Diagnostic accuracy of dried blood spots for serology of vaccine-preventable diseases: a systematic review

ABSTRACT

Introduction

Venous serum and plasma are optimal specimens for serological testing but may be logistically infeasible. Dried blood spots (DBS) are a feasible alternative, provided results are adequately sensitive and specific. We aimed to assess the diagnostic accuracy of DBS to measure IgG and IgM antibodies for vaccine-preventable diseases and compare test validity of DBS with venous blood.

Areas covered

In October 2020, we searched seven databases for peer-reviewed studies assessing the diagnostic accuracy of DBS specimens compared with serum in detecting antibodies to VPDs in humans. We extracted data and assessed risk of bias in all included studies. We calculated sensitivity and specificity with 95% confidence intervals for each index-reference test comparison. We narratively synthesized the identified evidence on diagnostic accuracy and blood collection and processing methods for DBS. Studies on measles and rubella IgG and IgM were the most frequently identified and reported generally high sensitivity and specificity.

Expert opinion

Lack of standardization in collection, storage, and testing methods limited systematic comparison across studies. Our findings indicate a need for additional validation studies on the diagnostic accuracy of DBS to expand their use in serological surveillance. We recommend practical considerations to improve standardized reporting for DBS validation studies.

KEYWORDS:

• Capillary blood
• diagnostic accuracy
• dried blood spots
• fingerprick
• serology
• serosurveillance
• venous blood

Article highlights

• Serological surveys, the systematic collection of blood from a target population and testing for pathogen-specific antibodies, are potentially the best way to identify susceptible populations.

• Venous serum and plasma are regarded as the gold standard specimens for measuring IgG and IgM antibodies for vaccine-preventable diseases (VPDs), but the collection, transport, processing, and storage of venous blood samples are particularly challenging in remote and low-resource settings.

• Studies of the diagnostic accuracy of DBS have been conducted, but their methods and results have been highly variable.

• We identified 28 studies that compared DBS with a reference specimen, usually serum. Most studies examined serology for measles, rubella, or dengue.

• We observed wide variation in risk of bias and applicability of the included studies; for most studies, the risk of bias and applicability were unclear due to lack of reported information.

• Few studies reported whether appropriate measures were taken to ensure sample quality.

• Lack of standardization in collection, storage, and testing methods limited systematic comparison across studies. Our findings indicate a need for additional validation studies on the diagnostic accuracy of DBS to enable their expanded use in serological surveillance.

Acknowledgments

This article is dedicated to Sara Lowther, PhD, MPH, who inspired the original work. We would like to thank the following data extractors for their dedicated work in the systematic review process: Mallory Trent, MSPH, Purnima Ravisankar, MHS, Saranya Seetharaman, MPH, and Amie Park, MHS. We would also like to thank Greer Waldrop, MD, ScM for her involvement in the preliminary planning stages. The results of this manuscript were previously presented as an abstract at the Annual Conference on Vaccine Research, Bethesda, MD (virtual conference) in April 2020.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Author contribution statement

We confirm that all authors (1) substantially contributed to the conception and design of the review article and interpreting the relevant literature, and (2) were involved in writing the review article or revised it for intellectual content.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

Funding for this systematic review was provided by the Bill & Melinda Gates Foundation (grant number OPP1094816). FS was supported by FONDECYT-CONCYTEC (grant contract number 246–2015-FONDECYT).