Introduction
This module defines serosurveys and describes the uses of serosurveys.
Learning Objectives
- Define serosurvey
- Identify uses of serosurveys
Topics covered in this module
- Key definitions including what is a serosurvey
- Uses of serosurveys
What is a Serosurvey?
A serosurvey is the collection and testing of blood (or proxy specimen such as oral fluid) from a specimen of a defined population over a specified period of time to estimate the prevalence of IgG antibodies against an infectious pathogen as an indicator of exposure, disease burden, or immunity.
Key Definitions
Seropositivity: Detection of an IgG antibody level above a predefined threshold for a specific infectious pathogen. This threshold determines the sensitivity and specificity of the assay and may vary depending on the purpose of the serosurvey. Seropositivity may be correlated with protection against infection or disease.
Seroprevalence: Proportion of people in a population who test seropositive for a specific infectious pathogen. This is often presented as a weighted percentage of the total number of individuals tested.
Seroprotection: Detection of IgG antibody levels above a protective threshold. Protective antibody thresholds are not well defined for many pathogens.
Serosurveillance: Systematic collection and testing of specimens for antibodies against a specific pathogen or group of pathogens on a periodic or ongoing basis to assess changes in seroprevalence over time.
Definitions modified from: WHO. Guidelines on the Use of Serosurveys in Support of Measles and Rubella Elimination. Available online
These modules focus on IgG antibodies as these are the most commonly detected antibodies in serosurveys and are typically the best correlate of protection. However, serosurveys can be used to detect IgM antibodies as markers of recent infection or IgA antibodies as markers of mucosal immunity. Some serosurvey detect pathogen antigens such as those for hepatitis B virus (hepatitis B surface antigen). And some serologic assays, such as plaque reduction neutralization assays, detect antibodies from different classes (i.e.., IgG and IgM antibodies).
Testing for presence of antibodies: IgG versus IgM
IgM: Immunoglobulin M is marker of current or recent infection. IgM antibodies persist only for several weeks to months.
IgG: Immunoglobulin G is a marker of exposure to the pathogen or a vaccine. IgG antibodies are longer lasting than IgM antibodies, sometimes for decades. Most often the target for serosurveys.
What are the Uses of Serosurveys?
Serosurveys can be used to estimate:
- Exposure to a pathogen
- Prevalence of infection
- Immunity gaps
- Key parameters for infectious disease modelling
Exposure to a pathogen
- Serosurveys can be used to estimate the cumulative exposure to a pathogen across age groups and in different geographical regions.
- Whether seroprevalence is an estimate of exposure depends in part on how fast antibodies wane. If antibodies are long lasting, seroprevalence may be a good estimate of cumulative exposure. If antibodies wane quickly, seroprevalence may only estimate recent exposure.
- Serosurveys can be particularly useful for detecting subclinical or asymptomatic infections (e.g. rubella virus or SARS-CoV-2) and thus can be useful in estimating infection mortality ratios.
- Serosurveys are also useful in estimating disease burden when disease surveillance systems are weak or lack sensitivity.
Prevalence of infection
- Serosurveys can be used to estimate the prevalence of chronic infections such as with HIV or hepatitis C virus infection, for which seropositivity is a marker of current infection.
Immunity gaps
- When seroprevalence is correlated with immunity, serosurveys can be used to identify immunity gaps in different age groups, geographical locations, or subpopulations.
- Identification of immunity gaps can inform assessments of outbreak risk and the need for targeted immunization activities.
- Serosurveys can be particularly useful in identifying immunity gaps within subpopulations for which vaccination coverage data may be missing or incomplete (e.g., adults, migrants, refugees or displaced populations).
Key parameters for infectious disease modelling
- Serosurveys can be used to estimate key parameters for infectious disease modelling, such as the reproductive number and the force of infection. Such parameters are estimated using age-specific seroprevalence curves.
For Vaccine-Preventable Diseases, Why Not Just Do a Vaccination Coverage Survey?
Vaccination coverage surveys estimate the proportion of persons vaccinated against a pathogen by recall, immunization card, or medical records. They do not estimate seroprotection to a pathogen. Not all vaccinated persons develop a measurable antibody response and protective immunity. Seropositivity may result from infection with the pathogen in addition to vaccination. Research has shown that it is difficult to predict immunity gaps to measles across age-groups using vaccination coverage data when immunity is conferred by both natural infection and vaccination.
Figure. Vaccination coverage versus immunity in a population.
Illustration of a routine immunization system with 85% measles vaccination coverage, 95% vaccine efficacy, and measles virus infection conferring immunity. Four subpopulations result: 1) unvaccinated but immune from natural infection (solid red); 2) vaccinated and immune (solid green); 3) unvaccinated and non-immune (open); and 4) vaccinated and non-immune because of vaccine failure (green hatched). The total proportion immune is the combination of those immune through vaccination and natural infection.
Table. Comparison of vaccination coverage surveys and serosurveys
| Vaccination coverage surveys | Serosurveys |
|---|---|
| Estimates proportion of population vaccinated but not proportion protected.
Vaccination does not always confer immunity. Immunity may wane over time. |
Provides direct estimate of seroprevalence and, if correlated, population immunity.
May be able to distinguish vaccination from natural infection for some pathogens. |
| Only relevant for populations receiving vaccines, such as young children through routine immunization.
Data on older children and adults are often not available. |
Can provide an estimate of seroprevalence in age groups for which one cannot conduct a vaccination coverage survey, such as adolescents, adults or refugee populations. |
| Requires data collection from home-based vaccination card, parental recall, or health facility records.
Parental recall may not be accurate. |
Requires biospecimen collection, transport, and laboratory testing with a valid test.
More logistically complicated, costly and requires high quality lab testing capacity. |
| May be prone to information bias related to vaccine receipt in the absence of a vaccination card or medical record. | May be prone to selection bias if high refusals for biospecimen collection. |
References
- World Health Organization. 2013. Guidance on conducting serosurveys in support of measles and rubella elimination in the WHO European Region. WHO Regional Office for Europe, Copenhagen.
- Cutts FT, Hanson M. 2016. Seroepidemiology: an underused tool for designing and monitoring vaccination programmes in low- and middle-income countries. Trop Med Int Health 21:1086-98.
- Metcalf CJ, Farrar J, Cutts FT, Basta NE, Graham AL, Lessler J, Ferguson NM, Burke DS, Grenfell BT. 2016. Use of serological surveys to generate key insights into the changing global landscape of infectious disease. Lancet 388:728-30.
- Travassos MA, Beyene B, Adam Z, Campbell JD, Mulholland N, Diarra SS, Kassa T, Oot L, Sequeira J, Reymann M, Blackwelder WC, Pasetti MF, Sow SO, Steinglass R, Kebede A, Levine MM. 2015. Strategies for Coordination of a Serosurvey in Parallel with an Immunization Coverage Survey. Am J Trop Med Hyg 93:416-424.
- Wilson SE, Deeks SL, Hatchette TF, Crowcroft NS. 2012. The role of seroepidemiology in the comprehensive surveillance of vaccine-preventable diseases. CMAJ 184:E70-6.