Zika virus

“ This suggests that, with the current Zika outbreak, the virus may spread so efficiently that by the time a vaccine becomes available to test in human clinical trials, identifying large naïve at-risk populations may be an obstacle to demonstrating efficacy.
Zika virus evolution and spread is constrained by both human and insect hosts, and this creates an opportunity to develop countermeasure strategies focusing on either or both. The interaction between pathogen and host biology will impact the incidence, prevalence and eventual distribution of the virus. ”

“ Clinical Manifestations and Pathogeny Humans Zika virus infection has been reported to be symptomatic only in around 18% of the cases ( [110] ) , in which it causes a mild, self-limiting disease with an incubation period of up to 10 days, often mistaken with other arboviral infections like dengue or chikungunya. Clinical manifestations in symptomatic cases resemble that of an influenza-like syndrome ( [68] ) , being the most common symptoms fever, rash, arthralgia, and conjunctivitis ”

“ To optimize MCM development, the link between infectious cause and clinical effect must be clearly established. However, as evidence has accumulated, skepticism about a causal link between Zika spread and primary microcephaly incidence has given way to growing acceptance that Zika virus infection during the first and second trimester may be a major contributing factor to the surge in microcephaly. The possible increase in GBS incidence, associated morbidity and mortality, and potential association of these disease symptoms with Zika is not as solid. ”

“ Zika virus (ZIKV) is also an arthropod-borne flavivirus, which was initially isolated in 1947 from a febrile sentinel rhesus monkey in the Zika forest in Entebbe, Uganda. ZIKV is transmitted by multiple Aedes mosquitoes (Lazear and Diamond, [2] ) . Historically, ZIKV infection typically caused a mild and self-limiting illness in human beings, accompanied by fever, headache, arthralgia, myalgia, and maculopapular rash (Ioos et al., [3] ) . ZIKV caught global attention in April 2007, when it caused a large epidemic of Asian genotype ZIKV in Yap Island and Guam, Micronesia. ”

“ Death after Zika virus infection of an otherwise healthy patient with sickle cell disease has also been reported, indicating increased risk to otherwise medically compromised individuals [ [23] ] . The more severe Zika disease symptoms were not observed during the 2007 Yap Island, Micronesia, Zika outbreak, although approximately 5,000 people were infected [ [24] ] . Zika virus infection and disease is now a reportable illness in the United States, and as of February 2016, has spread to the countries and territories summarized in Table 1. ”

“ In addition to mother-to-child transmission, during the last decade, cases of sexual transmission have been reported [ [10] – [11] ] , representing a non-vector borne form of transmission of Zika virus (Fig. 1) . Zika virus has been detected in human saliva [ [12] ] , blood, semen and urine [ [13] ] . It has been recently detected in semen and urine of, respectively, a patient after 62 days of infection [ [14] ] and another patient after 14 days of infection [ [15] ] . Also spread of the virus through blood transfusion and organ transplantation have been reported or suspected [ [16] ] . ”

“ Abstract Since the beginning of this century, humanity has been facing a new emerging, or re-emerging, virus threat almost every year: West Nile, Influenza A, avian flu, dengue, Chikungunya, SARS, MERS, Ebola, and now Zika, the latest newcomer. Zika virus (ZIKV) , a flavivirus transmitted by Aedes mosquitoes, was identified in 1947 in a sentinel monkey in Uganda, and later on in humans in Nigeria. ”

“ Abstract Introduction Reports of high rates of primary microcephaly and Guillain–Barré syndrome associated with Zika virus infection in French Polynesia and Brazil have raised concerns that the virus circulating in these regions is a rapidly developing neuropathic, teratogenic, emerging infectious public health threat. There are no licensed medical countermeasures (vaccines, therapies or preventive drugs) available for Zika virus infection and disease. ”

“ It is epidemic in a region with a high degree of global connectivity; cases will be widely disseminated. The Zika epidemic is moving very rapidly. Research reagents, animal models, and fundamental science knowledge are much less well developed than they were for Ebola. On the other hand, decades of experience with dengue, YFYF, and West Nile have equipped us with familiarity with ADE and flavivirus vaccine development strategies. Zika virus is likely a harbinger of future diseases driven by ecosystem change and global interconnectedness. ”

“ The Evolving Epidemiology of Zika Virus Spread into the Americas In contrast to the relatively slow spread of Ebola virus through West Africa, the Zika outbreak in the Americas appears to be moving very rapidly. While the potential association of Zika virus with teratology and neuropathology place a particular urgency on the development of MCM, strategies for developing and deploying MCM must account for the differences and similarities between the observed epidemiology and that of prior outbreaks. ”

“ Zika virus (ZIKV) , a mosquito borne flavivirus is a pathogen affecting humans in Asia and Africa. ZIKV infection diagnosis relies on serology–which is challenging due to cross-reactions with other flaviviruses and/or absence or low titer of IgM and IgG antibodies at early phase of infection- virus isolation, which is labor intensive, time consuming and requires appropriate containment. Therefore, real-time RT-PCR (rRT-PCR) is an appealing option as a rapid, sensitive and specific method for detection of ZIKV in the early stage of infection. ”

“ Nevertheless, in addition to all epidemiological implications of the outbreak in Latin America [ [3] ] the number of affected cases continue to rise and expected to reach over four million in 2016, adding to this the possibility of new modes of transmission.
Zika virus is a zoonotic pathogen, naturally and experimentally hosted in non-human primates [ [4] ] as well as experimentally in Swiss albino mices [ [5] , [6] ] . ”

“ To summarize these events and to help guide assessment of genetic and immunologic differences between historic and current Zika virus populations, we performed preliminary phylogeographic analyses of available molecular sequence data and metadata (place and time of isolation) from the viruses to connect these incidents via shared ancestry of the sequences. Based on data released as of January 18, 2016 we have focused on two genes to reconstruct the spread and evolution of Zika from Africa to Southeast Asia to the South Pacific and to South America ”

“ Given the recent spread of the virus, systematic investigation of spontaneous abortions and stillbirths may be warranted to evaluate the risk that ZIKV infection imparts on these outcomes.
Introduction
The current outbreak of microcephaly has raised speculations that Zika virus (ZIKV) causes a congenital syndrome. ZIKV, a mosquito-borne flavivirus, was detected in Brazil in early 2015 [1] , [2] and has rapidly spread throughout the Americas [3] . ”

“ Uncertainties about Zika virus transmission abound. The degree to which humans, non-human primates, or other animals can amplify and transmit the virus to insect vectors is poorly understood. The typical range and types of insect vectors observed in the past may not be predictive for the virus now circulating in the Americas. Infectivity of the circulating strain, viremia levels, duration, and risk of occult persistence are not yet understood. ”

“ The CD8+ T cell responses to dengue infection are primarily directed to nonstructural protein epitopes including NS3 and NS5. Human infection by dengue provides one of the most classic examples of antibody dependent enhancement of disease by pre-existing non-neutralizing antibody, resulting in dengue hemorrhagic fever [ [101] , [102] ] . The potential role of antibody dependent enhancement (ADE) of Zika infection and disease has not been examined.
The duration of viremia, infectivity, and persistence of Zika virus, is not known for either post-partum or intrauterine infection. ”

“ Preventing infections in only 1.6% of the population is likely achievable since previous attack rates of Zika virus in Yap Island and French Polynesia have been estimated to range between 62% and 77% [ [15] , [24] ] . ”

“ The Pan American Health Organization (PAHO) predicts that Zika virus will continue to spread and eventually reach all countries and territories in the Americas with endemic Aedes mosquitoes. This paper reviews the status of the Zika virus outbreak, including medical countermeasure options, with a focus on how the epidemiology, insect vectors, neuropathology, virology and immunology inform options and strategies available for medical countermeasure development and deployment. ”

“ Opportunities and strategies for Zika medical management and countermeasure development will benefit from answers to key questions concerning the virology and immunology of Zika infection in the human host. A better understanding of natural immune responses and viral infection may clarify the potential role of Zika in eliciting GBS or microcephaly. Targeted identification and design of antivirals, neutralizing antibody preparations and immunotherapeutics still require understanding of the underlying biology. ”

“ 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. ”

“ Our results indicated that ZIKV may have experienced recombination in nature and that, after it emerged from Uganda in the early of the 20th century, it moved to West Africa and Asia in the first half of the century, without any clear preference for host and vector species.
Introduction
Zika virus (ZIKV) is a mosquito-borne flavivirus, a member of the Spondweni serocomplex, whose natural transmission cycle involves mainly vectors from the Aedes genus (A. furcifer, A. taylori, A. luteocephalus and A. africanus) and monkeys [1] , while humans are occasional hosts. ”

“ Then, serological and entomological Zika infection were reported in different area in Africa (Burkina Faso, Ivory Cost, Egypt, Central African Republic, Mozambic, Nigeria, Uganda, Central African Republic and Senegal) [2] , [11] , [12] - [13] . Between 1968 and 2002, 606 strains including 10 human ZIKV strains were isolated in Central and West Africa countries and reported by the WHO Collaborating Center for Arbovirus and Viral Hemorrhagic Fever of Pasteur Institute in Dakar [14] . ”

“ In the case of many arboviruses, mosquito salivary gland products enhance viral infectivity and replication. Zika infection of the recipient host requires viral envelope protein binding and particle uptake into susceptible cells, is mediated by specific receptors which include DC-SIGN, AXL, Tyro3, and TIM-1, and triggers transcriptional activation of Toll-like receptor 3 (TLR3) , RIG-I, MDA5, interferon stimulated genes including OAS2, ISG15, and MX1, and beta interferon [ [97] ] . Primarily infected cells include skin fibroblasts, epidermal keratinocytes, and skin dendritic cells. ”

“ Areas in the southern parts of Texas demonstrated higher rates of poverty than some other regions under study (Fig. 3) . Coupled with the higher levels of travel from areas where transmission is occurring and the history of Ae. aegypti –borne virus outbreaks, this suggests that southern Texas may be a vulnerable region for Zika transmission.
Even if Zika virus arrives in the United States, transmission can be mitigated and reduced through the use of vector control strategies. ”

“ Recently, and albeit an estimated 80% of ZIKV infected people are asymptomatic3, during the ongoing outbreak in Brazil, ZIKV RNA has been identified in brain, placenta, and amniotic fluid specimens, and its presence has been associated to microcephaly in infants and miscarries during pregnancy ( [70] ; [71] ) .
One important aspect that still has to be clarified is whether ZIKV infection in humans drives to viral titers enough to initiate a new cycle when an infected person is bitten by a naïve mosquito. ”

“ In August 2008, a scientist was bitten many times while studying mosquitoes in south-eastern Senegal. Six days after returning to his home in Colorado (U.S.) , he felt ill with symptoms of Zika fever and hematospermia. By then, he had had unprotected intercourse with his wife, who had not been outside the U.S. during the previous year, which subsequently developed symptoms of Zika fever. Virus infection was confirmed by serologic testing in both, but the presence of ZIKV in the semen of the patient was not investigated ( [83] ) . ”

“ As a result of these data, it has been suggested to collect both blood and saliva samples to increase the sensitivity of molecular detection of viral RNA for Zika fever diagnosis in acute phase. On the other hand, urine sample can be associated at the late stages of the disease. Thus, when detection of ZIKV is of particular importance, using a combination of samples (blood/saliva/urine) is recommended ( [86] ) .
Prophylaxis Currently there are no specific antiviral agents, vaccine, or prophylaxis for ZIKV. Treatment is generally directed to symptom relief with analgesics and anti-pyretics. ”