Clinico-virological investigation of measles complications in immunocompromised pediatric patients

Measles is a highly contagious yet vaccine-preventable disease that is re-emerging in settings with suboptimal immunization, putting immunocompromised children at particular risk. Although measles complications are well documented in children, the data on measles-related complications in immunocompromised hosts remain scarce. We conducted a clinico-virological and bioinformatics investigation of five immunocompromised pediatric measles cases: four with measles-associated encephalitis consistent with measles inclusion body encephalitis (MIBE) and one with severe pneumonia. Cases were confirmed by serology and/or reverse transcription polymerase chain reaction (RT-PCR), and complete measles virus (MeV) genomes were generated directly from clinical specimens. Four children with hematolymphoid malignancies from Maharashtra were infected with MeV genotype D8, and one child with suspected primary immunodeficiency from Tamil Nadu harbored a genotype A strain closely related to the Edmonston-Zagreb vaccine strain. Phylogenetic analysis showed genotype-specific but not complication-specific clustering. Mutational mapping revealed an extensively hypermutated matrix (M) protein in the genotype A strain and conserved subacute sclerosing panencephalitis (SSPE)/ Measles inclusion body encephalitis (MIBE)-associated markers, including proline-glutamate-alanine (PEA) motif changes, in the D8 strains. Additional substitutions in fusion (F) and hemagglutinin (H) proteins localized to heptad-repeat regions, receptor-binding domains, and B-cell epitopes, suggesting effects on cell tropism, neuron-to-neuron spread, and immune evasion. All attempts at virus isolation in Vero and Vero-hSLAM cells failed, consistent with reduced in vitro fitness of these neurotropic variants. These findings demonstrate substantial intra-host evolution of MeV in immunocompromised children with severe complications and emphasize the critical importance of maintaining high measles vaccination coverage (>95%) to protect vulnerable populations through herd immunity.