n 2005, CDC published guidelines for using the QuantiFERON-TB Gold test (QFT-G) (Cellestis Limited, Carnegie, Victoria, Australia) (CDC. Guidelines for using the QuantiFERON-TB Gold test for detecting Mycobacterium tuberculosis infection, United States. MMWR;54[No. RR-15]:49-55). Subsequently, two new interferon gamma (IFN- gamma) release assays (IGRAs) were approved by the Food and Drug Administration (FDA) as aids in diagnosing M. tuberculosis infection, both latent infection and infection manifesting as active tuberculosis. These tests are the QuantiFERON-TB Gold In-Tube test (QFT-GIT) (Cellestis Limited, Carnegie, Victoria, Australia) and the T-SPOT.TB test (T-Spot) (Oxford Immunotec Limited, Abingdon, United Kingdom). The antigens, methods, and interpretation criteria for these assays differ from those for IGRAs approved previously by FDA. For assistance in developing recommendations related to IGRA use, CDC convened a group of experts to review the scientific evidence and provide opinions regarding use of IGRAs. Data submitted to FDA, published reports, and expert opinion related to IGRAs were used in preparing these guidelines. Results of studies examining sensitivity, specificity, and agreement for IGRAs and TST vary with respect to which test is better. Although data on the accuracy of IGRAs and their ability to predict subsequent active tuberculosis are limited, to date, no major deficiencies have been reported in studies involving various populations. This report provides guidance to U.S. public health officials, health-care providers, and laboratory workers for use of FDA-approved IGRAs in the diagnosis of M. tuberculosis infection in adults and children. In brief, TSTs and IGRAs (QFT-G, QFT-GIT, and T-Spot) may be used as aids in diagnosing M. tuberculosis infection. They may be used for surveillance purposes and to identify persons likely to benefit from treatment. Multiple additional recommendations are provided that address quality control, test selection, and medical management after testing. Although substantial progress has been made in documenting the utility of IGRAs, additional research is needed that focuses on the value and limitations of IGRAs in situations of importance to medical care or tuberculosis control. Specific areas needing additional research are listed.

Updated guidelines for using Interferon Gamma Release Assays to detect Mycobacterium tuberculosis infection - United States, 2010.

https://journal.chestnet.org/article/S0012-3692(10)60202-4/pdf

Evidence-Based Comparison of Commercial Interferon-γ Release Assays for Detecting Active TB: A Metaanalysis

rium tuberculosis have signifi cant risk of developing tuberculosis (TB) and can therefore benefi t from preventive therapy. OBJECTIVE: To assess the value of interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST) in the diagnosis of TB infection and disease in children. METHODS: Thirty-three studies were included, assessing commercial IGRAs (QuantiFERON®-TB [QFT] and T-SPOT.®TB) and TST. Reference standards for infection were incident TB or TB exposure. Test performance for disease diagnosis was evaluated in studies assessing children with confi rmed and/or clinically diagnosed TB, compared to children where TB was excluded. RESULTS: Two small studies measured incident TB in children tested with QFT and found weak positive predictive value. Association of test response with exposure —categorized dichotomously or as a gradient—was similar for all tests. The sensitivity and specifi city of all tests were similar in diagnosing the disease. Stratifi ed analysis suggested lower sensitivity for all tests in young or human immunodefi ciency virus infected children. CONCLUSIONS: Available data suggest that TST and IGRAs have similar accuracy for the detection of TB in

Interferon-gamma release assays and childhood tuberculosis: systematic review and meta-analysis.

Author(s): Alipanah, Narges; Jarlsberg, Leah; Miller, Cecily; Linh, Nguyen Nhat; Falzon, Dennis; Jaramillo, Ernesto; Nahid, Payam | Abstract: BackgroundIncomplete adherence to tuberculosis (TB) treatment increases the risk of delayed culture conversion with continued transmission in the community, as well as treatment failure, relapse, and development or amplification of drug resistance. We conducted a systematic review and meta-analysis of adherence interventions, including directly observed therapy (DOT), to determine which approaches lead to improved TB treatment outcomes.Methods and findingsWe systematically reviewed Medline as well as the references of published review articles for relevant studies of adherence to multidrug treatment of both drug-susceptible and drug-resistant TB through February 3, 2018. We included randomized controlled trials (RCTs) as well as prospective and retrospective cohort studies (CSs) with an internal or external control group that evaluated any adherence intervention and conducted a meta-analysis of their impact on TB treatment outcomes. Our search identified 7,729 articles, of which 129 met the inclusion criteria for quantitative analysis. Seven adherence categories were identified, including DOT offered by different providers and at various locations, reminders and tracers, incentives and enablers, patient education, digital technologies (short message services [SMSs] via mobile phones and video-observed therapy [VOT]), staff education, and combinations of these interventions. When compared with DOT alone, self-administered therapy (SAT) was associated with lower rates of treatment success (CS: risk ratio [RR] 0.81, 95% CI 0.73-0.89; RCT: RR 0.94, 95% CI 0.89-0.98), adherence (CS: RR 0.83, 95% CI 0.75-0.93), and sputum smear conversion (RCT: RR 0.92, 95% CI 0.87-0.98) as well as higher rates of development of drug resistance (CS: RR 4.19, 95% CI 2.34-7.49). When compared to DOT provided by healthcare providers, DOT provided by family members was associated with a lower rate of adherence (CS: RR 0.86, 95% CI 0.79-0.94). DOT delivery in the community versus at the clinic was associated with a higher rate of treatment success (CS: RR 1.08, 95% CI 1.01-1.15) and sputum conversion at the end of two months (CS: RR 1.05, 95% CI 1.02-1.08) as well as lower rates of treatment failure (CS: RR 0.56, 95% CI 0.33-0.95) and loss to follow-up (CS: RR 0.63, 95% CI 0.40-0.98). Medication monitors improved adherence and treatment success and VOT was comparable with DOT. SMS reminders led to a higher treatment completion rate in one RCT and were associated with higher rates of cure and sputum conversion when used in combination with medication monitors. TB treatment outcomes improved when patient education, healthcare provider education, incentives and enablers, psychological interventions, reminders and tracers, or mobile digital technologies were employed. Our findings are limited by the heterogeneity of the included studies and lack of standardized research methodology on adherence interventions.ConclusionTB treatment outcomes are improved with the use of adherence interventions, such as patient education and counseling, incentives and enablers, psychological interventions, reminders and tracers, and digital health technologies. Trained healthcare providers as well as community delivery provides patient-centered DOT options that both enhance adherence and improve treatment outcomes as compared to unsupervised, SAT alone.

/pdf/adherence-interventions-and-outcomes-of-tuberculosis-40ggewyaih.pdf

Adherence interventions and outcomes of tuberculosis treatment: A systematic review and meta-analysis of trials and observational studies.

CITATION: Grobler, L. et al. 2016. Nutritional supplements for people being treated for active tuberculosis. Cochrane Database of Systematic Reviews, 6:CD006086, doi:10.1002/14651858.CD006086.pub4.

Nutritional supplements for people being treated for active tuberculosis

OBJECTIVE To investigate the effects of nutritional supplementation on the outcome and nutritional status of south Indian patients with tuberculosis (TB) with and without human immunodeficiency virus (HIV) coinfection on anti-tuberculous therapy. METHOD Randomized controlled trial on the effect of a locally prepared cereal-lentil mixture providing 930 kcal and a multivitamin micronutrient supplement during anti-tuberculous therapy in 81 newly diagnosed TB alone and 22 TB-HIV-coinfected patients, among whom 51 received and 52 did not receive the supplement. The primary outcome evaluated at completion of TB therapy was outcome of TB treatment, as classified by the national programme. Secondary outcomes were body composition, compliance and condition on follow-up 1 year after cessation of TB therapy and supplementation. RESULTS There was no significant difference in TB outcomes at the end of treatment, but HIV-TB coinfected individuals had four times greater odds of poor outcome than those with TB alone. Among patients with TB, 1/35 (2.9%) supplemented and 5/42(12%) of those not supplemented had poor outcomes, while among TB-HIV-coinfected individuals, 4/13 (31%) supplemented and 3/7 (42.8%) non-supplemented patients had poor outcomes at the end of treatment, and the differences were more marked after 1 year of follow-up. Although there was some trend of benefit for both TB alone and TB-HIV coinfection, the results were not statistically significant at the end of TB treatment, possibly because of limited sample size. CONCLUSION Nutritional supplements in patients are a potentially feasible, low-cost intervention, which could impact patients with TB and TB-HIV. The public health importance of these diseases in resource-limited settings suggests the need for large, multi-centre randomized control trials on nutritional supplementation.

Pilot randomized trial of nutritional supplementation in patients with tuberculosis and HIV–tuberculosis coinfection receiving directly observed short-course chemotherapy for tuberculosis

OBJECTIVES To determine health care provider cost and household cost of the treatment of severe pneumonia in infants and young children admitted to secondary and tertiary level health care facilities METHODS The study was done in a private, not-for-profit medical college hospital, in Vellore, India, in mid-2008 Children aged 2-36 months admitted with severe pneumonia with no underlying chronic disease were included in the study The relatives were interviewed daily on matters relating to patients' view point of the costs These were direct medical costs, direct non-medical costs which comprised travel, accommodation and special food during the period of illness, and indirect costs of productivity loss for family members Patient specific resource consumption and related charges were recorded from charts, nursing records, pharmacy lists and hospital bills, and the providers view point of the costs was estimated Unit cost estimates for bed days, treatment and investigation inputs were calculated RESULTS Total cost to health care provider for one episode of hospitalized childhood pneumonia treated at secondary level was US$ 8389 (INR 3524) and US$ 14659 (INR 6158) at tertiary level At both levels the greatest single cost was the hospital stay itself, comprising 74% and 56% of the total cost, respectively Diagnostic investigations were a large expense and supportive treatment with nebulization and oxygen therapy added to the costs Mean household expenditure on secondary level was US$ 4135 (INR 1737) and at tertiary level was US$ 13462 (INR 5655), the largest single expense being medicines in the former and the hospitalization in the latter (one US$=INR 421 at time of study) CONCLUSIONS A considerable cost difference exists between secondary and tertiary level treatment Admission at lowest possible treatment level for appropriate patients could decrease the costs borne by the provider and the patient

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-3156.2009.02374.x

Costing of severe pneumonia in hospitalized infants and children aged 2-36 months, at a secondary and tertiary level hospital of a not-for-profit organization.

In India, little is known about health care-seeking behavior among HIV-infected individuals. Similarly, little is known about how HIV is being treated in the community, in particular by Indian Systems of Medicine (ISM) providers. Therefore, while ART implementation programs continue to expand, it is important to determine whether the knowledge, attitudes, and treatment practices of HIV-infected individuals and their health care providers are aligned with current treatment recommendations. We conducted in-depth qualitative interviews with persons with HIV (n = 9 men and 17 women), family members of persons with HIV (n = 14 men and 3 women), and ISM providers (n = 7). Many of the patients we studied turned at some point to ISM providers because they believed that such practitioners offer a cure for HIV. ISM treatments sometimes had negative impacts including side effects, unchecked progression of an underlying illness, and financial depletion. Indian women tended to be less knowledgeable about HIV ...

Knowledge beliefs and health care practices relating to treatment of HIV in Vellore India.

This study aimed to estimate the specificity and sensitivity of a whole blood IFN-g assay (ELISPOT) test for diagnosis in childhood tuberculosis. 96 patients, less than 18 years of age, diagnosed and commenced on anti-tubercular therapy were enrolled and tested. 47 age and sex matched controls were also tested. 23 tests were deemed invalid and analysis done on the remainder. The sensitivity was 53.3% in confirmed cases and less in other groups. The specificity was high at 97.9%. This test can be an useful aid in the diagnosis of tuberculosis.

T-cell assay as a diagnostic tool for tuberculosis

Summary

Objective To evaluate the cost-effectiveness of three strategies for the control of taeniasis in a community, in terms of cost per case treated.



Methods  A study was conducted in South India to determine the prevalence of taeniasis by screening stool samples from 653 randomly chosen subjects, for coproantigens. The costs incurred in the project were used to estimate the cost per case screened and treated. A one-way sensitivity analysis was carried out for varying rates of taeniasis, different screening strategies and mass therapy. Further sensitivity analysis was carried out with different manpower and test costs.



Results  The rate of taeniasis as detected by ELISA for coproantigen was 3 per 1000 (2 of 653 samples). Our study showed that mass therapy without screening for taeniasis would be the most economical strategy in terms of cost per case treated if field workers are employed exclusively for either mass therapy or screening. For each strategy, costs per case treated are higher at low prevalence of taeniasis, with a sharp rise below 15%.



Conclusions  In places that are endemic for taeniasis and neurocysticercosis, mass therapy or screening for taeniasis should be considered. Screening by stool microscopy is not cost-effective in terms of cost per case of taeniasis treated owing to its low sensitivity. Although the cost per case of taeniasis treated is high at low prevalence of taeniasis for all options, incorporating mass therapy into existing mass drug distribution programmes might prove to be the most cost-effective control strategy.




Objectif:  Evaluer la rentabilite de trois strategies pour le controle du teniasis dans une communaute, en termes de cout par cas traite.



Methodes:  Une etude a ete menee dans le sud de l’Inde afin de determiner la prevalence de teniasis par depistage de coproantigenes a partir d’echantillons de selles provenant de 653 sujets choisis aleatoirement. Les frais engages dans le projet ont ete utilises pour estimer le cout par cas depiste et traite. Une analyse de sensibilite a ete realisee pour des taux variables de teniasis, differentes strategies de depistage et le traitement de masse. Une analyse de sensibilite supplementaire a ete effectuee avec differents couts de la main-d’œuvre et des tests.



Resultats:  Le taux de teniasis detectes par ELISA pour coproantigenes etait de 3 pour 1000 (2 echantillons sur 653). Notre etude a montre que la therapie de masse sans depistage de teniasis serait la strategie la plus rentable en termes de cout par cas traite, si les agents de terrain sont employes exclusivement pour le traitement de masse ou de depistage. Pour chaque strategie, les couts par cas traite sont plus eleves pour des prevalences faibles de teniasis, avec une forte hausse en dessous de 15%.



Conclusions:  Dans les regions endemiques pour le teniasis et la neurocysticercose, le traitement de masse ou le depistage de teniasis devrait etre envisage. Le depistage par examen microscopique des selles n’est pas rentable en termes de cout par cas de teniasis traite en raison de sa faible sensibilite. Bien que le cout par cas traite est elevea faible prevalence de teniasis pour toutes les options, l’integration d’un traitement de masse dans les programmes existants de distribution de masse de medicaments pourrait s’averer etre la strategie de controle la plus rentable.





Objetivo:  Evaluar la costo-efectividad de tres estrategias para el control de la teniasis en una comunidad, en terminos de coste por caso tratado.



Metodos:  Se realizo un estudio en el sur de India para determinar la prevalencia de teniasis mediante la criba de muestras de heces de 653 sujetos elegidos al azar a los que se les realizo la deteccion de coproantigenos. Los costes en los que se incurrio durante el proyecto se utilizaron para estimar el coste por caso incluido en la criba y tratado. Se realizo un analisis de sensibilidad para tasas variables de teniasis, diferentes estrategias de cribaje y terapia masiva. Un analisis de sensibilidad mas profundo se realizo incluyendo los diferentes costes de recursos humanos y de las pruebas.



Resultados:  La tasa de teniasis detectada mediante ELISA para el coproantigeno era de 3 por 1000 (2 de 653 muestras). Nuestro estudio ha demostrado que la terapia masiva sin cribaje para la teniasis seria la estrategia mas economica, en terminos de coste por caso tratado, si los trabajadores de campo se dedican exclusivamente para el tratamiento masivo o para el cribaje. Para cada estrategia, el coste por caso tratado es mayor en zonas con baja prevalencia de teniasis, con un incremento acusado por debajo del 15%.



Conclusiones:  En lugares que son endemicos para la teniasis y la neurocisticercosis, la terapia masiva o el cribaje para teniasis deberia ser considerado. El cribaje mediante microscopia de heces no es costo efectivo en terminos de coste por caso de teniasis tratado debido a su baja sensibilidad. Aunque el coste por caso de teniasis tratado es alto, para todas las opciones, en zonas con una baja prevalencia de teniasis, incorporar la terapia masiva en los programas existentes de distribucion masiva de medicamentos podria ser la estrategia de control mas costo-efectiva.

/pdf/economic-implications-of-three-strategies-for-the-control-of-ovt5y7axf1.pdf

K. R. John

Papers

Pilot randomized trial of nutritional supplementation in patients with tuberculosis and HIV–tuberculosis coinfection receiving directly observed short-course chemotherapy for tuberculosis

Costing of severe pneumonia in hospitalized infants and children aged 2-36 months, at a secondary and tertiary level hospital of a not-for-profit organization.

Knowledge beliefs and health care practices relating to treatment of HIV in Vellore India.

T-cell assay as a diagnostic tool for tuberculosis

Economic implications of three strategies for the control of taeniasis.