Zika Virus Epidemic: Challenges and Road Ahead

The participation involved national public health institutes of countries in the Americas and the Caribbean, experts from PAHO, the National Institutes of Health of France (InVS), the U.S. Center for Disease Control, the Public Health Agency of Canada, the Public Health Agency of the UK, the Secretary for Access to Rights and Equity at the Organization of Americas State and some other international organizations.

The main goals of the meeting were to analyze public health priorities and research agenda of the Zika epidemic in the America Region and the role of IANPHI adding value to the regional public health structures and policies for building human resources, laboratory capacity, information and cooperation. The situation of the epidemic and surveillance strategies, preparedness and response with the population living the critical situation, in Brazil, Colombia and the French Caribbean territories, was discussed.

Zika virus infection (ZIKV) has spread rapidly in the American continent since its emergence as autochthonous epidemic in early 2015 in Brazil. Despite being a disease of mild clinical course, the result of complications associated with acute infection of prenatal ZIKV can lead to death and brain congenital malformations in the fetus as microcephaly; the potential complication with a neurological syndrome mostly Guillain Barré syndrome (GBS) is also described. PAHO / WHO and other international institutions such as U.S. CDC, consider ZIKV epidemic as a serious global health problem.

Understanding Impacts

The first day of the meeting summarized the situation of Zika virus epidemic in the Americas, lessons learned and balance of social and economic impacts in the region, development and reconciliation of surveillance methods, laboratory and clinical diagnosis and Public Health. Participation of PAHO representatives presented the main actions taken to support detection, prevention and control of the epidemic and the initiative of mapping all regional research projects using a special platform.

In addition, it was described the main challenges in the research projects to asses’ microcephaly, GBS or other neurological complications, such as the need to harmonize protocols and the specific designs to further support association. Epidemiological Surveillance experts from Ministry of Health of Brazil and Colombia, specifically described the epidemiological situation, strategies to analyze, manage and communicate risk using estimation numbers assuming than confirmation cases only represent a limited number of the cases within the epidemic. The public health institutes of Peru and México presented integrated entomology and epidemiological surveillance systems including use of the geospatial platform for early detection of risk dissemination of diseases associated to Aedes vector.

With regards to clinical and laboratory diagnosis, experts from CDC Arboviral Diseases Branch of CDC, discussed current state of the art on the development, validation, and harmonization of algorithms and techniques for Zika laboratory diagnosis. The use of Real time PCR in the first week of diseases as the most reliable test to confirm acute cases and the complicated situation of cross-reactivity using IgM and IgG as well as PRNT detection to further define previous exposition to the virus. In addition, it was mentioned a promising future availability of urine detection of Zika virus in acute infection in the first two weeks of diseases. Expert from the University of Texas Medical Branch - UTMB, USA presented some insights of the Zika virus perspectives, timeline of the infection and the spillover of the virus from sylvatic environments to urban epidemics. Phylogenetic studies were also presented in order to compare outbreaks in different parts of the world.

International Severe Acute Respiratory and Emergent Infection Consortium (ISARIC) representative, presented the global initiative aiming to ensure that clinical researchers have the open access protocols and data-sharing processes needed to facilitate a rapid response to emerging diseases that may turn into epidemics or pandemics. Presently, ISARIC is working on harmonization related to Zika virus disease.

The cohort research protocols offered an excellent opportunity for an overall discussion focused on methodologies to measure child development; ethical issues and methodological harmonization between sites. The need for national capacity building at every site in order to perform all testes and activities required, as well as the high cost of the projects were also stressed. Major conclusions of the first day meeting were mostly focused to the surveillance models, in general supporting a more proactive, qualitative, territorial approach, rather than the classical reactive quantitative approach of counting suspected and laboratory confirmed cases.  It was mentioned that politicians and donors, in general, should be aware of the fact that geographic distribution of the vector and the disease, severe clinical cases associated to these agents and the territorial clustering of social and environmental determinants is quite more important than counting cases.

The social determination of vector and disease distribution was considered of highest concern, and included the need for more multilateral financing of research instead of bilateral projects, prioritize medium and long term actions because of the neurologic implications and the need for adapting health services to this health impact not only on the affected children but also on their mothers.

Discussion on recommendations about pregnancy in risk areas were also cited. PAHO representatives emphasized the importance of Laboratory networks for information and sample sharing and the need for the establishment of very clear rules for the sharing of data, samples and protocols, keeping always in mind the absolute value of trust in inter-country relationships.

Zika and Microcephaly Link

In the second day of the meeting it was discussed in more detail the link between Zika virus infection with microcephaly and GBS, and lessons-learned from sequential arbovirus infection and and co-infection.

The World Health Organization and U.S. CDC have concluded that scientific evidence is supporting the link between Zika virus infection and microcephaly. Presentation from representatives of FIOCRUZ Brazil, concluded that there is very strong evidence of causal association, however there is a need of establishing and measuring its effect, to investigate associated mechanisms, possible interventions either preventive or treatment. Regional unit of the French Public Health Institute in the French Caribbean and Guiana described the challenges they have found facing this epidemic: high seroprevalence towards DENV challenges interpretation of serological results, the need to foster research in the field of new diagnostic techniques, specificity towards ZIKV infection ZIKV asymptomatic carriers induce delay in testing for Zika, additional diagnostic technique such as PRNT, the need to adapt surveillance system to the new events.

Representative from InVS France highlighted the imputability of microcephaly or other adverse pregnancy outcomes to Zika in the frame of medical investigation or surveillance data, in conditions of high attack rate and unknown potential co-factors, the uncertainty of full spectrum of phenotypes and late neurological outcomes and the urgent need of better performance of serodiagnosis, considering asymptomatic maternal infection. In particular, some challenges are the actual feasibility of pregnant women follow-up in all French territories in the Americas and the access to prenatal care in French Guiana and Mayotte. Finally, it was also stressed the the need of future follow-up and surveillance of late outcomes in preschoolers exposed to Zika in-utero even if they do not fulfill definition of Zika congenital infection.

In regards of GBS syndrome data from Colombia and Regional unit of the French Public Health Institute in the French Caribbean and Guiana also demonstrated a trend to increased number of cases following increased morbidity of Zika virus infection. Again it came up the need of harmonization of protocols to further support this causality. It is also a priority to considered the approach of congenital Zika Syndrome or Neurological syndrome other than microcephaly or GBS only.

Participation of the Public Health Agency of Canada described the importance of risk communication to helps decision-makers, stakeholders, and the public to make well-informed choices to protect against and minimize risk. Governments face challenges to implement strategies to protect populations during public health crisis such as inconsistent communication coordination among involved organizations, messaging that fails to build trust by acknowledging uncertainty, failing to reach at-risk populations with appropriate information, focusing on actual risk, failing to acknowledge risk perception and putting health information for the public up front, before government action. The best practice for risk communication are based on transparency, coordinated messaging, work with stakeholders, make information easy to find and understand, “call to action” must be clear, culturally and emotionally sensitive messaging, messaging responds to public information wants and needs and listen the audience and adapt as necessary.

The National Institute of Public Health of Chile discussed the current available guidelines for caring pregnant women during a Zika virus outbreak. The overall discussion highlighted the importance to a holistic approach of pregnant follow up, in general, during Zika outbreaks straighten prevention of mosquito vector exposure, not to forget possibility of sexual transmission, implementation of protocols to define brain congenital malformations including microcephaly, etc. Re-enforcement of contraceptive national programs in addition to counseling is a good strategy to provide a choice to women to become pregnant during this epidemic.

In regards of lessons-learned from sequential arbovirus infection and and co-infection, some question remains to be answered: How host genetics affect clinical outcomes? What is the role of intrinsic ZIKV virulence factors? Viral load? What is the role intra-host (vertebrate and vector) ZIKV genetic variation (quasispecies) in severity of clinical outcomes and transmission? Are there differences in clinical outcomes of ZIKV infections due to vector vs sexual transmission? What is the role of symptomatic ZIKV infection on neurologic (GBS) and other abnormalities? What is the role of asymptomatic ZIKV infections in development of MC, GBS and other abnormalities? What is the role of co-morbidities in clinical outcome of disease? What are the differences between African and Asian lineages? adaptive evolution?

There is some evidence that mosquitos or humans can be co-infected either with dengue, Chikungunya or Zika virus, however there is challenges with mosquito co-infection studies such as different viruses used, different doses, different timing of infection, different mosquito populations and different experimental conditions.

Peru representatives described the implementation of integrated entomology-epidemiological surveillance system to define entomology risk to focus vector control programs as a possible explanation of absence of Zika virus epidemic in the country.

Strategies for the Road Ahead

In the last day of the meeting the session was focused on vector control strategies. The Technical Advisory Group of Public Health Entomology of PAHO recommended that vector control and the response strategy to Zika Virus epidemic are a matter of international importance: Re-enforce surveillance and vector control national programs; focalize vector control actions; evaluation of use of the integrated approach of vector control programs; evaluate the use of new technology of vector control such as the use of symbiotic bacteria (Wolbachia) or transgenic mosquitos.

The representative of National Institute of Public Health of Mexico presented the main gaps in the most of the vector control programs: intervention strategies limited; not enough trained personnel, surveillance systems focused in human clinical cases and not integrated to entomology surveillance lacking opportunity to early intervention and risk communication ineffective.  The eco-health approach allow to identify ecological factors networks that can impact human health, include participation of economical, social and environmental factors, emphasize the need to understand the structure and functions within the ecosystem and promotes the holistic understanding of health determinants.

The sustainability of disease control programs requires a sense of community ownership, including the use of community resources, ideas, and leadership in providing program design and direction. It is necessary to explore strategies for enabling population and local governments leadership and inter-sectoral coordination to re-enforce vector control programs. In addition further detail was presented in regards on new vector control technology as the us of transgenic mosquito and symbiotic Wolbachia bacteria.

Summary of the Meeting's General Outcomes 

• There needs to be a development of methods and enhancement of surveillance approaches to include a standardization of indicators.
• Organize a workshop bringing together health surveillance experts from across the Institutes and identify the most appropriate model and subsequent training needs.
• Consider development of an algorithm to combine clinical, laboratory and epidemiological data
• Through this expert group identify collaborations and training programmed to aid improvements in surveillance capabilities. Excessive fragmentation in proposals must be avoided – overlapping areas should be considered for maximum benefit.
• There needs to be assistance in undertaking internal and external assessments of the public health institutes. This should focus on capacity building to enable compliance with International Health Regulations and development of good laboratory resources for detection of outbreaks and emerging pathogens.
• A corpus of Good Practices should be developed, to include social considerations, public health needs
• The concept of health security, with the recognition of economic impact, should be promoted with Local Governments to develop a process for unhindered access to funding for emergency management.
• Laboratory capacity building is key. Each country should be capable of diagnosis of novel pathogens, perhaps through a network of regional laboratories.
• Integrated vector control programs are essential and training experts in this field is a need in the region.

Participating NPHIs: 

PHAC, Canada  ·  CDC, Emory, USA  ·  INSP, Mexico  ·  INS, Colombia  ·  FiOCRUZ, Brazil  ·  InVS, France  ·  ANLIS, Argentina  ·  Gorgas Institute, Panama  ·  INLASA Bolivia  ·  INS Perú  ·  INSP, Salvador  ·  CNCS, Guatemala  ·  CARPHA, CARICOM  · INSP, Chile ·  INCIENSA, Costa Rica ·  INSPI, Ecuador ·  IMT Pedro Kouri, Cuba