Measuring changes in transmission of neglected tropical diseases, malaria, and enteric pathogens from quantitative antibody levels

• Published in: PLoS neglected tropical diseases 2017-05, Vol.11 (5), p.e0005616
• Main Authors: Arnold, Benjamin F, van der Laan, Mark J, Hubbard, Alan E, Steel, Cathy, Kubofcik, Joseph, Hamlin, Katy L, Moss, Delynn M, Nutman, Thomas B, Priest, Jeffrey W, Lammie, Patrick J
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Age Factors; Aged; Aged, 80 and over; Animals; Antibodies; Antibodies - blood; Antibody response; Antigens; Artificial intelligence; Assaying; Bacteria; Balances (scales); Biology and Life Sciences; Child; Child, Preschool; Children; Correlation analysis; Cross-Sectional Studies; Cryptosporidium; Cryptosporidium parvum; Disease control; Disease prevention; Disease transmission; Diseases; Distribution; Drugs; E coli; Elephantiasis, Filarial - epidemiology; Elephantiasis, Filarial - immunology; Exposure; Female; Filariasis; Gastrointestinal Diseases - epidemiology; Gastrointestinal Diseases - immunology; Giardia; Haiti - epidemiology; Human diseases; Humans; Humoral immunity; Immunity; Immunoglobulin G; Infant; Infant, Newborn; Infectious diseases; Inoculation; Insecticides; Intervention; Learning algorithms; Levels; Machine learning; Malaria; Malaria - epidemiology; Malaria - immunology; Male; Measurement; Measurement methods; Medical laboratories; Medicine and Health Sciences; Methods; Middle Aged; Multiplexing; Neglected Diseases - epidemiology; Neglected Diseases - immunology; Nigeria - epidemiology; Parasitic diseases; Pathogens; Physiological aspects; Plasmodium falciparum; Polynesia - epidemiology; Populations; Public health; Research and Analysis Methods; Resolution; Risk factors; Salmonella; Seroepidemiologic Studies; Serologic Tests - methods; Serology; Social Sciences; Studies; Surveillance; Surveys; Transmission; Tropical climate; Tropical diseases; United States - epidemiology; Vector-borne diseases; Viruses; Young Adult
• ISSN: 1935-2735; 1935-2727; 1935-2735
• DOI: 10.1371/journal.pntd.0005616

Serological antibody levels are a sensitive marker of pathogen exposure, and advances in multiplex assays have created enormous potential for large-scale, integrated infectious disease surveillance. Most methods to analyze antibody measurements reduce quantitative antibody levels to seropositive and seronegative groups, but this can be difficult for many pathogens and may provide lower resolution information than quantitative levels. Analysis methods have predominantly maintained a single disease focus, yet integrated surveillance platforms would benefit from methodologies that work across diverse pathogens included in multiplex assays. We developed an approach to measure changes in transmission from quantitative antibody levels that can be applied to diverse pathogens of global importance. We compared age-dependent immunoglobulin G curves in repeated cross-sectional surveys between populations with differences in transmission for multiple pathogens, including: lymphatic filariasis (Wuchereria bancrofti) measured before and after mass drug administration on Mauke, Cook Islands, malaria (Plasmodium falciparum) before and after a combined insecticide and mass drug administration intervention in the Garki project, Nigeria, and enteric protozoans (Cryptosporidium parvum, Giardia intestinalis, Entamoeba histolytica), bacteria (enterotoxigenic Escherichia coli, Salmonella spp.), and viruses (norovirus groups I and II) in children living in Haiti and the USA. Age-dependent antibody curves fit with ensemble machine learning followed a characteristic shape across pathogens that aligned with predictions from basic mechanisms of humoral immunity. Differences in pathogen transmission led to shifts in fitted antibody curves that were remarkably consistent across pathogens, assays, and populations. Mean antibody levels correlated strongly with traditional measures of transmission intensity, such as the entomological inoculation rate for P. falciparum (Spearman's rho = 0.75). In both high- and low transmission settings, mean antibody curves revealed changes in population mean antibody levels that were masked by seroprevalence measures because changes took place above or below the seropositivity cutoff. Age-dependent antibody curves and summary means provided a robust and sensitive measure of changes in transmission, with greatest sensitivity among young children. The method generalizes to pathogens that can be measured in high-throughput, multiplex serological assays, an