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- Lange, C, et al.
(författare)
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Clinical Application of Interferon-γ Release Assays for the Prevention of Tuberculosis in Countries with Low Incidence
- 2016
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Ingår i: Pathogens & immunity. - : Case Western Reserve University. - 2469-2964. ; 1:2, s. 308-329
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Tidskriftsartikel (refereegranskat)abstract
- Despite global efforts to control tuberculosis (TB) the estimated number of people who developed TB worldwide increased to an all-time record of more than 10 million in 2015. The goal of the World Health Organization (WHO) to reduce the global incidence of TB to less than 100 cases per million by 2035, cannot be reached unless TB prevention is markedly improved. There is a need for an improved vaccine that better protects individuals who are exposed to Mycobacterium tuberculosis from infection and active disease compared to the current M. bovis Bacille Calmette Guérin (BCG) vaccine. In the absence of such a vaccine, prevention relies on infection control measures and preventive chemotherapy for people with latent infection with M. tuberculosis (LTBI), who have the highest risk of progression to active TB. During the past decade, interferon-γ release assays (IGRAs) have increasingly replaced the tuberculin skin test as screening tools for the diagnosis of LTBI in countries with a low incidence of TB. Despite recent WHO guidelines on the management of LTBI, the definition of groups at risk for TB remains controversial, and the role of IGRAs for TB prevention in low-incidence countries remains uncertain. We reviewed the scientific literature and provide recommendations for the use of IGRAs for LTBI diagnosis in low-incidence countries. These recommendations are based on the number of patients needing treatment in order to prevent one case of TB. As the positive predictive value of IGRAs for the development of TB is sub-optimal, research must focus on the identification of alternative biomarkers that offer better predictive ability in order to substantially reduce the number needing treatment while improving the prevention of TB and improving the effectiveness of targeted preventive chemotherapy.
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- Miotto, P, et al.
(författare)
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A standardised method for interpreting the association between mutations and phenotypic drug resistance in Mycobacterium tuberculosis
- 2017
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Ingår i: The European respiratory journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 50:6
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Tidskriftsartikel (refereegranskat)abstract
- A clear understanding of the genetic basis of antibiotic resistance inMycobacterium tuberculosisis required to accelerate the development of rapid drug susceptibility testing methods based on genetic sequence.Raw genotype–phenotype correlation data were extracted as part of a comprehensive systematic review to develop a standardised analytical approach for interpreting resistance associated mutations for rifampicin, isoniazid, ofloxacin/levofloxacin, moxifloxacin, amikacin, kanamycin, capreomycin, streptomycin, ethionamide/prothionamide and pyrazinamide. Mutation frequencies in resistant and susceptible isolates were calculated, together with novel statistical measures to classify mutations as high, moderate, minimal or indeterminate confidence for predicting resistance.We identified 286 confidence-graded mutations associated with resistance. Compared to phenotypic methods, sensitivity (95% CI) for rifampicin was 90.3% (89.6–90.9%), while for isoniazid it was 78.2% (77.4–79.0%) and their specificities were 96.3% (95.7–96.8%) and 94.4% (93.1–95.5%), respectively. For second-line drugs, sensitivity varied from 67.4% (64.1–70.6%) for capreomycin to 88.2% (85.1–90.9%) for moxifloxacin, with specificity ranging from 90.0% (87.1–92.5%) for moxifloxacin to 99.5% (99.0–99.8%) for amikacin.This study provides a standardised and comprehensive approach for the interpretation of mutations as predictors ofM. tuberculosisdrug-resistant phenotypes. These data have implications for the clinical interpretation of molecular diagnostics and next-generation sequencing as well as efficient individualised therapy for patients with drug-resistant tuberculosis.
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