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Rapid spread of emerging Zika virus in the Pacific area
... However, in early 2015, a serious ZIKV outbreak was recorded in eastern regions of Brazil (i.e. Camaçari, Bahia) [4] and similar illnesses in several neighboring states prompted the Ministry of Health to issue a ZIKV alert in April [5]. By the end of the year the virus had spread to much of the northeastern part of the country. ...
... By the end of the year the virus had spread to much of the northeastern part of the country. Subsequently, the virus migrated throughout most other South and Central American countries [6] and the pandemic swept into the Caribbean with autochthonous transmission in at least six island states as well as in French Polynesia [5,6]. The rapid movement of ZIKV together with troubling reports of association between ZIKV and infants born with microcephaly prompted the WHO to issue an 'International Health Emergency' on 1 February 2016. ...
... The rapid movement of ZIKV together with troubling reports of association between ZIKV and infants born with microcephaly prompted the WHO to issue an 'International Health Emergency' on 1 February 2016. A direct link between ZIKV infection and increased incidence of neurologic disorders and microcephaly were established (reviewed in [4][5][6]. More recently, sexual transmissions of ZIKV, particularly in men who have cleared the virus from the blood and other bodily fluids, have been documented [5,7]. ...
Zika virus (ZIKV) is a serious public health concern that may lead to neurological disorders in affected individuals. The virus can be transmitted from an infected mother to her fetus, via mosquitoes, or sexually. ZIKV infections are associated with increased risk for Guillain-Barré syndrome (GBS) and congenital microcephaly in newborns infected prenatally. Dysregulations of intracellular microRNAs (miRNAs) in infected neurons have been linked to different neurological diseases. To determine the potential role of miRNAs in ZIKV infection we developed a chronically infected neuroblastoma cell line and carried out differential expression analyses of miRNAs with reference to an uninfected neuroblastoma cell line. A total of 3192miRNAs were evaluated and 389 were found to be upregulated < 2-fold and 1291 were downregulated < 2-fold. In particular, we determined that hsa-mir-431-5p, hsa-mir-3687, hsa-mir-4655-5p, hsa-mir-6071, hsa-mir-762, hsa-mir-5787, and hsa-mir-6825-3p were significantly downregulated, ranging from -5711 to -660-fold whereas, has-mir-4315, hsa-mir-5681b, hsa-mir-6511a-3p, hsa-mir-1264, hsa-mir-4418, hsa-mir-4497, hsa-mir-4485-3p, hsa-mir-4715-3p, hsa-mir-4433-3p, hsa-mir-4708-3p, hsa-mir-1973 and hsa-mir-564 were upregulated, ranging from 20-0.8-fold. We carried out target gene alignment of these miRNAs with the ZIKV genome to predict the function of the differentially expressed miRNAs and their potential impact on ZIKV pathogenesis. These miRNAs might prove useful as novel diagnostic or therapeutic markers and targets for further research on ZIKV infection and neuronal injury resulting from ZIKV infectivity in developing fetal brain neurons.
... Intrinsic pathway involves mitochondria that was recorded by the activation of caspase-8. The extrinsic pathway activators are not known until now (Musso et al., 2014). . It takes approximately one weak to initiate the appropriate adaptive immune response and the adaptive immune responses against CHIKV is generated by pattern recognition receptor, tool like receptor 3, 7 and 8 (Fox et al., 2016). ...
... Zika viru was 1 st identified in rhesus monkey in 1947 and 1 st infection in human was identified in 1952 (Yusuf et al., 2016). Although in Pakistan there is no clinical cases reported until now but serological diagnostic survey in 1983 showed the presence of antibodies against the Zika virus (Musso et al., 2014). The possible cause may be lack of proper diagnostic facilities in Pakistan and it is much difficult to differentiate between zika virus and other flaviviruses, especially from dengue virus (Wahid et al., 2016). ...
In Pakistan, water storage bodies are often the most plentiful and active habitats of immature stages of mosquitoes. Mosquitoes are blood feeding type of vectors that bite a particular host and suck blood. As a result, these vectors transmit disease causing agents to the host system. The most common mosquitoes borne viral diseases in Pakistan are Chicken gunya, Dengue fever, west nile and Zika fever. These diseases are common in low and poor living standard areas. Death rate increases due to more attack of these fatal diseases. Mosquitoes breeding sites are water bodies, discarded tyres, water tanks, bottles, cups and ant traps. Various environmental agents i.e. temperature fluctuations and water resources, now increase the rate of mosquitos in most areas of Pakistan. There is a lack of basic medical education and knowledge about its pervention techniques in mosquito affected areas in Pakistan. The purpose of this review is to highlight the current status of emerging mosquito borne viral diseases in Pakistan, i.e. Chicken gunya, Dengue fever, est nile and Zika fever. There is more need of prevention strategies and understanding about factors involved in spreading of mosquito borne diseases.
... Intrinsic pathway involves mitochondria that was recorded by the activation of caspase-8. The extrinsic pathway activators are not known until now (Musso et al., 2014). . It takes approximately one weak to initiate the appropriate adaptive immune response and the adaptive immune responses against CHIKV is generated by pattern recognition receptor, tool like receptor 3, 7 and 8 (Fox et al., 2016). ...
... Zika viru was 1 st identified in rhesus monkey in 1947 and 1 st infection in human was identified in 1952 (Yusuf et al., 2016). Although in Pakistan there is no clinical cases reported until now but serological diagnostic survey in 1983 showed the presence of antibodies against the Zika virus (Musso et al., 2014). The possible cause may be lack of proper diagnostic facilities in Pakistan and it is much difficult to differentiate between zika virus and other flaviviruses, especially from dengue virus (Wahid et al., 2016). ...
In Pakistan, water storage bodies are often the most plentiful and active habitats of immature stages of mosquitoes. Mosquitoes are blood feeding type of vectors that bite a particular host and suck blood. As a result, these vectors transmit disease causing agents to the host system. The most common mosquitoes borne viral diseases in Pakistan are Chicken gunya, Dengue fever, west nile and Zika fever. These diseases are common in low and poor living standard areas. Death rate increases due to more attack of these fatal diseases. Mosquitoes breeding sites are water bodies, discarded tyres, water tanks, bottles, cups and ant traps. Various environmental agents i.e. temperature fluctuations and water resources, now increase the rate of mosquitos in most areas of Pakistan. There is a lack of basic medical education and knowledge about its pervention techniques in mosquito affected areas in Pakistan. The purpose of this review is to highlight the current status of emerging mosquito borne viral diseases in Pakistan, i.e. Chicken gunya, Dengue fever, est nile and Zika fever. There is more need of prevention strategies and understanding about factors involved in spreading of mosquito borne diseases.
... Also Zika infection causes several major neurological problems, such as microcephaly in new born infants if the mother becomes infected with the virus during pregnancy [3,4] and it causes Guillain Barre syndrome (GBS) [5,6]. The ZIKV was first identified in Uganda in 1947 [7] and later it spread among different countries of North Pacific area [1], Southern and Central American countries, Brazil and Colombia [8][9][10]. The devastating spread of the ZIKV in world became a major global public health issue and drew worldwide attention, as a result, the science community have focused on formation of health policy to control and protect this re-emerging vector-borne disease. ...
Zika is a mosquito transmitted viral disease which may spread directly by the vector or sexual transmission. Zika virus may persist in semen and urine for a long time after disappearance from the blood, those persons are known as the convalescent human. It can also be transmitted vertically among mosquitoes. In this manuscript, we have considered an eight compartmental Zika model to study the effect of all the said aspects on the virus dynamics in deterministic as well as stochastic environment. In analytic part, we have computed basic reproduction number and discussed stability of different equilibrium. We have shown the proposed model undergoes through transcritical bifurcation when the reproduction number is unity and validate the model with real infection data of Dominican Republic in 2016. To study the model in stochastic environments the additive noise is taken into consideration which is formulated considering the standard Brownian white noises proportional to each class. We have obtained the condition for disease extinction and persistence in mean. All theoretical findings are justified by numerical simulations. Lastly the manuscript is ended with some conclusions.
... Zika virus disease is a flavivirus disease transmitted to humans mainly through bites of infected female aedes agypti mosquitoes [1,2]. Other ways through which the virus could be transmitted to humans include unprotected sex, unscreened blood transfusion and from mother to her unborn child [3,4,5,6]. Even though Zika virus disease has negligible mortality rate, its 'microcephalic' effect on children born to mothers who are exposed to the virus in their pregnancy cannot be overemphasized [7,8]. ...
This paper focuses on the use of wolbachia to control the spread of zika virus disease. Zika virus disease is an arboviral disease that spreads through bites of female mosquitoes in the aedes family especially, aedes aegypti. Experimental studies have indicated that wolbachia could be used to prevent the spread of zika virus disease by infecting aedes aegypti with wolbachia in a laboratory and releasing them in the wild to mate with the wild aedes aegypti. A system of nonlinear ordinary differential equations is used to model the use of wolbachia to stop the spread of zika virus disease in the human and mosquito populations. as well as the population of wolbachia-infected aedes aegypti used as control. It is shown through bifurcation analysis that the model exhibits forward bifurcation, which confirms that a unique endemic equilibrium exists in the model when the control reproduction number, . The existence of forward bifurcation in the model means that is enough to guarantee eradication of zika virus disease using wolbachia as a biocontrol. Hence, the spread of zika virus disease can be controlled irrespective of the initial sizes of infected human and mosquito populations
... Recent events concerning the outbreak of infectious diseases such as Ebola virus disease [1][2][3], Zika virus [4][5][6], a particularly deadly strain of Influenza [7,8], and COVID-19 [9] have brought to light the need to develop effective and integrated measures to both monitor and control the spread of epidemics. Only through such an integrated approach will one be able to prevent a regional outbreak from becoming a global pandemic and to mitigate the damage done to the affected areas. ...
As the recent COVID-19 pandemic has shown us, there is a critical need to develop new approaches to monitoring the outbreak and spread of infectious disease. Improvements in monitoring will enable a timely implementation of control measures, including vaccine and quarantine, to stem the spread of disease. One such approach involves the use of early warning signals to detect when critical transitions are about to occur. Although the early detection of a stochastic transition is difficult to predict using the generic indicators of early warning signals theory, the changes detected by the indicators do tell us that some type of transition is taking place. This observation will serve as the foundation of the method described in the article. We consider a susceptible-infectious-susceptible epidemic model with reproduction number R 0 > 1 so that the deterministic endemic equilibrium is stable. Stochastically, realizations will fluctuate around this equilibrium for a very long time until, as a rare event, the noise will induce a transition from the endemic state to the extinct state. In this article, we describe how metric-based indicators from early warning signals theory can be used to monitor the state of the system. By measuring the autocorrelation, return rate, skewness, and variance of the time series, it is possible to determine when the system is in a weakened state. By applying a control that emulates vaccine/quarantine when the system is in this weakened state, we can cause the disease to go extinct earlier than it otherwise would without control. We also demonstrate that applying a control at the wrong time (when the system is in a non-weakened, highly resilient state) can lead to a longer extinction time than if no control had been applied. This feature underlines the importance of determining the system's state of resilience before attempting to affect its behavior through control measures.
... albopictus (3). The specie Aedes aegypti is extensively circulated in the regions of tropical and sub-tropical domain (4,5). ...
Background: Zika virus was first discovered in Uganda in 1947 considered to be an emerging, arbovirus, mosquito-borne, Flavivirus, which is transmitted through Aedes mosquito possesses global health concerns. Distribution of zika virus all through much of Africa as well as Asia. In this study, using phylogenetic trees based analysis; we reported first full-length genome and partial capsid (C) gene of zika virus distributed over the globe. Materials and Methods: Herein, 22 full-length genome including a Spondweni virus and partial capsid (C) gene sequences of geographically diverse zika virus strains were retrieved from GenBank database. Phylogenetic investigation and evolutionary distances from nucleotide and amino acid sequences were calculated by using maximum likelihood (ML) methods choosing best fitted model in MEGA X software. Results: Phylogenetic and geographical distinct strains followed maximum-likelihood approach based full-length genome analysis showed that all strains fell into two main lineages which confined the genetically closeness. While, phylogenetic analysis of capsid (C) gene nucleotide and amino acid sequences revealed extensive differences in the topologies, followed by full genome sequences either in term of bo otstrap support or distribution of the strains into various groups. These results propose significant distinction in the evolutionary trail of the studied genome and gene. Conclusions: This data highlight the significance of studying the phylogenetic constructed viral evolution conferring to global perspective. This line of attack will expand our understanding the spread of zika virus to prevent their emergence as well as improve health surveillance.
... Recently, ZIKV has become a focus of intense research due to its unprecedented global spread, [4,[40][41][42][43][44] leading to outbreaks in different parts of the world. An upsurge in insecticide resistance, as well as climate change, has resulted in expansion of the geographical range of vector territories [8], which suggests an urgent need for alternative approaches to control mosquitoes and the pathogens they transmit. ...
Background
Vector-borne pathogens must survive and replicate in the hostile environment of an insect’s midgut before successful dissemination. Midgut microbiota interfere with pathogen infection by activating the basal immunity of the mosquito and by synthesizing pathogen-inhibitory metabolites.
Methods
The goal of this study was to assess the influence of Zika virus (ZIKV) infection and increased temperature on Aedes albopictus midgut microbiota. Aedes albopictus were reared at diurnal temperatures of day 28 °C/night 24 °C (L) or day 30 °C/night 26 °C (M). The mosquitoes were given infectious blood meals with 2.0 × 10 ⁸ PFU/ml ZIKV, and 16S rRNA sequencing was performed on midguts at 7 days post-infectious blood meal exposure.
Results
Our findings demonstrate that Elizabethkingia anophelis albopictus was associated with Ae. albopictus midguts exposed to ZIKV infectious blood meal. We observed a negative correlation between ZIKV and E. anophelis albopictus in the midguts of Ae. albopictus . Supplemental feeding of Ae. albopictus with E. anophelis aegypti and ZIKV resulted in reduced ZIKV infection rates. Reduced viral loads were detected in Vero cells that were sequentially infected with E. anophelis aegypti and ZIKV, dengue virus (DENV), or chikungunya virus (CHIKV).
Conclusions
Our findings demonstrate the influence of ZIKV infection and temperature on the Ae. albopictus microbiome along with a negative correlation between ZIKV and E. anophelis albopictus . Our results have important implications for controlling vector-borne pathogens.
Graphical Abstract
... 6,7 O ZIKV é um flavivírus que foi inicialmente isolado de um macaco Rhesus na floresta (fue inicialmente aislado de un mono Rhesus en el bosque) Zika (Uganda) em 1947, sendo transmitido por várias espécies de mosquitos Aedes. 8,9 Após a primeira infecção humana, casos esporádicos foram relatados no (después de la primera infección humana, los casos esporádicos fueron en el) sudeste da Ásia e na África subsahariana, 10 12 Apesar da infecção exantemática durante a gestação ser uma importante evidência para a orientação de investigação da infecção pelo ZIKV, este sinal não leva obrigatoriamente a ocorrência de microcefalia no feto, o que pode levar a superestimação de notificação dos casos gerando (esta evidencia no conduce necesariamente a la aparición de microcefalia en el feto, lo que puede dar lugar a una sobreestimación de la notificación de los casos, que generan) gastos públicos desnecessários ou ocorrer uma subnotificação dos casos, uma vez que um rash cutâneo pode ser passado despercebido ou não valorizado. Por isso, é fundamental a procura de outras evidências epidemiológicas que possam nortear as ações de investigação das possíveis hipóteses etiológicas determinantes dessa ocorrência (la búsqueda de otras pruebas epidemiológicas que puedan guiar las acciones de investigación de las posibles hipótesis etiológicas que determinan esta presentación). ...
... In October of 2013, a big outbreak ocurrs at French Polynesia where 396 laboratory confirmed cases was reported. Until now, for ZIKV two main distinct geographic lineages were described (African and Asian) [21,22]. ...
For many years marine algae has been subject of numerous researches and as a source of natural products with antiviral activity, such as terpenes, alkaloids and sulphated polysaccharides. However, the anti-Zika virus (ZIKV) potential of algae has not been studied. In this study we evaluated extracts seven species of the three major classes of seaweeds (Phaeophyceae, Chlorophyceae and Rhodophyceae) against ZIKV. All seaweeds tested are native of the Brazilian coast, except for Kappaphycus alvarezii that can be cultivated. ZIKV a mosquito-borne flavivirus, has become a public health problem. In recent years there has been an increase in the number of cases and a strong association between ZIKV outbreak and the spread of cases of Guillain-Barré Syndrome and microcephaly. All seaweed extracts tested in this work inhibits ZIKV replication in a dose-dependent manner. Caulerpa racemosa, Kappaphycus alvarezii and Osmundaria obtusiloba extracts were able to inhibit viral replication at low concentrations with EC50 values ranging from 1.38 to 1.98 µg/mL. We observed that O. obtusiloba presented a significant virucidal effect. Our results suggest that extracts of C. racemosa, K. alvarezii and O. obtusiloba presented very promising results, being excellent candidates for further studies, demonstrating that marine algae are an interesting source for the development of novel anti-ZIKV agents.
... 1,2 Concurrent infections with Dengue (DENV) and Chikungunya (CHIKV) virus have posed a significant burden for health care services, and new clinical challenges have been associated with these infections, in particular Guillain-Barré Syndrome, meningoencephalitis, autoimmune manifestations and, more recently, congenital abnormalities. [3][4][5][6][7][8][9][10] Since the first isolation of ZIKV in the Americas on March 26, 2015, an estimated 1.3 million individuals have been infected in northeastern Brazil, with an estimated attack rate of 5.5 cases per 1000. 11,12 ZIKV infection typically causes a self-limiting, Denguelike, illness characterized by cutaneous rash, low-grade fever, conjunctivitis, and arthralgia. ...
Several major epidemics of Zika fever, caused by the ZIKA virus (ZIKV), have emerged in Brazil since early 2015, eventually spreading to other countries on the South American continent. The present study describes the clinical manifestations and laboratory findings of patients with confirmed acute ZIKV infection during the first epidemic that occurred in Salvador, Brazil. All included patients were seen at the emergency room of a private tertiary hospital located in Salvador, Brazil from 2015 through 2017. Patients were considered eligible if signs of systemic viral febrile disease were present. All individuals were tested for ZIKV and Chikungunya infection using PCR, while rapid test was used to detect Dengue virus antibodies or, alternatively, the NS1 antigen. A diagnosis of acute ZIKV infection was confirmed in 78/434 (18%) individuals with systemic viral febrile illness. Positivity was mainly observed in blood, followed by saliva and urine. Coinfection with Chikungunya and/or Dengue virus was detected in 5% of the ZIKV-infected patients. The most frequent clinical findings were myalgia, arthralgia and low-grade fever. Laboratory analysis demonstrated normal levels of hematocrit, platelets and liver enzymes. In summary, in acute settings where molecular testing remains unavailable, clinicians face difficulties to confirm the diagnosis of ZIKV infection, as they rely only on clinical examinations and conventional laboratory tests.
... The discovery of the possible transmission of the virus through sexual contact or secretions (saliva, urine), and the absence of vaccines or specific treatments have been determinant for a high level of worldwide concern. However, diagnostic confirmation has been difficult due to the lack of markers or tests that have real diagnostic capacity, leading to constant false-positive cases 7,8 . In addition, during the outbreak in French Polynesia, it was observed that 42 patients with symptoms of ZIKV infection presented Guillain-Barré syndrome, which represented a considerable increase in the number of cases. ...
The lack of vaccines and antiviral treatment, along with the increasing number of cases of Zika virus (ZIKV) and Chikungunya virus (CHIKV) infections, emphasize the need for searching for new therapeutic strategies. In this context, the marine brown seaweed Canistrocarpus cervicornis has been proved to hold great antiviral potential. Hence, the aim of this work was to evaluate the anti-ZIKV and anti-CHIKV activity of a marine dolastane isolated from brown seaweed C. cervicornis and its crude extract. Vero cells were used in antiviral assays, submitted to ZIKV and CHIKV, and treated with different concentrations of C. cervicornis extract or dolastane. The crude extract of C. cervicornis showed inhibitory activities for both ZIKV and CHIKV, with EC50 values of 3.3 μg/mL and 3.1 μg/mL, respectively. However, the isolated dolastane showed a more significant and promising inhibitory effect (EC50 = 0.95 µM for ZIKV and 1.3 µM for CHIKV) when compared to both the crude extract and ribavirin, which was used as control. Also, the dolastane showed a very potent virucidal activity against CHIKV and was able to inhibit around 90% of the virus infectivity at 10 μM. For the ZIKV, the effects were somewhat lower, although interesting, at approximately 64% in this same concentration. Further, we observed that both the extract and the dolastane were able to inhibit the replication of ZIKV and CHIKV at different times of addition post-infection, remaining efficient even if added after 8 hours post-infection, but declining soon after. A synergistic effect using sub-doses of the extract and isolates was associated with ribavirin, inhibiting above 80% replication even at the lowest concentrations. Therefore, this work has unveiled the anti-ZIKV and CHIKV potential of C. cervicornis crude extract and an isolated dolastane, which, in turn, can be used as a preventive or therapeutic strategy in the future.
... AIDS and respiratory diseases 8,9 ), and also have important applications to biotechnology 10 and nanotechnology. 11 For instance, the recent Zika virus (ZIKV) epidemic in the Americas have led the World Health Organization to declare a 'public health emergency of international concern', 12,13 and just recently the novel coronavirus (2019-nCoV) outbreak in China was declared pandemic by the same organization. 14 Due to their complete reliance on the host gene expression machinery, viruses are under constant evolutionary pressure to effectively interact with the host intracellular factors, and at the same time effectively evade its immune system. ...
Viruses are under constant evolutionary pressure to effectively interact with the host intracellular factors, while evading its immune system. Understanding how viruses co-evolve with their hosts is a fundamental topic in molecular evolution, and may also aid in developing novel viral based applications such as vaccines, oncologic therapies, and anti-bacterial treatments. Here, based on a novel statistical framework and a large-scale genomic analysis of 2,625 viruses from all classes infecting 439 host organisms from all kingdoms of life, we identify short nucleotide sequences that are under-represented in the coding regions of viruses and their hosts. These sequences cannot be explained by the coding regions' amino acid content, codon and dinucleotide frequencies. We specifically show that short homooligonucleotide and palindromic sequences tend to be under-represented in many viruses probably due to their effect on gene expression regulation and the interaction with the host immune system. In addition, we show that more sequences tend to be under-represented in dsDNA viruses than in other viral groups. Finally, we demonstrate, based on in-vitro and in-vivo experiments, how under-represented sequences can be used to attenuated Zika virus strains.
... ZIKV (family Flaviviridae) has also become well reported with 440,000-1,300,000 reported cases from the 2015 Brazil epidemic alone [4] and can be asymptomatic or present as mild flulike symptoms concurrent with some DENV manifestations. ZIKV can also spread via intrauterine transmission leading to congenital microcephaly in unborn children [4][5][6], as well as Guillain-Barré syndrome [7]. Phylogenetic analysis of whole ZIKV genomes suggests the disease originated in East Africa in the 1920's [8] and until recent pandemics across the Pacific and the Americas, had a fairly slow epidemiology [9]. ...
Background:
The international movement of used tyres is a major factor responsible for global introductions of Aedes invasive mosquitoes (AIMs) (Diptera: Culicidae) that are major disease vectors (e.g. dengue, Zika, chikungunya and yellow fever). Surveillance methods are restricted by expense, availability and efficiency to detect all life stages. Currently, no tested method exists to screen imported used tyres for eggs in diapause, the life stage most at risk from accidental introduction. Here we test the efficiency of adhesive tape as an affordable and readily available material to screen tyres for eggs, testing its effect on hatch rate, larval development, DNA amplification and structural damage on the egg surface.
Results:
We demonstrated that the properties of adhesive tape can influence pick up of dormant eggs attached to dry surfaces. Tapes with high levels of adhesion, such as duct tape, removed eggs with high levels of efficiency (97% ± 3.14). Egg numbers collected from cleaned used tyres were found to explain larval hatch rate success well, particularly in subsequent larval to adult emergence experiments. The strength of this relationship decreased when we tested dirty tyres. Damage to the exochorion was observed following scanning electron microscopy (SEM), possibly resulting in the high variance in the observed model. We found that five days was the optimal time for eggs to remain on all tested tapes for maximum return on hatch rate success. Tape type did not inhibit amplification of DNA of eggs from three, five or ten days of exposure. Using this DNA, genotyping of AIMs was possible using species-specific markers.
Conclusions:
We demonstrated for the first time that adhesive tapes are effective at removing AIM eggs from tyres. We propose that this method could be a standardised tool for surveillance to provide public health authorities and researchers with an additional method to screen tyre cargo. We provide a screening protocol for this purpose. This method has a global applicability and in turn can lead to increased predictability of introductions and improve screening methods at high risk entry points.
... Apart from demographic changes, the number of blood donors is adversely affected by factors such as: -no opportunity to donate blood or economic reasons; -periodic disease outbreaks; -travel-associated risk of infections e.g. malaria or West Nile virus [13]; -emerging infectious diseases, e.g. the Zika virus epidemics [14][15][16]; -health condition of the population, including reduced hemoglobin levels (most common cause of deferral for the several last years) [17][18][19][20]. ...
... Only sporadic cases occurred in Africa and Asia and no large-scale outbreaks were observed (27). Recently, a largescale outbreak of ZIKV in the northeast of Brazil caused a myriad of neurological disorders, leading to the number of babies born with microcephaly (28). The ZIKV infection poses a serious pandemic threat to over 46 countries and more than 1.5 million people have been confirmed to be infected with ZIKV worldwide. ...
... In 2007, the Yap State, a Federated States of Micronesia, reported the first outbreak of Zika virus in areas different from Africa and Asia [4,5]. Subsequent infections of Zika virus in other Pacific islands were not reported until 2013 when this virus reappeared in French Polynesia and then disseminated throughout the Pacific [6,7]. ...
Zika fever is a febrile or sub-febrile illness caused by Zika virus, which mainly spreads through the bite of infected mosquitoes. Zika infection has as of late becoming an emerging infection of medical important. While clinical indications of the infection in adult cases are not serious and ailment isn't related with high death rates, Zika infection can affect foetogenesis and lead to extreme neuro developmental variations from the norm. For better understanding into various parts of Zika infection, this review was performed, with respect to the disease transmission, genetic and geographical distribution of Zika infection. We searched PubMed, Scopus, Embase, HINARI, AJOL, the Cochrane library, Web of Science, and Google Scholar. Zika virus is a member of the family Flaviviridae, which includes dengue viruses, West Nile, and yellow fever viruses. The most common symptoms reported in confirming Zika virus infections are fever, headache, malaise, maculopapular rash, fatigue or myalgia, arthritis and arthralgia. Zika virus was first isolated from the blood of a sentinel rhesus monkey from the Zika Forest in Uganda. The virus has a wide geographical distribution, including eastern and western Africa, south and Southeast Asia, and Micronesia, where in 2007, an outbreak of Zika fever was reported on Yap Island. Numerous conventional phylogenetic analyses of Zika virus genomes reveal the presence of two main viral lineages, that is, African and Asian lineages. However, it should be noted that phylogenetic analyses using E and NS5 genes reveal three major lineages of Zika virus with an additional lineage circulating in Africa which is designated African II lineage.
... Similar outbreaks were reported from other Pacific islands including Cook Islands, Easter Islands, New Caledonia and Solomon Islands (Dupont-Rouzeyrol et al. 2014;Musso et al. 2014a;Roth et al. 2016;Tognarelli et al. 2016). The outbreak of French Polynesia resulted in over 30,000 cases of illness however the precise number of infections is difficult to predict due to probability of silent infections. ...
Zika virus (ZIKV) is a mosquito-borne virus that was first isolated from Zika forest, Uganda, in 1947. Since its inception, major and minor outbreaks have been documented from several parts of world. Aedes spp. mosquitoes are the primary vectors of ZIKV, but the virus can also be transmitted through sexual practices, materno-fetal transmission, and blood transfusion. The clinical presentations of symptomatic ZIKV infections are similar to dengue and chikungunya, including fever, headache, arthralgia, retro-orbital pain, conjunctivitis, and rash. ZIKV often causes mild illness in the majority of cases, but in some instances, it is linked with congenital microcephaly and autoimmune disorders like Guillain–Barré syndrome. The recent Indian ZIKV outbreak suggests that the virus is circulating in the South East Asian region and may cause new outbreaks in future. At present, no specific vaccines or antivirals are available to treat ZIKV, so management and control of ZIKV infections rely mostly on preventive measures.
... Zika virüs insanlara temel olarak enfekte Aedes türü sivrisineklerin sokması ile bulaşır. Güney Amerika'daki Zika virüs salgınında temel vektör olan sivrisinekler Aedes aegypti, daha az etkili olarak da Aedes albopictus iken Yap Adası ve Fransız Polinezyası salgınında, Aedes hensilli, Aedes polynesiensis'in de bulaşta etkili diğer iki alt tür olduğu bildirilmiştir (2,3). ...
... In the Zika epidemics in South Africa the main vector was Aedes aegypti, and to a lesser degree Aedes albopictus. In the Yap Island and the French Polynesia epidemics, other sub-species, Aedes hensilli and Aedes polynesiensis were reported to be effective in transmission (2,3). ...
... 335were reported in Yap island in 2007 where the outbreak was poorly publicized despite the two 336 third of the population affected(21). Few years later, ZIKV hit French Polynesia(22) where 337 the first notification of severe symptoms associated to ZIKV infections were done, Guillain-338Barre syndrome(23) and microcephaly in new-born(24). After, ZIKV reached the American339 continent in 2015 (25), phylogenetic analysis indicated that the circulating ZIKV belonged to 340 the Asian clade (26, 27). ...
Mosquitoes are vectors of arboviruses affecting animal and human health. Arboviruses circulate primarily within an enzootic cycle and recurrent spillovers contribute to the emergence of human-adapted viruses able to initiate an urban cycle involving anthropophilic mosquitoes. The increasing volume of travel and trade offers multiple opportunities for arbovirus introduction in new regions. This scenario has been exemplified recently with the Zika pandemic. To incriminate a mosquito as vector of a pathogen, several criteria are required such as the detection of natural infections in mosquitoes. In this study, we used a high-throughput chip based on the BioMarkTM Dynamic arrays system capable of detecting 64 arboviruses in a single experiment. A total of 17,958 mosquitoes collected in Zika-endemic/epidemic countries (Brazil, French Guiana, Guadeloupe, Suriname, Senegal, and Cambodia) were analyzed. Here we show that this new tool can detect endemic and epidemic viruses in different mosquito species in an epidemic context. Thus, this fast and low-cost method can be suggested as a novel epidemiological surveillance tool to identify circulating arboviruses.
... The Zika virus, which is primarily transmitted through the bite of infected Aedes aegypti mosquitoes [1], was first discovered in Uganda in 1947 [2] from where it spread to Asia in the 1960s, where it has since caused small outbreaks. In 2007, Zika virus (ZIKV) caused an island-wide outbreak in Yap Island, Micronesia [3], followed by outbreaks in French Polynesia [4] and other Pacific islands between 2013 and 2014, where attack rates were up to 70% [5][6][7]. It reached Latin America between late 2013 and early 2014, but was not detected by public health authorities until May 2015 [8]. ...
Background:
In 2015, the Zika virus spread from Brazil throughout the Americas, posing an unprecedented challenge to the public health community. During the epidemic, international public health officials lacked reliable predictions of the outbreak's expected geographic scale and prevalence of cases, and were therefore unable to plan and allocate surveillance resources in a timely and effective manner.
Methods:
In this work, we present a dynamic neural network model to predict the geographic spread of outbreaks in real time. The modeling framework is flexible in three main dimensions (i) selection of the chosen risk indicator, i.e., case counts or incidence rate; (ii) risk classification scheme, which defines the high-risk group based on a relative or absolute threshold; and (iii) prediction forecast window (1 up to 12 weeks). The proposed model can be applied dynamically throughout the course of an outbreak to identify the regions expected to be at greatest risk in the future.
Results:
The model is applied to the recent Zika epidemic in the Americas at a weekly temporal resolution and country spatial resolution, using epidemiological data, passenger air travel volumes, and vector habitat suitability, socioeconomic, and population data for all affected countries and territories in the Americas. The model performance is quantitatively evaluated based on the predictive accuracy of the model. We show that the model can accurately predict the geographic expansion of Zika in the Americas with the overall average accuracy remaining above 85% even for prediction windows of up to 12 weeks.
Conclusions:
Sensitivity analysis illustrated the model performance to be robust across a range of features. Critically, the model performed consistently well at various stages throughout the course of the outbreak, indicating its potential value at any time during an epidemic. The predictive capability was superior for shorter forecast windows and geographically isolated locations that are predominantly connected via air travel. The highly flexible nature of the proposed modeling framework enables policy makers to develop and plan vector control programs and case surveillance strategies which can be tailored to a range of objectives and resource constraints.
... [3][4][5] Despite its spread, the reported ZIKV infections were not like the latest emerging outbreak in the year 2015 in Latin America. 6 ZIKV is transmitted through body fluids and sexually. A direct link between newborn microcephaly and pregnant women infection was confirmed in the year 2016. ...
Aim:
Zika virus (ZIKV) outbreak, which started in the year 2015, is considered the fastest and widely spread outbreak reported for this flavivirus. The polymerase domain of NS5 protein is targeted in other viral infections and recognized as a suitable target in ZIKV infection. Different novel modified compounds against ZIKV NS5 are tested in silico.
Main methods:
Few structures are solved for ZIKV polymerase and deposited in the protein data bank website. Two of these solved structures (with a resolution of less than 1.9 A) are used in this study to test the binding of 74 novel compounds in silico. Molecular docking is used to quantify the binding affinities of ZIKV polymerase and compare it to the Hepatitis C Virus (HCV) NS5B.
Key findings:
19 novel compounds revealed results that either similar to or better than the physiological molecule, GTP. Water molecules are found to facilitate the binding of the compounds to ZIKV RdRp structures.
Significance:
The presented 19 novel compounds represent good binders to ZIKV RdRp and could be suitable candidates for developing a new and effective anti-ZIKV polymerase nucleotide inhibitors. This article is protected by copyright. All rights reserved.
Flaviviruses pose a major public health concern across the globe. Among them, Zika virus (ZIKV) is an emerging and reemerging arthropod-borne flavivirus that has become a major international public health problem following multiple large outbreaks over the past two decades. The majority of infections caused by ZIKV exhibit mild symptoms. However, the virus has been found to be associated with a variety of congenital neural abnormalities, including microcephaly in children and Guillain–Barre syndrome in adults. The exact prediction of the potential of ZIKV transmission is still enigmatic and underlines the significance of routine detection of the virus in suspected areas. ZIKV transmission from mother to fetus (including fetal abnormalities), viral presence in immune-privileged areas, and sexual transmission demonstrate the challenges in understanding the factors governing viral persistence and pathogenesis. This review illustrates the transmission patterns, epidemiology, control strategies (through vaccines, antivirals, and vectors), oncolytic aspects, molecular insights into neuro-immunopathogenesis, and other neuropathies caused by ZIKV. Additionally, we summarize in vivo and in vitro models that could provide an important platform to study ZIKV pathogenesis and the underlying governing cellular and molecular mechanisms.
The Zika virus (ZIKV) is a serious global public health crisis. A major control challenge is its multiple transmission modes. This paper aims to simulate the transmission patterns of ZIKV using a dynamic process-based epidemiological model written in ordinary differential equations, which incorporates the human-to-mosquito infection by bites and sewage, mosquito-to-human infection by bites, and human-to-human infection by sex. Mathematical analyses are carried out to calculate the basic reproduction number and backward bifurcation, and prove the existence and stability of the equilibria. The model is validated with infection data by applying it to the 2015–2016 ZIKV epidemic in Brazil. The results indicate that the reproduction number is estimated to be 2.13, in which the contributions by mosquito bite, sex and sewage account for 85.7%, 3.5% and 10.8%, respectively. This number and the morbidity rate are most sensitive to parameters related to mosquito ecology, rather than asymptomatic or human-to-human transmission. Multiple transmission routes and suitable temperature exacerbate ZIKV infection in Brazil, and the vast majority of human infection cases were prevented by the intervention implemented. These findings may provide new insights to improve the risk assessment of ZIKV infection.
Arthropod-borne diseases currently constitute a source of major health concerns worldwide. They account for about 50% of global infectious diseases and cause nearly 700,000 deaths every year. Their rapid increase and spread constitute a huge challenge for public health, highlighting the need for early detection during epidemics, to curtail the virus spread, and to enhance outbreak management. Here, we compared a standard quantitative polymerase chain reaction (RT-qPCR) and a direct RT-qPCR assay for the detection of Zika (ZIKV), Chikungunya (CHIKV), and Rift Valley Fever (RVFV) viruses from experimentally infected-mosquitoes. The direct RT-qPCR could be completed within 1.5 h and required 1 µL of viral supernatant from homogenized mosquito body pools. Results showed that the direct RT-qPCR can detect 85.71%, 89%, and 100% of CHIKV, RVFV, and ZIKV samples by direct amplifications compared to the standard method. The use of 1:10 diluted supernatant is suggested for CHIKV and RVFV direct RT-qPCR. Despite a slight drop in sensitivity for direct PCR, our technique is more affordable, less time-consuming, and provides a better option for qualitative field diagnosis during outbreak management. It represents an alternative when extraction and purification steps are not possible because of insufficient sample volume or biosecurity issues.
In this paper, a mathematical model for controlling the spread of zika virus disease with wobachia-infected aedes aegypti mosquitoes was developed. The model consists a system of 14 non-linear ordinary differential equations. These equations were used to describe the transmission dynamics of zika virus disease in human and aedes aegypti populations, in the presence of wolbachia-infected mosquitoes used for control. Approximate analytical solution to the model was obtained through homotopy perturbation method, and was simulated at the baseline parameter values. Graphically, it was seen that the population of infected humans and the population of wolbachia-free mosquitoes diminished, while the population of wolbachia-infected mosquitoes remain on the increase as time was increased. This re sult showed that zika virus disease can be eradicated by introducing reasonable number of wolbachia-infected mosquitoes in the zika endemic area.
Zika virus (ZIKV) is transmitted mostly via mosquito bites and no vaccine is available, so it may reemerge. We and others previously demonstrated that neonatal infection of ZIKV results in heart failure and can be fatal. Animal models implicated ZIKV involvement in viral heart diseases. It is unknown whether and how ZIKV causes heart failure in adults. Herein, we studied the effects of ZIKV infection on the heart function of adult A129 mice. First, we found that ZIKV productively infects the rat-, mouse-, or human-originated heart cell lines and caused ubiquitination-mediated degradation of and distortive effects on connexin 43 (Cx43) protein that is important for communications between cardiomyocytes. Second, ZIKV infection caused 100% death of the A129 mice with decreasing body weight, worsening health score, shrugging fur, and paralysis. The viral replication was detected in multiple organs. In searching for the viral effects on heart of the A129 mice, we found that ZIKV infection resulted in the increase of cardiac muscle enzymes, implicating a viral acute myocardial injury. ZIKV-caused heart injury was also demonstrated by electrocardiogram (ECG) showing widened and fragmented QRS waves, prolonged PR interval, and slower heart rate. The intercalated disc (ICD) between two cardiomyocytes was destroyed, as shown by the electronic microscopy, and the Cx43 distribution in the ICDs was less organized in the ZIKV-infected mice compared to that in the phosphate-buffered saline (PBS)-treated mice. Consistently, ZIKV productively infected the heart of A129 mice and decreased Cx43 protein. Therefore, we demonstrated that ZIKV infection caused heart failure, which might lead to fatal sequelae in ZIKV-infected A129 mice. IMPORTANCE Zika virus (ZIKV) is a teratogen causing devastating sequelae to the newborns who suffer a congenital ZIKV infection while it brings about only mild symptoms to the health-competent older children or adults. Mouse models have played an important role in mechanistic and pathogenic studies of ZIKV. In this study, we employed 3 to 4 week-old A129 mice for ZIKV infection. RT-qPCR assays discovered that ZIKV replicated in multiple organs, including the heart. As a result of ZIKV infection, the A129 mice experienced weight loss, health score worsening, paralysis, and deaths. We revealed that the ZIKV infection caused abnormal electrocardiogram presentations, increased cardiac muscle enzymes, downregulated Cx43, and destroyed the gap junction and the intercalated disc between the cardiomyocytes, implicating that ZIKV may cause an acute myocardial injury in A129 mice. Therefore, our data imply that ZIKV infection may jeopardize the immunocompromised population with a severe clinical consequence, such as heart defect.
Zika virus (ZIKV) is an arbovirus belonging to the flavivirus genus and is transmitted in Aedes mosquito vectors. Since its discovery in humans in 1952 in Uganda, ZIKV has been responsible for many outbreaks in South America, Africa, and Asia. Patients infected with ZIKV are usually asymptomatic; mild symptoms include fever, joint and muscle pain, and fatigue. However, severe infections may have neurological implications, such as Guillain‐Barré syndrome and fetal microcephaly. To date, there are no existing approved therapeutic drugs or vaccines against ZIKV infections; treatments mainly target the symptoms of infection. Preventive measures against mosquito breeding are the main strategy for limiting the spread of the virus. Antiviral drug research for the treatment of ZIKV infection has been rapidly developing, with many drug candidates emerging from drug repurposing studies, and compound screening. In particular, several studies have demonstrated the potential of natural products as antivirals for ZIKV infection. Hence, this paper will review recent advances in natural products in ZIKV antiviral drug discovery.
ZIKV is a global health concern against which no vaccine or therapeutics are available. We characterized eight novel rabbit monoclonal antibodies recognizing ZIKV envelope and prM proteins and studied the relationship between somatic hypermutation of complementarity-determining regions, framework regions, mutations, antibody specificity, binding, and neutralizing activity.
Zika virus (ZIKV) is a mosquito-borne RNA virus belonging to the Flavivirus genus of the Flaviviridae family. During the 60 years following its discovery in 1947, ZIKV caused little concern for public health as the associated infection was reported as mostly asymptomatic or inducing mild symptoms. However, since 2013, severe neurological symptoms have been associated with ZIKV infection, compelling the World Health Organization to declare a Public Health Emergency of International Concern. Among those symptoms, neurological birth defects may affect children born to mothers infected during pregnancy. Additionally, during the past 8 years, ZIKV transmission through breastfeeding has repeatedly been suggested in epidemiological studies and demonstrated on a mouse model by our team. To better understand the biological factors controlling ZIKV transmission through breastfeeding, we investigated the nature of the viral entities excreted in the breast milk of infected dams and evaluated viral transmission to breastfed pups. We show that both cell-free and cell-associated virus is excreted into breast milk and that ZIKV is efficiently transmitted to the breastfed pups. Additionally, we studied murine breast milk cell types, and identified a majority of mammary luminal cells. Finally, we investigated the effect on ZIKV infectivity of several breast milk components that are antiviral against different viruses such as lactoferrin (LF) and lactalbumin (LA), or free fatty acids (FFA). We showed no effect of LF and LA, whereas FFA inactivated the virus. These results bring new insight concerning the mechanisms of ZIKV transmission during breastfeeding and identify biological factors modulating it. These elements should be considered in risk assessment of ZIKV mother-to-child transmission.
Zika virus a Flavivirus transmitted through the bite of a mosquito, has been considered as a neglected tropical disease for decades, until now. Due to its multiple outbreaks in the various regions of the world it has attained a significantly prominent position. The disease can be transmitted by various means, predominantly the common vector “Aedes aegypti” contributes to its high geographical distribution. The virus is important as it is responsible to cause permanent damage to infants and fetuses. e.g., microcephaly, cranial calcification and multiple neurotic abnormalities. The review comprehensively covers theepidemiology, distribution, transmission of the virus along with the measures that can be adopted to prevent its further dissemination.
The Zika virus (ZIKV) was first isolated from a rhesus macaque in the Zika forest of Uganda in 1947. Isolated cases were reported until 2007, when the first major outbreaks of Zika infection were reported from the Island of Yap in Micronesia and from French Polynesia in 2013. In 2015, ZIKV started to circulate in Latin America, and in 2016, ZIKV was considered by WHO to be a Public Health Emergency of International Concern due to cases of Congenital Zika Syndrome (CZS), a ZIKV-associated complication never observed before. After a peak of cases in 2016, the infection incidence dropped dramatically but still causes concern because of the associated microcephaly cases, especially in regions where the dengue virus (DENV) is endemic and co-circulates with ZIKV. A vaccine could be an important tool to mitigate CZS in endemic countries. However, the immunological relationship between ZIKV and other flaviviruses, especially DENV, and the low numbers of ZIKV infections are potential challenges for developing and testing a vaccine against ZIKV. Here, we discuss ZIKV vaccine development with the perspective of the immunological concerns implicated by DENV-ZIKV cross-reactivity and the use of a controlled human infection model (CHIM) as a tool to accelerate vaccine development.
Managing emerging infectious diseases is a current challenge in the fields of microbiology and epidemiology. Indeed, among other environmental and human-related factors, climate change and global warming favor the emergence of new pathogens. The recent Zika virus (ZIKV) epidemic, of which the large and rapid spread surprised the scientific community, is a reminder of the importance to study viruses currently responsible for sporadic infections. Increasing our knowledge of key factors involved in emerging infections is essential to implement specific monitoring that can be oriented according to the pathogen, targeted population, or at-risk environment. Recent technological developments, such as high-throughput sequencing, genome-wide association studies and CRISPR screenings have allowed the identification of human single nucleotide polymorphisms (SNPs) involved in infectious disease outcome. This review focuses on the human genetic host factors that have been identified and shown to be associated with the pathogenesis of ZIKV infection and candidate SNP targets.
Zika virus (ZIKV) has emerged as a particularly notorious mosquito-borne flavivirus, which can lead to a devastating congenital syndrome in the fetuses of pregnant mothers (e.g., microcephaly, spasticity, craniofacial disproportion, miscarriage, and ocular abnormalities) and cause the autoimmune disorder Guillain-Barre' syndrome of adults. Due to its severity and rapid dispersal over several continents, ZIKV has been acknowledged to be a global health concern by the World Health Organization. Unfortunately, the ZIKV has recently resurged in India with the potential for devastating effects. Researchers from all around the world have worked tirelessly to develop effective detection strategies and vaccines for the prevention and control of ZIKV infection. In this review, we comprehensively summarize the most recent research into ZIKV, including the structural biology and evolution, historical overview, pathogenesis, symptoms, and transmission. We then focus on the detection strategies for ZIKV, including viral isolation, serological assays, molecular assays, sensing methods, reverse transcription loop mediated isothermal amplification, transcription-mediated amplification technology, reverse transcription strand invasion based amplification, bioplasmonic paper-based device, and reverse transcription isothermal recombinase polymerase amplification. To conclude, we examine the limitations of currently available strategies for the detection of ZIKV, and outline future opportunities and research challenges.
The impact of Zika virus (ZIKV) is a global public health issue and its severity is ongoing. It is primarily transmitted via mosquitoes and sexual contacts. Sexual transmission experiences a longer period and strongly depends on the topological structure of sexual networks. However, relatively little work has been done to explore the characteristics of ZIKV infection in sexual networks, and further control ZIKV by changing contact patterns between individuals. In this paper, using the settings of Costa Rica as a case study, we developed a heterosexual network-based model, to study the effect of changing the degree heterogeneity by the measure of deleting the sexual contacts of individuals with small number but large degree in the sexually active places at different time, on ZIKV spread. We obtained a threshold time, which is later than the peak time of ZIKV infected cases. If applied prior to the threshold time, the measure will inhibit ZIKV infection and lower the final size; surprisingly if past the threshold time, the measure will boost ZIKV infection and increase the final size. In addition, our model yielded higher cumulative infection among females, which is in line with observations. Our results provide some guidelines for preventing and controlling mosquito-human and sexual transmissions against ZIKV, particularly for countries with a high rate of sexually transmitted infections.
Background:
Chikungunya (CHIKV), dengue (DENV), and Zika (ZIKV) viruses are of concern due to the potential of transfusion transmission in blood, especially in regions such as Southeast Asia where the viruses are endemic. The recent availability of nucleic acid testing (NAT) to screen blood donations on an automated platform provides the opportunity to detect potentially infectious units in asymptomatic donors.
Study design and methods:
Three thousand blood donations from Vietnam and 6000 from Thailand were screened with a real-time polymerase chain reaction (PCR) test (cobas CHIKV/DENV, Roche Diagnostics, Indianapolis, IN) and equal numbers on cobas Zika (Roche Diagnostics). Reactive samples were tested by alternative NAT with resolution of discordant results by heminested PCR. Throughput of simultaneous testing of the two assays on the cobas 8800 system (Roche Diagnostics) was evaluated.
Results:
In Vietnam, 9 of 3045 samples were reactive for DENV and all were confirmed, for a prevalence (with 95% confidence interval [CI]) of 0.296% (0.135-0.560). In Thailand, 2 of 6000 samples were reactive for CHIKV, 4 of 6000 for DENV, and 1 of 6005 for ZIKV, and all confirmed. The prevalence of CHIKV is 0.033% (0.004-0.120), DENV 0.067% (0.018-0.171), and ZIKV 0.017% (0.000-0.093). The overall specificity for the cobas CHIKV/DENV and cobas Zika tests was 100% (99.959-100). For the simultaneous assay testing, 960 test results were available in 7 hours and 53 minutes.
Conclusion:
Detection of CHIKV, DENV, and ZIKV RNA in donor samples in Vietnam and Thailand indicate the presence of the virus in asymptomatic blood donors. The cobas 6800/8800 systems (Roche Molecular Systems, Pleasanton, CA) enable screening blood donations in endemic areas for these viruses together or separately.
Understanding which mosquito species transmit an emerging arbovirus is critical to effective vector control. During the Zika virus epidemic in 2015 to 2016, Aedes mosquitoes were confirmed as vectors. However, studies addressing the vector status of Culex quinquefasciatus mosquitoes presented conflicting evidence and remain an outstanding source of confusion in the field. Here, we established a robust cell-based assay to identify infectious titers of Zika virus and assessed the virus titers in C. quinquefasciatus by quantitative real-time PCR (qRT-PCR). We found that while low levels of virus were detected in C. quinquefasciatus , these titers did not correspond to infectious virus, and these mosquitoes did not transmit virus in the saliva. We also present evidence that the virus may enter Culex cells before infection is disrupted. Our findings are important for future studies incriminating vector species using qRT-PCR for virus detection and offer new information on how virus transmission is blocked by mosquitoes.
Background:
Zika virus (ZIKV) is a mosquito-borne flavivirus that recently emerged in the South Pacific islands and Americas where unprecedented outbreaks were reported. Although Aedes aegypti is considered to be the main vector for ZIKV, other mosquito species have been shown to be potential vectors and differences in vector competence with respect to mosquito strain and ZIKV strain have been demonstrated. In this study we compared the vector competence of three mosquito species Aedes albopictus, Ae. aegypti and Culex quinquefasciatus from Reunion Island for three ZIKV strains.
Methods:
Five mosquito strains (2 strains of Ae. albopictus, 1 of Ae. aegypti and 2 of Cx. quinquefasciatus) were exposed to three ZIKV strains: one African strain (Dak84) and two Asian strains (PaRi_2015 and MAS66). The vector competence parameters (infection rate, dissemination efficiency and transmission efficiency) and viral loads were examined at 14 and 21 days post-infection.
Results:
The two Cx. quinquefasciatus strains did not become infected and were therefore unable to either disseminate or transmit any of the three ZIKV strains. Aedes albopictus and Ae. aegypti strains were poorly competent for the two Asian ZIKV strains, while both mosquito species displayed higher infection rates, dissemination and transmission efficiencies for the African ZIKV Dak84 strain. However, this African ZIKV strain was better transmitted by Ae. aegypti as compared to Ae. albopictus.
Conclusions:
Our results show that both Ae. albopictus and Ae. aegypti, from Reunion Island, are more likely to be competent for ZIKV in contrast to Cx. quinquefasciatus which appeared refractory to all tested ZIKV strains. This improves our understanding of the role of mosquito species in the risk of the ZIKV emergence on Reunion Island.
Zika virus (ZIKV) outbreaks and their adverse clinical consequences have raised concerns throughout the world. ZIKV was little known during the initial outbreaks in Yap islands and French Polynesia, but it came to attention after the series of Brazil outbreaks in which severe complications like microcephaly in newborn babies was detected. During 2018, outbreaks of ZIKV occurred in two states of India which, being a tropical country, has congenial climatic conditions, abundance of highly competent mosquito vectors such as Aedes aegypti and Aedes albopictus, and an immunologically naïve population. In this review, we will briefly discuss the history, epidemiology, evolution, transmission (vector‐borne and non‐vector borne), pathogenesis, clinical signs and unusual presentations, laboratory diagnosis, treatment, prevention and control of ZIKV. Finally, we suggest priorities for urgent research required to address unanswered questions about Zika infections and help bring this virus under control.
Les moustiques du genre Aedes, en particulier Ae. aegypti et Ae. albopictus, ont connu une augmentation considérable de leurs densités de population et de leurs distributions géographiques au cours des dernières décennies, en lien avec l’urbanisation croissante et l’augmentation des échanges internationaux. Parallèlement, nous avons observé une résurgence des maladies transmises par ces vecteurs, avec notamment les émergences récentes du chikungunya à partir de 2005 et du Zika à partir de 2007. Des maladies plus anciennes comme la dengue ou la fièvre jaune ont aussi causé des épidémies de taille inhabituelle en Afrique et en Amérique du sud. Dans ce contexte, un premier objectif de ce travail a été de montrer que des maladies différentes mais présentant un certain nombre de similitudes (transmission par les même vecteurs, circulation dans les même territoires dans les mêmes populations), avaient des dynamiques épidémiques semblables. Nous avons analysé conjointement dix-huit épidémies successives de Zika et de chikungunya dans neuf îles de Polynésie française et des Antilles françaises en estimant séparément les effets du virus, du territoire et des conditions météorologiques. Nous avons montré que le Zika et le chikungunya ont des niveaux de transmissibilité similaires quand ils circulent dans le même territoire (ratio de transmission 1,04 [intervalle de crédibilité à 95\%: 0.97-1.13]) mais que les taux de détection étaient plus faibles pour le Zika (odds-ratio 0,37 [IC95%: 0,34-0,40]). Des fortes précipitations étaient associées à une baisse de transmission deux semaines plus tard, puis à une augmentation renouvelée après un délai de quatre à six semaines. Après la prise en compte de ces facteurs, une hétérogénéité persistait entre les différentes îles, soulignant l'importance de caractéristiques spécifiques aux populations et aux territoires touchés. Ces résultats, en quantifiant les relations entre maladies différentes, suggèrent qu'il est possible de prévoir l'évolution d'une épidémie dans un territoire donné en utilisant des informations sur d'autres épidémies transmises par le même vecteur par le passé. Dans un second travail, nous avons examiné cette hypothèse, l'appliquant rétrospectivement aux émergences de Zika dans trois îles des Antilles françaises. Les résultats indiquent qu'en situation d’émergence épidémique de Zika, l’utilisation de données historiques concernant des épidémies antérieures de chikungunya dans les mêmes territoires permet d’améliorer considérablement la fiabilité des prédictions réalisées à un stade précoce. Cette approche, basée sur des modèles épidémiques hiérarchiques et sur l'utilisation de distributions a priori informatives, pourrait dans certaines situations améliorer l'état de préparation des systèmes sanitaires faisant face à une nouvelle émergence.
Viruses are under constant evolutionary pressure to effectively interact with the host intracellular factors, while evading its immune system. Understanding how viruses co-evolve with their hosts is a fundamental topic in molecular evolution, and may also aid in developing novel viral based applications such as vaccines, oncologic therapies, and anti-bacterial treatments. Here, based on a novel statistical framework and a large-scale genomic analysis of 2,625 viruses from all classes infecting 439 host organisms from all kingdoms of life, we identify short nucleotide sequences that are under-represented in the coding regions of viruses and their hosts. These sequences cannot be explained by the coding regions' amino acid content, codon and dinucleotide frequencies. We specifically show that short homooligonucleotide and palindromic sequences tend to be under-represented in many viruses probably due to their effect on gene expression regulation and the interaction with the host immune system. In addition, we show that more sequences tend to be under-represented in dsDNA viruses than in other viral groups. Finally, we demonstrate, based on in-vitro and in-vivo experiments, how under-represented sequences can be used to attenuated Zika virus strains.
This review provides a general overview on the positivity and persistence of Zika virus (ZIKV) in female genital tract (FGT) of non-pregnant women and animals, as well as in cell cultures, and its influence on FGT health. We performed a systematic review based on the PRISMA statement to identify studies focused on “Zika virus” and “non-pregnant female” in PubMed, Embase, Scopus Scholar and Web of Knowledge databases of full-text papers and abstracts published in English, with no restrictions regarding the initial date of publication, up to August 2019. Our search terms yielded 625 records, that were 108 after removal of duplicates, leaving 517 items for title and abstract reviews. Of these, 475 did not meet the inclusion criteria, leaving 42 records for full-text review and resulting in the exclusion of 6 additional records. The remaining 36 met our inclusion criteria. Variations were observed regarding the presence and persistence of ZIKV in lower and upper genital samples. However, the FGT was the place in which ZIKV RNA has been detected, sometimes for relatively long periods, even after the clearance from blood and urine. In addition to the vagina and cervix, the endometrium, uterus and ovary (oocytes and follicles) could also be involved in persistent ZIKV infections. Further prospective studies are needed to assess the effect of ZIKV on FGT health.
ZIKV emerged as a vector-borne pathogen capable of causing illness in infected adults and congenital birth defects in infants born to mothers infected during pregnancy. Despite the decrease in ZIKV cases since the 2015-2016 epidemic, questions concerning the prevalence and longevity of protective immunity have left vulnerable communities fearful that they may become the center of next ZIKV outbreak. Although preexisting herd immunity in regions of past outbreaks may dampen the potential for future outbreaks to occur, we currently do not know the longevity of protective immunity to ZIKV after a person becomes infected. Here, we establish a new experimentally defined minimal length of protective ZIKV immunity. We show that five rhesus macaques initially infected with ZIKV 22 to 28 months prior to rechallenge elicit a durable immune response that protected from detectable plasma viremia. This study establishes a new minimal length of protective immunity.
Mosquito-borne diseases, including arbovirus-related diseases, make up a large proportion of infectious disease cases worldwide, causing a serious global public health burden with over 700,000 deaths annually. Mosquito-borne arbovirus outbreaks can range from global to regional. In the East African Community (EAC) region, these viruses have caused a series of emerging and reemerging infectious disease outbreaks. Member states in the EAC share a lot in common including regional trade and transport, some of the factors highlighted to be the cause of mosquito-borne arbovirus disease outbreaks worldwide. In this review, characteristics of 24 mosquito-borne arboviruses indigenous to the EAC are reviewed, including lesser or poorly understood viruses, like Batai virus (BATV) and Ndumu virus (NDUV), which may escape their origins under perfect conditions to establish a foothold in new geographical locations. Factors that may influence the future spread of these viruses within the EAC are addressed. With the continued development observed in the EAC, strategies should be developed by the Community in improving mosquito and mosquito-borne arbovirus surveillance to prevent future outbreaks.
The discovery of new substances that present innumerable biological activities for the development of drugs is increasingly difficult. Natural marine products are a source of substances with a diversified chemical structure, a broad spectrum of biological activities and low cytotoxicity, which are the essential characteristics for the development of a new drug. An increasing number of reports of Chikungunya virus (CHIKV) infections, in addition to the lack of specific antiviral therapy or vaccines, emphasizes the importance of searching for effective therapy. Studies with the marine green alga Caulerpa racemosa showed antiviral potential. Hence, the aim of this work was to evaluate the anti-CHIKV activity of a marine alkaloid isolated from green alga C. racemosa. Vero cells were used in antiviral assays, submitted to CHIKV, and treated with different concentrations of caulerpin. In the antiviral activity, we observed that the isolated compound showed a much significant and promising EC 50 inhibitory effect of 0.8 µM. When evaluating the virucidal activity, we observed that caulerpin was very efficient against CHIKV, being able to inhibit around 90% of the viral infectivity when treated with 5 μM of the compound. We observed that caulerpin added at times 0, 1, 2, and 3 postinfection still maintains a 100% inhibitory potential of viral replication for CHIKV. These studies suggest that the said compounds might be potentially studied for use in the prevention and treatment of CHIKV infections. Derivatives can be considered as a promising new anti-CHIKV drug and can be used for clinical testing.
Functional constraints on viral proteins are often assessed by examining sequence conservation among natural strains, but this approach is relatively ineffective for Zika virus because all known sequences are highly similar. Here we take an alternative approach to map functional constraints on Zika virus's envelope (E) protein by using deep mutational scanning to measure how all amino-acid mutations to the protein affect viral growth in cell culture. The resulting sequence-function map is consistent with existing knowledge about E protein structure and function, but also provides insight into mutation-level constraints in many regions of the protein that have not been well characterized in prior functional work. In addition, we extend our approach to completely map how mutations affect viral neutralization by two monoclonal antibodies, thereby precisely defining their functional epitopes. Overall, our study provides a valuable resource for understanding the effects of mutations to this important viral protein, and also offers a roadmap for future work to map functional and antigenic selection to Zika virus at high resolution.
IMPORTANCE Zika virus has recently been shown to be associated with severe birth defects. The virus's E protein mediates its ability to infect cells, and is also the primary target of the antibodies that are elicited by natural infection and vaccines that are being developed against the virus. Therefore, determining the effects of mutations to this protein is important for understanding its function, its susceptibility to vaccine-mediated immunity, and its potential for future evolution. We completely mapped how amino-acid mutations to E protein affected the virus's ability to grow in cells in the lab and escape from several antibodies. The resulting maps relate changes in the E protein's sequence to changes in viral function, and therefore provide a valuable complement to existing maps of the physical structure of the protein.
Objective:
to describe the temporal and geographical expansion of Zika virus (ZIKV) circulation in countries and territories, from the time it was first isolated until 2018.
Methods:
This was a non-systematic literature review covering the period from 1947 to 2018 using the MEDLINE database and World Health Organization estimates.
Results:
Since its isolation in 1947, ZIKV circulation spread through Africa, Asia and the Pacific before reaching the Americas in 2013, causing serious clinical manifestations; the highest seroprevalence rates were recorded in Yap (74%) and in Brazil (63%); genetic mutations, absence of immunity and high vector susceptibility may have influenced ZIKV transmissibility and help to explain the magnitude of its expansion.
Conclusion:
The spread of ZIKV circulation in the Americas was the most extensive recorded thus far, possibly as a result of population and geographical characteristics of the sites where the virus circulated.
BACKGROUND Zika virus (ZIKV) infections reported in recent epidemics have been linked to clinical complications that had never been associated with ZIKV before. Adaptive mutations could have contributed to the successful emergence of ZIKV as a global health threat to a nonimmune population. However, the causal relationships between the ZIKV genetic determinants, the pathogenesis and the rapid spread in Latin America and in the Caribbean remain widely unknown.
OBJECTIVES The aim of this study was to characterise three ZIKV isolates obtained from patient samples during the 2015/2016 Brazilian epidemics.
METHODS The ZIKV genomes of these strains were completely sequenced and in vitro infection kinetics experiments were carried out in cell lines and human primary cells.
FINDINGS Eight nonsynonymous substitutions throughout the viral genome of the three Brazilian isolates were identified. Infection kinetics experiments were carried out with mammalian cell lines A549, Huh7.5, Vero E6 and human monocyte-derived dendritic cells (mdDCs) and insect cells (Aag2, C6/36 and AP61) and suggest that some of these mutations might be associated with distinct viral fitness. The clinical isolates also presented differences in their infectivity rates when compared to the well-established ZIKV strains (MR766 and PE243), especially in their abilities to infect mammalian cells.
MAIN CONCLUSIONS Genomic analysis of three recent ZIKV isolates revealed some nonsynonymous substitutions, which could have an impact on the viral fitness in mammalian and insect cells.
Since October 2013, French Polynesia has experienced the largest documented outbreak of Zika virus (ZIKAV) infection. To prevent transmission of ZIKAV by blood transfusion, specific nucleic acid testing of blood donors was implemented. From November 2013 to February 2014: 42 (3%) of 1,505 blood donors, although asymptomatic at the time of blood donation, were found positive for ZIKAV by PCR. Our results serve to alert blood safety authorities about the risk of post-transfusion Zika fever.
A Zika virus (ZIKAV) outbreak started in October 2013 in French Polynesia, South Pacific. We describe here the clinical and laboratory features of two mothers and their newborns who had ZIKAV infection as confirmed by ZIKAV RT-PCR performed on serum collected within four days post-delivery in date. The infants' infection most probably occurred by transplacental transmission or during delivery. Attention should be paid to ZIKAV-infected pregnant women and their newborns, as data on the impact on them are limited.
Zika fever, considered as an emerging disease of arbo-viral origin, because of its expanding geographic area, is known as a benign infection usually presenting as an influenza-like illness with cutaneous rash. So far, Zika virus infection has never led to hospitalisation. We describe the first case of Guillain-Barre syndrome (GBS) occurring immediately after a Zika virus infection, during the current Zika and type 1 and 3 dengue fever co-epidemics in French Polynesia. We report on a French Polynesian patient presenting a Zika virus (ZIKA) infection complicated by Guillain-Barre syndrome GBS).
Chikungunya and dengue viruses emerged in Gabon in 2007, with large outbreaks primarily affecting the capital Libreville and several northern towns. Both viruses subsequently spread to the south-east of the country, with new outbreaks occurring in 2010. The mosquito species Aedes albopictus, that was known as a secondary vector for both viruses, recently invaded the country and was the primary vector involved in the Gabonese outbreaks. We conducted a retrospective study of human sera and mosquitoes collected in Gabon from 2007 to 2010, in order to identify other circulating arboviruses.
Sample collections, including 4312 sera from patients presenting with painful febrile disease, and 4665 mosquitoes belonging to 9 species, split into 247 pools (including 137 pools of Aedes albopictus), were screened with molecular biology methods. Five human sera and two Aedes albopictus pools, all sampled in an urban setting during the 2007 outbreak, were positive for the flavivirus Zika (ZIKV). The ratio of Aedes albopictus pools positive for ZIKV was similar to that positive for dengue virus during the concomitant dengue outbreak suggesting similar mosquito infection rates and, presumably, underlying a human ZIKV outbreak. ZIKV sequences from the envelope and NS3 genes were amplified from a human serum sample. Phylogenetic analysis placed the Gabonese ZIKV at a basal position in the African lineage, pointing to ancestral genetic diversification and spread.
We provide the first direct evidence of human ZIKV infections in Gabon, and its first occurrence in the Asian tiger mosquito, Aedes albopictus. These data reveal an unusual natural life cycle for this virus, occurring in an urban environment, and potentially representing a new emerging threat due to this novel association with a highly invasive vector whose geographic range is still expanding across the globe.
Clinical and serologic evidence indicate that 2 American scientists contracted Zika virus infections while working in Senegal in 2008. One of the scientists transmitted this arbovirus to his wife after his return home. Direct contact is implicated as the transmission route, most likely as a sexually transmitted infection.
In 2007, physicians on Yap Island reported an outbreak of illness characterized by rash, conjunctivitis, and arthralgia. Although serum from some patients had IgM antibody against dengue virus, the illness seemed clinically distinct from previously detected dengue. Subsequent testing with the use of consensus primers detected Zika virus RNA in the serum of the patients but no dengue virus or other arboviral RNA. No previous outbreaks and only 14 cases of Zika virus disease have been previously documented.
We obtained serum samples from patients and interviewed patients for information on clinical signs and symptoms. Zika virus disease was confirmed by a finding of Zika virus RNA or a specific neutralizing antibody response to Zika virus in the serum. Patients with IgM antibody against Zika virus who had a potentially cross-reactive neutralizing-antibody response were classified as having probable Zika virus disease. We conducted a household survey to estimate the proportion of Yap residents with IgM antibody against Zika virus and to identify possible mosquito vectors of Zika virus.
We identified 49 confirmed and 59 probable cases of Zika virus disease. The patients resided in 9 of the 10 municipalities on Yap. Rash, fever, arthralgia, and conjunctivitis were common symptoms. No hospitalizations, hemorrhagic manifestations, or deaths due to Zika virus were reported. We estimated that 73% (95% confidence interval, 68 to 77) of Yap residents 3 years of age or older had been recently infected with Zika virus. Aedes hensilli was the predominant mosquito species identified.
This outbreak of Zika virus illness in Micronesia represents transmission of Zika virus outside Africa and Asia. Although most patients had mild illness, clinicians and public health officials should be aware of the risk of further expansion of Zika virus transmission.
The results of the yellow fever immunity survey of Central and East Africa reported by Sawyer & Whitman in 1936 prompted scientists to undertake well-planned epidemiological studies on yellow fever in eastern Africa. A Yellow Fever Research Institute (the present East African Virus Research Institute) was established at Entebbe in 1936 for this purpose. One of the areas where much work has been carried out is a strip of typical tropical forest, the Zika Forest, 12 kilometres from the Institute.
Routine surveillance work, particularly on the biting activity of the yellow fever vector mosquitoes, has been going on since 1946. It was during one of these studies in 1972 that the first yellow fever virus strain was isolated from the Entebbe area. 17 YF virus strains were isolated from Aedes africanus collected from the Zika and Sisa forests and one strain was isolated from Coquillettidia fuscopennata, also from the Zika Forest.
Three sentinel rhesus monkeys, nonimmune to YF, which were kept in the Zika Forest during the time of the epizootic died of YF disease.
The present observations indicate that YF is still present in Africa, and as such it still remains a potential menace to the human population. The epidemiological implications are discussed.
Population incidence of Guillain-Barré syndrome (GBS) is required to assess changes in GBS epidemiology, but published estimates of GBS incidence vary greatly depending on case ascertainment, definitions, and sample size. We performed a meta-analysis of articles on GBS incidence by searching Medline (1966-2009), Embase (1988-2009), Cinahl (1981-2009) and CABI (1973-2009) as well as article bibliographies. We included studies from North America and Europe with at least 20 cases, and used population-based data, subject matter experts to confirm GBS diagnosis, and an accepted GBS case definition. With these data, we fitted a random-effects negative binomial regression model to estimate age-specific GBS incidence. Of 1,683 nonduplicate citations, 16 met the inclusion criteria, which produced 1,643 cases and 152.7 million person-years of follow-up. GBS incidence increased by 20% for every 10-year increase in age; the risk of GBS was higher for males than females. The regression equation for calculating the average GBS rate per 100,000 person-years as a function of age in years was exp[-12.0771 + 0.01813(age in years)] × 100,000. Our findings provide a robust estimate of background GBS incidence in Western countries. Our regression model may be used in comparable populations to estimate the background age-specific rate of GBS incidence for future studies.
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