Mosquito-borne Zika Virus Research Articles

Preventative Vaccines for Zika Virus Outbreak: Preliminary Evaluation

Since it emerged in Brazil in May 2015, the mosquito-borne Zika virus (ZIKV) has raised global concern due to its association with a significant rise in the number of infants born with microcephaly and neurological disorders such as Guillain-Barré syndrome. We developed prototype subunit and adenoviral-based Zika vaccines encoding the extracellular portion of the ZIKV envelope gene (E) fused to the T4 fibritin foldon trimerization domain (Efl). The subunit vaccine was delivered intradermally through carboxymethyl cellulose microneedle array (MNA). The immunogenicity of these two vaccines, named Ad5.ZIKV-Efl and ZIKV-rEfl, was tested in C57BL/6 mice. Prime/boost immunization regimen was associated with induction of a ZIKV-specific antibody response, which provided neutralizing immunity. Moreover, protection was evaluated in seven-day-old pups after virulent ZIKV intraperitoneal challenge. Pups born to mice immunized with Ad5.ZIKV-Efl were all protected against lethal challenge infection without weight loss or neurological signs, while pups born to dams immunized with MNA-ZIKV-rEfl were partially protected (50%). No protection was seen in pups born to phosphate buffered saline-immunized mice. This study illustrates the preliminary efficacy of the E ZIKV antigen vaccination in controlling ZIKV infectivity, providing a promising candidate vaccine and antigen format for the prevention of Zika virus disease.

AXL-Mediated Productive Infection of Human Endothelial Cells by Zika Virus.

The mosquito-borne Zika virus (ZIKV) is now recognized as a blood-borne pathogen, raising an important question about how the virus gets into human bloodstream. The imminent threat of the ZIKV epidemic to the global blood supply also demands novel therapeutics to stop virus transmission though transfusion. We intend to characterize ZIKV tropism for human endothelial cells (ECs) and provide potential targets for intervention. We conducted immunostaining, plaque assay, and quantitative reverse transcription-polymerase chain reaction of ZIKV RNA to evaluate the possible infection of ECs by ZIKV. Both the African and the South American ZIKV strains readily infect human umbilical vein endothelial cells and human ECs derived from aortic and coronary artery, as well as the saphenous vein. Infected ECs released infectious progeny virus. Compared with the African strains, South American ZIKV isolates replicate faster in ECs and are partially cytopathic, suggesting enhanced virulence of these isolates. Flow cytometric analyses showed that the susceptibility of ECs positively correlated with the cell surface levels of tyrosine-protein kinase receptor UFO (AXL) receptor tyrosine kinase. Gain- and loss-of-function studies further revealed that AXL is required for ZIKV entry at a postbinding step. Finally, small-molecule inhibitors of the AXL kinase significantly reduced ZIKA infection of ECs. We identified EC as a key cell type for ZIKV infection. These data support the view of hematogenous dissemination of ZIKV and implicate AXL as a new target for antiviral therapy.

Potential for Zika virus introduction and transmission in resource-limited countries in Africa and the Asia-Pacific region: a modelling study

As the epidemic of Zika virus expands in the Americas, countries across Africa and the Asia-Pacific region are becoming increasingly susceptible to the importation and possible local spread of the virus. To support public health readiness, we aim to identify regions and times where the potential health, economic, and social effects from Zika virus are greatest, focusing on resource-limited countries in Africa and the Asia-Pacific region. Our model combined transportation network analysis, ecological modelling of mosquito occurrences, and vector competence for flavivirus transmission, using data from the International Air Transport Association, entomological observations from Zika's primary vector species, and climate conditions using WorldClim. We overlaid monthly flows of airline travellers arriving to Africa and the Asia-Pacific region from areas of the Americas suitable for year-round transmission of Zika virus with monthly maps of climatic suitability for mosquito-borne transmission of Zika virus within Africa and the Asia-Pacific region. An estimated 2·6 billion people live in areas of Africa and the Asia-Pacific region where the presence of competent mosquito vectors and suitable climatic conditions could support local transmission of Zika virus. Countries with large volumes of travellers arriving from Zika virus-affected areas of the Americas and large populations at risk of mosquito-borne Zika virus infection include India (67 422 travellers arriving per year; 1·2 billion residents in potential Zika transmission areas), China (238 415 travellers; 242 million residents), Indonesia (13 865 travellers; 197 million residents), Philippines (35 635 travellers; 70 million residents), and Thailand (29 241 travellers; 59 million residents). Many countries across Africa and the Asia-Pacific region are vulnerable to Zika virus. Strategic use of available health and human resources is essential to prevent or mitigate the health, economic, and social consequences of Zika virus, especially in resource-limited countries. Canadian Institutes of Health Research and the US Centers for Disease Control and Prevention.

Contraceptive Use Among Nonpregnant and Postpartum Women at Risk for Unintended Pregnancy, and Female High School Students, in the Context of Zika Preparedness - United States, 2011-2013 and 2015.

Zika virus infection during pregnancy can cause congenital microcephaly and brain abnormalities (1,2). Since 2015, Zika virus has been spreading through much of the World Health Organization's Region of the Americas, including U.S. territories. Zika virus is spread through the bite of Aedes aegypti or Aedes albopictus mosquitoes, by sex with an infected partner, or from a pregnant woman to her fetus during pregnancy.* CDC estimates that 41 states are in the potential range of Aedes aegypti or Aedes albopictus mosquitoes (3), and on July 29, 2016, the Florida Department of Health identified an area in one neighborhood of Miami where Zika virus infections in multiple persons are being spread by bites of local mosquitoes. These are the first known cases of local mosquito-borne Zika virus transmission in the continental United States.(†) CDC prevention efforts include mosquito surveillance and control, targeted education about Zika virus and condom use to prevent sexual transmission, and guidance for providers on contraceptive counseling to reduce unintended pregnancy. To estimate the prevalence of contraceptive use among nonpregnant and postpartum women at risk for unintended pregnancy and sexually active female high school students living in the 41 states where mosquito-borne transmission might be possible, CDC used 2011-2013 and 2015 survey data from four state-based surveillance systems: the Behavioral Risk Factor Surveillance System (BRFSS, 2011-2013), which surveys adult women; the Pregnancy Risk Assessment Monitoring System (PRAMS, 2013) and the Maternal and Infant Health Assessment (MIHA, 2013), which surveys women with a recent live birth; and the Youth Risk Behavior Survey (YRBS, 2015), which surveys students in grades 9-12. CDC defines an unintended pregnancy as one that is either unwanted (i.e., the pregnancy occurred when no children, or no more children, were desired) or mistimed (i.e., the pregnancy occurred earlier than desired). The proportion of women at risk for unintended pregnancy who used a highly effective reversible method, known as long-acting reversible contraception (LARC), ranged from 5.5% to 18.9% for BRFSS-surveyed women and 6.9% to 30.5% for PRAMS/MIHA-surveyed women. The proportion of women not using any contraception ranged from 12.3% to 34.3% (BRFSS) and from 3.5% to 15.3% (PRAMS/MIHA). YRBS data indicated that among sexually active female high school students, use of LARC at last intercourse ranged from 1.7% to 8.4%, and use of no contraception ranged from 7.3% to 22.8%. In the context of Zika preparedness, the full range of contraceptive methods approved by the Food and Drug Administration (FDA), including LARC, should be readily available and accessible for women who want to avoid or delay pregnancy. Given low rates of LARC use, states can implement strategies to remove barriers to the access and availability of LARC including high device costs, limited provider reimbursement, lack of training for providers serving women and adolescents on insertion and removal of LARC, provider lack of knowledge and misperceptions about LARC, limited availability of youth-friendly services that address adolescent confidentiality concerns, inadequate client-centered counseling, and low consumer awareness of the range of contraceptive methods available.

Female-to-Male Transmission of Zika Virus

Since the first descriptions of mosquito-borne Zika virus in South America and the Caribbean in 2015, evidence has been mounting that the infection can be spread through unprotected sexual intercourse from males to females who have not traveled to endemic areas. Now the Centers for Disease Control and Prevention and the New York City Department of Health and Mental Hygiene provide evidence that a …

Projected Zika Virus Importation and Subsequent Ongoing Transmission after Travel to the 2016 Olympic and Paralympic Games - Country-Specific Assessment, July 2016.

Zika virus belongs to the genus Flavivirus of the family Flaviviridae; it is transmitted to humans primarily through the bite of an infected Aedes species mosquito (e.g., Ae. aegypti and Ae. albopictus) (1). Zika virus has been identified as a cause of congenital microcephaly and other serious brain defects (2). As of June 30, 2016, CDC had issued travel notices for 49 countries and U.S. territories across much of the Western hemisphere (3), including Brazil, where the 2016 Olympic and Paralympic Games (Games of the XXXI Olympiad, also known as Rio 2016; Games) will be hosted in Rio de Janeiro in August and September 2016. During the Games, mosquito-borne Zika virus transmission is expected to be low because August and September are winter months in Brazil, when cooler and drier weather typically reduces mosquito populations (4). CDC conducted a risk assessment to predict those countries susceptible to ongoing Zika virus transmission resulting from introduction by a single traveler to the Games. Whereas all countries are at risk for travel-associated importation of Zika virus, CDC estimated that 19 countries currently not reporting Zika outbreaks have the environmental conditions and population susceptibility to sustain mosquito-borne transmission of Zika virus if a case were imported from infection at the Games. For 15 of these 19 countries, travel to Rio de Janeiro during the Games is not estimated to increase substantially the level of risk above that incurred by the usual aviation travel baseline for these countries. The remaining four countries, Chad, Djibouti, Eritrea, and Yemen, are unique in that they do not have a substantial number of travelers to any country with local Zika virus transmission, except for anticipated travel to the Games. These four countries will be represented by a projected, combined total of 19 athletes (plus a projected delegation of about 60 persons), a tiny fraction of the 350,000-500,000 visitors expected at the Games.* Overall travel volume to the Games represents a very small fraction (<0.25%) of the total estimated 2015 travel volume to Zika-affected countries,(†) highlighting the unlikely scenario that Zika importation would be solely attributable to travel to the Games. To prevent Zika virus infection and its complications among athletes and visitors to the Games and importation of Zika virus into countries that could sustain local transmission, pregnant women should not travel to the Games, mosquito bites should be avoided while traveling and for 3 weeks after returning home, and measures should be taken to prevent sexual transmission (Box).

Mechanisms of Zika Virus Infection and Neuropathogenesis.

A spotlight has been focused on the mosquito-borne Zika virus (ZIKV) because of its epidemic outbreak in Brazil and Latin America, as well as the severe neurological manifestations of microcephaly and Guillain-Barré syndrome associated with infection. In this review, we discuss the recent literature on ZIKV-host interactions, including new mechanistic insight concerning the basis of ZIKV-induced neuropathogenesis.

Characterization of a Novel Murine Model to Study Zika Virus.

The mosquito-borne Zika virus (ZIKV) is responsible for an explosive ongoing outbreak of febrile illness across the Americas. ZIKV was previously thought to cause only a mild, flu-like illness, but during the current outbreak, an association with Guillain–Barré syndrome and microcephaly in neonates has been detected. A previous study showed that ZIKV requires murine adaptation to generate reproducible murine disease. In our study, a low-passage Cambodian isolate caused disease and mortality in mice lacking the interferon (IFN) alpha receptor (A129 mice) in an age-dependent manner, but not in similarly aged immunocompetent mice. In A129 mice, viremia peaked at ∼107 plaque-forming units/mL by day 2 postinfection (PI) and reached high titers in the spleen by day 1. ZIKV was detected in the brain on day 3 PI and caused signs of neurologic disease, including tremors, by day 6. Robust replication was also noted in the testis. In this model, all mice infected at the youngest age (3 weeks) succumbed to illness by day 7 PI. Older mice (11 weeks) showed signs of illness, viremia, and weight loss but recovered starting on day 8. In addition, AG129 mice, which lack both type I and II IFN responses, supported similar infection kinetics to A129 mice, but with exaggerated disease signs. This characterization of an Asian lineage ZIKV strain in a murine model, and one of the few studies reporting a model of Zika disease and demonstrating age-dependent morbidity and mortality, could provide a platform for testing the efficacy of antivirals and vaccines.

Revision to CDC's Zika Travel Notices: Minimal Likelihood for Mosquito-Borne Zika Virus Transmission at Elevations Above 2,000 Meters.

Since May 2015, when Zika virus, a flavivirus transmitted primarily by Aedes aegypti mosquitoes, was reported in Brazil, the virus has rapidly spread across the Region of the Americas and the Caribbean. The association between maternal Zika virus infection and adverse fetal and reproductive outcomes, including microcephaly, prompted CDC to issue a Level 2 alert travel notice* for the 37 countries and U.S. territories (at the national and territorial level) that have reported recent Zika virus transmission as of March 11, 2016. In addition to mosquito bite precautions for all travelers, CDC advises that pregnant women postpone travel to affected countries and U.S. territories. Within a nation's borders, ecologic characteristics, which determine the distribution of mosquito vectors, can vary considerably. CDC conducted a spatial analysis, focusing on the probability of occurrence of Ae. aegypti, to support the demarcation for subnational travel alerts. Based on results of this analysis, travel that is limited to elevations higher than 2,000 m (6,562 ft) above sea level is considered to have minimal (approximately 1%) likelihood for mosquito-borne Zika virus transmission, even within countries reporting active transmission. Women who are pregnant should avoid travel to elevations <2,000 m in countries with active Zika virus transmission.

Revision to CDC’s Zika Travel Notices: Minimal Likelihood for Mosquito-Borne Zika Virus Transmission at Elevations Above 2,000 Meters

Since May 2015, when Zika virus, a flavivirus transmitted primarily by Aedes aegypti mosquitoes, was reported in Brazil, the virus has rapidly spread across the Region of the Americas and the Caribbean. The association between maternal Zika virus infection and adverse fetal and reproductive outcomes, including microcephaly, prompted CDC to issue a Level 2 alert travel notice* for the 37 countries and U.S. territories (at the national and territorial level) that have reported recent Zika virus transmission as of March 11, 2016. In addition to mosquito bite precautions for all travelers, CDC advises that pregnant women postpone travel to affected countries and U.S. territories. Within a nation's borders, ecologic characteristics, which determine the distribution of mosquito vectors, can vary considerably. CDC conducted a spatial analysis, focusing on the probability of occurrence of Ae. aegypti, to support the demarcation for subnational travel alerts. Based on results of this analysis, travel that is limited to elevations higher than 2,000 m (6,562 ft) above sea level is considered to have minimal (approximately 1%) likelihood for mosquito-borne Zika virus transmission, even within countries reporting active transmission. Women who are pregnant should avoid travel to elevations <2,000 m in countries with active Zika virus transmission.

Rapid Spread of Zika Virus in The Americas--Implications for Public Health Preparedness for Mass Gatherings at the 2016 Brazil Olympic Games.

Mass gatherings at major international sporting events put millions of international travelers and local host-country residents at risk of acquiring infectious diseases, including locally endemic infectious diseases. The mosquito-borne Zika virus (ZIKV) has recently aroused global attention due to its rapid spread since its first detection in May 2015 in Brazil to 22 other countries and other territories in the Americas. The ZIKV outbreak in Brazil, has also been associated with a significant rise in the number of babies born with microcephaly and neurological disorders, and has been declared a 'Global Emergency by the World Health Organization. This explosive spread of ZIKV in Brazil poses challenges for public health preparedness and surveillance for the Olympics and Paralympics which are due to be held in Rio De Janeiro in August, 2016. We review the epidemiology and clinical features of the current ZIKV outbreak in Brazil, highlight knowledge gaps, and review the public health implications of the current ZIKV outbreak in the Americas. We highlight the urgent need for a coordinated collaborative response for prevention and spread of infectious diseases with epidemic potential at mass gatherings events.

Mosquito Abatement, Crop Production and Mining Practices Monitoring for the Control of Mosquito-Borne Infectious Diseases

There is a plethora of articles and studies regarding the emerging and rapidly spreading mosquito borne Zika virus vectored by the Aedes egyptii mosquito. This article focuses on the methods used for mosquito control to reduce the the spread of mosquito borne viruses such as dengue, malaria and Zika virus with speculation regarding the origin and spread of the Zika virus. Other sources of what may have caused the same results as the Zika virus are explored, i.e., what chemicals in the water or crops may have polluted the water or infected the mosquitos through cross-transmission from crops to mosquitoes to simian species to humans that may result in deformities and neurological damage?

A Review on Zika Virus

The Zika virus is a mosquito-transmitted infection common in Africa and Asia, it did not begin spreading widely in the Western Hemisphere, when an outbreak occurred in Brazil. Few people with less immunity, showed rapidly spreading with infection. Millions of people in tropical regions of the Americas now have been infected. The infection causes no symptoms and leads to no lasting harm. Scientific concern is focused on women who become infected while pregnant and those who develop a temporary form of paralysis after exposure to the virus. The World Health Organization has declared the Zika virus an international public health emergency, that it causes birth defects. As many as four million people could be infected by the end of the year. Officials at the Centers for Disease Control and Prevention have urged pregnant women against travel to more than thirty countries, mostly in the Caribbean and Latin America, where the outbreak is growing. Some pregnant women who have been to these regions should be tested for the infection. The infection appears to be linked to the development of unusually small heads and brain damage in newborns - called microcephaly - as well as other neurological defects. In adults, the virus is linked to a form of temporary paralysis. The vast majority of Zika infections are transmitted by mosquitoes, sexually transmitted in only few cases (around dozen). Recently Bharat Biotech, a Hyderabad-based vaccines and bio-therapeutic manufacturer, developed a vaccine to fight against the dreaded mosquito-borne Zika virus. This review gives an idea about the recent advances or developments available for treating Zika infection.