Flaviviruses Flashcards
What is the family and genus of Japanese encephalitis virus?
Flaviviridae family, flavivirus genus
What is the vector of JEV?
What is the main amplifying host?
Which two animals get clinical symptoms?
Culex tritaeniorhynchus
Pigs are important amplifying hosts (herons are maintenance hosts!)
Pigs and horses get clinical symptoms
What are the transmission routes of JEV?
Mosquito bite
Occasional reports of lab associated, organ and NSI transmissions
Where is JEV endemic?
Most of Asia (as of 2022 Australia) - esp risk in rural areas of China with rice and pig farming
Vaccination has eliminated JEV from Japan, South Korea, Singapore, Taiwan
What % of JEV infections are asymptomatic?
> 99%
What is the fatality rate of JEV in severe cases?
30%
What are the symptoms of JEV?
Initial ILI followed by encephalitis
(also aseptic meningitis, AFP, coma, seizures)
Treatment for JEV
Supportive only
Risk of primary JEV in pregnancy
Miscarriage
What is the name of the UK licensed JEV vaccine?
What type of vaccine?
What age is it licensed in?
What is the schedule?
Are boosters required?
Ixiaro
Inactivated vaccine
> 2 months
Two doses 28 d apart (can have rapid course 7 d apart)
Booster required 1-2 y post primary course and this provides protection for 10 y
What is the family, genus and complex of WNV?
Flaviviridae family, flavivirus genus, JEV serogroup
What are the reservoir hosts of WNV?
Birds
What animal is most severely affected by WNV?
Horses have severe illness and are dead end hosts
Where does WNV circulate?
Mostly in Africa, post 1999 it was found in America and is now also seen in Europe and Australia
What is the vector of WNV?
Culex (esp C. pipiens) is the most important vector but other mosquitos and ticks can be infected
Do humans transmit WNV to mosquitos?
No, humans are dead end hosts
How is WNV transmitted to humans?
Mosquito bite
Rarely infected by handling infected tissues
Transplacental transmission is possible as is infection via breast milk
Possible sexual transmission
Transfusion and organ transmission have occurred
Where is WNV found in Europe?
What is the risk in the UK?
Outbreaks in Romania since 1996
Cases identified in France, Italy, Portugal, Spain
No locally acquired cases in UK
However, Culex modestus has been found around the Thames estuary so autochthonous transmission risk
What is the incubation of WNV?
Which patient groups are most at risk of severe disease?
2-14 d (average 2-6 d) can be up to 21 in immunocompromised
> 50 years and immunocompromised
Children rarely get WV encephalitis
Mortality highest in >70 y
Clinical presentations of WNV
1) Mostly asymptomatic
2) <20% get West Nile fever - ILI, rash, conjunctivitis
3) <1% Neuroinvasive disease - meningitis, encephalitis (10% mortality and high sequelae), AFP (known as WN polio) appears rapidly with no preceding signs of illness
What are some of the rarer manifestations of WNV?
Most commonly ocular complications
Myocarditis, pancreatitis, orchitis, fulminant hepatitis, kidney disease and haemorrhagic symptoms (rare)
Diagnosis of WNV?
IgM and rising IgG (serology complicated by cross reactivity with other flavis)
RNA in blood (early) and urine
In CNS infection, RNA or IgM in CSF
When to consider diagnosis of WNV?
In patients with travel to Southern/Eastern Europe, Africa/North America
With febrile or acute neurological illness
Also consider in patients living near the North Kent and Essex coastlines
Are there vaccines from WNV?
Only for animals
No human vaccine in phase III trials, development hindered by risk of ADE
How is the UK blood supply protected from WNV?
Donations deferred from patients for 28 days following WNV risk area
When was the recent Zika outbreak in Brazil and what were the symptoms?
2015 - causing microcephaly and GBS
Which lineage of Zika causes congenital disease?
Only the Asian lineage, the African lineage does not
Suggested that a SNP arose around 2013 linked to congenital infection
Where does Zika circulate?
Africa, Asia, the Pacific Islands, Central and South America and the Caribbean
What is the main vector of Zika?
Aedes aegyptii
What is the reservoir host of Zika?
Unknown
What are the transmission routes of Zika?
Mosquito bite or sexual transmission
How long is sexual transmission of Zika a risk?
3 months from males
2 months from females
What is the advice to couples trying to conceive after visiting a Zika risk country?
Barrier contraception for 3 months for males, or 2 months for females if trying to conceive. If male has been to at risk country then they should use barrier contraception for the duration of pregnancy
How long after Zika risk can negative serology be used to determine there has been no infection?
Negative serology 4 weeks after last risk indicates patients highly unlikely to have been infected
As per RCOG how should an asymptomatic pregnant traveller with Zika be managed?
Serum should be stored
Baseline foetal ultrasound repeated at 18-20 w
Consider a follow up at 28-30 w
Baby will need review
As per RCOG how should a symptomatic pregnant traveller with ?Zika be managed?
If current symptoms - serum and urine to RIPL and baseline foetal ultrasound if negative consider repeat serology and return to normal care
If history of compatible symptoms - serum to RIPL and baseline foetal ultrasound if negative consider repeat serology and return to normal care
If serology positive or inconclusive send further samples and refer to foetal medicine. MRI and amniocentesis may be required.
If serology positive neonate will need review and follow up at birth
Incubation and clinical features of Zika infection
Incubation 3-12 d
Mostly asymptomatic
Febrile illness with (itchy) rash
Conjunctivitis may be present
Severe disease unusual, GBS and congenital infection is a risk
Differential diagnosis of Zika?
Chikungunya
Dengue
Measles
Rubella
Parvovirus
Enterovirus
Malaria
What are the risk dates for congenital Zika syndrome?
When is the highest risk?
What are the symptoms?
8 weeks PRIOR to conception throughout pregnancy
Highest risk is in first trimester (8%), second (6%), third (4%)
Symptoms:
Microcephaly
Intracranial calcifications
Ventriculomegaly
Cell migration abnormalities
Congenital contractures
What tests should be performed on a baby with ?congenital Zika, or born to a mother with confirmed Zika during pregnancy (or pre-conception)?
When would baby receive follow up?
PCR and histology of placenta and umbilical cord at birth
Cranial ultrasound or MRI of brain
Ophthalmic and hearing review
Follow up at 3 months, then every 3 months until 12 months
What samples are useful for diagnosis of Zika infection?
Short viraemia so PCR in serum often not useful
Sheds for 2-3 weeks in urine so urine good sample
IgM can cross react with other flavis and can be neg in patients with previous dengue
Which groups are eligible for testing for Zika at RIPL?
1) Symptomatic travellers within 2 weeks of returning from risk countries
2) Symptomatic patient in contact with male sexual partner who has had Zika risk in the previous 3 months
What are the sample requirements for patients being tested for Zika at RIPL?
Serum sample and urine if within 21 days of symptom onset
Regarding organ donors, what two scenarios should Zika be considered in potential organ donors?
1) Return from a risk country within 28 days
2) Sexual partners of those who have return from a risk country
Is Zika virus infection a contraindication to a) organ b) tissue donation?
a) Yes unless in exceptional circumstances
b) Absolute contraindication
Name some flaviviruses other than: Dengue, JEV, TBEV, WNV, Yellow fever, Zika
Spondweni
Wesselsbron
St Louis Encephalitis
Usutu
Murray valley virus
Rocio virus
Louping Ill virus
Kyasanur Forest disease virus
Omsk haemorrhagic fever
Powassan virus
What virus other than Yellow fever is part of the Yellow fever complex?
Wesselsbron virus
Where does Wesselsbron circulate? What are the symptoms? What does it cause in ruminants and what is the main vector?
Africa
Mild disease but has caused encephalitis
Causes miscarriages in ruminants
Aedes sp.
What virus is Spondeweni virus phylogenetically and antigenically related to?
Zika
Name 6 viruses in the Japanese encephalitis complex. Which are HG3?
JEV
WNV
St Louis encephalitis
Murray Valley encephalitis
Usutu
Rocio virus
All are HG3, except Usutu which is HG2
Where does St Louis encephalitis virus circulate? What are the symptoms? What are the amplifying host? And what is the main vector?
Eastern and Central USA
Mild ILI but encephalitis can occur in older adults (case fatality 5-15%)
Wild birds
Culex sp.
Where does Usutu virus circulate? What virus is its close relate? What are the symptoms? What is the reservoir and spill over host? And what is the main vector?
Europe (France, Germany, Italy, Austria, Netherlands)
West Nile virus
Mostly asymptomatic but neuroinvasive cases in elderly and immunocompromised (like WNV)
Birds are reservoir, horses are spill over host
Culex sp.
Where does Murray Valley encephalitis virus circulate? What are the symptoms? What is the reservoir? And what is the main vector?
Australia and Papua New Guinea
Mostly asymptomatic but encephalitis and meningoencephalitis can occur
Water birds (herons and cormorants)
Culex annulirostris
Name 5 viruses in the Tick Borne encephalitis complex. What hazard group are they?
TBEV
Louping Ill
Powassan
Omsk haemorrhagic fever
Kyasanur Forest disease virus
All HG3
PLOK
Where does Louping Ill virus circulate? What are the symptoms? Which animals get severe illness? And what is the vector?
UK particularly Scotland
Rarely reported in humans, mostly ILI but can cause meningoencephalitis
Sheep and red grouse
Ixodes ricinus
Where does Kyasanur Forrest disease virus circulate? What is it otherwise known as? What are the symptoms? And what is the vector?
South India
Monkey fever
Febrile illness with haemorrhagic fever in 5-10% (high fatality rate)
Hemaphysalis spinigera (hard ticks)
Where does Omsk haemorrhagic fever virus circulate? What are the symptoms? And what are the vectors?
Siberia and Russia
Febrile illness with haemorrhage, can cause neurological disease
Spread by ticks and small mammals
Where does Powassan virus circulate? What are the symptoms? What are the maintenance hosts? And what is the vector? What is the incubation?
North America
Mostly asymptomatic or mild, if symptoms occur then febrile prodrome followed by headache and rash, neuroinvasive disease follows in the majority
Maintained in squirrels, groundhog, mice and deer. Spread by Ixodes spp.
Incubation of 1-5 weeks
