RESUMO
BACKGROUND: Whole-genome sequencing (WGS)-based prediction of drug resistance in Mycobacterium tuberculosis has the potential to guide clinical decisions in the design of optimal treatment regimens. METHODS: We utilized WGS to investigate drug resistance mutations in a 32-year-old Tanzanian male admitted to Kibong'oto Infectious Diseases Hospital with a history of interrupted multidrug-resistant tuberculosis treatment for more than three years. Before admission, he received various all-oral bedaquiline-based multidrug-resistant tuberculosis treatment regimens with unfavourable outcomes. RESULTS: Drug susceptibility testing of serial M. tuberculosis isolates using Mycobacterium Growth Incubator Tubes culture and WGS revealed resistance to first-line anti-TB drugs, bedaquiline, and fluoroquinolones but susceptibility to linezolid, clofazimine, and delamanid. WGS of serial cultured isolates revealed that the Beijing (Lineage 2.2.2) strain was resistant to bedaquiline, with mutations in the mmpR5 gene (Rv0678. This study also revealed the emergence of two distinct subpopulations of bedaquiline-resistant tuberculosis strains with Asp47f and Glu49fs frameshift mutations in the mmpR5 gene, which might be the underlying cause of prolonged resistance. An individualized regimen comprising bedaquiline, delamanid, pyrazinamide, ethionamide, and para-aminosalicylic acid was designed. The patient was discharged home at month 8 and is currently in the ninth month of treatment. He reported no cough, chest pain, fever, or chest tightness but still experienced numbness in his lower limbs. CONCLUSION: We propose the incorporation of WGS in the diagnostic framework for the optimal management of patients with drug-resistant and extensively drug-resistant tuberculosis.
Assuntos
Antituberculosos , Tuberculose Extensivamente Resistente a Medicamentos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis , Sequenciamento Completo do Genoma , Humanos , Masculino , Adulto , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Antituberculosos/uso terapêutico , Antituberculosos/farmacologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Farmacorresistência Bacteriana Múltipla/genética , Tanzânia , Mutação , Diarilquinolinas/uso terapêutico , Diarilquinolinas/farmacologia , Genoma Bacteriano , Linezolida/uso terapêutico , Linezolida/farmacologiaRESUMO
BACKGROUND: Chronic lung diseases (CLDs), responsible for 4 million deaths globally every year, are increasingly important in low- and middle-income countries where most of the global mortality due to CLDs currently occurs. As existing health systems in resource-poor contexts, especially sub-Saharan Africa (SSA), are not generally oriented to provide quality care for chronic diseases, a first step in re-imagining them is to critically consider readiness for service delivery across all aspects of the existing system. METHODS: We conducted a mixed-methods assessment of CLD service readiness in 18 purposively selected health facilities in two differing SSA health system contexts, Tanzania and Sudan. We used the World Health Organization's (WHO) Service Availability and Readiness Assessment checklist, qualitative interviews of key health system stakeholders, health facility registers review and assessed clinicians' capacity to manage CLD using patient vignettes. CLD service readiness was scored as a composite of availability of service-specific tracer items from the WHO service availability checklist in three domains: staff training and guidelines, diagnostics and equipment, and basic medicines. Qualitative data were analysed using the same domains. RESULTS: One health facility in Tanzania and five in Sudan, attained a CLD readiness score of ≥ 50 % for CLD care. Scores ranged from 14.9 % in a dispensary to 53.3 % in a health center in Tanzania, and from 36.4 to 86.4 % in Sudan. The least available tracer items across both countries were trained human resources and guidelines, and peak flow meters. Only two facilities had COPD guidelines. Patient vignette analysis revealed significant gaps in clinicians' capacity to manage CLD. Key informants identified low prioritization as key barrier to CLD care. CONCLUSIONS: Gaps in service availability and readiness for CLD care in Tanzania and Sudan threaten attainment of universal health coverage in these settings. Detailed assessments by health systems researchers in discussion with stakeholders at all levels of the health system can identify critical blockages to reimagining CLD service provision with people-centered, integrated approaches at its heart.
Assuntos
Instalações de Saúde , Pneumopatias , Acessibilidade aos Serviços de Saúde , Humanos , Sudão/epidemiologia , Tanzânia/epidemiologiaRESUMO
INTRODUCTION: Tuberculosis (TB) is significantly associated with multiple postinfectious, non-communicable diseases after microbiological cure. For example, those with a history of TB disease have a higher risk of developing chronic lung diseases at a younger age. However, the extent and nature of post-TB complications are not well described. Here, we present a protocol for a systematic review and meta-analysis, which aims to synthesise literature on the burden of post-TB lung disease (PTLD) in sub-Saharan Africa, describe phenotypes, long-term outcomes and the health-related quality of life of people with PTLD. METHODS AND ANALYSIS: A systematic search will be conducted using PubMed, EMBASE, Web of Science, African Journals Online and the Cochrane Library of Systematic Reviews. Papers published in English and French languages that report the prevalence, clinical features, quality of life and long-term outcomes of people with PTLD in sub-Saharan Africa will be considered. We will assess and critically appraise the methodological quality of all studies using the modified covidence. Qualitative and quantitative (network and meta-analysis) synthesis will be performed and STATA V.16 will be used to estimate the burden of PTLD. ETHICS AND DISSEMINATION: Ethical approval is not required for this systematic review and meta-analysis. Our results will be published in peer-reviewed journals. PROSPERO REGISTRATION NUMBER: CRD42021274018.
Assuntos
Pneumopatias , Tuberculose , África Subsaariana/epidemiologia , Humanos , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Metanálise como Assunto , Qualidade de Vida , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: While most Non-tuberculous mycobacteria (NTM) are saprophytic, several species have been associated with human diseases, from localized infection to disseminated diseases. Pulmonary NTM infections lead to TB-like disease called NTM pulmonary disease (NTM-PD). Due to variation in treatment options among NTM species, it is necessary to identify the species and determine drug susceptibility profiles to inform the choice of appropriate regimen for the disease. DESIGN: A total of 188 culture-positive isolates from patients diagnosed with TB were screened for NTM at the Central Tuberculosis Reference Laboratory. All NTM were further speciated using GenoType® Mycobacterium-Common Mycobacterium and Additional species (GenoType® CM/AS) kit. Mycobacteria avium complex (MAC) and Mycobacteria abscessus complex (MABC) which could not be identified with the test to species were subjected to GenoType® Mycobacteria NTM-DR for further speciation. Using the same test, identified MAC and MABC were genotyped to determine the drug susceptibility profile for each isolate to macrolide and aminoglycosides. RESULTS: Of all isolates identified as mycobacteria, 24 (13%) were NTM. Fifteen isolates could be identified to species level of which prevalent species was M. avium sub. intracellulare 4 (27%). A total of 10 isolates were MAC (n = 6) and MABC (n = 4) were subjected to GenoType® Mycobacteria NTM-DR for determination of macrolide and aminoglycoside susceptibility. Three of the four MABC had a mutation at the T28 position of the erm (41). All MAC were susceptible to both drugs. CONCLUSION: In this study, MAC was the most frequently isolated NTM species followed by MABC. While all MAC and MABC identified, were susceptible to aminoglycosides, three MABC were resistant to the macrolides due to mutation at position 28 of the erm (41) gene. For this, it is important for clinicians need to rule out NTM, understand species and their drug susceptibility for optimal case management.
Assuntos
Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Mycobacterium , Tuberculose Pulmonar , Tuberculose , Aminoglicosídeos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Macrolídeos/farmacologia , Testes de Sensibilidade Microbiana , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/genética , Complexo Mycobacterium avium/genética , Micobactérias não Tuberculosas/genética , Tanzânia/epidemiologia , Tuberculose Pulmonar/diagnósticoRESUMO
Globally, tuberculosis (TB) is a leading cause of death from a single infectious agent. Healthcare workers (HCWs) are at increased risk of hospital-acquired TB infection due to persistent exposure to Mycobacterium tuberculosis (Mtb) in healthcare settings. The World Health Organization (WHO) has developed an international system of infection prevention and control (IPC) interventions to interrupt the cycle of nosocomial TB transmission. The guidelines on TB IPC have proposed a comprehensive hierarchy of three core practices, comprising: administrative controls, environmental controls, and personal respiratory protection. However, the implementation of most recommendations goes beyond minimal physical and organisational requirements and thus cannot be appropriately introduced in resource-constrained settings and areas of high TB incidence. In many low- and middle-income countries (LMICs) the lack of knowledge, expertise and practice on TB IPC is a major barrier to the implementation of essential interventions. HCWs often underestimate the risk of airborne Mtb dissemination during tidal breathing. The lack of required expertise and funding to design, install and maintain the environmental control systems can lead to inadequate dilution of infectious particles in the air, and in turn, increase the risk of TB dissemination. Insufficient supply of particulate respirators and lack of direction on the re-use of respiratory protection is associated with unsafe working practices and increased risk of TB transmission between patients and HCWs. Delayed diagnosis and initiation of treatment are commonly influenced by the effectiveness of healthcare systems to identify TB patients, and the availability of rapid molecular diagnostic tools. Failure to recognise resistance to first-line drugs contributes to the emergence of drug-resistant Mtb strains, including multidrug-resistant and extensively drug-resistant Mtb. Future guideline development must consider the social, economic, cultural and climatic conditions to ensure that recommended control measures can be implemented in not only high-income countries, but more importantly low-income, high TB burden settings. Urgent action and more ambitious investments are needed at both regional and national levels to get back on track to reach the global TB targets, especially in the context of the COVID-19 pandemic.
Assuntos
COVID-19/complicações , Pessoal de Saúde , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Tuberculose/prevenção & controle , Tuberculose/transmissão , COVID-19/prevenção & controle , Humanos , Doença Iatrogênica/prevenção & controle , Incidência , Fatores de RiscoRESUMO
BACKGROUND: Adherence to tuberculosis (TB) treatment is challenging because of many factors. The World Health Organization has recommended the use of digital adherence monitoring technologies in its End TB Strategy. However, evidence on improving adherence is limited. EvriMED is a real-time medication-monitoring device which was found to be feasible and acceptable in a few studies in Asia. In Tanzania, however, there may be challenges in implementing evriMED due to stigmatization, network and power access, accuracy, and cost effectiveness, which may have implications for treatment outcome. We propose a pragmatic cluster randomized trial to investigate the effectiveness of evriMED with reminder cues and tailored feedback on adherence to TB treatment in Kilimanjaro, Tanzania. METHODS/DESIGN: We will create clusters in Kilimanjaro based on level of health care facility. Clusters will be randomized in an intervention arm, where evriMED will be implemented, or a control arm, where standard practice directly observed treatment will be followed. TB patients in intervention clusters will take their medication from the evriMED pillbox and receive tailored feedback. We will use the 'Stages of Change' model, which assumes that a person has to go through the stages of pre-contemplation, contemplation, preparation, action, and evaluation to change behavior for tailored feedback on adherence reports from the device. DISCUSSION: If the intervention shows a significant effect on adherence and the devices are accepted, accurate, and sustainable, the intervention can be scaled up within the National Tuberculosis Programmes. TRIAL REGISTRATION: Pan African Clinical Trials Registry, PACTR201811755733759 . Registered on 8 November 2018.