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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Microcephaly, Congenital Infection

Intervention / Treatment
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* Diagnostic Test: Differential diagnosis for infectious causes of microcephaly


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 2 Days

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cameroon<br>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<br>* Zika virus, cytomegalovirus, rubella, toxoplasmosis<br>|
| China<br>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<br>* Zika virus, cytomegalovirus, rubella, toxoplasmosis<br>|
| Ivory Coast<br>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<br>* Zika virus, cytomegalovirus, rubella, toxoplasmosis<br>|
| Sri Lanka<br>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<br>* Zika virus, cytomegalovirus, rubella, toxoplasmosis<br>|
| Vietnam<br>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<br>* Zika virus, cytomegalovirus, rubella, toxoplasmosis<br>|

What is the study measuring?
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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 |