Other viruses | Zika

Authors: Mazzetto E, Bortolami A, Bovo D, Stocchero M, Mazzacan E, Napolitan A, Panzarin V, Tran MR, Zamperin G, Milani A, Fortin A, Bigolaro M, Pirillo P, Pagliari M, Zanardello C, Giordano G, Gervasi MT, Baraldi E, Terregino C, Giaquinto C, Bonfante F.

Published in: Virus Research

Authors: Melbourne-Chambers, R., Palmer, P., Brown, Y., James-Powell, T., Tapper, J., Mowatt, L., … Thorne, C. (2025).

Published in: Paediatrics and International Child Health

Authors: CDC Christie, AM Lue, RH Melbourne-Chambers

Presented at: Current Opinion in Pediatrics

Authors: de Siquiera I.C, de Almeida B.L, Lage MLC, Serra L, Carvalho A, de Lima M.M, Góes MDFN, Crispim MDSIN, da Costa Pereira MM, Costa BGG, Bailey H, Byrne T, Giaquinto C, Fernandes G, Ruiz-Burga E, & Thorne C

Published in: Dialogues in Health, 2, 100104

Authors: Louis R, Pu R, Logan TD, Trimmer-Smith L, Chamblain R, Gallagher A, Beau De Rochars V M, Nelson E T, Cummings DA, Long MT, & Morris Jr JG

Published in: PLOS ONE

Authors: Ruiz-Burga E, Bruijning-Verhagen P, Palmer P, Sandcroft A, Fernandes G, de Hoog M, Bryan L, Pierre R, Bailey H, Giaquinto C, Thorne C, Christie CDC, ZIKAction Consortium

Published in: JMIR Formative Research

Authors: A Lue, M Richards-Dawson, G Gordon-Strachan, S Kodilinye, J Dunkley Thompson, T James-Powell, C Pryce, C Mears, J Anzinger, K Webster-Kerr and C Christie

Published in: Frontiers in Medicine

Authors: B.L de Almeida, I.C de Siqueira, M.L.C Lage, L.S Lopes, A.L de Carvalho, M.M de Lima, M.d.F.N Goes, M.N Crispim, B.G.G Costa, C Giaquinto, G Fernandes, E Ruiz-Burga, C Thorne on belhaf of Zikaction consortium

Presented at: WSPID 2022

Authors: J.J. Anzinger, C.D. Mears, A.E. Ades, K Francis, Y Phillips, Y.E. Leys, M.J. Spyer, D Brown, A.M.B.d Filippis, E Nastouli, T Byrne, H Bailey, P Palmer, L Bryan, K Webster-Kerr, C Giaquinto, C Thorne, C.D.C. Christie, and on behalf of the ZIKAction Consortium

Published in: Emerging Infectious Diseases Journal

Authors: G Berberian, R Bologna, MG Pérez, A Mangano, PhD, M Costa, MSc, S Calligaris, MA Morales, C Rugilo, E Ruiz-Burga, C Thorne

Published in: Sage Journals

Authors: A E Ades, Elizabeth B Brickley, Neal Alexander, David Brown, Thomas Jaenisch, Demócrito de Barros Miranda-Filho, Moritz Pohl, Kerstin D Rosenberger, Antoni Soriano-Arandes , Claire Thorne et al.

Published in: BMJ Journals

Authors: A E Ades, Antoni Soriano-Arandes, Ana Alarcon, Francesco Bonfante, Claire Thorne, Catherine S Peckham, Carlo Giaquinto

Published in: The Lancet Infectious Diseases

Authors: Soriano-Arandes A, Frick MA, García López-Hortelano M, et al.

Published in: Pathogens 2020;9(5):E352

Authors: Giovanetti M, Faria NR, Lourenco J, et al.

Published in:  Cell Rep. 2020;30(7):2275-2283

Authors: Ades AE, Thorne C, Soriano-Arandes A, et al.

Published in: Lancet Infect Dis. 2020 Feb 18

Abstract: Our understanding of congenital infections is based on prospective studies of women infected during pregnancy. The EU has funded three consortia to study Zika virus, each including a prospective study of pregnant women. Another multi-centre study has been funded by the US National Institutes of Health. This Personal View describes the study designs required to research Zika virus, and questions whether funding academics in the EU and USA to work with collaborators in outbreak areas is an effective strategy. 3 years after the 2015–16 Zika virus outbreaks, these collaborations have taught us little about vertical transmission of the virus. In the time taken to approve funding, agree contracts, secure ethics approval, and equip laboratories, Zika virus had largely disappeared. By contrast, prospective studies based on local surveillance and standard-of-care protocols have already provided valuable data. Threats to fetal and child health pose new challenges for global preparedness requiring support for the design and implementation of locally appropriate protocols. These protocols can answer the key questions earlier than externally designed studies and at lower cost. Local protocols can also provide a framework for recruitment of unexposed controls that are required to study less specific outcomes. Other priorities include accelerated development of non-invasive tests, and longer-term storage of neonatal and antenatal samples to facilitate retrospective reconstruction of cohort studies.

Authors: Celia C.

Published in: Oral presentation at 3rd international Conference on Zika Virus and aedes related infections, February 13th – 16th, 2020– Washington DC, USA.

Authors: Webster-Kerr K.

Published in: Oral presentation at 3rd international Conference on Zika Virus and aedes related infections, February 13th – 16th, 2020– Washington DC, USA.

Authors: Lue A.

Published in: Oral presentation at 3rd international Conference on Zika Virus and aedes related infections, February 13th – 16th, 2020– Washington DC, USA.

Authors: Pereira Gusmão Maia Z, Mota Pereira F, do Carmo Said RF, et al.

Published in: Emerg Microbes Infect. 2020;9(1):53-57

Abstract Between June 2017 and August 2018, several municipalities located in Bahia state (Brazil) reported a large increase in the number of patients presenting with febrile illness similar to that of arboviral infections. Using a combination of portable whole genome sequencing, molecular clock and epidemiological analyses, we revealed the return of the CHIKV-ECSA genotype into Bahia. Our results show local persistence of lineages in some municipalities and the re-introduction of new epidemiological strains from different Brazilian regions, highlighting a complex dynamic of transmission between epidemic seasons and sampled locations. Estimated climate-driven transmission potential of CHIKV remained at similar levels throughout the years, such that large reductions in the total number of confirmed cases suggests a slow, but gradual accumulation of herd-immunity over the 4 years of the epidemic in Bahia after its introduction in 2014. Bahia remains a reservoir of the genetic diversity of CHIKV in the Americas, and genomic surveillance strategies are essential to assist in monitoring and understanding arboviral transmission and persistence both locally and over large distances.

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.

Authors: Giovannetti M, de Mendonca MCL, Fonseca V, et al.

Published in: J Virol. 2019;94(1). pii: e01623-19

Abstract The recent reemergence of yellow fever virus (YFV) in Brazil has raised serious concerns due to the rapid dissemination of the virus in the southeastern region. To better understand YFV genetic diversity and dynamics during the recent outbreak in southeastern Brazil, we generated 18 complete and nearly complete genomes from the peak of the epidemic curve from nonhuman primates (NHPs) and human infected cases across the Espírito Santo and Rio de Janeiro states. Genomic sequencing of 18 YFV genomes revealed the estimated timing, source, and likely routes of yellow fever virus transmission and dispersion during one of the largest outbreaks ever registered in Brazil. We showed that during the recent epidemic, YFV was reintroduced from Minas Gerais to the Espírito Santo and Rio de Janeiro states multiple times between 2016 and 2019. The analysis of data from portable sequencing could identify the corridor of spread of YFV. These findings reinforce the idea that continued genomic surveillance strategies can provide information on virus genetic diversity and transmission dynamics that might assist in understanding arbovirus epidemics.

Authors: Goncalves BS, Nogueira RMR, Bispo de Filippis AM, Horta MAP

Published in: Trans R Soc Trop Med Hyg. 2019;113(11):670-677

Authors: Torres MC, de Bruycker Nogueira F, Fernandes CA, et al.

Published in: PLoS One. 2019;14(12):e0225879

Abstract The Asian/American genotype of dengue virus serotype 2 (DENV-2) has been introduced in Brazil through the state of Rio de Janeiro around 1990, and since then it has been spreading and evolving, leading to several waves of dengue epidemics throughout the country that cause a major public health problem. Of particular interest has been the epidemic of 2008, whose highest impact was evidenced in the state of Rio de Janeiro, with a higher number of severe cases and mortality rate, compared to previous outbreaks. Interestingly, no circulation of DENV-2 was witnessed in this region during the preceding 9-year period. By early 2010, phylogenetic analysis of the 2008 epidemic strain revealed that the outbreak was caused by a new viral lineage of the Asian/American genotype, which was pointed as responsible for the outbreak severity as well. The same scenario is repeating in 2019 in this state; however, only a few cases have been detected yet. To provide information that helps to the understanding of DENV-2 dynamics in the state of Rio de Janeiro, and thereafter contribute to public health control and prevention actions, we employed phylogenetic studies combined with temporal and dynamics geographical features to determine the origin of the current viral strain. To this effect, we analyzed a region of 1626 nucleotides entailing the Envelope/NS1 viral genes. Our study reveals that the current strain belongs to the same lineage that caused the 2008 outbreak, however, it is phylogenetically distant from any Brazilian strain identified so far. Indeed, it seemed to be originated in Puerto Rico around 2002 and has been introduced into the state in late 2018. Taking into account that no DENV-2 case was reported over the last decade in the state (representing a whole susceptible children generation), and the fact that a new viral strain may be causing current dengue infections, these results will be influential in strengthening dengue surveillance and disease control, mitigating the potential epidemiological consequences of virus spread.

Authors: Brenes-Chacón H, Ávila-Agüero ML, Camacho-Badilla K, Naranjo-Zuñiga G, Benavides-Lara A,  Soriano-Fallas A

Published in: ID Week, Washington DC, October 2nd – 6th 2019

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.

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.

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

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

No abstract available

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.

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.

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.

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.

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.

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.

Authors: Gray ER, Heaney J, Ferns RB, Sequeira PC, Nastouli E, Garson JA

Published in: J Virol Methods. 2019;268:17-23

Abstract Dengue is a vector-transmitted viral infection that is a significant cause of morbidity and mortality in humans worldwide, with over 50 million apparent cases and a fatality rate of 2.5 % of 0.5 million severe cases per annum in recent years. Four serotypes are currently co-circulating. Diagnosis of infection may be by polymerase chain reaction, serology or rapid antigen test for NS1. Both pan-serotype and serotype-specific genome detection assays have been described, however, achieving adequate sensitivity with pan-serotype assays has been challenging. Indeed, as we show here, inspection of components and cycling parameters of a pan-serotype RT-qPCR assay in use in laboratories worldwide revealed insufficient probe stability to accommodate potential nucleotide mismatches, resulting in false-negatives. A minor–groove binder (MGB)-modified version of the probe was designed and its performance compared with that of the original probe in 32 samples. Eight of the samples were undetected by the original probe but detected by the MGB modified probe and six out of seven of these that could be serotyped belonged to serotype 4. Sequencing of the region targeted by the probe in these samples revealed two mismatches which were also universally present in all other serotype 4 sequences in a public database. We therefore recommend adoption of this MGB modification in order to reduce the risk of false-negative results, especially with dengue serotype 4 infections.

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.

Authors: Mavian C, Dulcey M, Munoz O, Salemi M, Vittor AY, Capua I.

Published in: Viruses. 2019; 11(1):11

Abstract During the past ten years, an increasing number of arbovirus outbreaks have affected tropical islands worldwide. We examined the available literature in peer-reviewed journals, from the second half of the 20th century until 2018, with the aim of gathering an overall picture of the emergence of arboviruses in these islands. In addition, we included information on environmental and social drivers specific to island setting that can facilitate the emergence of outbreaks. Within the context of the One Health approach, our review highlights how the emergence of arboviruses in tropical islands is linked to the complex interplay between their unique ecological settings and to the recent changes in local and global sociodemographic patterns. We also advocate for greater coordination between stakeholders in developing novel prevention and mitigation approaches for an intractable problem.

Authors: Queiroz A,Dantas Pinto IF, Lima M, et al.

Published in: Front Microbiol. 2019;10:753

Abstract Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) in the Flavivirus genus of the Flaviviridae family. Since the large outbreaks in French Polynesia in 2013-2014 and in Brazil in 2015, ZIKV has been considered a new public health threat. Similar to other related flavivirus, ZIKV is associated with mild and self-limiting symptoms such as rash, pruritus, prostration, headache, arthralgia, myalgia, conjunctivitis, lower back pain and, when present, a short-term low grade fever. In addition, ZIKV has been implicated in neurological complications such as neonatal microcephaly and Guillain-Barré syndrome in adults. Herein, serum lipidomic analysis was used to identify possible alterations in lipid metabolism triggered by ZIKV infection. Patients who presented virus-like symptoms such as fever, arthralgia, headache, exanthema, myalgia and pruritus were selected as the control group. Our study reveals increased levels of several phosphatidylethanolamine (PE) lipid species in the serum of ZIKV patients, the majority of them plasmenyl-phosphatidylethanolamine (pPE) (or plasmalogens) linked to polyunsaturated fatty acids. Constituting up to 20% of total phospholipids in humans, plasmalogens linked to polyunsaturated fatty acids are particularly enriched in neural membranes of the brain. The biosynthesis of plasmalogens requires functional peroxisomes, which are important sites for viral replication, including ZIKV. Thus, increased levels of plasmalogens in serum of ZIKV infected subjects suggest a link between ZIKV life cycle and peroxisomes. Our data provide important insights into specific host cellular lipids that are likely associated with ZIKV replication and may serve as platform for antiviral strategy against ZIKV.

Authors: Rackow A, Ehmen C, von Possel R, et al.

Published in: Clin Chem. 2019;65(3):451-461.

Background The cellular surface molecule HsTOSO/FAIM3/HsFcμR has been identified as an IgM-specific Fc receptor expressed on lymphocytes. Here, we show that its extracellular immunoglobulin-like domain (HsFcμR-Igl) specifically binds to IgM/antigen immune complexes (ICs) and exploit this property for the development of novel detection systems for IgM antibodies directed against Crimean-Congo hemorrhagic fever virus (CCHFV) and Zika virus (ZIKV).

Methods His-tagged HsFcμR-Igl was expressed in Escherichia coli and purified by affinity chromatography, oxidative refolding, and size-exclusion chromatography. Specific binding of HsFcμR-Igl to IgM/antigen ICs was confirmed, and 2 prototypic ELISAs for the detection of anti-CCHFV and anti-ZIKV IgM antibodies were developed. Thereby, patient sera and virus-specific recombinant antigens directly labeled with horseradish peroxidase (HRP) were coincubated on HsFcμR-Igl-coated ELISA plates. Bound ICs were quantified by measuring turnover of a chromogenic HRP substrate.

Results Assay validation was performed using paired serum samples from 15 Kosovar patients with a PCR-confirmed CCHFV infection and 28 Brazilian patients with a PCR-confirmed ZIKV infection, along with a panel of a priori CCHFV/ZIKV-IgM-negative serum samples. Both ELISAs were highly reproducible. Sensitivity and specificity were comparable with or even exceeded in-house gold standard testing and commercial kits. Furthermore, latex beads coated with HsFcμR-Igl aggregated upon coincubation with an IgM-positive serum and HRP-labeled antigen but not with either component alone, revealing a potential for use of HsFcμR-Igl as a capture molecule in aggregation-based rapid tests.

Conclusions Recombinant HsFcμR-Igl is a versatile capture molecule for IgM/antigen ICs of human and animal origin and can be applied for the development of both plate- and bead-based serological tests.

Authors: Di Maio Ferreira FCPA, da Silva ASV, Bispo de Filippis AM, Brasil P

Published in: J  Pediatric Infect Dis Soc. 2019 Jan 18

Abstract We report here a probable case of vertical transmission of chikungunya infection with confirmed maternal viremia close to labor that led to severe infection in the newborn. The newborn progressed with cutaneous lesions and irritability 2 months after vertical transmission, when chikungunya virus was detected in the infant’s CSF by a molecular diagnostic test (real-time polymerase chain reaction).

Authors: Calvet GA, Brasil P, Siqueira AM, et al.

Published in: J Acquir Immune Defic Syndr. 2018;79:237-243

Background Zika virus (ZIKV) emergence in South America revealed the lack of knowledge regarding clinical manifestations in HIV-infected individuals.Objectives:We described the clinical characteristics, laboratory manifestations, differential diagnosis, and outcome of ZIKV infection in a large, single-center cohort of HIV-infected patients.

Methods HIV-infected patients aged 18 years and older with clinical suspected arboviral disease from an ongoing cohort were followed from February 2015 through December 2015. Acute serum samples were tested for ZIKV, dengue virus (DENV), and chikungunya virus by real-time reverse transcriptase polymerase chain reaction, anti-DENV immunoglobulin (Ig)M/IgG, and syphilis assays; convalescent samples were tested for anti-DENV IgM/IgG; and urine samples were tested for ZIKV by real-time reverse transcriptase polymerase chain reaction. ZIKV disease was defined according to the Pan American Health Organization (PAHO) guidelines.

Results Of 101 patients, ZIKV was confirmed in 43 cases and suspected in 34, and another diagnosis was assumed for 24 patients (dengue, secondary/latent syphilis, respiratory infections, human parvovirus B19, adverse drug reaction, musculoskeletal disorders, and acute gastroenteritis). ZIKV-confirmed and ZIKV-suspected patients reported similar signs and symptoms. Pruritic rash was the most common symptom, followed by myalgia, nonpurulent conjunctivitis, arthralgia, prostration, and headache. In the short-term follow-up [median 67.5 days (interquartile range: 32–104.5)], CD4 cell count (Z = −0.831, P = 0.406) and HIV viral load (Z = −0.447, P = 0.655) did not change significantly after ZIKV infection. There were no hospitalizations, complications, or deaths.

Conclusions Among HIV-infected patients with suspected arboviral disease, 42.6% were ZIKV-infected. CD4 cell counts and HIV viral load were not different after ZIKV infection. Differential diagnosis with other diseases and adverse drug reaction should be evaluated.

Authors: Read JS, Torres-Velasquez B, Lorenzi O, et al.

Published in: JAMA Pediatr. 2018;172(7):686-693

Importance  Little information is available regarding Zika virus (ZIKV) infection in children.

Objective  To describe patients younger than 18 years who were infected with ZIKV and were enrolled in the Sentinel Enhanced Dengue and Acute Febrile Illness Surveillance System (SEDSS).

Design, Setting, and Participants  Children infected with ZIKV with 7 or fewer days of fever or emancipated minors aged 14 to 17 years with a generalized maculopapular rash, arthritis or arthralgia, or nonpurulent conjunctivitis were eligible for enrollment on or before December 31, 2016, in Puerto Rico. Patients were evaluated using ZIKV polymerase chain reaction testing at 7 or fewer days after the onset of symptoms. Available ZIKV polymerase chain reaction–positive specimens were evaluated to determine viral loads.

Exposures  Confirmed polymerase chain reaction–positive ZIKV infection.

Main Outcomes and Measures  Clinical characteristics and viral loads of symptomatic children with confirmed ZIKV infection.

Results  Of 7191 children enrolled in SEDSS on or before December 31, 2016, only those with confirmed ZIKV infection (351 participants) were included in this study. Participants who had confirmed ZIKV infection included 25 infants (7.1%), 69 children (19.7%) aged 1 to 4 years, 95 (27.1%) aged 5 to 9 years, and 162 (46.1%) aged 10 to 17 years. Among these, 260 patients (74.1%) presented for evaluation of ZIKV infection at fewer than 3 days after the onset of symptoms, 340 (96.9%) were discharged to home after evaluation, and 349 (99.4%) had fever, 280 (79.8%) had a rash, 243 (69.2%) had facial or neck erythema, 234 (66.7%) had fatigue, 223 (63.5%) had headache, 212 (60.4%) had chills, 206 (58.7%) had pruritus, and 204 (58.1%) had conjunctival hyperemia. Of 480 specimens collected (317 serum and 163 urine specimens) from 349 children, the median number of days after the onset of symptoms was lower for children who had serum specimens (1 day [interquartile range (IQR), 1-2 days]) than for children who had urine specimens (2 [1-3] days) (P < .001). Of 131 children who had both serum and urine specimens collected on the same day, the median viral load was higher in serum than in urine (median [IQR], 23 098 [8784-88 242] copies/mL for serum vs 9966 [2815-52 774] copies/mL for urine; P = .02). When a single serum sample from each of 317 patients was analyzed, there were no statistically significant differences in median viral loads according to age, sex, or disposition. However, the median serum viral load varied significantly according to the number of days after the onset of symptoms (0 days, 106 778 [IQR, 9772-1 571 718] copies/mL; 1 day, 46 299 [10 663-255 030] copies/mL; 2 days, 20 678 [8763-42 458] copies/mL; and ≥3 days, 15 901 [5135-49 248] copies/mL; P = .001).

Conclusions and Relevance  This study represents the largest study to date of ZIKV infection in the pediatric population. Most children infected with ZIKV had fever, rash, and conjunctival hyperemia. The children usually presented for evaluation at fewer than 3 days after the onset of symptoms. Viral loads for ZIKV were higher in serum vs urine specimens. Median viral loads in serum specimens differed significantly according to the number of days after the onset of symptoms.

Authors: Giovanetti M, Goes de Jesus J, Lima de Maia M, Junior JX, et al.

Published in: Clin Microbiol Infect.2018;24(10):1111-1112

Abstract On the basis of the upsurge in the number of newborns with neurologic disorders in the northeast, in November 2015 the Brazilian Ministry of Health declared a public health emergency of national concern [1]. On the basis of evidence for a potential association between microcephaly and other neurologic disorders and Zika virus (ZIKV) infection, the World Health Organization declared a public health emergency of international concern on 1 February 2016. Here we report genetic evidence of ZIKV RNA in the mother’s breast milk and in the serum and urine of a newborn with severe congenital defects.

Authors: Azeredo EL, dos Santos FB, Barbosa LS, et al.

Published in: PLoS Curr. 2018 Feb 15;10

Authors: Badolato-Corrêa J, Sánchez-Arcila JC, et al.

Published in: Immun Inflamm Dis.2018; 6(2):194–206

Authors: Moreira-Soto A, Torres MC, Lima de Mendonça MC, et al.

Published in: Clin Microbiol Infect. 2018;24(9):1019.e1-1019.e4

Objectives Since December 2016, Brazil has experienced an unusually large outbreak of yellow fever (YF). Whether urban transmission may contribute to the extent of the outbreak is unclear. The objective of this study was to characterize YF virus (YFV) genomes and to identify spatial patterns to determine the distribution and origin of YF cases in Minas Gerais, Espírito Santo and Rio de Janeiro, the most affected Brazilian states during the current YFV outbreak.

Methods We characterized near-complete YFV genomes from 14 human cases and two nonhuman primates (NHP), sampled from February to April 2017, retrieved epidemiologic data of cases and used a geographic information system to investigate the geospatial spread of YFV.

Results All YFV strains were closely related. On the basis of signature mutations, we identified two cocirculating YFV clusters. One was restricted to the hinterland of Espírito Santo state, and another formed a coastal cluster encompassing several hundred kilometers. Both clusters comprised strains from humans living in rural areas and NHP. Another NHP lineage clustered in a basal relationship. No signs of adaptation of YFV strains to human hosts were detected.

Conclusions Our data suggest sylvatic transmission during the current outbreak. Additionally, cocirculation of two distinct YFV clades occurring in humans and NHP suggests the existence of multiple sylvatic transmission cycles. Increased detection of YFV might be facilitated by raised awareness for arbovirus-mediated disease after Zika and chikungunya virus outbreaks. Further surveillance is required, as reemergence of YFV from NHPs might continue and facilitate the appearance of urban transmission cycles.

Authors: Anzinger J, Christie CD, Brown D, Bispo A, Nastouli E, Kozlakidis Z, Thorne C, Ades T, Lundin R, Giaquinto C

Published in: 2nd International Conference on Zika Virus and Aedes Related Infections, June 14th – 17th 2018, Tallin-Estonia

Authors: Christie CD, Thorne C, Anzinger J, Bailey H, Palmer P, Morgan O, Bryan L, Mair S, Pierre R, Onyonyor A, Mitchell P, Melbourne-Chambers R, Webster-Kerr K, Lindo J, Lundin R, Brown D, Bispo A, Nastouli E, Giaquinto C

Published in: International Symposium on Zika Virus Research, June 4th – 6th 2018, Marseille – France

Authors: Blohm GM, Lednicky JA, Márquez M, et al.

Published in: Clin Infect Dis. 2018;66(7):1120-1121

Authors: Soriano-Arandes A, Rivero-Calle I, Nastouli E, et al.

Published in: Expert Rev Anti Infect Ther. 2018;16(3):243-254

Introduction: Zika virus (ZIKV) infection has caused the most challenging worldwide infectious epidemic outbreak in recent months. ZIKV causes microcephaly and other congenital malformations. There is a need to perform updated systematic reviews on ZIKV infection periodically because this epidemic is bringing up new evidence with extraordinary speed.

Areas covered: Evidence related to ZIKV infection in the gestational, perinatal, and early infant periods covering epidemiology, virology, pathogenesis, risk factors, time of infection during pregnancy, newborn symptoms, treatment, and vaccines. To this end, a search was performed using terms [‘Zika’] AND [‘Perinatal Infection’] OR [‘Congenital Infection’] in the PubMed® international electronic database. Out of a total of 1,538 articles published until 30 November 2017, we finally assessed 106 articles articles that were relevant to the research areas included in this study.

Expert commentary: ZIKV is a new teratogenic/neurotropic virus affecting fetuses. Many challenges are still far from being solved regarding the epidemiology, case definition, clinical and laboratory diagnosis, and preventive measures. An approach using ‘omics’ and new biomarkers for diagnosis, and a ZIKV-vaccine for treatment, might finally give us the tools to solve these challenges.

Authors: Theys K, Libin P, Dallmeier K, et al.

Published in: PLoS Pathog. 2017;13(9):e1006528