Assessing the aetiology of measles disease and measles-like illness in Uganda

Abstract

Globally, measles is estimated to cause 140,000 deaths annually. Measles and measles-like illness (MLI) remain a significant cause of morbidity and mortality in children in sub-Saharan Africa including Uganda. Understanding the occurrence of measles outbreaks is of importance as well as elucidating the causes of measles like illnesses among the measles negative individuals. Methods. Ministry of Health measles surveillance data between 2010 and 2023 was analysed. Additionally, measles IgG/avidity assays, measles B3 and Edmonston A neutralisation assays were used to assess the impact of vaccination. Positive samples were sequenced using measles virus-specific genotype B3 amplicon primers that targeted the full-length measles genome using the MinION platform. Metagenomic next generation sequencing and the illumina platform were used to identify viruses associated with MLI in patient samples that had tested negative for measles between 2010 and 2020. Of the 21,453 individuals from the UNEPI surveillance data with laboratory IgM results between 2010 and 2023, 3181 (15%) tested positive while 15,783 (74%) tested negative, and the other 2489 (11%) had no conclusive results. Of the IgM positives, 2660 (84%; with evidence 323 (12%) and without evidence 2337(88%)) were vaccinated while 521 (16%) were not vaccinated. The likelihood of a positive measles IgM test among measles-suspects was significantly lower in vaccinated versus unvaccinated individuals (p<0.0001). There was a strong correlation between the serum neutralizing antibodies against the measles A Edmonston vaccine strain and B3 strain (Pearson correlation coefficient 0.88; p<0.0001). Measles whole genome sequencing indicated minimal nucleotide changes in the B3 genotype circulating in Uganda over a decade. Using metagenomic next-generation sequencing, 133 viruses including rubella, parvovirus and saffold virus among others were identified in 271 samples. The study highlights the ongoing problem of endemic measles infection in Uganda. Our data confirm the effectiveness of measles vaccination in the Ugandan population and support the need to enhance the vaccination coverage of the recently rolled out second MCV2 to prevent significant morbidity and mortality in the country. The measles whole genome sequencing identified 2 clades of highly conserved measles genotype B3. Several MLI viruses were identified using NGS including measles and rubella viruses that were missed using the routine serological diagnostical diagnostic assay. As two dose vaccination is rolled out, vaccine effectiveness should be monitored in the Ugandan population. Mortality data will be very helpful in determining whether one dose is protective against death. Development and optimization of new diagnostic assays which can accurately and timely detect measles like illness viruses.