Viruses Flashcards
What type of organism is dengue?
Single chain RNA flavovirus
What is the vector for dengue?
Aedes Aegypti mosquito
Day biting urban mosquitos
Which viral protein allows entry into the dengue cell?
E - envelope
What serotypes of dengue exist
1,2,3,4
What is the incubation period for dengue?
4-7 days
What are the phases of dengue illness?
Day 1-3 Febrile
Day 4-5 Critical
Day 6-10 Recovery
What are the features of the critical phase in dengue illness?
Increase vascular permeability, plasma leakage, intravascular volume depletion
Hypovolaemic shock
Pleural effusion and ascites
Severe haemorrhage
Organ impairment
DIC
Severe hepatitis, myocarditis, pancreatitis, encephalitis may develop without obvious plasma leakage or shock
Bloods
Increase haematocrit level: >20%
Progressive leukopenia (can have severe neutropenia)
Raid decrease in platelet count
Metabolic acidosis
What are the features of the recovery phase for dengue?
Gradual absorption of extravascular compartment fluid in next 48-72h
Rash of ‘white islands in sea of red’
Generalised pruritus
Hypervolaemia if excessive IV fluid therapy -> pulmonary oedema, CCF
Bradycardia
Bloods
Haematocrit rises
WCC rises, and platelets rise later
What is the tourniquet test?
Test for dengue -
Test for capillary fragility
Petechiae appear after 2min, after inflating blood pressure cuff for 5mins, then release for 2mins.
What is the most important risk factor for severe dengue?
Most important risk factor: previous infection by other serotype
Other:
Young age, elderly
Female sex, pregnancy
Infants with primary infection born to dengue-immune mothers
Virus strain
Genetic variants of HLA
Increased interval between infections
Comorbidities: asthma, diabetes, HTN, sickle-cell
What is the definition of dengue haemorrhagic fever?
4 criteria:
Fever
Haemorrhagic manifestations
Thrombocytopenia
Evidence of increased capillary leak
How is dengue classified?
What are the main diagnostic tests for dengue?
NS1 (non-structural protein 1) capture ELISA (day 3-5)
IgM antibody ELISA (day 5 onwards)
Other:
PCR+
Viral culture+
IgM seroconversion in pair sera
IgG seroconversion in paired sera or 4-fold titre increase in paired sera
What does the dengue rapid test test for?
Combine NS1 antigen detection, and IgM detection
Which dengue patients need to be managed as inpatients?
Warning signs
Co-existing conditions that may complicate dengue
Live far from health facility
What is the vector for chickungunya?
Aedes agypti - stripes
What kind of virus is chickungunya?
Togavirus, Arbovirus, Alphavirus
Arbovirus - arthropod born virus
Symptoms of chickungunya?
Asympt or undifferentiated fever
Encephalitis (esp New World)
EEE, WEE, VEE, Semliki Forest
Fever, arthritis, rash (esp Old World)
What are the arthritogenic alpha viruses?
Chikungunya
O’nyong’nyong
Marayo fever - indistinguishable from chikungunga
Ross River
Sindbhi
Where is the hot spots for chickungunya?
Greatest numbers in South America, India, Indonesia
Symptoms of chickungunya?
Fevere, myalgia, rash - lasting for 1 week
polyarthralgia and arthritis - lasting weeks to months
Clinical presentation of arthralgia in chick?
Fever may be biphasic
Polyarthralgia symmetrical esp hands,
wrists, knees, and ankles often >10 joints
May present with tenosynovitis.
Last over 6 months
Difference of chickungunya to dengue?
Chickungunya:
- more rash
- more arthritis/arthralgia
- less haemorrhage
- less thrombocytopenia, not haemoconcentration
What rare and sinister complications of chickungunya may occur?
meningo-encephalitis cases in Brazil and India
Also associated with transverse myelitis
Investigations for chickungunya
What is the Rx for chickungunya?
Supportive!
NSAIDs
Persistent arthritis may require low dose steroids or disease modifying agents (MTX, sulfasalazine, hydroxychloroquine, anti-TNF agents)
What type of virus is Zika virus?
Arbovirus - Flavivirus
What is the problem with Zika?
Microcephaly in first trimester if pregnant - congenital zika syndrome
What is relationship between dengue and zika?
Areas where there is more dengue, less incidence of zika
How is dengue transmitted?
Mostly via mosquito vectors - aedes agypti mosquito
Sexual transmission - persists in semen for 6 months
Transplacental and perinatal infection
Blood transfusion
Symptoms of zika?
Fever, myalgia, arthralgia, rash, conjunctivitis
Rash different between zika and other arboviruses?
Maculopapular in zika, mild illness, lower fever and conjunctivitis
Chikungunya - symptomatic fever, arthralgias, rash
Differentiating zika from other viruses?
Increased chance of conjunctivitis
Increased rash and rash is different
Do not get haemorrhage
What are the congenital sequalae of Zika virus?
miscarriage, Fetal stillborn, prematurity
Microcephaly
Disabilities, small for age
Dysmorphic features
Joint problems, talipes
Strabismus, chorioretinitis
What do you see on CT/MRI of congenital zika syndrome?
Calcifications
Atrophy ± ventriculomegaly
Complication in mother from Zika?
Gillian Barre
Testing for Zika?
PCR - Urine more sensitive than serum for ZIKA <14 days
IgM antibody however cross reactivity >14 days
When do you test for zika in asymptomatic patient?
NAT 3 x during pregnancy
If PCR positive - definitive
If PCR negative, check IgM to all flaviviruses
How do you ensure that when you get a positive PCR for zika/dengue/chick it is real?
See table
How would you ensure the result is real if positive IgM for chick/zika/dengue?
plaque reduction neutralisation test
∆∆ for fever in returning traveller with meningoencephalitis
Viral meningitis
Bacterial meningits
Viral =
Dengue
Acute HIV
JE
West Nile virus
Zika
YF
Chickungunya
Can someone with JE have PMNs on their LP?
Yes - often initially have PMNs and then as disease progresses -> lymphocyte
How do you diagnose JE?
IgM (sens >90%)
PCR +ve viraemia only early on in disease (symptoms appear when viraemia coming down)
Where do you get JE?
Rural Asia and Western pacific where rice farming and pig faming exist
What is the usual presentation of JE?
Asymptomatic! (<1% develop clinical disease)
Presents with encephalitis, aseptic meningitis, acute flaccid paralysis
Risk factors for JE
Prolonged stays
Rural stay
Transmission?
Usually In monsoon season
What is the problem with IgM testing for JE?
Cross reactivity of IgM to dengue, Yellow fever, WNV, tick borne encephalitis (yellow virus)
Must confirm diagnosis
If catch JE what is outcomes?
30% die
50% neurological sequalae
20% recover
What is the vaccine for JE?
2 doses
28 days apart
Management of JE?
Prevention - vaccine
Supportive Rx
Serology test for JE - where is it best to test from?
CSF > blood
What are other flaviviruses?
Dengue, JE, YF, WNV
Symptoms of WNV?
80% asymptomatic
Neuroinvasive disease
Investigations for WNV?
Serology
Which virus common in Europe?
Tick borne encephalitis
Viral causes of encephalitis?
HSV, other Herpes viruses
Paramyxoviruses (SSPE, Henepahvirus)
Rabies
Arboviruses (flaviviruses, alpha viruses, Chik)
Flaviviruses?
JE
Dengue
YF
West Nile
Tick borne encephalitis
Where is JE?
South East Asia
Epidemic in some parts - Japan, Taiwan, Korea, China
Endemic in other parts - tropical - Malaysia, Thailand
Vector for JE?
Culex species
Hosts for JE?
Humans are dead end hosts
Herons and birds
What is an amplifying host for JE?
Pig
Virus replicates ++++
Clinical presentation of JE?
- 6 to 16 day incubation period
- Fever, chills, nausea, vomiting
- Days later neurologic disease: Photophobia, confusion, seizures
Neurological sequalae of JE?
Meningitis
Encephalitis
Acute Flaccid Paralysis (polio-like)
Ascending paralysis (Guillian-Barré)
Classic JE LP?
normal or raised protein, pleocytosis (<500) mainly lymphs
normal glucose
MRI findings of JE?
bilateral thalamic
and basal ganglia
involvement
Best diagnostic test for JE?
CSF IgM
Who should be vaccinated for JE?
Endemic areas, ≤17 yo
Vaccine recommended for travel >4 wks to endemic region during transmission season
What type of virus is influenza?
Orthomyxovirus family
* enveloped RNA with a segmented genome
Two strains infect humans:
A is most important: 16 HAs and 9 NA (also affects loads of animals)
B has two major types (Victoria & Yamagata)
Which strain infects birds and humans?
2,3 linkage HA influenza - gut epithelium of birds and (rare) lower airway of humans
What is genetic drift in virology?
increased immunity = increased mutations
H3N2 classically do this
What is genetic shift in virlogy?
When avian strains and human strains combine to produce sequences that are mixed to both (most to dangerous)
Four subtypes causing human disease?
H1N1, H1N2, H2N2, H3N2
Only 1 subtype will actively circulate
Most severe of the influenza virus subtypes?
H3N2 - most fatal against elderly
H1N1 exception to this
Complications one influenza?
Viral pneumonia ±ARDS (‘cytokine storm)
Encephalopathy
Pericarditis
Rhabdomyolysis
Secondary bacterial pneumonia (late 7-21 days)
Guillain Barré Syndrome
Post-infectious encephalomyelitis
Atypical symptoms of influenza?
Children - GI
Also pneumonia
What diseases will you die from
Agamma-globulinaemic
- Enteroviruses
- Pneumococcus, meningococcus, H.influenza (encapsulated)
- Giardia
All other pathogens develop cellular responses
What is the R0?
Basic reproduction rate
How many infections will occur if an individual with a disease enters a susceptible population
Antivirals - classes for influenza?
M2 ion channel blockers (amatidine, rimantidine)
- Complete resistance now exist because of giving these drugs to animals. Class resistance exists
Neuroaminidase inhibitors- oseltamivir (Tamiflu™)
- Resistance exists but no class resistance
Inhibition of polymerase acidic endonuclease
What is the value of antivirals?
Slow spread from person to person
Issues with egg based vaccines?
- delays in adapting strains to eggs
- adaptation to eggs changes antigens
- problems with scale-up in the event of a pandemic
- egg allergy (low risk if mild allergy)
- Guillain-Barré Syndrome
Which influenza vaccines for the elderly?
High dose IIV and new recombinant vaccine better in the elderly
What are the enteroviruses?
Polio viruses (1, 2, 3)
Coxsackie viruses
Echoviruses
Enteroviruses (hep A - EV 72)
Transmission of enteroviruses?
Ingestion and aerosol
Primary viraemia
Secondary viraemia in target organ - brain (polio), coxsackie and polio (meninges), hepatitis (liver)
All viruses can go everywhere
Which disease causes hand foot and mouth disease?
EV71
How can you Rx severe infection with enteroviruses?
IVIG (needs antibodies) specific to that enterovirus
Presentation of enteroviruses?
Rash on hands
Foruncles on hands
Lesions in mouth and palate
Dermatitis (Eczema cockasckium)
What causes viral myocarditis?
Cocksackie B infection (summer months and selenium deficiency)
What causes acute flaccid paralysis?
Polio virus
enterovirus 71 most frequent
enterovirus 13
coxsackievirus B5
Rx of most viruses
Ribavarin
Reservoir and transmission of polio?
Humans are the only reservoir
Fecal - oral route (WPV1) or vaccine
Polio symptoms?
Mild gastroentreritis
* Minor diarrhea with no dehydration
Painless, flaccid paralysis due to anterior horn infection
* Usually single limb
* Rare bulbar – quadriplegia - paralysis of resp muscles
* Post polio syndrome
What is the advantage of OPV vs IPV?
Spread from vaccinee to close contacts
No needles involved
Problem with OPV?
OPV has capacity to ‘reclaim’ environmental niche (cVDPV)
OPV may persist in immunocompromised for years
What type of virus is measles/mumps?
Paramyxovirus (rubella is togavirus)
What is the most contagious virus?
measles
Symptoms of measles?
Febrile illness with rash - Koplicks spots - macularpapular rash, cough, coryza, conjunctivitis viral pneumonia, diarrhoea, listless
Neurologic involvement - subacute sclerosing panencephalitis, post-infectious encephalomyelitis
Immunocompromised: encephalitis, pneumonitis
Why do children in developing countries develop blindness?
Vitamin A deficiency - commonest cause of blindness
Corenal dissolution (if have bitots spots on eye exam)
Risk factors for mortality in measles?
Malnutrition
Crowding & order of infection (inoculum) (child who gets it last in family)
Female sex (natural disease and high-titer vaccines)
Cause of death in measles?
pneumonia, encephalitis
What is skin disease in measles?
White dot with red base
Maculopapular rash. Starts behind ears. Peels off (desquamation)
Who are at risk in measles infection?
Measles in newborns of mothers with clinical measles (mother has not passed any antibodies to baby - not vaccinated)
Treatment of measles? Who?
Normally no therapy required
However - ‘in areas with mortality > 1%’ - Vitamin A for 2 days
Which IgG pass from mother to child and when?
IgG1
Last 2-3 weeks of pregnancy
Measles vaccine - biggest problem in developing countries?
Absolutely needs cold chain
Live attenuated vaccines - why is timing important? - including measles
Interference from maternal antibody (will impair babies ability to form antibodies)
Clinical presentation of mumps?
Parotiditis
Encephalomyelitis
Post infectious Encephalomyelitis
Orchitis and oopharatis - unilateral (if bilateral, sterility)
How does rubella present?
Mild febrile illness with rash
Arthralgia (esp if post puberty)
What is the issue if a patient presents with rubella?
Congenital rubella syndrome (early in pregnancy)
- deafness, cataracts
Why is vaccine important to prevent Congenital rubella syndrome?
An unsuccessful vaccination program (<90% coverage will increase the CRS rate
Stages of yellow fever infection?
Infection
Remission
Intoxication
Genotypes of yellow fever?
Type 1 (west Africa and South America) and Type 2 (East and South Africa)
Vector for Yellow Fever?
Aedes agypti
Incubation period and symptoms/pattern of disease of YF?
3-6 days
Flu like illness
1-2 days feeling well again
THEN
Haemorrhagic fever 5-10% and severe organ complications
Symptoms of intoxication phase of YF?
Fever
Vomiting, coffee ground/bleeding
Abdominal pain, jaundice, hepatomegaly
Shock, decreased GCS
Renal failure
Lab results in YF?
High bilirubin
High AST>ALT
Diagnosis of YF?
Serology for YF
PCR
∆∆ YF
Dengue
Malaria
Acute viral hepatitis particularly Hep D on top of Hep B
Salmonella
Brucella
Lepto
Serious risks of YF vaccine?
YEL-AVD and YEL-AND (associated neurotropic and and visceral disease)
neurotrophic side effects?
2-30 days after vaccine
Children more common
Meningitis, cranial nerve palsies, GBS
Viscerotropic side effects - what are they?
Get it if older (>60)
Rapidly progressing multi organ failure and death
Very poor prognosis
Absolute contraindications for YF vaccine?
Transplant
Patients on monoclonal antibodies
Primary immunodeficiency
Children <6 months
Breastfeeding
Caution:
Infants 6-8 months
Age >60
Pregnant
HIV/AIDS
Nipah virus - where? Reservoir? Transmission?
Bangladesh, india
Fruit bat - date palm sap
Intermediate host - pig
Human to human transmission or bat secretions
Clinical presentation of Nipah?
Non specific febrile illness
Plus neurological component
