With the advent of the World Health Organization End TB strategy, there has been renewed interest in screening for active tuberculosis (TB), and particularly latent tuberculous infection (LTBI). In ...low-incidence countries, a high proportion of TB cases are notified among migrants, which often occurs due to LTBI reactivation. We aimed to review the effectiveness and cost-effectiveness of screening migrants for active TB LTBI to inform and support the TB elimination strategy in low-incidence countries. We carried out a narrative review of English language articles published between 1 January 2000 and 31 June 2016 using the PubMed database. All studies that described the effectiveness or cost-effectiveness of active TB or LTBI screening among migrants were included. We identified 55 studies, and included 40 for the effectiveness of screening, 11 for cost-effectiveness and 4 that reported both. Screening for active TB can be effective and cost-effective depending on the setting, target group and screening approach. Pre-entry screening programmes have some impact on the epidemiology of the receiving countries. The effectiveness and cost-effectiveness of LTBI screening as predicted in mathematical models is also highly setting-specific, with best potential results achieved if screening is restricted to high-risk groups and/or to migrants from high-burden countries.
Treatment for latent tuberculous infection (LTBI) reduces the risk of tuberculosis (TB) disease. Shorter, rifamycin-containing regimens have been shown to be as effective as 6 months of isoniazid and ...superior with regard to safety and completion rate. It is unknown whether preventive therapy with rifamycins increases resistance to the drugs used.
To determine whether treatment for LTBI with rifamycin-containing regimens leads to significant development of resistance against rifamycins.
Systematic review and meta-analysis.
We included six randomised-controlled trials of rifamycin-containing regimens for LTBI treatment that reported drug resistance. There was no statistically significant increased risk of rifamycin resistance after LTBI treatment with rifamycin-containing regimens compared to non-rifamycin-containing regimens (RR 3.45, 95%CI 0.72-16.56; P = 0.12) or placebo (RR 0.20, 95%CI 0.02-1.66; P = 0.13).
Preventive treatment with rifamycin-containing regimens does not significantly increase rifamycin resistance. Programmatic management of LTBI requires the creation of sound surveillance systems to monitor drug resistance.
Extensively drug-resistant tuberculosis (XDR-TB) is present in all regions and poses serious challenges for public health and clinical management. Laboratory diagnosis is difficult and little ...evidence exists to guide clinicians in treating people with XDR-TB effectively. To summarise the available data on diagnosis and treatment, the current authors performed a systematic review on 13 recent studies of the epidemiology and clinical management of XDR-TB. Studies that met inclusion criteria were reviewed, in order to assess methodology, treatment regimens and treatment outcomes. Meta-analysis of currently available data is not possible because of inconsistent definitions and methodologies. Data show that XDR-TB can be successfully treated in up to 65% of patients, particularly those who are not co-infected with HIV. However, treatment duration is longer and outcomes are in general poorer than for non-XDR TB patients. To strengthen the evidence for extensively drug-resistant tuberculosis diagnosis, treatment and prevention, future studies should: 1) be prospective in design; 2) adopt standardised, internationally accepted definitions; 3) use quality-assured laboratory testing for all first- and second-line drugs; and 4) collect data on an agreed-upon set of standard variables, allowing for comparisons across studies. Early diagnosis and aggressive management of extensively drug-resistant tuberculosis provide the best chance of positive outcome, but prevention is still paramount.
In 2018, the WHO Member States committed to providing TB preventive treatment (TPT) to at least 30 million people by 2022. However, only 6.3 million people had initiated TPT by the end of 2019. Major ...knowledge gaps and research needs in diagnosis, treatment and the programmatic management of TPT (PMTPT) require to be addressed urgently.
In September 2019, a group of stakeholders involved in PMTPT in high TB burden countries met to develop an action agenda to support the global expansion of PMTPT.
Barriers at the health system level, and priorities for research to overcome these, were identified for each step of the PMTPT cascade. The need for data on TPT financing, gaps and coverage under national health insurance schemes, as well as the need for mathematical and cost-effectiveness modelling of the impact of TPT on TB incidence and mortality were highlighted. Specific research needs were identified for high-risk populations such as household contacts of any age and people living with HIV, as well as other people at risk.
The meeting facilitated agreement on a set of actions needed to ensure that PMTPT continues to expand to achieve the End TB Strategy targets.
Tuberculosis (TB) preventive therapy (TPT) decreases the risk of developing TB disease and its associated morbidity and mortality. The aim of these clinical standards is to guide the assessment, ...management of TB infection (TBI) and implementation of TPT.
A panel of global experts in the field of TB care was identified; 41 participated in a Delphi process. A 5-point Likert scale was used to score the initial standards. After rounds of revision, the document was approved with 100% agreement.
Eight clinical standards were defined: Standard 1, all individuals belonging to at-risk groups for TB should undergo testing for TBI; Standard 2, all individual candidates for TPT (including caregivers of children) should undergo a counselling/health education session; Standard 3, testing for TBI: timing and test of choice should be optimised; Standard 4, TB disease should be excluded prior to initiation of TPT; Standard 5, all candidates for TPT should undergo a set of baseline examinations; Standard 6, all individuals initiating TPT should receive one of the recommended regimens; Standard 7, all individuals who have started TPT should be monitored; Standard 8, a TBI screening and testing register should be kept to inform the cascade of care.
This is the first consensus-based set of Clinical Standards for TBI. This document guides clinicians, programme managers and public health officers in planning and implementing adequate measures to assess and manage TBI.
There is increasing interest in the introduction of public health policies relating to latent tuberculous infection (LTBI). However, there has been little previous systematic engagement with LTBI ...from an ethical perspective. This article offers a general overview of ethical issues in relation to LTBI, with particular focus on those aspects relevant to the development and implementation of public health policy. Key characteristics of LTBI are discussed from an ethical perspective, with examples of challenging situations for policy makers.
Low serum concentrations of first-line tuberculosis (TB) drugs have been widely reported. However, the impact of low serum concentrations on treatment outcome is less well studied. A systematic ...search of MEDLINE/Pubmed and the Cochrane Central Register of Controlled Trials up to 31 March 2018 was conducted for articles describing drug concentrations of first-line TB drugs and treatment outcome in adult patients with drug-susceptible TB. The search identified 3073 unique publication abstracts, which were reviewed for suitability: 21 articles were acceptable for inclusion in the qualitative analysis comprising 13 prospective observational cohorts, 4 retrospective observational cohorts, 1 case-control study and 3 randomised controlled trials. Data for meta-analysis were available for 15 studies, 13 studies of rifampicin (RMP), 10 of isoniazid (INH), 8 of pyrazinamide (PZA) and 4 of ethambutol (EMB). This meta-analysis revealed that low PZA concentration appears to increase the risk of poor outcomes (8 studies,
= 2727; RR 1.73, 95%CI 1.10-2.72), low RMP concentrations may slightly increase the risk of poor outcomes (13 studies,
= 2753; RR 1.40, 95%CI 0.91-2.16), whereas low concentrations of INH (10 studies,
= 2640; RR 1.32, 95%CI 0.66-2.63) and EMB (4 studies,
= 551; RR 1.12, 95%CI 0.41-3.05) appear to make no difference to treatment outcome. There was no significant publication bias or between-study heterogeneity in any of the analyses. The potential clinical impact of low concentrations of PZA and RMP warrants further evaluation. Also, comprehensive assessments of the complex pharmacokinetic-pharmacodynamic relationships in the treatment of TB are urgently needed.
Tuberculosis (TB) in migrants from endemic to low-incidence countries results mainly from the reactivation of latent tuberculous infection (LTBI). LTBI screening policies for migrants vary greatly ...between countries, and the evidence on the cost-effectiveness of the different approaches is weak and heterogeneous. The aim of this review was to assess the methodology used in published economic evaluations of LTBI screening among migrants to identify critical methodological options that must be considered when using modelling to determine value for money from different economic perspectives. Three electronic databases were searched and 10 articles were included. There was considerable variation across this small number of studies with regard to economic perspective, main outcomes, modelling technique, screening options and target populations considered, as well as in parameterisation of the epidemiological situation, test accuracy, efficacy, safety and programme performance. Only one study adopted a societal perspective; others adopted a health care or wider government perspective. Parameters representing the cascade of screening and treating LTBI varied widely, with some studies using highly aspirational scenarios. This review emphasises the need for a more harmonised approach for economic analysis, and better transparency in how policy options and economic perspectives influence methodological choices. Variability is justifiable for some parameters. However, sufficient data are available to standardise others. A societal perspective is ideal, but can be challenging due to limited data. Assumptions about programme performance should be based on empirical data or at least realistic assumptions. Results should be interpreted within specific contexts and policy options, with cautious generalisations.
Background
Non-tuberculous mycobacteria (NTM) are generally free-living organism, widely distributed in the environment, with sporadic potential to infect. In recent years, there has been a ...significant increase in the global incidence of NTM-related disease, spanning across all continents and an increased mortality after the diagnosis has been reported. The decisions on whether to treat or not and which drugs to use are complex and require a multidisciplinary approach as well as patients’ involvement in the decision process.
Methods and Results
This review aims at describing the drugs used for treating NTM-associated diseases emphasizing the efficacy, tolerability, optimization strategies as well as possible drugs that might be used in case of intolerance or resistance. We also reviewed data on newer compounds highlighting the lack of randomised clinical trials for many drugs but also encouraging preliminary data for others. We also focused on non-pharmacological interventions that need to be adopted during care of individuals with NTM-associated diseases
Conclusions
Despite insufficient efficacy and poor tolerability this review emphasizes the improvement in patients’ care and the needs for future studies in the field of anti-NTM treatments.
We describe the epidemiological pattern and genetic characteristics of 242 acute dengue infections imported to Europe by returning travellers from 2012 to 2014. The overall geographical pattern of ...imported dengue (South-east Asia > Americas > western Pacific region > Africa) remained stable compared with 1999 to 2010. We isolated the majority of dengue virus genotypes and epidemic lineages causing outbreaks and epidemics in Asia, America and Africa during the study period. Travellers acted as sentinels for four unusual dengue outbreaks (Madeira, 2012-13; Luanda, 2013; Dar es Salaam, 2014; Tokyo, 2014). We were able to characterise dengue viruses imported from regions where currently no virological surveillance data are available. Up to 36% of travellers infected with dengue while travelling returned during the acute phase of the infection (up to 7 days after symptom onset) or became symptomatic after returning to Europe, and 58% of the patients with acute dengue infection were viraemic when seeking medical care. Epidemiological and virological data from dengue-infected international travellers can add an important layer to global surveillance efforts. A considerable number of dengue-infected travellers are viraemic after arrival back home, which poses a risk for dengue introduction and autochthonous transmission in European regions where suitable mosquito vectors are prevalent.
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