Virology Flashcards
1
Q
- Virology:
- What virus causes rabies (Family and genus)?
- What kind of virus?
A
- Family: Rhabdoviridae (‘rhabdo’ = ‘rod’)
- Genus: Lyssavirus (‘lyssa’ = rage)
- Negative sense RNA
- Geography: Worldwide
- Natural Cycle: reservoirs in bats, raccoons, dogs, various mammals
- most commonly infects man via dog bites, occasionally bat bites
- Human Disease: ascending encephalitis, fatal once symptomatic
2
Q
How many genotypes of lyssavirus and what do they do?
A
- Rabies virus - widespread - dog, fox, raccoon, bat etc
- Lagos bat virus - Africa - bats, cats
- Mokola virus - Africa - shrews, cats
- Duvenhage virus Africa
- European bat Lyssavirus, Type 1
- European bat Lyssavirus, Type 2
- Australian bat Lyssavirus
All give “rabies” except Lagos virus (which causes no human disease) and Mokola virus (which causes fever and encephalopathy)
All are in bats except Mokola virus.
Only Rabies virus is in dog, fox, raccoon etc.
3
Q
How many deaths in India due to Rabies annually?
What percent in kids?
A
20,000
60% in kids
4
Q
- Describe rabies pathogenesis.
- What is the incubation period
A
Following transdermal or mucous membrane exposure to saliva, virus enters nerves and then is carried centripetally via retrograde transport.
Incubation period to development of symptomatic encephalitis is 20-90 days, depending on severity and location of bite.
Then centrifugal axonal transport to rest of body, esp Salivary glands (also skin, heart, lung, adrenal etc)
5
Q
What is the route of inoculation for rabies?
A
Broken skin
mucous membranes
transplants
(inhalation theoretically possible but extremely rare)
6
Q
What is the incubation period for Rabies?
A
Typically 20-90 days.
May be as short as 9 days or rarely as long as several years.
7
Q
What are the early clinical features of rabies?
A
- Skin itching, pain, paraesthesia in dermatome of inoculum (30-80%)
- Fever, insomnia, anxiety, headache
8
Q
What are the clinical features of FURIOUS rabies?
A
- Encephalopathy
- confusion, agitation, aggression
- phases of arousal and lucid intervals
- Autonomic stimulation
- excess salivation, frothing
- temp control
- priapism
- spasms, hydrophobia, aerophobia
- Cranial nerve lesions III, VII, VIII
- Paralysis
- Coma
9
Q
What is the differential diagnosis for furious rabies?
A
- hysterical pseudo-hydrophobia
- (cephalic) tetanus
- other brain stem encephalitides
- enterovirus, borrelia, brucella, mycoplasma
- other causes of muscle spasms
- eg phenothiazine dystonia, tetany, strychnine poisoning
- DT’s
- CVA
- Seizure
- porphyria
10
Q
What are the clinical features of Paralytic ‘dumb’ Rabies?
A
- ascending paralysis, loss of tendon reflexes
- fasciculation
- sphincter dysfunction
- fever, sweating, gooseflesh
- bulbar/respiratory paralysis
- (hydrophobia)
- survive < 30 days
11
Q
What is the differential diagnosis for paralytic rabies?
A
- post-vaccinal encephalomyelitis
- paralytic poliomyelitis
- other enteroviruses, eg cocksackie
- flavivirus myelitis eg West Nile
- other causes of acute ascending paralysis (e.g. Guillain-Barré syndrome)
- Herpes simiae (B virus) encephalomyelitis (after monkey bites)
- So provide full treatment until diagnosis of rabies is made.
12
Q
How do you make the diagnosis of Rabies?
A
- Skin biopsy
- in small container, wet ice
- Immune Fluorescent Antibody to detect antigen
- Saliva, tears via virus isolation in mouse tissue culture
- CSF RNA detection via PCR
- Serum, CSF serology via neutralizing antibody
- REPEAT SAMPLES DAILY UNTIL DIAGNOSIS MADE
- POST MORTEM, as above plus needle Biopsy of brain
13
Q
- What is immediate treatment of animal bite possible rabies?
A
- Clean wound
- ASAP
- Soap/detergent
- 10 minutes
- Don’t suture
- Give tetanus
14
Q
- How do you treat Rabies? (general)
A
- treatment with combination pre and post-exposure vaccine is 100% effective
- post-exposure vaccine alone is pretty effective if started early
- no effective treatment once symptomatic
- Pre-exposure vaccine simplifies post-exposure regimen
- active immunization using viral ag to stimulate immune response
- Post-exposure vaccination
- Active immunization
- passive immunization with Ab (Rabies immunoglobulin)
15
Q
Pre-exposure Vaccination: why, who, what, when?
A
- Why? simplifies post-exposure vaccination if bitten and improves efficacy
- Who?
- cave explorers, animal workers, zoologists, botanists
- plans to hike or cycle
- (health care and lab workers)
- What?
- Several different preps can be given 1 ml IM or 0.1 ml intradermal (if not on chloroquine, which reduces Ab response if intradermal)
- When?
- days 0, 7, 28
- booster q 2 yrs (off recc; but overkill)
16
Q
How do you treat with post-exposure vaccination if no pre-exposure vaccination?
A
- IM/deep subQ regimes (Human Diploid Cell Strain Vaccine, Purified Vero Cell V, Purified Chick Embryo Cell VaccineP)
- Standard (5 vials 5 visits)
- 1 vial into deltoid or thigh on days 0,3,7,14,28
- Alternative (4 vials 3 visits)
- 2 vials (deltoids) on day 0; 1 vial days 7 & 21
- Standard (5 vials 5 visits)
- Newer Intradermal
- 8 site (HDCSV, PCEVC) (< 2 vials, 4 visits)
- Day 0: 0.1 ml to L & R: deltoid, suprascapular, abdominal, thigh
- Day 7: 4 limbs
- Day 28: single site
- Day 90: single site
- 2 site (PVCV, PCECV) (<2 vials, 5 visits)
- Days 0,3,7,28,91
- (PVCV 0.2 ml; PCECV 0.1 ml new recc)
- PLUS PASSIVE IMMUNIZATION WITH IMMUNOGLOBULIN
- 8 site (HDCSV, PCEVC) (< 2 vials, 4 visits)
17
Q
Passive immunization: Who gets it and How?
A
- All patients with severe bites, high risk of exposure
- covers first 7 days while Ab against vaccine is raised
- Human rabies immune globuline (20 mg/kg)
- half into and around wound, half other limbs
- Equine rabies immune globuline (40 mg/kg)
- risk anaphylaxis/ serum sickness
- never into buttocks; keep adrenaline available
- Not available in tropical settings
18
Q
How do you administer Post-exposure vaccination if pre-vaccinated?
A
- 1 ml im or deep subcut days 0 & 3
- recc is changing to 1 dose
- No immunoglobulin
- All bite recipients
- don’t forget Td and antibiotics
19
Q
- What is the spectrum of human disease caused by arboviruses.
- What are the 3 clinical syndromes associated with arboviruses?
A
- majority of human infections with arboviruses are asymptomatic or cause mild non-specific febrile illness.
- FAR: Fever-Arthralgia-Rash
- VHF: Viral Hemorrhagic Fever
- CNS: Central Nervous System Infection
20
Q
Which arboviruses cause FAR syndromes?
A
- Alphavirus genus (Togaviridae)
- Chikungunya
- O’nyong nyong
- Ross River virus
- Venezuelan equine encephalitis
- Sindbis virus
- Coltivirus genus (Rheoviridae)
- Colorado Tick Fever
- Flavivirus genus (Rheoviridae)
- Dengue
- West Nile
- Zika Virus
21
Q
Which arboviruses cause CNS disease?
A
- Alphavirus genus (Togaviridae)
- Chikungunya
- Venezuelan Equine Encephalitis
- Eastern Equine Encephalitis
- Western Equine Encepatlitis
- Bunyavirus genus (Bunyaviridae)
- La Crosse Virus
- Flaviviruses (Flaviviridae)
- West Nile Virus
- Dengue Virus
- Japanese Encephalitis Virus
- St. Louis Encephalitis Virus
- Murray Valley Encephalitis Virus
- Tick Borne Encephalitis Virus
- Zika Virus
22
Q
- Which arboviruses cause Viral Hemorrhagic Fevers?
- Which other viruses cause Viral Hemorrhagic Fevers?
A
- Arboviruses
- Flavivirus genus (Flaviviridae)
- Dengue virus
- Yellow Fever
- Nairovirus genus (Bunyaviridae)
- Crimean-Congo Hemorrhagic Fever
- Phlebovirus genus (Bunyaviridae)
- Rift Valley Fever
- Flavivirus genus (Flaviviridae)
- Non-Arboviruses
- Arenavirus genus (Arenaviridae) (rodents)
- Lassa Fever Virus
- Lujo
- South American Hemorrhagic Fever Viruses
- Filovirus genus (Filoviridae)
- Ebola Virus
- Marburg Virus
- Bunyaviridae
- Hantaan and other Hantaviruses (HFRS, HFPS)
*
- Hantaan and other Hantaviruses (HFRS, HFPS)
- Arenavirus genus (Arenaviridae) (rodents)
23
Q
For each virus, what are the main catgories of information yu should know.
A
- Genus and Family
- Geographical area
- Natural cycle
- Human Disease
- is there human-human or nosocomial spread?
- mortality?
- treatement?
24
Q
Summarize Lassa virus.
A
- Genus: Arenavirus
- Family: Arenaviridae
- Geographic area: Western Africa
- Natural cycle: Mastomys rodent via urine and feces via aerosol or food contamination
- Human disease: Viral Hemorrhagic Fever
- Human-human spread occurs
- 2-15% mortality
- Treat with ribavirin (good evidence)
- directly transmissable VHF most often seen in returning travellers because of wide distribution & long incubation period (5 days to 3 weeks)
- usually presents as non-spec febrile illness then conjunctival injection, sore throat with pharyngeal exudate, retrosternal chest pain, vomiting, diarrhea
- some progress to faciall and laryngeal edema, mild bleeding diathesis, shock
- Sensorineural deafness late complication in 30%
25
Q
Summarize Lujo virus
A
- Genus: Arenavirus
- Family: Arenaviridae
- Geographic area: Zambia, uncertain range
- Natural cycle: Unknown
- Human disease: Viral Hemorrhagic Fever
- Human-human and nosocomal spread occurs
- 80% mortality in 5 cases
- name derived from Lusaka - index case; and Johannesburg, where the index case was transported and where 4 health workers contracted the disease. The 4th of these, identified early through contact tracing, was given ribavirin and survived. Not enough cases to know if effective.
26
Q
Summarize Ebola and Marburg virus.
A
- Genus: Filovirus
- Family: Filoviridae
- Geographic area: Sub-Saharan Africa
- (Ebola named for Ebola River in Congo, outbreaks also in Sudan, Uganda, Zaire)
- (Marburg Virus named for city in Germany where identified after oubreak through contact with grivet monkeys. There have since been several outbreaks in Sub-Saharan Africa.)
- Natural cycle: (Unknown) Bats implicated esp for Marburg, presumed zoonosis
- Human disease: Viral Hemorrhagic Fever
- usually initiate in rural areas, sometimes in association with bat-infested caves or mines, sometimes after contact with diseased primates
- Nosocomial spread common, possibly via small cuts or conjunctiva
- Incubation period 4-10 days
- present with febrile illness with myalgia, abd pain (sometimes mimicking peritonitis), sore throat, herpetic lesions mouth & pharynx, conjunctival injection, diarrhea, MP rash
- prostration, sometimes bleeding from gi tract, nose, injection sites
- petechiae, shock, neurological signs
- 25-90% mortality
- no antiviral treatment, supportive treatment
27
Q
Summarize Haemorrhagic Fever with Renal Syndrome
A
- Genus: Hantavirus (4 viruses)
- Family: Bunyaviridae
- Geographic area:
- Hantaan virus: epidemic HFRS in Far East (named after the Hantaan River in Korea where identified after soldiers there contracted it during Korean War)
- Seoul virus: Far East & Europe (milder)
- Dobrova virus: severe HFRS in Balkans
- Puumula virus: Scandinavia, Northern Europe, milder with renal predominance (nephropathia epidemica)
- Natural cycle: various rural rodents
- Human disease:
- Hemorrhagic fever with renal syndrome
- No human-human spread
- 5 phases:
- febrile
- hypotensive (with hemorrhage)
- oliguric
- diuretic
- convalescent
- 1-15% mortality depending on virus
- treat severe disease with ribavirin
- formalin inactivated vaccines in Asia
28
Q
Summarize Crimean-Congo hemorrhagic fever.
A
- Genus: Nairovirus
- Family: Bunyaviridae
- Geographic area: Eastern Europe, Asia, Africa, middle East, Subsaharan Africa
- Natural cycle: Hyalomma ticks
- livestock & wild animals as amplifying reservoir hosts
- Human disease: Hemorrhagic Fever
- Human-human spread
- differs from other VHFs in that major hemmorhage more important than vascular leakage in pathophysiology
- Councilman bodies
- 15-30% mortality
- Treat with ribavirin (controversial)
29
Q
Summarize Rift Valley Fever
A
- Genus: Phlebovirus
- Family: Bunyaviridae
- Geographic area: Africa, Middle-East
- Natural cycle: Aedes, Culex and others and livestock
- sheep, cattle, camels & goats
- (causes abortions in sheep and cattle)
- Aedes important epidemiologically because virus transmitted transovarially. Eggs resist dessication and epidemics may follow rain after long drought
- Human disease:
- transmission by mosquito and aerosolized infected blood
- epidemic form after rains hatch dried eggs of Aedes
- also veterinarians, butchers
- control measures include livestock vaccination, personal protection of livestock workers and mosquito control
- Tx with ribavirin
- 50% mortality for VHF
- Human to human spread not documented but possible
- Most infections assymptomatic or mild fever, 5% have hemmorhage (VHF), meningoencephalitis, conjunctivitis or retinitis
- epidemics associated with increased mosquito pops with heavy rains, irrigation projects
30
Q
Summarize Dengue Hemorrhagic Fever
A
- Genus: Flavivirus
- Family: Flaviviridae
- Geographic area: Tropics and Subtropics Worldwide
- Natural cycle:
- Vectors: Aedes mosquitoes - Aedes aegypti and Aedes albopictus
- Hosts: Humans only, no animal reservoir
- Human disease: Dengue Hemmorhagic Fever, also FAR syndrome “Breakbone fever” & CNS infection
- No Human to Human Spread
- but disease is disseminated geographically by humans not mosquitoes
- Mortality 1% with adequate fluid replacement
- No antivirals
31
Q
Summarize Yellow Fever
A
- Genus: Flavirus
- Family: Flaviviridae
- Geographic area: Africa, South America
- Natural Cycle: various mosquitoes and monkeys in jungle, transmitted via Aedes aegypti to humans in urban cycle
- Human Disease: VHF and hepatitis
- No human-human spread
- 20-50% mortality
- No antivirals
32
Q
Chikungunya
A
- Genus: Alphavirus
- Family: Togaviridae
- Geography: Africa, India, South-East Asia, Pacific Islands, Asia, Americas, Caribbean, southern Europe
- Natural Cycle:
- Humans and primates natural hosts
- Vectors: Aedes (esp A. aegypti and A. albopictus) & Culex
- Human Disease: FAR
- mainly frequent multiple joint pains that may last for months.
- Hemorrhagic complications rare, thrombocytopenia and neutropenia much less common than dengue
33
Q
List the 4 families of Arboviruses and their genuses and members.
A
- Togaviridae - all Alphavirus genus
- Chikungunya
- O’nyong nyong
- Ross River
- Venezualan Equine Encephalitis
- Eastern Equine Encephalitis
- Western Equine Encephalitis
- Bunyaviridae
- La Crosse Virus - Bunyavirus genus
- Crimean-Congo Hemorrhagic Fever - Nairovirus genus
- Rift Valley Fever - Phlebovirus genus
- Rheoviridae
- Colorado Tick Fever - Coltivirus Genus
- Flaviviridae - All Flavivirus genus
- Japanes Encephalitis
- St. Louis Encephalitis
- Murray Valley Encephalitis
- Tick borne encephalitis
- West Nile Virus
- Dengue
- Yellow Fever
- Zika Virus
34
Q
O’nyong nyong
A
- Genus: Alphavirus
- Family: Togaviridae
- Geography: Africa
- Natural cycle:
- humans only host
- only arbovirus transmitted by Anopheles
- Disease: FAR
- conjunctivitis common clinical feature
35
Q
Ross River Virus
A
- Genus: Alphavirus
- Family: Togaviridae
- Geography: Australia
- Natural Cycle: transmitted by Aedes & Culex
- Hosts: Wallabies & Kangaroos
- Human Disease: FAR syndrome, epidemic polyarthritis, ongoing depression and fatigue
36
Q
Colorado Tick Fever
A
- Genus: Coltivirus
- Family: Rheoviridae
- Geography: Rocky Mountains, USA and Canada
- Natural cycle: transmitted among small mammals by Dermatocentor ticks
- Human Disease: FAR, CNS Disease
- causes CNS disease in 10% of children
- hemorrhagic disease rarer
- not to be confused with Rocky Mountain Spotted Fever (caused by rickettsia rickettsi transmitted by Dermacentor variabilis - American dog tick)
37
Q
Which 4 families of virus cause Viral Hemorrhagic Fevers?
A
- Arenaviridae - Arenavirus
- Lassa
- Lujo
- South American Hemorrhagic Fevers
- Filoviridae - Filovirus
- Ebola
- Marburg
- Bunyaviridae
- Hantaan & others - Hantavirus
- (Hemorrhagic fever with renal syndrome)
- Crimean-Congo hemorrhagic fever - Nairovirus
- Rift Valley Fever - Phlebovirus
- Hantaan & others - Hantavirus
- Flaviviridae - Flavivirus
- Dengue
- Yellow Fever
38
Q
- What 4 families of arthropod viruses?
- What 4 families of virus cause VHF?
A
- FAR
- Togaviridae: Chikungunya, O’nyong nyong, Ross River, VEE, EEE, WEE
- Bunyaviridae: La Crosse, Crimean Congo HF, Rift Valley Fever
- Rheoviridae: Colorado Tick Fever
- Flaviridae: Japanese Encephalitis, St. Louis Encephalitis, Murray Valley Encephalitis, Tick Borne Encephalitis, West Nile, Dengue, Yellow Fever, Zika
- VHF
- Arenaviridae: Lassa, Lujo
- Filoviridae: Ebola, Marburg
- Bunyaviridae: Hantaan et al, Crimean-Congo HF, Rift Valley Fever
- Flaviridae: Dengue, Yellow Fever
39
Q
- Of the Viral Hemorrhagic Fevers, which are directly transmitted and capable of human to human transmission?
- Which are arthropd
A
- Directly transmitted but not capable of human to human transmission:
- Hantaan et al via various rural rodents (nb no human-human transmission)
- Directly transmitted and capable of human transmission but not arthropod borne.
- Lassa via Mastomys rodent
- Ebola & Marburg via ?bat?
-
Directly transmitted & capable of human transmission & arthropod borne
- CCHF via lifestock & Hyolamma ticks
- Rift Valley fever via livestock and Aedes & other mosquitoes
- Arthropod borne & not capable of direct human transmission
- Yellow fever via monkeys & various mosquitoes
- Dengue human to human only via Aedes mosquitoes
42
Q
Febrile Patients: clinical considerations wrt VHF?
A
- most febrile patients suspected to have VHF have something else, e.g. malaria, typhoid, hepatitis
- most vhf’s acquired in rural areas
- interval of 3 weeks between exposure rules out VHF
- most early sx non-specific but watch out for
- pharyngitis with ulcers
- difficulty swallowing
- retrosternal chest pain
- conjunctival injection
- prostration
- hemorrhagic manifestations may not be obvious, look for:
- petechiae in skin folds & axillae
- gum bleeding
- microscopic hematuria
- tourniquet test
- look repeatedly for
- rising hematocrit
- pleural effusions on dec chest xray
- leukopenia
- thrombocytopenia
- proteinuria
48
Q
What is the differential diagnosis of VHF?
A
- VHF’s in order of incidence
- Dengue hemorrhagic fever
- Hemorrhagic fever with pulmonary syndrome
- Yellow Fever
- Lassa Fever
- Crimean-Congo Hemorrhagic Fever
- South American Hemorrhagic Fever
- Rift Valley Fever
- Omsk Hemorrhagic Fever, Kyasanur Forest disease & Al Khurma virus
- Ebola & Marburg Hemorrhagic Fever
- Lujo Virus
- Treatable causes of fever with rash/hemorrhage
- Parasites
- Malaria (rash/hemorrhage rare)
- Bacteria
- Meningococcal
- Typhoid
- Septicemic plague
- Shigellosis
- any severe sepsis with DIC
- Rickettsia
- Tick and epidemic typhus
- Rocky Mountain Spotted Fever
- Spirochaetes
- Leptospirosis
- Borreliosis
- Parasites
- Causes of fulminant hepatic Failure
- Hepatitis viruses A-E
- Paracetamol and other drugs
- Reye’s syndrome
- Alcohol
- Arboviral causes of fever with rash
- Alphaviruses
- Chikungunya
- O’nyong nyong
- Sindbis
- Bunyaviruses
- Oropouche
- Phleboviruses
- Sandfly fever
- Coltiviruses
- Colorado tick fever
- Flaviviruses
- Zika virus
- Alphaviruses
- Non-arboviral causes of fever with rash
- Enteroviruses
- Cocksacke viruses
- Echoviruses
- Enteroviruses 68-71
- Paramyxoviruses
- Measles
- Herpes Viruses
- Herpes zoster virus
- Human herpes virus 6 & 7
- Orthomyxoviruses
- Influenza A & B
- Rubiviruses
- Rubella
- Enteroviruses
- Miscellaneous
- Drug reactions
- Toxins
- Acute surgical emergencies (Upper GI Bleeding)
61
Q
Describe new WHO classification of dengue.
A
- describes dengue as
- with or without warning signs of more severe disease or
- Severe Dengue
- Warning signs include
- abdominal pain or tenderness
- persistent vomiting
- clinical fluid accumulation
- mucosal bleeding
- lethargy or restlessness
- liver enlargement > 2 cm
- rise in hct concurrent with fall in platelets
- Patients with severe dengue have:
- signs of severe plasma leakage i.e. leading to shock or fluid accumulation with respiratory distress or
- severe hemorrhage (as defined by treating physician)
- severe organ impairment defined as
- ALT >1000 iu/L or
- impaired consciousness or
- severe involvement of heart or other organs
70
Q
In what diseases are Councilman bodies found and what are they?
A
- In pathology, a Councilman body, also known asCouncilman hyaline body or apoptotic body, is an acidophilic (eosinophilic / pink-staining on H&E) globule of cells that represents a dying hepatocyte often surrounded by normal parenchyma.
- Yellow Fever
- Crimean-Congo Hemorrhagic Fever
- Rift Valley Fever
77
Q
Viral hemorrhagic Fevers
List the 4 families of virus and their members
A
78
Q
- Which viruses belong to genus Flavivirus?
- Which family?
- What diseases?
- What do they have in common?
A
- Flaviviridae
- Primarily arboviruses (the ones listed here are all arboviruses)
- CNS disease
- Members:
- Dengue
- West Nile
- Zika
- JEV
- St. Louis Encephalitis
- Murray Valley Encephalitis
- Tick Borne Encephalitis
- Members:
- VHF
- Dengue
- Yellow Fever
92
Q
What are the main flavivirus encephalitis viruses and where are they distributed?
A
- St. Louis Encephalitis Virus: North and South America
- West Nile Virus: Africa, Mainland Europe and Eurasia and North America
- Japanese Encephalitis Virus: South and South-East Asia
- Murray Valley Encephalitis: Australia & NZ
- (Kunjin Virus, a subtype of West Nile is also found in Aus and NZ).
