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Zika virus: what do we know?

2016; Elsevier BV; Volume: 22; Issue: 6 Linguagem: Inglês

10.1016/j.cmi.2016.03.032

1469-0691

Didier Musso, David Baud, Duane J. Gubler,

Innovation and Socioeconomic Development

The global spread of epidemic Zika virus (ZIKV) began in Micronesia in 2007, followed by epidemics in French Polynesia in 2013–2014, other South Pacific islands in 2014–2015, and the Americas in 2015–2016 [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar]. Only 14 human infections were confirmed before 2007 [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar], but by early March 2016, 52 countries and Territories of the Americas, Africa, Asia and Pacific had reported autochthonous ZIKV transmission [[2]World Health Organization Zika situation report.10 March 2016http://www.who.int/emergencies/zika-virus/situation-report/10-march-2016/en/Google Scholar]. A dramatic increase in severe congenital malformations (microcephaly) potentially associated with ZIKV in Brazil, combined with the rapid geographical spread, led the WHO to declare the ZIKV epidemic a Public Health Emergency of International Concern. Although ZIKV was first isolated nearly 70 years ago, very little was known about the biology, epidemiology and clinical manifestations because transmission has been sporadic and silent for most of that time [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar]. Here we review what is and is not known about ZIKV, with emphasis on the gaps in knowledge about ZIKV and the possible inaccurate assumptions made based on what we know about related viruses. The increase in Guillain–Barré syndrome [[3]Oehler E. Watrin L. Larre P. Leparc-Goffart I. Lastere S. Valour F. et al.Zika virus infection complicated by Guillain–Barré syndrome—case report, French Polynesia, December 2013.Euro Surveill. 2014; 19 (pii: 20720)Crossref PubMed Google Scholar] and potential materno–fetal [[4]Besnard M. Lastère S. Teissier A. Cao-Lormeau V. Musso D. Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014.Euro Surveill. 2014; 19 (pii: 20751)Crossref PubMed Scopus (590) Google Scholar], sexual (detection of ZIKV in semen) [[5]Musso D. Roche C. Robin E. Nhan T. Teissier A. Cao-Lormeau V.M. Potenial sexual transmission of Zika virus.Emerg Infect Dis. 2015; 21: 359-361Crossref PubMed Scopus (852) Google Scholar] and blood transfusion [[6]Musso D. Nhan T. Robin E. Roche C. Bierlaire D. Zisou K. et al.Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014.Euro Surveill. 2014; 19 (pii: 20771)Crossref Scopus (511) Google Scholar] transmission were first described in French Polynesia [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar], but they were not taken seriously by the public health community until the dramatic increase in severe disease associated with the Brazil epidemic. The reasons for the recent emergence of ZIKV and its association with severe neurological complications remain unknown. However, the change in epidemiology fits the pattern seen with dengue, chikungunya and West Nile viruses, all of which have emerged as important global epidemic viruses in recent years [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar]. It seems likely that the same demographic, environmental, technological and societal pressures that influenced the emergence of epidemic strains of these viruses may have also led to increased transmission, so increasing viral genetic changes and the emergence of a ZIKV strain with increased epidemic potential and possibly virulence [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar]. The burden of ZIKV disease is unknown because there has been no laboratory-based surveillance for the disease and laboratory diagnosis is challenging. In the Pacific area, several countries reported cases of 'fever and rash' without specifically identifying the causative pathogen [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar]. In many countries where dengue virus is endemic, dengue-like illness is not confirmed by laboratory testing. Hence, ZIKV infections could be misdiagnosed as dengue or chikungunya. This type of silent transmission was underscored in June 2015, when a ZIKV infection was detected in a traveller returning from the Maldives Islands where ZIKV had never been detected [[7]Korhonen E.M. Huhtamo E. Smura T. Kallio-Kokko H. Raassina M. Vapalahti O. Zika virus infection in a traveller returning from the Maldives, June 2015.Euro Surveill. 2016; 21Crossref Scopus (69) Google Scholar], confirming that ZIKV was circulating undetected. Acute-phase diagnosis of ZIKV relies on molecular tests, which may be limited or used with poor quality assurance. In many countries where ZIKV is endemic, the capacity to perform molecular detection of ZIKV is very limited [[8]Samarasekera U. Triunfol M. Concern over Zika virus grips the world.Lancet. 2016; 387: 521-524Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar] and most of the cases are currently diagnosed clinically. The duration of the viraemic phase of ZIKV is not well established, but the window of detection might be increased by the use of urine [[9]Gourinat A.C. O'Connor O. Calvez E. Goarant C. Dupont-Rouzeyrol M. Detection of Zika virus in urine.Emerg Infect Dis. 2015; 21: 84-86Crossref PubMed Scopus (546) Google Scholar]. Serological diagnosis by IgM is limited by the occurrence of cross-reactions between members of the Flavivirus genus [[10]Lanciotti R.S. Kosoy O.L. Laven J.J. Velez J.O. Lambert A.J. Johnson A.J. et al.Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007.Emerg Infect Dis. 2008; 14: 1232-1239Crossref PubMed Scopus (1606) Google Scholar]. Serological diagnosis by IgM detection requires confirmation by neutralization test, which is only available in highly specialized laboratories [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar]. Hence, serological diagnosis of ZIKV infection remains problematic because all endemic areas for ZIKV are also endemic for DENV, and often other flaviviruses [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar]. It is assumed that mosquito transmission by urban/peridomestic species such as Aedes aegypti and Aedes albopictus is the predominant mode of transmission of ZIKV [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar]. The epidemiological importance of other modes of transmission is unknown. For example, sexual transmission of ZIKV has been documented in areas with no mosquito vectors [[11]Hills S.L. Russell K. Hennessey M. Williams C. Oster A.M. Fischer M. et al.Transmission of Zika virus through sexual contact with travelers to areas of ongoing transmission—continental United States, 2016.MMWR Morb Mortal Wkly Rep. 2016; 65: 215-216Crossref PubMed Scopus (330) Google Scholar], but the frequency and duration of infectious semen is unknown [[11]Hills S.L. Russell K. Hennessey M. Williams C. Oster A.M. Fischer M. et al.Transmission of Zika virus through sexual contact with travelers to areas of ongoing transmission—continental United States, 2016.MMWR Morb Mortal Wkly Rep. 2016; 65: 215-216Crossref PubMed Scopus (330) Google Scholar]. Only time and good clinical and epidemiological surveillance will answer that question. The increased severe disease could be due to mutation and increased virulence of the infecting virus strain or could simply represent the 'iceberg' rising farther out of the water as a result of increased transmission [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar]. Recent data suggest that ZIKV can emerge even if the main vectors (Aedes aegypti and Aedes albopictus) are of low competence [[12]Chouin-Carneiro T. Vega-Rua A. Vazeille M. Yebakima A. Girod R. Goindin D. et al.Differential susceptibilities of Aedes aegypti and Aedes albopictus from the Americas to Zika Virus.PLoS Negl Trop Dis. 2016; 10: e0004543Crossref Scopus (438) Google Scholar]. The link between ZIKV infection and severe neurological disease is still uncertain, although evidence is mounting. The increase in Guillain–Barré syndrome that was observed in French Polynesia is now being reported in nine Countries and Territories [[2]World Health Organization Zika situation report.10 March 2016http://www.who.int/emergencies/zika-virus/situation-report/10-march-2016/en/Google Scholar], and its link with ZIKV has recently been confirmed by a case–control study conducted in French Polynesia [[13]Cao-Lormeau V. Blake A. Mons S. Lastere S. Roche C. Vanhomwegen J. et al.Guillain–Barré Syndrome outbreak caused by ZIKA virus infection in French Polynesia: a case control study.Lancet. 2016; (pii: S0140-6736(16) 00562–6)PubMed Google Scholar]. Materno–fetal transmission of ZIKV has been confirmed, but the association between ZIKV and microcephaly remains controversial. The number of cases of microcephaly related to ZIKV in Brazil is unknown because of reporting bias; although notification became mandatory in 2015, different notification systems were used and the microcephaly case definition changed during the outbreak. Moreover, very few cases have been confirmed as ZIKV infections [[8]Samarasekera U. Triunfol M. Concern over Zika virus grips the world.Lancet. 2016; 387: 521-524Abstract Full Text Full Text PDF PubMed Scopus (90) Google Scholar]. This suspected link relies (i) on the temporal association between ZIKV outbreaks and increased incidence of microcephaly (Brazil and, retrospectively, in French Polynesia) and (ii) detection of ZIKV in newborn infants with microcephaly. Even if a cohort study of pregnant women with confirmed ZIKV infection being conducted in Rio de Janeiro (Brazil) strongly supports the link between maternal ZIKV infection and fetal or placental abnormalities [[14]Brasil P. Pereira J.P. Raja Gabaglia C. Damasceno L. Wakimoto M. Ribeiro Nogueira R.M. et al.Zika virus infection in pregnant women in Rio de Janeiro—preliminary report.N Engl J Med. 2016; (Epub ahead of print)Crossref PubMed Scopus (1291) Google Scholar], there is an urgent need to conduct a case–control study to definitively prove a causative association [[15]Musso D. Baud D. Zika virus : time to move from case reports to case control.Lancet Infect Dis. 2016; 3099 (pii: S1473-3099(16) 00096–7)Google Scholar]. Some guidelines regarding management of ZIKV infections in pregnant women recommend serological screening of pregnant women and amniocentesis if the results are positive or inconclusive [[16]Oduyebo T. Petersen E.E. Rasmussen S.A. Mead P.S. Meaney-Delman D. Renquist C.M. et al.Update: interim guidelines for health care providers caring for pregnant women and women of reproductive age with possible Zika virus exposure—United States, 2016.MMWR Morb Mortal Wkly Rep. 2016; 65: 122-127Crossref PubMed Scopus (142) Google Scholar]. In endemic areas these recommendations are questionable because, in most cases, serological confirmation will not be possible and amniocentesis conducted on the basis of false-positive serological results will lead to unnecessary invasive testing of unaffected fetuses [[17]Vouga M. Musso D. Van Mieghem T. Baud D. CDC guidelines for pregnant women during the Zika outbreak.Lancet. 2016; 287: 843-844Abstract Full Text Full Text PDF Scopus (44) Google Scholar]. Molecular detection of ZIKV in the amniotic fluid requires advanced laboratory techniques, so amniocentesis should only be performed in advanced materno–fetal centres [[18]Baud D. Mieghem T.V. Musso D. Truttmann A.C. Manchaud A. Vouga M. Materno-fetal specialist's guidelines for clinical management of pregnant women exposed to Zika virus.Lancet Infect Dis. 2016; (Epub ahead of print)Google Scholar]. The predictive value of detecting ZIKV RNA in amniotic fluid for fetal outcome is unknown. Finally, there is no specific treatment for infected pregnant women and abortion is outlawed in several countries where the virus is endemic [[12]Chouin-Carneiro T. Vega-Rua A. Vazeille M. Yebakima A. Girod R. Goindin D. et al.Differential susceptibilities of Aedes aegypti and Aedes albopictus from the Americas to Zika Virus.PLoS Negl Trop Dis. 2016; 10: e0004543Crossref Scopus (438) Google Scholar]. Latin American country health authorities recommend postponing pregnancy in ZIKV-infected areas, but the impact of this recommendation in countries where half of the pregnancies are unintended is unknown [[19]Roa M. Zika virus outbreak: reproductive health and rights in Latin America.Lancet. 2016; 387: 843Abstract Full Text Full Text PDF PubMed Scopus (56) Google Scholar]. A recent phylogenetic study found no similar amino acid changes in three microcephaly case genomes [[20]Faria N.R. Azevedo Rdo S. Kraemer M.U. Souza R. Cunha M.S. Hill S.C. et al.Zika virus in the Americas: early epidemiological and genetic findings.Science. 2016; (pii: aaf5036. (Epub ahead of print))Crossref PubMed Scopus (717) Google Scholar]. However, this does not exclude genetic changes responsible for potential increased virulence and/or epidemic potential of ZIKV occurring on the ancestral branches to the French Polynesian and American lineages, because severe disease and epidemic transmission were reported in both locations. With more than half of the world's human population living in areas infested with Aedes Stegomyia mosquitoes, one of the main challenges is to develop new tools to control the mosquito vectors. Evidence suggests that ZIKV is maintained in both a sylvatic and urban/peri-urban cycle. Although the recent epidemic spread suggests that Aedes aegypti is the main vector, there is clearly a lack of information on the role of this and other species. For example, ZIKV has been isolated from Culex species in Africa, but no data are available on whether Culex species can transmit the virus [[1]Musso D. Gubler D.J. Zika virus.Clin Microbiol Rev. 2016; 29 (Epub ahead of print)Crossref Scopus (967) Google Scholar]. However, data suggest that any area infested with Stegomyia species is at risk for epidemic transmission. There is therefore an urgent need to develop and implement more effective prevention strategies, including effective mosquito control, information about personal protection against mosquito bites, preventing sexual transmission, strengthening laboratory facilities, training medical staff to manage at-risk pregnancies with multidisciplinary teams (materno–fetal specialists, sonographers, geneticists, paediatricians and neurologists), training neurologists for care of patients with Guillain–Barré syndrome (number of intensive care unit beds, adequate immunoglobulin stock, plasma exchange capacity) [[21]Shakir R. Neurological expertise is essential for Zika virus infection.Lancet Neurol. 2016; 15: 353-354Abstract Full Text Full Text PDF Scopus (3) Google Scholar], implementing measures to prevent ZIKV transmission by blood transfusion [[22]Food and Drug Administration Recommendations for donor screening, deferral, and product management to reduce the risk of transfusion–transmission of Zika virus guidance for industry.2016http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/Blood/UCM486360.pdfGoogle Scholar], and developing a contingency plan to deal with increased severe disease case load [[23]International Federation of Red Cross and Red Crescent Societies, World Health Organization, UNICEF Risk communication and community engagement for Zika virus prevention and control.2016http://www.who.int/csr/resources/publications/zika/community-engagement/en/Google Scholar]. Finally, microcepahly and Guillain–Barré syndrome may only be the tip of the iceberg because other complications are now reported in neonates (ocular and auditory) and adults (ocular, meningoencephalitis, acute myelitis), although the incidence is unknown. We thank Manon Vouga for critical review of the manuscript. DB is supported by the Department 'Femme-Mère-Enfant', by the 'Fondation Leenaards' through the 'Bourse pour la relève académique', and by the SNSF (no. 310030_156169/1).