Numbers needed to treat to prevent tuberculosis Sester, Martina; van Crevel, Reinout; Leth, Frank van ...
European respiratory journal/The European respiratory journal,
12/2015, Letnik:
46, Številka:
6
Journal Article
Recenzirano
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A new action framework advocacy document for tuberculosis elimination in low-incidence countries has recently been published in this journal 1. We completely agree with the importance of addressing ...the goal of elimination of tuberculosis, which may be achievable in regions such as Western Europe and North America, but we are concerned that this goal may be overly ambitious at this point in time. As protective immunity can, unfortunately, not be achieved by a vaccine or other immune-based intervention, tuberculosis control still relies on early identification and treatment of active tuberculosis, and preventive chemotherapy of individuals with latent Mycobacterium tuberculosis infection (LTBI). However, both the tuberculin skin test (TST) and interferon- gamma release assays (IGRAs) (the ELISA-based QuantiFERON-TB Gold In-Tube assay (QIAGEN, Venlo, the Netherlands) or the ELISPOT-based T-SPOT.TB assay (Oxford Immunotec, Oxford, UK)) that are recommended to diagnose LTBI have a low positive predictive value for the future development of tuberculosis, and are therefore insufficient as biomarkers to identify individuals developing active disease. With tuberculosis being a rare event, the vast majority of individuals with positive test results will never develop disease 2. Moreover, in immunocompromised individuals, especially in patients with HIV infection, the negative predictive value of an immunodiagnostic test is insufficient to rule out the future development of tuberculosis, as was recently demonstrated in a large study in Europe 3. Thus, systematic testing and treatment of LTBI of risk groups 1 is considered difficult to implement.
Patients infected with HIV-1 initiating antiretroviral therapy (ART) containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) show presumably fewer atherogenic lipid changes than those ...initiating most ARTs containing a protease inhibitor. We analysed whether lipid changes differed between the two most commonly used NNRTIs, nevirapine (NVP) and efavirenz (EFV).
Prospective analysis of lipids and lipoproteins was performed in patients enrolled in the NVP and EFV treatment groups of the 2NN study who remained on allocated treatment during 48 wk of follow-up. Patients were allocated to NVP (n = 417), or EFV (n = 289) in combination with stavudine and lamivudine. The primary endpoint was percentage change over 48 wk in high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), TC:HDL-c ratio, non-HDL-c, low-density lipoprotein cholesterol, and triglycerides. The increase of HDL-c was significantly larger for patients receiving NVP (42.5%) than for patients receiving EFV (33.7%; p = 0.036), while the increase in TC was lower (26.9% and 31.1%, respectively; p = 0.073), resulting in a decrease of the TC:HDL-c ratio for patients receiving NVP (-4.1%) and an increase for patients receiving EFV (+5.9%; p < 0.001). The increase of non-HDL-c was smaller for patients receiving NVP (24.7%) than for patients receiving EFV (33.6%; p = 0.007), as were the increases of triglycerides (20.1% and 49.0%, respectively; p < 0.001) and low-density lipoprotein cholesterol (35.0% and 40.0%, respectively; p = 0.378). These differences remained, or even increased, after adjusting for changes in HIV-1 RNA and CD4+ cell levels, indicating an effect of the drugs on lipids over and above that which may be explained by suppression of HIV-1 infection. The increases in HDL-c were of the same order of magnitude as those seen with the use of the investigational HDL-c-increasing drugs.
NVP-containing ART shows larger increases in HDL-c and decreases in TC:HDL-c ratio than an EFV-containing regimen. Based on these findings, protease-inhibitor-sparing regimens based on non-nucleoside reverse transcriptase inhibitor, particularly those containing NVP, may be expected to result in a reduced risk of coronary heart disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Introduction
There are concerns that immediate ART initiation (regardless of CD4 count) negatively affects HIV status disclosure, ART adherence and healthcare interactions. We assessed changes in ...these factors after the ‘Early access to ART for all’ intervention, a universal test‐and‐treat study in Swaziland.
Methods
We recruited two samples of participants between 2014 and 2017. The first group was interviewed before the intervention (control); the second group at the implementation and 6 months thereafter (intervention).
Results
High levels of disclosure to partners (controls and intervention: 94%) and family members (controls: 78%, intervention: 79%) were reported, and high levels of adherence (85% did not miss a dose among the controls, 84% in the intervention group). There were no changes in patients reporting feeling pressured to initiate ART (controls: 10%, intervention: 11%). The quality of interaction with healthcare workers improved after the intervention; healthcare workers explained more often the choice of ART initiation (controls: 88%, intervention: 93%) and the meaning of both CD4 and viral load test results (controls: 15%, intervention: 47%). More patients in the intervention group reported receiving test results (controls: 13%, intervention: 46%). We observed no changes in disclosure, adherence or patient experiences 6 months into the intervention compared to its start.
Conclusion
Our results suggest that both reported adherence and disclosure levels remain high after the introduction of immediate ART in Swaziland. We observed an improvement in the healthcare interactions, possibly due to training at participating facilities, which will be an important element for a successful roll‐out of immediate ART.
Objectif
Il y a des craintes que l'initiation de l’ART immédiat (quel que soit la numération des CD4) affecte négativement la divulgation du statut VIH, l'adhésion au traitement et les interactions avec les soins de santé. Nous avons évalué les modifications de ces facteurs après l'intervention «Accès précoce à l’ART pour tous», une étude universelle de dépistage et traitement au Swaziland.
Méthodes
Nous avons recruté deux échantillons de participants entre 2014 et 2017. Le premier groupe a été interviewé avant l'intervention (témoins), le deuxième groupe lors de l'implémentation et six mois après (intervention).
Résultats
Des niveaux élevés de divulgation aux partenaires (témoin et intervention: 94%) et aux membres de la famille (témoins: 78%, intervention: 79%) ont été rapportés, ainsi que des taux élevés d'adhésion (85% n'ont pas oublié une dose chez les témoins, 84% dans le groupe d'intervention). Aucun changement n'a été observé chez les patients déclarant se sentir poussés à commencer l’ART (témoins: 10%, intervention: 11%). La qualité de l'interaction avec les agents de la santé s'est améliorée après l'intervention; les agents de santé expliquent plus souvent le choix de l'initiation de l’ART (témoins: 88%, intervention: 93%) et la signification des résultats des tests de CD4 et de la charge virale (témoins: 15%, intervention: 47%). Plus de patients du groupe d'intervention ont déclaré avoir reçu les résultats des tests (témoins: 13%, intervention: 46%). Nous n'avons observé aucun changement dans la divulgation, l'adhésion ou l'expérience des patients six mois après le début de l'intervention par rapport à son début.
Conclusion
Nos résultats suggèrent que les taux d'adhésion et de divulgation rapportés restent élevés après l'introduction de l’ART immédiat au Swaziland. Nous avons observé une amélioration des interactions avec les soins de santé, probablement due à la formation dispensée dans les établissements participants, ce qui constituera un élément important pour le succès du déploiement de l’ART immédiat.
Individuals with bacteriologically confirmed pulmonary tuberculosis (TB) disease who do not report symptoms (subclinical TB) represent around half of all prevalent cases of TB, yet their contribution ...to
(
) transmission is unknown, especially compared to individuals who report symptoms at the time of diagnosis (clinical TB). Relative infectiousness can be approximated by cumulative infections in household contacts, but such data are rare.
We reviewed the literature to identify studies where surveys of
infection were linked to population surveys of TB disease. We collated individual-level data on representative populations for analysis and used literature on the relative durations of subclinical and clinical TB to estimate relative infectiousness through a cumulative hazard model, accounting for sputum-smear status. Relative prevalence of subclinical and clinical disease in high-burden settings was used to estimate the contribution of subclinical TB to global
transmission.
We collated data on 414 index cases and 789 household contacts from three prevalence surveys (Bangladesh, the Philippines, and Viet Nam) and one case-finding trial in Viet Nam. The odds ratio for infection in a household with a clinical versus subclinical index case (irrespective of sputum smear status) was 1.2 (0.6-2.3, 95% confidence interval). Adjusting for duration of disease, we found a per-unit-time infectiousness of subclinical TB relative to clinical TB of 1.93 (0.62-6.18, 95% prediction interval PrI). Fourteen countries across Asia and Africa provided data on relative prevalence of subclinical and clinical TB, suggesting an estimated 68% (27-92%, 95% PrI) of global transmission is from subclinical TB.
Our results suggest that subclinical TB contributes substantially to transmission and needs to be diagnosed and treated for effective progress towards TB elimination.
JCE, KCH, ASR, NS, and RH have received funding from the European Research Council (ERC) under the Horizon 2020 research and innovation programme (ERC Starting Grant No. 757699) KCH is also supported by UK FCDO (Leaving no-one behind: transforming gendered pathways to health for TB). This research has been partially funded by UK aid from the UK government (to KCH); however, the views expressed do not necessarily reflect the UK government's official policies. PJD was supported by a fellowship from the UK Medical Research Council (MR/P022081/1); this UK-funded award is part of the EDCTP2 programme supported by the European Union. RGW is funded by the Wellcome Trust (218261/Z/19/Z), NIH (1R01AI147321-01), EDTCP (RIA208D-2505B), UK MRC (CCF17-7779 via SET Bloomsbury), ESRC (ES/P008011/1), BMGF (OPP1084276, OPP1135288 and INV-001754), and the WHO (2020/985800-0).
Drug-resistant tuberculosis is a substantial health-care concern worldwide. Despite culture-based methods being considered the gold standard for drug susceptibility testing, molecular methods provide ...rapid information about the Mycobacterium tuberculosis mutations associated with resistance to anti-tuberculosis drugs. This consensus document was developed on the basis of a comprehensive literature search, by the TBnet and RESIST-TB networks, about reporting standards for the clinical use of molecular drug susceptibility testing. Review and the search for evidence included hand-searching journals and searching electronic databases. The panel identified studies that linked mutations in genomic regions of M tuberculosis with treatment outcome data. Implementation of molecular testing for the prediction of drug resistance in M tuberculosis is key. Detection of mutations in clinical isolates has implications for the clinical management of patients with multidrug-resistant or rifampicin-resistant tuberculosis, especially in situations when phenotypic drug susceptibility testing is not available. A multidisciplinary team including clinicians, microbiologists, and laboratory scientists reached a consensus on key questions relevant to molecular prediction of drug susceptibility or resistance to M tuberculosis, and their implications for clinical practice. This consensus document should help clinicians in the management of patients with tuberculosis, providing guidance for the design of treatment regimens and optimising outcomes.
BACKGROUND:Tuberculosis-HIV (TB-HIV) coinfection remains an important cause of mortality in antiretroviral therapy (ART) programs. In a cohort of TB-HIV-coinfected patients starting ART, we examined ...the incidence and predictors of early mortality.
METHODS:Consecutive TB-HIV-coinfected patients eligible for ART were enrolled in a cohort study at the Mulago National Tuberculosis and Leprosy Program clinic in Kampala, Uganda. Predictors of mortality were assessed using Cox proportional hazards analysis.
RESULTS:Three hundred and two patients median CD4 count 53 cells/μL (interquartile range, 20-134) were enrolled. Fifty-three patients died, 36 (68%) of these died within the first 6 months of TB diagnosis. Male sex hazard (HR)2.19; 95% confidence interval (CI)1.19 to 4.03; P = 0.011, anergy to tuberculin skin test HR2.59 (1.10 to 6.12); P = 0.030, a positive serum cryptococcal antigen result at enrollment (HR4.27; 95% CI1.50 to 12.13; P = 0.006) and no ART use (HR4.63; 95% CI2. 37 to 9.03; P < 0.001) were independent predictors of mortality by multivariate analysis. Six (10%) patients with TB immune reconstitution inflammatory syndrome died, and in most, an alternative contributing cause of death was identified.
CONCLUSIONS:Mortality among these TB-HIV-coinfected patients was high particularly when presenting with advanced HIV disease and not starting ART, reinforcing the need for timely and joint treatment for both infections. Screening for a concomitant cryptococcal infection and antifungal treatment for patients with cryptococcal antigenemia may further improve clinical outcome.
Eswatini has a high HIV prevalence but has made progress towards improving HIV-status awareness, ART uptake and viral suppression. However, there is still a delay in ART initiation, which could ...partly be attributed to positive HIV-retesting. This study examines reasons for, and factors associated with, positive HIV-retesting among MaxART participants in Eswatini. Data from 601 participants is included in this cross-sectional study. Descriptive statistics and logistic regressions were used. Of the participants, 32.8% has ever retested after a previous positive result. Most participants who retested did this because they could not accept their results (61.9% of all retesters). Other main reasons are related to external influences, gender or the progression of their HIV infection (respectively 18.3%, 10.2%, and 6.1% of all retesters). Participants without a current partner and participants with less time since their first positive test have lower odds of retesting. To decrease retesting and reduce the delay in ART initiation resulting from it, efforts could be made on increasing the acceptance of positive HIV results. Providing more information on the process of testing and importance of early ART initiation, could be part of the solution.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Current antimicrobial resistance surveillance (AMR) is mainly laboratory based. This approach can have inherent biases given the potential for selective specimen submission for microbiological ...analysis and for its inability to map antibiotic susceptibility test results to a clinical syndrome.
To discuss the need for population-based surveillance of AMR, and highlight the pros and cons of threshold surveys.
Studies on methodology for AMR surveillance published in the last 10 years, obtained through a PubMed search on antimicrobial resistance (all fields) and surveillance/method (MeSH term).
We discuss the use of threshold surveys to overcome the challenge of sample size in population-bases AMR surveys, which are a suitable approach in both low- and high-resource settings.
Scale up in the use of population-based threshold survey on the prevalence of AMR will provide necessary information to triangulate the data from routinely-reported laboratory-based AMR surveillance at the local, national, and global level.
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All newly diagnosed HIV-infected patients in the Netherlands should be screened for latent tuberculosis infection (LTBI) and offered preventive therapy if infected without evidence of active ...tuberculosis. This guideline, endorsed by the national professional body of HIV physicians is in line with international recommendations, and based on the increased risk of progression from LTBI to active tuberculosis in HIV-infected patients. The objective of the study is to assess the intention of HIV physicians to implement this national guideline.
A mixed method design triangulating results from two surveys among all (n = 80) HIV physicians in The Netherlands and qualitative interviews among 11 Dutch HIV physicians performed in 2014.
The majority of physicians used a risk-stratification approach based on individual a priori risk of tuberculosis to identify HIV-infected patients for LTBI screening, rather than screening all new HIV-infected patients. The intended and actual provision of preventive treatment was low, due to expressed doubts on the accuracy of diagnostic tools for LTBI. Interviewees reported that the guidelines did not match their clinical experience and lacked evidence for the recommendations. Screening for and treatment of LTBI was approached at a patient-level only. None of the interviewees referred to potential public health implications of the guidelines.
Intended implementation of the national HIV-TB guidelines in the Netherlands is poor, due to a disconnect between clinical practice and evidence-based recommendations in the guideline. There is an urgent need to reconcile the views of HIV-physicians, public health experts, and guideline committee members, regarding the best strategy to address HIV-TB co-infection in the Netherlands.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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