ABSTRACT
BACKGROUND: Adverse effects (AE) to TB treatment cause morbidity, mortality and treatment interruption. The aim of these clinical standards is to encourage best practise for the diagnosis and management of AE.METHODS: 65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.RESULTS: We identified eight clinical standards. Each person commencing treatment for TB should: Standard 1, be counselled regarding AE before and during treatment; Standard 2, be evaluated for factors that might increase AE risk with regular review to actively identify and manage these; Standard 3, when AE occur, carefully assessed and possible allergic or hypersensitivity reactions considered; Standard 4, receive appropriate care to minimise morbidity and mortality associated with AE; Standard 5, be restarted on TB drugs after a serious AE according to a standardised protocol that includes active drug safety monitoring. In addition: Standard 6, healthcare workers should be trained on AE including how to counsel people undertaking TB treatment, as well as active AE monitoring and management; Standard 7, there should be active AE monitoring and reporting for all new TB drugs and regimens; and Standard 8, knowledge gaps identified from active AE monitoring should be systematically addressed through clinical research.CONCLUSION: These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Hypersensitivity , Tuberculosis , Humans , Tuberculosis/diagnosis , Tuberculosis/drug therapy , Drug-Related Side Effects and Adverse Reactions/etiology , Health PersonnelABSTRACT
BACKGROUND: The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).METHODS: A panel of 54 global experts in the field of TB care, public health, microbiology, and pharmacology were identified; 46 participated in a Delphi process. A 5-point Likert scale was used to score draft standards. The final document represents the broad consensus and was approved by all 46 participants.RESULTS: Seven clinical standards were defined: Standard 1, all patients (adult or child) who have symptoms and signs compatible with PTB should undergo investigations to reach a diagnosis; Standard 2, adequate bacteriological tests should be conducted to exclude drug-resistant TB; Standard 3, an appropriate regimen recommended by WHO and national guidelines for the treatment of PTB should be identified; Standard 4, health education and counselling should be provided for each patient starting treatment; Standard 5, treatment monitoring should be conducted to assess adherence, follow patient progress, identify and manage adverse events, and detect development of resistance; Standard 6, a recommended series of patient examinations should be performed at the end of treatment; Standard 7, necessary public health actions should be conducted for each patient. We also identified priorities for future research into PTB.CONCLUSION: These consensus-based clinical standards will help to improve patient care by guiding clinicians and programme managers in planning and implementation of locally appropriate measures for optimal person-centred treatment for PTB.
Subject(s)
Tuberculosis, Pulmonary , Adult , Child , Humans , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/microbiologyABSTRACT
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.
Subject(s)
Lung Diseases , Quality of Life , Tuberculosis , Humans , Consensus , Lung Diseases/diagnosis , Lung Diseases/therapy , Tuberculosis/complicationsABSTRACT
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.
Subject(s)
Antitubercular Agents/therapeutic use , Diarylquinolines/therapeutic use , Nitroimidazoles/therapeutic use , Oxazoles/therapeutic use , Tuberculosis, Multidrug-Resistant/epidemiology , Adult , Female , Humans , Male , Middle Aged , Prospective Studies , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapyABSTRACT
The role of interleukin-22 (IL-22) in the pathogenesis or tissue repair in human tuberculosis (TB) remains to be established. Here, we aimed to explore the ex-vivo and in-vitro T helper 22 (Th22) response in TB patients and healthy donors (HD) induced by different local multi-drug-resistant (MDR) Mvcobacterium tuberculosis (Mtb) strains. For this purpose, peripheral blood mononuclear cells from drug-susceptible (S-TB) MDR-TB patients and HD were stimulated with local MDR strains and the laboratory strain H37Rv. IL-22 and IL-17 expression and senescent status were assessed in CD4+ and CD8+ cells by flow cytometry, while IL-22 amount was measured in plasma and culture supernatants by enzyme-linked immunosorbent assay (ELISA). We found lower IL-22 amounts in plasma from TB patients than HD, together with a decrease in the number of circulating T cells expressing IL-22. In a similar manner, all Mtb strains enhanced IL-22 secretion and expanded IL-22+ cells within CD4+ and CD8+ subsets, being the highest levels detected in S-TB patients. In MDR-TB, low systemic and Mtb-induced Th22 responses associated with high sputum bacillary load and bilateralism of lung lesions, suggesting that Th22 response could be influencing the ability of MDR-TB patients to control bacillary growth and tissue damage. In addition, in MDR-TB patients we observed that the higher the percentage of IL-22+ cells, the lower the proportion of programmed cell death 1 (PD-1)+ or CD57+ T cells. Furthermore, the highest proportion of senescent T cells was associated with severe lung lesions and bacillary load. Thus, T cell senescence would markedly influence Th22 response mounted by MDR-TB patients.
Subject(s)
Lung/immunology , Mycobacterium tuberculosis/immunology , T-Lymphocytes, Helper-Inducer/immunology , Tuberculosis, Multidrug-Resistant/immunology , Tuberculosis, Pulmonary/immunology , Adult , Antigens, Bacterial/immunology , CD4-Positive T-Lymphocytes/immunology , CD57 Antigens/immunology , CD8-Positive T-Lymphocytes/immunology , Female , Humans , Interferon-gamma/immunology , Interleukin-17/immunology , Interleukins/immunology , Leukocytes, Mononuclear/immunology , Leukocytes, Mononuclear/microbiology , Lung/microbiology , Male , Middle Aged , Programmed Cell Death 1 Receptor/immunology , Sputum/microbiology , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Pulmonary/microbiology , Young Adult , Interleukin-22ABSTRACT
Mycobacterium tuberculosis (Mtb) causes nearly 10 millions of new tuberculosis disease cases annually. However, most individuals exposed to Mtb do not develop tuberculosis, suggesting the influence of a human genetic component. Here, we investigated the association of the rs2275913 SNP (G â A) from IL-17A and tuberculosis in Argentina by a case-control study. Furthermore, we evaluated in vitro the functional relevance of this SNP during the immune response of the host against Mtb and analyzed its impact on clinical parameters of the disease. We found an association between the AA genotype and tuberculosis resistance. Additionally, within the healthy donors population, AA cells stimulated with a Mtb lysate (Mtb-Ag) produced the highest amounts of IL-17A and IFN-γ, which further support the genetic evidence found. In contrast, within the tuberculosis patients population, AA Mtb-Ag stimulated cells showed the lowest immunological parameters and we evidenced an association between the AA genotype and clinical parameters of disease severity, such as severe radiological lesions and higher bacilli burden in sputum. Overall, our findings demonstrated that the AA genotype from the IL-17A rs2275913 SNP is positively associated with protection to active tuberculosis but related to higher disease severity in the Argentinean population.
Subject(s)
Alleles , Genetic Predisposition to Disease , Interleukin-17/genetics , Polymorphism, Single Nucleotide , Tuberculosis/genetics , Adult , Argentina , Female , Gene Frequency , Genotype , Humans , Interferon-gamma/blood , Interleukin-17/blood , Male , Middle Aged , Severity of Illness Index , Tuberculosis/diagnosisABSTRACT
A case of a 39 year old HIV negative female patient with a Mycobacterium fortuitum mastitis without previous pathogenic history is reported. She was treated on the bases of drug-susceptibility testing and bibliographic empirical evidence with kanamycin, doxicicline, ciprofloxacin and trimetoprim-sulfametoxazol. A complete remission of her lesions was obtained after 15 months of treatment. Lesions due to this rapidly growing mycobacterium, diagnosis and treatment are commented.
Se presenta el caso de una paciente HIV negativa de 39 años con una mastitis por Mycobacterium fortuitum, sin antecedentes patogénicos previos. Fue tratada en base a las pruebas de susceptibilidad a antibióticos y quimioterápicos y a la evidencia empírica citada por la bibliografía, con kanamicina, doxiciclina, ciprofloxacina y trimetoprima-sulfametoxazol. Se obtuvo la remisión completa de sus lesiones luego de 15 meses de tratamiento. Se comenta la capacidad de producir lesiones de esta micobacteria de crecimiento rápido, su diagnóstico y tratamiento
Subject(s)
Humans , Female , Adult , Mycobacterium Infections, Nontuberculous , Mycobacterium fortuitum , Mastitis/microbiology , Anti-Bacterial Agents/therapeutic use , HIV Seronegativity , Mycobacterium Infections, Nontuberculous/drug therapy , Mastitis/drug therapy , Mycobacterium fortuitum/pathogenicityABSTRACT
La tuberculosis y otras micobacteriosis constituyen asociaciones o coinfecciones frecuentes en pacientes con sida y se asocian con una elevada mortalidad. En esta revisión se actualizan los tratamientos de las principales enfermedades micobacterianas asociadas al sida (tuberculosis y micobacteriosis por Mycobacterium avium), con especial énfasis en las interacciones farmacológicas entre antimicobacterianos, principalmente rifampicina y claritromicina, y fármacos antirretrovirales. Se analizan los esquemas de tratamiento, su duración, la quimioprofilaxis primaria y secundaria y el momento óptimo de iniciación del tratamiento antirretroviral. Finalmente se describe el síndrome inflamatorio de reconstitución inmune y su tratamiento.
Subject(s)
Humans , AIDS-Related Opportunistic Infections/drug therapy , Acquired Immunodeficiency Syndrome/drug therapy , Anti-Bacterial Agents/therapeutic use , Anti-Retroviral Agents/therapeutic use , Mycobacterium Infections/drug therapy , Acquired Immunodeficiency Syndrome/diagnosis , Clarithromycin/therapeutic use , Drug Interactions , Mycobacterium Infections/diagnosis , Rifampin/therapeutic use , Tuberculosis/diagnosis , Tuberculosis/drug therapyABSTRACT
La tuberculosis y otras micobacteriosis constituyen asociaciones o coinfecciones frecuentes en pacientes con sida y se asocian con una elevada mortalidad. En esta revisión se actualizan los tratamientos de las principales enfermedades micobacterianas asociadas al sida (tuberculosis y micobacteriosis por Mycobacterium avium), con especial énfasis en las interacciones farmacológicas entre antimicobacterianos, principalmente rifampicina y claritromicina, y fármacos antirretrovirales. Se analizan los esquemas de tratamiento, su duración, la quimioprofilaxis primaria y secundaria y el momento óptimo de iniciación del tratamiento antirretroviral. Finalmente se describe el síndrome inflamatorio de reconstitución inmune y su tratamiento. (AU)
Subject(s)
Humans , Acquired Immunodeficiency Syndrome/drug therapy , Mycobacterium Infections/drug therapy , AIDS-Related Opportunistic Infections/drug therapy , Anti-Retroviral Agents/therapeutic use , Anti-Bacterial Agents/therapeutic use , Acquired Immunodeficiency Syndrome/diagnosis , Mycobacterium Infections/diagnosis , Tuberculosis/drug therapy , Tuberculosis/diagnosis , Clarithromycin/therapeutic use , Rifampin/therapeutic use , Drug InteractionsABSTRACT
SETTING: An Argentinean reference hospital specialising in infectious diseases. OBJECTIVE: To assess the outcomes of all human immunodeficiency virus (HIV) negative multidrug-resistant tuberculosis (MDR-TB) patients referred to or diagnosed at Hospital Muñiz. DESIGN: Clinical study for the period 1996-1999, with follow-up until June 2002. RESULTS: One hundred and forty-one adult patients (52.5% female) with resistance to two to seven drugs were studied. Fifty patients (35.5%) had not been treated previously. The most frequently used second-line drugs were 5-F-quinolones, cycloserine and ethionamide in susceptibility based individually tailored three- to five-drug regimens. Hospital admission was associated with treatment success. Forty-five episodes of severe toxicity occurred. Treatment was successful in 51.8% of cases, but follow-up of 73 patients yielded 11.9% relapse. The mortality rate was 19.1% and default was 19.9%. Logistic regression analysis was statistically significant for treatment success in relation to patient admission, residence and resistance pattern. CONCLUSION: The burden of MDR-TB in this setting--prolonged infection, treatment cost and difficulties, low rates of cure and treatment adherence and high rates of fatality and relapse--can be improved by strengthening TB control programme activities and fighting against poverty and HIV/AIDS.
Subject(s)
Antitubercular Agents/pharmacology , HIV Seronegativity , Microbial Sensitivity Tests , Mycobacterium tuberculosis/drug effects , Treatment Outcome , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Pulmonary/drug therapy , AIDS-Related Opportunistic Infections/complications , Antitubercular Agents/adverse effects , Antitubercular Agents/therapeutic use , Argentina/epidemiology , Cycloserine/adverse effects , Cycloserine/pharmacology , Cycloserine/therapeutic use , Drug Combinations , Ethionamide/adverse effects , Ethionamide/pharmacology , Ethionamide/therapeutic use , Female , Follow-Up Studies , Hospitalization , Hospitals, Special , Humans , Logistic Models , Male , Mycobacterium tuberculosis/isolation & purification , Prognosis , Tuberculosis, Multidrug-Resistant/complications , Tuberculosis, Multidrug-Resistant/diagnosis , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/diagnosisABSTRACT
A case of a 39 year old HIV negative female patient with a Mycobacterium fortuitum mastitis without previous pathogenic history is reported. She was treated on the bases of drug-susceptibility testing and bibliographic empirical evidence with kanamycin, doxicicline, ciprofloxacin and trimetoprim-sulfametoxazol. A complete remission of her lesions was obtained after 15 months of treatment. Lesions due to this rapidly growing mycobacterium, diagnosis and treatment are commented.(AU)
Se presenta el caso de una paciente HIV negativa de 39 años con una mastitis por Mycobacterium fortuitum, sin antecedentes patogénicos previos. Fue tratada en base a las pruebas de susceptibilidad a antibióticos y quimioterápicos y a la evidencia empírica citada por la bibliografía, con kanamicina, doxiciclina, ciprofloxacina y trimetoprima-sulfametoxazol. Se obtuvo la remisión completa de sus lesiones luego de 15 meses de tratamiento. Se comenta la capacidad de producir lesiones de esta micobacteria de crecimiento rápido, su diagnóstico y tratamiento(AU)
Subject(s)
Humans , Female , Adult , Mastitis/microbiology , Mycobacterium Infections, Nontuberculous , Mycobacterium fortuitum , Anti-Bacterial Agents/therapeutic use , HIV Seronegativity , Mastitis/drug therapy , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium fortuitum/pathogenicityABSTRACT
A prospective cohort study was carried out in patients assisted in the F. J. Muñiz Infectious Disease Hospital, with the aim of determining the effectiveness of highly active antiretroviral therapy (HAART) implemented as soon as the sputum smear microscopy became negative (1 to 3 months) in the survival improvement of HIV/AIDS related multidrug-resistant tuberculosis patients. The cohort was recruited from June 1997 to February 1999 and compared with a pre-HAART control group that consisted of 43 patients. The follow-up of the patients was terminated June 2000. A total of 48 patients who received HAART precociously were included. The mortality rate in this group was 31.2% and the survival time of deceased patients 15.8 +/- 8.5 months. The T lymphocytes CD4+ count was initially 40.1 +/- 30.2/microL, while at the end of the observation period it was 140.4 +/- 73.04/microL and 79.1% of these patients presented undetectable viral load. In the control group the overall mortality was 90.7% and the survival time of deceased patients 8.95 +/- 3.72 months. We conclude that the early anti-retroviral therapy, together with the treatment of the multidrug-resistant tuberculosis and of other AIDS associated diseases represent a useful approach to achieve a longer and better survival in these severely immunodepressed patients.
Subject(s)
AIDS-Related Opportunistic Infections/drug therapy , Antiretroviral Therapy, Highly Active/methods , Tuberculosis, Multidrug-Resistant/drug therapy , AIDS-Related Opportunistic Infections/mortality , Acquired Immunodeficiency Syndrome/drug therapy , Adult , Female , Humans , Male , Prognosis , Prospective Studies , Quality of Life , Retrospective Studies , Survival Analysis , Time Factors , Treatment Outcome , Tuberculosis, Multidrug-Resistant/mortalityABSTRACT
A prospective cohort study was carried out in patients assisted in the F. J. Muñiz Infectious Disease Hospital, with the aim of determining the effectiveness of highly active antiretroviral therapy (HAART) implemented as soon as the sputum smear microscopy became negative (1 to 3 months) in the survival improvement of HIV/AIDS related multidrug-resistant tuberculosis patients. The cohort was recruited from June 1997 to February 1999 and compared with a pre-HAART control group that consisted of 43 patients. The follow-up of the patients was terminated June 2000. A total of 48 patients who received HAART precociously were included. The mortality rate in this group was 31.2
and the survival time of deceased patients 15.8 +/- 8.5 months. The T lymphocytes CD4+ count was initially 40.1 +/- 30.2/microL, while at the end of the observation period it was 140.4 +/- 73.04/microL and 79.1
of these patients presented undetectable viral load. In the control group the overall mortality was 90.7
and the survival time of deceased patients 8.95 +/- 3.72 months. We conclude that the early anti-retroviral therapy, together with the treatment of the multidrug-resistant tuberculosis and of other AIDS associated diseases represent a useful approach to achieve a longer and better survival in these severely immunodepressed patients.
ABSTRACT
A case of an HIV negative female patient with coxofemoral arthritis of tuberculous etiology, multidrug-resistant strain, and connective tissue disease associated to glucocorticoid therapy is reported. The patient was treated with cycloserine, ethambutol, p-aminosalicylic acid and ofloxacin, with improvement of the joint lesions. Previous publications on this subject are reviewed.
Subject(s)
Arthritis, Infectious/microbiology , Hip Joint/microbiology , Mycobacterium tuberculosis , Tuberculosis, Multidrug-Resistant/complications , Tuberculosis, Osteoarticular/complications , Adult , Arthritis, Infectious/drug therapy , Female , Femur/microbiology , Humans , Tuberculosis, Multidrug-Resistant/drug therapy , Tuberculosis, Multidrug-Resistant/microbiology , Tuberculosis, Osteoarticular/drug therapy , Tuberculosis, Osteoarticular/microbiologyABSTRACT
A case of an HIV negative female patient with coxofemoral arthritis of tuberculous etiology, multidrug-resistant strain, and connective tissue disease associated to glucocorticoid therapy is reported. The patient was treated with cycloserine, ethambutol, p-aminosalicylic acid and ofloxacin, with improvement of the joint lesions. Previous publications on this subject are reviewed.
ABSTRACT
A patient with pulmonary disease due to Mycobacterium terrae, a soil saprophyte seldom encountered as a pathogen, is described. The strain was isolated repeatedly from the sputum and gastric washings of the patient in whom no evidence of impairment of cellular or humoral immunity was found. Bacteriological conversion followed initial therapy with isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin and pefloxacin for two months, followed by maintenance therapy of isoniazid, rifampicin and pefloxacin.
Subject(s)
Tuberculosis, Pulmonary/drug therapy , Adult , Antitubercular Agents/therapeutic use , Drug Therapy, Combination , Humans , Male , Mycobacterium Infections, Nontuberculous/drug therapyABSTRACT
Se controle el estado de salud de 379 pacientes TBC pulmonares tratados en LALAT durante el quinquenio 1975-1979, a traves de citaciones y concurrencia espontanea.Se observaron 15 reinfecciones la mayoria sin haber utilizado RMP en su primer tratamiento. Es destacada la importancia del estudio bacteriologico de sintomaticos respiratorios ex-TBC, con alta proporcion de casos positivos
Subject(s)
Child, Preschool , Child , Adolescent , Adult , Middle Aged , Humans , Male , Female , Tuberculosis, Pulmonary , Argentina , Health SurveysABSTRACT
Se efectuo la lectura comparativa de las intradermorreacciones de Mantoux efectuadas con dos tuberculinas de distinto origen: PPD RT 23 provista por el Statens Serum Institut de Copenhagen, fraccionada y distribuida por el Instituto Malbran (Prueba tuberculinica estandar de las OMS) y el PPD que distribuye un laboratorio de plaza, de origen frances. Se testificaron 258 sujetos, contactos de pacientes tuberculosos atendidos en el Dispensario de Adultos de la Liga Argentina contra la Tuberculosis aplicandose simultaneamente ambas tuberculinas, una en cada antebrazo.Efectuado el analisis estadistico comparativo entre las lecturas efectuadas a doble ciego de ambas testificaciones, se arribo a la conclusion de que no existen diferencias significativas entre las respuestas cutaneas a ambos PPD
Subject(s)
Child , Adolescent , Adult , Middle Aged , Humans , Male , Female , Tuberculin TestABSTRACT
Se controle el estado de salud de 379 pacientes TBC pulmonares tratados en LALAT durante el quinquenio 1975-1979, a traves de citaciones y concurrencia espontanea.Se observaron 15 reinfecciones la mayoria sin haber utilizado RMP en su primer tratamiento. Es destacada la importancia del estudio bacteriologico de sintomaticos respiratorios ex-TBC, con alta proporcion de casos positivos
