RESUMO
BACKGROUND: Increasing evidence suggests that post-TB lung disease (PTLD) causes significant morbidity and mortality. The aim of these clinical standards is to provide guidance on the assessment and management of PTLD and the implementation of pulmonary rehabilitation (PR).METHODS: A panel of global experts in the field of TB care and PR was identified; 62 participated in a Delphi process. A 5-point Likert scale was used to score the initial ideas for standards and after several rounds of revision the document was approved (with 100% agreement).RESULTS: Five clinical standards were defined: Standard 1, to assess patients at the end of TB treatment for PTLD (with adaptation for children and specific settings/situations); Standard 2, to identify patients with PTLD for PR; Standard 3, tailoring the PR programme to patient needs and the local setting; Standard 4, to evaluate the effectiveness of PR; and Standard 5, to conduct education and counselling. Standard 6 addresses public health aspects of PTLD and outcomes due to PR.CONCLUSION: This is the first consensus-based set of Clinical Standards for PTLD. Our aim is to improve patient care and quality of life by guiding clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage PTLD.
Assuntos
Pneumopatias , Qualidade de Vida , Tuberculose , Humanos , Consenso , Pneumopatias/diagnóstico , Pneumopatias/terapia , Tuberculose/complicaçõesRESUMO
The World Health Organization (WHO) recommends countries introduce new anti-TB drugs in the treatment of multidrug-resistant tuberculosis. The aim of the study is to prospectively evaluate the effectiveness of bedaquiline (and/or delamanid)- containing regimens in a large cohort of consecutive TB patients treated globally. This observational, prospective study is based on data collected and provided by Global Tuberculosis Network (GTN) centres and analysed twice a year. All consecutive patients (including children/adolescents) treated with bedaquiline and/or delamanid were enrolled, and managed according to WHO and national guidelines. Overall, 52 centres from 29 countries/regions in all continents reported 883 patients as of January 31st 2021, 24/29 countries/regions providing data on 100% of their consecutive patients (10-80% in the remaining 5 countries). The drug-resistance pattern of the patients was severe (>30% with extensively drug-resistant -TB; median number of resistant drugs 5 (3-7) in the overall cohort and 6 (4-8) among patients with a final outcome). For the patients with a final outcome (477/883, 54.0%) the median (IQR) number of months of anti-TB treatment was 18 (13-23) (in days 553 (385-678)). The proportion of patients achieving sputum smear and culture conversion ranged from 93.4% and 92.8% respectively (whole cohort) to 89.3% and 88.8% respectively (patients with a final outcome), a median (IQR) time to sputum smear and culture conversion of 58 (30-90) days for the whole cohort and 60 (30-100) for patients with a final outcome and, respectively, of 55 (30-90) and 60 (30-90) days for culture conversion. Of 383 patients treated with bedaquiline but not delamanid, 284 (74.2%) achieved treatment success, while 25 (6.5%) died, 11 (2.9%) failed and 63 (16.5%) were lost to follow-up.
Assuntos
Antituberculosos/uso terapêutico , Diarilquinolinas/uso terapêutico , Nitroimidazóis/uso terapêutico , Oxazóis/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológicoRESUMO
SETTING: Data were collected from patients starting one of the shorter treatment regimens (STRs) for multidrug-resistant tuberculosis (MDR-TB) in Bangladesh, Niger or Cameroon.OBJECTIVE: To estimate the effect of either a gatifloxacin (GFX), moxifloxacin (MFX) or levofloxacin (LVX) based STR on bacteriological effectiveness.DESIGN: Retrospective study of prospectively collected data.RESULTS: Among 1530 patients, bacteriological effectiveness was 96.7% overall. Stratified by treatment with a GFX-, LVX- or MFX-based regimen effectiveness was respectively 97.5%, 95.5% and 94.7%. Compared to those on a GFX-based regimen, the estimated summary odds ratio of having an adverse outcome was more than double (OR 2.05, 95% CI 1.09-3.90) in patients treated with either an LVX-based or MFX-based regimen. After adjusting for initial resistance, patients treated with an LVX-based regimen and MFX-based regimen had respectively a 4.5- and 8.4-fold times larger odds of an adverse bacteriological outcome. None among 859 patients at risk treated with a GFX-based compared to at least 4 of 228 among those on an MFX-based regimen acquired fluoroquinolone resistance.CONCLUSION: GFX-based regimens had superior bacteriological effectiveness than MFX-based or LVX-based regimens. As GFX is currently unavailable in most MDR-TB programs, its reintroduction should be prioritised.
Assuntos
Antituberculosos/administração & dosagem , Gatifloxacina/administração & dosagem , Levofloxacino/administração & dosagem , Moxifloxacina/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bangladesh , Camarões , Criança , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Níger , Estudos Retrospectivos , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto JovemRESUMO
Assuntos
Antituberculosos/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adulto , África , Esquema de Medicação , Humanos , Falha de Tratamento , Resultado do TratamentoRESUMO
Assuntos
Antituberculosos/administração & dosagem , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , Idoso , Antituberculosos/efeitos adversos , Criança , Estudos de Coortes , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Programas Nacionais de Saúde , Níger , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
People living with the human immunodeficiency virus (HIV) (PLHIV) are at high risk for tuberculosis (TB), and TB is a major cause of death in PLHIV. Preventing TB in PLHIV is therefore a key priority. Early initiation of antiretroviral therapy (ART) in asymptomatic PLHIV has a potent TB preventive effect, with even more benefits in those with advanced immunodeficiency. Applying the most recent World Health Organization recommendations that all PLHIV initiate ART regardless of clinical stage or CD4 cell count could provide a considerable TB preventive benefit at the population level in high HIV prevalence settings. Preventive therapy can treat tuberculous infection and prevent new infections during the course of treatment. It is now established that isoniazid preventive therapy (IPT) combined with ART among PLHIV significantly reduces the risk of TB and mortality compared with ART alone, and therefore has huge potential benefits for millions of sufferers. However, despite the evidence, this intervention is not implemented in most low-income countries with high burdens of HIV-associated TB. HIV and TB programme commitment, integration of services, appropriate screening procedures for excluding active TB, reliable drug supplies, patient-centred support to ensure adherence and well-organised follow-up and monitoring that includes drug safety are needed for successful implementation of IPT, and these features would also be needed for future shorter preventive regimens. A holistic approach to TB prevention in PLHIV should also include other important preventive measures, such as the detection and treatment of active TB, particularly among contacts of PLHIV, and control measures for tuberculous infection in health facilities, the homes of index patients and congregate settings.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Antituberculosos/administração & dosagem , Infecções por HIV/epidemiologia , Tuberculose/prevenção & controle , Contagem de Linfócito CD4 , Países em Desenvolvimento , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Isoniazida/administração & dosagem , Pobreza , Tuberculose/epidemiologiaRESUMO
Current World Health Organization guidelines for the formulation of treatment regimens for multidrug-resistant tuberculosis (MDR-TB) pay too little attention to the microbiological activity of anti-tuberculosis drugs. Here, we draw lessons from the pioneering work done on shorter MDR-TB treatment regimens and the current knowledge of the bactericidal and sterilizing properties of the drugs to inform the composition of treatment regimens for MDR-TB. We propose to reserve the term 'core drug' for the one drug in a regimen that contributes most to relapse-free cure. The core drug has both moderate to high bactericidal and sterilizing activity, is given throughout treatment, is well tolerated, and has no cross-resistance with the core drug used in the previous regimen. Currently used core drugs include rifampicin in the first-line 6-month regimen, and fourth-generation fluoroquinolones and bedaquiline in regimens for drug-resistant TB. All other drugs are 'companion drugs', used to avert treatment failure due to acquired drug resistance against the core drug. Some also help further reduce the risk of relapse. Moreover, toxic drugs should be avoided if there is an alternative. A regimen must always include the core drug, plus at least one companion drug with high bactericidal activity, a second bactericidal companion drug, plus two sterilizing companion drugs.
Assuntos
Antituberculosos/uso terapêutico , Protocolos Clínicos , Medicamentos Essenciais/uso terapêutico , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Farmacorresistência Bacteriana , Humanos , Testes de Sensibilidade Microbiana , Prevenção SecundáriaRESUMO
SUMMARY
Multidrug-resistant (MDR) and extensively drug-resistant tuberculosis (XDR-TB) are global concerns, with stagnant treatment success rates of roughly 54% and 30%, respectively. Despite adverse events associated with several DR-TB drugs, newly developed drugs and shorter regimens are bringing hope; recent concern has focused on drugs that prolong the corrected QT interval (QTc). QTc prolongation is a risk factor for torsades de pointe (TdP), a potentially lethal cardiac arrhythmia. While QTc prolongation is used in research as a surrogate marker for drug safety, the correlation between QTc and TdP is not perfect and depends on additional risk factors. The electrocardiogram (ECG) monitoring that has been recommended when new drugs are used has created alarm among clinicians and National Tuberculosis Programmes (NTPs). ECG monitoring is often challenging in high-burden settings where treatment alternatives are limited. According to a review of studies, the prevalence of sudden death directly attributable to TdP by QTc-prolonging DR-TB drugs is likely less than 1%. The risk of death from an ineffective MDR-TB/XDR-TB regimen thus far exceeds the risk of death from arrhythmia. In patients with QTc prolongation who develop cardiac events, other significant risk factors in addition to the drugs themselves are nearly always present. Clinicians and NTPs should be aware of and manage all possible circumstances that may trigger an arrhythmia (hypopotassaemia and human immunodeficiency virus infection are probably the most frequent in DR-TB patients). We present the limited but growing evidence on QTc prolongation and DR-TB management and propose a clinical approach to achieve an optimal balance between access to life-saving drugs and patient safety.RESUMO
SETTING: Nine countries in West and Central Africa. OBJECTIVE: To assess outcomes and adverse drug events of a standardised 9-month treatment regimen for multidrug-resistant tuberculosis (MDR-TB) among patients never previously treated with second-line drugs. DESIGN: Prospective observational study of MDR-TB patients treated with a standardised 9-month regimen including moxifloxacin, clofazimine, ethambutol (EMB) and pyrazinamide (PZA) throughout, supplemented by kanamycin, prothionamide and high-dose isoniazid during an intensive phase of a minimum of 4 to a maximum of 6 months. RESULTS: Among the 1006 MDR-TB patients included in the study, 200 (19.9%) were infected with the human immunodeficiency virus (HIV). Outcomes were as follows: 728 (72.4%) cured, 93 (9.2%) treatment completed (81.6% success), 59 (5.9%) failures, 78 (7.8%) deaths, 48 (4.8%) lost to follow-up. The proportion of deaths was much higher among HIV-infected patients (19.0% vs. 5.0%). Treatment success did not differ by HIV status among survivors. Fluoroquinolone resistance was the main cause of failure, while resistance to PZA, ethionamide or EMB did not influence bacteriological outcome. The most important adverse drug event was hearing impairment (11.4% severe deterioration after 4 months). CONCLUSIONS: The study results support the use of the short regimen recently recommended by the World Health Organization. Its high level of success even among HIV-positive patients promises substantial improvements in TB control.
Assuntos
Antituberculosos/administração & dosagem , Infecções por HIV/epidemiologia , Perda Auditiva/induzido quimicamente , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Adolescente , Adulto , África/epidemiologia , Idoso , Antituberculosos/efeitos adversos , Antituberculosos/farmacologia , Farmacorresistência Bacteriana , Feminino , Perda Auditiva/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Falha de Tratamento , Resultado do Tratamento , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Adulto JovemRESUMO
OBJECTIVE: To determine the prevalence of and factors associated with pulmonary tuberculosis (PTB) in an urban prison in sub-Saharan Africa. DESIGN: A cross-sectional survey. SETTING: The Central Prison of Douala, Cameroon. RESULTS: Two thousand four hundred and seventy four (87.4%) out of 2830 inmates underwent screening. Twenty seven (1.1%) of the inmates were under treatment for smear-positive PTB on commencement of the survey while 60 (2.4%) were diagnosed with smear and/or culture-positive PTB during the active case finding, resulting in a point prevalence of PTB of 3.5%. HIV seroprevalence in inmates without clinical signs of PTB was 111/1067 (10.4%) while it amounted to 6/24 (25%) in PTB patients. In multiple stepwise regression analysis, a low BMI, a prison stay of < or = 12 months, and a history of previous incarceration were positively associated with PTB. CONCLUSION: The study results confirm the high prevalence rates of PTB in prison populations and underscore the need for urgent preventive measures.
Assuntos
Inquéritos Epidemiológicos , Prisioneiros/estatística & dados numéricos , Prisões , Tuberculose Pulmonar/epidemiologia , Adolescente , Adulto , Idoso , Camarões/epidemiologia , Estudos Transversais , Feminino , Soropositividade para HIV/epidemiologia , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Prevalência , Tuberculose Pulmonar/diagnósticoRESUMO
SETTING: Niger National Tuberculosis Programme. Regions supported by the Damien Foundation. OBJECTIVE: To evaluate the effectiveness of a short-course standardised treatment regimen for patients with proven multidrug-resistant tuberculosis (MDR-TB) previously untreated with second-line drugs. METHODS: Prospective study including all patients enrolled from 2008 to 2010. The 12-month standardised regimen comprised high doses of gatifloxacin, clofazimine, ethambutol and pyrazinamide throughout, supplemented by kanamycin, prothionamide and medium-high doses of isoniazid during the intensive phase of a minimum of 4 months. Patients were monitored using sputum smear and culture at start of treatment and every 2 months. Cured patients were followed up 6-monthly for 24 months. RESULTS: Sixty-five patients with MDR-TB were included and analysed. One of 58 patients tested for human immunodeficiency virus (1.7%) infection was positive. Twenty-five patients (39.7%) were severely affected (body mass index â©¿16 kg/m(2)). Cure was achieved in 58 patients (89.2%, 95%CI 81.7-96.7), 6 died and 1 defaulted. All 49 patients assessed at the 24-month follow-up after cure remained smear- and culture-negative. The main adverse events were vomiting (26.2%) and hearing impairment (20%), but no treatment had to be stopped. CONCLUSION: Standardised 12-month treatment for MDR-TB was highly effective and well tolerated in patients not previously exposed to second-line drugs in Niger.