Understanding the burden of ZIKV disease in Brazil, and anticipating further spread (or even decline) of infection are crucial requirements for policy makers, regarding vaccine decisions, prioritizing interventions and allocating resources.

Overall Objectives

  • Prospectively assess the evolution of the ZIKV outbreak in 17,000 subjects aged 2-59 in 14 different locations in Brazil over 3 years,
  • Strengthen the surveillance of birth defects in Latin America in order to facilitate rapid response to infectious disease outbreaks, in particular Zika, and to analyse and report data collected by regional and national birth defect surveillance systems on congenital Zika syndrome/microcephaly over 3 years in Latin America,
  • Document and anticipate regional and global geographic spread of Zika infections,
  • Estimate the burden of Zika in international travellers to Zika affected countries.

Specific Objectives

Butantan Phase III trial

  • Determine the annual incidence and describe the full spectrum from mild to severe disease of ZIKV infection in a prospective cohort study of 17,000 subjects aged 2-59 in 14 different geographic locations in Brazil (active febrile episode surveillance over 3 years),
  • Document the seroprevalence of ZIKV infection stratified by age, gender, prior dengue exposure, and geographic distribution in 17,000 subjects in 14 different geographic locations in Brazil at baseline, with repeat seroprevalence one year later,
  • Calculate the Basic Reproduction Number and force of infection of ZIKV in this cohort,
  • Determine the ratio of asymptomatic to symptomatic ZIKV infections,
  • Model the optimum age to vaccinate in case of the advent of an effective vaccine against ZIKV based on above findings,
  • Describe spatio-temporal and demographic factors associated with ZIKV infections in Brazil.

International Traveler Surveillance and Study

Conduct sentinel surveillance and a prospective cohort study in travelers to Latin America and other Zika affected countries in order to assess the risk of Zika to travelers.

Birth Defect Surveillance

  • Inventory and develop tools for birth defects surveillance, with particular attention to congenital Zika syndrome,
  • Develop and implement a model for networking birth defect surveillance across Latin America, including harmonization of data and monitoring, which could detect a new outbreak of congenital Zika syndrome and monitor its evolution over time,
  • Analyze and report data on microcephaly and congenital Zika syndrome from Latin American birth defects surveillance systems over a period of 3 years.

Work and Achievements

Butantan Phase III Trial

About 17,000 participants aged 2 to 59 in 16 research sites across Brazil have been recruited to test the efficacy of a live attenuated tetravalent dengue vaccine. This trial provides a unique opportunity to conduct a seroprevalence study for Zika as baseline samples have been taken from all trial participants. Trial participants will be randomly selected to determine past infection with Zika virus. An assay with the least cross-reactivity against other flaviviruses is currently being evaluated. The next step is the analyses of the stored samples.

International Traveler Surveillance and Study

In parallel with the decline in the incidence of Zika infections globally, cases in travelers have dropped dramatically. The ongoing projects in this study group are as follows:

  • International travelers bound for Brazil are being recruited and equipped with credit-card-size mosquito traps to collect mosquito-saliva. This will be used to assess the arbovirom in the local mosquito population along the travelers’ routes.
  • In a second ongoing study, based in Barcelona, international travelers are being equipped with a smartphone app., which assesses the incidence of arbovirus-compatible symptoms in international travelers and links the travelers in real-time with a physician.

Birth Defect Surveillance

  • Associação Técnica-Científica de Estudo Colaborativo Latino Americano de Malformações Congênitas (ECLAMC) is in the process of creating a Latin American network for congenital anomaly surveillance (Rede Latino Americana de Malformaciones Congénitas (RELAMC) providing an online platform and database with ready-to-use tools. Manuals have been drafted and data sharing agreements are in progress. The third meeting was held in Buenos Aires in November 2018.
  • A protocol for the surveillance of microcephaly and other congenital anomalies associated with maternal infections has been drafted and was presented to 16 Latin American Congenital Anomaly registries in Buenos Aires during the Annual ECLAMC meeting in November 2017.
  • All published data on ZIKA and cases of Microcephaly published by the Pan American Health Organization (PAHO) from over 40 countries from 2015-2017 has been collated and an analysis of this data is ongoing.
  • Establishment of the International Committee for Birth Defect Surveillance Tools for Infection Disease Response Preparedness. Inventory has been completed with input from the International Committee. This inventory is now available on www.globalbirthdefects.tghn.org and should greatly facilitate the establishment, quality improvement and harmonization of birth defects surveillance worldwide, whether in preparedness for Zika or other epidemics or teratogenic exposures.
  • Creation of an Application (app) for the Description and Coding of Birth Defects including diagrams and photos of birth defects, ICD codes and definitions. The app will fill a gap in capacity for the accurate description and coding of birth defects in low resource environments. This currently hampers both birth defect surveillance and pregnancy cohort studies. Externally visible major birth defects are included in the app. The app will be ready for field testing shortly.

International Committee for Birth Defect Surveillance Tools

  • Prof Helen Dolk (ZikaPLAN Co-investigator, Chair), Ulster University
  • Prof Ieda Orioli (ZikaPLAN Co-investigator), representing ECLAMC/RELAMC
  • Prof Ingeborg Barisic, Children’s University Hospital Zagreb, representing EUROCAT
  • Dr Linda Barlow, The Makerere University-John Hopkins University Research Collaboration (MUHJU) Kampala
  • Prof Lorenzo Botto, University of Utah, representing ICBDMSR
  • Ester Garne, Lillebaelt Hospital Denmark, representing EUROCAT
  • Dr Pilar Guatibonza, representing ECLAMC
  • Dr Christine Halleux, WHO-TDR, Geneva
  • Prof Lewis Holmes, Massachusetts General Hospital Boston, representing WHO-TDR
  • Dr Neena Raina WHO, Regional Office for South East Asia (WHO SEARO), New Delhi, India
  • Ms Diana Valencia, Centres for Disease Control Atlanta, representing CDC

Participating Organisations

Group leader: Prof. Annelies Wilder-Smith, Umeå University

  • London School of Hygiene & Tropical Medicine
  • Queen Mary University of London
  • Ulster University
  • Fundação de Apoio à Universidade de São Paulo
  • Instituto Butantan
  • Associação Técnica–Científica de Estudo Colaborativo Latino Americano de Malformações Congênitas
  • Schweizerisches Tropen- und Public Health-Institut
Prospective cohort study of 17,000 subjects aged 2-59

Prospective cohort study of 17,000 subjects aged 2-59 in 14 clinical sites in Brazil (Aracajú, Belo Horizonte, Boa Vista, Brasília, Campo Grande, Cuiabá, Fortaleza, Mananus, São José do Rio Preto, São Paulo (2): Hospital das Clínicas – FMUSP and Santa Casa de Misericóridua, Porto Alegre, Porto Velho and Recife)