Abstract
Background
Zika Virus (ZIKV), member of Flaviviridae family and Flavivirus genus, has recently emerged as international public health emergency after its association with neonatal microcephaly cases. Clinical diagnosis hindrance involves symptom similarities produced by other arbovirus infections, therefore laboratory confirmation is of paramount importance.
Discussion
The most reliable test available is based on ZIKV RNA detection from body fluid samples. However, short viremia window periods and asymptomatic infections diminish the success rate for RT-PCR positivity. Beyond molecular detection, all serology tests in areas where other Flavivirus circulates proved to be a difficult task due to the broad range of cross-reactivity, especially with dengue pre-exposed individuals.
Conclusion
Altogether, lack of serological diagnostic tools brings limitations to any retrospective evaluation. Those studies are central in the context of congenital infection that could occur asymptomatically and mask prevalence and risk rates.
Similar content being viewed by others
References
Faye O, Freire CCM, Iamarino A et al (2014) Molecular evolution of Zika virus during its emergence in the 20th century. PLoS Negl Trop Dis 8:e2636. https://doi.org/10.1371/journal.pntd.0002636
Zanluca C, de Melo VCA, Mosimann ALP et al (2015) First report of autochthonous transmission of Zika virus in Brazil. Mem Inst Oswaldo Cruz 110:569–572. https://doi.org/10.1590/0074-02760150192
Gould EA, de Lamballerie X, Zanotto PM, Holmes EC (2003) Origins, evolution, and vector/host coadaptations within the genus Flavivirus. Adv Virus Res 59:277–314
Lanciotti RS, Kosoy OL, Laven JJ et al (2008) Genetic and serologic properties of Zika virus associated with an epidemic, Yap State, Micronesia, 2007. Emerg Infect Dis 14:1232–1239. https://doi.org/10.3201/eid1408.080287
Cao-Lormeau V-M, Roche C, Teissier A et al (2014) Zika virus, French Polynesia, South Pacific, 2013. Emerg Infect Dis 20:1084–1086. https://doi.org/10.3201/eid2006.140138
Musso D, Cao-Lormeau VM, Gubler DJ et al (2015) Zika virus: following the path of dengue and chikungunya? Lancet 386:243–244. https://doi.org/10.1016/S0140-6736(15)61273-9
Campos GS, Bandeira AC, Sardi SI (2015) Zika virus outbreak, Bahia, Brazil. Emerg Infect Dis 21:1885–1886. https://doi.org/10.3201/eid2110.150847
Brasil P, Calvet GA, Siqueira AM et al (2016) Zika virus outbreak in Rio de Janeiro, Brazil: clinical characterization, epidemiological and virological aspects. PLoS Negl Trop Dis 10:e0004636. https://doi.org/10.1371/journal.pntd.0004636
Hayes EB (2009) Zika virus outside Africa. Emerg Infect Dis 15:1347–1350. https://doi.org/10.3201/eid1509.090442
Schuler-Faccini L, Ribeiro EM, Feitosa IML et al (2016) Possible association between Zika virus infection and microcephaly—Brazil, 2015. MMWR Morb Mortal Wkly Rep 65:59–62. 10.15585/mmwr.mm6503e2
Brasil P, Pereira JP, Moreira ME et al (2016) Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med 375:2321–2334. https://doi.org/10.1056/NEJMoa1602412
Calvet G, Aguiar RS, Melo ASO et al (2016) Detection and sequencing of Zika virus from amniotic fluid of fetuses with microcephaly in Brazil: a case study. Lancet Infect Dis 16:653–660. https://doi.org/10.1016/S1473-3099(16)00095-5
Culjat M, Darling SE, Nerurkar VR et al (2016) Clinical and imaging findings in an infant with Zika embryopathy. Clin Infect Dis 63:805–811. https://doi.org/10.1093/cid/ciw324
Haddow AD, Schuh AJ, Yasuda CY et al (2012) Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage. PLoS Negl Trop Dis 6:e1477. https://doi.org/10.1371/journal.pntd.0001477
Faria NR, Azevedo RDSDS, Kraemer, MUG, et al (2016) Zika virus in the Americas: early epidemiological and genetic findings. Science 352(6283):345-349. https://doi.org/10.1126/science.aaf5036
Kuno G, Chang G-JJ (2007) Full-length sequencing and genomic characterization of Bagaza, Kedougou, and Zika viruses. Arch Virol 152:687–696. https://doi.org/10.1007/s00705-006-0903-z
Plotkin JB, Kudla G (2011) Synonymous but not the same: the causes and consequences of codon bias. Nat Rev Genet 12:32–42. https://doi.org/10.1038/nrg2899
Longdon B, Brockhurst MA, Russell CA et al (2014) The evolution and genetics of virus host shifts. PLoS Pathog 10:e1004395. https://doi.org/10.1371/journal.ppat.1004395
de M Freire CC, Iamarino A, de L Neto DF, et al (2015) Spread of the pandemic Zika virus lineage is associated with NS1 codon usage adaptation in humans. bioRxiv 032839; https://doi.org/10.1101/032839
Brown WC, Akey DL, Konwerski JR et al (2016) Extended surface for membrane association in Zika virus NS1 structure. Nat Struct Mol Biol 23:865–867. https://doi.org/10.1038/nsmb.3268
Logan IS (2016) ZIKA—how fast does this virus mutate? Dongwuxue Yanjiu = Zool Res 37:110–115. 10.13918/j.issn.2095-8137.2016.2.110
Lee E, Leang SK, Davidson A, Lobigs M (2010) Both E protein glycans adversely affect dengue virus infectivity but are beneficial for virion release. J Virol 84:5171–5180. https://doi.org/10.1128/JVI.01900-09
Weltman JK (2016) An immuno-bioinformatic analysis of Zika virus (ZIKV) envelope E protein. J Med Microb Diagn. https://doi.org/10.4172/2161-0703.1000228
Musso D, Nhan T, Robin E et al (2014) Potential for Zika virus transmission through blood transfusion demonstrated during an outbreak in French Polynesia, November 2013 to February 2014. Euro Surveill 19:(14)
Motta IJF, Spencer BR, Cordeiro da Silva SG et al (2016) Evidence for transmission of Zika virus by platelet transfusion. N Engl J Med 375:1101–1103. https://doi.org/10.1056/NEJMc1607262
Musso D, Roche C, Robin E et al (2015) Potential sexual transmission of Zika virus. Emerg Infect Dis 21:359–361. https://doi.org/10.3201/eid2102.141363
Venturi G, Zammarchi L, Fortuna C et al (2016) An autochthonous case of Zika due to possible sexual transmission, Florence, Italy, 2014. Eur Secur 21:30148. https://doi.org/10.2807/1560-7917.ES.2016.21.8.30148
Davidson A, Slavinski S, Komoto K et al (2016) Suspected female-to-male sexual transmission of Zika virus—New York City, 2016. MMWR Morb Mortal Wkly Rep 65:716–717. 10.15585/mmwr.mm6528e2
McCarthy M (2016) Zika virus was transmitted by sexual contact in Texas, health officials report. BMJ 352:i720
Colt S, Garcia-Casal MN, Peña-Rosas JP et al (2017) Transmission of Zika virus through breast milk and other breastfeeding-related bodily-fluids: a systematic review. PLoS Negl Trop Dis 11:e0005528. https://doi.org/10.1371/journal.pntd.0005528
Leung GHY, Baird RW, Druce J, Anstey NM (2015) ZIKA virus infection in AUSTRALIA following a monkey bite in INDONESIA. Southeast Asian J Trop Med Public Health 46:460–464
Drebot M, MacDonald J, Lindsay R et al (2014) First case of Zika virus infection in a returning Canadian traveler. Am J Trop Med Hyg 91:1035–1038. https://doi.org/10.4269/ajtmh.14-0151
Visseaux B, Mortier E, Houhou-Fidouh N et al (2016) Zika virus in the female genital tract. Lancet Infect Dis 16:1220. https://doi.org/10.1016/S1473-3099(16)30387-5
Prisant N, Bujan L, Benichou H et al (2016) Zika virus in the female genital tract. Lancet Infect Dis 16:1000–1001. https://doi.org/10.1016/S1473-3099(16)30193-1
Barzon L, Pacenti M, Berto A et al (2016) Isolation of infectious Zika virus from saliva and prolonged viral RNA shedding in a traveller returning from the Dominican Republic to Italy, January 2016. Eur Secur 21:30159. https://doi.org/10.2807/1560-7917.ES.2016.21.10.30159
Musso D, Roche C, Nhan T-X et al (2015) Detection of Zika virus in saliva. J Clin Virol 68:53–55. https://doi.org/10.1016/j.jcv.2015.04.021
Bonaldo MC, Ribeiro IP, Lima NS et al (2016) Isolation of infective Zika virus from urine and saliva of patients in Brazil. PLoS Negl Trop Dis 10:e0004816. https://doi.org/10.1371/journal.pntd.0004816
Rozé B, Najioullah F, Fergé J-L et al (2016) Zika virus detection in urine from patients with Guillain-Barré syndrome on Martinique, January 2016. Eur Secur 21:30154. https://doi.org/10.2807/1560-7917.ES.2016.21.9.30154
Gourinat A-C, O’Connor O, Calvez E et al (2015) Detection of Zika virus in urine. Emerg Infect Dis 21:84–86. https://doi.org/10.3201/eid2101.140894
Slavov SN, Otaguiri KK, Kashima S, Covas DT (2016) Overview of Zika virus (ZIKV) infection in regards to the Brazilian epidemic. Braz J Med Biol Res = Rev Bras Pesqui medicas e Biol 49:e5420. https://doi.org/10.1590/1414-431X20165420
Dick GWA, Kitchen SF, Haddow AJ (1952) Zika virus. I. Isolations and serological specificity. Trans R Soc Trop Med Hyg 46:509–520
Safronetz D, Sloan A, Stein DR et al (2017) Evaluation of 5 commercially available Zika virus immunoassays. Emerg Infect Dis. https://doi.org/10.3201/eid2309.162043
Alcon-LePoder S, Sivard P, Drouet MT et al (2006) Secretion of flaviviral non-structural protein NS1: from diagnosis to pathogenesis. Novartis Found Symp 277:233–247 discussion 247–53
Ambrose JH, Sekaran SD, Azizan A (2017) Dengue virus NS1 protein as a diagnostic marker: commercially available ELISA and comparison to qRT-PCR and serological diagnostic assays currently used by the state of Florida. J Trop Med 2017:1–6. https://doi.org/10.1155/2017/8072491
de M Campos R, Cirne-Santos C, Meira GLS et al (2016) Prolonged detection of Zika virus RNA in urine samples during the ongoing Zika virus epidemic in Brazil. J Clin Virol 77:69–70. https://doi.org/10.1016/j.jcv.2016.02.009
Nicastri E, Castilletti C, Liuzzi G et al (2016) Persistent detection of Zika virus RNA in semen for six months after symptom onset in a traveller returning from Haiti to Italy, February 2016. Eur Secur 21:30314. https://doi.org/10.2807/1560-7917.ES.2016.21.32.30314
Atkinson B, Hearn P, Afrough B et al (2016) Detection of Zika virus in semen. Emerg Infect Dis 22:940–940. https://doi.org/10.3201/eid2205.160107
Rabe IB, Staples JE, Villanueva J et al (2016) Interim guidance for interpretation of Zika virus antibody test results. MMWR Morb Mortal Wkly Rep 65:543–546. 10.15585/mmwr.mm6521e1
Halstead SB (2017) Biologic evidence required for Zika disease enhancement by dengue antibodies. Emerg Infect Dis 23:569–573. https://doi.org/10.3201/eid2304.161879
Faye O, Faye O, Dupressoir A et al (2008) One-step RT-PCR for detection of Zika virus. J Clin Virol 43:96–101. https://doi.org/10.1016/j.jcv.2008.05.005
M-Y X, Liu S-Q, Deng C-L et al (2016) Detection of Zika virus by SYBR green one-step real-time RT-PCR. J Virol Methods 236:93–97. https://doi.org/10.1016/j.jviromet.2016.07.014
Barreto-Vieira DF, Barth OM, da Silva MAN et al (2016) Ultrastructure of Zika virus particles in cell cultures. Mem Inst Oswaldo Cruz 111:532–534. https://doi.org/10.1590/0074-02760160104
Landry ML, St. George K (2017) Laboratory diagnosis of Zika virus infection. Arch Pathol Lab Med 141:60–67. https://doi.org/10.5858/arpa.2016-0406-SA
Waggoner JJ, Pinsky BA (2016) Zika virus: diagnostics for an emerging pandemic threat. J Clin Microbiol 54:860–867. https://doi.org/10.1128/JCM.00279-16
Cardoso CW, Paploski IAD, Kikuti M et al (2015) Outbreak of exanthematous illness associated with Zika, chikungunya, and dengue viruses, Salvador, Brazil. Emerg Infect Dis 21:2274–2276. https://doi.org/10.3201/eid2112.151167
Plourde AR, Bloch EM (2016) A literature review of Zika virus. Emerg Infect Dis 22:1185–1192. https://doi.org/10.3201/eid2207.151990
Leder K, Druce JD, Kwong JC (2013) Zika virus infection acquired during brief travel to Indonesia. Am J Trop Med Hyg 89:516–517. https://doi.org/10.4269/ajtmh.13-0029
Sumita LM, Rodrigues JP, Ferreira NE et al (2016) Detection of human anti-Zika virus IgG by ELISA using an antigen from in vitro infected Vero cells: preliminary results. Rev Inst Med Trop Sao Paulo 58:89. https://doi.org/10.1590/S1678-9946201658089
Oom AL, Smith D, Akrami K (2017) Identification of putative unique immunogenic ZIKV and DENV1-4 peptides for diagnostic cellular based tests. Sci Rep 7:6218. https://doi.org/10.1038/s41598-017-05980-z
Acknowledgements
We thank Fernandes Figueira Institute Pediatric Infectious Disease Team for helpful discussions during this work and field expertise from ZIKVIRUSIFF Cohort study registered on clinicaltrials.gov with identifier NCT03255369.
Funding
This work was supported by Fernandes Figueira Institute Research Program (Programa de Incentivo a Pesquisa II), Rio de Janeiro State Research Grant (Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro—grant E-26/201.840/2017), National Research Grant (Conselho Nacional de Desenvolvimento Científico e Tecnológico—grant 441098/2016-9), and CAPES/FIOCRUZ fellowship (Plano Brasil sem Miséria).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no financial interests.
Rights and permissions
About this article
Cite this article
de Vasconcelos, Z.F.M., Azevedo, R.C., Thompson, N. et al. Challenges for molecular and serological ZIKV infection confirmation. Childs Nerv Syst 34, 79–84 (2018). https://doi.org/10.1007/s00381-017-3641-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00381-017-3641-5