This study will investigate different hypotheses for the mechanisms underlying excess delayed mortality after measles or high titre measles Vaccines. Morbidity will be monitored after mild measles (among children recruited through community-based surveillance) or complicated measles (recruited at hospital), and compared to controls (a cohort of healthy children and a cohort of children hospitalised with other illnesses). 110 children will be recruited in each group, and will be examined twice weekly in the first 6 weeks then weekly until 8 months after recruitment. To investigate the hypothesis that measles virus causes a prolonged bias to a type 2 helper T cell response (which is predicted to increase the antibody response to infectious agents), the response to the hepatitis B vaccine series commenced 6 weeks after recruitment will be compared between cases and controls. In each analysis, age, sex, socioeconomic status, nutritional status and micronutrient levels will be assessed as possible confounders.
On a subsample of subjects aged 6-11 months, (n=25 per group), the study will measure the lymphoproliferative response to stimulation with measles virus and measles virus purified membrane proteins, cytokine profiles, and changes in surface molecules, particularly those involved in the MV receptor complex, on sub-populations of peripheral blood mononuclear cells (PBMCS). Two groups of measles vaccines (n=25 per group) will also be studied, one group receiving two doses of standard titre measles vaccines at ages 6 and 9 months, the other a single dose at 9 months, to allow comparison of the effects of wild versus vaccine virus on cellular function. The presence of measles virus in PBMC samples and subpopulations in children with acute measles will be compared to Vaccinees at different time points following exposure. These studies will help to understand the basis for immune suppression after measles, to determine the extent of immunosuppression after measles vaccination, and to raise hypotheses for the mechanism of differences in persistence of immunity after measles or measles vaccination. This information will be invaluable in the development and evaluation of novel measles vaccines.
Funding SchemeCSC - Cost-sharing contracts