Iron-deficiency, Iron Deficiency Anemia, Vaccination, Pediatric ALL
Conditions
Brief summary
ID/IDA affects many young children in Africa. Vaccines provide tremendous benefits in LMIC; however, they currently fail to reach their full potential. We need to better understand the causes of vaccine failure, in order to develop new strategies to improve vaccine immunogenicity. This study will contribute to children's health by: (1) providing updated guidelines to better define the prevalence of ID/IDA in early infancy, and its safe and effective control using iron; and (2) providing a new approach to improve response to pediatric vaccines in LMIC, by ensuring adequate iron status at time of vaccination.
Detailed description
Two major pediatric public health goals in LMIC are increasing immunization effectiveness and reducing ID/IDA in children. ID/IDA affects many young children in Africa. Current guidelines do not recommend routine testing of hemoglobin in early infancy, as it is generally believed that most infants are born with adequate iron stores to last 6 months. However, many African infants are born with low iron stores and ID/IDA may develop earlier than generally appreciated, within 2-3 months after birth. Vaccines provide tremendous benefits in LMIC; however, they currently fail to reach their full potential. We need to better understand the causes of vaccine failure, in order to develop new strategies to improve vaccine immunogenicity. Despite lower efficacy in LMIC, these vaccines provide a major benefit because the disease burden is so high; however, if approaches can be found to improve immunogenicity, these vaccines would be even more powerful. For this study, 6 weeks old infants will be randomly assigned to two study groups. Group 1 will receive iron at time of pediatric vaccinations from age 6-24 weeks. Group 2 will receive no iron at time of pediatric vaccinations. All infants will receive a multivitamin syrup from age 6-24 weeks. All infants remaining ID/IDA at age 24 weeks will receive iron. Infants will be followed-up until age 52 weeks.
Interventions
DIETARY_SUPPLEMENTIron syrup
Daily supplementation with iron
DIETARY_SUPPLEMENTMultivitamin syrup
Daily supplementation with multivitamins
Sponsors
Jomo Kenyatta University of Agriculture and Technology Kenya
Karolinka Institute Sweden
University of Oxford
National Institute for Public Health and Environment Netherlands
Jessica Rigutto
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
39 Days to 45 Days
Healthy volunteers
Yes
Inclusion criteria
* Mother at least ≥15 years of age. * 6 weeks (+/- 3 days) of age * Iron deficient (erythrocyte zinc protoporphyrin (ZnPP) \>61 μmol/mol heme) * With or without anemia, but not severely anemic (Hb \>70 g/L) * No malaria * No medical condition that precludes study involvement * Mother HIV negative * Vaginal delivery * No iron supplementation prior to study enrolment * Not wasted (length for height z score of ≥-2) * Not underweight (weight for age z score ≥-2) * From the hospital record, term or late preterm delivery (≥34 weeks) * Full-time breastfed at least until the screening * No vaccines beyond the birth dose of OPV and BCG prior to enrolment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Diphtheria antibody profile | from 6 to 24 weeks |
| Pertussis antibody profile | from 6 to 24 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| infant antiviral immunoglobulin G response | 52 weeks of age | Immunoassay |
| immune cell populations | 6 weeks of age | number and type of immune cells |
| Proteomics | 6 weeks of age | Proteins involved in immune response |
| Transcriptomics | 24 weeks of age | Genes involved in immune response |
| Intestinal fatty acid binding protein | 6 weeks of age | Gut inflammation |
| Calprotectin | 6 weeks of age | Gut inflammation |
| Hemoglobin | 6 weeks of age | — |
| Plasma iron | 6 weeks of age | — |
| Plasma ferritin | 6 weeks of age | — |
| soluble transferrin receptor | 6 weeks of age | — |
| C-reactive protein | 6 weeks of age | — |
| Alpha-glycoprotein | 6 weeks of age | — |
| Tetanus antibody profile | from 6 to 24 weeks | — |
| Haemophilus influenzae b antibody profile | from 6 to 24 weeks | — |
| Pneumococcus antibody profile | from 6 to 24 weeks | — |
| Polio antibody profile | from 6 to 24 weeks | — |
| Anti-vaccine antibody titers | 38 weeks of age | — |
| Anti-vaccine seroconversion | 14 weeks of age | — |
| Anti-vaccine antibody avidity index | 14 weeks of age | percentage of antibodies that remain bound to beads |
| Rotavirus antibody profile | from 6 to 24 weeks | — |
| antiviral immunoglobulin G response | 6 weeks of age | Immunoassay |
Other
| Measure | Time frame | Description |
|---|---|---|
| Human milk oligosaccharide secretor type | 14 weeks of age | secretor yes or no |
| Erythrocyte zinc protoporphyrin | 6 weeks of age | — |
Countries
Kenya, Switzerland
Outcome results
None listed