DOCSLIB.ORG

Rift Valley Fever Virus Nipah Virus

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Rift Valley Fever Virus Nipah Virus Rift Valley fever virus Nipah virus (henipaviruses) Zoonotic viruses cross inter-species barrier Hana Weingartl Adjunct professor, Medical Microbiology, University of Manitoba Head, Special Pathogens Unit National Centre for Foreign Animal Disease Canadian Food Inspection Agency Canadian Science Centre for Human and Animal Health It is not in virus interest to kill the host /cell Zoonotic viruses often cause diseases with high fatality rate in humans with short clinical phase - survival of a human host is irrelevant Productive infections of multiple species, and successful intra- and inter- (optional) species transmission without a requirement for adaptation in a “new” host Interspecies barriers geographical, ecological (Wallace’s line) - Entry into the host cell: attachment to the host cell = interaction with a specific host cell receptor ability to enter the host cell to deliver the genetic information - Replication within the host cell: interaction with cell factors (molecules) in the nucleus and/or cytoplasm virus needs to gain (partial) control over specific cell functions, such as metabolism and replication to produce progeny host defence mechanisms Reservoir host Amplifying host Enzootic x Epizootic Sporadic x Endemic x Epidemic x Pandemic Dead-end host Goals of (zoonotic) viruses 1. Find/encounter a new host 2. Enter the cell by a pathway that ensures replication 3. Produce mRNA, replicate the genome, generate virus proteins, evade host defences – stage I 4. Assemble progeny virus, leave the cell 5. Evade host defences – stage II, re-infect other cells 6. Transfer to a new host or persist in the environment until 1. (Or stay within the host) Rift Valley fever virus (Phlebovirus, Bunyaviridae) disease in domestic ruminants (sheep, goats, cattle, camels) and humans (transmission from mosquitoes or due to contact to blood and infected tissues) Rift Valley fever first described in 1915, virus isolated in 1930 More then 10% Case/Fatality in humans, no treatment, no vaccine Recognition of RVF outbreak Clinical signs in animals are nonspecific, epizootics usually recognized due to 90% mortality in newborn ruminants (calves, lambs), and abortions in adult animals Innaparently infected animals high viremia - transmitting species accompanied by concurrent outbreak of febrile disease in humans: influenza-like >5% serious; >1% fatal (but could be 10 – 35%) high viremia - transmitting species (amplifying host) Rift Valley fever virus (Phlebovirus, Bunyaviridae) • L segment • Transcriptase (RdRp) • M segment • Glycoprotein (Gn) • Glycoprotein (Gc) • Nonstructural NSm1 = large 78kDa glycoprotein • Nonstructural (NSm2) • S segment • Nucleocapsid (N) • Nonstructural (NSs) Glycoprotein Gn/Gc heterodimers in lipid envelope (lipid composition) Genome (negative and ambisense coding strategy) 6404 Nt 3885 Nt 1690 Nt (Flick and Bouloy, 2005) Consensus terminal nucleotide sequences: 3’ UGUGUUUC- 5’ ACACAAAG- Segment reassortments occur in nature Life Domain Virus is genetically conserved Kingdom Phylum 72 different strains/isolates – L segment – one real time RT-PCR assay Class ONE serotype Order Family Arthropode-borne virus (Arthropoda) infecting mammals (Chordata): Genus ruminants, humans, etc. Species RVF ENZOOTIC CYCLE RVF EPIZOOTIC CYCLE 1. Find/encounter a new host LIVESTOCK EPIDEMIC CULICINE CULICINE MOSQUITOES, MOSQUITOES, BITING FLIES BITING FLIES HUMANS LIVESTOCK LIVESTOCK AEDINE AEDINE AEDINE AEDINE MOSQUITOES MOSQUITOES MOSQUITOES MOSQUITO ES EGGS EGGS DAMBO DAMBO R. Swanepoel 2. Enter the cell by a pathway that ensures replication Virus attachment and entry, preferred target cell Gn/Gc virus attachment proteins (high-mannose N-glycans on the viral glycoproteins produced in mosquitoes – DC-SIGN binding) Receptor unknown, likely a protein dermal Dendritic Cells C-type-lectin (DC-SIGN) – attachment Virus entry and uncoating Virus egress RNA synthesis Virion assembly ? Protein synthesis Protein processing Virus entry and uncoating Endocytosis Virus egress via non-coated (smooth surfaced) vesicles (2/3) and via clathrin-coated vesicles (1/3) early endosomes dissociation from the receptor RNA synthesis late endosomes (& lysosomes)Virion assembly - acidification pH dependent fusion Gc postulated as a fusion protein based on similarity to fusion proteins of viruses in Flaviviridae and Togaviridae – or is it necessary to have the herodimer? ? Ribonucleoprotein, Protein synthesisRNP = RNA, L, NProtein processing uncoating TubularVirus entry viral andfactories uncoating (Golgi connected to mitochondria and RER) connect replication with assembly Virus egress RNPs accumulate in Golgi and form tubular Golgi stacks Mammalian L (polymerase) Globular part of the stack = site of cell mRNA, cRNA + vRNA synthesis already in forms of S, M , L RNP RNA synthesis Virion assembly ? Protein processing Virus entry and uncoating RNA synthesis only within RNP = ribonucleocapsids (requires RNA, L and N proteins) Virus egress L polymerase protein (RNA dependent RNA polymerase; RdRp): Endonuclease activity cap snatching from host mRNA (10-18 Nt primers) = primed mRNA synthesis RNA synthesis mRNA does not have poly-A tail (transcription termination signal) switch to replication (trigger unknown; encapsidation by N as antitermination signal?) priming not required for cRNA and vRNA synthesis Virus entry and uncoating First 10-13 Nt on the 3’end = genome promoters in vitro; (contain signals for mRNA and cRNA synthesis) requirement in vivo (cells) for RNA synthesis – aroundVirus 100 egress Nt, on both 3’ and 5’ ends of the RNA prime and re-align model (transcription and replication)? NSs mRNA synthesis some antigenomes are encapsidated NSs primary mRNA synthesis RNA synthesis from the cRNA Primary transcription (mRNA) Protein synthesis required for genome replication and Protein synthesis secondary transcription (and virion formation) Virus egress Virion assembly Golgi Protein processing Tubular viral factories (Golgi connected to mitochondria and RER) connect replication with assembly Virus assembly RVFV assembles in the Golgi apparatus Budding into the Golgi cisternae Transport to the cell membrane within vesicles similar to those in secretory pathways Exocytosis (lysis of mammalian cells, in insect cells the CPE is non-cytolytic) (Gerrard and Nichol 2007) Pathogenesis Can mosquitoes clear the virus? DRAIANAGE/DRYING OR FLOODING OF DAMBOS: EFFECTS ON FLOODWATER-BREEDING AEDES MOSQUITOES If not: in long term, all the infected FLOODING LEVELS mosquitoes die & RVFV with them POROUS SOIL MOSQUITO EGGS IMPERVIOUS LAYER uninfected C6/36 mosquito cells transovarial transmission (Aedes) – virus survives in eggs periods of draught up to several years; however drop in egg numbers and survival, and the overall reproductive fitness RVFV infected C6/36 mosquito cells Disease in humans Virus is genetically conserved incubation period: 2 – 6 days eye disease – 1 – 3 weeks after the first symptoms (retinal lesions; some permanent visual RVFV needs a loss (5%), death uncommon) mammalian host acute neurological disease - 1 – 3 weeks after the first symptoms (meningo-encephalitis; death uncommon) hemorrhagic fever – 2 – 4 days after the first symptoms (severe liver disease, jaundice, vomiting blood, passing blood in feces, purpuric rash (bleeding in the skin), bleeding from gums; patients viremic for 10 days; case-fatality rate 50% Total case/fatality rate 1-3% Sheep and goat fever, inappetence, listlesness mucopurulent nasal discharge bloody diarrhea 90 - 100% of pregnant animals abort 90% mortality in lambs/kids within 36hrs after the onset of signs 20 - 60% mortality in adult animals if the animals survive the hepatic infection, some of them develop encephalitis Cattle less severe clinical signs, dysgalactia 10 - 30% mortality in calves 90 - 100% of pregnant cows abort Camels high antibody levels, viremia, 90-100% abortion rates some early post-natal deaths Infections in healthy (not pregnant) adult animals – innaparent sheep Disease time course) and clinical manifestation human Bird et al, 2009 Calf (infected at 10 days of age), 28 dpi Experimental Infection With RVFV lamb, infected at 14 days of age, 2 dpi LESIONS IN LIVESTOCK LIVER – NECROTIC FOCI HAEMORRHAGE INTO ABOMASUM/ INTESTINES PATHOGNOMONIC LIVER NECROSIS WITH PRIMARY FOCI LIVER – INTRANUCLEAR INCLUSIONS neglected tropical disease Pathogenesis – not well known Underlying cellular mechanisms - not well known evade host defences = switch from arthropode host to mammalian host Other arboviruses (West Nile virus) Infection of dendritic cells with “insect” virions: no IFN- type I induction – facilitates first round of infection in the mammalian host (linked to a lipid composition of the “insect” virion) This step occurs already prior to virus replication in the cell C6/36 * * Vero E6 RVFV – in addition to insect cell derived envelope, large glycoprotein (Nsm1, LGp) in present in the virions Pathogenesis – molecular/cellular mechanisms Non-structural protein NSs For Bunyaviridae, unique nuclear localization of NSs in mammalian cells Bouloy and Weber, 2010 Cellular DNA mostly excluded from the filaments BUT Nss interacts with pericentromeric gamma satelite sequences chromosome cohesion and segregation defects NSs expression linked to cell cycle arrest (G0/G1 or S) fetal and newborn death? Nonstructural protein NSs – Inhibits host cellular transcription, impact on production of interferon α/β, IFN signaling as well NSs (has to be in form of filaments) interacts with SAP30 belongs to repressor complex intervening in
Load more

Recommended publications
  • The Ecology of Nipah Virus in Bangladesh: a Nexus of Land-Use Change and Opportunistic Feeding Behavior in Bats
    viruses Article The Ecology of Nipah Virus in Bangladesh: A Nexus of Land-Use Change and Opportunistic Feeding Behavior in Bats Clifton D. McKee 1,* , Ausraful Islam 2 , Stephen P. Luby 3, Henrik Salje 4, Peter J. Hudson 5, Raina K. Plowright 6 and Emily S. Gurley 1 1 Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA; [email protected] 2 Infectious Diseases Division, icddr,b, Dhaka 1212, Bangladesh; [email protected] 3 Infectious Diseases and Geographic Medicine Division, Stanford University, Stanford, CA 94305, USA; [email protected] 4 Department of Genetics, Cambridge University, Cambridge CB2 3EJ, UK; [email protected] 5 Center for Infectious Disease Dynamics, Pennsylvania State University, State College, PA 16801, USA; [email protected] 6 Department of Microbiology and Immunology, Montana State University, Bozeman, MT 59717, USA; [email protected] * Correspondence: [email protected] Abstract: Nipah virus is a bat-borne paramyxovirus that produces yearly outbreaks of fatal en- cephalitis in Bangladesh. Understanding the ecological conditions that lead to spillover from bats to humans can assist in designing effective interventions. To investigate the current and historical processes that drive Nipah spillover in Bangladesh, we analyzed the relationship among spillover events and climatic conditions, the spatial distribution and size of Pteropus medius roosts, and patterns of land-use change in Bangladesh over the last 300 years. We found that 53% of annual variation Citation: McKee, C.D.; Islam, A.; in winter spillovers is explained by winter temperature, which may affect bat behavior, physiology, Luby, S.P.; Salje, H.; Hudson, P.J.; Plowright, R.K.; Gurley, E.S.
    [Show full text]
  • Molecular Detection of a Novel Paramyxovirus in Fruit Bats from Indonesia
    Sasaki et al. Virology Journal 2012, 9:240 http://www.virologyj.com/content/9/1/240 RESEARCH Open Access Molecular detection of a novel paramyxovirus in fruit bats from Indonesia Michihito Sasaki1†, Agus Setiyono3†, Ekowati Handharyani3†, Ibenu Rahmadani4, Siswatiana Taha5, Sri Adiani6, Mawar Subangkit3, Hirofumi Sawa1, Ichiro Nakamura2 and Takashi Kimura1* Abstract Background: Fruit bats are known to harbor zoonotic paramyxoviruses including Nipah, Hendra, and Menangle viruses. The aim of this study was to detect the presence of paramyxovirus RNA in fruit bats from Indonesia. Methods: RNA samples were obtained from the spleens of 110 fruit bats collected from four locations in Indonesia. All samples were screened by semi-nested broad spectrum reverse transcription PCR targeting the paramyxovirus polymerase (L) genes. Results: Semi-nested reverse transcription PCR detected five previously unidentified paramyxoviruses from six fruit bats. Phylogenetic analysis showed that these virus sequences were related to henipavirus or rubulavirus. Conclusions: This study indicates the presence of novel paramyxoviruses among fruit bat populations in Indonesia. Background indicate the presence of henipavirus or henipa-like The genus Henipavirus in the subfamily Paramyxoviri- viruses in Indonesian fruit bats, suggesting the need for nae, family Paramyxoviridae, contains two highly patho- further epidemiological investigations. genic viruses, i.e., Hendra virus and Nipah virus. Hendra Menangle virus, belonging to the genus Rubulavirus of virus causes fatal pneumonia and encephalitis in horses the Paramyxoviridae family, has been identified in ptero- and humans. The first case was identified in 1994 and pus bats from Australia [14]. Menangle virus is a zoo- Hendra virus disease still continues to arise sporadically notic paramyxovirus that causes febrile illness with rash in Australia [1,2].
    [Show full text]
  • Presentation
    COMPLETE HEMORRHAGIC FEVER VIRUS INACTIVATION DURING LYSIS IN THE FILMARRAY BIOTHREAT-E ASSAY DEMONSTRATES THE BIOSAFETY OF THIS TEST. Olivier Ferraris (3), Françoise Gay-Andrieu (1), Marie Moroso (2), Fanny Jarjaval (3), Mark Miller (1), Christophe N. Peyrefitte (3) (1) bioMérieux, Marcy l’Etoile, France, (2) Fondation Mérieux, France (3) Unité de Virologie, Institut de recherche biomédicale des armées, Brétigny sur Orge, France Background : Viral hemorrhagic fevers (VHFs) are a group of illnesses caused by mainly five families of viruses namely Arenaviridae, Filoviridae , Bunyaviridae (Orthonairovirus genus ), Flaviviruses and Paramyxovirus (Henipavirus genus). The filovirus species known to cause disease in humans, Ebola virus (Zaire Ebolavirus), Sudan virus (Sudan Ebolavirus), Tai Forest virus (Tai Forest Ebolavirus), Bundibugyo virus (Bundibugyo Ebolavirus), and Marburg virus are restricted to Central Africa for 35 years, and spread to Guinea, Liberia, Sierra Leone in early 2014. Lassa fever is responsible for disease outbreaks across West Africa and in Southern Africa in 2008, with the identification of novel world arenavirus (Lujo virus). Henipavirus spread South Asia to Australia. CCHFv spread asia to south europa. They are transmitted from host reservoir by direct contacts or through vectors such as ticks bits. Working with VHF viruses, need a Biosafety Level 4 (BSL-4) laboratory, however during epidemics such observed with Ebola virus in 2014, the need to diagnose rapidly the patients raised the necessity to develop local laboratories These viruses represents a threat to healthcare workers and researches who manage infected diagnostic samples in laboratories. Aim : 1 Inactivation step An FilmArray Bio Thereat-E assay for detection of Hemorrhagic fever viruse Interfering substance HF virus + FA Lysis Buffer such as Ebola virus was developed to respond to Hemorrhagic fever virus 106 Ebola virus Whole blood + outbreak.
    [Show full text]
  • Zika Virus Infection
    ZIKA VIRUS UPDATE 2016 LARRY M. BUSH, MD, FACP Affiliated Professor of Clinical Biomedical Sciences Charles E. Schmidt College of Medicine Florida Atlantic University Affiliate Associate Professor of Medicine University of Miami – Miller School of Medicine / Palm Beach County NEWLY IDENTIFIED INFECTIOUS DISEASES AND PATHOGENS (2) Year Disease or Pathogen 2012 MERS-CoV 2009 H1N1 2004 Avian influenza (human cases) 2003 SARS 1999 Nipah virus 1997 H5N1 (avian influenza A virus) 1996 New variant Creutzfelt-Jacob disease; Australian bat lyssavirus 1995 Human herpesvirus 8 (Kaposi’s sarcoma virus) 1994 Savia virus; Hendra virus Source: Workshop presentation by David Heymann, World Health Organization, 1999 NEWLY IDENTIFIED INFECTIOUS DISEASES AND PATHOGENS (2) Year Disease or Pathogen 2012 MERS-CoV 2009 H1N1 2004 Avian influenza (human cases) 2003 SARS 1999 Nipah virus 1997 H5N1 (avian influenza A virus) 1996 New variant Creutzfelt-Jacob disease; Australian bat lyssavirus 1995 Human herpesvirus 8 (Kaposi’s sarcoma virus) 1994 Savia virus; Hendra virus Source: Workshop presentation by David Heymann, World Health Organization, 1999 Emerging and Re-emerging Infectious Diseases • Emerging infectious diseases: Infectious diseases that have newly appeared in a population. • Global : • Regional: • Re-emerging Diseases: Diseases’ incidence in human has increased during the last 20 years or threatens to increase in the near future. • Global: • Regional: GLOBAL EXAMPLES OF EMERGING AND RE-EMERGING INFECTIOUS DISEASES AS Fauci Factors responsible for emerging
    [Show full text]
  • Nipah Virus (Niv)
    Nipah Virus (NiV) Nipah virus (NiV) is a member of the family Paramyxoviridae, genus Henipavirus. NiV was initially isolated and identified in 1999 during an outbreak of encephalitis and respiratory illness among pig farmers and people with close contact with pigs in Malaysia and Singapore. Its name originated from Sungai Nipah, a village in the Malaysian Peninsula where pig farmers became ill with encephalitis. Given the relatedness of NiV to Hendra virus, bat species were quickly singled out for investigation and flying foxes of the genus Pteropus were subsequently identified as the reservoir for NiV (Distribution Map). In the 1999 outbreak, Nipah virus caused a relatively mild disease in pigs, but nearly 300 human cases with over 100 deaths were reported. In order to stop the outbreak, more than a million pigs were euthanized, causing tremendous trade loss for Malaysia. Since this outbreak, no subsequent cases (in neither swine nor human) have been reported in either Malaysia or Singapore. In 2001, NiV was again identified as the causative agent in an outbreak of human disease occurring in Bangladesh. Genetic sequencing confirmed this virus as Nipah virus, but a strain different from the one identified in 1999. In the same year, another outbreak was identified retrospectively in Siliguri, India with reports of person-to-person transmission in hospital settings (nosocomial transmission). Unlike the Malaysian NiV outbreak, outbreaks occur almost annually in Bangladesh and have been reported several times in India. Transmission Transmission of Nipah virus to humans may occur after direct contact with infected bats, infected pigs, or from other NiV infected people.
    [Show full text]
  • To Ebola Reston
    WHO/HSE/EPR/2009.2 WHO experts consultation on Ebola Reston pathogenicity in humans Geneva, Switzerland 1 April 2009 EPIDEMIC AND PANDEMIC ALERT AND RESPONSE WHO experts consultation on Ebola Reston pathogenicity in humans Geneva, Switzerland 1 April 2009 © World Health Organization 2009 All rights reserved. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of the World Health Organization concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted lines on maps represent approximate border lines for which there may not yet be full agreement. The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by the World Health Organization in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distin- guished by initial capital letters. All reasonable precautions have been taken by the World Health Organization to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either express or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall the World Health Organization be liable for damages arising from its use. This publication contains the collective views of an international group of experts and does not necessarily represent the decisions or the policies of the World Health Organization.
    [Show full text]
  • Hantavirus Infection Is Inhibited by Griffithsin in Cell Culture
    BRIEF RESEARCH REPORT published: 04 November 2020 doi: 10.3389/fcimb.2020.561502 Hantavirus Infection Is Inhibited by Griffithsin in Cell Culture Punya Shrivastava-Ranjan 1, Michael K. Lo 1, Payel Chatterjee 1, Mike Flint 1, Stuart T. Nichol 1, Joel M. Montgomery 1, Barry R. O’Keefe 2,3 and Christina F. Spiropoulou 1* 1 Division of High Consequence Pathogens and Pathology, Viral Special Pathogens Branch, Centers for Disease Control and Prevention, Atlanta, GA, United States, 2 Molecular Targets Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, United States, 3 Division of Cancer Treatment and Diagnosis, Natural Products Branch, Developmental Therapeutics Program, National Cancer Institute, Frederick, MD, United States Andes virus (ANDV) and Sin Nombre virus (SNV), highly pathogenic hantaviruses, cause hantavirus pulmonary syndrome in the Americas. Currently no therapeutics are approved for use against these infections. Griffithsin (GRFT) is a high-mannose oligosaccharide-binding lectin currently being evaluated in phase I clinical trials as a topical microbicide for the prevention of human immunodeficiency virus (HIV-1) infection (ClinicalTrials.gov Identifiers: NCT04032717, NCT02875119) and has shown Edited by: broad-spectrum in vivo activity against other viruses, including severe acute respiratory Alemka Markotic, syndrome coronavirus, hepatitis C virus, Japanese encephalitis virus, and Nipah virus. University Hospital for Infectious Diseases “Dr. Fran Mihaljevic,” Croatia In this study, we evaluated the in vitro antiviral activity of GRFT and its synthetic trimeric Reviewed by: tandemer 3mGRFT against ANDV and SNV. Our results demonstrate that GRFT is a Zhilong Yang, potent inhibitor of ANDV infection. GRFT inhibited entry of pseudo-particles typed with Kansas State University, United States ANDV envelope glycoprotein into host cells, suggesting that it inhibits viral envelope Gill Diamond, University of Louisville, United States protein function during entry.
    [Show full text]
  • Serologic Evidence of Nipah Virus Infection in Bats, Vietnam
    LETTERS Serologic Evidence dilution) was designated as 1:1,000 Medicine, Nagasaki University. No ELISA units. ELISA titers of sample specimens of C. sphinx bats were of Nipah Virus serum specimens were obtained at positive by NT; however, 2 specimens Infection in Bats, a single dilution (1,000×) by using a from R. leschenaulti bats, both positive Vietnam standard curve of positive serum with with low titers, were confi rmed to be high titers. A sample titer >3,000 was positive by NT (50% cytopathic effect To the Editor: Bats are potential considered positive for IgG against after NT, titers of 33.6 and 14.1). reservoir for highly pathogenic NiV. However, the latter specimen was viruses, such as Nipah virus (NiV) Positive results were detected negative by WB analysis. and Hendra virus, which can cross from only 2 fruit bat species, R. Seroepidemiologic studies in species barriers (1). However, leschenaulti (31 bats [49.1%]) and other countries have indicated that only limited surveillance has been Cynopterus sphinx (3 bats [2.8%]) Pteropus spp. bats (fruit-eating bats) conducted to assess risk for infection (Table). Of the 34 samples positive are the main reservoirs for NiV (3–6). by these deadly emerging viruses. We by ELISA, only 22 (20 from the Pteropid bats are usually found only in conducted a study in Vietnam from former and 2 from the latter bat southern Vietnam. We could not obtain 2007 to 2008 to assess the prevalence species), which had enough volume these bats for our study. However, a of these pathogens in bats.
    [Show full text]
  • Nipah Virus in People and Swine
    ANIMAL HEALTH FACT SHEET Animal Health and Food Safety Services Malaysian outbreak of Nipah Virus in People and Swine This report is edited from the "Emergency Report" by the closely related to the Hendra virus, a paramyxovirus Director General of the Malaysian Veterinary Services, first isolated in Brisbane, Australia, in 1994. On Dr. Mohd Nordin Mohd Nor, Office International des April 10, 1999, the isolate was officially called the Epizooties DISEASE INFORMATION, May 28, 1999, Nipah virus, named after the village where the Vol. 12 - No. 20. worker from whom the virus was isolated had died. Disease in people The disease spread to more farms and, from March 1 to May 10, 1999, a total of 224 suspected cases of The outbreak of Nipah disease in Malaysia, viral encephalitis in swine workers occurred with 80 which has caused human fatalities, has been fatalities. To date, 261 persons are suspected of attributed to a viral infection in pigs. The being infected with the Nipah virus and 103 have outbreak in 1998/99 has been investigated and died. After an incubation period believed to be traced back to earlier incidences which were between one and three weeks, clinical signs in provisionally diagnosed as Japanese encephalitis people include: fever and headaches of varying (JE). severity, and drowsiness and disorientation, later falling into a coma and requiring artificial In 1997, the illness was reported in a number of respiration. swine workers, one of whom died. In 1998, more cases of viral encephalitis were reported and two As a measure to control the spread of the new virus, more villages were affected.
    [Show full text]
  • Themis CEPI Press Release Cfp3
    CEPI awards up to US$23.4 million to Valneva for late-stage development of a single-dose Chikungunya vaccine Oslo, Norway, and Saint-Herblain, France, July 25, 2019—Valneva SE (“Valneva”), a biotech company developing and commercializing vaccines for infectious diseases with major unmet needs, and the Coalition for Epidemic Preparedness Innovations (CEPI) hereby announce a new partnering agreement. With support from the European Union’s (EU’s) Horizon 2020 programme, CEPI will provide Valneva up to US$23.4 million for vaccine manufacturing and late-stage clinical development of a single-dose, live-attenuated vaccine (VLA1553) against Chikungunya. In line with CEPI’s committment to equitable access, the funding will underwrite a partnership effort to accelerate regulatory approval of Valneva’s single-dose Chikungunya vaccine for use in regions where outbreaks occur and support WHO prequalification to facilitate broader access in lower and middle income countries. Valneva will also maintain a stockpile of the vaccine candidate and work to transfer the secondary manufacturing of the drug product to partners for lower and middle income countries—where outbreaks of Chikungunya have occurred—to improve access to the vaccine for at-risk populations. The investment is part of CEPI’s third call for proposals, launched earlier this year with support from the EU’s Horizon 2020 research and innovation programme under grant agreement No. 857934.1 Since the launch of this call in January 2019, over US$66 million has been invested in two Chikungunya vaccine candidates and two RVF vaccine candidates. Chikungunya virus was first identified in Tanzania in 1952, with sporadic outbreaks of the disease reported subsequently across Africa and Asia.2,3 In 2004, the disease began to spread quickly, causing large-scale outbreaks around the world.
    [Show full text]
  • 1998/99), Hendra Virus (1994) (Henipavirus, Paramyxoviridae
    Nipah virus (1998/99), Hendra virus (1994) (Henipavirus, Paramyxoviridae) Disease in humans, pigs and horses. Virus transmitted from Pteropus bats to humans by contaminated sap, from pigs or horses. Up to 90% C/F, no treatment, no vaccine for NiV HeV vaccine for horses NiV disease in humans during the outbreak in Malaysia: primarily encephalitis (40% cases pulmonary involvement) epidemic in humans masked by Japanese encephalitis outbreak 40% C/F; handling of pigs a critical factor NiV disease in pigs highly contagious (100%) “general clinical signs” - respiratory, some CNS signs mortality during the outbreak max.5% NiV disease in humans in Bangladesh/India outbreaks: Primarily pulmonary, high % of encephalitis 70% C/F drinking contaminated date palm sap and fruit critical factor Human HeV disease: flue-like symptoms respiratory and renal failure, C/F 50% relapsing encephalitic disease Current veterinarian cases 2008/2009/2010 – vaccine for horses Acute equine respiratory syndrome two days from the onset of the disease to death Other species susceptible to henipaviruses cats, dogs, goats Nipah virus, Hendra virus, Cedar virus (Henipavirus, Paramyxoviridae) Negative single strand RNA viruses, nonsegmented genome (15 – 18kb), enveloped 5’ L G F M P/V/W/C N 3’ Equine morbillivirus – Morbillivirus (measles virus) –most related virion proteins (Mononegavirales, Paramyxoviridae, Henipavirus) L - “polymerase” P - polymerase associated protein (V/W/C) G - glycoprotein F - fusion protein N - nucleocapsid protein M - matrix protein N+ P+ L + RNA Wang et al., 2001 Life Virus is genetically conserved Domain ONE serotype Kingdom NiV two genotypes, HeV one Phylum Class NiV and HeV use same receptor, & are antigenically cross-reacting Order Family Henipaviruses infect Genus different orders of mammals (Chiroptera, Artiodactyla, Carnivora Species Perissodactyla, and Primates.
    [Show full text]
  • Treatment of West Nile Virus Encephalitis with Intravenous
    Letters Treatment of West Nile Virus Encephalitis with immunoglobulin preparations from donors in Israel, such as Intravenous Immunoglobulin our patient received, contained high titers (1:1,600) of such antibodies, while those from the USA had no detectable To the Editor: West Nile virus is endemic in Israel. The antibody. We suggest that the use of such antibody-contain- overwhelming majority of infections are mild and asymp- ing immunoglobulin may provide a specific and effective tomatic, but there have been periodic symptomatic out- treatment for serious cases of West Nile virus infections, breaks (1). In August 2000, an epidemic of West Nile virus and therefore that formal trials of its use should be carried broke out in Israel, with >260 confirmed cases and 20 out. deaths by the end of September 2000. Hitherto, the only treatment for this condition has been supportive with no Acknowledgment proven in vivo specific therapy, although ribavirin has We thank Ella Mendelson, Director of the Central Virology shown promise in in vitro studies (2). We report an Laboratory, Ministry of Health of Israel, for the measurements of West Nile virus antibody. apparent dramatic response to intravenous immunoglobulin in an immunosuppressed patient and suggest that this was Zvi Shimoni,* Mark J. Niven,* the result of specific antibodies in the Israeli immunoglobu- Silvio Pitlick,† and Shlomo Bulvik* lin used. *Laniado Hospital, Kiryat Sanz, Netanya, Israel, and A 70-year-old woman was admitted to the hospital †Beilinson Hospital, Petach Tikva, Israel because of fever and vomiting of 24 hours’ duration. She had a 12-year history of chronic lymphatic leukemia (Rai References stage II) but was not on treatment.
    [Show full text]