Other viruses

1

Oct, 2019

Experimental infection of pregnant female sheep with Zika Virus during early gestation

 

Authors: Schwarz ER, Pozor MA, Pu R, et al.

Published in: Viruses. 2019;11(9)

Abstract Zika virus (ZIKV) is a vertically and sexually transmissible virus resulting in severe congenital malformation. The goal of this study was to develop an ovine model of ZIKV infection. Between 28–35 days gestation (DG), four pregnant animals were infected with two doses of 6 × 106 PFU of ZIKV; four control animals received PBS. Animals were evaluated for 45 days (D) post-infection (PI) and necropsies were performed. Viral RNA was detected in infected ewe peripheral blood mononuclear cells (PBMC) during the first week PI; however, all fluids and tissues were negative upon culture. Anti-ZIKV IgM (1:400) and neutralizing antibodies were detected in all infected animals. Clinical disease, virus, or ZIKV antibodies were not detected in control ewes. After two weeks PI, fetal loss occurred in two infected animals, and at necropsy, three infected animals had placental petechiation and ecchymosis and one had hydramnion. Fetal morphometrics revealed smaller cranial circumference to crown-rump length ratios (p < 0.001) and relative brain weights (p = 0.038) in fetuses of infected animals compared with control fetuses. Immunophenotyping indicated an increase in B cells (p = 0.012) in infected sheep. Additionally, in vitro experiments using both adult and fetal cell lines demonstrated that ovine cells are highly permissive to ZIKV infection. In conclusion, ZIKV infection of pregnant sheep results in a change in fetal growth and gestational outcomes.

Read

1

Oct, 2019

Pregnancy outcomes after maternal Zika virus infection in a non-endemic region: prospective cohort study

 

Authors: Sulleiro E, Rando A, Alejo I, et al.

Published in: Clin Microbiol Infect. 2019;25(5):633.e5-633.e9

Objectives The aim was to describe pregnancy outcomes after Zika virus (ZIKV) infection in a non-endemic region.

Methods According to the Spanish protocol issued after the ZIKV outbreak in Brazil in 2015, all pregnant women who had travelled to high-burden countries were screened for ZIKV. Serological and molecular tests were used to identify ZIKV-infected pregnant women. They were classified as confirmed ZIKV infection when reverse transcription (RT) PCR tested positive, or probable ZIKV infection when ZIKV immunoglobulin M and/or immunoglobulin G and ZIKV plaque reduction neutralization tests were positive. Women found positive using molecular or serological tests were prospectively followed-up with ultrasound scans and neurosonograms on a monthly basis until delivery; magnetic resonance imaging and amniotic fluid testing were performed after signed informed consent. Samples of placenta, and fetal and neonatal tissues were obtained.

Results Seventy-two pregnant women tested positive for ZIKV infection: ten were confirmed by RT-PCR, and 62 were probable cases based on serological tests. The prevalence of adverse perinatal outcomes was 33.3% (three out of nine, 95% CI 12.1-64.6%): two cases of congenital ZIKV syndrome (CZS) and one miscarriage, all born to women infected in the first trimester of gestation. All ZIKV-confirmed women had persistent viraemias beyond 2 weeks (median 61.50 days; IQR 35.50-80.75). Amniotic fluid testing was only positive in the two fetuses with anomalies.

Conclusions The prevalence of perinatal adverse outcomes for women with ZIKV-confirmed infection was 33.3%. Amniocentesis for ZIKV RT-PCR is recommended when fetal abnormalities are found. Intensive prenatal and postnatal follow-up of ZIKV-infected pregnancies is advised in confirmed cases.

1

Oct, 2019

Screening for Zika virus infection in 1057 potentially exposed pregnant women, Catalonia (northeastern Spain)

 

Authors: Sulleiro E, Rando A, Alejo I, et al.

Published in: Travel Med Infect Dis. 2019;29:69-71

No abstract available

1

Oct, 2019

Development of secondary microcephaly after delivery: possible consequence of mother-baby transmission of Zika Virus in breast milk

 

Authors: Siqueira Mello A, Pascalicchio Bertozzi APA, Rodrigues MMD, et al.

Published in: Am J Case Rep. 2019 May 21;20:723-725

Background The Zika virus is an arbovirus that has as main source of transmission the bite of infected insects of the genus Aedes and has been associated with cases of congenital malformation and microcephaly in neonates. However, other sources of transmission have been identified since the emergence of this virus in the world population, such as vertical transmission by semen and possibly other body fluids such as vaginal secretion and breast milk.
Case Report An infant, born to a mother whose previous delivery was a baby with severe microcephaly, was normal and was negative for Zika virus at birth but developed secondary microcephaly 1 month later, that persisted. The baby was exclusively breast-fed and Zika virus was present in the mother’s milk.
Conclusions We report the detection of Zika virus exclusively in the breast milk of a woman after her second delivery of an infant, who later developed microcephaly. This case is consistent with possible vertical transmission.

Read

1

Oct, 2019

Detection of Zika virus in paired urine and amniotic fluid samples from symptomatic and asymptomatic women and their babies during a disease outbreak: association with neurological symptoms in newborns

 

Authors: Vedovello D, Witkin SS, Silva ACB, et al.

Published in: J Neurovirol 2019 Sep 9. doi: 10.1007/s13365-019-00797-0

Abstract Paired maternal and newborn urine and amniotic fluid from 138 subjects collected during a Zika virus (ZIKV) outbreak was analyzed for ZIKV by gene amplification (RT-qPCR), and the findings were correlated with clinical symptoms and neurological anomalies in the babies. ZIKV was detected in 1 of 9 symptomatic women (11.1%) and in 19 of 129 asymptomatic women (14.7%). Neurological manifestations were present in 19 babies (13.7%), 10 of 20 (50%) positive and 9 of 119 (7.6%) negative (p < 0.001) for ZIKV. Twelve (8.6%) urines collected during gestation were ZIKV-positive; only 2 remained positive for ZIKV postpartum. Six (4.1%) newborn urines collected within 1 day of delivery were ZIKV-positive cases. In 3 of these cases, ZIKV was detected in mother’s urine pre- and postpartum and in both mother’s urine and babies’ urine. Four of the amniotic fluid samples (2.9%) were ZIKV-positive. Among ZIKV-negative babies with neurological sequel, 87.5% were female; in contrast, 72.7% ZIKV-positive babies with neurological abnormalities were male (p = 0.019). We conclude that during a ZIKV outbreak, clinical symptoms and ZIKV detection in biological fluids are poor predictors of infection and adverse neurologic sequel in newborns.

Read

27

Sep, 2019

The challenge of the laboratory diagnosis in a confirmed congenital Zika virus syndrome in utero: a case report

 

Authors: Sulleiro E, Frick MA, Rodó C, et al.

Published in: Medicine (Baltimore). 2019;98(20):e15532

Introduction Zika virus (ZIKV) has caused one of the most challenging global infectious epidemics in recent years because of its causal association with severe microcephaly and other congenital malformations. The diagnosis of viral infections usually relies on the detection of virus proteins or genetic material in clinical samples as well as on the infected host immune responses. Serial serologic testing is required for the diagnosis of congenital infection when diagnostic molecular biology is not possible.

Patient concerns A 2-year-old girl, born to a mother with confirmed ZIKV infection during pregnancy, with a confirmed ZIKV infection in utero, showed at birth a severe microcephaly and clinical characteristics of fetal brain disruption sequence compatible with a congenital ZIKV syndrome (CZS).

Diagnosis ZIKV-RNA and ZIKV-IgM serological response performed at birth and during the follow-up time tested always negative. Serial serologic ZIKV-IgG tests were performed to assess the laboratory ZIKV diagnosis, ZIKV-IgG seroreversion was observed at 21 months of age. ZIKV diagnosis of this baby had to be relied on her clinical and radiological characteristics that were compatible with a CZS.

Interventions The patient was followed-up as per protocol at approximately 1, 4, 9, 12, 18-21, and 24 months of age. Neurological, radiological, audiological, and ophthalmological assessment were performed during this period of time. Prompt rehabilitation was initiated to prevent potential adverse long-term neurological outcomes.

Outcomes The growth of this girl showed a great restriction at 24 months of age with a weight of 8.5 kg (-2.5 z-score) and a head circumference of 40.5 cm (-4.8 z-score). She also had a great neurodevelopmental delay at the time of this report.

Conclusions We presume that as a consequence of prenatal ZIKV infection, the fetal brain and other organs are damaged before birth through direct injury. Following this, active infection ends during intrauterine life, and as a consequence the immune system of the infant is unable to build up a consistent immune response thereafter. Further understanding of the mechanisms taking part in the pathogenesis of ZIKV congenital infection is needed. This finding might change our paradigm regarding serological response in the ZIKV congenital infection.

Read

14

Sep, 2019

Follow up of Children with Confirmed Perinatal Zika Virus (ZIKV) Exposure: The First 2 years-experience in the Costa Rican Tertiary Pediatric Hospital

 

Authors: Tedder RS, Dicks S, Ijaz S, et al.

Published in: PLoS One. 2019;14(8):e0215708

Abstract The accurate diagnosis and seroprevalence investigations of Zika virus (ZKV) infections remain complex due to cross reactivity with other flaviviruses. Two assay formats, both using labelled Zika virus NS1 antigen as a revealing agent (a double antigen binding assay, DABA, and an immunoglobulin Ig capture assay, G capture) were initially developed and compared with the indirect EuroimmunZ assay for the detection of anti-Zika antibody. Of 147 pre-Zika period serum samples, 39 (27%) were reactive in the EuroimmunZ or the DABA assays, 28 sera concordantly so. Such false reactivity was influenced by the serotype of Dengue virus (DV) to which individuals had been exposed to. Thus, of sera from patients undergoing secondary Dengue virus infection of known serotype, 91%, 45% and 28% of Dengue virus serotype 2, 3 and 4 respectively were reactive in one or more of the three assays. A novel method of quenching false sero-reactivity was therefore developed for the DABA and G capture assays. Initial addition of a single homologous Dengue virus serotype 3 NS1Ag quench significantly ablated false reactivities in the pre-Zika period sera. An equipotent quadrivalent quench comprising homologous Dengue virus serotypes 1 to 4 NS1Ag was shown to be optimum yet retained sensitivity for the detection of specific anti-Zika antibody. Comparing DABA and G capture assays using quenched and unquenched conjugates in comparison with EuroimmunZ early in the course of PCR-confirmed infection indicated that a significant component of the apparent early anti-ZIKA antibody response is likely to be due to a Zika virus-driven anamnestic anti-Dengue virus response. The increased specificity provided by homologous antigen quenching is likely to provide a significant improvement in sero-diagnostics and to be of clinical value.

Read

9

Sep, 2019

Past and future spread of the arbovirus vectors Aedes aegypti and Aedes albopictus

 

Authors: Kraemer MUG, Reiner RC Jr, Brady OJ, et al.

Published in: Nat Microbiol. 2019;4:900

Abstract The global population at risk from mosquito-borne diseases—including dengue, yellow fever, chikungunya and Zika—is expanding in concert with changes in the distribution of two key vectors: Aedes aegypti and Aedes albopictus. The distribution of these species is largely driven by both human movement and the presence of suitable climate. Using statistical mapping techniques, we show that human movement patterns explain the spread of both species in Europe and the United States following their introduction. We find that the spread of Ae. aegypti is characterized by long distance importations, while Ae. albopictus has expanded more along the fringes of its distribution. We describe these processes and predict the future distributions of both species in response to accelerating urbanization, connectivity and climate change. Global surveillance and control efforts that aim to mitigate the spread of chikungunya, dengue, yellow fever and Zika viruses must consider the so far unabated spread of these mosquitos. Our maps and predictions offer an opportunity to strategically target surveillance and control programmes and thereby augment efforts to reduce arbovirus burden in human populations globally.

Read

1

Sep, 2019

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

 

Authors: Wilder-Smith A, Wei Y, Araújo TVB et al;Zika Virus Individual Participant Data Consortium

Published in: BMJ Open. 2019;9(6):e026092. doi: 10.1136/bmjopen-2018-026092.

Introduction Zika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.

Methods and analysis We will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.

Ethics and dissemination The IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.

Read

7

Jul, 2019

Field diagnosis and genotyping of chikungunya virus using a dried reverse transcription loop-mediated isothermal amplification (LAMP) assay and MinION sequencing

 

Authors: Hayashida K, Orba Y, Sequeira PC, et al.

Published in: PLoS Negl Trop Dis. 2019;13(6):e0007480

Abstract Detection and sequencing of chikungunya virus (CHIKV) genome was performed using a combination of a modified reverse transcription loop-mediated isothermal amplification (RT-LAMP) method and a MinION sequencer. We developed the protocol for drying all the reagents for the RT-LAMP in a single reaction tube. Using this system, the CHIKV genome was effectively amplified under isothermal conditions, and used as a template for MinION sequencing with a laptop computer. Our in-house RT-LAMP method and MinION sequencing system were also validated with RNAs and serum samples from recent outbreaks of CHIKV patients in Brazil. The obtained sequence data confirmed the CHIKV outbreaks and identified the genotype. In summary, our established inexpensive on-site genome detection and sequencing system is applicable for both diagnosis of CHIKV infected patients and genotyping of the CHIKV virus in future outbreak in remote areas.

Read