Integrated Serologic Surveillance of Population Immunity and Disease Transmission

Abstract

Antibodies are unique among biomarkers in their ability to identify persons with protective immunity to vaccine-preventable diseases and to measure past exposure to diverse pathogens. Most infectious disease surveillance maintains a single-disease focus, but broader testing of existing serologic surveys with multiplex antibody assays would create new opportunities for integrated surveillance. In this perspective, we highlight multiple areas for potential synergy where integrated surveillance could add more value to public health efforts than the current trend of independent disease monitoring through vertical programs. We describe innovations in laboratory and data science that should accelerate integration and identify remaining challenges with respect to specimen collection, testing, and analysis. Throughout, we illustrate how information generated through integrated surveillance platforms can create new opportunities to more quickly and precisely identify global health program gaps that range from undervaccination to emerging pathogens to multilayered health disparities that span diverse communicable diseases.

Keywords: Cambodia; United States; antibodies; communicable diseases; disease elimination; disease surveillance; emerging; immunity; immunologic surveillance; malaria; multiplex antibody assays; neglected diseases; neglected tropical diseases; transmission; vaccination.

Figure 1

Tetanus toxoid antibody response of 2,150 women, by age and reproductive status, Cambodia, 2012. Specimens were collected from women who had (parous) and had not (nulliparous) previously given birth in a nationally representative immunization coverage survey (23) and measured by using the Luminex platform (Luminex Corporation, Austin, TX, USA). A) Mean antibody response. B) Percentage and 95% CIs of women seroprotected (>100 MFI) (23). We estimated age-dependent means and seroprevalence using previously described methods (24). Data set and computational notebook are available through the Open Science Framework (https://osf.io/2kr8b). MFI – bg, mean fluorescence intensity minus background.

Figure 2

Antibody response to tetanus toxoid and causative agents of malaria and NTDs measured by multiplex bead assay among 2,150 women, Cambodia, 2012. Specimens were measured by using the Luminex platform (Luminex Corporation, Austin, TX, USA) (25). A) Relationship between pairs of antibodies measured by mean antibody response (log₁₀ MFI – bg) in each of the 100 sampling clusters. Scatter plots include nonparametric locally weighted regression fits trimmed to reduce edge effects. Correlation ellipses depict the strength of the association on the basis of the Pearson correlation (r estimates). Both axes indicate mean antibody response. B) Heatmap of mean antibody response to tetanus toxoid and pathogens that cause malaria and NTDs in 100 sampling clusters stratified by region and then sorted by mean antibody response. Data set and computational notebook are available through the Open Science Framework (https://osf.io/2kr8b). MFI – bg, mean fluorescence intensity minus background; MSP, merozoite surface protein; NTDs, neglected tropical diseases; SAG2A, surface antigen 2A; VPDs, vaccine-preventable diseases.