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Update on Zika: What You Need to Know

By Sáfadi MA, Nascimento-Carvalho CM

After remaining related to few sporadic cases in limited regions for more than half century since its discovery, Zika virus (ZIKV) was recently introduced into the Western Hemisphere, first in Brazil and then spreading very rapidly in the Americas. Unexpectedly, an increased incidence of microcephaly and other neurologic malformations in fetuses born to mothers infected with ZIKV during pregnancy was reported in Brazil, leading the World Health Organization to declare this situation a Public Health Emergency of International Concern

Published in: Pediatr Infect Dis J. 2017 Mar;36(3):333-336. doi: 10.1097/INF.0000000000001449.

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Zika virus disrupts molecular fingerprinting of human neurospheres

By Garcez PP, Nascimento JM, de Vasconcelos JM, Madeiro da Costa R, Delvecchio R, Trindade P, Loiola EC, Higa LM, Cassoli JS, Vitória G, Sequeira PC, Sochacki J, Aguiar RS, Fuzii HT, de Filippis AMB, da Silva Gonçalves Vianez Júnior JL, Tanuri A, Martins-de-Souza D, Rehen SK. 

Zika virus (ZIKV) has been associated with microcephaly and other brain abnormalities; however, the molecular consequences of ZIKV to human brain development are still not fully understood. Here we describe alterations in human neurospheres derived from induced pluripotent stem (iPS) cells infected with the strain of Zika virus that is circulating in Brazil. Combining proteomics and mRNA transcriptional profiling, over 500 proteins and genes associated with the Brazilian ZIKV infection were found to be differentially expressed. These genes and proteins provide an interactome map, which indicates that ZIKV controls the expression of RNA processing bodies, miRNA biogenesis and splicing factors required for self-replication. It also suggests that impairments in the molecular pathways underpinning cell cycle and neuronal differentiation are caused by ZIKV. These results point to biological mechanisms implicated in brain malformations, which are important to further the understanding of ZIKV infection and can be exploited as therapeutic potential targets to mitigate it.

Published in: Sci Rep. 2017 Jan 23;7:40780.

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The clinically approved antiviral drug sofosbuvir inhibits Zika virus replication

By Sacramento CQ, de Melo GR, de Freitas CS, Rocha N, Hoelz LV, Miranda M, Fintelman-Rodrigues N, Marttorelli A, Ferreira AC, Barbosa-Lima G, Abrantes JL, Vieira YR, Bastos MM, de Mello Volotão E, Nunes EP, Tschoeke DA, Leomil L, Loiola EC, Trindade P, Rehen SK, Bozza FA, Bozza PT, Boechat N, Thompson FL, de Filippis AMB, Brüning K, Souza TM. 

Zika virus (ZIKV) is a member of the Flaviviridae family, along with other agents of clinical significance such as dengue (DENV) and hepatitis C (HCV) viruses. Since ZIKV causes neurological disorders during fetal development and in adulthood, antiviral drugs are necessary. Sofosbuvir is clinically approved for use against HCV and targets the protein that is most conserved among the members of the Flaviviridae family, the viral RNA polymerase. Indeed, we found that sofosbuvir inhibits ZIKV RNA polymerase, targeting conserved amino acid residues. Sofosbuvir inhibited ZIKV replication in different cellular systems, such as hepatoma (Huh-7) cells, neuroblastoma (SH-Sy5y) cells, neural stem cells (NSC) and brain organoids. In addition to the direct inhibition of the viral RNA polymerase, we observed that sofosbuvir also induced an increase in A-to-G mutations in the viral genome. Together, our data highlight a potential secondary use of sofosbuvir, an anti-HCV drug, against ZIKV.

Published in: Sci Rep. 2017 Jan 18;7: 40920

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Persistent Zika Virus Detection in Semen in a Traveler Returning the United Kingdom from Brazil, 2016

by Gaskell KM, Houlihan C, Nastouli E, Checkly AM.

This case study of a male patient presenting in the UK with symptomatic Zika virus infection after travelling to Brazil found that the virus persisted in semen for 92 dyas., supporting recommendations for 6 months of barrier contraceptive use after symptomatic Zika virus infection.

Published in: Emerg Infect Dis. 2017 Jan.

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Outcomes of dengue in Jamaican children

By Davidson T., Vickers I., Christie CD. 

Dengue fever is hyper-endemic in Jamaica with exponential rates of infection in successive outbreaks. The absence of local data and the potential for massive outbreaks in a country where a third of the population are children formed the basis for this study.

Published in: West Indian Medical Journal 2016;65(3);442-449. Epub, Oct, 2016.

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Chikungunya fever in Jamaican children: public health effects and clinical features.

By Christie CD, Melbourne-Chambers R, Ennevor J, Young-Peart S, Buchanan T, Scott-Brown P, McNeil-Beecher N, Fulford-Ramdial T, Richards-Dawson M, James-Powell T, Jackson ST. 

Chikungunya virus entered the Caribbean for the first time in 2013 and Jamaica experienced its maiden epidemic with Chikungunya Fever in 2014. We aimed to describe the public health effects and describe the clinical features in children and adolescents in Jamaica.

Published in: West Indian Medical Journal 2016;65(3);431-437. Epub, Oct, 2016; DOI:10.7727/wimj.2016.529.

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Acute Paralysis and Neuro-inflammation in Jamaican Children during Zika Virus and Dengue Epidemics of 2016

By R Melbourne-Chambers, CDC Christie, E Greenaway, R Bullock

Dengue, Chikungunya virus (CHIKV) and Zika virus (ZIKV) are all transmitted by the Aedes aegypti mosquito and are currently circulating in Jamaica. Jamaica has been experiencing a ZIKV epidemic since February 2016. At the University Hospital of the West Indies (UHWI), Kingston, Jamaica, a cluster of five cases of paralysis attributed to neuro-inflammation was noted amongst adolescents admitted to the institution. Three were diagnosed with acute myelitis and one each with acute disseminated encephalomyelitis (ADEM) and Guillain Barre syndrome (GBS). In these patients, there were common presenting symptoms, characteristic findings of peripheral nerve involvement and a history of contact with persons with symptoms of possible ZIKV in the majority. In only one case was a viral association, Dengue infection, confirmed. This case series suggests a unique clinical pattern of neuro-inflammation in Jamaican adolescents occurring during the ZIKV epidemic and questions the role of the three circulating arboviruses in the pathogenesis.

Published in: West Indian Med J 2016; 65 (3): 425

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Neurological Syndromes in Children during the Zika virus and dengue fever outbreak in Jamaica

By Melbourne-Chambers R., Christie CD, Greenaway E., Bullock R.

Dengue, Chikungunya Fever (CHIKV) and Zika virus (ZIKV) are all transmitted by the Aedes aegypti mosquito and are currently circulating in Jamaica. Jamaica has been experiencing a ZIKV epidemic since February 2016. At the University Hospital of the West Indies (UHWI), Kingston, Jamaica, a cluster of five cases of paralysis attributed to neuro-inflammation was noted amongst adolescents admitted to the institution. Three were diagnosed with acute myelitis and one each with acute disseminated encephalomyelitis (ADEM) and guillain barre syndrome (GBS). In these patients, there were common presenting symptoms, characteristic findings of peripheral nerve involvement and a history of contact with persons with symptoms of possible ZIKV in the majority. In only one case was a viral association, Dengue infection, confirmed. This case series suggests a unique clinical pattern of neuro-inflammation in Jamaican adolescents occurring during the ZIKV epidemic and questions the role of the three circulating arboviruses in the pathogenesis.

Published in: West Indian Medical Journal 2016;65(3):425-430. Epub, Oct 2016; DOI:10.772/wimj.2016.526

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Coinfection with Zika and Dengue-2 Viruses in a Traveler Returning from Haiti, 2016: Clinical Presentation and Genetic Analysis.

by Iovine NM, Lednicky J, Cherabuddi K, Crooke H, White SK, Loeb JC, Cella E, Ciccozzi M, Salemi M, Morris JG Jr.

This case study provides details on the clinical presentation and genetic analysis of a student diagnosed with Zika and Dengue-2 virus co-infection in the United States after travel to Haiti.

Published in:Clinical Infectious Diseases, Volume 64, Issue 1, 1 January 2017, Pages 72–75.

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Emergence of the Zika Virus Epidemic in Jamaica and the National Respons Emergence of the Zika Virus Epidemic in Jamaica and the National Response.

By Webster-Kerr K, Christie CDC, Grant A., Chin, D.; Burrowes, H.; Clarke, K.; Wellington, I.; Shaw, K.; De La Haye W. 

Jamaica, along with the Americas, experienced major epidemics of arboviral diseases transmitted by the Aedes aegypti mosquito in recent years. These include dengue fever in 2012, Chikungunya fever in 2014 and Zika virus infection (ZIKV) in 2016. We present the emergence of the ZIKV epidemic in Jamaica and outline the national response.

Published in: West Indian Medical Journal 2016;65(1):243-249. Epub, Sept; DOI:10.772/wimj.2016.488

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