The risk of exposure, progression to active tuberculosis (TB) and then to cure is a process affected by several risk factors. Along with well known risk factors such as human immunodeficiency virus ...(HIV), use of immunosuppressive drugs and being of young age, emerging risk factors such socio-economic and behavioral aspects play a significant role in increasing the susceptibility to infection, and unsuccessful treatment outcomes. This paper summarizes the effects of these socio-economic determinants and co-morbidities (including HIV) on TB infection and disease.
Tuberculosis (TB) is the ninth cause of global death, more than any other infectious disease. With growing drug resistance the epidemic remains and will require significant attention and investment ...for the elimination of this disease to occur. With susceptible TB treatment not changing over the last four decades and the advent of drug resistance, new drugs and regimens are required. Recently, through greater collaboration and research networks some progress with significant advances has taken place, not withstanding the comparatively low amount of resources invested. Of late the availability of the new drugs bedaquiline, delamanid and repurposed drugs linezolid, clofazimine and carbapenems are being used more frequently in drug-resistant TB regimens. The WHO shorter multidrug-resistant tuberculosis regimen promises to reach more patients and treat them more quickly and more cheaply. With this new enthusiasm and hope we this review gives an update on the new drugs and perspectives for the treatment of drug-susceptible and drug-resistant tuberculosis.
Approximately 2 billion people are infected with Mycobacterium tuberculosis (Mtb), resulting in 1.4 million deaths every year. Among Mtb-infected individuals, clinical isolates belonging to the ...W-Beijing lineage are increasingly prevalent, associated with drug resistance, and cause severe disease immunopathology in animal models. Therefore, it is exceedingly important to identify the immune mechanisms that mediate protection against rapidly emerging Mtb strains, such as W-Beijing lineage. IL-22 is a member of the IL-10 family of cytokines with both protective and pathological functions at mucosal surfaces. Thus far, collective data show that IL-22 deficient mice are not more susceptible to aerosolized infection with less virulent Mtb strains. Thus, in this study we addressed the functional role for the IL-22 pathway in immunity to emerging Mtb isolates, using W-Beijing lineage member, Mtb HN878 as a prototype. We show that Mtb HN878 stimulates IL-22 production in TLR2 dependent manner and IL-22 mediates protective immunity during chronic stages of Mtb HN878 infection in mice. Interestingly, IL-22-dependent pathways in both epithelial cells and macrophages mediate protective mechanisms for Mtb HN878 control. Thus, our results project a new protective role for IL-22 in emerging Mtb infections.
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).
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).
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.
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.
Evidence on the impact of tuberculosis (TB) treatment on lung function is scarce. The aim of this study was to evaluate post-treatment sequelae in drug-susceptible and drug-resistant-TB (DR-TB) cases ...in Mexico and Italy.
At the end of TB treatment the patients underwent complete clinical assessment, functional evaluation of respiratory mechanics, gas exchange and a 6-minute walking test. Treatment regimens (and definitions) recommended by the World Health Organization were used throughout.
Of 61 patients, 65.6% had functional impairment, with obstruction in 24/61 patients (39.4%), and 78% with no bronchodilator response. These effects were more prevalent among DR-TB cases (forced expiratory volume in 1 s/forced vital capacity FEV
/FVC < lower limit of normality, 14/24 vs. 10/34;
= 0.075). DR-TB patients showed moderately severe (FEV
< 60%) and severe obstruction (FEV
< 50%) (
= 0.008). Pre- and post-bronchodilator FEV
and FEV
/FVC (% of predicted) were significantly lower among DR-TB cases. Plethysmography abnormalities (restriction, hyperinflation and/or air trapping) were more frequent among DR-TB cases (
= 0.001), along with abnormal carbon monoxide diffusing capacity (DLCO) (
= 0.003).
The majority of TB patients suffer the consequences of post-treatment sequelae (of differing levels), which compromise quality of life, exercise tolerance and long-term prognosis. It is therefore important that lung function is comprehensively evaluated post-treatment to identify patient needs for future medication and pulmonary rehabilitation.
The aim of these clinical standards is to provide guidance on 'best practice´ for diagnosis, treatment and management of drug-susceptible pulmonary TB (PTB).
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.
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.
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.
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.
...65/81 invited experts participated in a Delphi process using a 5-point Likert scale to score draft standards.
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.
These standards provide a person-centred, consensus-based approach to minimise the impact of AE during TB treatment.
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