Investigation of Immune Amnesia Following Measles Infection in Select African Regions

Investigation of Immune Amnesia Following Measles Infection in Select African Regions

The goal of this observational study is to investigate the effects of measles virus (MeV) infection on pre-existing immunity, vaccine response, and susceptibility to subsequent illness in children aged 1-15 either with or without acute MeV infection.

This is a prospective, observational, longitudinal study to be conducted in West Africa. Eligible children will be enrolled into 1 of 2 arms: acute MeV infection (cases) or no acute MeV infection (controls) as assessed using upper respiratory specimens and blood samples. Blood samples will be collected at screening/enrollment (Day 0) and follow-up visits on Day 14, Week 13, and Week 52, and tested for humoral and cellular immune responses to endemic pathogens to determine changes in antibody diversity and antibody secreting cells (ASCs). All children in each arm will receive rabies vaccination (standard 3-dose series given as pre-exposure prophylaxis [PrEP]), with the first dose randomized to either Week 8 or Week 47 after enrollment. Biological samples will be collected after vaccination to assess if the immune stimulus (rabies vaccine) response differs: 1) between children with and without MeV infection, and 2) based on the timing of the receipt of the rabies vaccine.

Inclusion Criteria:

• Aged 1 to 15 years.
• Ability of the participant's legal or culturally acceptable representative to provide informed consent.
• Ability to give assent, as appropriate.
• Stated willingness of parent/guardian and participant as appropriate, to comply with all study procedures.
• Willingness to receive rabies vaccine.
• Meet the criteria for assignment to Group 1 or Group 2, as follows:
• Group 1, cases (acute MeV infection):
• Clinical signs and symptoms suggestive of acute MeV infection (Koplik spots or skin rash) AND
• Laboratory confirmed measles:
• Upper respiratory specimen (swab) PCR for measles positive, OR
• Serum IgM for measles positive.
• Group 2, controls (no acute MeV infection):
• No clinical signs and symptoms suggestive of acute MeV infection (Koplik spots or skin rash) AND
• Upper respiratory specimen (swab) PCR negative for MeV AND
• Serum measles IgM negative AND
• Serum measles IgG positive and previously vaccinated for measles (2nd dose will be offered if appropriate). If serum measles IgG is negative, participant must be willing to be vaccinated regardless of prior measles vaccine history to meet this criterion.

Exclusion Criteria:

• HIV infection or any other immunosuppressive condition or medications.
• Pregnant or lactating.
• History of prior measles or immunologic evidence of prior measles in the absence of prior measles vaccination.
• Severe anemia, defined as hemoglobin less than 8 g/dL.
• Any acute or chronic condition which, in the opinion of the investigator, constitutes a contraindication to participation in this study.