Determination of Rifampin Concentrations by Urine Colorimetry and Mobile Phone Readout for Personalized Dosing in Tuberculosis Treatment.

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.

Resurgence of measles in the United States: how did we get here?

PURPOSE OF REVIEW: In September 2019, the United States was at risk of losing measles elimination status due to several large-scale outbreaks resulting in more than 1200 confirmed cases across 31 states. This resurgence caps approximately 10 years of increasing incidence, marked by a highly publicized outbreak in 2015 associated with Disneyland when an infected traveler from the Philippines unknowingly spread the virus to susceptible park visitors and the recently ended large outbreak in undervaccinated Orthodox Jewish communities in New York City and Rockland counties. This review highlights current literature elucidating factors associated with current trends in measles epidemiology in the United States, the public health implications of current measles outbreaks and a path forward for addressing challenges contributing to the resurgence of measles in the United States and globally. RECENT FINDINGS AND SUMMARY: As the most highly transmissible vaccine preventable disease, measles is especially sensitive to changes in herd immunity, the impact of vaccine refusal and globalization. Results highlight the confluence of these factors in current outbreaks, provide tools to predict outbreak risk, demonstrate the growing impact of misinformation and evaluate the impact of policy approaches for outbreak control and prevention.