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The Spectrum of ZIKA virus Disease in Grenada

Principal Investigators: A. Desiree LaBeaud, MD (USA), Calum MacPherson, PhD, DIC (Grenada)

A large outbreak of Zika virus occurred in Grenada in 2016 for the first time in history. At that time, the Grenada Ministry of Health estimated that 50% of the population had been infected with this mosquito-borne virus. Alarmed by the potential long-term harms associated with the infection, a collaborative research team of investigators from St. George’s University in Grenada and Stanford University (USA) decided to investigate factors associated with maternal to child transmission, an aspect of the disease which remains unknown.  Specifically, the research team intended to: 1) Identify demographic and exposure factors associated with severe ZIKV disease, 2) Identify demographic and exposure factors associated with maternal to child transmission of ZIKV, and 3) define medical consequences of congenital ZIKV disease in babies.

The study involved a cohort of 383 mothers and their babies who may have been exposed to the Zika virus during and after the outbreak. Between April 2016 and February 2017, study participants were asked to complete a comprehensive questionnaire regarding their health during pregnancy, exposure to mosquito-borne diseases, and details of the delivery. In addition, blood samples were collected to test for exposure to Zika and dengue viruses. Babies were examined at approximately 6 weeks after birth and a blood sample obtained. At this point a preliminary dataset has shown that the majority of the pregnant women were asymptomatic. Among symptomatic mothers, the most commonly observed symptoms (rash, fever, headache, chills, lymphadenopathy, nausea or vomiting and diarrhea) were similar to the symptoms of other diseases such as chikungunya and dengue. The research team intends, upon availability of funds, to 1) further define the spectrum of long-term infant outcomes by examining the range of cognitive deficits in congenital Zika virus syndrome and the medical consequences of congenital Zika disease; and 2) use sensitive and specific testing procedures to distinguish co-infections and identify linkages between mothers and children to identify the true incidence and nature of the impact of infection in children.

Neurodevelopment and Vector-borne Diseases: Building a Research Capacity in the Tropics

Principal Investigators: A. Desiree LaBeaud, MD (USA), Randall Waechter, BBA, PhD (Grenada)

Chikungunya (CHIKV), a mosquito-borne viral disease has been linked to neurodevelopmental problems among children such as delayed coordination and language development. Grenada and other Caribbean nations have experienced a rapid spread of CHIKV since 2013. This trend motivated investigators from St. George’s University in Grenada and Stanford University (USA) to build capacity for arboviral and neurodevelopmental research at St. George’s University. They specifically aimed to 1) assess the burden of confounding factors to better understand the specific impact of CHIKV on neurodevelopment and inform public health priorities; 2) determine the prevalence of mother to child transmission of CHIKV in Grenadian pregnant mothers; and 3) measure neurodevelopment in children at 2 years of age exposed at different trimesters in utero to CHIKV and compare with unexposed children.

The study, which is still enrolling participants, has so far enrolled 526 mothers and 381 children born during and up to one year after the 2014 CHIKV outbreak. The study measures several variables: 1) a questionnaire about the home environment, relationships, food security and pregnancy outcomes; 2) multidimensional and objective assessment of early neurodevelopment in infants using a robust multi-dimensional clinical tool (Intergrowth-21st Neurodevelopmental Assessment); and 3) blood samples to measure CHIKV exposure of mothers and their children.  Results to date indicate that: a) most mothers included in the study were infected with CHIKV during the first and second trimester, b) the most frequent maternal symptoms were joint pain, fever, rash, itchiness, headache, muscle pains and generalized body aches, and c) Mothers infected during pregnancy appear to be more symptomatic compared to those infected outside of pregnancy. Further recruitment, testing and analysis is ongoing to confirm these initial findings.  

WINDREF Receives $380,000 in Grants to Study Vector-Borne Diseases

The Windward Islands Research and Education Foundation (WINDREF) has received two grants, valued at $380,000, to study the prevalence and impact of the Zika and Chikungunya viruses in Grenada and surrounding countries.

windref

A two-year, $300,000 USD grant from the National Institutes of Health (NIH) – Fogarty International Center will allow researchers to examine the neurodevelopmental impact of the chikungunya virus (CHIKV) in infants in Grenada. In addition, WINDREF, which is based on the St. George’s University campus, has been granted $80,000 USD by the United States Naval Medical Research Center (NMRC) to study the Zika virus in the Southern Caribbean.

Dr. Randall Waechter, Research Grants Coordinator and faculty member in St. George’s University’s Department of Bioethics, and Dr. Angelle Desiree LaBeaud, Associate Professor at Lucile Packard Children’s Hospital Stanford, will serve as Co-Principal Investigators for the NIH study, which is titled “Neurodevelopment and Vector-borne Diseases: Building Research Capacity in the Tropics.” They will be assisted by SGU faculty members Barbara Landon and Trevor Noel and also work in conjunction with researchers from Stanford University, Oxford University, and Université de La Réunion.

“The recent discovery of the potential impact of the Zika virus on neurodevelopment in utero has researchers all over the world wondering if other vector-borne viruses can also impact neurodevelopment. We have put together a global team of leading experts to address this question. We are very excited to carry out this study, get SGU students involved, and build further research capacity in Grenada”

CHIKV’s spread through the Caribbean beginning in December 2013, including Grenada from August to December 2014, was followed by the recent emergence of the Zika virus in the region, highlighting the need to investigate, predict, contain and respond to vector-borne diseases. Through the NIH study, researchers will determine the prevalence of mother-to-child transmission of CHIKV in Grenadian pregnant mothers, compare the neurodevelopment of children born to infected mothers versus unexposed children, assess the burden of confounding factors to better understand the specific impact of VBD on neurodevelopment, and build local capacity for arboviral and neurodevelopmental testing at SGU.

Past WINDREF research endeavors have been supported by the NIH, including a $50,000 grant through the NIH and the Caribbean Public Health Association (CARPHA) to research the efficacy and awareness of breast and cervical screening in the region earlier this year. However, the CHIKV study marks the first time that the NIH has directly funded a WINDREF research project. It comes on the heels of another neurodevelopmental study, funded by Grand Challenges Canada, for which WINDREF examined the connection between corporal punishment and cognitive outcomes. Through this previous grant, the capacity to examine neurodevelopment in association with CHIKV has already been established.

“In the recent UNESCO Science Report titled: ‘Toward 2030’,  the remarkable increase in research output from Grenada over the last decade – largely as a result of St. George’s University – was acknowledged,” Dr. Waechter said. “Grenada is now the number three producer in the Caribbean of the most internationally respected publications, behind Jamaica and Trinidad. SGU has a promising future as an international research center and we are excited by the opportunities this offers to Grenadians and other CARICOM citizens.”

Titled “Zika virus surveillance in the Southern Caribbean and Reference Lab Support,” the NMRC study will be led by Dr. Calum Macpherson, Director of Research at SGU, Todd Myers from the NMRC, and William Nelson, the President and Chief Executive Officer of Tetracore. Zika dominated headlines around the world in the spring and summer of 2016 and Grenada was among more than 55 countries whose residents were afflicted with the virus.

The study is only the latest partnership between SGU and Tetracore. In July, the Maryland-based biotechnology company donated a Real Time Polymerase Chain Reaction thermocycler device to assist with the diagnostics and surveillance for Zika and other vector-borne infections in Grenada. The device can identify multiple genetic markers for Zika and can process six samples simultaneously.

“This collaboration between WINDREF, the Ministry of Health, Grenada, and the US NIDDL and Tetracore provides an essential diagnostic service, using the latest technology for the diagnosis of Zika, Chikungunya, and dengue,” said Dr. Macpherson. “This information is important for many at-risk sectors of the population.”

Published on 10/5/16