Tuberculosis (TB) remains the leading infectious killer worldwide. The World Health Organization's (WHO) End-TB strategy is falling short of the 2020 mileposts in several domains. Undernutrition remains the leading population-level risk factor for TB. Studies have consistently found that undernutrition is associated with increased TB incidence, increased severity, worse treatment outcomes, and increased mortality. Modeling studies support implementing nutritional interventions for persons living with TB (PLWTB) and those at risk of TB disease to ensure the success of the End-TB strategy. In this Personal Views essay, we highlight nutrition-related immunocompromise, implications of undernutrition for TB treatment and prevention, the role of nutritional supplementation, pharmacokinetics and pharmacodynamics of antimycobacterial
Background
Individual pharmacokinetic variability is a driver of poor tuberculosis (TB) treatment outcomes. We developed a method for measurement of rifampin concentrations by urine colorimetry and a mobile phone photographic application to predict clinically important serum rifampin pharmacokinetic measurements in children treated for TB.
Methods
Among spiked urine samples, colorimetric assay performance was tested with conventional spectrophotometric and the mobile phone/light box methods under various environmental and biologic conditions. Urine rifampin absorbance (Abs) was then determined from timed specimens from children treated for TB in Tanzania, and compared to serum pharmacokinetic measurements collected throughout the dosing interval.
Results
Both the mobile phone/light box and spectrophotometry demonstrated excellent correlation across a wide range of urine rifampin concentrations (7.8–1000 mg/L) in intra- and interday trials, 24-hour exposure to ambient light or darkness, and varying urinalysis profiles (all r ≥ 0.98). In 12 Tanzanian children, the urine mobile phone/light box measurement and serum peak concentration (Cmax) were significantly correlated (P = .004). Using a Cmax target of 8 mg/L, the area under the receiver operating characteristic curve was 80.1% (range, 47.2%–100%). A urine mobile phone/light box threshold of 50 Abs correctly classified all patients (n = 6) with serum measurements below target.
Conclusions
The urine colorimetry with mobile phone/light box assay accurately measured rifampin absorbance in varying environmental and biological conditions that may be observed clinically. Among children treated for TB, the assay was sensitive for detection of low rifampin serum concentrations. Future work will identify the optimal timing for urine collection, and operationalize use in TB-endemic settings.
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