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Is the Zika threat over?

2018; Elsevier BV; Volume: 24; Issue: 6 Linguagem: Inglês

10.1016/j.cmi.2018.03.007

1469-0691

Didier Musso, Van‐Mai Cao‐Lormeau,

Viral Infections and Vectors

Nobody knows why, 60 years after its discovery, and with less than 20 confirmed human infections reported in Africa and later in Asia, Zika virus (ZIKV) emerged in the Pacific and subsequently spread to the Americas causing severe neurological complications in adults and dramatic central nervous system congenital malformations [1Panchaud A. Stojanov M. Ammerdorffer A. Vouga M. Baud D. Emerging role of Zika virus in adverse fetal and neonatal outcomes.Clin Microbiol Rev. 2016; 29: 659-694Crossref PubMed Scopus (120) Google Scholar, 2Baud D. Gubler D.J. Schaub B. Lanteri M.C. Musso D. An update on Zika virus infection.Lancet. 2017; 390: 2099-2109Abstract Full Text Full Text PDF PubMed Scopus (385) Google Scholar]. The exact number of infections caused by ZIKV during the recent outbreaks worldwide is unknown. The lack of laboratory capacity to confirm ZIKV infections in endemic areas, the lack of standardized diagnosis tools for case confirmation, and a decrease in case reporting as ZIKV is no longer in the spotlight, may have contributed to an underestimate of the number of ZIKV infections. On the other hand, the number of ZIKV infections reported in the Americas in 2016 might have been overestimated as many patients initially thought to have Zika disease were infected with chikungunya virus [[3]Mehta R. Soares C.N. Medialdea-Carrera R. Ellul M. da Silva M.T.T. Rosala-Hallas A. et al.The spectrum of neurological disease associated with Zika and chikungunya viruses in adults in Rio de Janeiro, Brazil: a case series.PLoS Negl Trop Dis. 2018; 12: e0006212Crossref PubMed Scopus (69) Google Scholar], thus highlighting the difficulty in case confirmation in the context of arboviruses co-circulation. Moreover, evaluating the burden of Zika may have been complicated by variations in case reporting between countries and different areas within countries, and also by changes made to case definition during outbreaks, including complications potentially associated with ZIKV infection [[2]Baud D. Gubler D.J. Schaub B. Lanteri M.C. Musso D. An update on Zika virus infection.Lancet. 2017; 390: 2099-2109Abstract Full Text Full Text PDF PubMed Scopus (385) Google Scholar]. From the beginning of 2017, or perhaps earlier, ZIKV circulation has declined in the Americas. According to the Pan American Health Organization - World Health Organization, 712 000 cumulated cases (suspected and confirmed) were reported in 2015-2016, 95 000 in 2017, and no additional countries or territories of the Americas have confirmed autochthonous vector-borne transmission of ZIKV in 2017. The decrease is also confirmed by the drop of confirmed ZIKV infections in the Americas (178 000 cases in 2015-2016 and 45 000 in 2017), with only 4000 reported cases (3000 confirmed) in the last trimester of 2017 (PAHO - WHO website: http://www.paho.org/hq/). Does it mean that the Zika threat is over? Probably not. The main suggested explanation for the decline of ZIKV is a protective level of herd immunity in affected areas [[4]Cohen J. Where has all the Zika gone?.Science. 2017; 357: 631-632Crossref PubMed Scopus (18) Google Scholar]. There are no clear data on the duration and magnitude of anti-Zika protective immunity post infection. The impact of pre-existing immunity (post infection and vaccination) against closely related viruses such as dengue and yellow fever on the immune response to ZIKV is still a matter of debate [[5]Priyamvada L. Suthar M.S. Ahmed R. Wrammert J. Humoral immune responses against Zika virus infection and the importance of preexisting flavivirus immunity.J Infect Dis. 2017; 216: S906-S911Crossref PubMed Scopus (29) Google Scholar]. Most of the affected countries are low and middle income countries with high nativity rates and thus a high rate of non-immune population. Background immunity against ZIKV in endemic areas, such as Africa and Asia, is unknown and is challenging to assess because of cross-reactive antibodies. Nevertheless, the background immunity appears as a reasonable argument in countries where the population was highly infected such as in the Yap Islands and French Polynesia in the Pacific, and some parts of North Eastern Brazil, where post-outbreak seroprevalence was over 70%, 50%, and 60%, respectively [[6]Netto E.M. Moreira-Soto A. Pedroso C. Höser C. Funk S. Kucharski A.J. et al.High dsZika virus seroprevalence in salvador, northeastern Brazil limits the potential for further outbreaks.MBio. 2017; 8 (e01390–17)Crossref PubMed Scopus (132) Google Scholar]. The situation is different in Latin America, the Caribbean, and Asia. In Latin America and the Caribbean, 807 000 cumulated cases were reported for a population of 642 million inhabitants, thus resulting in an incidence rate of 0.13%. If we consider that up to 75% of cases were not reported because of either asymptomatic or mild disease, only a maximum of 0.52% of Latin American and Caribbean people might have been infected by ZIKV despite living in areas highly infested by Aedes aegypti, the main ZIKV mosquito vector. If we consider only Brazil, 369 000 cumulated cases were reported for a population of 210 million people thus resulting in an incidence of 0.18% of symptomatic cases corresponding to a maximum of 0.72% of infected people, if we include asymptomatic infections as well. In Asia, only limited ZIKV outbreaks were reported in Singapore (455 cases for 5.6 million people), Vietnam (145 cases (Ho Chi Minh city) for 95 million people) and Thailand (about 1000 cases for 69 million people), while about 800 million people are at risk of infection [[7]Siraj A.S. Perkins T.A. Assessing the population at risk of Zika virus in Asia – is the emergency really over?.BMJ Glob Heal. 2017; 2: e000309Crossref PubMed Scopus (18) Google Scholar]. Even if ZIKV circulation declined in 2017, this virus is still circulating at low level in the Americas, Asia, Pacific, and Africa, thus making those areas possible sources for ZIKV to be (re)seeded to other places. In addition, the recent demonstration that Brazilian monkeys living close to human populations can be viremic after ZIKV infection suggests that they could serve as an animal reservoir for ZIKV to be maintained in sylvatic transmission cycle, mimicking the cycle of ZIKV in Africa [[8]Vanchiere J.A. Ruiz J.C. Brady A.G. Kuehl T.J. Williams L.E. Baze W.B. et al.Experimental Zika virus infection of neotropical primates.Am J Trop Med Hyg. 2018; 98: 173-177Crossref PubMed Scopus (32) Google Scholar]. Other factors such as the expansion of the area of distribution of competent mosquito vectors, adaptation of ZIKV to new vectors, introduction of ZIKV into naïve human populations, are unpredictable events that could contribute to the re-emergence of ZIKV. The decline of ZIKV in the Americas is not synonymous to the end of the ZIKV story. Nobody can predict the future of ZIKV, as nobody was previously able to predict its emergence. It calls for maintaining surveillance in all areas where competent mosquito vectors are established, including areas already stricken by ZIKV. The authors declare no conflict of interest. The study received no external funding. The authors contributed equally.