Vector-borne diseases (VBD) pose a significant economic and public health threat throughout developing tropical regions worldwide, including the Caribbean. The introduction in December 2013 and rapid spread of the chikungunya virus (CHIKV) throughout all the Caribbean nations, and more recently the emergence of the zika virus in Suriname and Martinique highlights the need to develop regional capacity to investigate, predict, contain, and respond to VBD. For example, recent evidence from la Runion suggests that CHIKV can negatively impact neurodevelopment among infants born to mothers who were infected with the virus during pregnancy. However, these results have not yet been replicated in other sites internationally ? such as the Caribbean ? nor have any longitudinal studies been carried out to follow children who have experienced neurocognitive delay related to CHIKV infection. To address the paucity of data while building VBD research capacity in tropical LMICs where these diseases are endemic and the burden of impaired neurodevelopment is felt most, researchers from St. George's University (SGU) in Grenada will partner with researchers from Stanford University, Oxford University, and the Universit de La Runion to: (1) Determine the prevalence of mother to child transmission of CHIKV in Grenadian pregnant mothers; (2) Measure the neurodevelopment of children at 2 years of age exposed at different trimesters in utero to CHIKV and compare them with unexposed children; (3) Assess the burden of confounding factors to better understand the specific impact of VBD on neurodevelopment and inform public health priorities; (4) Build local capacity for arboviral and neurodevelopmental testing at SGU. To achieve Aim 1, 379 moms and their infants who were born during the CHIKV outbreak in Grenada, 473 moms and their infants who were born after the outbreak and may have been exposed to the virus in utero, and 190 moms and their infants who were born at least nine months after the outbreak (and thus, very unlikely to be exposed to the virus in utero) will complete a survey detailing the onset and symptoms related to their CHIKV infection and will then be tested for exposure to CHIKV by ELISA. Non CHIKV-exposed infants and moms, CHIKV-exposed moms but not infants, CHIKV-exposed moms and infants, and time of exposure during pregnancy will be used to divide groups for neurocognitive comparison at 2-years of age. To achieve Aims 2 and 3, we will administer the intergrowth 21st Neurodevelopment Assessment ? a holistic assessment of early child development developed at Oxford University ? while controlling for confounding neurodevelopmental factors. To achieve Aim 4, we will establish a Regional Center for Child Neurodevelopment while addressing seven key areas of needed research support: (1) Financial (i.e., granting); (2) Expertise; (3) On-the-ground human resources; (4) Student trainees to build local capacity; (5) Equipment, IT, and facilities support; (6) On-the-ground university and research institute administrative support; and (7) Local and regional government, relevant NGO, and professional/academic institutional support.

Public Health Relevance

There is preliminary evidence of a link between infection with chikungunya ? a virus that is spread by mosquitos in tropical regions ? and impaired cognitive functioning among infants born to mothers infected with the virus. This could significantly impact the neurodevelopment of millions of children in developing regions worldwide, complicating efforts to reduce inequality and promote sustainable development. The proposed research program will build research capacity in neurodevelopment in a tropical middle-income developing country while examining the link between chikungunya infection and neurodevelopment in children at two years of age who were exposed to the virus during fetal development.

National Institute of Health (NIH)
Fogarty International Center (FIC)
Exploratory/Developmental Grants (R21)
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Special Emphasis Panel (ZRG1)
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Michels, Kathleen M
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Windward Islands Research & Ed Fdn
Great River
United States
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Contopoulos-Ioannidis, Despina; Newman-Lindsay, Shoshana; Chow, Camille et al. (2018) Mother-to-child transmission of Chikungunya virus: A systematic review and meta-analysis. PLoS Negl Trop Dis 12:e0006510