-up for culture conversion/TB treatment outcome till 31 January 2020. We described socio-demographic, behavioral, and clinical characteristics, the level of depressive symptoms, and TB treatment outcomes in three groups: 1) patients with AUD who received mental health interventions (MHI); 2) patients with AUD who did not receive MHI; 3) patients with no AUD. We also found three potential contributors to declining to receive MHI. RESULTS: Main characteristics of the study groups did not differ substantially. Those receiving MHI (mean: nine sessions) were rated for alcohol consumption as 'hazardous' (41%), 'harmful' (43%) and 'dependence' (36%) and had higher depression scores versus the second (p=0.009) and third (p=0.095) groups at baseline. Depressive symptoms declined at 9-month follow-up for all patients. Culture conversion was seen at 77%, 73%, and 83% for each group respectively. We also found three reasons for declining from MHI. CONCLUSIONS: We detected little differences across the groups. However, our study cohort demonstrated substantially higher adherence rates, culture conversion and reduction of depressive symptoms than reported globally. We recommend further research on the effectiveness of MHI in changing the drinking habits, quality of life and/or TB treatment outcomes of patients with AUD.

Pragmatic Management of Drug-Resistant Tuberculosis: A Qualitative Analysis of Human Resource Constraints in a Resource-Limited Country context-Ethiopia.

Objectives: Existing evidence suggests that drug-resistant tuberculosis (DR-TB) remains a huge public health threat in high-burden TB countries such as Ethiopia. The purpose of this qualitative study was to explore the challenges of healthcare workers (HCWs) involved in providing DR-TB care in Addis Ababa, Ethiopia. Methods: We conducted in-depth interviews with 18 HCWs purposively selected from 10 healthcare facilities in Addis Ababa, Ethiopia. We then transcribed the audiotaped interviews, and thematically analysed the transcripts using Braun and Clark's reflexive thematic analysis framework. Results: We identified five major themes: 1) inadequate training and provision of information on DR-TB to HCWs assigned to work in DR-TB services, 2) fear of DR-TB infection, 3) risk of contracting DR-TB, 4) a heavy workload, and 5) resource limitations. Conclusion: Our findings highlight major human resource constraints that current DR-TB care policies need to foresee and accommodate. New evidence and best practices on what works in DR-TB care in such resource-limited countries are needed in order to address implementation gaps and to meet global TB strategies.

Toward a Phage Cocktail for Tuberculosis: Susceptibility and Tuberculocidal Action of Mycobacteriophages against Diverse Mycobacterium tuberculosis Strains.

The global health burden of human tuberculosis (TB) and the widespread antibiotic resistance of its causative agent Mycobacterium tuberculosis warrant new strategies for TB control. The successful use of a bacteriophage cocktail to treat a Mycobacterium abscessus infection suggests that phages could play a role in tuberculosis therapy. To assemble a phage cocktail with optimal therapeutic potential for tuberculosis, we have explored mycobacteriophage diversity to identify phages that demonstrate tuberculocidal activity and determined the phage infection profiles for a diverse set of strains spanning the major lineages of human-adapted strains of the Mycobacterium tuberculosis complex. Using a combination of genome engineering and bacteriophage genetics, we have assembled a five-phage cocktail that minimizes the emergence of phage resistance and cross-resistance to multiple phages, and which efficiently kills the M. tuberculosis strains tested. Furthermore, these phages function without antagonizing antibiotic effectiveness, and infect both isoniazid-resistant and -sensitive strains.IMPORTANCE Tuberculosis kills 1.5 million people each year, and resistance to commonly used antibiotics contributes to treatment failures. The therapeutic potential of bacteriophages against Mycobacterium tuberculosis offers prospects for shortening antibiotic regimens, provides new tools for treating multiple drug-resistant (MDR)-TB and extensively drug-resistant (XDR)-TB infections, and protects newly developed antibiotics against rapidly emerging resistance to them. Identifying a suitable suite of phages active against diverse M. tuberculosis isolates circumvents many of the barriers to initiating clinical evaluation of phages as part of the arsenal of antituberculosis therapeutics.

Patients' perceptions regarding multidrug-resistant tuberculosis and barriers to seeking care in a priority city in Brazil during COVID-19 pandemic: A qualitative study.

This study aimed to analyze the discourses of patients who were diagnosed with multidrug-resistant tuberculosis, the perception of why they acquired this health condition and barriers to seeking care in a priority city in Brazil during the COVID-19 pandemic. This was an exploratory qualitative study, which used the theoretical-methodological framework of the Discourse Analysis of French matrix, guided by the Consolidated Criteria for Reporting Qualitative Research. The study was conducted in Ribeirão Preto, São Paulo, Brazil. Seven participants were interviewed who were undergoing treatment at the time of the interview. The analysis of the participants' discourses allowed the emergence of four discursive blocks: (1) impact of the social determinants in the development of multidrug-resistant tuberculosis, (2) barriers to seeking care and difficulties accessing health services, (3) perceptions of the side effects and their impact on multidrug-resistant tuberculosis treatment, and (4) tuberculosis and COVID-19: a necessary dialogue. Through discursive formations, these revealed the determinants of multidrug-resistant tuberculosis. Considering the complexity involved in the dynamics of multidrug-resistant tuberculosis, advancing in terms of equity in health, that is, in reducing unjust differences, is a challenge for public policies, especially at the current moment in Brazil, which is of accentuated economic, political and social crisis. The importance of psychosocial stressors and the lack of social support should also be highlighted as intermediary determinants of health. The study has also shown the situation of COVID-19, which consists of an important barrier for patients seeking care. Many patients reported fear, insecurity and worry with regard to returning to medical appointments, which might contribute to the worsening of tuberculosis in the scenario under study.

Identification of CTL Epitopes on Efflux Pumps of the ATP-Binding Cassette and the Major Facilitator Superfamily of Mycobacterium tuberculosis.

Tuberculosis is the world's most deadly infectious disease, with 10 million people falling ill and 1.5 million people dying from the disease every year. With the increasing number of drug-resistant Mycobacterium tuberculosis (MTB) strains and prevalence of coinfection of MTB with human immunodeficiency virus, many challenges remain in the prevention and treatment of tuberculosis. Therefore, the development of safe and effective tuberculosis vaccines is an urgent issue. In this study, we identified cytotoxic T lymphocyte epitopes on drug resistance-associated membrane protein efflux pumps of MTB, the ATP-binding cassette and the major facilitator superfamilies. First, three online software were used to predict HLA-A2-restricted epitopes. Then, the candidate epitopes were confirmed with the T2A2 cell binding affinity and peptide/MHC (pMHC) complex stability assays and in vitro immune activity experiments. Two drug-resistant T lymphocyte epitopes, designated Rv1218c-p24 and Rv2477c-p182, were selected, and their immunogenic activities studied in vivo in genetically engineered mice. The immune activities of these two epitopes were improved with the help of complete Freund's adjuvant (CFA). The epitopes identified here provide a foundation for the diagnosis and treatment of patients infected with drug resistant and the future development of a multiepitope vaccine.

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.

Mycobacteriophages as Potential Therapeutic Agents against Drug-Resistant Tuberculosis.

The current emergence of multi-, extensively-, extremely-, and total-drug resistant strains of Mycobacterium tuberculosis poses a major health, social, and economic threat, and stresses the need to develop new therapeutic strategies. The notion of phage therapy against bacteria has been around for more than a century and, although its implementation was abandoned after the introduction of drugs, it is now making a comeback and gaining renewed interest in Western medicine as an alternative to treat drug-resistant pathogens. Mycobacteriophages are genetically diverse viruses that specifically infect mycobacterial hosts, including members of the M. tuberculosis complex. This review describes general features of mycobacteriophages and their mechanisms of killing M. tuberculosis, as well as their advantages and limitations as therapeutic and prophylactic agents against drug-resistant M. tuberculosis strains. This review also discusses the role of human lung micro-environments in shaping the availability of mycobacteriophage receptors on the M. tuberculosis cell envelope surface, the risk of potential development of bacterial resistance to mycobacteriophages, and the interactions with the mammalian host immune system. Finally, it summarizes the knowledge gaps and defines key questions to be addressed regarding the clinical application of phage therapy for the treatment of drug-resistant tuberculosis.

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).

Safety and immunogenicity of the adjunct therapeutic vaccine ID93 + GLA-SE in adults who have completed treatment for tuberculosis: a randomised, double-blind, placebo-controlled, phase 2a trial.

BACKGROUND: A therapeutic vaccine that prevents recurrent tuberculosis would be a major advance in the development of shorter treatment regimens. We aimed to assess the safety and immunogenicity of the ID93 + GLA-SE vaccine at various doses and injection schedules in patients with previously treated tuberculosis. METHODS: This randomised, double-blind, placebo-controlled, phase 2a trial was conducted at three clinical sites near Cape Town, South Africa. Patients were recruited at local clinics after receiving 4 months of tuberculosis treatment, and screened for eligibility after providing written informed consent. Participants were aged 18-60 years, BCG-vaccinated, HIV-uninfected, and diagnosed with drug-sensitive pulmonary tuberculosis. Eligible patients had completed standard treatment for pulmonary tuberculosis in the past 28 days. Participants were enrolled after completing standard treatment and randomly assigned sequentially to receive vaccine or placebo in three cohorts: 2 µg intramuscular ID93 + 2 µg GLA-SE on days 0 and 56 (cohort 1); 10 µg ID93 + 2 µg GLA-SE on days 0 and 56 (cohort 2); 2 µg ID93 + 5 µg GLA-SE on days 0 and 56 and placebo on day 28 (cohort 3); 2 µg ID93 + 5 µg GLA-SE on days 0, 28, and 56 (cohort 3); or placebo on days 0 and 56 (cohorts 1 and 2), with the placebo group for cohort 3 receiving an additional injection on day 28. Randomisation was in a ratio of 3:1 for ID93 + GLA-SE and saline placebo in cohorts 1 and 2, and in a ratio of 3:3:1 for (2 ×) ID93 + GLA-SE, (3 ×) ID93 + GLA-SE, and placebo in cohort 3. The primary outcomes were safety and immunogenicity (vaccine-specific antibody response and T-cell response). For the safety outcome, participants were observed for 30 min after each injection, injection site reactions and systemic adverse events were monitored until day 84, and serious adverse events and adverse events of special interest were monitored for 6 months after the last injection. Vaccine-specific antibody responses were measured by serum ELISA, and T-cell responses after stimulation with vaccine antigens were measured in cryopreserved peripheral blood mononuclear cells specimens using intracellular cytokine staining followed by flow cytometry. This study is registered with ClinicalTrials.gov, number NCT02465216. FINDINGS: Between June 17, 2015, and May 30, 2016, we assessed 177 patients for inclusion. 61 eligible patients were randomly assigned to receive: saline placebo (n=5) or (2 ×) 2 µg ID93 + 2 µg GLA-SE (n=15) on days 0 and 56 (cohort 1); saline placebo (n=2) or (2 ×) 10 µg ID93 + 2 µg GLA-SE (n=5) on days 0 and 56 (cohort 2); saline placebo (n=5) on days 0, 28 and 56, or 2 µg ID93 + 5 µg GLA-SE (n=15) on days 0 and 56 and placebo injection on day 28, or (3 ×) 2 µg ID93 + 5 µg GLA-SE (n=14) on days 0, 28, and 56 (cohort 3). ID93 + GLA-SE induced robust and durable antibody responses and specific, polyfunctional CD4 T-cell responses to vaccine antigens. Two injections of the 2 µg ID93 + 5 µg GLA-SE dose induced antigen-specific IgG and CD4 T-cell responses that were significantly higher than those with placebo and persisted for the 6-month study duration. Mild to moderate injection site pain was reported after vaccination across all dose combinations, and induration and erythema in patients given 2 µg ID93 + 5 µg GLA-SE in two or three doses. One participant had grade 3 erythema and induration at the injection site. No vaccine-related serious adverse events were observed. INTERPRETATION: Vaccination with ID93 + GLA-SE was safe and immunogenic for all tested regimens. These data support further evaluation of ID93 + GLA-SE in therapeutic vaccination strategies to improve tuberculosis treatment outcomes. FUNDING: Wellcome Trust (102028/Z/13/Z).

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.

Ease and equity of access to free DR-TB services in Nigeria- a qualitative analysis of policies, structures and processes.

INTRODUCTION: Persistent low rates of case notification and treatment coverage reflect that accessing diagnosis and treatment for drug-resistant tuberculosis (DR-TB) in Nigeria remains a challenge, even though it is provided free of charge to patients. Equity in health access requires availability of comparable, appropriate services to all, based on needs, and irrespective of socio-demographic characteristics. Our study aimed to identify the reasons for Nigeria's low rates of case-finding and treatment for DR-TB. To achieve this, we analyzed elements that facilitate or hinder equitable access for different groups of patients within the current health system to support DR-TB management in Nigeria. METHODS: We conducted documentary review of guidelines and workers manuals, as well as 57 qualitative interviews, including 10 focus group discussions, with a total of 127 participants, in Nigeria. Between August and November 2017, we interviewed patients who were on treatment, their treatment supporter, and providers in Ogun and Plateau States, as well as program managers in Benue and Abuja. We adapted and used Levesque's patient-centered access to care framework to analyze DR-TB policy documents and interview data. RESULTS: Thematic analysis revealed inequitable access to DR-TB care for some patient socio-demographic groups. While patients were mostly treated equally at the facility level, some patients experienced more difficulty accessing care based on their gender, age, occupation, educational level and religion. Health system factors including positive provider attitudes and financial support provided to the patients facilitated equity and ease of access. However, limited coverage and the absence of patients' access rights protection and considerations in the treatment guidelines and workers manuals likely hampered access. CONCLUSION: In the context of Nigeria's low case-finding and treatment coverage, applying an equity of access framework was necessary to highlight gaps in care. Differing social contexts of patients adversely affected their access to DR-TB care. We identified several strengths in DR-TB care delivery, including the current financial support that should be sustained. Our findings highlight the need for government's commitment and continued interventions.

A comparison of patient treatment pathways among multidrug-resistant and drug-sensitive TB cases in Delhi, India: A cross-sectional study.

BACKGROUND: The delay in the diagnosis and treatment initiation of patients with MDR-TB worsens individual prognosis and increases the risk of disease transmission in the community. These delays have been attributed to delay in treatment-seeking by the patient and shifting to multiple healthcare facilities before being tested and diagnosed through India's National Tuberculosis Elimination Program (NTEP). OBJECTIVE: to identify treatment pathways in patients with MDR-TB from the time of onset of symptoms and treatment seeking until diagnosis at a PMDT site and subsequent treatment initiation. We also compared these characteristics with those of patients with DS-TB. METHODS: We recruited a total of 168 patients with MDR-TB and DS-TB each, in Delhi. Data were analyzed using IBM SPSS Version 25. RESULTS: The mean (SD) patient delay for initial treatment-seeking was 20.9 (15.9) days in patients with MDR-TB, and 16.1 (17.1) days in patients with DS-TB (p < 0.001). The median time from visit to the first healthcare facility (HCF) until confirmation of MDR-TB diagnosis was 78.5 days, and until treatment initiation was 102.5 days. Among patients with DS-TB, the time interval from a visit to the first HCF until the initiation of ATT-DOTS was 61.5 days.. Patients diagnosed with DS-TB, whose first source of treatment was a private facility (n = 49), reported a significant delay in the initiation of ATT-DOTS (p < 0.001). CONCLUSIONS: Despite the introduction of universal drug sensitivity testing in individuals having presumptive MDR-TB, a significant delay in the diagnosis and initiation of effective MDR-TB treatment persists as a major public health challenge in India.

Drug resistant TB spine in a two year old child: A case report.

Spinal tuberculosis (TB) is a disease of high morbidity that is associated with deformity and neurological sequelae, especially in growing children. Children diagnosed with spinal TB need to be monitored closely for clinical improvements. Previous history of antituberculous therapy (ATT), poor adherence to previous ATT, contact with persons having known drug-resistant (DR) TB, or clinical worsening despite regular ATT are strong indicators for the diagnosis of DR TB of the spine. We report a case of spinal DRTB in a two year old child with no previous history of ATT and contact with a person on irregular treatment for drug sensitive TB that did not show regression of the spinal lesions despite standard ATT.

What causes high costs for rural tuberculosis inpatients? Evidence from five counties in China.

BACKGROUND: Tuberculosis (TB) still causes high economic burden on patients in China, especially for rural patients. Our study aims to explore the risk factors associated with the high costs for TB inpatients in rural China from the aspects of inpatients' socio-demographic and institutional attributes. METHODS: Generalized linear models were utilized to investigate the factors associated with TB inpatients' total costs and out-of-pocket (OOP) expenditures. Quantile regression (QR) models were applied to explore the effect of each factor across the different costs range and identify the risk factors of high costs. RESULTS: TB inpatients with long length of stay and who receive hospitalization services cross provincially, in tertiary and specialized hospitals were likely to face high total costs and OOP expenditures. QR models showed that high total costs occurred in Dingyuan and Funan Counties, but they were not accompanied by high OOP expenditures. CONCLUSIONS: Early diagnosis, standard treatment and control of drug-resistant TB are still awaiting for more efforts from the government. TB inpatients should obtain medical services from appropriate hospitals. The diagnosis and treatment process of TB should be standardized across all designated medical institutions. Furthermore, the reimbursement policy for migrant workers who suffered from TB should be ameliorated.