Viruses Flashcards

1
Q

What type of organism is dengue?

A

Single chain RNA flavovirus

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2
Q

What is the vector for dengue?

A

Aedes Aegypti mosquito
Day biting urban mosquitos

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3
Q

Which viral protein allows entry into the dengue cell?

A

E - envelope

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4
Q

What serotypes of dengue exist

A

1,2,3,4

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5
Q

What is the incubation period for dengue?

A

4-7 days

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6
Q

What are the phases of dengue illness?

A

Day 1-3 Febrile
Day 4-5 Critical
Day 6-10 Recovery

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7
Q

What are the features of the critical phase in dengue illness?

A

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

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8
Q

What are the features of the recovery phase for dengue?

A

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

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9
Q

What is the tourniquet test?

A

Test for dengue -
Test for capillary fragility
Petechiae appear after 2min, after inflating blood pressure cuff for 5mins, then release for 2mins.

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10
Q

What is the most important risk factor for severe dengue?

A

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

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11
Q

What is the definition of dengue haemorrhagic fever?

A

4 criteria:
Fever
Haemorrhagic manifestations
Thrombocytopenia
Evidence of increased capillary leak

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12
Q

How is dengue classified?

A
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13
Q

What are the main diagnostic tests for dengue?

A

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

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14
Q

What does the dengue rapid test test for?

A

Combine NS1 antigen detection, and IgM detection

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15
Q

Which dengue patients need to be managed as inpatients?

A

Warning signs
Co-existing conditions that may complicate dengue
Live far from health facility

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16
Q

What is the vector for chickungunya?

A

Aedes agypti - stripes

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17
Q

What kind of virus is chickungunya?

A

Togavirus, Arbovirus, Alphavirus
Arbovirus - arthropod born virus

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18
Q

Symptoms of chickungunya?

A

Asympt or undifferentiated fever
Encephalitis (esp New World)
EEE, WEE, VEE, Semliki Forest
Fever, arthritis, rash (esp Old World)

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19
Q

What are the arthritogenic alpha viruses?

A

Chikungunya
O’nyong’nyong
Marayo fever - indistinguishable from chikungunga
Ross River
Sindbhi

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20
Q

Where is the hot spots for chickungunya?

A

Greatest numbers in South America, India, Indonesia

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21
Q

Symptoms of chickungunya?

A

Fevere, myalgia, rash - lasting for 1 week
polyarthralgia and arthritis - lasting weeks to months

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22
Q

Clinical presentation of arthralgia in chick?

A

Fever may be biphasic
Polyarthralgia symmetrical esp hands,
wrists, knees, and ankles often >10 joints
May present with tenosynovitis.
Last over 6 months

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23
Q

Difference of chickungunya to dengue?

A

Chickungunya:
- more rash
- more arthritis/arthralgia
- less haemorrhage
- less thrombocytopenia, not haemoconcentration

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24
Q

What rare and sinister complications of chickungunya may occur?

A

meningo-encephalitis cases in Brazil and India
Also associated with transverse myelitis

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25
Q

Investigations for chickungunya

A
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26
Q

What is the Rx for chickungunya?

A

Supportive!
NSAIDs
Persistent arthritis may require low dose steroids or disease modifying agents (MTX, sulfasalazine, hydroxychloroquine, anti-TNF agents)

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27
Q

What type of virus is Zika virus?

A

Arbovirus - Flavivirus

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28
Q

What is the problem with Zika?

A

Microcephaly in first trimester if pregnant - congenital zika syndrome

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29
Q

What is relationship between dengue and zika?

A

Areas where there is more dengue, less incidence of zika

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30
Q

How is dengue transmitted?

A

Mostly via mosquito vectors - aedes agypti mosquito
Sexual transmission - persists in semen for 6 months
Transplacental and perinatal infection
Blood transfusion

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31
Q

Symptoms of zika?

A

Fever, myalgia, arthralgia, rash, conjunctivitis

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32
Q

Rash different between zika and other arboviruses?

A

Maculopapular in zika, mild illness, lower fever and conjunctivitis

Chikungunya - symptomatic fever, arthralgias, rash

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33
Q

Differentiating zika from other viruses?

A

Increased chance of conjunctivitis
Increased rash and rash is different
Do not get haemorrhage

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34
Q

What are the congenital sequalae of Zika virus?

A

miscarriage, Fetal stillborn, prematurity
Microcephaly
Disabilities, small for age
Dysmorphic features
Joint problems, talipes
Strabismus, chorioretinitis

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35
Q

What do you see on CT/MRI of congenital zika syndrome?

A

Calcifications
Atrophy ± ventriculomegaly

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36
Q

Complication in mother from Zika?

A

Gillian Barre

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37
Q

Testing for Zika?

A

PCR - Urine more sensitive than serum for ZIKA <14 days
IgM antibody however cross reactivity >14 days

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38
Q

When do you test for zika in asymptomatic patient?

A

NAT 3 x during pregnancy
If PCR positive - definitive
If PCR negative, check IgM to all flaviviruses

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39
Q

How do you ensure that when you get a positive PCR for zika/dengue/chick it is real?

A

See table

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40
Q

How would you ensure the result is real if positive IgM for chick/zika/dengue?

A

plaque reduction neutralisation test

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41
Q

∆∆ for fever in returning traveller with meningoencephalitis

A

Viral meningitis
Bacterial meningits

Viral =
Dengue
Acute HIV
JE
West Nile virus
Zika
YF
Chickungunya

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42
Q

Can someone with JE have PMNs on their LP?

A

Yes - often initially have PMNs and then as disease progresses -> lymphocyte

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43
Q

How do you diagnose JE?

A

IgM (sens >90%)

PCR +ve viraemia only early on in disease (symptoms appear when viraemia coming down)

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44
Q

Where do you get JE?

A

Rural Asia and Western pacific where rice farming and pig faming exist

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45
Q

What is the usual presentation of JE?

A

Asymptomatic! (<1% develop clinical disease)

Presents with encephalitis, aseptic meningitis, acute flaccid paralysis

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46
Q

Risk factors for JE

A

Prolonged stays
Rural stay

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47
Q

Transmission?

A

Usually In monsoon season

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48
Q

What is the problem with IgM testing for JE?

A

Cross reactivity of IgM to dengue, Yellow fever, WNV, tick borne encephalitis (yellow virus)

Must confirm diagnosis

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49
Q

If catch JE what is outcomes?

A

30% die
50% neurological sequalae
20% recover

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50
Q

What is the vaccine for JE?

A

2 doses
28 days apart

51
Q

Management of JE?

A

Prevention - vaccine
Supportive Rx

52
Q

Serology test for JE - where is it best to test from?

A

CSF > blood

53
Q

What are other flaviviruses?

A

Dengue, JE, YF, WNV

54
Q

Symptoms of WNV?

A

80% asymptomatic
Neuroinvasive disease

55
Q

Investigations for WNV?

A

Serology

56
Q

Which virus common in Europe?

A

Tick borne encephalitis

57
Q

Viral causes of encephalitis?

A

HSV, other Herpes viruses
Paramyxoviruses (SSPE, Henepahvirus)
Rabies
Arboviruses (flaviviruses, alpha viruses, Chik)

58
Q

Flaviviruses?

A

JE
Dengue
YF
West Nile
Tick borne encephalitis

59
Q

Where is JE?

A

South East Asia
Epidemic in some parts - Japan, Taiwan, Korea, China
Endemic in other parts - tropical - Malaysia, Thailand

60
Q

Vector for JE?

A

Culex species

61
Q

Hosts for JE?

A

Humans are dead end hosts

Herons and birds

62
Q

What is an amplifying host for JE?

A

Pig
Virus replicates ++++

63
Q

Clinical presentation of JE?

A
  • 6 to 16 day incubation period
  • Fever, chills, nausea, vomiting
  • Days later neurologic disease: Photophobia, confusion, seizures
64
Q

Neurological sequalae of JE?

A

Meningitis
Encephalitis
Acute Flaccid Paralysis (polio-like)
Ascending paralysis (Guillian-Barré)

65
Q

Classic JE LP?

A

normal or raised protein, pleocytosis (<500) mainly lymphs
normal glucose

66
Q

MRI findings of JE?

A

bilateral thalamic
and basal ganglia
involvement

67
Q

Best diagnostic test for JE?

A

CSF IgM

68
Q

Who should be vaccinated for JE?

A

Endemic areas, ≤17 yo
Vaccine recommended for travel >4 wks to endemic region during transmission season

69
Q

What type of virus is influenza?

A

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)

70
Q

Which strain infects birds and humans?

A

2,3 linkage HA influenza - gut epithelium of birds and (rare) lower airway of humans

71
Q

What is genetic drift in virology?

A

increased immunity = increased mutations
H3N2 classically do this

72
Q

What is genetic shift in virlogy?

A

When avian strains and human strains combine to produce sequences that are mixed to both (most to dangerous)

73
Q

Four subtypes causing human disease?

A

H1N1, H1N2, H2N2, H3N2
Only 1 subtype will actively circulate

74
Q

Most severe of the influenza virus subtypes?

A

H3N2 - most fatal against elderly
H1N1 exception to this

75
Q

Complications one influenza?

A

Viral pneumonia ±ARDS (‘cytokine storm)
Encephalopathy
Pericarditis
Rhabdomyolysis
Secondary bacterial pneumonia (late 7-21 days)
Guillain Barré Syndrome
Post-infectious encephalomyelitis

76
Q

Atypical symptoms of influenza?

A

Children - GI
Also pneumonia

77
Q

What diseases will you die from

A

Agamma-globulinaemic

  • Enteroviruses
  • Pneumococcus, meningococcus, H.influenza (encapsulated)
  • Giardia

All other pathogens develop cellular responses

78
Q

What is the R0?

A

Basic reproduction rate
How many infections will occur if an individual with a disease enters a susceptible population

79
Q

Antivirals - classes for influenza?

A

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

80
Q

What is the value of antivirals?

A

Slow spread from person to person

81
Q

Issues with egg based vaccines?

A
  • 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
82
Q

Which influenza vaccines for the elderly?

A

High dose IIV and new recombinant vaccine better in the elderly

83
Q

What are the enteroviruses?

A

Polio viruses (1, 2, 3)
Coxsackie viruses
Echoviruses
Enteroviruses (hep A - EV 72)

84
Q

Transmission of enteroviruses?

A

Ingestion and aerosol
Primary viraemia
Secondary viraemia in target organ - brain (polio), coxsackie and polio (meninges), hepatitis (liver)

All viruses can go everywhere

85
Q

Which disease causes hand foot and mouth disease?

A

EV71

86
Q

How can you Rx severe infection with enteroviruses?

A

IVIG (needs antibodies) specific to that enterovirus

87
Q

Presentation of enteroviruses?

A

Rash on hands
Foruncles on hands
Lesions in mouth and palate
Dermatitis (Eczema cockasckium)

88
Q

What causes viral myocarditis?

A

Cocksackie B infection (summer months and selenium deficiency)

89
Q

What causes acute flaccid paralysis?

A

Polio virus
enterovirus 71 most frequent
enterovirus 13
coxsackievirus B5

90
Q

Rx of most viruses

A

Ribavarin

91
Q

Reservoir and transmission of polio?

A

Humans are the only reservoir
Fecal - oral route (WPV1) or vaccine

92
Q

Polio symptoms?

A

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

93
Q

What is the advantage of OPV vs IPV?

A

Spread from vaccinee to close contacts
No needles involved

94
Q

Problem with OPV?

A

OPV has capacity to ‘reclaim’ environmental niche (cVDPV)
OPV may persist in immunocompromised for years

95
Q

What type of virus is measles/mumps?

A

Paramyxovirus (rubella is togavirus)

96
Q

What is the most contagious virus?

A

measles

97
Q

Symptoms of measles?

A

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

98
Q

Why do children in developing countries develop blindness?

A

Vitamin A deficiency - commonest cause of blindness
Corenal dissolution (if have bitots spots on eye exam)

99
Q

Risk factors for mortality in measles?

A

Malnutrition
Crowding & order of infection (inoculum) (child who gets it last in family)
Female sex (natural disease and high-titer vaccines)

100
Q

Cause of death in measles?

A

pneumonia, encephalitis

101
Q

What is skin disease in measles?

A

White dot with red base
Maculopapular rash. Starts behind ears. Peels off (desquamation)

102
Q

Who are at risk in measles infection?

A

Measles in newborns of mothers with clinical measles (mother has not passed any antibodies to baby - not vaccinated)

103
Q

Treatment of measles? Who?

A

Normally no therapy required
However - ‘in areas with mortality > 1%’ - Vitamin A for 2 days

104
Q

Which IgG pass from mother to child and when?

A

IgG1
Last 2-3 weeks of pregnancy

105
Q

Measles vaccine - biggest problem in developing countries?

A

Absolutely needs cold chain

106
Q

Live attenuated vaccines - why is timing important? - including measles

A

Interference from maternal antibody (will impair babies ability to form antibodies)

107
Q

Clinical presentation of mumps?

A

Parotiditis
Encephalomyelitis
Post infectious Encephalomyelitis
Orchitis and oopharatis - unilateral (if bilateral, sterility)

108
Q

How does rubella present?

A

Mild febrile illness with rash
Arthralgia (esp if post puberty)

109
Q

What is the issue if a patient presents with rubella?

A

Congenital rubella syndrome (early in pregnancy)
- deafness, cataracts

110
Q

Why is vaccine important to prevent Congenital rubella syndrome?

A

An unsuccessful vaccination program (<90% coverage will increase the CRS rate

111
Q

Stages of yellow fever infection?

A

Infection
Remission
Intoxication

112
Q

Genotypes of yellow fever?

A

Type 1 (west Africa and South America) and Type 2 (East and South Africa)

113
Q

Vector for Yellow Fever?

A

Aedes agypti

114
Q

Incubation period and symptoms/pattern of disease of YF?

A

3-6 days
Flu like illness
1-2 days feeling well again
THEN
Haemorrhagic fever 5-10% and severe organ complications

115
Q

Symptoms of intoxication phase of YF?

A

Fever
Vomiting, coffee ground/bleeding
Abdominal pain, jaundice, hepatomegaly
Shock, decreased GCS
Renal failure

116
Q

Lab results in YF?

A

High bilirubin
High AST>ALT

117
Q

Diagnosis of YF?

A

Serology for YF
PCR

118
Q

∆∆ YF

A

Dengue
Malaria
Acute viral hepatitis particularly Hep D on top of Hep B
Salmonella
Brucella
Lepto

119
Q

Serious risks of YF vaccine?

A

YEL-AVD and YEL-AND (associated neurotropic and and visceral disease)

120
Q

neurotrophic side effects?

A

2-30 days after vaccine
Children more common
Meningitis, cranial nerve palsies, GBS

121
Q

Viscerotropic side effects - what are they?

A

Get it if older (>60)
Rapidly progressing multi organ failure and death
Very poor prognosis

122
Q

Absolute contraindications for YF vaccine?

A

Transplant
Patients on monoclonal antibodies
Primary immunodeficiency
Children <6 months
Breastfeeding

Caution:
Infants 6-8 months
Age >60
Pregnant
HIV/AIDS

123
Q

Nipah virus - where? Reservoir? Transmission?

A

Bangladesh, india
Fruit bat - date palm sap
Intermediate host - pig
Human to human transmission or bat secretions

124
Q

Clinical presentation of Nipah?

A

Non specific febrile illness
Plus neurological component