Childhood tuberculosis in the United States: shifting the focus to prevention

Cruz, Andrea T.; Martinez, Bertha

doi:10.5588/ijtld.15.0418

Cited by 7 publications

(3 citation statements)

References 6 publications

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“…In attempts to improve completion rates, some experts have increasingly used the 4-month regimen of rifampin, which had typically been recommended for LTBI treatment among those exposed to isoniazid-resistant strains. 104,105 …”

Section: Managementmentioning

confidence: 99%

Tuberculosis in Children

Thomas

2017

Pediatric Clinics of North America

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Synopsis Mycobacterium tuberculosis is the leading cause of death worldwide from a single bacterial pathogen. World Health Organization (WHO) estimates that annually, 1 million children have TB disease and many more harbor a latent form of infection. However, accurate estimates are hindered by under-recognition and challenges in diagnosis; to date, an accurate diagnostic test to confirm TB in children does not exist. TB treatment is lengthy, but outcomes are generally favorable with timely initiation. As we move toward the End TB Strategy, there is an urgent need for improved diagnostics and treatment to prevent the unnecessary morbidity and mortality from TB in children.

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Section: Managementmentioning

confidence: 99%

Tuberculosis in Children

Thomas

2017

Pediatric Clinics of North America

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“…12 Research has already demonstrated that the ingestible sensor has no risk of mechanical injury or toxicology concern. 7,11,13 The ingestible sensor technology has been used in monitoring different diseases such as diabetes, 14 hypertension, 15 mental health disorder, 16 and tuberculosis 13,17 as well as care for kidney transplant patients, 11,13,[17][18][19][20] and has been wellaccepted. 21,22 To use the ingestible sensor to monitor medication taking and measure adherence, the medication must be coencapsulated with the sensor.…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics of Coencapsulated Antiretrovirals with Ingestible Sensors

Liu

Daar

Wang³

et al. 2020

AIDS Research and Human Retroviruses

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We investigated the use of a system with an ingestible sensor (Proteus Digital Health Feedback system) coencapsulated with antiretrovirals (ARVs) to measure real-time adherence. To assess the safety and impact, if any, coencapsulation might have on ARV concentrations, we evaluated the pharmacokinetics of ARVs coencapsulated with an ingestible sensor for eight commonly used fixed-dose combination ARVs: emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF); FTC/tenofovir alafenamide (TAF); efavirenz (EFV)/FTC/TDF; abacavir (ABC)/lamivudine (3TC); dolutegravir (DTG)/ABC/3TC; rilpivirine (RPV)/TAF/FTC; elvitegravir (EVG)/cobicistat (COBI)/FTC/TAF; and bictegravir (BIC)/FTC/TAF. The steady-state apparent peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) were determined from plasma concentrations measured at predose, 1, 2, 4, and 6 h postdose, and compared with literature values. A total of 49 unique patients on stable regimens for at least 12 weeks with undetectable viral loads were recruited. Cmax and AUC values were not statistically significantly different from literature values for all of the formulations except the Cmax of FTC/TDF, Cmax of BIC, and the Cmax of RPV. In a subsequent evaluation of FTC/TDF and BIC/FTC/TAF using a crossover design, the geometric mean ratio (GMR) between the coencapsulated and the unencapsulated formulations for FTC/TDF were the following: FTC, 84.6% (90% confidence interval [CI] 66.6-107.4) for AUC and 77.5% (60.1-99.9) for Cmax. For tenofovir (TFV), the GMR was 96.2% (90% CI 89.2-103.8) for AUC and 87.3% (64.2-118.7) for Cmax. The GMR for BIC (from the BIC/FTC/TAF formulation) was 98.0% (90% CI 84.5-113.5) for AUC and 89.9% (84.5-95.7) for Cmax. The observed deviation in FTC/TDF (Truvada) may be due to participant characteristics, fasted/fed conditions, and/or random variation and may warrant further investigations with a larger sample size. These findings provide assurance for use of coencapsulated ARVs for future HIV treatment-adherence research.

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“…Young children (aged <5 years) exposed to Mycobacterium tuberculosis ( Mtb ) are at the highest risk of disseminated disease [ 1 ]. The number of tuberculosis cases in children varies between 3.5% and 11% of the total reported global tuberculosis cases, and an estimated 332 000 children are left undiagnosed or not reported in national surveys [ 2 , 3 ].…”

mentioning

confidence: 99%

A Combination Regimen Design Program Based on Pharmacodynamic Target Setting for Childhood Tuberculosis: Design Rules for the Playground

et al. 2016

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Children with tuberculosis are treated with drug regimens copied from adults despite significant differences in antibiotic pharmacokinetics, pathology, and the microbial burden between childhood and adult tuberculosis. We sought to develop a new and effective oral treatment regimen specific to children of different ages. We investigated and validated the concept that target drug concentrations associated with therapy failure and death in children are different from those of adults. On that basis, we proposed a 4-step program to rapidly develop treatment regimens for children. First, target drug concentrations for optimal efficacy are derived from preclinical models of disseminated tuberculosis that recapitulate pediatric pharmacokinetics, starting with monotherapy. Second, 2-drug combinations were examined for zones of synergy, antagonism, and additivity based on a whole exposure–response surface. Exposures associated with additivity or synergy were then combined and the regimen was compared to standard therapy. Third, several exposures of the third drug were added, and a 3-drug regimen was identified based on kill slopes in comparison to standard therapy. Fourth, computer-aided clinical trial simulations are used to identify clinical doses that achieve these kill rates in children in different age groups. The proposed program led to the development of a 3-drug combination regimen for children from scratch, independent of adult regimens, in <2 years. The regimens and doses can be tested in animal models and in clinical trials.

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Childhood tuberculosis in the United States: shifting the focus to prevention

Cited by 7 publications

References 6 publications

Tuberculosis in Children

Tuberculosis in Children

Pharmacokinetics of Coencapsulated Antiretrovirals with Ingestible Sensors

A Combination Regimen Design Program Based on Pharmacodynamic Target Setting for Childhood Tuberculosis: Design Rules for the Playground

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