Investigation of Immune Amnesia Following Measles Infection in Select African Regions

Recruiting

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Group 1 - Actue MeV Infection	Verorab	Participants have acute MeV infection.
Group 2 - No Actue MeV Infection	Verorab	Participants do not have acute MeV infection.

Primary Outcome Measures

Name	Time	Method
Effect of MeV infection on immune response to a controlled immune stimulus	5-6 weeks after the first rabies vaccine dose	Geometric mean RVNA titer
Change in pre-existing immunity	Week 13 after baseline	Mean change in a panel of antibody levels over 13 weeks as measured by multiplex serological methods and targeted ELISAs for confirmation.
Effect of MeV infection on immune response to a controlled immune stimulus (rabies vaccination)	14 days after last PrEP regimen vaccination	Proportion of subjects with rabies virus neutralizing antibodies (RVNA) titer ≥ 0.5 IU/mL as measured by rapid fluorescent focus inhibition test

Secondary Outcome Measures

Name	Time	Method
Change in pre-existing immunity	Week 52 after baseline	Mean change in a panel of antibody levels over 52 weeks as measured by multiplex serological methods and targeted ELISAs for confirmation.
Change in healthcare system encounters	1 year following enrollment	Mean number of non-study sick visit healthcare system encounters during the 1-year follow-up.

Locations (2): University Clinical Research Center (UCRC) University of Sciences, Techniques and Technologies of Bamako
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Bamako, Mali
Partnership of Clinical Research in Guinea, Partenariat Pour La Recherche Clinique en Guinée (PREGUI)
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Conakry, Guinea