CompletedNot Applicable

Causes of Rotavirus Vaccine Failure in Zambian Children

Zambia420 participantsStarted 2012-04-01

Plain-language 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.

Who can participate

Age range

6 Weeks – 15 Weeks

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

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.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Proportion of Immunized Infants Exposed to High Breast Milk Anti-rotavirus Immunoglobulin-A Who Fail to Seroconvert

Timeframe: 1 month following full immunization

Proportion of Immunized Infants Exposed to Transplacentally-acquired, Rotavirus-specific, Infant Serum IgG Who Fail to Sero-convert.

Timeframe: 1 month after full immunisation

Proportion of Immunized Infants Exposed to Maternal HIV Infection Who Fail to Seroconvert

Timeframe: 1 month after the two vaccine doses

Trial details

NCT IDNCT01886833

SponsorCentre for Infectious Disease Research in Zambia

Sponsor typeOTHER

Study typeOBSERVATIONAL

Primary completion2015-04-30

Results submitted2016-05-30

View on ClinicalTrials.gov More Diarrhoea trials