Flavivirus Diseases PDF

2023. 10. 25. Diseases caused by flaviviruses Flaviviridae – enveloped, icosahedral symmetry, +ssRNA viruses – Orthoflavivirus, Pestivirus, Hepacivirus genus – Orthoflavivirus genus 53 species, most of them are exotic, characteristic geographic presence 1...

2023. 10. 25. Diseases caused by flaviviruses Flaviviridae – enveloped, icosahedral symmetry, +ssRNA viruses – Orthoflavivirus, Pestivirus, Hepacivirus genus – Orthoflavivirus genus 53 species, most of them are exotic, characteristic geographic presence 1 World distribution of flaviviruses Alfuy virus Jugra virus Rocio virus Apoi virus Jutiapa virus Saboya virus Aroa virus Kadam virus Sal Vieja virus Bagaza virus Karshi virus San Perlita virus Banzi virus Kedougou virus Saumarez Reef virus Batu Cave virus Kokobera virus Sepik virus Bouboui virus Koutango virus Sokoluk virus Bukalasa bat virus Kunjin virus Spondweni virus Bussuquara virus Kyasanur Forest disease virus St. Louis encephalitis virus Cacipacore virus Langat virus Stratford virus Carey Island virus Louping ill virus Tamana bat virus Cell fusing agent virus Meaban virus Tembusu virus Cowbone Ridge virus Modoc virus Tick-borne encephalitis virus Dakar bat virus Montana myotis Tyuleniy virus Dengue virus leukoencephalitis virus Uganda S virus Edge Hill virus Murray Valley encephalitis virus Usutu virus Entebbe bat virus Naranjal virus Wesselsbron virus Gadgets Gully virus Negishi virus West Nile virus Iguape virus Ntaya virus Yaounde virus Ilheus virus Omsk hemorrhagic fever virus Yellow fever virus Israel turkey Phnom Penh bat virus Yokose virus meningoencephalomyelitis virus Potiskum virus Zika virus Japanese encephalitis virus Powassan virus Rio Bravo virus World-wide: 2 1  2023. 10. 25. 3 4 2  2023. 10. 25. Diseases caused by flaviviruses Flaviviridae – enveloped, icosahedral symmetry, +ssRNA viruses – Orthoflavivirus, Pestivirus, Hepacivirus genus – Orthoflavivirus genus 53 species, most of them are exotic, characteristic geographic presence weak resistance (pH, 40 ℃, detergents, disinfectants: sensitive) tick-transmitted / mosquito-transmitted / non-arbovirus groups – biological vectors – possible non-vectorial transmission (air-borne, p.o.) euryxen, many zoonotic fever and rash – encephalitis/meningitis – haemorrhage antigenicity – strong antigens – serological cross-reactions! – sometimes cross-protection 5 Louping ill Tick-transmitted febrile illness with general signs and meningo- encephalomyelitis in sheep and rarely other animal species. Occurrence – British isles, Scandinavia, Spain, Greece, Turkey Epizootiology – Principle vector: Ixodes ricinus → seasonal outbreaks – Susceptibility: sheep, domesticated and wild mammals, red grouse, humans Clinical signs – 1-3 weeks incubation – biphasic fever – depression, salivation, trembling, convulsions, tic – ataxia (louping ill), coma, death – frequent permanent damages after recovery (from mild symptoms) – virus shedding in milk → infection of young animals Histopathology – lymphocytic encephalitis, neuron necrosis, glia-proliferation 6 3  2023. 10. 25. 7 Louping ill Diagnosis – epizootiology, case history, clinical signs, histopathology – isolation, RT-PCR – serology: HAI, VN, ELISA Differential diagnosis – listeriosis – histopathology, bacteriology tests – rabies – occurrence, course, laboratory – scrapie – occurrence, course, no fever, laboratory Prevention – tick thinning – inactivated vaccine is available in endemic countries Public health considerations – human infection is rare – tick-bite, air-borne, p.o. – fever, meningoencephalitis 8 4  2023. 10. 25. Tick-borne encephalitis A human febrile illness with meningo-encephalomyelitis in certain cases, in animals usually asymptomatic infection. Occurrence – Central-European and Far-Eastern lineages (I. ricinus / I. persulcatus) 9 Galgani et al., 2017 10 5  2023. 10. 25. Tick-borne encephalitis A human febrile illness with meningo-encephalomyelitis in certain cases, in animals usually asymptomatic infection. Occurrence – Central-European and Far-Eastern lineages – Endemic in Central Europe – focal infections ECDC 2020 11 Reported TBE cases in Hungary 1977-2018 (Zöldi and Sztikler 2019) 12 6  2023. 10. 25. Tick-borne encephalitis A human febrile illness with meningo-encephalomyelitis in certain cases Occurrence – Central-European and Far-Eastern lineages – Endemic in Central Europe – focal infections Epidemiology – Principle vector: Ixodes ricinus (Asia: Ixodes persulcatus) biological vector, transovarial transmission Ixodes ricinus Ixodes persulcatus 13 14 7  2023. 10. 25. 15 Tick-borne encephalitis A human febrile illness with meningo-encephalomyelitis in certain cases Occurrence – Central-European and Far-Eastern lineages – Endemic in Central Europe – focal infections Epidemiology – Principle vector: Ixodes ricinus (Asia: Ixodes persulcatus) biological vector, transovarial transmission – Susceptibility: human, domesticated and wild mammals, birds – Natural cycle: rodents, small mammals, (birds) – ticks – Infection of humans, domesticated animals tick-bite – seasonal consumption of raw milk (goat!) 16 8  2023. 10. 25. TBE cases linked to consumption of raw goat milk in Hungary T ej TBE eredetű cases linkedKE esetek to consumption of Magyarországon raw 1955-2008 goat milk in Hungary 1955-2008 17 Tick-borne encephalitis A human febrile illness with meningo-encephalomyelitis in certain cases Occurrence – Central-European and Far-Eastern lineages – Endemic in Central Europe – focal infections Epidemiology – Principle vector: Ixodes ricinus (Siberia: Ixodes persulcatus) – Susceptibility: human, domesticated and wild mammals, birds – Natural cycle: rodents, small mammals, (birds) – ticks – Infection of humans, domesticated animals tick-bite – seasonal consumption of raw milk (goat!) Pathogenesis – infection – local multiplications – viraemia – visceral organs (CNS) 18 9  2023. 10. 25. Tick-borne encephalitis Clinical signs – In animals usually, in humans frequently subclinical infections – 1-2 weeks incubation – 1st fever + influenza-like disease – 7-10 days after: 2nd fever, CNS signs – headache, restlessness, neck stiffness, weak limbs, paralysis – usually complete recovery, but permanent lesions may also remain – rarely in foals, dogs, goats clinical signs occur: depression, ataxia, convulsions, tremor Diagnosis – direct: isolation (suckling mouse brain), RT-PCR, HA – indirect: IF, ELISA, HAI, VN (PRNT) Differential diagnosis – entero-, toga-, flavi-, herpesviruses, bacterial meningitis Prevention, control – prevention from tick-bite – inactivated vaccine (2× + 1× + in 3-4 years) 19 Tick-borne encephalitis https://www.ecdc.europa.eu/en/tick-borne-encephalitis https://www.eurosurveillance.org/search?value1=tick- borne+encephalitis+tbe&option1=fulltext https://www.ejinme.com/article/S0953-6205(19)30016-0/pdf https://www.cdc.gov/vhf/tbe/index.html https://www.who.int/health-topics/tick-borne-encephalitis#tab=tab_1 20 10  2023. 10. 25. West Nile fever Mosquito-transmitted zoonotic disease with fever, general signs, sometimes meningo-encephalomyelitis and death. 21 West Nile fever First isolation: Uganda 1937, human encephalitis → West-Nile virus (WNV) Occurrence: 22 11  2023. 10. 25. Fall et al., 2019 23 OIE 2005-2021 24 12  2023. 10. 25. West Nile fever First isolation: Uganda 1937, human encephalitis → West-Nile virus (WNV) Occurrence: Africa, Europe, Asia, Australia (Kunjin virus) – sporadic Europe: ▪ First detection: Albania 1958 (serology) ▪ Cases, outbreaks: – 1960’s: France, Russia, Spain, Romania – 1970-90’s: Byelorussia, Ukraine, Romania, Czech Republic – 2018: extreme high incidence comparing to previous years 25 1800 1600 1400 1200 1000 800 600 400 200 0 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 EU cases (ECDC): human horse bird 26 13  2023. 10. 25. Human 2022 (ECDC) Horse & bird 2022 (ECDC) 27 2023 human 2023 animals 28 14  2023. 10. 25. 2022: W32-W39 2023: W28-W38 (aug. 8. – oct. 2.) (july. 10. – oct. 1.) 29 West Nile fever First isolation: Uganda 1937, human encephalitis → West-Nile virus (WNV) Occurrence: Africa, Europe, Asia, Australia (Kunjin virus) – sporadic Europe: ▪ First detection: Albania 1958 (serology) ▪ Cases, outbreaks: – 1960’s: France, Russia, Spain, Romania – 1970-90’s: Byelorussia, Ukraine, Romania, Czech Republic – 2018: extreme high incidence comparing to previous years USA introduction: NY 1999 → spread all over the country until 2007 wild birds, humans, horses 30 15  2023. 10. 25. 10000 USA human cases (CDC) 9000 8000 7000 6000 5000 4000 3000 2000 1000 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 31 West Nile Fever Aetiology: – Japanese encephalitis serocomplex: serological cross reactions Japanese Encephalitis virus (JEV), West Nile virus (WNV), Usutu virus (USUV), St Louis Encephalitis virus (SLEV), Murray Valley encephalitis virus (MVEV), Kunjin virus (KUNV), etc. – 9 genetic lineages Pathogenic: Lineage 1 strains (worldwide) Lineage 2 strains (Europe), since 2004 all cases in Hungary 32 16  2023. 10. 25. West Nile Fever Epidemiology 33 West Nile Fever Epidemiology – Natural hosts: birds detected in several bird species 20-100 days viraemia differences in the level of viraemia ~ ability of transmission migratory birds play a role in the long-distance spread – Arthropod vectors: mosquitoes (ticks) detected in more than 60 mosquito species principle vector: Culex pipiens biological vector, vertical transmission – Incidental, dead-end hosts: human, horse, small mammals, amphibians, reptiles – Non-vectorial transmission: rare, mainly human 34 17  2023. 10. 25. West Nile fever Pathogenesis vector → local multiplication → viraemia ~ 80-90% of the infections are subclinical neuroinvasive → inflammation ✓ serous-lymphoid cell infiltration ✓ neuron cell degeneration, apoptosis ✓ inflammation of the peripheric nerves, demyelinisation antibodies emerge on 7-11. days post infection persisting infections are rare in mammals, frequent in birds 35 West Nile fever Clinical signs horse ~ 80-90% of the infections are subclinical febrile general signs, anorexia, depression CNS signs (WNND): < 1% – skin oversensitivity – weakness of the hind limbs – teeth grinding, – convulsions, seizures – incoordination, ataxia, aimless wandering, circling, – partial paralysis, – coma, →~9-90% lethality 36 18  2023. 10. 25. 37 West Nile fever Clinical signs horse ~ 80-90% of the infections are subclinical febrile general signs, anorexia, depression CNS signs (WNND): < 1% – skin oversensitivity – weakness of the hind limbs – teeth grinding, – convulsions, seizures – incoordination, aimless wandering, circling, – partial paralysis, – coma, →~9-90% lethality sheep teeth grinding, ataxia dog, cat asymptomatic seroconversion, rarely fever, CNS signs 38 19  2023. 10. 25. West Nile fever Clinical signs horse ~ 80-90% of the infections are subclinical febrile general signs, anorexia, depression CNS signs (WNND): < 1% →~9-90% lethality sheep teeth grinding, ataxia dog, cat asymptomatic seroconversion, rarely fever, CNS signs geese 3-12 weeks of age seizures, ataxia, abnormal head position, wing paralysis 14-40% lethality 39 40 20  2023. 10. 25. 41 West Nile fever Clinical signs horse ~ 80-90% of the infections are subclinical febrile general signs, anorexia, depression CNS signs (WNND): < 1% →~9-90% lethality sheep teeth grinding, ataxia dog, cat asymptomatic seroconversion, rarely fever, CNS signs geese 3-12 weeks of age seizures, ataxia, abnormal head position, wing paralysis 14-40% lethality wild birds stork, birds of prey, crow, magpie, sparrow, seagull, blackbird… penguin asymptomatic infection ↔ death asymptomatic seroconversion / seizures, ataxia, paralysis, sudden death 42 21  2023. 10. 25. West Nile Fever Pathology (horse, bird) petechial haemorrhages ✓ pericardium ✓ muscles serous fluid accumulation in the epicardium Histopathology (horse, bird) CNS ✓multifocal cellular infiltration ✓haemorrhages ✓neuron cell degeneration & apoptosis ✓glia cell proliferation myocardium ✓serous-cellular inflammation ✓cell degeneration, apoptosis 43 West Nile Fever Diagnosis – Differential dg.: from febrile illnesses with CNS signs – Epizootiology, clinical signs seasonal (midsummer to fall) ~ infected mosquitoes ↑ suspicion if CNS signs are seen - notifiable disease! – Laboratory diagnosis RT-PCR virus isolation – suckling mouse brain, Vero cell line, embryonated egg – usually successful in the early stage of the infection – in BSL3 laboratory immunohistochemistry – successful in ~ 50%, if death is within 1 week serology – cross-reactions! – TBEV, Usutu virus – virus neutralisation – in BSL-3 laboratory – haemagglutination-inhibition, indirect immunofluorescence, ELISA 44 22  2023. 10. 25. West Nile Fever Diagnosis – Differential dg.: from febrile illnesses with CNS signs – Epizootiology, clinical signs seasonal (midsummer to fall) ~ infected mosquitoes ↑ suspicion if CNS signs are seen - notifiable disease! – Laboratory diagnosis acute case ✓ non-coagulated blood (rbc, buffy coat), liquor (brain if dead): RT-PCR ✓ coagulated blood: IgM ELISA (but: previous basic immunisation! → VN titer increase serosurvey (vaccination necessary?, former infection?) coagulated blood (serum) ✓ IgG ELISA ✓ cross reactions! – TBE, USUV → VN 45 West Nile Fever Prevention and control mosquito-control use of repellents restriction measures immunisation ✓ inactivated vaccines Equip (Duvaxyn) WNV for horses ✓ recombinant canary pox vaccine: Proteq West Nile ✓ every year(?) before mosquito season https://www.woah.org/en/disease/west-nile-fever/ https://www.woah.org/fileadmin/Home/eng/Health_standards/tahm/3.01.24_WEST_NILE.pdf 46 23  2023. 10. 25. West Nile Fever – Public health – human is susceptible – usually (80%) asymptomatic seroconversion – or 3-14 days after mosquito bite flu-like symptoms fever, headache, weakness, muscle & joint pain, discomfort, loss of appetite, swelling of lymp nodes, rash recovery in 3-6 days – or severe cases: CNS signs, encephalitis (>60 years of age) headache, fever, neck stiffness stupor, disorientation, coma, tremors, convulsions, muscle weakness, vision loss, numbness, paralysis recovery: weeks or months, permanent damages may remain immunosuppression increases the risk of death – no vaccine; avoid mosquito bite, protective clothing – heterologous flavivirus immunity cross protection??? https://www.ecdc.europa.eu/en/west-nile-virus-infection 47 Other, mosquito-borne flavivirus infections Japanese encephalitis (notifiable disease!) – Far East; human, horse (encephalitis), swine (abortion), other mammals, birds – Vaccines are available, suggested before travelling to endemic regions St. Louis encephalitis – notifiable disease! – America, (EU); horse, human encephalitis; bird monitoring (seropositivity) Murray-valley encephalitis – Australia, New-Guinea, human (children) – wild bird reservoir, occurs in mammals too Wesselsbron disease – Sub-Saharan Africa; sheep, other mammals, human – sheep foetopathogen, abortion; lamb haemorrhage, icterus, encephalitis – in human usually subclinical, or fever and muscle pains Turkey meningoencephalitis – Israel, South Africa, (Hungary?), turkey – CNS signs, ataxia, reduced egg production, mortality – haemorrhages, inflammatory and necrotic foci, encephalitis – attenuated live vaccine in endemic countries available 48 24  2023. 10. 25. Other, mosquito-borne flavivirus infections Usutu – Africa, Central-Europe (Austria, Hungary, Switzerland, Italy, Germany) – encephalitis in wild birds (blackbird, sparrow, owls); other animals? Duck egg-drop syndrome – Baiyangdian (BYD) virus – China, 2010 – duck, egg-drop syndrome-like disease Dengue fever – world-wide on tropics, human – antibody-dependent enhancement (ADE) – Dengue-fever – Dengue haemorrhagic fever and dengue shock syndrome – in 2011 autochthonous cases in Croatia! Yellow fever – world-wide on tropics, human, monkeys – fever, haemorrhage, rash, liver dystrophy – vaccination is necessary before travel to endemic areas 49 Zika virus infection Occurrence – native in Africa – detection in Asia (India, Far-East) – 2007: significant outbreak in Micronesia – 2015: emergence in Brazil, rapid spread in south- and central America – imported cases in Europe human febrile disease with rash, conjunctivitis foetopathy: microcephaly, Guillain-Barré syndrome vectors – several tropical mosquito species – Aedes aegypti can be principle vector – Aedes albopictus is competent vector 50 25  2023. 10. 25. Thank you for your attention! 51 26