Surveillance and agnostic capture sequencing of samples from individuals with rash-associated illness in Mali indicates regional transmission of measles virus from West and Central Africa

Abstract

Measles is vaccine-preventable extremely contagious disease caused by the measles virus. High vaccination coverage is needed to prevent outbreaks of disease. Although molecular surveillance of measles is critical to characterize outbreaks and track viral evolution, few whole-genome sequences of measles virus from West Africa are available despite continual outbreaks in the region. Using VirCapSeq-VERT, an enhanced and comprehensive metagenomic sequencing technique that allows for simultaneous identification of all vertebrate viruses, 23 wild-type near-complete genomes of measles virus from across Mali were obtained from samples collected between January 2012 to October 2022. Other febrile rash illnesses were also identified by VirCapSeq-VERT, demonstrating the advantage of using broad detection agnostic methods when the clinical diagnosis is unclear. Whereas one measles virus sequence was consistent with measles vaccine-associated rash illness (VARI), the remaining 38 were classified within the B3.1 genotype. Broad surveillance throughout Mali reveals regional measles virus transmission across West and Central Africa into Mali, while local clinical testing in Bamako shows stable sequence conservation within genotype B3.1 evolving from Nigerian sequences. The genomic information generated in this study is critical in addressing the lack of whole genome sequences available in West Africa and these findings show the importance of phylogenetically tracking measles outbreaks given recent increases in measles cases globally.

Keywords: Genome; Mali; Measles; Phylogeny.

Fig. 1.

Map of Mali displaying the location of measles cases identified by VirCapSeq-VERT from ECERID and INSP samples. The 6 Communes of Bamako, where ECERID samples were collected, is shown as a detailed insert. Green circles indicate where measles-positive ECERID participants resided. Red circles indicate where measles-positive samples were collected as part of the measles public health surveillance activities of INSP. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)

Fig. 2.

Baseline signs and symptoms of ECERID study participants with measles infections detected by VirCapSeq-VERT. Detailed clinical data was collected during the baseline visit for all ECERID patients. Study inclusion criteria included the presence of an acute fever of unknown origin. This presentation of signs and symptoms appears to be a subset of the overall sign/symptom data from ECERID.

Fig. 3.

Maximum clade credibility tree (MCC) consisting of measles virus genotype B3 nucleoprotein sequences from West and Central Africa, generated by Bayesian Markov chain Monte Carlo method. Clusters of sequences are noted in the column at right, distinguished by INSP (N=11) and ECERID (N=17) study collections.

Fig. 4.

Maximum-likelihood phylogenetic analysis of measles virus genotype A vaccine strains and the vaccine derived sequence obtained from this study (MLS0151).