Zika virus (ZIKV) is an arbovirus belonging to the genus Flavivirus (family Flaviviridae) and was first described in 1947 in Uganda following blood analyses of sentinel Rhesus monkeys. Until the twentieth century, the African and Asian lineages of the virus did not cause meaningful infections in humans. However, in 2007, vectored by Aedes aegypti mosquitoes, ZIKV caused the first noteworthy epidemic on the Yap Island in Micronesia. Patients experienced fever, skin rash, arthralgia and conjunctivitis. From 2013 to 2015, the Asian lineage of the virus caused further massive outbreaks in New Caledonia and French Polynesia. In 2013, ZIKV reached Brazil, later spreading to other countries in South and Central America. In Brazil, the virus has been linked to congenital malformations, including microcephaly and other severe neurological diseases, such as Guillain-Barre syndrome. Despite clinical evidence, direct experimental proof showing that the Brazilian ZIKV (ZIKV(BR)) strain causes birth defects remains absent. Here we demonstrate that ZIKV(BR) infects fetuses, causing intrauterine growth restriction, including signs of microcephaly, in mice. Moreover, the virus infects human cortical progenitor cells, leading to an increase in cell death. We also report that the infection of human brain organoids results in a reduction of proliferative zones and disrupted cortical layers. These results indicate that ZIKV(BR) crosses the placenta and causes microcephaly by targeting cortical progenitor cells, inducing cell death by apoptosis and autophagy, and impairing neurodevelopment. Our data reinforce the growing body of evidence linking the ZIKV(BR) outbreak to the alarming number of cases of congenital brain malformations. Our model can be used to determine the efficiency of therapeutic approaches to counteracting the harmful impact of ZIKV(BR) in human neurodevelopment.

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The Brazilian Zika virus strain causes birth defects in experimental models

An update on Zika virus infection

First discovered in 1947, Zika virus (ZIKV) infection remained a little-known tropical disease until 2015, when its apparent association with a considerable increase in the incidence of microcephaly in Brazil raised alarms worldwide. There is limited information on the key factors that determine the extent of the global threat from ZIKV infection and resulting complications. Here, we review what is known about the epidemiology, natural history, and public health effects of ZIKV infection, the empirical basis for this knowledge, and the critical knowledge gaps that need to be filled.

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Assessing the global threat from Zika virus

Arthropod-borne viruses (arboviruses) have a long history of emerging to infect humans, but during recent decades, they have been spreading more widely and affecting larger populations. This is due to several factors, including increased air travel and uncontrolled mosquito vector populations. Emergence can involve simple spillover from enzootic (wildlife) cycles, as in the case of West Nile virus accompanying geographic expansion into the Americas; secondary amplification in domesticated animals, as seen with Japanese encephalitis, Venezuelan equine encephalitis, and Rift Valley fever viruses; and urbanization, in which humans become the amplification hosts and peridomestic mosquitoes, mainly Aedes aegypti, mediate human-to-human transmission. Dengue, yellow fever, chikungunya, and Zika viruses have undergone such urban emergence. We focus mainly on the latter two, which are recent arrivals in the Western Hemisphere. We also discuss a few other viruses with the potential to emerge through all of these mechanisms.

Zika, Chikungunya, and Other Emerging Vector-Borne Viral Diseases

Both rhesus and cynomolgus macaques are susceptible to subcutaneous infection with Zika virus; longitudinal studies of infected animals provide information about the temporal dynamics of Zika virus in distinct cells, tissues and body fluids, as well as the immune response to the virus.

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Zika viral dynamics and shedding in rhesus and cynomolgus macaques.

Background
In 2015, Brazil was faced with the cocirculation of three arboviruses of major public health importance. The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between diseases caused by
ZIKV, Dengue (DENV) and Chikungunya (CHIKV) and the lack of validated serological
assays for ZIKV make accurate diagnosis difficult.
Methodology / Principal Findings
The outpatient service for acute febrile illnesses in Fiocruz initiated a syndromic clinical observational study in 2007 to capture unusual presentations of DENV infections. In January
2015, an increase of cases with exanthematic disease was observed. Trained physicians
evaluated the patients using a detailed case report form that included clinical
assessment and laboratory investigations. The laboratory diagnostic algorithm included
assays for detection of ZIKV, CHIKV and DENV. 364 suspected cases of Zika virus disease
were identified based on clinical criteria between January and July 2015. Of these, 262
(71.9%) were tested and 119 (45.4%) were confirmed by the detection of ZIKV RNA. All of
the samples with sequence information available clustered within the Asian genotype. Conclusions / Significance
This is the first report of a ZIKV outbreak in the state of Rio de Janeiro, based on a large
number of suspected (n = 364) and laboratory confirmed cases (n = 119). We were able to
demonstrate that ZIKV was circulating in Rio de Janeiro as early as January 2015. The
peak of the outbreak was documented in May/June 2015. More than half of the patients
reported headache, arthralgia, myalgia, non-purulent conjunctivitis, and lower back pain,
consistent with the case definition of suspected ZIKV disease issued by the Pan American
Health Organization (PAHO). However, fever, when present, was low-intensity and shorttermed.
In our opinion, pruritus, the second most common clinical sign presented by the
confirmed cases, should be added to the PAHO case definition, while fever could be given
less emphasis. The emergence of ZIKV as a new pathogen for Brazil in 2015 underscores
the need for clinical vigilance and strong epidemiological and laboratory surveillance.

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Zika Virus Outbreak in Rio de Janeiro, Brazil: Clinical Characterization, Epidemiological and Virological Aspects

https://www.arca.fiocruz.br/bitstream/icict/35688/2/ve_Lupi_Otilia_etal_INI_2013.pdf

Carolina Romero

Papers

Zika Virus Outbreak in Rio de Janeiro, Brazil: Clinical Characterization, Epidemiological and Virological Aspects

Cluster of leptospirosis cases among military personnel in Rio de Janeiro, Brazil