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
Investigations for chickungunya
26
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)
27
What type of virus is Zika virus?
Arbovirus - Flavivirus
28
What is the problem with Zika?
Microcephaly in first trimester if pregnant - congenital zika syndrome
29
What is relationship between dengue and zika?
Areas where there is more dengue, less incidence of zika
30
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
31
Symptoms of zika?
Fever, myalgia, arthralgia, rash, conjunctivitis
32
Rash different between zika and other arboviruses?
Maculopapular in zika, mild illness, lower fever and conjunctivitis Chikungunya - symptomatic fever, *arthralgias*, rash
33
Differentiating zika from other viruses?
Increased chance of conjunctivitis Increased rash and rash is different Do not get haemorrhage
34
What are the congenital sequalae of Zika virus?
miscarriage, Fetal stillborn, prematurity Microcephaly Disabilities, small for age Dysmorphic features Joint problems, talipes Strabismus, chorioretinitis
35
What do you see on CT/MRI of congenital zika syndrome?
Calcifications Atrophy ± ventriculomegaly
36
Complication in mother from Zika?
Gillian Barre
37
Testing for Zika?
PCR - Urine more sensitive than serum for ZIKA <14 days IgM antibody however cross reactivity >14 days
38
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
39
How do you ensure that when you get a positive PCR for zika/dengue/chick it is real?
See table
40
How would you ensure the result is real if positive IgM for chick/zika/dengue?
plaque reduction neutralisation test
41
∆∆ for fever in returning traveller with meningoencephalitis
Viral meningitis Bacterial meningits Viral = Dengue Acute HIV JE West Nile virus Zika YF Chickungunya
42
Can someone with JE have PMNs on their LP?
Yes - often initially have PMNs and then as disease progresses -> lymphocyte
43
How do you diagnose JE?
IgM (sens >90%) PCR +ve viraemia only early on in disease (symptoms appear when viraemia coming down)
44
Where do you get JE?
Rural Asia and Western pacific where rice farming and pig faming exist
45
What is the usual presentation of JE?
Asymptomatic! (<1% develop clinical disease) Presents with encephalitis, aseptic meningitis, acute flaccid paralysis
46
Risk factors for JE
Prolonged stays Rural stay
47
Transmission?
Usually In monsoon season
48
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
49
If catch JE what is outcomes?
30% die 50% neurological sequalae 20% recover
50
What is the vaccine for JE?
2 doses 28 days apart
51
Management of JE?
Prevention - vaccine Supportive Rx
52
Serology test for JE - where is it best to test from?
CSF > blood
53
What are other flaviviruses?
Dengue, JE, YF, WNV
54
Symptoms of WNV?
80% asymptomatic Neuroinvasive disease
55
Investigations for WNV?
Serology
56
Which virus common in Europe?
Tick borne encephalitis
57
Viral causes of encephalitis?
HSV, other Herpes viruses Paramyxoviruses (SSPE, Henepahvirus) Rabies Arboviruses (flaviviruses, alpha viruses, Chik)
58
Flaviviruses?
JE Dengue YF West Nile Tick borne encephalitis
59
Where is JE?
South East Asia Epidemic in some parts - Japan, Taiwan, Korea, China Endemic in other parts - tropical - Malaysia, Thailand
60
Vector for JE?
Culex species
61
Hosts for JE?
Humans are dead end hosts Herons and birds
62
What is an amplifying host for JE?
Pig Virus replicates ++++
63
Clinical presentation of JE?
- 6 to 16 day incubation period - Fever, chills, nausea, vomiting - Days later neurologic disease: Photophobia, confusion, seizures
64
Neurological sequalae of JE?
Meningitis Encephalitis Acute Flaccid Paralysis (polio-like) Ascending paralysis (Guillian-Barré)
65
Classic JE LP?
normal or raised protein, pleocytosis (<500) mainly lymphs normal glucose
66
MRI findings of JE?
bilateral thalamic and basal ganglia involvement
67
Best diagnostic test for JE?
CSF IgM
68
Who should be vaccinated for JE?
Endemic areas, ≤17 yo Vaccine recommended for travel >4 wks to endemic region during transmission season
69
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)
70
Which strain infects birds and humans?
2,3 linkage HA influenza - gut epithelium of birds and (rare) lower airway of humans
71
What is genetic drift in virology?
increased immunity = increased mutations H3N2 classically do this
72
What is genetic shift in virlogy?
When avian strains and human strains combine to produce sequences that are mixed to both (most to dangerous)
73
Four subtypes causing human disease?
H1N1, H1N2, H2N2, H3N2 Only 1 subtype will actively circulate
74
Most severe of the influenza virus subtypes?
H3N2 - most fatal against elderly H1N1 exception to this
75
Complications one influenza?
Viral pneumonia ±ARDS (‘cytokine storm) Encephalopathy Pericarditis Rhabdomyolysis Secondary bacterial pneumonia (late 7-21 days) Guillain Barré Syndrome Post-infectious encephalomyelitis
76
Atypical symptoms of influenza?
Children - GI Also pneumonia
77
What diseases will you die from
Agamma-globulinaemic - Enteroviruses - Pneumococcus, meningococcus, H.influenza (encapsulated) - Giardia All other pathogens develop cellular responses
78
What is the R0?
Basic reproduction rate How many infections will occur if an individual with a disease enters a susceptible population
79
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
80
What is the value of antivirals?
Slow spread from person to person
81
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
82
Which influenza vaccines for the elderly?
High dose IIV and new recombinant vaccine better in the elderly
83
What are the enteroviruses?
Polio viruses (1, 2, 3) Coxsackie viruses Echoviruses Enteroviruses (hep A - EV 72)
84
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
85
Which disease causes hand foot and mouth disease?
EV71
86
How can you Rx severe infection with enteroviruses?
IVIG (needs antibodies) specific to that enterovirus
87
Presentation of enteroviruses?
Rash on hands Foruncles on hands Lesions in mouth and palate Dermatitis (Eczema cockasckium)
88
What causes viral myocarditis?
Cocksackie B infection (summer months and selenium deficiency)
89
What causes acute flaccid paralysis?
Polio virus enterovirus 71 most frequent enterovirus 13 coxsackievirus B5
90
Rx of most viruses
Ribavarin
91
Reservoir and transmission of polio?
Humans are the only reservoir Fecal - oral route (WPV1) or vaccine
92
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
93
What is the advantage of OPV vs IPV?
Spread from vaccinee to close contacts No needles involved
94
Problem with OPV?
OPV has capacity to ‘reclaim’ environmental niche (cVDPV) OPV may persist in immunocompromised for years
95
What type of virus is measles/mumps?
Paramyxovirus (rubella is togavirus)
96
What is the most contagious virus?
measles
97
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
98
Why do children in developing countries develop blindness?
Vitamin A deficiency - commonest cause of blindness Corenal dissolution (if have bitots spots on eye exam)
99
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)
100
Cause of death in measles?
pneumonia, encephalitis
101
What is skin disease in measles?
White dot with red base Maculopapular rash. Starts behind ears. Peels off (desquamation)
102
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)
103
Treatment of measles? Who?
Normally no therapy required However - ‘in areas with mortality > 1%’ - Vitamin A for 2 days
104
Which IgG pass from mother to child and when?
IgG1 Last 2-3 weeks of pregnancy
105
Measles vaccine - biggest problem in developing countries?
Absolutely needs cold chain
106
Live attenuated vaccines - why is timing important? - including measles
Interference from maternal antibody (will impair babies ability to form antibodies)
107
Clinical presentation of mumps?
Parotiditis Encephalomyelitis Post infectious Encephalomyelitis Orchitis and oopharatis - unilateral (if bilateral, sterility)
108
How does rubella present?
Mild febrile illness with rash Arthralgia (esp if post puberty)
109
What is the issue if a patient presents with rubella?
Congenital rubella syndrome (early in pregnancy) - deafness, cataracts
110
Why is vaccine important to prevent Congenital rubella syndrome?
An unsuccessful vaccination program (<90% coverage will increase the CRS rate
111
Stages of yellow fever infection?
Infection Remission Intoxication
112
Genotypes of yellow fever?
Type 1 (west Africa and South America) and Type 2 (East and South Africa)
113
Vector for Yellow Fever?
Aedes agypti
114
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
115
Symptoms of intoxication phase of YF?
Fever Vomiting, coffee ground/bleeding Abdominal pain, jaundice, hepatomegaly Shock, decreased GCS Renal failure
116
Lab results in YF?
High bilirubin High AST>ALT
117
Diagnosis of YF?
Serology for YF PCR
118
∆∆ YF
Dengue Malaria Acute viral hepatitis particularly Hep D on top of Hep B Salmonella Brucella Lepto
119
Serious risks of YF vaccine?
YEL-AVD and YEL-AND (associated neurotropic and and visceral disease)
120
neurotrophic side effects?
2-30 days after vaccine Children more common Meningitis, cranial nerve palsies, GBS
121
Viscerotropic side effects - what are they?
Get it if older (>60) Rapidly progressing multi organ failure and death Very poor prognosis
122
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
123
Nipah virus - where? Reservoir? Transmission?
Bangladesh, india Fruit bat - date palm sap Intermediate host - pig Human to human transmission or bat secretions
124
Clinical presentation of Nipah?
Non specific febrile illness Plus neurological component