The Emergence of Zika Virus as a Global Health Security Threat: A Review and a Consensus Statement of the INDUSEM Joint working Group (JWG).
TL;DR: Given the rapid geographic spread of ZIKV in recent years, a coordinated local, regional, and global effort is needed to generate sufficient resources and political traction to effectively halt and contain further expansion of the current outbreak.
Abstract: The Zika virus (ZIKV), first discovered in 1947, has emerged as a global public health threat over the last decade, with the accelerated geographic spread of the virus noted during the last 5 years. The World Health Organization (WHO) predicts that millions of cases of ZIKV are likely to occur in the Americas during the next 12 months. These projections, in conjunction with suspected Zika-associated increase in newborn microcephaly cases, prompted WHO to declare public health emergency of international concern. ZIKV-associated illness is characterized by an incubation period of 3-12 days. Most patients remain asymptomatic (i.e., ~80%) after contracting the virus. When symptomatic, clinical presentation is usually mild and consists of a self-limiting febrile illness that lasts approximately 2-7 days. Among common clinical manifestations are fever, arthralgia, conjunctivitis, myalgia, headache, and maculopapular rash. Hospitalization and complication rates are low, with fatalities being extremely rare. Newborn microcephaly, the most devastating and insidious complication associated with the ZIKV, has been described in the offspring of women who became infected while pregnant. Much remains to be elucidated about the timing of ZIKV infection in the context of the temporal progression of pregnancy, the corresponding in utero fetal development stage(s), and the risk of microcephaly. Without further knowledge of the pathophysiology involved, the true risk of ZIKV to the unborn remains difficult to quantify and remediate. Accurate, portable, and inexpensive point-of-care testing is required to better identify cases and manage the current and future outbreaks of ZIKV, including optimization of preventive approaches and the identification of more effective risk reduction strategies. In addition, much more work needs to be done to produce an effective vaccine. Given the rapid geographic spread of ZIKV in recent years, a coordinated local, regional, and global effort is needed to generate sufficient resources and political traction to effectively halt and contain further expansion of the current outbreak.
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TL;DR: The speed, sensitivity, and selectivity of this first-of-its-kind graphene-enabled Zika biosensor make it an ideal candidate for development as a medical diagnostic test.
299 citations
Cites background from "The Emergence of Zika Virus as a Gl..."
...Zika is a vector borne viral infection originating in the Zika Forest of Uganda in the mid-20th century (Sikka et al., 2016)....
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TL;DR: The current world‐wide event has now been declared a pandemic by the World Health Organization (WHO) and the associated disease has been named COVID‐19.
Abstract: Over the past 3 months, the world witnessed historic and dramatic developments related to the rapid emergence of a novel coronavirus. Real‐time, detailed global media coverage brought live updates on the infection to every corner of the planet. Social media outlets are abuzz with minute-to-minute alerts, reflections, witness accounts, and personal reactions. We are witnessing stories of human suffering, including overwhelmed health-care systems, limited access to emergency care, vacationing passengers stranded on cruise ships, large-scale evacuations, overnight economic shutdown, and empty streets in China and Italy.[1-3] The imagery is comparable to an epic movie depicting martial law with large populations confined to their homes in the wake of a deadly virus. This time, it is a novel coronavirus, and the associated disease has been named COVID‐19. Moreover, the current world‐wide event has now been declared a pandemic by the World Health Organization (WHO).[4,5]
146 citations
Cites background from "The Emergence of Zika Virus as a Gl..."
...further strengthening the efficacy of the emergency response infrastructure.[41,42] Spatiotemporal analyses of telehealth data, specifically those focusing on calls regarding the complaint of “fever,” have in the past provided a timely and useful picture of the evolution of a national influenza outbreak in the United Kingdom (UK)....
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La Jolla Institute for Allergy and Immunology1, Genentech2, University of Miami3, University of São Paulo4, Oswaldo Cruz Foundation5, Universidade Federal do Estado do Rio de Janeiro6, Vanderbilt University7, Murdoch University8, University of North Carolina at Chapel Hill9, Johns Hopkins University10, University of Vermont11, University of California, Berkeley12, Vanderbilt University Medical Center13, Systems Research Institute14, Universidad Veracruzana15, Vaccine Research Center16, Royal Liverpool University Hospital17, University of Liverpool18, Walton Centre19
TL;DR: The kinetics and viral epitopes targeted by T cells responding to ZIKV and whether preexisting dengue virus (DENV) T cell immunity modulates these responses are investigated and it is found that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent d Dengue attenuated vaccines (TDLAV) recognize ZikV-derived peptides.
Abstract: While progress has been made in characterizing humoral immunity to Zika virus (ZIKV) in humans, little is known regarding the corresponding T cell responses to ZIKV. Here, we investigate the kinetics and viral epitopes targeted by T cells responding to ZIKV and address the critical question of whether preexisting dengue virus (DENV) T cell immunity modulates these responses. We find that memory T cell responses elicited by prior infection with DENV or vaccination with tetravalent dengue attenuated vaccines (TDLAV) recognize ZIKV-derived peptides. This cross-reactivity is explained by the sequence similarity of the two viruses, as the ZIKV peptides recognized by DENV-elicited memory T cells are identical or highly conserved in DENV and ZIKV. DENV exposure prior to ZIKV infection also influences the timing and magnitude of the T cell response. ZIKV-reactive T cells in the acute phase of infection are detected earlier and in greater magnitude in DENV-immune patients. Conversely, the frequency of ZIKV-reactive T cells continues to rise in the convalescent phase in DENV-naive donors but declines in DENV-preexposed donors, compatible with more efficient control of ZIKV replication and/or clearance of ZIKV antigen. The quality of responses is also influenced by previous DENV exposure, and ZIKV-specific CD8 T cells from DENV-preexposed donors selectively upregulated granzyme B and PD1, unlike DENV-naive donors. Finally, we discovered that ZIKV structural proteins (E, prM, and C) are major targets of both the CD4 and CD8 T cell responses, whereas DENV T cell epitopes are found primarily in nonstructural proteins.IMPORTANCE The issue of potential ZIKV and DENV cross-reactivity and how preexisting DENV T cell immunity modulates Zika T cell responses is of great relevance, as the two viruses often cocirculate and Zika virus has been spreading in geographical regions where DENV is endemic or hyperendemic. Our data show that memory T cell responses elicited by prior infection with DENV recognize ZIKV-derived peptides and that DENV exposure prior to ZIKV infection influences the timing, magnitude, and quality of the T cell response. Additionally, we show that ZIKV-specific responses target different proteins than DENV-specific responses, pointing toward important implications for vaccine design against this global threat.
140 citations
TL;DR: The history of the first commercial antibiotics is briefly reviewed, together with data from the US and WHO, showing the decrease in death due to infectious diseases over the 20th century, from just under half of all deaths, to less than 10%.
124 citations
TL;DR: Research is urgently needed to identify Zika virus epitopes that do not cross-react with other flavivirus antigens, and development of accurate antibody tests for the diagnosis of recent Zika infection.
Abstract: Context.—The rapid and accurate diagnosis of Zika virus infection is an international priority. Objective.—To review current recommendations, methods, limitations, and priorities for Zika virus testing. Data Sources.—Sources include published literature, public health recommendations, laboratory procedures, and testing experience. Conclusions.—Until recently, the laboratory diagnosis of Zika infection was confined to public health or research laboratories that prepared their own reagents, and test capacity has been limited. Furthermore, Zika cross-reacts serologically with other flaviviruses, such as dengue, West Nile, and yellow fever. Current or past infection, or even vaccination with another flavivirus, will often cause false-positive or uninterpretable Zika serology results. Detection of viral RNA during acute infection using nucleic acid amplification tests provides more specific results, and a number of commercial nucleic acid amplification tests have received emergency use authorization. In additi...
100 citations
References
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TL;DR: This outbreak of Zika virus illness in Micronesia represents transmission of Zikairus outside Africa and Asia and clinicians and public health officials should be aware of the risk of further expansion of Zika viruses transmission.
Abstract: BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.
2,717 citations
"The Emergence of Zika Virus as a Gl..." refers background in this paper
...Symptoms and signs of ZIKV infection usually occur 3-12 days after the mosquito-vector bite and resolve within 2-7 days.[48] Although asymptomatic infection is common, approximately 20% of infected humans with ZIKV become symptomatic with the acute onset of a fever, maculopapular rash, conjunctivitis (and other ophthalmologic manifestations), and arthralgias....
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TL;DR: Cross neutralization tests indicate that Zika virus is not related to yellow fever, Hawaii dengue nor to the FA and GD VII strains of Theiler's mouse encephalomyelitis virus.
Abstract: 1. (1) The isolation of what is believed to be a hitherto unrecorded virus is described. The first isolation was made in April 1947 from the serum of a pyrexial rhesus monkey caged in the canopy of Zika Forest. The second isolation was made from a lot of A. africanus taken in January, 1948, in the same forest. The virus has been called Zika virus after the locality from where the isolations were made. 2. (2) Cross neutralization tests indicate that Zika virus is not related to yellow fever, Hawaii dengue nor to the FA and GD VII strains of Theiler's mouse encephalomyelitis virus. Neutralization tests with Zika virus and the antisera of some other viruses which are neurotropic in mice gave no evidence of any identity of these with Zika virus.
2,338 citations
"The Emergence of Zika Virus as a Gl..." refers background in this paper
...[2,18] The serum was subsequently inoculated into mice, followed by successful isolation of a viral agent (ZIKV) from brains of the inoculated animals.[2,18] Shortly after this discovery, ZIKV was isolated from Aedes africanus mosquitoes inhabiting the Zika forest....
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...fi rst isolated from a rhesus monkey in 1947.[1-3] ZIKV has The Emergence of Zika Virus as a Global Health Security Threat: A Review and a Consensus Statement of the INDUSEM Joint Working Group (JWG)...
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...It was named after the Zika forest near Entebbe, Uganda[2,21] and was fi rst identifi ed in the late 1940s from the serum of a febrile rhesus macaque (known as “Rhesus 766”)....
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...It was named after the Zika forest near Entebbe, Uganda[2,21] and was fi rst identifi ed in the late 1940s from the serum of a febrile rhesus macaque (known as “Rhesus 766”).[2,18] The serum was subsequently inoculated into mice, followed by successful isolation of a viral agent (ZIKV) from brains of the inoculated animals....
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TL;DR: The full coding region nucleic acid sequence and serologic properties of the virus were identified and the virus was identified as Crimean-Congo-Wales coronavirus.
Abstract: Zika virus (ZIKV) is a mosquito-borne flavivirus first isolated in Uganda from a sentinel monkey in 1947. Mosquito and sentinel animal surveillance studies have demonstrated that ZIKV is endemic to Africa and Southeast Asia, yet reported human cases are rare, with <10 cases reported in the literature. In June 2007, an epidemic of fever and rash associated with ZIKV was detected in Yap State, Federated States of Micronesia. We report the genetic and serologic properties of the ZIKV associated with this epidemic.
1,944 citations
TL;DR: The first structure of a flavivirus has been determined by using a combination of cryoelectron microscopy and fitting of the known structure of glycoprotein E into the electron density map, suggesting that flaviviruses employ a fusion mechanism in which the distal beta barrels of domain II of the glycop Protein E are inserted into the cellular membrane.
1,477 citations
TL;DR: Three examples of emerging and resurging diseases of global significance are described: the resurgence of dengue in tropical and subtropical areas of the world, and the spread and establishment of Japanese encephalitis and West Nile viruses in new habitats and environments.
Abstract: Mosquito-borne flaviviruses provide some of the most important examples of emerging and resurging diseases of global significance. Here, we describe three of them: the resurgence of dengue in tropical and subtropical areas of the world, and the spread and establishment of Japanese encephalitis and West Nile viruses in new habitats and environments. These three examples also illustrate the complexity of the various factors that contribute to their emergence, resurgence and spread. Whereas some of these factors are natural, such as bird migration, most are due to human activities, such as changes in land use, water impoundments and transportation, which result in changed epidemiological patterns. The three examples also show the ease with which mosquito-borne viruses can spread to and colonize new areas, and the need for continued international surveillance and improved public health infrastructure to meet future emerging disease threats.
1,265 citations
"The Emergence of Zika Virus as a Gl..." refers background in this paper
...6 Journal of Global Infectious Diseases / Jan-Mar 2016 / Vol-8 / Issue-1 are transmitted by mosquitoes [Figure 2].[41] Other viruses that are classifi ed in the Flaviviridae, such as human hepatitis C virus (member of Hepacivirus genus), do not involve the mosquito vector and are transmitted directly from human to human....
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