No evidence of vaccine escape by measles virus: icddr,b study

Preliminary findings from an icddr,b investigation have found no genetic evidence that the measles virus circulating in Bangladesh has escaped the protection provided by the existing vaccine.

According to a press release issued by icddr,b on Sunday, the investigation, conducted jointly with Bangladesh Shishu Hospital and Institute (BSH&I), involved 341 children aged up to 14 years who were admitted to Bangladesh Shishu Hospital & Institute with suspected measles between 20 April and 21 May. Laboratory testing confirmed measles infection in 324 of them.

The findings showed that children who had received both recommended doses of the measles-rubella vaccine were less likely to test positive for measles than those who were unvaccinated or had received only one dose.

Among 146 infants below nine months of age, who were not yet eligible for routine vaccination, 142 tested positive for measles. Of 126 children old enough to be vaccinated but who had received no dose, 122 tested positive. Among 48 children who had received one dose, 44 tested positive, while 16 of the 21 children who had received both recommended doses tested positive.

The researchers cautioned that these figures should not be interpreted as showing that 76% of fully vaccinated children contract measles, as the investigation included only children who had already been admitted to hospital with suspected measles. They said the progressively lower positivity rate among fully vaccinated children was consistent with vaccination providing protection, although a larger population-based study would be needed to determine vaccine effectiveness during the outbreak.

Genetic analysis found that the circulating virus belongs to the B3 genotype, which has been associated with outbreaks in several other countries.

icddr,b conducted phylogenetic analysis of 55 whole-genome virus sequences, including 18 sequenced by icddr,b and 37 by the Institute of Epidemiology, Disease Control and Research (IEDCR). The analysis showed that all viruses belonged to the B3 subclade and were closely related to strains reported elsewhere, with no evidence that the virus had evolved to evade vaccine-induced immunity.

Researchers identified four mutations in regions of the virus's H protein recognised by antibodies. However, they said similar mutations had previously been reported in measles viruses circulating in other countries and that their presence does not indicate resistance to the vaccine. Further laboratory studies are needed to determine whether the mutations have any measurable effect on antibody protection.

The investigation also highlighted a period of vulnerability among young infants before they receive the first routine measles-rubella vaccine at nine months of age. An initial analysis of stored samples from 16 mother-child pairs from an earlier icddr,b birth cohort found that maternal measles antibodies declined rapidly during the first months of life. However, researchers said the sample size was too small to draw definitive conclusions and that further investigation was required.

"The size of this outbreak has understandably raised concerns about whether the vaccine is still working. Our findings provide no evidence that the virus has escaped vaccine protection. We observed lower positivity among children who had received both doses, although this hospital-based investigation cannot provide a population-level estimate of vaccine effectiveness," said Dr Noorjahan Maliha, associate scientist at the Virology Laboratory of the Infectious Diseases Division at icddr,b.

Dr Mustafizur Rahman, senior director of the Infectious Diseases Division at icddr,b, said vaccination remains the most effective way to prevent measles and reduce the risk of severe illness. He said further research is needed to determine why the outbreak became so widespread despite comparatively high reported national vaccination coverage and whether immunity gaps exist in some communities.

Dr KamrunNahar, assistant scientist at the Virology Laboratory, said studies would also examine why some children miss vaccination and help refine Bangladesh's immunisation strategy.

icddr,b Executive Director Dr Tahmeed Ahmed said the organisation had initiated a broader research programme to investigate why some vaccinated children became infected, factors contributing to severe disease and death, the role of malnutrition, and the decline of maternal antibodies in infants.

In response to the outbreak, icddr,b has launched a clinical cohort study across four divisional hospitals, expanded laboratory and genomic surveillance, an enlarged birth-cohort immunology study, a pilot study on zinc alongside standard measles treatment, and community research into why children miss vaccination.

The researchers urged parents and caregivers not to delay routine measles-rubella vaccination and to ensure that children receive all recommended doses in accordance with the government's immunisation programme.