Zika virus, pathology, and control: Zika vaccine strategies in development

AbstractAlthough live attenuated vaccines (LAVs) have been effective in the control of flavivirus infections, to date they have been excluded from Zika virus (ZIKV) vaccine trials due to safety concerns. We have previously reported two ZIKV mutants, each of which has a single substitution in either envelope (E) glycosylation or nonstructural (NS) 4B P36 and displays a modest reduction in mouse neurovirulence and neuroinvasiveness, respectively. Here, we generated a ZIKV mutant, ZE4B-36, which combines mutations in both E glycosylation and NS4B P36. The ZE4B-36 mutant is stable and attenuated in viral replication. Next-generation sequence analysis showed that the attenuating mutations in the E and NS4B proteins are retained during serial cell culture passages. The mutant exhibits a significant reduction in neuroinvasiveness and neurovirulence and low infectivity in mosquitoes. It induces robust ZIKV-specific memory B cell, antibody, and T cell-mediated immune responses in type I interferon receptor (IFNR) deficient mice. ZIKV-specific T cell immunity remains strong months post-vaccination in wild-type C57BL/6 (B6) mice. Vaccination with ZE4B-36 protects mice from ZIKV-induced diseases and vertical transmission. Our results suggest that combination mutations in E glycosylation and NS4B P36 contribute to a candidate LAV with significantly increased safety but retain strong immunogenicity for prevention and control of ZIKV infection.

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Vectors, Hosts, and Control Measures for Zika Virus in the Americas

EcoHealth ◽

10.1007/s10393-017-1277-2 ◽

2017 ◽

Vol 14 (4) ◽

pp. 821-839 ◽

Cited By ~ 3

Author(s):

Sarah J. Thompson ◽

John M. Pearce ◽

Andrew M. Ramey

Keyword(s):

Zika Virus ◽

Control Measures ◽

And Control

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Times to Key Events in the Course of Zika Infection and their Implications for Surveillance: A Systematic Review and Pooled Analysis

10.1101/041913 ◽

2016 ◽

Cited By ~ 9

Author(s):

Justin Lessler ◽

Cassandra T. Ott ◽

Andrea C. Carcelen ◽

Jacob M. Konikoff ◽

Joe Williamson ◽

...

Keyword(s):

Systematic Review ◽

Blood Supply ◽

Zika Virus ◽

Blood Donation ◽

Case Reports ◽

Fold Increase ◽

Pooled Analysis ◽

Control Measures ◽

History Of ◽

And Control

Background Evidence suggests that Zika virus has driven a 10-fold increase in babies born with microcephaly in Brazil, prompting the WHO to declare a Public Health Emergency of International Concern. However, little is known about the natural history of infection. These data are critical for implementation of surveillance and control measures such as protecting the blood supply. Methods We conducted a systematic review and pooled analysis to estimate the distribution of times from Zika infection to symptom onset, seroconversion, and viral clearance, and analyzed their implications for surveillance and blood supply safety. Results Based on 25 case reports, we estimate the median incubation period of Zika virus infection is 5.9 days (95% CI: 4.4-7.6), and that 95% of cases will develop symptoms by 11.1 days post-infection (95% CI: 7.6-18.0). On average seroconversion occurs 9.0 days (95% CI, 7.0-11.6) after infection, and virus is detectable in blood for 9.9 days (95% CI: 6.8-21.4). In 5% of cases detectable virus persists for over 18.9 days (95% CI: 12.6-79.5). The baseline (no screening) risk of a blood donation being infected with Zika increases by approximately 1 in 10,000 for every 1 per 100,000 person-days increase in Zika incidence. Symptom based screening reduces this by 7% (RR 0.93, 93% CI 0.86-0.99), and antibody screening by 29% (RR 0.71, 95% CI: 0.28-0.88). Conclusions Symptom or antibody-based surveillance can do little to reduce the risk of Zika contaminated blood donations. High incidence areas may consider PCR testing to identify lots safe for use in pregnant women.

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Examining Mosquito Surveillance and Control Capacity in the Top 10 Areas at Risk for Zika Virus Exposure in the United States

Journal of Public Health Management and Practice ◽

10.1097/phh.0000000000000646 ◽

2017 ◽

Vol 23 (5) ◽

pp. 515-517 ◽

Cited By ~ 1

Author(s):

Chelsea L. Gridley-Smith

Keyword(s):

United States ◽

At Risk ◽

Zika Virus ◽

The United States ◽

Mosquito Surveillance ◽

Virus Exposure ◽

And Control

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Emergence of Epidemic Zika Virus Transmission and Congenital Zika Syndrome: Are Recently Evolved Traits to Blame?

mBio ◽

10.1128/mbio.02063-16 ◽

2017 ◽

Vol 8 (1) ◽

Cited By ~ 30

Author(s):

Scott C. Weaver

Keyword(s):

Zika Virus ◽

Virus Transmission ◽

Severe Infection ◽

Human Infection ◽

Conclusive Evidence ◽

Control Measures ◽

Human Populations ◽

Reverse Genetic ◽

Congenital Zika Syndrome ◽

And Control

ABSTRACT The mechanisms responsible for the dramatic emergence of Zika virus (ZIKV), accompanied by congenital Zika syndrome and Guillain-Barré syndrome (GBS), remain unclear. However, two hypotheses are prominent: (i) evolution for enhanced urban transmission via adaptation to mosquito vectors, or for enhanced human infection to increase amplification, or (ii) the stochastic introduction of ZIKV into large, naive human populations in regions with abundant Aedes aegypti populations, leading to enough rare, severe infection outcomes for their first recognition. Advances in animal models for human infection combined with improvements in serodiagnostics, better surveillance, and reverse genetic approaches should provide more conclusive evidence of whether mosquito transmission or human pathogenesis changed coincidentally with emergence in the South Pacific and the Americas. Ultimately, understanding the mechanisms of epidemic ZIKV emergence, and its associated syndromes, is critical to predict future risks as well as to target surveillance and control measures in key locations.

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Desafios para o controle e prevenção do mosquito aedes aegypiti

Revista de Enfermagem UFPE on line ◽

10.5205/1981-8963-v11i12a25059p4913-4918-2017 ◽

2017 ◽

Vol 11 (12) ◽

pp. 4913 ◽

Cited By ~ 2

Author(s):

Lays Santos França ◽

Camilla Massaranduba Alves De Macedo ◽

Sheylla Nayara Sales Vieira ◽

Andresa Teixeira Santos ◽

Gislene De Jesus Cruz Sanches ◽

...

Keyword(s):

Aedes Aegypti ◽

Dengue Virus ◽

Community Health ◽

Zika Virus ◽

Public Management ◽

Prevention And Control ◽

Structured Interview ◽

Endemic Diseases ◽

Virus Zika ◽

And Control

RESUMOObjetivo: identificar os desafios enfrentados pelos agentes comunitários de saúde e agentes de combate a endemias na prevenção e controle da disseminação do mosquito Aedes aegypti. Método: estudo qualitativo realizado com 12 agentes comunitários de saúde e sete agentes de combate a endemias. Os dados foram produzidos a partir de entrevista semiestruturada e analisados com a técnica do Discurso do Sujeito Coletivo. Resultados: verificou-se que as maiores dificuldades enfrentadas por estes agentes são o descaso, a falta de compromisso e a conscientização da comunidade, além da gestão, que não se apresenta de modo efetivo no processo. Conclusão: propõe-se, assim, uma maior efetivação das ações de educação em saúde junto à população, investimento em educação permanente e sensibilização da gestão pública. Descritores: Prevenção e controle; Participação da Comunidade; Saúde Pública; Vírus da Dengue; Zika Vírus; Vírus Chikungunya.ABSTRACT Objective: to identify the challenges faced by community health agents and agents to combat endemic diseases in the prevention and control of the spread of the Aedes aegypti mosquito. Method: a qualitative study carried out with 12 community health agents and seven agents to combat endemic diseases. The data were produced from a semi-structured interview and analyzed using the Collective Subject Discourse technique. Results: it was verified that the greatest difficulties faced by these agents are the neglect, lack of commitment and awareness of the community, besides the management, that is not presented in an effective way in the process. Conclusion: it is proposed, therefore, a greater effectiveness of the actions of health education with the population, investment in permanent education and public management awareness. Descriptors: Prevention and Control; Community Participation; Public Health; Dengue Virus; Zika Virus; Chikungunya Virus.RESUMEN Objetivo: identificar los desafíos enfrentados por los agentes comunitarios de salud y agentes de combate a endemias en la prevención y control de la diseminación del mosquito Aedes aegypti. Método: estudio cualitativo, realizado con 12 agentes comunitarios de salud y siete agentes de combate a endemias. Los datos fueron producidos a partir de entrevista semiestructurada y analizados con la técnica del Discurso del Sujeto Colectivo. Resultados: se verificó que las mayores dificultades enfrentadas por estos agentes son el descuido, la falta de compromiso y la concientización de la comunidad, además de la gestión, que no se presenta de modo efectivo en el proceso. Conclusión: se propone, así una mayor efectividad de las acciones de educación en salud junto a la población, inversión en educación permanente y sensibilización de la gestión pública. Descriptores: Prevención y Control; Participación de la Comunidad; Salud Pública; Virus del Dengue; Virus Zika; Virus Chikungunya.

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Zika virus: epidemiology, clinical aspects, diagnosis, and control of infection

European Journal of Clinical Microbiology & Infectious Diseases ◽

10.1007/s10096-018-3354-z ◽

2018 ◽

Vol 37 (11) ◽

pp. 2035-2043 ◽

Cited By ~ 11

Author(s):

Ahmad Karkhah ◽

Hamid Reza Nouri ◽

Mostafa Javanian ◽

Veerendra Koppolu ◽

Jila Masrour-Roudsari ◽

...

Keyword(s):

Zika Virus ◽

Clinical Aspects ◽

And Control

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Genomic epidemiology supports multiple introductions and cryptic transmission of Zika virus in Colombia

BMC Infectious Diseases ◽

10.1186/s12879-019-4566-2 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Allison Black ◽

Louise H. Moncla ◽

Katherine Laiton-Donato ◽

Barney Potter ◽

Lissethe Pardo ◽

...

Keyword(s):

Zika Virus ◽

Genomic Sequence ◽

Sequence Data ◽

Pcr Amplification ◽

Epidemiological Studies ◽

Multiple Introductions ◽

Genomic Epidemiology ◽

Definition Of ◽

And Control ◽

Affected Country

Abstract Background Colombia was the second most affected country during the American Zika virus (ZIKV) epidemic, with over 109,000 reported cases. Despite the scale of the outbreak, limited genomic sequence data were available from Colombia. We sought to sequence additional samples and use genomic epidemiology to describe ZIKV dynamics in Colombia. Methods We sequenced ZIKV genomes directly from clinical diagnostic specimens and infected Aedes aegypti samples selected to cover the temporal and geographic breadth of the Colombian outbreak. We performed phylogeographic analysis of these genomes, along with other publicly-available ZIKV genomes from the Americas, to estimate the frequency and timing of ZIKV introductions to Colombia. Results We attempted PCR amplification on 184 samples; 19 samples amplified sufficiently to perform sequencing. Of these, 8 samples yielded sequences with at least 50% coverage. Our phylogeographic reconstruction indicates two separate introductions of ZIKV to Colombia, one of which was previously unrecognized. We find that ZIKV was first introduced to Colombia in February 2015 (95%CI: Jan 2015 – Apr 2015), corresponding to 5 to 8 months of cryptic ZIKV transmission prior to confirmation in September 2015. Despite the presence of multiple introductions, we find that the majority of Colombian ZIKV diversity descends from a single introduction. We find evidence for movement of ZIKV from Colombia into bordering countries, including Peru, Ecuador, Panama, and Venezuela. Conclusions Similarly to genomic epidemiological studies of ZIKV dynamics in other countries, we find that ZIKV circulated cryptically in Colombia. More accurately dating when ZIKV was circulating refines our definition of the population at risk. Additionally, our finding that the majority of ZIKV transmission within Colombia was attributable to transmission between individuals, rather than repeated travel-related importations, indicates that improved detection and control might have succeeded in limiting the scale of the outbreak within Colombia.

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Zika virus: an emerging challenge to public health worldwide

Canadian Journal of Microbiology ◽

10.1139/cjm-2019-0331 ◽

2020 ◽

Vol 66 (2) ◽

pp. 87-98 ◽

Cited By ~ 12

Author(s):

Vikrant Sharma ◽

Manisha Sharma ◽

Divya Dhull ◽

Yashika Sharma ◽

Sulochana Kaushik ◽

...

Keyword(s):

Zika Virus ◽

Preventive Measures ◽

East Asian ◽

Sexual Practices ◽

South East Asian Region ◽

East Asian Region ◽

Clinical Presentations ◽

Orbital Pain ◽

Congenital Microcephaly ◽

And Control

Zika virus (ZIKV) is a mosquito-borne virus that was first isolated from Zika forest, Uganda, in 1947. Since its inception, major and minor outbreaks have been documented from several parts of world. Aedes spp. mosquitoes are the primary vectors of ZIKV, but the virus can also be transmitted through sexual practices, materno-fetal transmission, and blood transfusion. The clinical presentations of symptomatic ZIKV infections are similar to dengue and chikungunya, including fever, headache, arthralgia, retro-orbital pain, conjunctivitis, and rash. ZIKV often causes mild illness in the majority of cases, but in some instances, it is linked with congenital microcephaly and autoimmune disorders like Guillain–Barré syndrome. The recent Indian ZIKV outbreak suggests that the virus is circulating in the South East Asian region and may cause new outbreaks in future. At present, no specific vaccines or antivirals are available to treat ZIKV, so management and control of ZIKV infections rely mostly on preventive measures.

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