N/A
N=420
Causes of Rotavirus Vaccine Failure in Zambian Children
Diarrhoea
Bottom Line
View on ClinicalTrials.gov: NCT01886833 ↗Enrolled (actual)
420
Serious AEs
12.1%
Results posted
Aug 2018
Primary outcome: Primary: Proportion of Immunized Infants Exposed to High Breast Milk Anti-rotavirus Immunoglobulin-A Who Fail to Seroconvert — 0.602 Proportion of exposed infants
Study Design & Population
- Study type
- Observational
- Phase
- N/A
- Interventions
- —
- Age
- Pediatric · 0+ yrs
- Sex
- All
- Sponsor
- Centre for Infectious Disease Research in Zambia
- Primary completion
- Apr 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Proportion of Immunized Infants Exposed to High Breast Milk Anti-rotavirus Immunoglobulin-A Who Fail to Seroconvert |
0.602 | — |
| PRIMARY Proportion of Immunized Infants Exposed to Transplacentally-acquired, Rotavirus-specific, Infant Serum IgG Who Fail to Sero-convert. |
— | — |
| PRIMARY Proportion of Immunized Infants Exposed to Maternal HIV Infection Who Fail to Seroconvert |
0.704 | — |
| SECONDARY Proportion of Immunized Infants With Low Micronutrient Levels (as Indicated by Serum Zinc and Vitamin A), Who Fail to Seroconvert |
0.5 | — |
Summary
Zambia recently introduced routine infant immunization against rotavirus - the most important cause of severe gastroenteritis and diarrhoea mortality in children. Although vaccines like Rotarix are a cost effective tool against infectious diseases, live oral vaccines can be less immunogenic and efficacious in developing world settings as compared with industrialized countries. Reasons behind this phenomenon are not well understood, but may relate to continued maternal antigen exposure and high level maternal immunity that is passed to the foetus/newborn transplacentally and/or through breast milk.
Therefore, three arising hypotheses include: (i) high-level rotavirus-specific maternal immunity (in the form of anti-rotavirus breast-milk immunoglobulin A (IgA) and transplacental serum IgG) is a major contributor to failed seroconversion following infant vaccination. (ii) Malnutrition negatively impacts infant immunity and increases the risk of post-vaccination rotavirus gastroenteritis. (iii) Introduction of rotavirus vaccine will alter the molecular epidemiology of circulating rotavirus strains detected in vaccinated children presenting with severe diarrhea.
To address these hypotheses, the proposed study will recruit a prospective cohort of 420 mother-infant pairs. These will be enrolled at the time of vaccination and followed for up to four years. Baseline immunological status will be ascertained and seroconversion rates determined a month after full immunization. Incident rotavirus gastroenteritis will be monitored in the vaccinated infants whenever episodes of diarrhoea occur; through this surveillance, the sero-strains of rotaviruses causing disease will be tracked over the four year period. Contributions of HIV infection both in mothers and infants, vitamin A and zinc deficiency, weight for age Z-scores as well as mid upper arm circumference will also be assessed. Knowledge gained from this study will inform future interventional trials on strategies to improve rotavirus vaccine effectiveness in the developing world.
Eligibility Criteria
Inclusion Criteria
- Mother willing to participate voluntarily and able to provide signed informed consent (with witness in the case of illiterate participant)
- Infant eligible for rotavirus vaccine immunization as per national policy (male or female infant, 6-12 weeks old)
- Mother willing to undergo study procedures, including questionnaires, HIV counselling and testing, CD4 testing, and provide breast milk and blood sample at enrolment.
- Mother willing for child to undergo study procedures including full-course rotavirus vaccination, phlebotomy at enrolment and 1 month post-rotavirus vaccination, and presentation to clinic for collection of stool sample when infant has diarrhoea.
- Plans to remain resident in the area and willing to come for scheduled visits for the duration of the study.
Exclusion Criteria
- Contraindication to rotavirus vaccination.
- Previous administration of rotavirus vaccine to child.
- Recent immunosuppressive therapy in child (including high-dose systemic corticosteroids).
- History of ever receiving a blood transfusion or blood products, including immunoglobulins within the last 6 months, for mother and child.
- Mother plans for herself or child to move away from the study catchment area within the next two years.
- Any condition deemed by the study investigator to pose potential harm to the participants or jeopardize the validity of study results.
Data sourced from ClinicalTrials.gov (NCT01886833). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.