Framework for the evaluation of new tests for tuberculosis infection

The scale-up of tuberculosis (TB) preventive treatment (TPT) must be accelerated to achieve the targets set by the United Nations High-level Meeting on TB and the End TB Strategy. The scale-up of effective TPT is hampered by concerns about operational challenges to implement the existing tests for TB infection. New simpler tests could facilitate the scale-up of testing for TB infection. We present a framework for evaluation of new immunodiagnostic tests for the detection of TB infection, with an aim to facilitate their standardised evaluation and accelerate adoption into global and national policies and subsequent scale-up. The framework describes the principles to be considered when evaluating new tests for TB infection and provides guidance to manufacturers, researchers, regulators and other users on study designs, populations, reference standards, sample size calculation and data analysis and it is also aligned with the Global Strategy for TB Research and Innovation adopted by the World Health Assembly in 2020. We also briefly describe technical issues that should be considered when evaluating new tests, including the safety for skin tests, costs incurred by patients and the health system patient, and operational characteristics

Analysis of multi drug resistant tuberculosis (MDR-TB) financial protection policy : MDR-TB health insurance schemes, in Chhattisgarh state, India

INTRODUCTION: There are significant financial barriers to access treatment for multi drug resistant tuberculosis (MDR-TB) in India. To address these challenges, Chhattisgarh state in India has established a MDR-TB financial protection policy by creating MDR-TB benefit packages as part of the universal health insurance scheme that the state has rolled out in their effort towards attaining Universal Health Coverage for all its residents. In these schemes the state purchases health insurance against set packages of services from third party health insurance agencies on behalf of all its residents. Provider payment reform by strategic purchasing through output based payments (lump sum fee is reimbursed as per the MDR-TB benefit package rates) to the providers - both public and private health facilities empanelled under the insurance scheme was the key intervention. AIM: To understand the implementation gap between policy and practice of the benefit packages with respect to equity in utilization of package claims by the poor patients in public and private sector. METHODS: Data from primary health insurance claims from January 2013 to December 2015, were analysed using an extension of 'Kingdon's multiple streams for policy implementation framework' to explain the implementation gap between policy and practice of the MDR-TB benefit packages. RESULTS: The total number of claims for MDR-TB benefit packages increased over the study period mainly from poor patients treated in public facilities, particularly for the pre-treatment evaluation and hospital stay packages. Variations and inequities in utilizing the packages were observed between poor and non-poor beneficiaries in public and private sector. Private providers participation in the new MDR-TB financial protection mechanism through the universal health insurance scheme was observed to be much lower than might be expected given their share of healthcare provision overall in India. CONCLUSION: Our findings suggest that there may be an implementation gap due to weak coupling between the problem and the policy streams, reflecting weak coordination between state nodal agency and the state TB department. There is a pressing need to build strong institutional capacity of the public and private sector for improving service delivery to MDR-TB patients through this new health insurance mechanism

Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?

BACKGROUND: Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority

The impact of digital health technologies on tuberculosis treatment: a systematic review

Digital technologies are increasingly harnessed to support treatment of persons with tuberculosis (TB). Since in-person directly observed treatment (DOT) can be resource intensive and challenging to implement, these technologies may have the potential to improve adherence and clinical outcomes. We reviewed the effect of these technologies on TB treatment adherence and patient outcomes. We searched several bibliographical databases for studies reporting the effect of digital interventions, including short message service (SMS), video-observed therapy (VOT) and medication monitors (MMs), to support treatment for active TB. Only studies with a control group and which reported effect estimates were included. Four trials showed no statistically significant effect on treatment completion when SMS was added to standard care. Two observational studies of VOT reported comparable treatment completion rates when compared with in-person DOT. MMs increased the probability of cure (RR 2.3, 95% CI 1.6–3.4) in one observational study, and one trial reported a statistically significant reduction in missed treatment doses relative to standard care (adjusted means ratio 0.58, 95% CI 0.42–0.79). Evidence of the effect of digital technologies to improve TB care remains limited. More studies of better quality are needed to determine how such technologies can enhance programme performance

GeneXpert—A Game-Changer for Tuberculosis Control?

Carlton Evans considers whether the new tuberculosis diagnostic test, GeneXpert, is the solution for TB control that it's said to be

The road to tuberculosis treatment in rural Nepal: A qualitative assessment of 26 journeys

BACKGROUND: The fact that tuberculosis can be treated with the DOTS strategy (Directly Observed Treatment, Short-course) is not enough to control the disease. Patients have to find their way to tuberculosis treatment first. To better understand the route to tuberculosis treatment in rural Nepal we interviewed twenty-six patients under treatment. METHODS: In semi-structured interviews patients shared their disease history and health seeking behaviour. The analysis focused on the encounters with the health care system before enrolment in the tuberculosis treatment program. RESULTS: Patient routes often started in the medical shop and led via intricate routes with multiple providers to facilities with higher qualified and more competent staff where tuberculosis was diagnosed. Several factors influenced the route to tuberculosis treatment. Besides known patients factors (such as severity of complaints, the ability to pay for services, availability of services and peer support for choosing a provider) specific health services factors were also identified. These included the perceived quality, costs and service level of a provider, and lack of provider initiated referral. Self referral because of waned trust in the provider was very common. In contrast, once tuberculosis was considered a possible diagnosis, referral to diagnostic testing and tuberculosis treatment was prompt. CONCLUSION: Patient routes towards tuberculosis treatment are characterised by self referral and include both private and public health care providers. Once tuberculosis is suspected referral for diagnosis and treatment is prompt. Given the importance of the private practitioners in the patient routes, quality improvement initiatives need to address not only the public sector but the private health care sector as well

Systematic review of cost and cost-effectiveness of different TB-screening strategies

<p>Abstract</p> <p>Background</p> <p>Interferon-γ release assays (IGRAs) for TB have the potential to replace the tuberculin skin test (TST) in screening for latent tuberculosis infection (LTBI). The higher per-test cost of IGRAs may be compensated for by lower post-screening costs (medical attention, chest x-rays and chemoprevention), given the higher specificity of the new tests as compared to that of the conventional TST. We conducted a systematic review of all publications that have addressed the cost or cost-effectiveness of IGRAs. The objective of this report was to undertake a structured review and critical appraisal of the methods used for the model-based cost-effectiveness analysis of TB screening programmes.</p> <p>Methods</p> <p>Using Medline and Embase, 75 publications that contained the terms "IGRA", "tuberculosis" and "cost" were identified. Of these, 13 were original studies on the costs or cost-effectiveness of IGRAs.</p> <p>Results</p> <p>The 13 relevant studies come from five low-to-medium TB-incidence countries. Five studies took only the costs of screening into consideration, while eight studies analysed the cost-effectiveness of different screening strategies. Screening was performed in high-risk groups: close contacts, immigrants from high-incidence countries and healthcare workers. Two studies used the T-SPOT.TB as an IGRA and the other studies used the QuantiFERON-TB Gold and/or Gold In-Tube test. All 13 studies observed a decrease in costs when the IGRAs were used. Six studies compared the use of an IGRA as a test to confirm a positive TST (TST/IGRA strategy) to the use of an IGRA-only strategy. In four of these studies, the two-step strategy and in two the IGRA-only strategy was more cost-effective. Assumptions about TST specificity and progression risk after a positive test had the greatest influence on determining which IGRA strategy was more cost-effective.</p> <p>Conclusion</p> <p>The available studies on cost-effectiveness provide strong evidence in support of the use of IGRAs in screening risk groups such as HCWs, immigrants from high-incidence countries and close contacts. So far, only two studies provide evidence that the IGRA-only screening strategy is more cost-effective.</p

Tuberculosis screening of travelers to higher-incidence countries: A cost-effectiveness analysis

Abstract Background Travelers to countries with high tuberculosis incidence can acquire infection during travel. We sought to compare four screening interventions for travelers from low-incidence countries, who visit countries with varying tuberculosis incidence. Methods Decision analysis model: We considered hypothetical cohorts of 1,000 travelers, 21 years old, visiting Mexico, the Dominican Republic, or Haiti for three months. Travelers departed from and returned to the United States or Canada; they were born in the United States, Canada, or the destination countries. The time horizon was 20 years, with 3% annual discounting of future costs and outcomes. The analysis was conducted from the health care system perspective. Screening involved tuberculin skin testing (post-travel in three strategies, with baseline pre-travel tests in two), or chest radiography post-travel (one strategy). Returning travelers with tuberculin conversion (one strategy) or other evidence of latent tuberculosis (three strategies) were offered treatment. The main outcome was cost (in 2005 US dollars) per tuberculosis case prevented. Results For all travelers, a single post-trip tuberculin test was most cost-effective. The associated cost estimate per case prevented ranged from $21,406 for Haitian-born travelers to Haiti, to$161,196 for US-born travelers to Mexico. In all sensitivity analyses, the single post-trip tuberculin test remained most cost-effective. For US-born travelers to Haiti, this strategy was associated with cost savings for trips over 22 months. Screening was more cost-effective with increasing trip duration and infection risk, and less so with poorer treatment adherence. Conclusion A single post-trip tuberculin skin test was the most cost-effective strategy considered, for travelers from the United States or Canada. The analysis did not evaluate the use of interferon-gamma release assays, which would be most relevant for travelers who received BCG vaccination after infancy, as in many European countries. Screening decisions should reflect duration of travel, tuberculosis incidence, and commitment to treat latent infection.</p

Screening for latent tuberculosis infection among undocumented immigrants in Swiss healthcare centres; a descriptive exploratory study

BACKGROUND: Migration is one of the major causes of tuberculosis in developed countries. Undocumented patients are usually not screened at the border and are not covered by a health insurance increasing their risk of developing the disease unnoticed. Urban health centres could help identify this population at risk. The objective of this study is to assess the prevalence of latent tuberculosis infection (LTBI) and adherence to preventive treatment in a population of undocumented immigrant patients. METHODS: All consecutive undocumented patients that visited two urban healthcare centres for vulnerable populations in Lausanne, Switzerland for the first time were offered tuberculosis screening with an interferon-gamma assay. Preventive treatment was offered if indicated. Adherence to treatment was evaluated monthly over a nine month period. RESULTS: Of the 161 participants, 131 (81.4%) agreed to screening and 125 had complete examinations. Twenty-four of the 125 patients (19.2%; CI95% 12.7;27.2) had positive interferon-gamma assay results, two of which had active tuberculosis. Only five patients with LTBI completed full preventive treatments. Five others initiated the treatment but did not follow through. CONCLUSION: Screening for tuberculosis infection in this hard-to-reach population is feasible in dedicated urban clinics, and the prevalence of LTBI is high in this vulnerable population. However, the low adherence to treatment is an important public health concern, and new strategies are needed to address this problem