Zika Virus Outbreak Research Articles

β-Catenin Restricts Zika Virus Internalization by Downregulating Axl.

The latest outbreak of Zika virus (ZIKV) in the Americas was associated with significant neurologic complications, including microcephaly of newborns. We evaluated mechanisms that regulate ZIKV entry into human fetal astrocytes (HFAs). Astrocytes are key players in maintaining brain homeostasis. We show that the central mediator of canonical Wnt signaling, β-catenin, regulates Axl, a receptor for ZIKV infection of HFAs, at the transcriptional level. In turn, ZIKV inhibited β-catenin, potentially as a mechanism to overcome its restriction of ZIKV internalization through regulation of Axl. This was evident with three ZIKV strains tested but not with a laboratory-adapted strain which has a large deletion in its envelope gene. Finally, we show that β-catenin-mediated Axl-dependent internalization of ZIKV may be of increased importance for brain cells, as it regulated ZIKV infection of astrocytes and human brain microvascular cells but not kidney epithelial (Vero) cells. Collectively, our studies reveal a role for β-catenin in ZIKV infection and highlight a dynamic interplay between ZIKV and β-catenin to modulate ZIKV entry into susceptible target cells. IMPORTANCE ZIKV is an emerging pathogen with sporadic outbreaks throughout the world. The most recent outbreak in North America was associated with small brains (microcephaly) in newborns. We studied the mechanism(s) that may regulate ZIKV entry into astrocytes. Astrocytes are a critical resident brain cell population with diverse functions that maintain brain homeostasis, including neurogenesis and neuronal survival. We show that three ZIKV strains (and not a heavily laboratory-adapted strain with a large deletion in its envelope gene) require Axl for internalization. Most importantly, we show that β-catenin, the central mediator of canonical Wnt signaling, negatively regulates Axl at the transcriptional level to prevent ZIKV internalization into human fetal astrocytes. To overcome this restriction, ZIKV downregulates β-catenin to facilitate Axl expression. This highlights a dynamic host-virus interaction whereby ZIKV inhibits β-catenin to promote its internalization into human fetal astrocytes through the induction of Axl.

Zika Virus Antibody Titers Three Years after Confirmed Infection

Background: In 2015–2016, a large Zika virus (ZIKV) outbreak occurred in the Americas. Although the exact ZIKV antibody kinetics after infection are unknown, recent evidence indicates the rapid waning of ZIKV antibodies in humans. Therefore, we aimed to determine the levels of ZIKV antibodies more than three years after a ZIKV infection. Methods: We performed ZIKV virus neutralization tests (VNT) and a commercial ZIKV non-structural protein 1 (NS1) IgG ELISA in a cohort of 49 participants from Suriname who had a polymerase-chain-reaction-confirmed ZIKV infection more than three years ago. Furthermore, we determined the presence of antibodies against multiple dengue virus (DENV) antigens. Results: The ZIKV seroprevalence in this cohort, assessed with ZIKV VNT and ZIKV NS1 IgG ELISA, was 59.2% and 63.3%, respectively. There was, however, no correlation between these two tests. Furthermore, we did not find evidence of a potential negative influence of DENV immunity on ZIKV antibody titers. Conclusions: ZIKV seroprevalence, assessed with two commonly used serological tests, was lower than expected in this cohort of participants who had a confirmed previous ZIKV infection. This can have implications for future ZIKV seroprevalence studies and possibly for the duration of immunological protection after a ZIKV infection.

Public health messages on arboviruses transmitted by Aedes aegypti in Brazil

BackgroundThe outbreak of Zika virus in Brazil in 2015 followed the arrival of chikungunya in 2014 and a long history of dengue circulation. Vital to the response to these outbreaks of mosquito-borne pathogens has been the dissemination of public health messages, including those promoted through risk communication posters. This study explores the content of a sample of posters circulated in Brazil towards the end of the Zika epidemic in 2017 and analyses their potential effectiveness in inducing behaviour change.MethodsA content analysis was performed on 37 posters produced in Brazil to address outbreaks of mosquito-borne pathogens. The six variables of the Health Belief Model were used to assess the potential effectiveness of the posters to induce behaviour change.ResultsThree overarching key messages emerged from the posters. These included (i) the arboviruses and their outcomes, (ii) a battle against the mosquito, and (iii) a responsibility to protect and prevent. Among the six variables utilised through the Health Belief Model, cues to action were most commonly featured, whilst the perceived benefits of engaging in behaviours to prevent arbovirus transmission were the least commonly featured.ConclusionsThe posters largely focused on mosquito-borne transmission and the need to eliminate breeding sites, and neglected the risk of the sexual and congenital transmission of Zika and the importance of alternative preventive actions. This, we argue, may have limited the potential effectiveness of these posters to induce behaviour change.

Cytomegalovirus infection in Guillain-Barré syndrome: a retrospective study in Brazil.

Guillain-Barré syndrome (GBS) is currently the most common cause of acute flaccid paralysis worldwide. Risk factors for GBS include previous viral or bacterial infections or vaccination. Recently, an outbreak of Zika virus led to an outbreak of GBS in Latin America, mostly in Brazil, concomitant to continuous circulation of dengue virus serotypes. However, there is no study about cytomegalovirus (CMV) infection as a risk for GBS in Brazil. In this study, we report a series of cases of GBS with the aim of determining the prevalence of CMV and the characteristics associated with the infection. A cohort of 111 GBS cases diagnosed between 2011 and 2017 in Natal, northeastern Brazil, was studied. Presence of CMV IgM antibodies was determined by means of electrochemiluminescence. The analysis was performed considering CMV infection status and the clinical outcome. We found seroprevalence of 15.3% (n = 17) for CMV. CMV patients were younger (26 vs. 40; p = 0.016), with no apparent gastrointestinal (p = 0.762) or upper respiratory infections (p = 0.779) or sensory loss (p = 0.03). They presented more often with a classic GBS sensorimotor variant (p = 0.02) and with a demyelinating pattern in electrophysiological studies (p < 0.001). In Brazil, the clinical-epidemiological profile of GBS associated with CMV infection is similar to that described in other countries. Better understanding of the relationship between infectious processes and GBS is a key component of the research agenda and assistance strategy for global health initiatives relating to peripheral neuropathic conditions.

Impact of a Health Communication Campaign on Uptake of Contraceptive Services during the 2016-2017 Zika Virus Outbreak in Puerto Rico

ABSTRACT The Zika Contraception Access Network (Z-CAN) was established during the 2016–2017 Zika virus outbreak in Puerto Rico as a short-term emergency response program providing client-centered contraceptive counseling and same-day access to the full range of reversible contraceptive methods at no cost to women wishing to delay pregnancy. An evidence-based communication campaign, Ante La Duda, Pregunta (ALDP), was launched to encourage utilization of Z-CAN services. We assessed the effectiveness of campaign tactics in increasing awareness of Z-CAN among women in Puerto Rico. Data on campaign exposure and awareness were obtained through a self-administered online survey approximately two weeks after an initial Z-CAN visit, while the number of searches for participating clinics were obtained from monitoring the campaign website. Findings demonstrated that the most common ways survey respondents learned about Z-CAN were through friends or family (38.3%), social media (23.9%), a clinical encounter (12.7%), and website (11.7%). Nearly two-thirds (61.1%) of respondents had heard of the ALDP campaign. Over the campaign’s duration, there were 27,273 searches for Z-CAN clinics. Findings suggest that evidence-based communication campaigns may increase awareness of needed public health services during emergencies. Word of mouth, social media, and digital engagement may be appropriate communication tactics for emergency response mobilization.

An epidemic Zika virus isolate suppresses antiviral immunity by disrupting antigen presentation pathways

Zika virus (ZIKV) has emerged as an important global health threat, with the recently acquired capacity to cause severe neurological symptoms and to persist within host tissues. We previously demonstrated that an early Asian lineage ZIKV isolate induces a highly activated CD8 T cell response specific for an immunodominant epitope in the ZIKV envelope protein in wild-type mice. Here we show that a contemporary ZIKV isolate from the Brazilian outbreak severely limits CD8 T cell immunity in mice and blocks generation of the immunodominant CD8 T cell response. This is associated with a more sustained infection that is cleared between 7- and 14-days post-infection. Mechanistically, we demonstrate that infection with the Brazilian ZIKV isolate reduces the cross-presentation capacity of dendritic cells and fails to fully activate the immunoproteasome. Thus, our study provides an isolate-specific mechanism of host immune evasion by one Brazilian ZIKV isolate, which differs from the early Asian lineage isolate and provides potential insight into viral persistence associated with recent ZIKV outbreaks.

#20: Modeling Zika virus tissue tropism in rhesus macaques to define the risk of donor derived transmission

Abstract Background Almost 115,000 people in the United States are currently on a transplant waitlist, which vastly exceeds the number of organ donors every year. This discrepancy emphasizes the need for retention of all possible donors. Those who have recently traveled to an area with an active outbreak of Zika virus (ZIKV) are often disqualified as a donor because immunosuppressed recipients would be at risk of a donor-derived ZIKV infection. Therefore, we define ZIKV tissue tropism and the risk of donor derived transmission. Methods We subcutaneously inoculated 15 Indian-origin rhesus macaques (RM) with a Puerto Rican isolate of ZIKV (PRVABC59). All RMs were inoculated in mid to early gestation.We inoculated during pregnancy because plasma viremia is typically prolonged in pregnancy and we wanted to model tissue tropism for donor derived transmission in the worst scenario of prolonged viremia. At 30, 65, and 105 days post-infection (dpi), the animals were euthanized and comprehensive necropsies were performed, which evaluated a minimum of 60 tissues per animal. ZIKV RNA was quantified in tissues via qRT-PCR. Results Plasma viremia duration was &amp;gt;10 days in 13 of 15 RMs. ZIKV RNA was most commonly detected in lymph nodes, with 19/45 lymph nodes that were vRNA positive in 5 RMs at 30 dpi. There were 15/45 vRNA positive lymph nodes at 60 dpi and 8/38 at 105 dpi. Reproductive and maternal fetal-interface (MFI) tissues were the second most commonly positive tissues. Twenty-five MFI tissues, including the amniotic/chorionic membrane, decidua, placenta, uterus, and placental bed, were positive, with 10/53 positive at 30 dpi, 14/24 positive at 60 dpi and 1/47 positive at 105 dpi. Other vRNA positive tissues included the primary bronchus, femoral vein, kidney, thyroid, lung, colon, mammary gland, pericardium, hand nerve, and sciatic nerve in 1–2 RMs at one of the three timepoints. Conclusions We found ZIKV RNA most frequently within lymph nodes. Lymph nodes are included in lung and small bowel transplants, indicating that these transplants could pose a risk of donor-derived ZIKV transmission. Virus detection within other commonly transplanted tissues, such as the kidney and blood vessels was much less common. We did not determine what fraction of vRNA comes from replication-competent virus in each tissue; some tissues with vRNA might not contain virions that could initiate new infections. Donor-derived Zika virus transmission from other commonly transplanted organs, such as liver, seems unlikely since no viral RNA was detected in this organ.

Zika Virus Infection Activates Proinflammatory Cytokines and Triggers Monocyte Differentiation

In 2015, Zika virus (ZIKV) outbreak in several countries of South America was linked to microcephaly in newborns. Microcephaly, a severe clinical presentation, was first diagnosed in association with ZIKV, which primarily considered self-limiting infection. From infected keratinocytes, virus disseminates crossing blood-tissue barriers and is detected in various tissues including brain, muscles and placenta. One of the mechanisms utilized by viruses to cross tissue barriers involves leukocytes, where monocytes are often identified as the carriers. Recently, circulating monocytes were shown to harbor ZIKV, suggesting that these leukocyte populations could serve as vehicle to transport ZIKV to the fetus. We speculate that ZIKV infection could promote monocyte activation and release of cytokines causing tissue damage. However, little is known about monocyte susceptibility to ZIKV infection. Also, effect of ZIKV infection on transcriptional activation and production remains unclear.Materials and methods. Monocytes were isolated from cord blood buffy coats (University of Colorado Cord Blood Bank, Aurora) using Miltenyi magnetic bead separation kit (CD14 Microbeads; Miltenyi, Auburn, CA). Monocytes were infected with two ZIKV strains, PRVABC59 (South America) and IBH30656 (Nigeria), ATCC (Manassas, VA). Total RNA was extracted and used for Next generation Sequencing (Illustra RNAspin Mini kit (GE Healthcare, Marlborough, MA)). FastQ data generated by the MiSeq (Illumina, San Diego CA) was annotated and the sequence reads were analyzed by CLC workbench 9.0.1 (Qiagen, Germantown, MD) for the detection of viral and cellular genes. Differential expressions of cellular genes based on the Reads Per Kilobase of transcript per Million mapped reads were determined by comparing with mock-infected cells using RNA-seq analysis tool of CLC Workbench. Differentially regulated genes due to ZIKV infection, identified by CLC Workbench, were subjected for determining the deregulated pathways using IPA Ingenuity Pathways analysis tool (Qiagen Germantown, MD). Viral replication was determined by qPCR, Western blot and immunofluorescence. Cytokine activation was analyzed using Bio-Plex Pro Human Cytokine 27-plex Panel (Bio-Rad, Hercules, CA, USA) following manufacturer's instructions.Results. We have shown that South American and Nigerian strains of ZIKV can infect monocytes and actively replicate. Presence of capsid protein and accumulation of viral transcripts was demonstrated in vitro. Infection with PRVABC59 strain changes transcriptional activity of 332 cellular genes, while the Nigerian strain affected the transcription of 521 cellular genes compared to the mock-infected controls. Interestingly, 195 genes were commonly deregulated in cells infected with both strains. Analysis of these commonly affected genes identified multiple pathways including apoptosis, chemotaxis, cell proliferation, inflammation, acute phase response, mitochondria activation. The most amazing observation was upregulation of mitochondrial and inflammasome genes. Mitochondrial genes (MT-ND2, MT-ND5 and MT-ATP8) activated in ZIKV infected monocytes were shown to play a key role in pathogenesis of other neurodegenerative disease.Analysis of cytokine production revealed early activation of proinflammatory cytokines (IL-1β, IL-6 and IL-8) (Table 1). Upregulation of IL-1β by ZIKV infected monocytes is evident for inflammasome activation. Upregulation of IL-6, IL-10 and IL-17α suggested an activation of Th17 pathway in ZIKV infected monocytes. Besides only Nigerian ZIKV strain increased the production of IL-4 in monocytes. IL-4 together with IL-10 could promote Th2 type immune response to ZIKV. Finally, both strains increased production of FGF, while levels of VEGF were increased only in supernatants of PRVABC59 infected monocytes.Conclusions. Human monocytes are susceptible to infection with ZIKV strains, PRVABC59 and IBH30656 and support viral replication. ZIKV infection affects cellular pathways, including mitochondrial and inflammasome ones that could play significant role in pathogenesis. ZIKV infection of monocytes upregulates cytokine production, which can trigger inflammation and leukocyte migration. Analysis of cytokine production by ZIKV infected monocytes suggests activation of Th2 and Th17 leukocytes, supporting the role of this signaling in ZIKV pathogenesis. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Circle-to-circle amplification coupled with microfluidic affinity chromatography enrichment for in vitro molecular diagnostics of Zika fever and analysis of anti-flaviviral drug efficacy

Sensitive viral diagnostic methods are increasingly in demand to tackle emerging epidemics. The Zika virus (ZIKV) is particularly relevant in tropical resource limited settings (RLS) and is associated with intermittent epidemics such as the recent 2016 ZIKV outbreak in South America, wherein Zika fever was classified by WHO as a public health emergency of international concern. Thus, there is an urgent need for widespread Zika fever diagnostics and efficient drug therapies. ZIKV diagnostics are typically performed using RT-qPCR in centralized laboratories. While extremely sensitive, RT-qPCR requires rapid heating-cooling cycles, combined with continuous fluorescence measurements to allow quantification, implying high costs and limiting availability of molecular diagnostics in RLS. Here, we report isothermal amplification of ZIKV cDNA using padlock probes followed by two rounds of Rolling Circle Amplification (RCA), termed as circle-to-circle amplification (C2CA), combined with a microfluidic affinity chromatography enrichment (μACE) platform. This platform allowed the detection of <17 vRNA copies per reaction mixture, equivalent to ∼3 aM, showed a positive correlation with RT-qPCR in both average (r = 0.80) and discrete (r = 0.95) signal modes, and was validated for drug efficiency tests using in vitro infected peripheral blood mononuclear cells from 3 healthy donors. This performance shows significant promise towards highly sensitive, albeit simple and cost-effective point-of-care viral diagnostics.

An Unsupervised Algorithm for Host Identification in Flaviviruses.

Early characterization of emerging viruses is essential to control their spread, such as the Zika Virus outbreak in 2014. Among other non-viral factors, host information is essential for the surveillance and control of virus spread. Flaviviruses (genus Flavivirus), akin to other viruses, are modulated by high mutation rates and selective forces to adapt their codon usage to that of their hosts. However, a major challenge is the identification of potential hosts for novel viruses. Usually, potential hosts of emerging zoonotic viruses are identified after several confirmed cases. This is inefficient for deterring future outbreaks. In this paper, we introduce an algorithm to identify the host range of a virus from its raw genome sequences. The proposed strategy relies on comparing codon usage frequencies across viruses and hosts, by means of a normalized Codon Adaptation Index (CAI). We have tested our algorithm on 94 flaviviruses and 16 potential hosts. This novel method is able to distinguish between arthropod and vertebrate hosts for several flaviviruses with high values of accuracy (virus group 91.9% and host type 86.1%) and specificity (virus group 94.9% and host type 79.6%), in comparison to empirical observations. Overall, this algorithm may be useful as a complementary tool to current phylogenetic methods in monitoring current and future viral outbreaks by understanding host–virus relationships.

A purified inactivated vaccine derived from Vero cell-adapted zika virus elicits protection in mice

The Zika virus (ZIKV) outbreak in 2015–2016 raised public health concerns and created a pressing need for vaccine development. However, no vaccine has been developed and most of the ones under development use a single serotype of ZIKV. In this study, we established a Vero cell-adapted ZIKV strain (GMZ-002) and developed a purified inactivated virus (PIV) vaccine. GMZ-002 presented significantly increased productivity in Vero cells, and IFNAR1-blocked C57BL/6 mice administered two doses of the PIV were fully protected against lethal challenge. Vaccine efficacy was illustrated by the high level of serum neutralizing antibodies and strong innate immune response, along with an absence of detectable viremia in vaccinated mice. Furthermore, anti-sera neutralized both African and Asian genetic lineages of the virus in vitro. Our results suggest that GMZ-002 PIV elicited robust and persistent protective immunity, and therefore represents a promising vaccine candidate for ZIKV.

Placental Sampling for Understanding Viral Infections - A Simplified Protocol for the COVID-19 Pandemic.

The coronavirus disease 2019 (COVID-19) is a pandemic viral disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The impact of the disease among the obstetric population remains unclear, and the study of the placenta can provide valuable information. Adequate sampling of the placental tissue can help characterize the pathways of viral infections. A protocol of placental sampling is proposed, aiming at guaranteeing representativity of the placenta and describing the adequate conservation of samples and their integrity for future analysis. The protocol is presented in its complete and simplified versions, allowing its implementation in different complexity settings. Sampling with the minimum possible interval from childbirth is the key for adequate sampling and storage. This protocol has already been implemented during the Zika virus outbreak. A protocol for adequate sampling and storage of placental tissue is fundamental for adequate evaluation of viral infections on the placenta. During the COVID-19 pandemic, implementation of this protocol may help to elucidate critical aspects of the SARS-CoV-2 infection.

Plasma lipidome profiling of newborns with antenatal exposure to Zika virus.

The 2015-2016 Zika virus (ZIKV) outbreak in Brazil was remarkably linked to the incidence of microcephaly and other deleterious clinical manifestations, including eye abnormalities, in newborns. It is known that ZIKV targets the placenta, triggering an inflammatory profile that may cause placental insufficiency. Transplacental lipid transport is delicately regulated during pregnancy and deficiency on the delivery of lipids such as arachidonic and docosahexaenoic acids may lead to deficits in both brain and retina during fetal development. Here, plasma lipidome profiles of ZIKV exposed microcephalic and normocephalic newborns were compared to non-infected controls. Our results reveal major alterations in circulating lipids from both ZIKV exposed newborns with and without microcephaly relative to controls. In newborns with microcephaly, the plasma concentrations of hydroxyoctadecadienoic acid (HODE), primarily as 13-HODE isomer, derived from linoleic acid were higher as compared to normocephalic ZIKV exposed newborns and controls. Total HODE concentrations were also positively associated with levels of other oxidized lipids and several circulating free fatty acids in newborns, indicating a possible plasma lipidome signature of microcephaly. Moreover, higher concentrations of lysophosphatidylcholine in ZIKV exposed normocephalic newborns relative to controls suggest a potential disruption of polyunsaturated fatty acids transport across the blood-brain barrier of fetuses. The latter data is particularly important given the neurocognitive and neurodevelopmental abnormalities observed in follow-up studies involving children with antenatal ZIKV exposure, but normocephalic at birth. Taken together, our data reveal that plasma lipidome alterations associated with antenatal exposure to ZIKV could contribute to identification and monitoring of the wide spectrum of clinical phenotypes at birth and further, during childhood.

Diagnostic performance of anti-Zika virus IgM, IgAM and IgG ELISAs during co-circulation of Zika, dengue, and chikungunya viruses in Brazil and Venezuela.

BackgroundSerological diagnosis of Zika virus (ZIKV) infection is challenging because of the antibody cross-reactivity among flaviviruses. At the same time, the role of Nucleic Acid Testing (NAT) is limited by the low proportion of symptomatic infections and the low average viral load. Here, we compared the diagnostic performance of commercially available IgM, IgAM, and IgG ELISAs in sequential samples during the ZIKV and chikungunya (CHIKV) epidemics and co-circulation of dengue virus (DENV) in Brazil and Venezuela.Methodology/Principal findingsAcute (day of illness 1–5) and follow-up (day of illness ≥ 6) blood samples were collected from nine hundred and seven symptomatic patients enrolled in a prospective multicenter study between June 2012 and August 2016. Acute samples were tested by RT-PCR for ZIKV, DENV, and CHIKV. Acute and follow-up samples were tested for IgM, IgAM, and IgG antibodies to ZIKV using commercially available ELISAs. Among follow-up samples with a RT-PCR confirmed ZIKV infection, anti-ZIKV IgAM sensitivity was 93.5% (43/46), while IgM and IgG exhibited sensitivities of 30.3% (10/33) and 72% (18/25), respectively. An additional 24% (26/109) of ZIKV infections were detected via IgAM seroconversion in ZIKV/DENV/CHIKV RT-PCR negative patients. The specificity of anti-ZIKV IgM was estimated at 93% and that of IgAM at 85%.Conclusions/SignificanceOur findings exemplify the challenges of the assessment of test performance for ZIKV serological tests in the real-world setting, during co-circulation of DENV, ZIKV, and CHIKV. However, we can also demonstrate that the IgAM immunoassay exhibits superior sensitivity to detect ZIKV RT-PCR confirmed infections compared to IgG and IgM immunoassays. The IgAM assay also proves to be promising for detection of anti-ZIKV seroconversions in sequential samples, both in ZIKV PCR-positive as well as PCR-negative patients, making this a candidate assay for serological monitoring of pregnant women in future ZIKV outbreaks.

Evaluation of Zika Diagnostics for Epidemic Preparedness

Background: Development and evaluation of diagnostics for diseases of epidemic potential are often funded during epidemics and left unfinished once the epidemic is over, leaving countries ill-prepared to combat the next epidemic. UNICEF partnered with USAID to address this important gap by investing in an advance purchase commitment (APC) mechanism to accelerate the development and availability of Zika diagnostics. A central pillar of this initiative was a process for rigorous test evaluations. Methods: A network of EU-funded ZikaPLAN sites in Africa, Asia, Latin America with access to well-characterized clinical specimens were selected to evaluate rapid diagnostic tests (RDTs) for the detection of antibodies against Zika virus (ZIKV), chikungunya virus (CHIKV), yellow fever virus (YFV), and dengue virus (DENV) using a standardised protocol. Evaluation panels included Zika specimens collected during acute and convalescent stages of ZIKV outbreaks and specimens that assess potential cross-reactive antibody responses. Findings: Of five Zika RDTs evaluated, three were found to meet criteria for UNICEF procurement. The sensitivity/specificity for ChemBio ZCD system for anti-ZIKV IgM was 79.0%/97.1%, anti-DENV IgM was 90.0%/89.2%, anti-CHIKV IgM was 90.6%/97.2%. The sensitivity and specificity of the test for anti-ZIKV IgM and IgG antibodies was 86.4% and 92.7%, and 82.8% and 59.6%, respectively. The sensitivity/specificity for the SD Biosensor anti-ZIKV IgM was 96.8%/90.8%, anti-DENV IgM was 71.8%/80.7%, the DENV NS1 glycoprotein was 90.0%/90.2%, anti-YFV IgM was 84.6%/98.6%, anti-CHIKV IgM was 86.3%/92.0%. Interpretation: Biobanking networks provide access to specimens that were used to rapidly evaluate diagnostic tests for diseases of epidemic potential and facilitated procurement of tests eligible for procurement by funders. Funding: This work was supported by the USAID grant GHA-G-00-07-00007 and ZikaPLAN (European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 734584). Declaration of Interest: We declare that we have no conflicts of interest. Ethical Approval: All sites have institutional and ethics committee approval for the use of archived left over clinical or surveillance specimens for this evaluation.

Transmission dynamics of zika virus in presence of vertical transmission and some preventive measures

Zika virus (ZIKV) infection is a vector-born human disease which enhances the chance of various types of neurological complications in affected individual. In this work we have studied a mathematical model of ZIKV by incorporating vector, direct (sexual) and vertical transmission paths of the virus. In our model also we have considered different kind of preventive measures like as: protection of susceptible individuals from mosquito bites, isolation of infected individuals from mosquito, protection of susceptible individuals from sexual interaction with infected individuals, and mosquitoes control effort. We have found the analytical expression of basic reproduction number and studied the stability of the disease free equilibrium point. Existence of endemic equilibrium point and its stability are also studied. The proposed model exhibits a backward bifurcation when the virus transmission probability from infected human to mosquito crosses the crucial value. We have fitted the model to real data and estimated the key model parameters and their 95% confidence interval which depict the ZIKV outbreak in French Polynesia in 2013-14. We also have estimated the basic reproduction number using first nine epidemic weeks (EW) data and the estimated value is 2.87 with lower and upper values are 2.47 and 3.32 respectively. The effective reproduction number of the outbreak also has been studied and which decreases gradually from 5.404 to 0.2499 during the period 11th October, 2013 and 28th March, 2014. According to our sensitivity analysis, the basic reproduction number is the most sensitive with controllable parameters, biting rate, mosquito recruitment rate, mosquito death rate and recovery rate from infection. Finally, numerically we have studied the impact of different parameters on the basic reproduction number and on the number of infected human population.

Zika virus outbreak in Brazil-Lessons learned and perspectives for a safe and effective vaccine.

Zika virus (ZIKV) is an emerging pathogen of public health concern, associated with a dramatic burden in places where the virus caused outbreaks between 2015 and 2017. In the Americas, the ZIKV was first reported in Brazil and rapidly spread through the Americas. Since its first report, a number of studies have been published as we continue to learn, not only about modes of transmission, but also clinical manifestations, risk of congenital anomalies, including microcephaly and neurological malformations in fetuses born from mothers infected during pregnancy. Interventions to reduce the burden of ZIKV infection are restricted to mosquito control, and for Aedes spp mosquitoes the strategies implemented to that end proved to be unsuccessful so far. Hence the lessons we can learn following the ZIKV epidemics become of paramount importance in the development of drug treatments and in search for a vaccine.

Identification and Characterization of Zika Virus NS5 Methyltransferase Inhibitors.

The recurring outbreak of Zika virus (ZIKV) worldwide makes an emergent demand for novel, safe and efficacious anti-ZIKV agents. ZIKV non-structural protein 5 (NS5) methyltransferase (MTase), which is essential for viral replication, is regarded as a potential drug target. In our study, a luminescence-based methyltransferase assay was used to establish the ZIKV NS5 MTase inhibitor screening model. Through screening a natural product library, we found theaflavin, a polyphenol derived from tea, could inhibit ZIKV NS5 MTase activity with a 50% inhibitory concentration (IC50) of 10.10 μM. Molecular docking and site-directed mutagenesis analyses identified D146 as the key amino acid in the interaction between ZIKV NS5 MTase and theaflavin. The SPR assay indicated that theaflavin had a stronger binding activity with ZIKV NS5 wild-type (WT)-MTase than it with D146A-MTase. Moreover, theaflavin exhibited a dose dependent inhibitory effect on ZIKV replication with a 50% effective concentration (EC50) of 8.19 μM. All these results indicate that theaflavin is likely to be a promising lead compound against ZIKV.

A systematic examination of international funding flows for Ebola virus and Zika virus outbreaks 2014–2019: donors, recipients and funding purposes

IntroductionThere has been no systematic comparison of how the policy response to past infectious disease outbreaks and epidemics was funded. This study aims to collate and analyse funding for the...

Optimal control strategies of a fractional order model for Zika virus infection involving various transmissions

According to the world health organization (WHO), more than 17% of infectious diseases represented in vector-borne diseases (VBDs). So, more than 700,000 deaths annually caused by the spread of these diseases. Basically, VBDs are a usually used term that characterizes a disease transmitted to a host population, by vectors like mosquitoes, insects and ticks through feeding activity. Being a vector means that it carries a disease from an infective to a healthy host. In this paper, we address the fractional mathematical model which describes the transmission dynamics for one of the VBDs, that is Zika virus. We incorporated various combinations between four controls to reduce the transmission of this disease, the measures taken to reduce the contact among vectors and humans such as asleep under a bed net, wearing full clothes, stay in places with a screen window to keep the vector outside; the efforts to reduce the transmission rate from vectors to humans by increasing the autoimmunity; the efforts made to change sexual habits among a susceptible and infected human by using a condom at the period of Zika virus outbreak; and the measures taken to increase the death rate of vectors by using the insecticide spraying. The stability of all equilibrium points (EPs) of the fractional order model (FOM) is investigated. The control reproduction number R c of the FOM is computed and the effect of the suggested controls on the behavior of R c are presented graphically. Moreover, we characterized a fractional optimal control problem (FOCP) as well as used Pontryagin’s maximum principle to derive a fractional order necessary optimality conditions (NOCs). We solved these NOCs numerically by developing the forward-backward sweep method (FBSM) using the predictor-corrector method (PCM), where the state and adjoint equations in the form of the left Caputo fractional derivative (CFD). Furthermore, the outcomes are discussed with some figures and the approximate values for the cost functional are given based on the proposed strategies. Comparing all strategies with the uncontrolled case in order to choose the best strategy for reducing the spread of Zika virus infection.