Characterization of Pertussis Risk and Antibody Transfer in Infants in Sarlahi District, Nepal: A Community-Based Prospective Cohort Study
Hughes, Michelle Mergler
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Background: Pertussis is estimated to cause 2% of childhood deaths globally and is a growing public health problem. Infants are at greatest risk of morbidity and mortality. Maternal vaccination during pregnancy may be effective to prevent pertussis in young infants but population-based estimates of disease burden in infants, an understanding of maternal and infant pertussis antibody levels, and of efficiency of maternal to infant antibody transfer in a low-income South Asian setting are lacking. This dissertation provides a population-based estimate of the incidence of infant pertussis and associated clinical symptoms in Nepal. The timing of infant pertussis vaccination and risk factors for delay in Nepal are examined. The prevalence of maternal and infant pertussis toxin antibody and the efficiency of transfer were estimated. Methods: The pertussis study was nested within a prospective, community-based, randomized controlled trial of maternal influenza vaccination during pregnancy. In Sarlahi District, Nepal, over a two-year period between April 2011 and April 2013, approximately 3,700 women were enrolled. From birth to 6 months infants were visited in their homes weekly to ascertain if they had experienced any respiratory symptoms or received any vaccinations in the prior week. If any respiratory symptoms had occurred, a nasal swab was collected and tested with a multi-target pertussis PCR assay. A subset of paired blood samples from mothers and infants were collected at delivery and tested for pertussis toxin (PT) antibodies by ELISA. Infant, maternal, and household characteristics were captured at enrollment, birth and at 6 months follow-up. The incidence of pertussis from age 0 to 6 months was estimated. Pertussis vaccination coverage and time to vaccination were estimated. Multivariate regression models were used to determine risks associated with vaccination delays. PT antibody levels and the maternal to infant transfer efficiency were estimated. Infant, maternal, and household characteristics associated with non-presence and low levels of PT antibody were calculated through multivariate regression models. Results: Only 7% of infants had received all three recommended pertussis vaccinations by age 6 months. The incidence of PCR-confirmed Bordetella pertussis was 5.2 cases per 1000 infant-years (95% CI, 2.1 – 10.7) and cases were generally mild. The PT infant to mother ratio was 1.1 (95% CI: 1.0 – 1.2). Mother and infant pairs with detectable PT antibody were correlated but the majority of mothers and infants had antibody levels below the level of quantification. Conclusion: Population-based active home surveillance for respiratory illness identified a low incidence of pertussis among infants in rural Nepal. Nepal's immunization program, which includes 3 childhood whole cell pertussis vaccine doses, appears to be controlling pertussis in infants despite substantial delays in time to vaccination. Maternal and infant PT antibody levels were low. Overall transport was active for mothers with antibody titers above detectable levels and there was an association between these mothers and their infant PT antibody levels. Maternal immunization could be an important intervention to support infant pertussis immunity before infants are fully vaccinated.