Evaluation of Medical Conditions Associated With Zika Virus Infection in Managua, Nicaragua

NCT ID: NCT04182685

Last Updated: 2024-12-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 410 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2019-10-01
• Study Completion Date: 2020-12-31

Brief Summary

Zika virus (ZIKV) infection spread throughout the Americas with devastating consequences. Recent limited evidence suggests the potential for neurological effects associated with postnatally acquired ZIKV infection in humans; however, the impact on children is unknown. The researchers will conduct a longitudinal study of approximately 450 Nicaraguan children who were ages 2-12 in 2016 to evaluate the presence and persistence of neurological symptoms associated with ZIKV infection and to test whether ZIKV-infected children are at greater risk for developing neurological outcomes compared to uninfected children.

Detailed Description

In 2016, the World Health Organization designated the Zika virus (ZIKV) epidemic as a Public Health Emergency of International Concern because of the emerging association between microcephaly and ZIKV infection during pregnancy. Although many studies have evaluated the biochemical pathways for congenital ZIKV infection and related severe neurodevelopmental fetal and neonatal outcomes, research on health outcomes related to postnatally acquired ZIKV infection in children is lacking. The few existing epidemiological reports describe incidence rates of acquired ZIKV infection among symptomatic children only, and they predominantly include probable cases based on clinical signs and symptoms. Case reports and surveillance of acute central nervous system disease in adults and adolescents secondary to ZIKV infection suggest that ZIKV may have a broader impact on neurological health beyond that observed in congenitally exposed newborns, including neuropsychological deficits, long-term fatigue, and spinal cord lesions with unilateral paresthesia and muscle weakness. The neurotropic properties of ZIKV and its impact on developing neural cells in postnatally infected mice and nonhuman primates also raise concerns about the potential neurological sequelae of postnatal ZIKV infection, particularly in children. However, the extent to which acquired ZIKV infection can negatively affect the nervous systems and cause long-term neurological damage or cognitive effects is currently unknown. Although the existing evidence is limited, it provides the scientific premise for the hypothesis that ZIKV-infected children are at greater risk for developing neurological sequelae (e.g., cognitive, behavioral, sensory, motor deficits) compared to uninfected children. The researchers will conduct a longitudinal study of approximately 450 Nicaraguan children in the Pediatric Dengue Cohort Study (PDCS) who were ages 2- 12 during January 2016-January 2017, with and without acquired ZIKV infection, to accomplish the following aims:

Aim 1: Evaluate the presence and persistence of neurological symptoms among children with acquired ZIKV infection. Children from the PDCS who presented to a local clinic with ZIKV-like symptoms from January 2016 through January 2017 were tested for ZIKV and given a baseline symptoms questionnaire that included neurological symptoms (e.g., seizures, headaches, muscle weakness, fatigue). The researchers will enroll 225 symptomatic ZIKV-infected children who were ages 2-12 during that time period and give them the same symptoms questionnaire at a follow-up visit in 2019. The researchers will analyze the baseline and follow-up symptoms data to evaluate ZIKV-associated neurological symptom severity and persistence.

Aim 2: Test for associations between neurological sequelae and acquired ZIKV infection.

Hypothesis: ZIKV-infected children are at greater risk for developing neurological sequelae (e.g., cognitive, behavioral, sensory, and motor deficits) compared to uninfected children. The researchers will enroll an equal number of ZIKV-uninfected PDCS children matched by age and sex to the ZIKV-infected children described in Aim 1 to provide a comparison group. For both ZIKV-infected and uninfected children, at the 2019/2020 study visit, the researchers will assess (1) clinical indicators of neurological impairment (e.g., vision, hearing, motor, and sensory functioning) by direct observation; (2) functioning across a wide range of domains (e.g., executive function, visual-spatial thinking, processing speed, attention, adaptive behavior) by administering a comprehensive neuropsychological assessment battery; and (3) factors related to neurological functioning (e.g., mood and sleep disorders).

The researchers will use regression models to calculate relative risks and 95% confidence intervals for the relationship between ZIKV status, clinical indicators of neurological impairment, and neuropsychological functioning across a wide range of domains. Additionally, we the researchers will assess the role of sex as a biological variable in stratified analyses. By leveraging the existing PDCS cohort and locally tested neurodevelopmental assessment tools, our cost-effective the study will provide invaluable information for determining the merit of conducting a larger and more in-depth study of the neurological impacts of acquired ZIKV infection that could be used to inform clinical practice and support the establishment of school-based educational interventions for affected children.

Conditions

Zika Virus

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

ZIKV-exposed children

Children age 5-15 with a positive Zika virus PCR test result.

No interventions assigned to this group

ZIKV-unexposed children

Children age 5-15 who have not had a Zika virus infection as determined by serological assays.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 5-15 years of age at the time of enrollment;
• Active in the PDCS
• Complete data on age, sex, and ZIKV status;
• Willingness to participate in the study visit;
• Written parental permission and assent to participate, as appropriate by age.

Exclusion Criteria

• Children with evidence in their medical charts of a diagnosis of a neurological (e.g., traumatic brain injuries, seizure disorder, stroke) or neurodevelopmental disorder (e.g., ADHD, Autism, Intellectual Disability) before January 2016.

• Minimum Eligible Age: 5 Years
• Maximum Eligible Age: 15 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: collaborator

Sustainable Sciences Institute (Managua, Nicaragua)

UNKNOWN

Sponsor Role: collaborator

Ministry of Health Nicaragua

UNKNOWN

Sponsor Role: collaborator

RTI International

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jill F. Lebov, PhD

Role: PRINCIPAL_INVESTIGATOR

RTI International

Locations

Health Center Socrates Flores Vivas

Managua, , Nicaragua

Countries

Nicaragua

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

Other Identifiers

1R21HD095420-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CNDR CIRE-16/07/19-099.Ver2

Identifier Type: -

Identifier Source: org_study_id