An update on Zika Virus and Congenital Zika Syndrome Clarissa Oeser Shamez Ladhani Abstract Zika virus was a little known virus until recent years, when its introduc- tion to South America caused a widespread epidemic. The subse- quent unprecedented number of cases with congenital microcephaly and neurological abnormalities in newborn babies prompted the declaration of a public health emergency of international concern. Since then, through concerted efforts by the international research community substantial knowledge has been gained about the epide- miology and physiopathology of this disease. However, the full spec- trum of this condition and long term sequelae in the population of children with congenital Zika virus syndrome are as yet unknown. Here we summarize key facts known on Zika virus and congenital Zika syndrome to date and current guidance for the treating clinician. Keywords congenital infection; diagnosis; epidemiology; prevention; Zika virus Introduction Today, Zika virus (ZIKV) can be found in most countries in the Southern hemisphere. The virus is mainly transmitted through mosquitoes. Infection is often asymptomatic but can cause a usually brief and self-limiting viral illness with a rash, and, rarely, immune-mediated neuropathy such as Guillan Barr e syndrome. Of greatest concern is infection during pregnancy, which is associated with congenital microcephaly and other fetal developmental abnormalities. Epidemiology ZIKV is a member of the family of Flaviviridae. Other common viruses belonging to this family are Dengue, Yellow fever, Jap- anese encephalitis and West Nile virus. First isolated in 1947 in the Zika forest in Uganda, sporadic cases of ZIKV infection have been reported from Africa and Southeast Asia since; however, due to its often asymptomatic or mild clinical course and the similarity to other tropical viral infections, detailed epidemiology is not known. In 2007, an outbreak occurred on the island of Yap in the Federated States of Micronesia. Five years later, another outbreak was reported in French Polynesia. In 2015, locally transmitted ZIKV infection was reported for the first time in Brazil. Since then, the virus has spread across most countries in South and Central America and the Caribbean. The main route of transmission of ZIKV is through mosquito bites. The principal vector is the Aedes aegyptii mosquito; how- ever, other Aedes species, such as Aedes albopictus have also been shown to be able to transmit the virus. A. aegyptii is one of the most widespread invasive species globally and its current distribution is extending. It is established in most countries of the Southern Hemisphere, including the East coast of Australia, southern states of the US and also parts of Europe (Madeira, Russia, Georgia). A. albopictus has adapted to survive colder climates and is established in many countries in Southern Europe. Consequently, 84 countries, territories or subnational regions have reported vector-borne ZIKV transmission so far. In a further 64 countries or territories, a competent vector is estab- lished, but there has been no documented past or current Zika virus transmission. Pathology and pathogenesis Unlike most other flaviviruses, ZIKV has the potential for human- to-human transmission, most significantly vertical transmission from the mother to the unborn child. To date, 31 countries have reported more than 3,000 cases of Congenital Zika Syndrome (CZS), including travel-associated cases in Europe, Canada and the US. Female-to-male, male-to-female and male-to-male sexual transmissions of ZIKV have been reported in multiple studies. Additionally, ZIKV has been transmitted by blood and platelet transfusions. ZIKV has been shown to persist in several body fluids (e.g., semen, saliva, tears and urine) and target organs, including immune-privileged sites (e.g. eyes, brain, and testes) and the female genital tract. ZIKV RNA and infectious virus has been recovered from conjunctival fluid and ZIKV RNA persistence has been identified in vaginal secretions for more than 11 weeks and in sperm and semen for up to 6 months. Little is known about the pathogenesis of ZIKV infection. It is thought that, after an infected mosquito bite, viral replication occurs in local dendritic cells with subsequent spread to lymph nodes and the bloodstream. Clinical studies and animal models have established that ZIKV is strongly neurotropic. One potential mechanism for the observed characteristic abnormalities of CZS such as micro- cephaly is that ZIKV preferentially infects and triggers apoptosis in neural progenitor cells, thereby affecting neurodevelopment of the brain. ZIKV RNA has been detected in cord blood, placenta, amniotic fluid, and neonatal human brain as well as the brain and placenta of spontaneously aborted fetuses in the first and second trimesters. Other features of CZS, such as arthrogryposis, are most likely caused by reduction in fetal mobility resulting from intrauterine infection occurring in early pregnancy. In the future, as addi- tional cases of CSZ are identified and documented, and clinical follow-up of affected children progresses, it is likely that new features will be recognized as components of CZS. More studies are required to define the effects of gestational age on ZIKV pathogenesis during pregnancy; current Clarissa Oeser PhD MRCPCH MSc PH is a Clinical Research Fellow in Emerging Infections and Zoonoses, National Infection Service, Public Health England, London, UK. Conflict of interest: none declared. Shamez Ladhani PhD MRCPCH is a Consultant in Paediatric Infectious Diseases Immunisations with the National Infection Service, Public Health England and St George’s, University of London, UK. Conflict of interest: none declared. OCCASIONAL REVIEW PAEDIATRICS AND CHILD HEALTH --:- 1 Crown Copyright Ó 2018 Published by Elsevier Ltd. All rights reserved. Please cite this article in press as: Oeser C, Ladhani S, An update on Zika Virus and Congenital Zika Syndrome, Paediatrics and Child Health (2018), https://doi.org/10.1016/j.paed.2018.10.010