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The reemergence of Zika virus: a review on pathogenesis, clinical manifestations, diagnosis, and treatment
Abstract
Zika virus (ZKV) is an arbovirus of the Flaviviridae family, which includes West Nile, Dengue Fever, Chikungunya Virus, Yellow Fever, and Japanese encephalitis virus. It is transmitted by the Aedes genus of mosquitoes. Prior to 2015, ZKV outbreaks occurred in areas of Africa, the Pacific Islands and Southeast Asia. The current large outbreak, which began in Brazil, has also emerged throughout a large part of South/Central America, a number of islands in the Caribbean, including Puerto Rico, the Virgin Islands, and Mexico. A sudden rise in the numbers of infants reported born with microcephaly in Brazil, and the detection of the single-stranded positive RNA virus in the amniotic fluid of affected newborns, has captured medical, mainstream media, and global political attention, causing considerable concern in a post-Ebola global community considerably more focused on the threat of internationally transmissible diseases. The goal of this article is to provide an overview of ZKV for clinicians, with the emphasis on pathogenesis, clinical manifestations, diagnosis, and treatment/preventive measures.
... However, different research groups are working on the development of ZIKV vaccination. Considering, there is a lack of target treatment available for ZIKV, the best strategy to adopt for its eradication is to create a barrier for viral transmission [13][14] . This includes endorsing protective measures at an individual level from mosquito bites. ...
... All these measures are similar to the prevention of malaria and dengue. [13][14] Additionally, care should be taken in sexual relations to prevent transmission via semen which can be done by the use of contraceptives. Importantly, proper screening of blood should be done before blood transfusions thereby ensuring that the donor blood is not infected by Zika Virus [13][14] . ...
... [13][14] Additionally, care should be taken in sexual relations to prevent transmission via semen which can be done by the use of contraceptives. Importantly, proper screening of blood should be done before blood transfusions thereby ensuring that the donor blood is not infected by Zika Virus [13][14] . ...
Zika Virus (ZIKV) having its name originated from Zika forest belongs to the family of Flaviviradae, which is a clinical classifying group of Arboviruses. In 1952 the first human case was being reported and since then, more cases have been reported specifically in the African-Asian equatorial belt. Zika virus spread around the globe makes it an alarming concern, thus it has been declared by WHO as a state of international emergency . The Infected Aedes aegypti species mosquito is a vector of transmission in the African region, while Aedes albopictus is a vector of transmission in the Asian region. Zika Virus is transmitted through blood and lymphatics, saliva, semen, and more importantly transmitted from an infected mother to an infant, during anytime of pregnancy. No anti-viral treatment exists for ZIKV so as no vaccination is present for ZIKV. The best preventive measure is to create a barrier for viral transmission. Moreover, public awareness carries great importance in preventing infection of Zika Virus.
... Dengue virus (DENV) is also a member of this family, and both ZIKV and DENV are found in tropical and subtropical regions where Aedes mosquitoes, their main vector, co-circulate [1]. Most ZIKV-infected patients are asymptomatic, whereas others exhibit mild symptoms resemble those of other arbovirus infections, especially DENV, making clinical-symptom-based diagnosis inadequate [2]. During major outbreaks in French Polynesia in 2013 and Brazil in 2015, ZIKV infection was linked to increased neurological complications, including Guillain-Barre syndrome in adults and microcephaly in infants [3]. ...
... These viruses not only share a high degree of sequence and structural homology, but also cause similar clinical symptoms, making diagnosis of a specific virus infection difficult, especially in highly endemic regions where secondary infections are prevalent [1,3,25,32,33]. Although most ZIKV-infected patients develop mild illnesses, the virus infection can also lead to serious neurological diseases in certain cases, particularly in older adults and infants [2,3]. ...
The frequency of Zika virus (ZIKV)-specific IgA and IgM and the cytokine expression profile of ZIKV-infected patients in hyperendemic areas remain unclear. This study investigated the rates of ZIKV non-structural protein 1 (NS1)-specific IgA and IgM and evaluated serum cytokine levels of ZIKV and Dengue virus (DENV) cases in Thailand to identify potential diagnostic biomarkers, elucidate the immunity against ZIKV and DENV, and investigate the association between cytokine levels and ZIKV symptoms. Low rates of positivity for ZIKV NS1-specific IgA and IgM were detected in our study. ZIKV NS1 IgA/M (11%, 11/101) in combination was more frequently detected than ZIKV NS1 IgM (2%, 2/101) or ZIKV NS1 IgA (4%, 4/96) alone, especially in acute ZIKV cases with previous DENV exposure (14%, 10/72). Cytokine analysis showed that both ZIKV and DENV infections induced polyfunctional immunity, and the latter triggered more prolonged responses. The existence of significant differences in IL-4 and IL-10 levels between acute ZIKV and acute DENV cases suggested that IL-4 (p = 0.0176) and IL-10 (p = 0.0003) may represent biomarkers for acute ZIKV and acute DENV infections, respectively. Analysis of the association between increased cytokine levels and ZIKV symptoms indicated that CXCL10 (p = 0.0029) was associated with exanthema, while IL-5 (p = 0.0496) was linked to headache. The detection of ZIKV NS1 IgA and IgM in combination may enhance the diagnosis of early ZIKV infection, particularly when levels of IgM or IgA alone are low or undetectable. IL-4 and IL-10 may serve as targets for the development of diagnostic tools to detect ZIKV and DENV infections early, respectively, in flavivirus-endemic regions.
... from 2014 to 2015, which correlated with increased microcephaly among infants born to mothers infected with ZIKV while pregnant (6,7). Spread into immunologically naive populations linked ZIKV infection to various neurological sequelae and ocular disease among both adults and fetuses (6,(8)(9)(10). ...
... When considered together, other than due to the capacity of arthropods to serve as efficient transmission vehicles, it seems counterintuitive that arthropod-borne RNA viruses exist. However, not only do these pathogens exist, they thrive, as evidenced by dengue infecting millions of people every year and new arthropod-borne epidemics emerging regularly (1-3), as was the case with ZIKV in the new world (6,7). One recent finding that may begin to elucidate the mechanisms behind the efficient transmission of arthropod-borne viruses is the discovery that virions do not always travel as individual units but instead can be delivered to subsequent cells and organisms as collectives (35)(36)(37)(39)(40)(41). ...
Zika virus (ZIKV, Flaviviridae, Flavivirus) is an arthropod-borne infection that can result in severe outcomes, particularly in fetuses infected in utero. It has been assumed that infection by ZIKV, as well as other viruses, is largely initiated by individual virus particles binding to and entering a cell. However, recent studies have demonstrated that multiple virus particles are frequently delivered to a cell simultaneously, and that this collective particle delivery enhances infection. ZIKV is maintained in nature between Aedes aegypti mosquitos and vertebrate hosts, including humans. Human infection is initiated through the injection of a relatively small initial inoculum comprised of a genetically complex virus population. Since most mutations decrease virus fitness, collective particle transmission could benefit ZIKV and other arthropod-borne diseases by facilitating the maintenance of genetic complexity and adaptability during infection, or through other mechanisms. Therefore, we utilized a barcoded ZIKV to quantify the number of virus genomes that initiate a plaque. We found that individual plaques contain a mean of 10 infecting viral genomes (range 1 to 212). Few plaques contained more than two dominant genomes. To determine whether multi-genome infectious units consist of collectively transmitting virions, infectious units of ZIKV were then separated mechanically by centrifugation and heavier fractions found to contain more genomes per plaque forming unit, with larger diameters. Finally, larger/heavier infectious units reformed after removal. These data suggest that ZIKV populations consist of a variety of infectious unit sizes, likely mostly made up of aggregates, and only rarely begin with a single virus genome.
IMPORTANCE
The arthropod-borne Zika virus (ZIKV) infects humans and can cause severe neurological sequelae, particularly in fetuses infected in utero. How this virus has been able to spread across vast geological ranges and evolve in new host populations is not yet understood. This research demonstrates a novel mechanism of ZIKV transmission through multi-genome aggregates, providing insight into ZIKV evolution, immunologic evasion, and better future therapeutic design. This work shows that ZIKV plaques result from collections of genomes rather than individual genomes, increasing the potential for interactions between ZIKV genotypes.
... Sexual contact Virus is seen to get transferred tough sexual contact also. the presence of side effects 31 . ...
... There is no specific treatment for the zika infection. Symptoms for joint pain and aches can be treated using acetaminophen drug 31 . ...
The outbreak of zika virus belonging to the flavivirus genus was first reported in 1947 in the monkey species in Uganda. Then it was first isolated from the Aedes mosquito’s species. Recent outbreaks have been reported in India also. The main host of the virus is humans like all other flaviviruses. Although the fatality rate is not so high but the effects are seen majorly on the fetus when pregnant women gets infected. No perfect treatment or vaccine has been developed yet to treat the disease. In India also few cases are now being reported and it shows that the outbreak of the virus is just not limited to Brazil and America but now also to Asian countries as well and gradually worldwide its infection will spread through. This article deals with the development of the zika virus from 1947 to 2018 and the preventive measures in order to prevent future outbreaks have been considered. © 2019 Oriental Scientific Publishing Company. All rights reserved.
... 3 Initially thought to be transmitted almost exclusively by Aedes Aegypti mosquitoes, we now know there are at least 5 different mosquitoes capable of transmitting ZIKV, the 2 most common being A. aegypti and A. albopicutus. 4 Additionally, we now understand horizontal and vertical transmission in humans is possible. 5 The past 2 years have been dedicated to learning more about this previously unknown viral illness. ...
... 3,8,12 Recent seroprevalence indicates asymptomatic infections in children and adolescents may be lower than adults, with only 29% of children 6 to 16 years of age experiencing asymptomatic infections versus of the 80% of adults experiencing asymptomatic infections. 4 Individuals who are symptomatic typically present with symptoms within 2 weeks of exposure and experience mild symptoms that only last between 2-7 days. 5,10 Clinical symptoms of children are similar to adults presenting with ZIKV. ...
In our previous article on Zika, we established that it is a member of the Flaviviridae virus family. In this article, we discuss updated information regarding transmission and complications of Zika. In addition to contracting Zika virus from an infected mosquito, it has been transmitted between mother and fetus/infant and between sexual partners. Zika has been associated with Guillain-Barré syndrome, although the causal link has yet to be established. Microcephaly is a primary concern for fetuses of pregnant women infected with Zika virus. The most effective prevention strategy is to avoid mosquito bites in high-risk Zika areas.
... MERS is now classified as one of the most prominent viral threats to the Middle East and has caused hundreds of deaths and thousands of infections in a short time. Moreover, in the past few years, the world witnessed the worst Ebola outbreak ever that started to hit West Africa in early 2014 and the pandemic reemergence of Zika virus in 2016 [11,12,24]. With these evident possibilities of massive outbreaks and implications, the situation is rapidly growing more serious, and the demand for the development of rapid diagnostics and effective control strategies is becoming more urgent. ...
... In the early 1980s, the field of diagnostic virology was boosted with two other major developments: 1) the birth of various immunoassays; and 2) the invention of polymerase chain reaction (PCR). This was followed by the development of a very wide range of serological and molecular detection techniques, which rapidly evolved to constitute the mainstream approaches of both laboratory research and the clinical diagnosis of viruses ( Fig. 1) [24,29]. ...
Viruses are the smallest known microbes, yet they cause the most significant losses in human health. Most of the time, the best-known cure for viruses is the innate immunological defense system of the host; otherwise, the initial prevention of viral infection is the only alternative. Therefore, diagnosis is the primary strategy toward the overarching goal of virus control and elimination. The introduction of a new class of nanoscale materials with multiple unique properties and functions has sparked a series of breakthrough applications. Gold nanoparticles (AuNPs) are widely reported to guide an impressive resurgence in biomedical and diagnostic applications. Here, we review the applications of AuNPs in virus testing and detection. The developed AuNP-based detection techniques are reported for various groups of clinically relevant viruses with a special focus on the applied types of bio-AuNP hybrid structures, virus detection targets, and assay modalities and formats. We pay particular attention to highlighting the functional role and activity of each core Au nanostructure and the resultant detection improvements in terms of sensitivity, detection range, and time. In addition, we provide a general summary of the contributions of AuNPs to the mainstream methods of virus detection, technical measures, and recommendations required in guidance toward commercial in-field applications.
... Infection with ZIKV, the causal agent of Zika fever (ZIKF), leads to a temporary febrile illness that affects around 20% of individuals who contract the virus [11]. During the acute phase of ZIKV infection, patients have elevated serum levels of pro-and anti-inflammatory cytokines, including tumor necrosis factor alpha (TNFα), interleukin (IL) 1β (IL1β), IL2, IL4, IL6, IL9, IL10, IL13, and IL17. ...
Monocytes are the primary targets of Zika virus (ZIKV) and are associated with ZIKV pathogenesis. Currently, there is no effective treatment for ZIKV infection. It is known that 1,25-dihydroxy vitamin D3 (VitD3) has strong antiviral activity in dengue virus-infected macrophages, but it is unknown whether VitD3 inhibits ZIKV infection in monocytes. We investigated the relationship between ZIKV infection and the expression of genes of the VitD3 pathway, as well as the inflammatory response of infected monocytes in vitro. ZIKV replication was evaluated using a plaque assay, and VitD3 pathway gene expression was analyzed by RT-qPCR. Pro-inflammatory cytokines/chemokines were quantified using ELISA. We found that VitD3 did not suppress ZIKV replication. The results showed a significant decrease in the expression of vitamin D3 receptor (VDR), cytochrome P450 family 24 subfamily A member 1 (CYP24A1), and cathelicidin antimicrobial peptide (CAMP) genes upon ZIKV infection. Treatment with VitD3 was unable to down-modulate production of pro-inflammatory cytokines, except TNF-α, and chemokines. This suggests that ZIKV infection inhibits the expression of VitD3 pathway genes, thereby preventing VitD3-dependent inhibition of viral replication and the inflammatory response. This is the first study to examine the effects of VitD3 in the context of ZIKV infection, and it has important implications for the role of VitD3 in the control of viral replication and inflammatory responses during monocyte infection.
... The specific clinical diagnosis of Zika is difficult because it usually causes mild and self-limited disease or can develop as an asymptomatic infection in about 20% of cases [2,3]. However, Zika virus infection is associated with harmful outcomes for pregnancy and neonates. ...
Brazil reported 18,282 suspected congenital Zika syndrome (CZS) cases up to 2018 and accounts for 61.4% of the total reported Zika cases in the Americas in the period. To detect high-risk areas for children with CZS in the city of Rio de Janeiro, we used cluster detection and thematic maps. We analyzed data using a Poisson model in Satscan 10.1.3 software. We also analyzed the records of children with CZS from 2015 to 2016 to describe the clinical and epidemiological maternal and child profile, as well as live births in 2016 and the social development index (SDI) by neighborhood. In 2015 and 2016, the incidence rates of CZS were 8.84 and 46.96 per 100,000 live births in the city, respectively. Severe congenital findings such as microcephaly and brain damage, osteoarticular impairment, ocular abnormalities, and hearing loss were observed in 47 children. The spatial distribution of CZS was concentrated in the north and west zones in heterogeneous neighborhoods. The neighborhoods with the highest occurrence of CZS cases were found to have the worst SDIs. Stascan detected three spatial clusters in the north zone, where the SDI is lower. The clusters presented high relative risks for CZS (7.86, 1.46, and 2.08), although they were not statistically significant. Our findings highlight a higher occurrence of CZS in areas with less favorable socioeconomic conditions.
... Some viruses re-emerge after a period of time without notable outbreaks, and such was the case for Ebola virus (EBOV) in 2014 [41]. In addition, the resurgence of Zika virus (ZIKV) occurred between 2015 and 2016 [42]. The World Health Organization in 2015 issued new guidance for best practices in viral disease nomenclature to lessen secondary burdens from the incredible human health impact of these viral disease pandemics that had been observed because "certain disease names provoke a backlash against members of particular religious or ethnic communities, create unjustified barriers to travel, commerce and trade, and trigger needless slaughtering of food animals" [43]. ...
Metabolomics is an analytical approach that involves profiling and comparing the metabolites present in biological samples. This scoping review article offers an overview of current metabolomics approaches and their utilization in evaluating metabolic changes in biological fluids that occur in response to viral infections. Here, we provide an overview of metabolomics methods including high-throughput analytical chemistry and multivariate data analysis to identify the specific metabolites associated with viral infections. This review also focuses on data interpretation and applications designed to improve our understanding of the pathogenesis of these viral diseases.
... Mild fever and muscle pain are the primary symptoms. In some pregnant women it causes microcephaly in the fetus [4]. Guillain-Barré syndrome has been reported in the case of an epidemic in French Polynesia [5]. ...
Zika virus (ZV) infection causes fatal hemorrhagic fever. Most patients are unaware of their symptoms; therefore, a rapid diagnostic tool is required to detect ZV infection. To solve this problem, we developed a rapid electrical biosensor composed of a truncated DNA aptamer immobilized on an interdigitated gold micro-gap electrode and alternating current electrothermal flow (ACEF) technique. The truncated ZV aptamer (T-ZV apt) was prepared to reduce the manufacturing cost for biosensor fabrication, and it showed binding affinity similar to that of the original ZV aptamer. This pulse-voltammetry-based biosensor was composed of a T-ZV apt immobilized on an interdigitated micro-gap electrode. Atomic force microscopy was used to confirm the biosensor fabrication. In addition, the optimal biosensor performance conditions were investigated using pulse voltammetry. ACEF promoted aptamer-target binding, and the target virus envelope protein was detected in the diluted serum within 10 min. The biosensor waveform increased linearly as the concentration of the Zika envelope in the serum increased, and the detection limit was 90.1 pM. Our results suggest that the fabricated biosensor is a significant milestone for rapid virus detection.
... ZIKV was first discovered in Rhesus monkeys in Uganda's Zika rainforest in 1947 [1]. However, the virus remained undiagnosed for a long time due to the disease's nonspecific flu-like symptoms and a lack of diagnostic screening [2,3]. In 2007, ZIKV re-emerged in the Pacific islands, spreading to over 80 countries/territories, including Latin America, the United States, and Southeast Asia [4][5][6][7][8]. ...
Zika virus (ZIKV), a re-emerging virus, causes congenital brain abnormalities and Guillain–Barré syndrome. It is mainly transmitted by Aedes mosquitoes, but infections are also linked to sexual transmissions. Infectious ZIKV has been isolated, and viral RNA has been detected in semen over a year after the onset of initial symptoms, but the mode of long-term persistence is not yet understood. ZIKV can proliferate in human Sertoli cells (HSerC) for several weeks in vitro, suggesting that it might be a reservoir for persistent ZIKV infection. This study determined proteomic changes in HSerC during ZIKV infections by TMT-mass spectrometry analysis. Levels of 4416 unique Sertoli cell proteins were significantly altered at 3, 5, and 7 days after ZIKV infection. The significantly altered proteins include enzymes, transcription regulators, transporters, kinases, peptidases, transmembrane receptors, cytokines, ion channels, and growth factors. Many of these proteins are involved in pathways associated with antiviral response, antigen presentation, and immune cell activation. Several immune response pathway proteins were significantly activated during infection, e.g., interferon signaling, T cell receptor signaling, IL-8 signaling, and Th1 signaling. The altered protein levels were linked to predicted activation of immune response in HSerC, which was predicted to suppress ZIKV infection. ZIKV infection also affected the levels of critical regulators of gluconeogenesis and glycolysis pathways such as phosphoglycerate mutase, phosphoglycerate kinase, and enolase. Interestingly, many significantly altered proteins were associated with cardiac hypertrophy, which may induce heart failure in infected patients. In summary, our research contributes to a better understanding of ZIKV replication dynamics and infection in Sertoli cells.
... However, these resources have limited effectiveness, emphasizing the importance of research investment in developing new anti-ZIKV agents. [27][28][29][30][31] In the context of antivirals, the NS2B-NS3 protease (NS2B-NS3 pro) complex of ZIKV has been described as a promising molecular target for developing drugs against this emerging flavivirus 32 ( Figure 1A). The NS2B-NS3 pro complex is a chymotrypsin-like serine protease with a central role in processing the ZIKV polyprotein, ...
Zika virus (ZIKV) infections are associated with severe neurological complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B‐NS3 protease (NS2B‐NS3 pro), which is essential for viral replication, is a promising molecular target for anti‐ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; 7 relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B‐NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off‐label use against ZIKV. The 50% inhibitory concentration values of these compounds for the inhibition of NS2B‐NS3 pro ranged at 0.38–21.6 µM; most compounds exhibited non‐competitive inhibition (66%). All compounds that could inhibit the NS2B‐NS3 pro complex showed potent in vitro anti‐ZIKV activity with a 50% effective concentration ranging 0.024–50 µM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL‐69 cell lines ranged at 0.6–1,388.02 µM and the selectivity index was 3.07–1,698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases. This article is protected by copyright. All rights reserved.
... A new avian IAV strain (H7N9), "Bird flu, " and the Middle East respiratory syndrome (MERS)-CoV in 2013 also emerged . Some viruses re-emerged after a number of years, such as the reemergence of the Ebola virus (EBOV) in 2014 (Shen et al., 2015), resurgences of the Zika virus (ZIKV) in 2015 and 2016 (Shuaib et al., 2016), and so forth (Chauhan et al., 2020;Guo, 2020). The ongoing pandemic caused by SARS-CoV-2 has already ravaged humanity and is still on the rise across the globe. ...
Viral infections can cause rampant disease in human beings, ranging from mild to acute, that can often be fatal unless resolved. An acute viral infection is characterized by sudden or rapid onset of disease, which can be resolved quickly by robust innate immune responses exerted by the host or, instead, may kill the host. Immediately after viral infection, elements of innate immunity, such as physical barriers, various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, provide the first line of defense for viral clearance. Innate immunity not only plays a critical role in rapid viral clearance but can also lead to disease progression through immune-mediated host tissue injury. Although elements of antiviral innate immunity are armed to counter the viral invasion, viruses have evolved various strategies to escape host immune surveillance to establish successful infections. Understanding complex mechanisms underlying the interaction between viruses and host’s innate immune system would help develop rational treatment strategies for acute viral infectious diseases. In this review, we discuss the pathogenesis of acute infections caused by viral pathogens and highlight broad immune escape strategies exhibited by viruses.
... Additionally, tree shrews have already been successfully developed as animal models of different viral infections including influenza (Yang et al., 2013), herpes simplex , hepatitis C virus (Feng et al., 2017), and ZIKV (Abdullah et al., 2019). Successful establishment of the tree shrew model of ZIKV has been demonstrated by SC inoculation (Shuaib et al., 2016;Abdullah et al., 2019). In this study, all animals were regularly monitored for Tb, animal weight, etc. throughout the experiment period. ...
Sexual transmission of Zika Virus (ZIKV) elevates the risk of its dissemination in the female reproductive tract and causes a serious threat to the fetus. However, the available animal models are not appropriate to investigate sexual transmission, dynamics of ZIKV infection, replication, and shedding. The use of tree shrew as a small animal model of ZIKV vaginal infection was assessed in this study. A total of 23 sexually mature female tree shrews were infected with ZIKV GZ01 via the intravaginal route. There was no significant difference in change of body weight, and the temperature between ZIKV infected and control animals. Viral RNA loads were detected in blood, saliva, urine, and vaginal douching. ZIKV RNA was readily detected in vaginal lavage of 22 animals (95.65%, 22/23) at 1 dpi, and viral load ranged from 104.46 to 107.35 copies/ml, and the peak of viral load appeared at 1 dpi. The expression of key inflammatory genes, such as IL6, 8, CCL5, TNF-a, and CXCL9, was increased in the spleen of ZIKV infected animals. In the current study, female tree shrews have been successfully infected with ZIKV through the vaginal route for the first time. Interestingly, at first, ZIKV replicates at the local site of infection and then spreads throughout the host body to develop a robust systemic infection and mounted a protective immune response. This small animal model is not only valuable for exploring ZIKV sexual transmission and may also help to explain the cause of debilitating manifestations of the fetus in vivo.
... Strong evidence has since confirmed the association between ZIKV infection in pregnant women and the development of fetal malformations (e.g., microcephaly, congenital contractures, hypertonia, macular and retinal damage) [7,8]; in severe cases, in utero ZIKV infection can result in premature fetal death. In contrast, ZIKV infections in healthy adults are relatively mild and often asymptomatic with self-limited illness lasting two to seven days [9]. Nevertheless, the incidence of GBS among older adults rose sharply in conjunction with ZIKV outbreaks in Brazil and French Polynesia, [4,10] indicating these individuals are also at risk for ZIKV-associated neurological complications. ...
Once an obscure pathogen, Zika virus (ZIKV) has emerged as a significant global public health concern. Several studies have linked ZIKV infection in pregnant women with the development of microcephaly and other neurological abnormalities, emphasizing the need for a safe and effective vaccine to combat the spread of this disease. Preclinical studies and vaccine development efforts have largely focused on the role of humoral immunity in disease protection. Consequently, relatively little is known in regard to cellular immunity against ZIKV, although an effective vaccine will likely need to engage both the humoral and cellular arms of the immune system. To that end, we utilized two-dimensional liquid chromatography coupled with tandem mass spectrometry to identify 90 ZIKV peptides that were naturally processed and presented on HLA class I and II molecules (HLA-A*02:01/HLA-DRB1*04:01) of an immortalized B cell line infected with ZIKV (strain PRVABC59). Sequence identity clustering was used to filter the number of candidate peptides prior to evaluating memory T cell recall responses in ZIKV convalescent subjects. Peptides that individually elicited broad (4 of 7 subjects) and narrow (1 of 7 subjects) T cell responses were further analyzed using a suite of predictive algorithms and in silico modeling to evaluate HLA binding and peptide structural properties. A subset of nine broadly reactive peptides was predicted to provide robust global population coverage (97.47% class I; 70.74% class II) and to possess stable structural properties amenable for vaccine formulation, highlighting the potential clinical benefit for including ZIKV T cell epitopes in experimental vaccine formulations.
... A new avian IAV strain (H7N9), "Bird flu, " and the Middle East respiratory syndrome (MERS)-CoV in 2013 also emerged . Some viruses re-emerged after a number of years, such as the reemergence of the Ebola virus (EBOV) in 2014 (Shen et al., 2015), resurgences of the Zika virus (ZIKV) in 2015 and 2016 (Shuaib et al., 2016), and so forth (Chauhan et al., 2020;Guo, 2020). The ongoing pandemic caused by SARS-CoV-2 has already ravaged humanity and is still on the rise across the globe. ...
Viral infections can cause rampant disease in human beings, ranging from mild to acute, that can often be fatal unless resolved. An acute viral infection is characterized by sudden or rapid onset of disease, which can be resolved quickly by robust innate immune responses exerted by the host or, instead, may kill the host. Immediately after viral infection, elements of innate immunity, such as physical barriers, various phagocytic cells, group of cytokines, interferons (IFNs), and IFN-stimulated genes, provide the first line of defense for viral clearance. Innate immunity not only plays a critical role in rapid viral clearance but can also lead to disease progression through immune-mediated host tissue injury. Although elements of antiviral innate immunity are armed to counter the viral invasion, viruses have evolved various strategies to escape host immune surveillance to establish successful infections. Understanding complex mechanisms underlying the interaction between viruses and host’s innate immune system would help develop rational treatment strategies for acute viral infectious diseases. In this review, we discuss the pathogenesis of acute infections caused by viral pathogens and highlight broad immune escape strategies exhibited by viruses.
... Several infectious diseases have expanded their geographical range, or their incidence has incremented in areas where they were usually constrained [4], in some cases, in association with temperature increases. Moreover, some diseases have more recently reemerged in South America (e.g., Dengue fever and the Zika virus) in places where they had been gone for more than 100 years [5,6]; or the diseases have expanded their range of occurrence (e.g., canine visceral leishmaniasis [7]). In this regard, vector-borne diseases (VBDs) are particularly susceptible to ongoing climate change since their incidence depends on the vector's distribution, abundance, lifehistory traits, and vital rates; and most such disease-vectors are ectothermic arthropods [8]. ...
Vector-borne diseases (VBD) are particularly susceptible to climate change because most of the diseases’ vectors are ectotherms, which themselves are susceptible to thermal changes. The Chagas disease is one neglected tropical disease caused by the protozoan parasite, Trypanosoma cruzi. One of the main vectors of the Chagas disease in South America is Triatoma infestans, a species traditionally considered to be restricted to domestic or peridomestic habitats, but sylvatic foci have also been described along its distribution. The infestation of wild individuals, together with the projections of environmental changes due to global warming, urge the need to understand the relationship between temperature and the vector’s performance. Here, we evaluated the impact of temperature variability on the thermal response of T. infestans. We acclimated individuals to six thermal treatments for five weeks to then estimate their thermal performance curves (TPCs) by measuring the walking speed of the individuals. We found that the TPCs varied with thermal acclimation and body mass. Individuals acclimated to a low and variable ambient temperature (18°C ± 5°C) exhibited lower performances than those individuals acclimated to an optimal temperature (27°C ± 0°C); while those individuals acclimated to a low but constant temperature (18°C ± 0°C) did not differ in their maximal performance from those at an optimal temperature. Additionally, thermal variability (i.e., ± 5°C) at a high temperature (30°C) increased performance. These results evidenced the plastic response of T. infestans to thermal acclimation. This plastic response and the non-linear effect of thermal variability on the performance of T. infestans posit challenges when predicting changes in the vector’s distribution range under climate change.
... Moreover, after infection, the amount of antibodies usually takes one or two weeks to reach a detectable level, making this technique more suitable for population infection study [8]. Since molecular techniques such as reverse transcription polymerase chain reaction (RT-PCR) can directly detect a specific sequence of virus genome with high sensitivity and specificity, they have become the standard virus detection techniques [9,10]. Nonetheless, standard RT-PCR approaches rely heavily on expensive Diagnostics 2021, 11, 9 3 of 18 equipment, well-trained staff, and equipped laboratories. ...
The recent outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated serious respiratory disease, coronavirus disease 2019 (COVID-19), poses a major threat to global public health. Owing to the lack of vaccine and effective treatments, many countries have been overwhelmed with an exponential spread of the virus and surge in the number of confirmed COVID-19 cases. Current standard diagnostic methods are inadequate for widespread testing as they suffer from prolonged turn-around times (>12 h) and mostly rely on high-biosafety-level laboratories and well-trained technicians. Point-of-care (POC) tests have the potential to vastly improve healthcare in several ways, ranging from enabling earlier detection and easier monitoring of disease to reaching remote populations. In recent years, the field of POC diagnostics has improved markedly with the advent of micro- and nanotechnologies. Due to the COVID-19 pandemic, POC technologies have been rapidly innovated to address key limitations faced in existing standard diagnostic methods. This review summarizes and compares the latest available POC immunoassay, nucleic acid-based and clustered regularly interspaced short palindromic repeats- (CRISPR)-mediated tests for SARS-CoV-2 detection that we anticipate aiding healthcare facilities to control virus infection and prevent subsequent spread.
... The pathogenesis of the Zika virus in humans remains to be elucidated, but it is thought to spread next to the lymph nodes and then into systemic circulation. 16 It is not clear if and how other means of transmission can occur, but it appears that the virus can be transferred by mother to foetus, by sexual contact with an infected man, and by blood transfusion. [17][18][19] When humans encroach on the natural habitat of other species, the result is either extinction of the invaded species or commensalism, that is, the invaded species continues to breed in a human-dominated environment. ...
What is known and objective
The sudden and extensive outbreak of coronavirus (SARS‐CoV‐2) has overshadowed another developing viral threat: the Zika flavivirus. Of particular concern is that pregnant women can pass Zika virus to the foetus, and there is a strong implication of an association between Zika virus infection and foetal microcephaly. Currently, there is no vaccine, and there is no cure.
Methods
Published literature and Internet sources were searched for information related to Zika virus, its transmission, its clinical presentation and sequalae, prevention and implications (practice and regulatory) for healthcare providers. The identified English sources were reviewed, assessed and synthesized. Emphasis was placed on providing an overview of the problem, and identification of unmet needs and future directions.
Results and discussion
Zika virus poses a major challenge for healthcare providers, particularly in areas unaccustomed to it, since it is transmitted to humans by the vector Aedes aegypti mosquito. The outbreak impacts every healthcare provider, because every provider is required to report cases of Zika infection to their state or local health agencies––whether the infection is confirmed or merely suspected. Since the virus has become a worldwide crisis, healthcare providers will need to work across national boundaries and medical disciplines in order to educate patients about Zika symptoms and the mosquito vector. Until further information is known, infected patients (male and female) are being advised to avoid conceiving a child.
What is new and Conclusion
Until a vaccine is developed or effective treatment for Zika virus is discovered, healthcare providers must be AVP (aware, vigilant and proactive) in order to lessen the spread and impact of the implicated devastating birth defects (microcephaly) and other neurological disorders (eg Guillain‐Barré Syndrome) of this infection. Unfortunately, many knowledge gaps exist. There is an urgent need for a reliable, inexpensive diagnostic test, an effective treatment and an approved and readily available vaccine.
... The outbreak was characterized by rash, conjunctivitis, and arthralgia and was clinically distinct from previously detected dengue illness. Nearly 80% of ZIKV infections are asymptomatic, while 20% typically present as a mild form of dengue-like disease with low-grade fever, skin rash, muscle, and joint pain, conjunctivitis, vomiting, headache, malaise, prostration, and edema of the hands and feet [6]. ...
Zika virus is a mosquito-borne flavivirus that has emerged recently and affected in many countries. Since its discovery in Uganda in 1947, two major outbreaks were reported from Yap Islands in 2007 and French Polynesia in 2013. In 2015, the first case of ZIKV infection was confirmed from Brazil followed by a report of cases from American and Caribbean countries. In February 2016, the World Health Organization declared ZIKV infection a Public Health Emergency of International Concern. India reported the first Zika case in 2017. Subsequently, 157 laboratory-confirmed cases of ZIKV including 63 pregnant women were reported from Rajasthan, India in 2018. Since 2014, many countries took initiatives to boost their public health system to combat ZIKV. However, there is still scope for the improvement. This review describes ZIKV outbreaks, diagnostic challenges, surveillance and control measures in India and the future perspective to deal with the ZIKV outbreak in India.
... In adults, most infections (~80%) are asymptomatic, with only about 20% of infections developing a self-limiting illness. Symptoms vary in severity, and may include fever, headache, maculopapular rash, arthralgia, myalgia, fatigue, and conjunctivitis [14]. Additionally, ZIKV infection during pregnancy can cross the placenta, where it targets neural stem and progenitor cells in ...
Due to the recent epidemic of Zika virus (ZIKV) infection and resulting sequelae, as well as concerns about both the sexual and vertical transmission of the virus, renewed attention has been paid to the pathogenesis of this unique arbovirus. Numerous small animal models have been used in various ZIKV pathogenicity studies, however, they are often performed using immunodeficient or immunosuppressed animals, which may impact disease progression in a manner not relevant to immunocompetent humans. The use of immunocompetent animal models, such as macaques, is constrained by small sample sizes and the need for specialized equipment/staff. Here we report the establishment of ZIKV infection in an immunocompetent small animal model, the guinea pig, using both subcutaneous and vaginal routes of infection to mimic mosquito-borne and sexual transmission. Guinea pigs developed clinical signs consistent with mostly asymptomatic and mild disease observed in humans. We demonstrate that the route of infection does not significantly alter viral tissue tropism but does impact mucosal shedding mechanics. We also demonstrate persistent infection in sensory and autonomic ganglia, identifying a previously unrecognized niche of viral persistence that could contribute to viral shedding in secretions. We conclude that the guinea pig represents a useful and relevant model for ZIKV pathogenesis.
... Although ZIKV is primarily spread through the bite of an infected Aedes species mosquito, cases of sexual, blood-borne and maternal-fetal transmission have been reported [4,5]. Until recently ZIKV was linked to an endemic, self-limiting, mild symptomatic disease characterized by low-grade fever and rash [6]. Importantly, in the recent outbreaks, ZIKV infection is now known to be associated with microcephaly and other neurodevelopmental birth defects in newborns, through its ability to infect human neural progenitor cells, and Guillain-Barr e syndrome in adults, making ZIKV an emerging global public health issue [7À12]. ...
Background:
Zika virus (ZIKV) infection can cause severe birth defects in newborns with no effective currently available treatment. Adoptive transfer of virus-specific T cells has proven to be safe and effective for the prevention or treatment of many viral infections, and could represent a novel treatment approach for patients with ZIKV infection. However, extending this strategy to the ZIKV setting has been hampered by limited data on immunogenic T-cell antigens within ZIKV. Hence, we have generated ZIKV-specific T cells and characterized the cellular immune responses against ZIKV antigens.
Methods:
T-cell products were generated from peripheral blood of ZIKV-exposed donors, ZIKV-naive adult donors and umbilical cord blood by stimulation with pentadecamer (15mer) overlapping peptide libraries spanning four ZIKV polyproteins (C, M, E and NS1) using a Good Manufacturing Practice-compliant protocol.
Results:
We successfully generated T cells targeting ZIKV antigens with clinically relevant numbers. The ex vivo-expanded T cells comprised both CD4+ and CD8+ T cells that were able to produce Th1-polarized effector cytokines and kill ZIKV-infected HLA-matched monocytes, confirming functionality of this unique T-cell product as a potential "off-the-shelf" therapeutic. Epitope mapping using peptide arrays identified several novel HLA class I and class II-restricted epitopes within NS1 antigen, which is essential for viral replication and immune evasion.
Discussion:
Our findings demonstrate that it is feasible to generate potent ZIKV-specific T cells from a variety of cell sources including virus naïve donors for future clinical use in an "off-the-shelf" setting.
... Since its isolation, ZIKV has infected people in Africa, Asia, Pacific Islands, and more recently in Brazil, where large-scale spreading occurred. Zika symptoms are usually mild, characterized by low-grade fever, pruritic maculopapular rash, myalgia, arthralgia, conjunctivitis, and headache (2). Hospitalization due to severe clinical manifestation is uncommon, but the increasing number of cases of Guillain-Barré syndrome and congenital Zika virus syndrome occurring concomitantly to Zika outbreaks has created global concern around this disease (3). ...
Clinical manifestations of Zika, dengue, and chikungunya virus infections are very similar, making it difficult to reach a diagnosis
based only on clinical grounds. In addition, there is an intense cross-reactivity between antibodies directed to Zika virus and
other flaviviruses, and an accurate Zika diagnosis is best achieved by real-time RT-PCR. However, some real-time RT-PCR
show better performance than others. To reach the best possible Zika diagnosis, the analytic sensitivity of some probe-based
real-time RT-PCR amplifying Zika virus RNA was evaluated in spiked and clinical samples. We evaluated primers and probes to
detect Zika virus, which had been published before, and tested sensitivity using serum spiked and patient samples by real-time
RT-PCR. When tested against spiked samples, the previously described primers showed different sensitivity, with very similar
results when samples from patients (serum and urine) were analyzed. Real-time RT-PCR designed to amplify Zika virus NS1
showed the best analytical sensitivity for all samples.
... who.int/emergencies/zika-virus/en/). In Brazil alone, 1.3 million persons had been infected (Shuaib et al., 2016), prompting the WHO to declare ZIKV a public health emergency of international concern. Currently, there are no specific treatments or vaccines against ZIKV making development of effective preventive measures an urgent public health need (Barrows et al., 2016;Paixão et al., 2016). ...
Ebola (EBOV) and Zika viruses (ZIKV) are responsible for recent global health threats. As no preventive vaccines or antiviral drugs against these two re-emerging pathogens are available, we evaluated whether the molecular tweezer CLR01 may inhibit EBOV and ZIKV infection. This small molecule previously has been shown to inactivate HIV-1 and herpes viruses through a selective interaction with lipid-raft-rich regions in the viral envelope, which results in membrane disruption and loss of infectivity. We found that CLR01 indeed blocked infection of EBOV and ZIKV in a dose-dependent manner. The tweezer inhibited infection of epidemic ZIKV strains in cells derived from the anogenital tract and the central nervous system, and remained antivirally active in the presence of semen, saliva, urine and cerebrospinal fluid. Our findings show that CLR01 is a broad-spectrum inhibitor of enveloped viruses with prospects as a preventative microbicide or antiviral agent.
La palabra “virus” significa veneno; es el nombre que se le daba a ciertas sustancias que tenían poder patógeno a fines del siglo XVIII. Fue hasta el advenimiento del microscopio electrónico en 1931, creado por Ernst Ruska, que se pudo definir que estas sustancias o entidades correspondían a elementos particulados denominados virus.
Los virus están constituidos por macromoléculas que les confieren propiedades biológicas y fisicoquímicas como: a) ácido nucleico DNA o RNA, b) proteínas, c) lípidos, y d) hidratos de carbono.
Estos componentes organizados crean una estructura conocida como nucleocápside, que le confiere propiedades de estabilidad termodinámica y de almacenar un máximo de masa en el menor volumen.
El genoma viral está constituido por DNA o RNA, este le confiere la información genética, el análisis y secuenciación de los ácidos nucleicos virales permiten conocer la naturaleza de las proteínas de un virus.
En algunos virus es posible conocer la secuencia nucleotídica completa y en otros, la naturaleza de ciertos genes.
The study of communicable diseases, also known as infectious diseases, is a critical
branch of medicine concerned with the spread, prevention, diagnosis, and treatment
of illnesses caused by pathogenic agents. This textbook is designed to provide a
comprehensive understanding of this vast field for students and healthcare
professionals alike.
Throughout this book, we delve into the fundamentals of infectious diseases,
exploring the different types of pathogens, transmission routes, and the human
immune response. We then explore specific diseases in detail, covering their
epidemiology, pathogenesis, clinical presentation, diagnosis, treatment, and
preventive measures.
This book emphasizes the public health aspects of communicable diseases,
recognizing their significant impact on global health. We discuss disease
surveillance, outbreak investigation, and control strategies employed to mitigate the
spread of infections.
By equipping readers with a thorough understanding of communicable diseases, this
book empowers them to participate effectively in patient care, public health
initiatives, and the ongoing fight against infectious diseases.
Key Features:
Covers a wide range of infectious diseases, from common illnesses to
emerging threats.
Presents information in a clear, concise, and easy-to-understand manner.
Provides comprehensive coverage of epidemiology, pathogenesis, clinical
presentation, diagnosis, treatment, and prevention.
Emphasizes the public health aspects of communicable diseases.
Includes illustrations, figures, and tables to enhance learning.
We believe this textbook will be a valuable resource for students, healthcare
professionals, and anyone interested in learning more about communicable
diseases.
This study presents a comprehensive mathematical model to analyze the dynamics of co‐infection between dengue and malaria using delay differential equations. The model investigates the transmission dynamics of both diseases, focusing on the stability of equilibrium points and the basic reproductive ratio, which measures the number of secondary infections caused by a single infected individual. A time‐delay component is incorporated to account for the incubation periods, enhancing the model's realism. The study performs a detailed sensitivity analysis and global stability assessments, providing insights into the control and management of diseases. Numerical simulations are conducted to illustrate the effect of various transmission parameters on disease spread. This research highlights the importance of mathematical modeling in understanding co‐infection dynamics and provides critical insights for public health interventions, particularly in regions where both diseases are endemic. The results emphasize the role of controlling transmission rates and the use of vector management strategies in mitigating disease outbreaks.
This research aims to synthesize computational approaches in diagnosing, monitoring, controlling, and developing treatments and vaccines against the Zika virus (ZIKV). Specific objectives are identifying computational approaches to diagnose ZIKV, monitoring and controlling ZIKV, and developing medicines and vaccines against ZIKV. The research questions guiding this investigation are as follows: RQ1: What computational approaches are used to diagnose ZIKV? RQ2: What computational approaches are used to monitor and control ZIKV? RQ3: What computational approaches are used to develop drugs and vaccines against ZIKV? Therefore, the work analyzes current methodologies, their applications, and challenges to guide future research and improve strategies against ZIKV. Furthermore, it addresses the general aspects of Congenital Zika Syndrome, such as pathogenesis, clinical manifestations, types of transmission, factors favorable to incidence, and complications. The study was based on reading 96 articles from primary IT databases, such as ACM, Digital Library, IEEE Xplore, and Science Direct, as well as health databases, such as Pubmed LILACS and SciELO.
In this paper, a deterministic mathematical model for Dengue Fever (DF) and Zika virus (ZIKV) co-infection transmission dynamics is formulated and analyzed. Two sub-models, namely ZIKV-only and DF-only sub-models, are considered first of all. Rigorous
qualitative analysis of the sub-models reveals
that each of the diseases undergoes the phenomenon
of backward bifurcation when the associated reproduction
number of both ZIKV-only and DF-only submodels
(denoted by R+0z and R0d respectively) is less
than unity. It is shown, using the centre manifold theory
that the full ZIKV-DF co-infection model undergoes a
backward bifurcation phenomenon. In addition, simulation
of the full ZIKV-DF model shows the clear picturization
of disease transmission and also we provide
the solution of model numerically in detail.
Estratégias de vigilância, prevenção e controle dos acidentes ofídicos, escorpiônicos, araneídicos e por lagartas
Guia de Vigilância em Saúde, 5ª ed.: Vigilância da Síndrome Congênita Associada à Infecção pelo Vírus Zika
A filariose linfática, doença parasitaria crônica, e uma das maiores causas mundiais de incapacidades permanentes ou de longo prazo. Acomete, principalmente, os membros inferiores e o trato urogenital, sendo as suas principais apresentações clinicas o linfedema e a hidrocele. É também conhecida como bancroftose, filaríase de Bancrofti, e elefantíase em uma das manifestações crônicas. Causada por vermes nematoides das especies Wuchereria bancrofti, Brugia malayi e Brugia timori. Nas Américas e na África, apenas a espécie W. bancrofti causa a filariose linfatica. Os vermes adultos medem em torno de 4 cm (machos) a até 10 cm (fêmeas) e vivem nos vasos linfáticos dos indivíduos infectados. O único reservatório do parasito e o ser humano que apresenta microfilárias no sangue. Pacientes com formas crônicas avançadas da doença, incluindo elefantíase, raramente apresentam microfilaremia. Desse modo, na maioria das formas crônicas, os indivíduos são amicrofilaremicos, portanto não transmitem o parasito filarial. No Brasil, mosquitos da espécie Culex quinquefasciatus, também conhecidos como pernilongo ou muriçoca, são os responsáveis pela transmissão da W. bancrofti. A transmissão ocorre unicamente pela picada da femea do mosquito vetor com larvas infectantes do parasito. No Brasil, as microfilarias apresentam periodicidade noturna no sangue periférico, com pico de microfilaremia ocorrendo entre 23h e 1h. Durante o dia, as microfilárias localizam-se nos capilares profundos, principalmente nos pulmões e, durante a noite, aparecem no sangue periférico, com maior concentração em torno da meia-noite.
Chapter 8: Chagas Disease - In: Brasil. Ministério da Saúde. Secretaria de Vigilância em Saúde. Departamento de Articulação Estratégica de Vigilância em Saúde. Guia de Vigilância em Saúde. 5. ed. – Brasília : Ministério da Saúde, 2021. 1.126 p.
As infecções virais são causas conhecidas de manifestações reumatológicas, geralmente como diagnóstico diferencial de poliartrites agudas. Neste artigo, abordaremos os aspectos clínicos, diagnósticos e de tratamento de algumas viroses comuns na prática clínica, que devem ser reconhecidas pelo reumatologista, tanto pelas manifestações articulares quanto autoimunes. Unitermos: Arbovírus. Parvovírus B19. Herpes-vírus. Artrite. Autoimunidade.
Zika virus (ZIKV) was identified in 1947 in the Zika forest of Uganda and it has emerged recently as a global health threat, with recurring outbreaks and its associations with congenital microcephaly through maternal fetal transmission and Guillain-Barré syndrome. Currently, there are no United States (US) Food and Drug Administration (FDA)-approved vaccines or antivirals to treat ZIKV infections, which underscores an urgent medical need for the development of disease intervention strategies to treat ZIKV infection and associated disease. Drug repurposing offers various advantages over developing an entirely new drug by significantly reducing the timeline and resources required to advance a candidate antiviral into the clinic. Screening the ReFRAME library, we identified ten compounds with antiviral activity against the prototypic mammarenavirus lymphocytic choriomeningitis virus (LCMV). Moreover, we showed the ability of these ten compounds to inhibit influenza A and B virus infections, supporting their broad-spectrum antiviral activity. In this study, we further evaluated the broad-spectrum antiviral activity of the ten identified compounds by testing their activity against ZIKV. Among the ten compounds, Azaribine (SI-MTT = 146.29), AVN-944 (SI-MTT = 278.16), and Brequinar (SI-MTT = 157.42) showed potent anti-ZIKV activity in post-treatment therapeutic conditions. We also observed potent anti-ZIKV activity for Mycophenolate mofetil (SI-MTT = 20.51), Mycophenolic acid (SI-MTT = 36.33), and AVN-944 (SI-MTT = 24.51) in pre-treatment prophylactic conditions and potent co-treatment inhibitory activity for Obatoclax (SI-MTT = 60.58), Azaribine (SI-MTT = 91.51), and Mycophenolate mofetil (SI-MTT = 73.26) in co-treatment conditions. Importantly, the inhibitory effect of these compounds was strain independent, as they similarly inhibited ZIKV strains from both African and Asian/American lineages. Our results support the broad-spectrum antiviral activity of these ten compounds and suggest their use for the development of antiviral treatment options of ZIKV infection.
In this paper, we formulate and analyse a nonlinear optimal control problem for a Zika virus (ZIKV) infection model with sexual transmission route. An existing deterministic 11-dimensional autonomous system of differential equations is extended to include five time-dependent control functions, namely personal protection, condom use, vaccination, treatment and spraying of insecticide. The necessary conditions for the existence of optimal control quintuple are shown, and we determine the control strategies to minimize the spread dynamics of the ZIKV in the population at the minimum cost of control implementation. The derived optimality system is solved numerically to demonstrate the effectiveness of the different combinations of the five optimal controls in curtailing the transmission and spread of the disease. More importantly, we conduct a cost-effectiveness analysis on the combinations of at least four optimal controls to ascertain the most cost-effective strategy that can be used to hamper the ZIKV spread in the population.
An ethanol extract of the powdered twigs of Podocarpus imbricatus afforded 14 new diterpenoids (1-14), which all share an aromatized C ring. These isolates belong to five diterpenoid types that include abietanes (1-3), semperviranes (4-9), totaranes (10-12), a C-17 norabietane (13), and an icetexane (14). Their structures were assigned mainly by analysis of the spectroscopic data, and the absolute configuration of 1 was determined by X-ray crystallography. A biosynthetic pathway for five of the biogenetically related types of diterpenoids was proposed. Compound 7 showed moderate inhibitory activity against Zika virus with an IC50 value of 2.5 μM.
Infection is defined as invasion and colonization processes of pathogenic or harmful microorganisms on host cells. A diverse array of microorganisms such as bacteria, virus, fungi, and protozoa attack or infect host cell. They deploy enormous strategies to target or manipulate the host cell or to escape from host immunity. Virulence factors have been secreted as a either cell associated or secreted out of cells upon infection. Infection also depends on health of host cells. Pathogens secrete different types of toxins or enzymes or some molecules to destroy the immunity of the host cells. These are encoded by either chromosome or plasmid of host cells. Even drug resistant property is one of the tactics to destroy the antibiotics. Sometimes they modify themselves or mimic like host molecules upon infection and hence immune cells do not identify them. Nowadays these peculiar behaviors of microbial pathogen draw attention to many scientists worldwide. They not only affect humans, but they also infect other organisms that are economically important for human welfare. Some deadly diseases such as swine flu or dengue or other fatal diseases are really concern for human society. Every year these deadly diseases affect more than half of the people have been infected by these deadly diseases. In this section, we will discuss and shed the light on human pathogens and their disease characteristic. We will even discuss the virulence factors that aid the pathogen to progress the disease.
https://research-repository.griffith.edu.au/handle/10072/382736
In 2007 the Indonesian government cited the United Nations’ Convention on Biological Diversity (CBD) when it claimed sovereignty over influenza viruses isolated from within its territory, denying the World Health Organization (WHO) access to physical samples of H5N1 influenza virus. In response, WHO Member States adopted the Pandemic Influenza Preparedness Framework (PIP Framework) for the sharing of influenza viruses with human pandemic potential. This ended the political stalemate between Indonesia and the WHO, but the international community never addressed the broader legal issue at the core of Indonesia’s claim: do countries have sovereign authority over viruses isolated from within their territories? Answering this question is the starting point of this thesis and is crucial to creating legal certainty for international virus sharing and defending global health security. Genetic resources were largely treated as global public goods under international law until the entry into force of the CBD in 1993. This binding and widely-adopted convention situates genetic resources within the sovereign domain of the Nation State, allowing national governments to regulate access to genetic resources pursuant to their own environmental policies. The domestic laws and policies implemented in the wake of the CBD have created a diverse and complicated regime for accessing genetic resources and sharing benefits associated with their utilisation, referred to as ‘access and benefit-sharing’ (ABS). Until the present research, it has not been clear how these rules apply to viruses outside the narrow remit of pandemic influenza viruses under the PIP Framework. Virus samples are essential for ecological, agricultural and medical research and are vital inputs for the production of vaccines and antivirals. Most viruses are still accessed freely from the environment and shared informally between networks of scientific colleagues without regard to the domestic ABS policies of originating Nation States. This is starting to change as States begin to restrict access to virus samples to exchange them for monetary or non-monetary benefits. This trend is likely to impact scientific research and the development of novel biotechnologies, but it has the most disturbing consequences in the field of public health, where international negotiations over access to pathogenic virus samples can delay outbreak response efforts. This research examines the legalities of claiming sovereignty over viruses under international law and represents the first systematic effort to situate viruses within the international ABS regime. This research aims to: (1) clarify the status of viruses under international ABS law, (2) examine the facets of the international ABS regime that will shape future virus sharing practices, and (3) determine the impact of virus ABS on virological research. It draws together the key themes of law, scientific research and viruses. The legal question originally posed by Indonesia in 2007 and restated here as the first aim of this research is addressed by means of a textual analysis of the CBD and its Nagoya Protocol. Chapter 2 (published in the European Intellectual Property Review) demonstrates that all viruses are unequivocally ‘genetic resources’ within the remit of these international instruments. This finding clarifies the previously ambiguous status of all viruses as sovereign genetic resources under international law and forms the theoretical basis for the preponderance of this research. In effect, influenza viruses with human pandemic potential are regulated by the PIP Framework and all other viruses are subject to regulation under the CBD and Nagoya Protocol. Four chapters of this thesis address the second aim of this research, examining the facets of the current international ABS regime that will shape future virus sharing arrangements. Chapter 3 (published in the Journal of Law and Medicine) analyses temporality and the conceivable extension of sovereign rights to virus isolates collected before the entry into force of the CBD on 29 December 1993, using the ex situ repositories of smallpox virus held by the United States of America and the Russian Federation as a case study. Chapters 4 and 5 (published in the Journal of Law and Medicine and the Journal of World Intellectual Property respectively) are the first published papers to examine how provisions of the CBD and Nagoya Protocol relating to ‘traditional knowledge associated with genetic resources’ apply to viruses. These chapters provide proof of principle that Indigenous Peoples and Local Communities could possess virus-associated traditional knowledge that can be subject to benefit-sharing obligations. Chapter 6 (published in The Milbank Quarterly) critiques the ABS provisions of the PIP Framework as the only international virus-specific de facto ABS instrument. The Nagoya Protocol creates the flexibility to adopt specialised instruments outside of the default bilateral ABS system created by the CBD and Nagoya Protocol. Chapter 6 demonstrates that while the PIP Framework may be considered a multilateral ABS agreement, it secures just the access side of the ABS ‘grand bargain’ enshrined by the CBD. Chapter 6 cautions against the current proposals to expand the scope of the PIP Framework to include other pathogens. Chapter 7 (published in the Journal of Science Policy and Governance) addresses the third aim of this research by examining how ABS measures have impacted scientific research in the biological disciplines. It shows how domestic legislative, administrative and policy measures implementing the CBD and Nagoya Protocol create legal barriers to accessing genetic resources for biological research and can limit scientific innovation. It demonstrates that ABS policies will have a cooling effect on biotechnological research utilising viral genetic resources if countries start to impose similar legal barriers to accessing virus samples. Chapter 8 concludes that the international ABS regime already fetters virus sharing with unforeseen adverse impacts on global health security. Scientists require access to virus samples for research and development, and timely access to viruses that can cause diseases in humans, plants and animals is critical. As countries start to exercise their sovereign authority over viruses and restrict access to virus samples in order to influence benefit-sharing negotiations, it is ever more important that the international community comprehends the form and structure of virus ABS. This thesis fills the literature void as the first published research to explore the legal and practical issues of accessing virus samples and sharing the benefits associated with their use under the CBD and Nagoya Protocol. Given the deficiencies of the current ABS regime, this research forms the basis for an international debate about alternative models for regulating access to viruses and sharing the associated benefits. During public health emergencies, legal ambiguities around who can control access to viruses and at what price can delay the public health response and ultimately cost lives.
Recent data in a nonhuman primate model showed that infants postnatally infected with Zika virus (ZIKV) were acutely susceptible to high viremia and neurological damage, suggesting the window of vulnerability extends beyond gestation. In this pilot study, we addressed the susceptibility of two infant rhesus macaques born healthy to dams infected with Zika virus during pregnancy. Passively acquired neutralizing antibody titers dropped below detection limits between 2 and 3 months of age, while binding antibodies remained detectable until viral infection at 5 months. Acute serum viremia was comparatively lower than adults infected with the same Brazilian isolate of ZIKV (n = 11 pregnant females, 4 males, and 4 non-pregnant females). Virus was never detected in cerebrospinal fluid nor in neural tissues at necropsy two weeks after infection. However, viral RNA was detected in lymph nodes, confirming some tissue dissemination. Though protection was not absolute and our study lacks an important comparison with postnatally infected infants born to naïve dams, our data suggest infants born healthy to infected mothers may harbor a modest but important level of protection from postnatally acquired ZIKV for several months after birth, an encouraging result given the potentially severe infection outcomes of this population.
Zika virus (ZIKV) has become a public health concern worldwide due to its association with congenital abnormalities and neurological diseases. To date, no effective vaccines or antiviral drugs have been approved for the treatment of ZIKV infection, and new inexpensive therapeutic options are urgently needed. In this study, we have used an in vitro plaque assay to assess an antiviral activity of the second generation of anti-ZIKV compounds, based on 1,3-disubstituted (thio)urea scaffold. Several compounds in the library were found to possess excellent activity against Zika virus with IC50 values <200 pM. The most active analog, A5 exhibited an exceptional IC50 = 85.1 ± 1.7 pM. Further analysis delineated structural requirements necessary for potent antiviral effects of this class of compounds. Collectively, our findings suggest that 1,3-disubstituted (thio)urea derivatives are excellent preclinical candidates for the development of anti-ZIKV therapeutics.
Chlamydia psittaci infection among humans (psittacosis) and pet birds (avian chlamydiosis), also known as parrot disease, parrot fever, and ornithosis, is a zoonotic bacterial disease. Humans most often become infected by inhaling the organism when urine, respiratory secretions, or dried feces of infected birds are dispersed in the air as very fine droplets or dust particles. C. psittaci infection of humans can cause influenza-like symptoms, such as fever of abrupt onset, pronounced headache, and dry cough, and can lead to severe pneumonia and non-respiratory health problems. Infection can also be asymptomatic. There is no vaccine for this infection. The disease is treatable with a tetracycline antibiotic, usually doxycycline, or a second-line therapy such as erythromycin or azithromycin. With appropriate treatment, the infection is rarely fatal. This report describes a case of severe, community-acquired pneumonia possibly due to C. psittaci in a resident of Colorado and examines significant clinical and epidemiological characteristics of psittacosis that affect confirming the diagnosis and managing the risks of exposure to psittacine (parrot-type) birds.
Chikungunya virus (CHIKV) and Zika virus (ZIKV) are 2 reemerging arboviruses that have been the focus of public health institutions worldwide, since the last decades and following a spate of outbreaks in tropical and subtropical areas. The disease caused by both viruses manifests itself first as an acute stage of severe inflammation into the infected tissues, which later progresses to arthritis and chronic polyarthralgia in the case of CHIKV or congenital microcephaly and neurological disorders such as Guillain-Barré syndrome in the case of ZIKV. This review aims to summarize on current knowledge of the role of different pattern recognition receptors that leads to an elevated production and secretion of antiviral response (interferon) and severe inflammation in response to CHIKV and ZIKV infection.
Zika virus (ZIKV) is an arbovirus that caused widespread panic beginning in 2015 in northeastern Brazil due to the threatening link between infection and fetal abnormalities such as microcephaly, spontaneous abortions, and stillbirths. Since the epidemic began, the virus has been further investigated, unveiling that the long-term dangers of ZIKV infection go beyond fetal neurological impairment. Characterization of the active infection has proven difficult as only 20% of infected individuals are symptomatic. Additionally, ZIKV is often misdiagnosed due to serological cross-reactivity with similar flaviviruses such as dengue, yellow fever, and West Nile. To date, there is no approved vaccine or therapy against ZIKV, highlighting the urgent need to accurately identify active infection to help minimize the spread of the virus. Herein, we describe a highly specific and sensitive enzyme-linked immunosorbent assay to detect early active ZIKV using neutralizing human monoclonal antibodies isolated from infected patients in Brazil that do not cross-react with dengue viruses 1-4 and bind directly to a ZIKV immunodominant epitope. The calculated limits of detection of active ZIKV fall within the physiological ranges of the virus in human bodily fluids. This selective immunoassay creates the platform required for future translation toward a point-of-care assay for ZIKV, a necessity to diagnose active ZIKV in the remote regions of which it thrives.
Zika virus (ZIKV), a mosquito-borne flavivirus, is a global health concern because of its association with severe neurological disorders. Currently, there are no antiviral therapies that have been specifically approved to treat ZIKV, and there is an urgent need to develop effective anti-ZIKV agents. Here, we report anti-ZIKV activity of 16 synthetic carbohydrate receptors (SCRs) that inhibit ZIKV infection in Vero and HeLa cells. Using a ZIKV Reporter Virus Particle-based infection assay, our data demonstrates these SCRs are highly potent with IC50’s as low as 0.16 µM and negligible toxicity at several fold higher concentrations. Time-of-addition studies showed that these SCRs inhibit the early stages of the virus infection, which is consistent with the proposed mode of action, where the SCRs likely inhibit binding between the virus and cell-surface glycans, thereby preventing viral entry into the cells, and, as such, this study demonstrates a potential new strategy against ZIKV.
Background:
The current triple epidemic caused by dengue, zika and chikungunya constitutes a serious health problem in Brazil. The aim of this study was to investigate acute samples (up to the 7 days of symptoms) from patients presenting acute fever syndrome suspected as arboviral infection and characterize the clinical and laboratorial profile during the co-circulation of dengue, zika and chikungunya in Campo Grande, Mato Grosso do Sul (MS), midwest region of Brazil.
Methods:
All suspected cases (n=134) were tested by using serological and molecular diagnostic tests including DENV, ZIKV and CHIKV RT-PCR, Dengue nonstructural protein 1 (NS1) antigen capture ELISA, anti- DENV IgM ELISA and anti-CHIKV IgM ELISA. In addition, clinical, hematological and biochemical parameters of infected patients were analyzed.
Results:
It was observed that 79.1% of the blood samples were confirmed for ZIKV and/or DENV infection Of those, 38.0% patients were DENV monoinfected, 26.8% were ZIKV monoinfected and 13.4% were DENV/ZIKV co-infected. Seven patients presented Chikungunya IgM antibodies indicating a previous CHIKV infection. Common symptoms included fever, rash, arthralgia, myalgia, prostration, headache and conjunctivitis. Statistical analysis showed that pruritus and edema were associated with ZIKV infection while prostration and vomiting were more associated with dengue. Additionally, total protein and ALT levels were significantly different in DENV patients compared to ZIKV ones. Some DENV infected patients as well as co-infected needed hospitalization and venous hydration. Otherwise, most ZIKV infected patients presented mild clinical course. Among the pregnant women studied (n=11), three were ZIKV monoinfected while four were DENV monoinfected and two were DENV-1/ZIKV coinfected. In general, normal birth outcomes were observed except for the death due to respiratory insufficiency of one baby born to a mother coinfected with DENV-1/ZIKV.
Conclusions:
Herein, we provide evidence of the co-circulation of DENV, ZIKV and CHIKV infections in the Campo Grande, MS, Brazil, with a high frequency of DENV-1/ZIKV coinfection. Laboratorial diagnosis poses a challenge where those arboviruses are endemic and differential diagnosis proved to imperative for cases characterization. The knowledge about disease severity during arbovirus coinfections is still scarce and there are several issues emphasizing the importance of adequate management of patients at risk areas.
On March 26, 2015, serum samples were obtained from 24 patients (Table) at Santa Helena Hospital in Camaçari who were given a presumptive diagnosis of an acute viral illness by emergency department physicians. These patients were given treatment for a dengue-like illness, and blood samples were obtained for complete blood counts and serologic testing by using an ELISA specific for IgG and IgM against DENV.
Serum samples were analyzed at the Federal University of Bahia by reverse transcription PCR (RT-PCR) to detect DENV, CHIKV, WNV, Mayaro virus, and ZIKV. In brief, serum samples were subjected to RNA extraction by using the QIAamp Viral RNA Mini Kit (QIAGEN, Hilden, Germany). RNA was reverse transcribed by using the SuperScript II Reverse Transcription Kit (Invitrogen, Carlsbad, CA, USA) and subjected to PCRs specific for DENV (5) CHIKV (6), WNV (7) and Mayaro virus (8). A positive RT-PCR for a partial region of the envelope gene with primers ZIKVENF and ZIKVENVR (positions 1538–1558 and 1902–1883, respectively) (9) was considered indicative of ZIKV infection. PCR products (362 bp) were sequenced at the ACTGene Analises Moleculares, Alvorada, Rio Grande do Sul (Porto Allegre, Brazil), and sequences were deposited in GenBank under accession nos. KR816333–KR816336.
All patients were negative by RT-PCR for DENV, Mayaro virus, and WNV. Samples from 7 (29.2%) patients were positive by RT-PCR for ZIKV (369-bp fragment) and from 3 (12.5%) patients for CHIKV (305-bp fragment). There was no simultaneous detection of ZIKV and CHIKV. Most (85.7%) patients positive for ZIKV were women; they had a median age of 28 years and no history of international travel. Patients positive for ZIKV sought medical care after a 4-day (range 1–5 days) history of rash, myalgias, arthralgias, or fever. Three patients had IgG against DENV, which is consistent with a previous DENV infection, and none of the 7 ZIKV-positive patients had a positive response for DENV.
Mean laboratory findings for patients with acute ZIKV infection were a leukocyte count of 3,750 cells/mm3 (range 2,790 cells/mm3–6,150 cells/mm3) and a platelet count of 180,000 platelets/mm3 (range 151,000 platelets/mm3–274,000 platelets/mm3). The mean C-reactive protein level was 16.3 mg/L (range 0.9 mg/L–19.7 mg/L). Sign and symptom duration was 1–5 days, and most patients had a maculopapular rash, myalgias, fever, and headache. Arthralgia was seen less frequently.
ZIKV infections were assessed by sequencing partial ZIKV envelope gene regions of isolates. Phylogenetic analysis rooted with Spondwei virus showed that ZIKV sequences obtained belonged to the Asian lineage and showed 99% identity with a sequence from a ZIKV isolate from French Polynesia (KJ776791) (10).
We report ZIKV infection in Brazil in association with an ongoing outbreak of an acute maculoexantematic illness. Although the patient population samples were not randomly selected, 42% (10/24) of the patients were positive for ZIKV (n = 7) or CHIKV (n = 3) and had maculopapular rash, fever, myalgias and headache. After detection of ZIKV in Bahia, many cases have been identified in other states (http://www.promedmail.org, archive no. 20152015602.343.1158).
Cases of infection with DENV, CHIKV, and ZIKV in Brazil and elsewhere will make diagnosis based on clinical and epidemiologic grounds unreliable. These issues show the need for laboratory confirmation of these arboviral infections. More studies are needed to address the effects of these concurrent arboviruses infections in Brazil.
Unlabelled:
Zika virus (ZIKV) is an emerging arbovirus of the Flaviviridae family, which includes dengue, West Nile, yellow fever, and Japanese encephalitis viruses, that causes a mosquito-borne disease transmitted by the Aedes genus, with recent outbreaks in the South Pacific. Here we examine the importance of human skin in the entry of ZIKV and its contribution to the induction of antiviral immune responses. We show that human dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells are permissive to the most recent ZIKV isolate, responsible for the epidemic in French Polynesia. Several entry and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1, permitted ZIKV entry, with a major role for the TAM receptor AXL. The ZIKV permissiveness of human skin fibroblasts was confirmed by the use of a neutralizing antibody and specific RNA silencing. ZIKV induced the transcription of Toll-like receptor 3 (TLR3), RIG-I, and MDA5, as well as several interferon-stimulated genes, including OAS2, ISG15, and MX1, characterized by strongly enhanced beta interferon gene expression. ZIKV was found to be sensitive to the antiviral effects of both type I and type II interferons. Finally, infection of skin fibroblasts resulted in the formation of autophagosomes, whose presence was associated with enhanced viral replication, as shown by the use of Torin 1, a chemical inducer of autophagy, and the specific autophagy inhibitor 3-methyladenine. The results presented herein permit us to gain further insight into the biology of ZIKV and to devise strategies aiming to interfere with the pathology caused by this emerging flavivirus.
Importance:
Zika virus (ZIKV) is an arbovirus belonging to the Flaviviridae family. Vector-mediated transmission of ZIKV is initiated when a blood-feeding female Aedes mosquito injects the virus into the skin of its mammalian host, followed by infection of permissive cells via specific receptors. Indeed, skin immune cells, including dermal fibroblasts, epidermal keratinocytes, and immature dendritic cells, were all found to be permissive to ZIKV infection. The results also show a major role for the phosphatidylserine receptor AXL as a ZIKV entry receptor and for cellular autophagy in enhancing ZIKV replication in permissive cells. ZIKV replication leads to activation of an antiviral innate immune response and the production of type I interferons in infected cells. Taken together, these results provide the first general insights into the interaction between ZIKV and its mammalian host.
In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen. ZIKV transmission by sexual intercourse has been previously suspected. This observation supports the possibility that ZIKV could be transmitted sexually.
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.
A person in Texas, USA, has become infected with the Zika virus after sexual contact with someone who had acquired the infection while travelling abroad, health officials have reported.
The US Centers for Disease Control and Prevention (CDC) confirmed this as the first known case of Zika virus to be locally acquired in the continental United States during the current outbreak.
Almost all cases of Zika virus infection are transmitted by mosquito bites, although cases of sexual transmission have been reported previously.1 2 Dallas County health department officials said that the traveler …
Maternal-fetal transmission of Zika virus has been documented throughout pregnancy (4,7,8). Although Zika virus RNA has been detected in the pathologic specimens of fetal losses (4), it is not known if Zika virus caused the fetal losses. Zika virus infections have been confirmed in infants with microcephaly (4), and in the current outbreak in Brazil, a marked increase in the number of infants born with microcephaly has been reported (9). However, it is not known how many of the microcephaly cases are associated with Zika virus infection. Studies are under way to investigate the association of Zika virus infection and microcephaly, including the role of other contributory factors (e.g., prior or concurrent infection with other organisms, nutrition, and environment). The full spectrum of outcomes that might be associated with Zika virus infections during pregnancy is unknown and requires further investigation.
Zika virus testing of maternal serum includes reverse transcription-polymerase chain reaction (RT-PCR) testing for symptomatic patients with onset of symptoms within the previous week. Immunoglobulin M (IgM) and neutralizing antibody testing should be performed on specimens collected ≥4 days after onset of symptoms. Cross-reaction with related flaviviruses (e.g., dengue or yellow fever) is common with antibody testing, and thus it might be difficult to distinguish Zika virus infection from other flavivirus infections. Consultation with state or local health departments might be necessary to assist with interpretation of results (18). Testing of asymptomatic pregnant women is not recommended in the absence of fetal microcephaly or intracranial calcifications.
The explosive pandemic of Zika virus infection occurring throughout South America, Central America, and the Caribbean (see map) and potentially threatening the United States is the most recent of four unexpected arrivals of important arthropod-borne viral diseases in the Western Hemisphere over the past 20 years. It follows dengue, which entered this hemisphere stealthily over decades and then more aggressively in the 1990s; West Nile virus, which emerged in 1999; and chikungunya, which emerged in 2013. Are the successive migrations of these viruses unrelated, or do they reflect important new patterns of disease emergence? Furthermore, are there secondary health consequences . . .
The Zika virus (ZIKV) is a mosquito-borne flavivirus (Aedes), similar to other arboviruses, first identified in Uganda in 1947. Few human cases were reported until 2007, when a Zika outbreak occurred in Yap, Micronesia, even though ZIKV activity had been reported in Africa and in Asia through virological surveillance and entomological studies. French Polynesia has recorded a large outbreak since October 2013. A great number of cases and some with neurological and autoimmune complications have been reported in a context of concurrent circulation of dengue viruses. The clinical presentation is a "dengue-like syndrome". Until the epidemic in French Polynesia, no severe ZIKV disease had been described so far. The diagnosis is confirmed by viral genome detection by genomic amplification (RT- PCR) and viral isolation. These two large outbreaks occurred in a previously unaffected area in less than a decade. They should raise awareness as to the potential for ZIKV to spread especially since this emergent disease is not well known and that some questions remain on potential reservoirs and transmission modes as well as on clinical presentations and complications. ZIKV has the potential to spread to new areas where the Aedes mosquito vector is present and could be a risk for Southern Europe. Strategies for the prevention and control of ZIKV disease should include the use of insect repellent and mosquito vector eradication.
• 1.(1) A description is given of the adaptation to mice of two strains of Zika virus. Zika is the name of a forest area near Entebbe, Uganda, where both strains of virus were isolated. One of the strains was isolated from a pyrexial rhesus monkey which was being employed as a yellow fever sentinel and the other was obtained from a batch of A. africanus.
• 2.(2) The signs of infection in mice are described. While mice of all ages tested are susceptible to intracerebral inoculations with Zika mouse brain virus, mice of 2 weeks of age and over can rarely be infected by the intraperitoneal route. Mice younger than 2 weeks are highly susceptible to intraperitoneal inoculation of the virus.
• 3.(3) Zika virus is highly neurotropic in mice and no virus has been recovered from tissues other than the brains of infected mice.
• 4.(4) Cotton-rats, guineapigs and rabbits show no clinical signs of infection after intracerebral inoculation of late passage mouse brain virus.
• 5.(5) Monkeys develop an inapparent infection after subcutaneous inoculation with mouse brain virus. After intracerebral inoculation one of five monkeys showed a mild pyrexia, the others showed no signs of infection. Viraemia during the first week after inoculation has been found in all monkeys tested and antibody has been demonstrated by the 14th day after inoculation.
• 6.(6) Of 99 human sera tested, 6 (6.1 per cent.)-have neutralized more than 100 LD50 of virus. Antibody has also been found in the serum of one of 15 wild monkeys tested.
• 7.(7) The size of Zika virus is estimated to eb in the region of 30 to 45 mμ in diameter. The virus may be preserved up to 6 months in 50 per cent. glycerol and up to 30 months after drying. It is susceptible to anaesthetic ether and the thermal death point is 58°C. for 30 minutes.
• 8.(8) Neuronal degeneration, cellular infiltration and areas of softening are present in infected mouse brains. Cowdry type A inclusion bodies have been found, particularly in the brains of young mice showing extensive lesions.