pediatric pk studies under pressure: DBS vs. VAMS in Côte d’Ivoire

Scientists and researchers from the Swiss Tropical and Public Health Institute recently provided new, strong evidence for the efficacy of pediatric pharmacokinetic (PK) studies using Mitra^® devices.

They tested Mitra technology against standard-issue DBS cards, within the framework of a randomized controlled trial, on 35 school-aged children in rural Côte d’Ivoire infected with Schistosoma haematobium.

For those who have been curious about the capabilities of microsampling technology in areas with limited access to standard laboratory facilities, this is exciting news indeed.

Thanks to significant scientific and technological advances, it is now possible to collect a large amount of information from a small amount of biological fluid. This allows for the elimination of cold-chain shipping and storage, among other bulky and expensive requirements of wet blood collection, and thus opens new frontiers for blood collection in low-resourced regions. However, this process has long been stymied by the limitations of common DBS technology, chief among them the “hematocrit effect,” which hamper the reliability of resultant data.

Mitra devices, based on Volumetric Absorptive Microsamping technology, are changing all this. They are designed to collect volumetrically accurate samples, thus eliminating the primary drawbacks formerly associated with dried blood specimen collection. To Jennifer Keiser, Ph.D., at the Swiss TPH, this innovation is of special interest.

A pharmacist by training, Keiser has a professorship in neglected tropical diseases. With the Swiss TPH, she has been involved in research in Africa for many years. “The Centre Suisse de Recherches Scientifiques in Abidjan is one of our main partner institutions,” says Keiser. “One of my postdocs is Ivorian and based in Abidjan.”

The Swiss TPH’s Mitra study stems from its ongoing work in the Côte d’Ivoire area. “I started my research group about twelve years ago,” says Keiser. “Since then, we are trying to improve treatment options for helminthiases, mainly schistosomiasis and soil-transmitted helminthiasis. We work from bench to field. I love the interdisciplinarity nature of the work and that our findings might result in policy changes, and in improved treatment options.”

For this project, the Swiss TPH scientists developed, optimized, and validated an extraction method for the study drug, praziquantel (PZQ), from VAMS^® tips on Mitra devices. Using liquid chromatography-tandem mass spectrometry, they measured the analytes R- and S-praziquantel (R-/SPZQ) and the main human metabolite, R-trans-4-OH-praziquantel. Then, they compared results with Bland-Altman analysis to determine agreement between matrices.

For the Swiss TPH, this project required significant fieldwork, including screening stool of the study population for Schistosoma mansoni eggs and assessing infection intensity, performing physical and medical examination of infected children, proceeding with treatment with the study drug, and monitoring pharmacokinetics of same.

The results are impressive – from the perspective of microsampling, the study was a hands-down success. Strong positive correlation (R2 > 0.98) and agreement were observed between both matrices, but Mitra devices with VAMS tips revealed higher concentrations of all analytes in most patient samples compared to DBS: 63% for RPZQ, 49% for SPZQ, and 78% for the metabolite.

What’s more, Keiser's team found Mitra devices easier to use, too.

“The nurses taking the blood samples preferred this method over the DBS-method,” says Keiser. “Mitra doesn't need a ‘drying period,’ because the packaging is designed to not touch anything. Therefore, the Mitra stick can be put away immediately. DBS cards need to dry, which is in tropical area in not that fast. Having a couple of hundred cards standing around for drying is inconvenient, especially if working space is limited in the field and the DBS are exposed to sand, dirt, and wind.”

This is in keeping with the overall improved user experience of Mitra devices and Volumetric Absorptive Microsamping technology. The goal is to improve patient experience (which in turn promotes adherence, compliance, and subject retention), and at the same time create a better experience for providers, practitioners, and professionals.

If it can happen in some of the most underserved places on the globe, the world is truly and open landscape for this innovative, transformative sampling solution.