Dried Blood Spots for Global Health Diagnostics and Surveillance: Opportunities and Challenges

Most diagnostics and surveillance programs rely on measurements from an individual’s blood specimen to guide a clinical or public health decision. To minimize pre-analytical sources of data variability, processes for venipuncture collection are standardized through devices such as analyte-specific blood collection tubes and evidence-based best practices, guidelines, and protocols.1,2 Global health settings often lack infrastructure for quality-assured venipuncture,3 sparking significant interest in the use of dried blood spot (DBS) cards as a universal solution.4–11 The intent of this review is to underscore the need to assess the reliability of DBS-based bioanalysis in context to a specific biomarker and envisioned field-to-laboratory workflow, before applying this technology into a remote health or surveillance program. Compared with venipuncture, the value proposition of DBS is simplified logistics for remote sampling through: Reduced workforce requirements Smaller volumes of blood and components (plasma and serum) Direct heelprick/fingerprick-to-DBS or indirect capillary-to-DBS deposition of blood Collection of nonblood biofluids such as saliva Simplified transport, shipment, and disposal Simplified biobanking for retrospective analysis Commercially available DBS cards are not designed for the minimally resourced environments typical of remote health settings and instead are primarily used in newborn screening and preclinical drug development by highly proficient personnel within controlled clinical and laboratory environments. For instance, most DBS are susceptible to contamination by the user, patient, environment, insects, equipment, or contact with other cards. Health-care workers also have a risk of exposure to potentially infectious agents until blood is dried and contained in secure packaging. Most of these risks can be mitigated through standard operating procedures and accessories, but the impact of these variables on data quality needs to be assessed through careful studies simulating the pre-analytical workflow, starting with specimen acquisition to DBS preparation for analysis. Readers are advised to review the comprehensive review of mass spectrometry (MS) methods12 and the collection of reports compiled by Li and Lee discussing various use cases, techniques, and technologies for DBS-based bioanalysis.13 Two primary global health applications envision that the use of DBS can extend either health-care services or research and surveillance studies into harder-to-reach populations. The clinical scenario aims to measure health-related diagnostic data to stratify at-risk individuals for additional confirmatory testing or to guide individual- or population-level treatment decisions. The other scenario aims to extend epidemiological surveillance that monitors population-level transmission of infection or tracks emerging or recrudescing disease. Both scenarios rely on tools that provide high-sensitivity analysis of individual samples to minimize the risk of missed positive cases, particularly in geographies where loss to follow-up remains a significant challenge. In other words, for both scenarios, false-negative test results typically have higher consequences for these programs than false-positive test results if there is an opportunity to further confirm the clinical or epidemiological status of test-positive individuals or populations. The weakest link for sensitivity within a bioanalytical workflow is the quality of the specimen.2 The concept of DBS is appealing; however, these broad remote-sampling aspirations should consider the extensive literature evaluating the reliability of DBS for high-sensitivity analysis of specific biomarkers. In most instances, quantitative studies have demonstrated the feasibility of DBS if standardized collection and laboratory protocols are followed.12,14–18 However, there are examples where DBS fails to provide reliable results and this review includes a sample of these reports.