Abstract
Purpose
The purpose of this review is to comprehensively review Congenital Zika Syndrome in regard to their epidemiology and clinical manifestations.
Methods
This subject review of congenital Zika syndrome was composed after conducting a thorough review of the available literature on this topic using PubMed and other primary sources.
Results
The first epidemic of Zika virus infection in Brazil was followed by an unexpected sharp increase in the incidence of infants born with microcephaly and the description of a new disease, the congenital Zika syndrome. This review focuses on the epidemiological and clinical aspects of Zika infection in children. We conducted a brief historical account of the virus description in 1947, the rare cases of Zika infection occurring up to 2007, and the first epidemics in the Pacific between 2007 and 2014. We also discussed the isolation of the virus in Brazil in 2015 and its spread in the Americas, the microcephaly outbreak in Brazil and its association with Zika virus, and the current epidemiological panorama. We address the known clinical spectrum of Zika virus infection in the pediatric population, including manifestations of acute infection and congenital Zika syndrome, with emphasis on cranial, ophthalmic, and orthopedic abnormalities.
Conclusion
While much has been learned about congenital Zika syndrome, the full spectrum of this infection is not yet known. This review is based on current, limited data about Zika vírus infection. As more information becomes available, we will have a more accurate picture of this new disease.
Similar content being viewed by others
Reference list
Brasil P, Pereira JP, Moreira ME, Nogueira RMR, Damasceno L, Wakimoto M, Rabello RS, Valderramos SG, Halai U-A, Salles TS, Zin AA, Horovitz D, Daltro B, Boechat M, Gabaglia CR, Sequeira PC, Pilotto JH, Medialdea-Carrera R, Cunha DC, Carvalho LMA, Pone M, Siqueira AM, Calvet GA, Baião ERA, Neves ES, Carvalho PRN, Hasue RH, Marschik PB, Einspieler C, Janzen C, Cherry JD, Filippis AMB, Saines-Nielsen K (2016) Zika virus infection in pregnant women in Rio de Janeiro. N Engl J Med 375(24):2321–2334. https://doi.org/10.1056/NEJMoa1602412
Moore CA, Staples JE, Dobyns WB, Pessoa A, Ventura CV, Fonseca EB, Ribeiro EM, Ventura LO, Neto NN, Arena JF, Rasmussen SA (2016) Characterizing the pattern of anomalies in congenital Zika syndrome for pediatric clinicians. JAMA Pediatr 171(3):288–295. https://doi.org/10.1001/Jamapediatrics.2016.3982
Dick GW, Kitchen S, Haddow A (1952) Zika virus. (I). Isolations and serological specificity. Trans R Soc Trop Med Hyg 46(5):509–520
Haddow AD, Schuh AJ, Yasuda CY, Kasper MR, Heang V, Huy R, Guzman H, Tesh RB, Weaver SC (2012) Genetic characterization of Zika virus strains: geographic expansion of the Asian lineage. PLoS Negl Trop Dis 6(2):e1477. https://doi.org/10.1371/journal.pntd.0001477
Rathore MH, Runyon J, Haque T (2017) Emerging infectious disease. Adv Pediatr 64:27–71. https://doi.org/10.1016/j.yapd.2017.04.002
Wilder-Smith A, Gubler JD, Weaver SC, Monath TP, Heymann DL, Scott TW (2017) Epidemic arboviral diseases: priorities for research and public health. Lancet 17:e101–e106. https://doi.org/10.1016/ S1473-3099(16)30518-7
Rodriguez-Morales AJ, Bandeira AC, Franco-Paredes C (2016) The expanding spectrum of modes of transmission of Zika virus: a global concern. Ann Clin Microbiol Antimicrob 15:13. https://doi.org/10.1186/s12941-016-0128-2
Paixão ES, Barreto F, Teixeira MG, Costa MC, Rodrigues LC (2016) History, epidemiology, and clinical manifestations of Zika: a systematic review. Am J Public Health 106:606–612. https://doi.org/10.2105/AJPH. 2016.303112
Fauci AS, Morens DM (2016) Zika virus in the Americas—yet another arbovirus threat. N Engl J Med 374(7):601–603. https://doi.org/10.1056/NEJMp1002530
Posen HJ, Keystone JS, Gubbay JB, Morris SK (2016) Epidemiology of Zika virus, 1947–2007. BMJ Glob Health 1:e000087. https://doi.org/10.1136/ bmjgh-2016-000087
Gonzalez MT, Filipe AR (1977) Antibodies to arboviruses in northwestern Spain. Am J Trop Med Hyg 26(4):792–797
Duffy MR, Chen TH, Hancock WT, Powers AM, Kool JL, Lanciotti RS, Pretrick M, Marfel M, Holzbauer S, Dubray C, Guillaumot L, Griggs A, Bel M, Lambert AJ, Laven J, Kosoy O, Panella A, Biggerstaff BJ, Fischer M, Haves EB (2009) Zika virus outbreak on Yap Island, Federated States of Micronesia. N Engl J Med 360(24):2536–2543. https://doi.org/10.1056/NEJMoa0805715
Roth A, Mercier A, Lepers C, Duituturaga S, Benyon E, Guillaumot L, Souarès Y (2014) Concurrent outbreaks of dengue, chikungunya and Zika virus infections—an unprecedented epidemic wave of mosquitoborne viruses in the Pacific 2012–2014. Euro Surveill 19(41). https://doi.org/10.2807/1560-7917.ES2014.19.41.20929
Oehler E, Watrin L, Larre P, Leparc-Goffart I, Lastere S, Valour F, Baudouin L, Mallet H, Musso D, Ghawche F (2014) Zika virus infection complicated by Guillain-Barre syndrome—case report, French Polynesia, December 2013. Euro Surveill 19(9):7–9. https://doi.org/10.2807/1560-7917.ES2014.19.9.20720
Zanluca C, Melo VC, Mosimann AL, Santos GI, Santos CN, Luz K (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
Faria NR, Quick J, Claro IM, Thézé J, de Jesus JG, Giovanetti M, Kraemer MUG, Hill SC, Black A, da Costa AC, Franco LC, Silva SP, Wu CH, Raghwani J, Cauchemez S, du Plessis L, Verotti MP, de Oliveira WK, Carmo EH, Coelho GE, Santelli ACFS, Vinhal LC, Henriques CM, Simpson JT, Loose M, Andersen KG, Grubaugh ND, Somasekar S, Chiu CY, Muñoz-Medina JE, Gonzalez-Bonilla CR, Arias CF, Lewis-Ximenez LL, Baylis SA, Chieppe AO, Aguiar SF, Fernandes CA, Lemos PS, Nascimento BLS, Monteiro HAO, Siqueira IC, de Queiroz MG, de Souza TR, Bezerra JF, Lemos MR, Pereira GF, Loudal D, Moura LC, Dhalia R, França RF, Magalhães T, Marques ET Jr, Jaenisch T, Wallau GL, de Lima MC, Nascimento V, de Cerqueira EM, de Lima MM, Mascarenhas DL, Neto JPM, Levin AS, Tozetto-Mendoza TR, Fonseca SN, Mendes-Correa MC, Milagres FP, Segurado A, Holmes EC, Rambaut A, Bedford T, Nunes MRT, Sabino EC, Alcantara LCJ, Loman NJ, Pybus OG (2017) Establishment and cryptic transmission of Zika virus in Brazil and the Americas. Nature 546(7658):406–410. https://doi.org/10.1038/nature22401
Metsky HC, Matranga CB, Wohl S, Schaffner SF, Freije CA, Winnicki SM, West K, Qu J, Baniecki ML, Gladden-Young A, Lin AE, Tomkins-Tinch CH, Ye SH, Park DJ, Luo CY, Barnes KG, Shah RR, Chak B, Barbosa-Lima G, Delatorre E, Vieira YR, Paul LM, Tan AL, Barcellona CM, Porcelli MC, Vasquez C, Cannons AC, Cone MR, Hogan KN, Kopp EW, Anzinger JJ, Garcia KF, Parham LA, Ramírez RMG, Montoya MCM, Rojas DP, Brown CM, Hennigan S, Sabina B, Scotland S, Gangavarapu K, Grubaugh ND, Oliveira G, Robles-Sikisaka R, Rambaut A, Gehrke L, Smole S, Halloran ME, Villar L, Mattar S, Lorenzana I, Cerbino-Neto J, Valim C, Degrave W, Bozza PT, Gnirke A, Andersen KG, Isern S, Michael SF, Bozza FA, Souza TML, Bosch I, Yozwiak NL, MacInnis BL, Sabeti PC (2017) Zika virus evolution and spread in the Americas. Nature 546(7658):411–415. https://doi.org/10.1038/nature22402
Schuler-Faccini L, Ribeiro EM, Feitosa IML, Horovitz DDG, Cavalcanti DP, Pessoa A, Doriqui MJR, Neri JI, Neto JMP, Wanderley HYC, Cernach M, El-Husny AS, Pone MVS, Serao CLC, Sanseverino MTV (2015) Possible association between Zika virus infection and microcephaly—Brazil, 2015. MMWR Morb Mort Wkly Rep 65(3):59–62. 10.15585/mmwr.mm6503e2
Brasil, Ministério da Saúde (2015) Portaria no 1.813, de 11 de novembro de 2015 - Declara Emergência em Saúde Pública de importância Nacional (ESPIN) por alteração do padrão de ocorrência de microcefalias no Brasil. Diário Oficial da União 216: 51. Available via http://bvsms.saude.gov.br/bvs/saudelegis/gm/2015/prt1813_11_11_2015.html Accessed at 24/08/2017
WHO (2016) Who director-general summarizes the outcome of the emergency committee regarding clusters of microcephaly and Guillain-Barré syndrome. Available via http://wwwwhoint/mediacentre/news/statements/2016/emergency-committee-zika-microcephaly/en/ Accessed 3 Feb 2016
Besnard M, Eyrolle-Guignot D, Guillemette-Artur P, Lastère S, Bost-Bezeaud F, Marcelis L, Abadie V, Garel C, Moutard M, Jouannic J, Rozenberg F, Leparc-Goffart I, Mallet H (2016) Congenital cerebral malformations and dysfunction in fetuses and newborns following the 2013 to 2014 Zika virus epidemic in French Polynesia. Euro Surveill 21(13). https://doi.org/10.2807/1560-7917.ES.2016.21.13.30181
Cauchemez S, Besnard M, Bompard P, Dub T, Guillemette-Artur P, Eyrolle-Guignot D, Salje H, Van Kerkhove MD, Abadie V, Garel C, Fontanet A, Mallet HP (2016) Association between Zika virus and microcephaly in French Polynesia, 2013-15: a retrospective study. Lancet 387(10033):2125–2132. https://doi.org/10.1016/S0140-6736(16)00651-6
Johansson MA, Mier-y-Teran-Romero L, Reefhuis J, Gilboa SM, Hills SL (2016) Zika and the risk of microcephaly. N Engl J Med 375(1):1–4. https://doi.org/10.1056/NEJMp1605367
Calvet G, Aguiar RS, Melo ASO, Sampaio SA, Filippis I, Fabri A, Araujo ESM, Sequeira PC, Mendonça MCL, Oliveira L, Tschoeke DA, Schrago CG, Thompson FL, Brasil P, Santos FB, Nogueira RMR, Tanuri A, Filippis AMB (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
Martines RB, Bhatnagar J, Keating MK, Silva-Flannery L, Muehlenbachs A, Gary J, Goldsmith C, Hale G, Ritter J, Rollin D, Shieh W, Luz KG, Ramos AMO, Davi HPF, Oliveira WK, Lanciotti R, Lambert A, Zaki S (2015) Notes from the field: evidence of Zika virus infection in brain and placental tissues from two congenitally infected newborns and two fetal losses—Brazil, 2015. Mmwr Morb Mortal Wkly Rep 65:159–160. 10.15585/mmwr.mm6506e1
Oliveira MAS, Malinger G, Ximenes R, Szejnfeld PO, Sampaio SA, Filippis AMB (2016) Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg? Ultrasound Obstet Gynecol 47(1):6–7. https://doi.org/10.1002/uog.15831
Rasmussen SA, Jamieson DJ, Honein MA, Petersen LR (2016) Zika virus and birth defects—reviewing the evidence for causality. N Engl J Med 374(20):1981–1987. https://doi.org/10.1056/NEJMsr1604338
Ikejezie J, Shapiro CN, Kim J, Chiu M, Almiron M, Ugarte C, Espinal MA, Aldighieri S (2017) Zika virus transmission—region of the Americas, May 15, 2015–December 15, 2016. MMWR Morb Mortal Wkly Rep 66(12):329–334. https://doi.org/10.1111/ajt.14333
WHO (2017) Situation report— Zika virus microcephaly and GuillainBarré syndrome. Available at: http://reliefwebint/report/world/zikavirusmicrocephalyandguillainbarrsyndromesituationreport10march2017 Accessed 26 May 2017
McCarthy M (2016) Four in Florida are infected with Zika from local mosquitoes. BMJ 354:i4235. https://doi.org/10.1136/bmj.i4235
Reynolds MR, Jones AM, Petersen EE, Lee HE, Rice ME, Bingham A, Ellington SR, Evert N, Reagan-Steiner S, Oduyebo T, Brown CM, Martin S, Ahmad N, Bhatnagar J, Macdonald J, Gould C, Fine AD, Polen KD, Lake-Burger H, Hillard CL, Hall N, Yazdy MM, Slaughter K, Sommer JN, Adamski A, Raycraft M, Fleck-Derderian S, Gupta J, Newsome K, Baez-Santiago M, Slavinski S, White JL, Moore CA, Shapiro-Mendoza CK, Petersen L, Boyle C, Jamieson DJ, Meaney-Delman D, Honein MA (2017) Vital signs: update on Zika virus-associated birth defects and evaluation of all U.S. infants with congenital Zika virus exposure—U.S. Zika Pregnancy Registry. MMWR Morb Mortal Wkly Rep 66:366–373. 10.15585/mmwr.mm6613e1
Hurtado-Villa P, Puerto AK, Victoria S, Gracia G, Guasmayán L, Arce P, Álvarez G, Blandón E, Rengifo N, Holguín JA, Durán A, Zarante I (2017) Raised frequency of central nervous system malformations related to Zika virus infection in two birth defects surveillance systems in Bogotá and Cali, Colombia. Ped Inf Dis J doi. https://doi.org/10.1097/INF.0000000000001670
Oliveira WK, França GVA, Carmo EH, Duncan BB, Kuchenbecker RS, Schmidt MI Infection-related microcephaly after the 2015 and 2016 Zika virus outbreaks in Brazil: a surveillance-based analysis. Lancet. https://doi.org/10.1016/S0140-6736(17)31368-5
Brasil, Ministério da Saúde – Secretaria de Vigilância em Saúde (2017) Monitoramento integrado de alterações no crescimento e desenvolvimento relacionadas à infecção pelo vírus Zika e outras etiologias infecciosas, até a Semana Epidemiológica 28/2017. Boletim Epidemiológico 48 (24): 1–9. Available via: http://portalarquivos.saude.gov.br/images/pdf/2017/agosto/16/BE-2017_024-Monitoramento-integrado-de-alteracoes-no-crescimento-e-desenvolvimento-relacionadas-a-infeccao-pelo-virus-Zika.pdf Accessed 16 Aug 2017
Cerbino-Neto J, Mesquita EC, Souza TML, Parreira V, Wittlin BB, Durovni B, Lemos MCF, Vizzoni A, Filippis AMP, Sampaio AS, Gonçalves BS, Bozza FA (2016) Clinical manifestations of Zika virus infection, Rio de Janeiro, Brazil, 2015. Emerg Infect Dis 22(7):1318–1320. https://doi.org/10.3201/eid2207.160375
Atif M, Azeem M, Sarwar MR, Bashir A (2016) Zika virus disease: a current review of the literature. Infection 44(6):695–705. https://doi.org/10.1007/s15010-016-0935-6
Karwowski MP, Nelson JM, Staples JE, Fischer M, Fleming-Dutra KE, Villanueva J, Powers AM, Mead P, Honein MA, Moore CA, Rasmussen SA (2016) Zika virus disease: a CDC update for pediatric health care providers. Pediatrics 137(5):e20160621–e20160621. https://doi.org/10.1542/peds.2016-0621
Goodman AB, Dziuban EJ, Powell K, Bitsko RH, Langley G, Lindsey N, Franks JL, Russel K, Dasgupta S, Barfield WD, Odom E, Kahn E, Martin S, Fischer M, Staples E (2016) Characteristics of children aged <18 years with Zika virus disease acquired postnatally—U.S. states, January 2015–July 2016. Mmwr Morb Mortal Wkly Rep 65(39):1082–1085. 10.15585/mmwr.mm6539e2
Besnard M, Lastère S, Teissier A, Cao-Lormeau VM, Musso D (2014) Evidence of perinatal transmission of Zika virus, French Polynesia, December 2013 and February 2014. Eur Secur 19(13):8–11. https://doi.org/10.2807/1560-7917.ES2014.19.13.20751
Besnard M, Dub T, Gérardin P (2017) Outcomes for 2 children after peripartum acquisition of Zika virus infection, French Polynesia, 2013–2014. Emerg Infect Dis 23(8):1421–1423. https://doi.org/10.3201/eid2308.170198
De Oliveira CS, Da Costa Vasconcelos PF (2016) Microcephaly and Zika virus. J Pediatr 92(2):103–105. https://doi.org/10.1016/j.jped.2016.02.003
Russell K, Oliver SE, Lewis L, Barfield WD, Cragan J, Meaney-Delman D, Staples JE, Fischer M, Peacock G, Oduyebo T, Petersen EE, Zaki S, Moore CA, Rasmussen SA (2016) Update: interim guidance for the evaluation and management of infants with possible congenital Zika virus infection—United States, August 2016. MMWR Morb Mortal Wkly Rep 65(33):870–878. 10.15585/mmwr.mm6533e2
Miranda-Filho DB, Martelli CM, Ximenes RA, Araújo TV, Rocha MA, Ramos RC, Dhalia R, França RF, Marques Junior ET, Rodrigues LC (2016) Initial description of the presumed congenital Zika syndrome. Am J Public Health 106(4):598–600. https://doi.org/10.2105/AJPH.2016.303115
Klase ZA, Khakhina S, Schneider ADB (2016) Zika fetal neuropathogenesis: etiology of a viral syndrome. PLoS Negl Trop Dis 10(8):e0004877. https://doi.org/10.1371/journal.pntd.0004877
França GVA, Schuler-Faccini L, Oliveira WK, Henriques CMP, Carmo EH, Pedi VD, Nunes ML, Castro MC, Serruya S, Silveira MF, Barros FC, Victora CG (2016) Congenital Zika virus syndrome in Brazil: a case series of the first 1501 livebirths with complete investigation. Lancet 388:891–897. https://doi.org/10.1016/ S0140-6736(16)30902-3
Rocha NACF, de Campos AC, Rocha FCF, Silva FPS (2017) Microcephaly and Zika virus: neuroradiological aspects, clinical findings and a proposed framework for early evaluation of child development. Infant Behav Dev 49:70–82. https://doi.org/10.1016/j.infbeh.2017.07.002
Horovitz DDGG, Pone MVS, Pone SM, Salles TRDS, MCB B (2016) Cranial bone collapse in microcephalic infants prenatally exposed to Zika virus infection. Am Acad Neurol 87:118–119. https://doi.org/10.1212/WNL.0000000000002814
Culjat M, Darling SE, Nerurkar VR, Ching N, Kumar M, Min SK, Wong R, Grant L, Melish ME (2016) Clinical and imaging findings in an infant with Zika embryopathy. Clin Infect Dis 63(6):805–811. https://doi.org/10.1093/cid/ciw324
Leal MC, van der Linden V, Bezerra TP, de Valois L, Borges ACG, Antunes MMC, Brandt KG, Moura CX, Rodrigues LC, Ximenes CR (2017) Characteristics of dysphagia in infants with microcephaly caused by congenital Zika virus infection, Brazil, 2015. Emerg Infect Dis 23(8):1253–1259. https://doi.org/10.3201/eid2308.170354
Freitas BP, Dias JRO, Prazeres J, Sacramento GA, Ko AI, Maia M, Belfort R Jr (2016) Ocular findings in infants with microcephaly associated with presumed Zika virus congenital infection in Salvador, Brazil. JAMA Ophthalmol 134(5):529–535. https://doi.org/10.1001/jamaophthalmol.2016.0267
Freitas BP, Ko AI, Khouri R, Mayoral M, Henriques DF, Maia M, Belfort R Jr (2017) Glaucoma and congenital Zika syndrome. Ophthalmology 124:407–408. https://doi.org/10.1016/j.ophtha.2016.10.004
Ventura CV, Maia M, Bravo-Filho V, Góis AL, Belfort R Jr (2016) Zika virus in Brazil and macular atrophy in a child with microcephaly. Lancet 387:228. https://doi.org/10.1016/S0140-6737(16)00006-4
Ventura CV, Maia M, Ventura BV, Van der Linden V, Araújo EB, Ramos RC, Rocha MAW, Carvalho MDCG, Belfort R Jr, Ventura LO (2016) Ophthalmological findings in infants with microcephaly and presumable intra-uterus Zika virus infection. Arq Bras Oftalmol 79(1):1–3. https://doi.org/10.5935/0004-2749.20160002
Yepes JB, Murati FA, Pettito M, Peñaranda CF, de Yepez J, Maestre G, Arevalo JF (2017) Ophthalmic manifestations of congenital Zika syndrome in Colombia and Venezuela. JAMA Ophthalmol 135:440–445. https://doi.org/10.1001/jamaophthalmol.2017.0561
Zin AA, Tsui I, Rossetto J, Vasconcelos Z, Adachi K, Valderramos S, Halai UA, Pone MVDS, Pone SM, Silveira Filho JCB, Aibe MS, da Costa ACC, Zin OA, Belfort R Jr, Brasil P, Nielsen-Saines K, Moreira MEL (2017) Screening criteria for ophthalmic manifestations of congenital Zika virus infection. JAMA Pediatr. https://doi.org/10.1001/jamapediatrics.2017.1474
Meneses JDA, Ishigami AC, de Mello LM, de Albuquerque LL, de Brito CAA, Cordeiro MT, Pena LJ (2017) Lessons learned at the epicenter of Brazil's congenital Zika epidemic: evidence from 87 confirmed cases. Clin Infect Dis 64(10):1302–1308. https://doi.org/10.1093/cid/cix166
Van der Linden V, Filho ELR, Lins OG, van der Linden A, Aragão MFVV, Brainer-Lima AM, Cruz DDCS, Rocha MAW, Silva PFS, Carvalho MDCGC, Amaral FJ, Gomes JA, Medeiros ICR, Ventura CV, Ramos RC (2016) Congenital Zika syndrome with arthrogryposis: retrospective case series study. BMJ 354:i3899. https://doi.org/10.1136/bmj.i3899
Martines RB, Bhatnagar J, Ramos AMO, Davi HP, Iglezias SD, Kanamura CT, Keating MK, Hale G, Silva-Flannery L, Muehlenbachs A, Ritter J, Gary J, Rollin D, Goldsmith CS, Reagan-Stainer S, Ermias Y, Suzuki T, Luz KG (2016) Pathology of congenital Zika syndrome in Brazil: a case series. Lancet 388:898–904. https://doi.org/10.1016/S0140-6736(16)30883-2
Parrott J, Boyd RN, Dobson F, Lancaster A, Love S, Oates J, Wolfe R, Nattrass GR, Graham HK (2002) Hip displacement in spastic cerebral palsy: repeatability of radiological measurement. J Pediatr Orthop 22(5):660–667
Chimelli L, Melo ASO, Avvad-Portari E, Wiley CA, Camacho AHS, Lopes VS, Machado HN, Andrade CV, Dock DCA, Moreira ME, Tovar-Moll F, Oliveira-Szejnfeld PS, Carvalho ACG, Ugarte ON, Batista AGM, Amorim MMR, Melo FO, Ferreira TA, Marinho JRL, Azevedo JS, Leal JIBF, Costa RFM, Rehen S, Arruda MB, Brindeiro RM, Delvechio R, Aguiar RS, Tanuri A (2017) The spectrum of neuropathological changes associated with congenital Zika virus infection. Acta Neuropathol 133:983–999. https://doi.org/10.1007/s00401-017-1699-5
Brasil, Ministério da Saúde, Secretaria de Atenção à Saúde (2016) Protocolo de atenção à saúde e resposta à ocorrência de microcefalia. Ministério da Saúde, Secretaria de Atenção à Saúde. Available via http://combateaedes.saude.gov.br/images/sala-de-situacao/04-04_protocolo-SAS.pdf. Accessed 15 Nov 2016
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
da Silva Pone, M.V., Moura Pone, S., Araujo Zin, A. et al. Zika virus infection in children: epidemiology and clinical manifestations. Childs Nerv Syst 34, 63–71 (2018). https://doi.org/10.1007/s00381-017-3635-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00381-017-3635-3