52. West Nile fever, disease caused by Usutu virus and other mosquito-borne flaviviral diseases.

Question 1

West Nile fever- notifiable Occurrence and ethiology?

Answer 1

West Nile fever - Notifiable

• Mosquito transmitted zoonotic disease with fever, general signs, sometimes meningoencephalomyelitis and death.

Occurrence

• First isolation: Uganda 1937, human encephalitis ➝ West Nile virus (WNV)
• Africa, Europe, Asia, Australia (Kunjin virus) ➝ sporadic
• Europe

‣ First detection: Albania 1958 (serology)

‣ Cases, outbreaks

๏ 1960s: France, Russia, Spain, Romania

๏ 1970-1990s: Byelorussia, Ukraine, Romania, Czech Republic

๏ 2018: extreme high incidence comparing to previous years

• USA

‣ Introduction: New York 1999 ➝ spread all over the country until 2007

‣ Wild birds, humans, horses

Etiology

• 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)

• 9 genetic lineages ➝ pathogenic

‣ Lineage 1 strains: worldwide

‣ Lineage 2 strains: Europe, since 2004 all cases in Hungary

Question 2

(Epidemiology)Natural hosts : Birds?

Answer 2

Natural hosts: birds

o Detected in several bird sp. (Prey)

o 20-100 days viraemia

o Differences in the level of viraemia ~ ability of transmission

o Migratory birds play a role in the long-distance spread

Question 3

(Epidemiology) Arthropod vectors?

Answer 3

Arthropod vectors: mosquitoes (ticks)

o Detected in more than 60 mosquito sp.

o Principle: Culex pipiens

o Biological vector, vertical transmission

Question 4

(Epidemiology) Dead end hosts?

Answer 4

• Incidental, dead-end hosts

‣ Human, horse, small mammals, amphibians, reptiles

• Non-vectoral transmission: rare, mainly human

Question 5

Pathogenesis?

Answer 5

Pathogenesis

• Vector ➝ local multiplication ➝ viraemia
• 80-90% of infectious are subclinical
• Neuroinvasive ➝ inflammation

‣ Serous-lymphoid cell infiltration

‣ Neuron cell degeneration, apoptosis

‣ Inflammation of the peripheral nerves, demyelinisation

• Antibodies emerge on days 7-11 post infection
• Persisting infections are rare in mammals, frequent in birds

Question 6

Clinical signs?

Answer 6

Clinical signs

- Horse

‣ 80-90% of infections are subclinical

‣ Febrile general signs, anorexia, depression

‣ CNS signs (WNND): 1%

๏ Skin oversensitivity

๏ Weakness of hindlimb

๏ 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

- 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 or seizures, ataxia, paralysis, sudden death

Question 7

Pathology and Histopathology in Horse and Bird?

Answer 7

Pathology in horse and bird

• Petechial haemorrhage

‣ Pericardium

‣ Muscles

• Serous fluid accumulation in epicardium

Histopathology in horse and bird

• CNS

‣ Multifocal cellular infiltration

‣ Haemorrhages

‣ Neuron cell degeneration and apoptosis

‣ Glia cell proliferation

• Myocardium

‣ Serous cellular inflammation

‣ Cell degeneration, apoptosis

Question 8

Diagnosis?

Answer 8

Diagnosis

• Differential diagnosis: from febrile illnesses with CNS signs
• Epizootiology, clinical signs

‣ Seasonal (midsummer to fall) ➝ higher number of 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 infection

๏ In BSL3 laboratory

‣ Immunohistochemistry ➝ successful in 50%, if death is within 1 week

‣ Serology

๏ Cross reactions ➝ TBEV, Usutu virus

๏ Virus neutralisation ➝ in BSL3 laboratory

๏ Haemagglutination inhibition, indirect immunofluorescence, ELISA

‣ Acute case

๏ Non-coagulated blood (buffy coat), liquor (brain if dead): RT-PCR

๏ Coagulated blood: IgM, ELISA

‣ Serosurvey (is vaccination necessary? Former ifnection?)

๏ Coagulated blood (serum): IgG ELISA, cross-reactions: TB, USUV ➝ VN

Question 9

Differential diagnosis?

Answer 9

Differential diagnosis:

• from febrile illnesses with CNS signs

Question 10

Prevention & Control?

Answer 10

Prevention & control

• Mosquito control
• Use of repellants
• Restriction measures
• Immunisation

‣ Inactivated vaccines Equip (Duvaxyn) WNV for horses

‣ Recombinant canary pox vaccine: Proteq West Nile

‣ Every year before mosquito season

Question 11

Public health aspects?

Answer 11

Public health aspects

• Humans susceptible
• Usually (80%) symptomatic seroconversion
• 3-14 days after mosquito bite, flu-like symptoms

‣ Fever, headache, weakness

‣ Muscle and joint pain

‣ Discomfort, loss of appetite

‣ Swelling of lymph nodes, rash

‣ Recovery in 3-6 days

• Severe cases: CNS signs, encephalitis

‣ Over 60 years of age

‣ Headache, fever, neck stiffness

‣ Stupor, disorientation, coma, tremors, convulsions, muscle weakness, vision loss, numbness, paralysis

‣ Recovery: weeks or months, permanent damage may remain

‣ Immunosuppression increases the risk of death

• No vaccine: avoid mosquito bite, protective clothing
• Heterologous flavivirus immunity cross protection

Question 12

Other mosquito borne flavivirus infections?

Answer 12

• 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

• 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

• Worldwide in tropics, human
• Antibody-dependent enhancement (ADE)
• Dengue fever
• Dengue haemorrhagic fever and dengue shock syndrome
• In 2011 autochthonous cases in Croatia

• Yellow fever

• Worldwide in tropics, human, monkeys
• Fever, haemorrhage, rash, liver dystrophy
• Vaccination is necessary before travel to endemic areas

• 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