The Zika Virus Epidemic Four Years After: Where are We?Funding None.
25 June 2019 (online)
Zika virus (ZIKV), an emerging arthropod-borne, single-stranded RNA virus, member of the Spondweni serocomplex (genus Flavivirus, family Flaviviridae), was first isolated in 1947 from a sentinel (monkeys held captive with the purpose of identifying yellow fever activity) rhesus monkey in a forest in Uganda. After its discovery, ZIKV was associated only with few sporadic mild cases in humans in Africa and Asia over the next 60 years. However, since 2007, when the first outbreak of ZIKV outside Africa and Asia was reported in the Federated States of Micronesia (Yap), it has been identified in subsequent outbreaks in French Polynesia, Pacific islands, and more recently, from 2015, Brazil was the first country in the Western Hemisphere to confirm autochthonous transmission of ZIKV associated with an outbreak of “dengue-like syndrome” cases.
Interestingly, the potential for severe neurological outcomes after ZIKV infection was reported only after the outbreaks in French Polynesia, in 2013, and subsequently in Brazil. Furthermore, the most striking finding, the established relationship between ZIKV infection during pregnancy and a devastating congenital syndrome, was identified for the first time during the ZIKV outbreak in Brazil, leading to a dramatic increase in newborns with severe congenital malformations associated with ZIKV. The unique characteristics of the ZIKV outbreak in Brazil, where the population was completely susceptible (naïve) to the virus, affecting highly populated urban poor areas with high density of Aedes aegypti, and the established surveillance reporting system, are possible reasons to explain why the role of the ZIKV as a potential cause of congenital disease has only been recognized after circulation in Brazil. After the reports from Brazil raised a causal relationship between ZIKV infection in pregnancy and microcephaly and other congenital malformations; a retrospective analysis conducted in French Polynesia found an association between ZIKV and microcephaly.
Although it is still unknown whether ZIKV infection provides life-long immunity, it is expected that in endemic places in Africa and Asia, where the virus is circulating for decades, a proportion of the women in childbearing age is likely to have been infected during childhood, limiting the number of susceptible women. It is also possible that the more severe outcomes of ZIKV infection, observed in Brazil and other countries, may be related to genome mutation in virulence characteristics of the ZIKV circulating strain or even immune interaction between consecutive Flavivirus infections.
The ZIKV outbreak spread very rapidly in the Americas after the outbreak in Brazil. As of March 2019, 89 countries and territories reported current or past local transmission, among which several have reported microcephaly and/or central nervous system (CNS) malformation cases and Guillain-Barré Syndrome (GBS), potentially associated with ZIKV infection. Uruguay is currently the only country in the Americas, with evidence of established competent vector, but no known documented transmission of ZIKV ([Fig. 1]).
Brazil was the most affected country in the Americas, reporting 216,207 probable cases in 2016; 17,594 cases in 2017; 8,104 cases in 2018; and by week 10, in 2019, only 2,062 cases. The substantial decline in cases of ZIKV infection reported in the last 2 years is probably a result of a combination of “herd immunity” of the population, that became immune after being infected in previous years, reducing the number of susceptible, naive subjects and, thus, limiting the transmission of the virus in the community, together with a cyclical natural pattern, common to other Flavivirus like dengue that ebbs and flows in periodic waves.
Since 2015, the Ministry of Health in Brazil confirmed 3,332 cases of microcephaly and/or CNS malformation associated with ZIKV infection, with the majority occurring between 2015 and 2016 in the Northeast region. In those places, a common feature of the epidemic was the fact that most of the cases and the associated complications occurred in the poor urban areas, characterized by limited sanitary infrastructure, crowding, and poor quality of housing conditions that clearly facilitate the transmission of the virus by the A. aegypti mosquitoes.
- 1 Musso D, Gubler DJ. Zika Virus. Clin Microbiol Rev 2016; 29 (03) 487-524
- 2 Sáfadi MAP, Nascimento-Carvalho CM. Update on Zika: what you need to know. Pediatr Infect Dis J 2017; 36 (03) 333-336
- 3 Cauchemez S, Besnard M, Bompard P. , et al. Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. Lancet 2016; 387 (10033): 2125-2132
- 4 CDC. Zika virus. Available at: https://www.cdc.gov/zika/index.html . Accessed March 27, 2019
- 5 . Ministério da Saúde. Boletins epidemiológicos. Available at: http://portalms.saude.gov.br/boletins-epidemiologicos . Accessed March 23, 2019
- 6 Secretaria de Vigilância em Saúde; Ministério da Saúde; Situação epidemiológica. Monitoramento integrado de alterações no crescimento e desenvolvimento relacionadas à infecção pelo vírus Zika e outras etiologias infecciosas, até a Semana Epidemiológica 52 de 2018. Boletim Epidemiológico 2019; 50 (08) 1-8 Available at: http://portalarquivos2.saude.gov.br/images/pdf/2019/marco/22/2019-001.pdf
- 7 Snyder RE, Boone CE, Cardoso CAA, Aguiar-Alves F, Neves FPG, Riley LW. Zika: A scourge in urban slums. PLoS Negl Trop Dis 2017; 11 (03) e0005287
- 8 Oliveira DB, Almeida FJ, Durigon EL. , et al. Prolonged shedding of Zika virus associated with congenital infection. N Engl J Med 2016; 375 (12) 1202-1204
- 9 Satterfield-Nash A, Kotzky K, Allen J. , et al. Health and development at age 19-24 months of 19 children who were born with microcephaly and laboratory evidence of congenital Zika virus infection during the 2015 Zika virus outbreak - Brazil, 2017. MMWR Morb Mortal Wkly Rep 2017; 66 (49) 1347-1351
- 10 American Academy of Pediatrics. Zika Virus. In: Kimberlin DW, Brady MT, Jackson MA, Long SS. , eds. Red Book: 2018–2021 Report of the Committee on Infectious Disease. 31st ed. Elk Grove Village, IL: American Academy of Pediatrics; 2018: 894-901
- 11 Dowd KA, DeMaso CR, Pelc RS. , et al. Broadly neutralizing activity of zika virus-immune sera identifies a single viral serotype. Cell Reports 2016; 16 (06) 1485-1491
- 12 Poland GA, Kennedy RB, Ovsyannikova IG, Palacios R, Ho PL, Kalil J. Development of vaccines against Zika virus. Lancet Infect Dis 2018; 18 (07) e211-e219
- 13 Halstead SB. Achieving safe, effective, and durable Zika virus vaccines: lessons from dengue. Lancet Infect Dis 2017; 17 (11) e378-e382
- 14 Durbin A, Wilder-Smith A. An update on Zika vaccine developments. Expert Rev Vaccines 2017; 16 (08) 781-787