#Zika Virus #Infection in #Pregnant Women, #Yucatan, #Mexico (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 8—August 2019 / CME ACTIVITY – Synopsis

Zika Virus Infection in Pregnant Women, Yucatan, Mexico

Yamila Romer  , Nina Valadez-Gonzalez, Silvina Contreras-Capetillo, Pablo Manrique-Saide, Gonzalo Vazquez-Prokopec, and Norma Pavia-Ruz

Author affiliations: Emory University, Atlanta, Georgia, USA (Y. Romer, G. Vazquez-Prokopec); Universidad Autónoma de Yucatan, Yucatan, Mexico (N. Valadez-Gonzalez, S. Contreras-Capetillo, P. Manrique-Saide, N. Pavia-Ruz)



We report demographic, epidemiologic, and clinical findings for a prospective cohort of pregnant women during the initial phase of Zika virus introduction into Yucatan, Mexico. We monitored 115 pregnant women for signs of active or recent Zika virus infection. The estimated cumulative incidence of Zika virus infection was 0.31 and the ratio of symptomatic to asymptomatic cases was 1.7 (range 1.3–4.0 depending on age group). Exanthema was the most sensitive clinical sign but also the least specific. Conjunctival hyperemia, joint edema, and exanthema were the combination of signs that had the highest specificity but low sensitivity. We did not find evidence of vertical transmission or fetal anomalies, likely because of the low number of pregnant women tested. We also did not find evidence of congenital disease. Our findings emphasize the limited predictive value of clinical features in areas where Zika virus cocirculates with other flaviviruses.

Keywords: Zika Virus; Pregnancy; Yucatan; Mexico.



Low #seroprevalence rates of #Zika virus in Kuala Lumpur, #Malaysia (Trans R Soc Trop Med Hyg., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Trans R Soc Trop Med Hyg. 2019 Jul 11. pii: trz056. doi: 10.1093/trstmh/trz056. [Epub ahead of print]

Low seroprevalence rates of Zika virus in Kuala Lumpur, Malaysia.

Sam IC1, Montoya M2, Chua CL1, Chan YF1, Pastor A2, Harris E2.

Author information: 1 Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. 2 Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA.




Zika virus (ZIKV) is believed to be endemic in Southeast Asia. However, there have been few Zika cases reported to date in Malaysia, which could be due to high pre-existing levels of population immunity.


To determine Zika virus (ZIKV) seroprevalence in Kuala Lumpur, Malaysia, 1085 serum samples from 2012, 2014-2015 and 2017 were screened for anti-ZIKV antibodies using a ZIKV NS1 blockade-of-binding assay. Reactive samples were confirmed using neutralization assays against ZIKV and the four dengue virus (DENV) serotypes. A sample was possible ZIKV seropositive with a ZIKV 50% neutralization (NT50) titre ≥20. A sample was probable ZIKV seropositive if, in addition, all DENV NT50 titres were <20 or the ZIKV NT50 titre was >4-fold greater than the highest DENV NT50 titre.


We found low rates of possible ZIKV seropositivity (3.3% [95% confidence interval {CI} 2.4 to 4.6]) and probable ZIKV seropositivity (0.6% [95% CI 0.3 to 1.4]). Possible ZIKV seropositivity was independently associated with increasing age (odds ratio [OR] 1.04 [95% CI 1.02 to 1.06], p<0.0001) and male gender (OR 3.5 [95% CI 1.5 to 8.6], p=0.005).


The low ZIKV seroprevalence rate, a proxy for population immunity, does not explain the low incidence of Zika in dengue-hyperendemic Kuala Lumpur. Other factors, such as the possible protective effects of pre-existing flavivirus antibodies or reduced transmission by local mosquito vectors, should be explored. Kuala Lumpur is at high risk of a large-scale Zika epidemic.

© The Author(s) 2019. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

KEYWORDS: Malaysia; NS1 blockade-of-binding ELISA; Zika virus; dengue virus; neutralization test; seroprevalence

PMID: 31294807 DOI: 10.1093/trstmh/trz056

Keywords: Zika Virus; Malaysia; Seroprevalence.


#Human Polyclonal #Antibodies Prevent Lethal #Zika Virus #Infection in Mice (Sci Rep., abstract)

[Source: Scientific Reports, full page: (LINK). Abstract, edited.]

Article | OPEN | Published: 08 July 2019

Human Polyclonal Antibodies Prevent Lethal Zika Virus Infection in Mice

Emilie Branche, Ayo Yila Simon, Nicholas Sheets, Kenneth Kim, Douglas Barker, Anh-Viet T. Nguyen, Harpreet Sahota, Matthew Perry Young, Rebecca Salgado, Anila Mamidi, Karla M. Viramontes, Trevor Carnelley, Hongyu Qiu, Annie Elong Ngono, Jose Angel Regla-Nava, Mercylia Xevana Susantono, Joan M. Valls Cuevas, Kieron Kennedy, Shantha Kodihalli & Sujan Shresta

Scientific Reports, volume 9, Article number: 9857 (2019)



Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that represents a major threat to global health. ZIKV infections in adults are generally asymptomatic or present with mild symptoms. However, recent outbreaks of ZIKV have revealed that it can cause Congenital Zika Syndrome in neonates and Guillain-Barré syndrome in adults. Currently, no ZIKV-specific vaccines or antiviral treatments are available. In this study, we tested the efficacy of convalescent plasma IgG hyperimmune product (ZIKV-IG) isolated from individuals with high neutralizing anti-ZIKV titers as a therapeutic candidate against ZIKV infection using a model of ZIKV infection in Ifnar1−/− mice. ZIKV-IG successfully protected mice from lethal ZIKV challenge. In particular, ZIKV-IG treatment at 24 hours after lethal ZIKV infection improved survival by reducing weight loss and tissue viral burden and improving clinical score. Additionally, ZIKV-IG eliminated ZIKV-induced tissue damage and inflammation in the brain and liver. These results indicate that ZIKV-IG is efficacious against ZIKV, suggesting this human polyclonal antibody is a viable candidate for further development as a treatment against human ZIKV infection.

Keywords: Zika Virus; Serotherapy; Animal models.


#Vertical #Transmission of #Zika Virus (Flaviviridae, #Flavivirus) in #Amazonian #Aedes aegypti (Diptera: Culicidae) Delays Egg Hatching and Larval Development of Progeny (J Med Entomol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

J Med Entomol. 2019 Jul 6. pii: tjz110. doi: 10.1093/jme/tjz110. [Epub ahead of print]

Vertical Transmission of Zika Virus (Flaviviridae, Flavivirus) in Amazonian Aedes aegypti (Diptera: Culicidae) Delays Egg Hatching and Larval Development of Progeny.

Chaves BA1,2, Junior ABV1, Silveira KRD3, Paz ADC1, Vaz EBDC1, Araujo RGP3, Rodrigues NB3, Campolina TB3, Orfano ADS3, Nacif-Pimenta R3, Villegas LEM3, Melo FF4, Silva BM5, Monteiro WM1,2, Guerra MDGVB1,2, Lacerda MVG1,6, Norris DE7, Secundino NFC3, Pimenta PFP1,3.

Author information: 1 Tropical Medicine Foundation Dr. Heitor Vieira Dourado, Manaus, Amazonas, Brazil. 2 Amazonas State University, Minas Gerais, Belo Horizonte, Brazil. 3 Laboratory of Medical Entomology, Rene Rachou Research Institute – FIOCRUZ, Minas Gerais, Belo Horizonte, Brazil. 4 Multidisciplinary Health Institute, Federal University of Bahia, Bahia, Brazil. 5 Department of Biological Sciences, Federal University of Ouro Preto, Minas Gerais, Ouro Preto, Brazil. 6 Leonidas and Maria Deane Research institute – FIOCRUZ, Amazonas, Brazil. 7 The Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.



Zika virus (ZIKV) has emerged as a globally important arbovirus and has been reported from all states of Brazil. The virus is primarily transmitted to humans through the bite of an infective Aedes aegypti (Linnaeus, 1762) or Aedes albopictus (Skuse, 1895). However, it is important to know if ZIKV transmission also occurs from Ae. aegypti through infected eggs to her offspring. Therefore, a ZIKV and dengue virus (DENV) free colony was established from eggs collected in Manaus and maintained until the third-fourth generation in order to conduct ZIKV vertical transmission (VT) experiments which used an infectious bloodmeal as the route of virus exposure. The eggs from ZIKV-infected females were allowed to hatch. The resulting F1 progeny (larvae, pupae, and adults) were quantitative polymerase chain reaction (qPCR) assayed for ZIKV. The viability of ZIKV vertically transmitted to F1 progeny was evaluated by cultivation in C6/36 cells. The effects of ZIKV on immature development of Ae. aegypti was assessed and compared with noninfected mosquitoes. AmazonianAe. aegypti were highly susceptible to ZIKV infection (96.7%), and viable virus passed to their progeny via VT. Moreover, eggs from the ZIKV-infected mosquitoes had a significantly lower hatch rate and the slowest hatching. In addition, the larval development period was slower when compared to noninfected, control mosquitoes. This is the first study to illustrate VT initiated by oral infection of the parental population by using mosquitoes, which originated from the field and a ZIKV strain that is naturally circulating in-country. Additionally, this study suggests that ZIKV present in the Ae. aegypti can modify the mosquito life cycle. The data reported here suggest that VT of ZIKV to progeny from naturally infected females may have a critical epidemiological role in the dissemination and maintenance of the virus circulating in the vector.

© The Author(s) 2019. Published by Oxford University Press on behalf of Entomological Society of America.

KEYWORDS: Aedes aegypti ; Zika virus; fitness cost; vertical transmission

PMID: 31278737 DOI: 10.1093/jme/tjz110

Keywords: Flavivirus; Zika Virus; Aedes aegypti.


Underreporting of #Fatal #Congenital #Zika #Syndrome, #Mexico, 2016–2017 (Emerg Infect Dis., abstract)

[Source: US Centers for Disease Control and Prevention (CDC), Emerging Infectious Diseases Journal, full page: (LINK). Abstract, edited.]

Volume 25, Number 8—August 2019 / Dispatch

Underreporting of Fatal Congenital Zika Syndrome, Mexico, 2016–2017

Victor M. Cardenas  , Angel Jose Paternina-Caicedo, and Ernesto Benito Salvatierra

Author affiliations: University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA (V.M. Cardenas); Universidad Nacional de Colombia, Bogota, Colombia (A.J. Paternina-Caicedo); Unidad San Cristóbal, Chiapas, Mexico (E.B. Salvatierra)



To determine completeness of fatal congenital Zika syndrome reporting in Mexico, we examined data from the Mexican National Institute of Statistics and Geography. We found that an estimated 50% more infants died from microcephaly attributable to congenital Zika syndrome during 2016–2017 than were reported by the existing surveillance system.

Keywords: Zika Virus; Microcephaly; Zika Congenital Syndrome; Mexico.


High-throughput #screening identifies mixed lineage kinase 3 as a key #host regulatory #factor in #Zika virus #infection (J Virol., abstract)

[Source: Journal of Virology, full page: (LINK). Abstract, edited.]

High-throughput screening identifies mixed lineage kinase 3 as a key host regulatory factor in Zika virus infection

Hua Xu, Min Cheng, Xiaojing Chi, Xiuying Liu, Jia Zhou, Tianli Lin, Wei Yang

DOI: 10.1128/JVI.00758-19



The Zika virus (ZIKV) life cycle involves multiple steps and requires interactions with host factors. However, the inability to systematically identify host regulatory factors for ZIKV has hampered antiviral development and our understanding of pathogenicity. Here, using a bioactive compound library with 2659 small molecules, we applied a high-throughput and imaging-based screen to identify host factors that modulate ZIKV infection. The screen yielded hundreds of hits that markedly inhibited or potentiated ZIKV infection in SNB-19 glioblastoma cells. Among the hits, URMC-099, a mixed lineage kinase 3 (MLK3) inhibitor, significantly facilitated ZIKV replication in both SNB-19 cells and the neonatal mouse brain. Using gene silencing and overexpression, we further confirmed that MLK3 was a host restriction factor against ZIKV. Mechanistically, MLK3 negatively regulated ZIKV replication through inducing the inflammatory cytokines IL-6, IL-8, TNF-α and MCP-1 but did not modulate host interferon related pathways. Importantly, ZIKV activated the MLK3/MKK7/JNK pathway in both SNB-19 cells and neonatal mouse brain. Together, these findings reveal a critical role for MLK3 in regulating ZIKV infection and facilitate the development of anti-ZIKV therapeutics by providing a number of screening hits.



Zika fever, an infectious disease caused by the Zika virus (ZIKV), normally results in mild symptoms. Severe infection can cause Guillain–Barré syndrome in adults and birth defects, including microcephaly, in newborns. Although ZIKV was first identified in Uganda in 1947 in rhesus monkeys, a widespread epidemic of ZIKV infection in South and Central America in 2015-2016 raised major concerns. To date, there is no vaccine or specific medicine for ZIKV. The significance of our research is the systematic discovery of small molecule candidates that modulate ZIKV infection, which will allow the development of antiviral therapeutics. In addition, we identified MLK3, a key mediator of host signaling pathways that can be activated during ZIKV infection and limits virus replication by inducing multiple inflammatory cytokines. These findings broaden our understanding of ZIKV pathogenesis.

Copyright © 2019 American Society for Microbiology. All Rights Reserved.

Keywords: Zika Virus; Viral pathogenesis.


#Zika Virus-Immune #Plasmas from Symptomatic and Asymptomatic Individuals Enhance Zika #Pathogenesis in #Adult and #Pregnant Mice (mBio, abstract)

[Source: mBio, full page: (LINK). Abstract, edited.]

Zika Virus-Immune Plasmas from Symptomatic and Asymptomatic Individuals Enhance Zika Pathogenesis in Adult and Pregnant Mice

Byoung-Shik Shim, Young-Chan Kwon, Michael J. Ricciardi, Mars Stone, Yuka Otsuka, Fatma Berri, Jaclyn M. Kwal, Diogo M. Magnani, Cody B. Jackson, Audrey S. Richard, Philip Norris,Michael Busch, Christine L. Curry, Michael Farzan, David Watkins, Hyeryun Choe

Mark R. Denison, Editor

DOI: 10.1128/mBio.00758-19



Preexisting immunity against dengue virus or West Nile virus was previously reported to mediate antibody-dependent enhancement (ADE) of Zika virus (ZIKV) infection in a mouse model. We show here that ZIKV-immune plasma samples from both symptomatic and asymptomatic individuals mediated ZIKV ADE of infection in vitro and in mice. In a lethal infection model with a viral inoculum 10 times higher, both ADE and protection were observed, depending on the amount of infused immune plasma. In a vertical-transmission model, ZIKV-immune plasma infused to timed pregnant mice increased fetal demise and decreased the body weight of surviving fetuses. Depletion of IgG from an immune plasma abolished ADE of infection, and the presence of purified IgG alone mediated ADE of infection. Higher viral loads and proinflammatory cytokines were detected in mice treated with ZIKV-immune plasma samples compared to those receiving control plasma. Together, these data show that passive immunization with homotypic ZIKV antibodies, depending on the concentration, could either worsen or limit a subsequent ZIKV infection.



Antibody-dependent enhancement (ADE) of virus infection is common to many viruses and is problematic when plasma antibody levels decline to subneutralizing concentrations. ADE of infection is especially important among flaviviruses, many of which are the cause of global health problems. Recently, human plasma samples immune to heterologous flaviviruses were shown to promote Zika virus (ZIKV) infection. Here we showed in immunocompromised mouse models that homologous immune plasma samples protect mice from subsequent infection at high antibody concentrations but that they mediate ADE of infection and increase ZIKV pathogenesis in adult mice and fetal demise during pregnancy at low concentrations.

Keywords: Zika Virus; ADE; Pregnancy; Immunopathology; Animal models.