Evaluating scope and bias of population-level measles serosurveys: a systematic review and bias assessment

BackgroundMeasles seroprevalence data has potential to be a useful tool for understanding transmission dynamics and for decision making efforts to strengthen immunization programs. In this study, we conducted a systematic review and bias assessment of all primary data on measles seroprevalence in low- and middle-income countries published from 1962 to 2021. MethodsOn March 9, 2022, we searched PubMed for all available data. We included studies containing primary data on measles seroprevalence and excluded studies if they were clinical trials or brief reports, from only health care workers, suspected measles cases, or only vaccinated persons. We extracted all available information on measles seroprevalence, study design, and seroassay protocol. We conducted a bias assessment based on multiple categories and classified each study as having low, moderate, severe, or critical bias. This review was registered with PROSPERO (CRD42022326075). FindingsWe identified 221 relevant studies across all World Health Organization regions, decades and unique age ranges. The overall crude mean seroprevalence across all studies was 78.00% (SD: 19.29%) and median seroprevalence was 84.00% (IQR: 72.75 - 91.66%). We classified 80 (36.2%) studies to have severe or critical overall bias. Studies from country-years with lower measles vaccine coverage or higher measles incidence had higher overall bias. InterpretationWhile many studies have underlying bias, many studies provide data that can be used to inform modelling efforts to examine measles dynamics and programmatic decisions to reduce measles susceptibility. FundingBill & Melinda Gates Foundation; Gavi, the Vaccine Alliance; US National Institutes of Health Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSOn August 20, 2023, we searched PubMed for systematic reviews published from January 1, 1980 to August 20, 2023 using the search terms "measles" AND "sero*". We included studies if they were a systematic review of measles seroprevalence data and excluded studies that did not contain information on measles seroprevalence, were not systematic reviews, only included data from persons within a subpopulation (e.g., pregnant people or healthcare workers), or were of head-to-head laboratory comparisons of assay methodology. We identified one previous systematic review, by Thompson and Odahowski, published in 2016 and including data through mid-2014. That review identified 220 measles and/or rubella seroprevalence studies from all countries globally. Study authors published a descriptive summary of seroprevalence trends by age in a five select countries and a narrative summary of high-level epidemiologic trends in the underlying data, including information available on maternal antibody waning. Beyond these select summary findings, that study did not separately report seroprevalence from each study identified in the analysis, nor did it include any information on study design or population-representativeness. While study authors noted general limitations related to the different methods used across studies, they did not include any specific information on assay type, selection biases or other characteristics that could influence the accuracy of results or include data in a tabular format, which limits the utility of this study for subsequent analyses. Added value of this studyOur study builds upon the known body of data on measles seroprevalence from low- and middle-income countries in multiple ways. First, we included data published up to December 31, 2021 and from non-English language studies. Second, we extracted all available relevant information on study design characteristics and assay protocol used in each study to measure seroprevalence. Then, we constructed a bias assessment framework and conducted a bias assessment across multiple categories (study selection of participants, measurement tool and classification of immunity, and reporting of results) to classify the underlying bias in each study. Finally, we compared seroprevalence estimates across regions and bias levels, and bias levels among various study location characteristics. Implications of all the available evidenceAccounting for study design and seroassay protocol used in serosurveys can influence interpretation of population-level seroprevalence estimates. Our systematic review and bias assessment provides an updated landscape of serological studies and highlights key biases in the current literature. It provides a repository of measles seroprevalence data, along with corresponding critical information on factors that influence population-representativeness and overall sensitivity of the measurement assay used in each study, that can be used to inform measles susceptibility estimates useful for planning targeted vaccination efforts.