Measles Infection
Conditions
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.
Interventions
BIOLOGICALVerorab
Participants in each group will receive rabies vaccination (standard 3-dose series given as PrEP), with the first dose randomized to either Week 8 or Week 47 after enrollment.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Johns Hopkins University
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
1 Years to 15 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Effect of MeV infection on immune response to a controlled immune stimulus | 5-6 weeks after the first rabies vaccine dose | Proportion of subjects with an RVNA titer ≥ lower limit of quantification |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
Countries
Guinea, Mali
Contacts
STUDY_DIRECTORSally Hunsberger, Ph.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Outcome results
None listed