Surveillance of Zika-related Microcephaly in Sub-Saharan Africa and Asia

This study will explore whether ZIKV is currently responsible for neurological complications, and particularly microcephaly, in Aedes-infested regions of Sub-Saharan Africa (SSA) and Asia. This will inform regional public health strategies, such as vaccination of women of child-bearing age. It will also demonstrate the public health impact of ZIKV infection and increase the understanding of other regional infectious (e.g. cytomegalovirus) causes of microcephaly.

Study Overview

• Status: Terminated
• Conditions: Microcephaly; Congenital Infection
• Intervention / Treatment: Diagnostic test: Differential diagnosis for infectious causes of microcephaly

Detailed Description

This study will last for 2 years, and will include only new cases of microcephaly.

Surveillance will take place in large maternities in urban areas (standard procedure)

• In each city, ~3000 live births per month will be monitored, so that on average one microcephaly will be diagnosed per month per city (i.e., 24 per city in 2 years)
• Microcephaly is defined as less than -3 standard deviation (SD), according to the INTERGROWTH standards by age and sex with abnormal ultrasound and/or clinical examination.

Data collection (study activity)

• A questionnaire with demographic, exposure and pregnancy details for all mothers Clinical exam and laboratory testing (standard procedure and study activity)
• Various biological samples (e.g. blood, placenta) will be collected from mothers and newborns/fetuses and tested for presence of ZIKV, and for other infectious (e.g. rubella, cytomegalovirus) causes of microcephaly
• Physical, neurological, hearing and visual examinations for all live births will be performed where possible.

Analysis and reporting (study activity)

o All results will be shared publically through conferences and peer-reviewed publications.

• Study Type: Observational
• Enrollment (Actual): 150

Contacts and Locations

Study Locations

• Cameroon
  • Yaoundé, Cameroon
    • Central Hospital Maternity
  • Yaoundé, Cameroon
    • Essos Hospital Centre Maternity
• China
  • Guangzhou, China
    • Guangzhou Women's and Children's Hospital
• Côte D'Ivoire
  • Abidjan, Côte D'Ivoire
    • General Hospital Abobo-Sud
  • Abidjan, Côte D'Ivoire
    • General Hospital of Yopougon-Attie
• Sri Lanka
  • Colombo, Sri Lanka
    • Castle Street Hospital for Women
  • Colombo, Sri Lanka
    • De Soyza Hospital for Women
• Vietnam
  • Ho Chi Minh City, Vietnam
    • Tu Du Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 2 days (CHILD)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Fetuses or newborns (still-born, medical abortions [China and Vietnam only] or alive) with microcephaly defined as head circumference ≤-3SD according to INTERGROWTH standards for gestational age and sex with abnormal ultrasound and/or clinical examination findings for newborns.

Description

Inclusion Criteria:

• All infants or fetuses with microcephaly, (defined as head circumference ≤-3SD according to INTERGROWTH standards for gestational age and sex, detected during the mother's pregnancy, or at the end of the mother's pregnancy at one of the participating maternities)
• and with abnormal ultrasound and/or clinical examination findings for newborns.

Exclusion Criteria:

• Infants/fetuses with microcephaly whose mothers are under the age of 18 years,
• or inability or refusal of mothers/ guardians to give informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

5

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cameroon; Live newborns with microcephaly defined as head circumference ≤-3SD according to INTERGROWTH standards for gestational age and sex with abnormal ultrasound and/or clinical examination findings for newborns	Diagnostic test: Differential diagnosis for infectious causes of microcephaly; Zika virus, cytomegalovirus, rubella, toxoplasmosis
China; Fetuses or newborns (still-born, medical abortions or alive) with microcephaly defined as head circumference ≤-3SD according to INTERGROWTH standards for gestational age and sex with abnormal ultrasound and/or clinical examination findings for newborns	Diagnostic test: Differential diagnosis for infectious causes of microcephaly; Zika virus, cytomegalovirus, rubella, toxoplasmosis
Ivory Coast; Live newborns with microcephaly defined as head circumference ≤-3SD according to INTERGROWTH standards for gestational age and sex and severely disproportionate length or weight according to INTERGROWTH standards for gestational age and sex with abnormal ultrasound and/or clinical examination findings for newborns	Diagnostic test: Differential diagnosis for infectious causes of microcephaly; Zika virus, cytomegalovirus, rubella, toxoplasmosis
Sri Lanka; Live newborns with microcephaly defined as head circumference ≤-3SD according to INTERGROWTH standards for gestational age and sex with abnormal ultrasound and/or clinical examination findings for newborns	Diagnostic test: Differential diagnosis for infectious causes of microcephaly; Zika virus, cytomegalovirus, rubella, toxoplasmosis
Vietnam; Fetuses or newborns (still-born, medical abortions or alive) with microcephaly defined as head circumference ≤-3SD according to INTERGROWTH standards for gestational age and sex with abnormal ultrasound and/or clinical examination findings for newborns	Diagnostic test: Differential diagnosis for infectious causes of microcephaly; Zika virus, cytomegalovirus, rubella, toxoplasmosis

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of microcephaly (per 10,000 live births)	Incidence of microcephaly (per 10,000 live births)	At birth
Proportion of microcephaly attributable to ZIKV	Proportion of microcephaly attributable to Zika virus infection	At birth
Proportion of microcephaly linked to other infectious etiologies	Proportion of microcephaly linked to other infectious etiologies (non-ZIKV)	At birth

Collaborators and Investigators

• Sponsor: Institut Pasteur
• Collaborators: The University of Hong Kong; University of Lausanne; University of Lausanne Hospitals; Pasteur Institute, Ho Chi Minh City; Guangzhou Women and Children's Medical Center; Tu Du Hospital; Centre Pasteur du Cameroun; University of Colombo; Ministry of Health of Sri Lanka; Institut Pasteur of Cote d'Ivoire; Perinatal Society of Sri Lanka; Central Hospital Maternity; Essos Hospital Center; Guangzhou Baiyun Maternal and Child Health Hospital; General Hospital of Yopougon-Attie; General Hospital Abobo-Sud; Castle Street Hospital for Women; De Soyza Hospital for Women
• Investigators: Principal Investigator: Arnaud Fontanet, Institut Pasteur

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 20, 2019
• Primary Completion (ACTUAL): August 31, 2021
• Study Completion (ACTUAL): August 31, 2021

Study Registration Dates

• First Submitted: April 17, 2019
• First Submitted That Met QC Criteria: April 17, 2019
• First Posted (ACTUAL): April 22, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 20, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Congenital Abnormalities; Musculoskeletal Diseases; Craniofacial Abnormalities; Musculoskeletal Abnormalities; Malformations of Cortical Development, Group I; Malformations of Cortical Development; Nervous System Malformations; Microcephaly
• Other Study ID Numbers: ZIKA_2016-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No