To understand the current measles mortality burden, and to mitigate the future burden, it is crucial to have robust estimates of measles case fatalities. Estimates of measles case-fatality ratios (CFRs) that are specific to age, location, and time are essential to capture variations in underlying population-level factors, such as vaccination coverage and measles incidence, which contribute to increases or decreases in CFRs. In this study, we updated estimates of measles CFRs by expanding upon previous systematic reviews and implementing a meta-regression model. Our objective was to use all information available to estimate measles CFRs in low-income and middle-income countries (LMICs) by country, age, and year. For this systematic review and meta-regression modelling study, we searched PubMed on Dec 31, 2020 for all available primary data published from Jan 1, 1980 to Dec 31, 2020, on measles cases and fatalities occurring up to Dec 31, 2019 in LMICs. We included studies that previous systematic reviews had included or which contained primary data on measles cases and deaths from hospital-based, community-based, or surveillance-based reports, including outbreak investigations. We excluded studies that were not in humans, or reported only data that were only non-primary, or on restricted populations (eg, people living with HIV), or on long-term measles mortality (eg, death from subacute sclerosing panencephalitis), and studies that did not include country-level data or relevant information on measles cases and deaths, or were for a high-income country. We extracted summary data on measles cases and measles deaths from studies that fitted our inclusion and exclusion criteria. Using these data and a suite of covariates related to measles CFRs, we implemented a Bayesian meta-regression model to produce estimates of measles CFRs from 1990 to 2019 by location and age group. This study was not registered with PROSPERO or otherwise. We identified 2705 records, of which 208 sources contained information on both measles cases and measles deaths in LMICS and were included in the review. Between 1990 and 2019, CFRs substantially decreased in both community-based and hospital-based settings, with consistent patterns across age groups. For people aged 0-34 years, we estimated a mean CFR for 2019 of 1·32% (95% uncertainty interval [UI] 1·28-1·36) among community-based settings and 5·35% (5·08-5·64) among hospital-based settings. We estimated the 2019 CFR in community-based settings to be 3·03% (UI 2·89-3·16) for those younger than 1 year, 1·63% (1·58-1·68) for age 1-4 years, 0·84% (0·80-0·87) for age 5-9 years, and 0·67% (0·64-0·70) for age 10-14 years. Although CFRs have declined between 1990 and 2019, there are still large heterogeneities across locations and ages. One limitation of this systematic review is that we were unable to assess measles CFR among particular populations, such as refugees and internally displaced people. Our updated methodological framework and estimates could be used to evaluate the effect of measles control and vaccination programmes on reducing the preventable measles mortality burden. Bill & Melinda Gates Foundation; Gavi, the Vaccine Alliance; and the US National Institutes of Health.

A better understanding of population-level factors related to measles case fatality is needed to estimate measles mortality burden and impact of interventions such as vaccination. This study aimed to develop a conceptual framework of mechanisms associated with measles case fatality ratios (CFRs) and assess the scope of evidence available for related indicators. Using expert consultation, we developed a conceptual framework of mechanisms associated with measles CFR and identified population-level indicators potentially associated with each mechanism. We conducted a literature review by searching PubMed on 31 October 2021 to determine the scope of evidence for the expert-identified indicators. Studies were included if they contained evidence of an association between an indicator and CFR and were excluded if they were from non-human studies or reported non-original data. Included studies were assessed for study quality. Expert consultation identified five mechanisms in a conceptual framework of factors related to measles CFR. We identified 3772 studies for review and found 49 studies showing at least one significant association with CFR for 15 indicators (average household size, educational attainment, first- and second-dose coverage of measles-containing vaccine, human immunodeficiency virus prevalence, level of health care available, stunting prevalence, surrounding conflict, travel time to major city or settlement, travel time to nearest health care facility, under-five mortality rate, underweight prevalence, vitamin A deficiency prevalence, vitamin A treatment, and general malnutrition) and only non-significant associations for five indicators (antibiotic use for measles-related pneumonia, malaria prevalence, percent living in urban settings, pneumococcal conjugate vaccination coverage, vitamin A supplementation). Our study used expert consultation and a literature review to provide additional insights and a summary of the available evidence of these underlying mechanisms and indicators that could inform future measles CFR estimations.

Evaluating vaccine-related research is critical to maximize the potential of vaccination programmes. The WHO Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) provides an independent review of research that estimates the performance, impact and value of vaccines, with a particular focus on transmission and economic modelling. On 11-13 September 2023, IVIR-AC was convened for a bi-annual meeting where the committee reviewed research and presentations across eight different sessions. This report summarizes the background information, proceedings and recommendations from that meeting. Sessions ranged in topic from timing of measles supplementary immunization activities, analyses of conditions necessary to meet measles elimination in the South-East Asia region, translating modelled evidence into policy, a risk-benefit analysis of dengue vaccine, COVID-19 scenario modelling in the African region, therapeutic vaccination against human papilloma virus, the Vaccine Impact Modelling Consortium, and the Immunization Agenda 2030 vaccine impact estimates.

Background Measles 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. Methods On 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). Findings We 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. Interpretation While 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. Funding Bill & Melinda Gates Foundation; Gavi, the Vaccine Alliance; US National Institutes of Health Evidence before this study On 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 study Our 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 evidence Accounting 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.