Virology Flashcards
(95 cards)
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
Summarize Lujo virus
* 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
Summarize Ebola and Marburg virus.
* 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
Summarize Haemorrhagic Fever with Renal Syndrome
* 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:
1. febrile
2. hypotensive (with hemorrhage)
3. oliguric
4. diuretic
5. convalescent
* 1-15% mortality depending on virus
* treat severe disease with ribavirin
* formalin inactivated vaccines in Asia
28
Summarize Crimean-Congo hemorrhagic fever.
* 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
Summarize Rift Valley Fever
* 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
Summarize Dengue Hemorrhagic Fever
* 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
Summarize Yellow Fever
* 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
Chikungunya
* 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: F**A**R
* mainly frequent multiple joint pains that may last for months.
* Hemorrhagic complications rare, thrombocytopenia and neutropenia much less common than dengue
33
List the 4 families of Arboviruses and their genuses and members.
1. Togaviridae - all Alphavirus genus
1. Chikungunya
2. O'nyong nyong
3. Ross River
4. Venezualan Equine Encephalitis
5. Eastern Equine Encephalitis
6. Western Equine Encephalitis
2. Bunyaviridae
1. La Crosse Virus - Bunyavirus genus
2. Crimean-Congo Hemorrhagic Fever - Nairovirus genus
3. Rift Valley Fever - Phlebovirus genus
3. Rheoviridae
1. Colorado Tick Fever - Coltivirus Genus
4. Flaviviridae - All Flavivirus genus
1. Japanes Encephalitis
2. St. Louis Encephalitis
3. Murray Valley Encephalitis
4. Tick borne encephalitis
5. West Nile Virus
6. Dengue
7. Yellow Fever
8. Zika Virus
34
O'nyong nyong
* Genus: *Alphavirus*
* Family: Togaviridae
* Geography: Africa
* Natural cycle:
* humans only host
* only arbovirus transmitted by *Anopheles*
* Disease: FAR
* conjunctivitis common clinical feature
35
Ross River Virus
* 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
Colorado Tick Fever
* 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
Which 4 families of virus cause Viral Hemorrhagic Fevers?
* 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*
* Flaviviridae - *Flavivirus*
* Dengue
* Yellow Fever
38
* What 4 families of arthropod viruses?
* What 4 families of virus cause VHF?
* FAR
1. Togaviridae: Chikungunya, O'nyong nyong, Ross River, VEE, EEE, WEE
2. Bunyaviridae: La Crosse, **Crimean Congo HF, Rift Valley Fever**
3. Rheoviridae: Colorado Tick Fever
4. Flaviridae: Japanese Encephalitis, St. Louis Encephalitis, Murray Valley Encephalitis, Tick Borne Encephalitis, West Nile, **Dengue, Yellow Fever,** Zika
* VHF
1. Arenaviridae: Lassa, Lujo
2. Filoviridae: Ebola, Marburg
3. Bunyaviridae: Hantaan et al, **Crimean-Congo HF, Rift Valley Fever**
4. Flaviridae: **Dengue, Yellow Fever**
39
* Of the Viral Hemorrhagic Fevers, which are directly transmitted and capable of human to human transmission?
* Which are arthropd
* 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
40
Viral Hemorrhagic Fevers: What are the primary pathophysiological processes?
1. increased vascular permeability
2. hemorrhage, from minor (e.g. petechiae) to major (eg GI bleedingin Crimean-Congo HF)
3. hepatic & renal failure
4. encephalopathy
41
What period of time between exposure and onset rules out Viral Hemorrhagic Fever?
* 3 weeks
42
Febrile Patients: clinical considerations wrt VHF?
* 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
43
Viral Hemorrhagic Fevers: Geography
* Which in?
* Africa
* Middle East
* Asian subcontinent
* Europe
* Far East
* Americas
* Dengue everywhere but Europe
* Africa:
* Directly Transmissable: Ebola/Marburg, Lassa, CCHF, RVF
* Non-directly Transmissable: DHF, Yellow Fever
* Middle East:
* DT:CCHF, RVF
* NonDT: Dengue
* Asian Subcontinent
* CCHF, Dengue
* Europe
* CCHF and nonDT: Hem Fever with Renal Syndrome
* Far East: CCHF and Dengue
* SA: South American Viral Hem Fevers (Arenaviridae), DHF, Yellow Fever
44
Which VHF's can be transmitted directly human to human?
* Ebola/Marburg
* Lassa
* South American VHF's
* CCHF
* RVF
* (Hantaan viruses et al are capable of direct rodent to human transmission but not human to human)
45
* Which VHF's natural cycle may include:
* monkeys?
* Bats?
* Rodents?
* Livestock?
* Mosquitoes?
* Monkeys
* Yellow fever
* ?Ebola/Marburg?
* Bats: ?Ebola/Marburg?
* Rodents:
* Lassa (urban)
* SAVHF's (rural)
* HFRS (rural)
* Livestock: CCHF & RVF
* Mosquitoes:
* Dengue HF - urban mosquitoes
* Yellow Fever - jungle mosquitoes
46
* For which viral hemorrhagic fevers may ribavirin improve prognosis?
* For which does it not help?
* Possible Helps: (But **evidence poor except for Lassa and possibly CCHF**)
* **Lassa**
* SAVHF
* **CCHF**
* **RVF**
* **HFRS** (Hantaan et al)
* ?Lujo
* Doesn't
* Ebola/Marburg
* Dengue
* Yellow Fever
47
What lab diagnositic techniques are available for early diagnosis of VHF?
* Need biosafety level-4 facilities
1. virus isolation
2. reverse transcriptase PCR
3. Ag capture ELISAs
4. subsequently IgM and IgG ELISA
48
What is the differential diagnosis of VHF?
* 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
* 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
* 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
* Miscellaneous
* Drug reactions
* Toxins
* Acute surgical emergencies (Upper GI Bleeding)
49
Outline Treatment for Viral Hemorrhagic Fevers
* encourage oral rehydration with ORS if pt cannot sit up
* for pts with suspected Lassa Fever, CCHF, Rift Valley Fever, HRRS:
* start Ribavirin ASAP
* 30 mg/kg loading then 16 mg/kg qid x 4 days then 8 mg/kg tid x 6 days
* treat hemorrhagic shock with crystalloids & colloids & inotropes
* Blood transfusions not needed for most but FFP may be needed
* Isolate pt, strict barrier nursing with goggles, mask etc
50
Summarize South American Hemorrhagic Fevers
* Genus: Arenavirus (several similar viruses: Junin, Machupo and Guanarito viruses cause Argentine, Bolivian and Venezualan hemorrhagic fever respectively)
* Family: Arenaviridae
* Geography: South America
* Natural Cycle: human to human via rodents via feces or urine cont food, aerosol (similar to Lassa Fever)
* Human Disease: VHF similar to Lassa Fever
* Human-human contact can occur
51
Summarize Hantavirus
* Genus: *Hantavirus (new world hantaviruses)*
* Family: Hantaviridae
* Geography: Americas
* Natural cycle: humans infected via rodents
* Disease: Hantavirus pulmonary syndrome
* No human to human spread
52
Which of VHF diseases poses greatest risk of healthcare associated transmission?
* CCHF
* wide distribution across Africa & Asia
* rarely imported by travellers returning from these areas
53
What are the commonest diagnoses in returning travellers suspected to have VHF?
* malaria
* arboviral infections
* enteroviral infections
54
* What is the arbovirus that infects most humans?
* How many cases of this virus per year?
* Dengue virus
* 100 million cases per year
55
Dengue: what are the reasons for the global pandemic following WWII?
* poor control of vectors
* rebound of *Aedes aegypti* in 60's after spray with DDT abandoned
* transport of *Aedes albopictus* via car tyres
* overcrowding of refugee and urban populations
* increasing human travel
56
* Dengue:
* how many viral serotypes?
* what is hyperendemic transmission?
* what is the epidemiologic pattern in hyperendemic areas?
* 4 viral serotypes
* hyperendemic transmission refers to continuous transmission of multiple dengue virus serotypes
* in hyperendemic areas of Asia disease is seen primarily in children because adults are immune from prior exposure
* increasingly in non-immune adults travelling to hyperendemic areas
57
*Aedes* mosquitoes: what are their living and feeding habits, distribution?
* *Aedes* peri-domestic, breed in collections of fresh water around the house (eg water storage jars)
* anthrophilic by day, feed repeatedly on different human hosts
58
* Dengue Hemorrhagic Fever:
* Epidemiologic History?
* Clinical Course?
* emerged as apparently new disease in South East Asia in 1950's
* Clinical course:
* initially non-specific febrile illness, possible petechial rash
* 3rd to 7th day, as fever subsides massive increase in vascular permeability leading to plasma leakage from blood vessels into tissue
* elevated hematocrit
* edema, effusions
* thrombocytopenia, hemorrhage
59
Describe Dengue Fever Presentation
* Classic FAR syndrome
* retro-orbital pain
* photophobia
* lymphadenopathy
* 50% have rash, usually MP, but may be mottlein or flushing
* may be petechiae and other bleeding manifestations including gum, nose or GI
* 1/3 have +ve tournique test: 5 minutes produces \>20 petechiae in 1 inch square on forearm
60
* Dengue Fever and DHF: what is traditional WHO Classification?
* What were its limitations?
* **Limitations of this classification** were that
* it implied that hemorrhage is the cardinal manifestation of disease, whereas plasma leakage into the interstitia is more important.
* Many patients with severe disease did not meet criteria for DHF
* it required regular platelet and HCT measurements, which were not possible in many dengue areas
* **_Traditional WHO classification of Dengue Fever and Dengue Hemorrhagic Fever_**
* DF
* no plasma leakage
* variable platelet count, absent circulatory collapse
* variable hemorrhagic manifestations
* DHF I
* **Plasma Leakage present** as identified by Hct 20% above normal, or clinical signs of plasma leakage
* **Platelets \< 100,000**
* circulatory collapse absent
* **Positive tourniquet test (or easy bruising)**
* DHF II
* as above + **spontaneous bleeding** as defined by presence of skin petechiae, mucosal or GI bleeding
* DHF III
* as above + **signs of circulatory collapse present:** **PP\<20 mm Hg or hypotension for age**
* DHF IV
* as above but **Pulse and BP undetectable**
61
Describe new WHO classification of dengue.
* 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
62
* What is differential diagnosis of dengue?
* Fever with arthralgia or rash
* Arboviruses: Chikungunya, O'nyong nyong, sinbis, West Nile, Ross River, Oropouche, sandfly fevers, Colorado tick fever, Zika virus
* Other viruses: rubella, measles, herpes, enterovirus
* Bacteria: meningococcus, typhoid
* Spirochetes: leptospirosis, Lyme disease, relapsing fevers
* Parasites: malaria
* Fever with hemorrhage
* Arboviruses: Yellow Fever, Crimean-Congo HF, Rift Valley Fever, Omsk haemorrhagic fever
* Other viruses: hantaviruses, fulminant hepatitis (A-E), Lassa, South American hemorrhagic fevers, Ebola, Marburg
* Any severe sepsis with DIC
* Drug reactions
63
Outline management of Dengue Fever (not DHF)
* **Supportive Care:**
* Most cases self-limiting
* Encourage oral fluids
* acetaminophen prn
* May have MP recovery rash
* prolonged lethargy and depression after recovery common
* **avoid ASA**
64
Outline management of Dengue Hemorrhagic Fever
* DHF I & II: **Support and monitor**
* encourage oral fluids
* closely monitor VSS, Hct, plt count
* DHF III & IV: **Monitor &** **Fluid Replacement**
* if possible monitor CVP
* IV crystalloid 10-20 mg/kg/hr then colloid if persistent shock
* watch for fluid overload
65
List some complications of DHF
* hepatitis, fulminant hepatic failure (Reye-like syndrome)
* neurologic
* metabolic encephalopathy
* cerebral edema
* occasionally viral encephalitis
66
* Describe 2 mechanisms underlying development of DHF.
1. *Antibody dependant enhancemant*
* *antibodies against previous infection one dengue virus serotype enhance entry of second dengue virus into macrophages leading to more severe infection*
2. *Viral strain differences - eg increased virulence of SE Asian strains of dengue-2 virus*
67
Describe preventive strategies and possible future developments for control of Dengue infections.
* Control *Aedes* mosquitoes
* larvicide for stored water
* education about removing collections of water around houses
* spraying
* Future
* tetravalent vaccines against all 4 dengue serotypes in development
68
* Outline Yellow Fever Epidemiology
* Jungle cycle:
* natural host primates in jungles in Africa and South America
* vectors various mosquitoes
* Urban cycle
* *Aedes aegypti* transmits to humans
* Geography:
* jungles of Africa and Central America
* re-emerged since 1970s after *Aedes* eradication program relaxed
* Human Disease:
* ranges from mild to fulminant hepatitis
* 200,000 cases annually, 30,000 deaths
69
* Outline factors contributing to reemergence of Yellow Fever over past 2 decades
* relaxation of *Aedes* control measures since 60's
* declining population immunity to infection
* deforestation
* urbanization
* climate change
* population movements
70
In what diseases are Councilman bodies found and what are they?
* 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
71
Outline clinical features of Yellow Fever.
* biphasic: flu-like illness for 3-4 days followed in 15% to 25% of cases by a fulminant illness with a case-fatality rate of 20% to 50%
* Severe disease
* characterized by jaundice, fulminant hepatic failure and GI bleeding
* Faget's sign (also seen in Typhoid fever, Tularemia, Colorado Tick Fever, brucellosis, some atypical pneumonias -Legionella and mycoplasma, Drug reaction to Beta blocker (beta Fagets)
* elevated liver fx tests, leukopenia, thrombocytopenia, clotting abnormalities
* Liver histology Councilman bodies (also seen in Crimean Congo Hemorrhagic Fever & Rift Valley Fever)
72
What is Faget's sign and what does it indicate.
In with which diseases is it associated?
* Faget's sign is the failure of the heart rate to rise with a rising temperature.
* It indicates cardiac damage
* Yellow fever
* Typhoid fever
* Tularaemia
* Brucellosis
* Colorado tick fever
* Some pneumonias - Legionella pneumonia and Mycoplasma pneumonia
* Drug fever (e.g. beta-blockers,[3] known as the Beta-Faget sign)
73
* Discuss Yellow Fever Vaccine:
* Type?
* Effectiveness and time to effect?
* Adverse Reactions?
* Contraindications
* 17D live attenuated vaccine
* highly effective immunity within 1 week for 95% of persons vaccinated
* recent years reports of adverse infections in older adults receiving immunization for first time
* Contraindications
* children \< 9 months for routine immunization (\<6 months during epidemic)
* pregnant women - except during outbreak when risk of infection high
* allergies to egg protein
* Severe immunodeficiency due to hiv/aids or other causes
* or thymus disorder
* older travellers visiting low risk areas in a country where yellow fever occurs (individual risk assessment)
74
La Crosse Virus
* arbovirus
* Genus Bunyavirus
* Family Bunyaviridae
* Vectors: Aedes species esp Aedes triseriatus, Aedes albopictus
* Geography: US, midwest, Appalachia, ?Eastern US
* Human Disease: viral encephalitis, most serious bunyavirus disease in US
* first recognized after fatal case in La Crosse Wisconsin 1960
* children, affects boys more than girls because more often exposed
* *Aedes triseriatis* breeds in tree holes
* chipmunks, squirrels amplifying rodents
75
* Which arboviruses belong to the genus *Alphavirus?*
* What family of viruses?
* What spectrum of disease?
* Togaviridae
* CNS disease
* Venezualan EE
* WEE
* EEE
* Chikungunya
* FAR disease
* O'NyongNyong
* Ross River
76
* Which virus(es) belong to genus Bunyavirus?
* To which Family?
* What kind of disease?
* arbovirus
* Bunyaviridae
* La Cross Virus - FAR
* Crimean-Congo Hemorrhagic Fever - VHF
* Hemorrhagic Fever with Renal Syndrom (Hantaan virius) - VF
* Oropouche - FAR
77
Viral hemorrhagic Fevers
List the 4 families of virus and their members
78
* Which viruses belong to genus *Flavivirus?*
* Which family?
* What diseases?
* What do they have in common?
* 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
* VHF
* Dengue
* Yellow Fever
79
* Japanese Encephalitis Virus
* Natural Host?
* Habitat?
* Vector?
* Where?
* Clinically?
* What kind of disease
* # cases annually
* mortality
* Vaccines available?
* Antiviral treatment?
* Seasonality
* Nosocomial Spread?
* Natural Host? Birds (Esp. Cattle Egret) ⇒Pigs
* pigs act as amplifying host with high level viremia
* Habitat? Rural
* Vector? Culex (tritaeniorhynchus and others)
* Where? Asia (S, SE, W Pacific)
* Clinically?
* CNS
* 70,000 cases annually, 10-30% mortality Vaccines expensive, not available to most (there are both live and dead vaccine)
* However only 1/300 infections are symptomatic.
* No antiviral tx
* Seasonality: north of southern tips of india and thailand/myanmar there are summer epidemics; in south (Indonesia, PNG, southern Philippines it is endemic, year round)
* Nosocomial Spread? No
80
Natural Host?
Habitat?
Vector?
Where?
Clinically?
Nosocomial Spread?
Dengue
Natural Host? Humans
Habitat? Urban
Vector? Aedes
Where? DF: 'Tropics'; DHF: SEA, W. Pacific,
Caribbean
Clinically? FAR ⇒ VHF
Nosocomial Spread? No
81
* Yellow Fever
* Family, Species?
* Natural Host?
* Habitat?
* Vector?
* Where?
* Clinically?
* Nosocomial Spread?
* Flavivirus, Flaviviridae
* Natural Host? Primates⇒Humans
* Habitat? Rural ⇒ Urban
* Vector? Aedes
* Where? South America, Africa
* Clinically?
* VHF
* Nosocomial Spread? No
82
What is Parvovirus 4?
* a cause of encephalitis in India
83
What is the differential diagnosis for Japanese Encephalitis?
(eg presenting with fever, vomiting, headaches, then seizures and coma. Non-purulent CSF.
* Viral encephalitides
* JE, herpes, enteroviruses, adenovirus, influenza etc
* other arboviruses (Den, WNE) others depending on location
* ADEM
* post vaccine, post viral
* Bacterial infections
* partially treated bact meningitis
* early TBM
* abscess
* Fungal: cryptococcus, histo, blasto etc
* Parasites: falciparum malaria, toxo, trypanosomiasis
* Infectious encephalopathies
* typhoid, shigella, tetanus, typhus, leptospirosis, febrile convulstions
* Non-infectious: Reye's syndrome, epilepsy, tumours, vascular, toxins eg organophosphates, alcohol, metabolic
84
What atypical presentation may JEV take?
What other viruses may cause this syndrome?
* poliomyelitis like illness with acute flaccid paralysis duet to Anterior Horn Cell involvement
* 50% of acute flaccid paralysis cases in JEV endemic areas are JEV positive
* ddx
* Polio
* enteroviruses 70 & 71
* Coxsackie, Echo
* JEV
* West Nile Virus
85
What are the clinical features possible in JEV?
* fever, headache, coma
* convulsions, poss subtle motor sz
* raised ICP
* Polio-like flaccid paralysis
* Parkinsonism
* mask like facies
* cogwheel rigidity
* tremor
* outcome: 20% fatal, 40% sequelae, 30% recovery
* complications:
* pneumonia
* malnutrition
* contractures
* bedsores
86
87
Sindbis virus
* Togaviridae
* Alphavirus
* Geography: South and East Africa, Middle East, Asia, parts of Australia
* Vector: Culex
* Natural host: birds
* Human Disease: FAR
88
How do you confirm a case of Dengue?
* virus isolation/PCR
* first few days
* Ab detection
* after first few days
* IgM & IgG Elisa distinguish primary from secondary
* rapid kit forms
89
What is Mesocyclops?
For what disease is Mesocyclops in intermediate host?
Does Mesocyclops have any uses?
* It is a copepod, one of several that acts as intermediate host for Guineau Worm larvae
* as it eats mosquito larvae as well it has been placed in water storage containers for control of Aedes species in Dengue control.
* easy to recognize and harvest from natural sources
* however, clearly not a good idea in areas where Guineau worm still endemic
90
* what is the vector for Dengue?
* Outline several methods used for control of this vector in areas where Dengue is endemic.
* larvicides in water - temephos organophosphate
* mesocyclops, a larvicidal copepod (aka Guineau worm int host)
* Bacillus thuingiensis toxin (Bti)
* larvivorous fish in domestic water tanks in China
* Netting screens over water
* legislation on rubbish
* legislation on car tires
* insecticide spraying/fogging during outbreaks
* Personal protection: lemon eucalyptus and DEET
91
Toscana Virus
* Bunyavirus
* Geography: mediterranean, esp Italy
* Vector: Phlebotomus sand fly
* disease varies from low grade FAR with headache, myalgias to meningoencephalitis
92
What are the main flavivirus encephalitis viruses and where are they distributed?
* 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).
93
St. Louis Encephalitis Virus
* Flavivirus related to JEV
* Geography: North America
* Vector: Culex
* Risk Groups: Elderly, Outdoor Occupation
* Human Disease: Meningitis, Encephalitis
* most infections are subclinical or mild
94
West Nile Virus
* Flavivirus
* Geography: Africa, West Asia, Middle East, North America
* Virus: ***Culex pipiens and Cx. modestus***; some Aedes
* Reservoir: humans, birds, mosquitos, horses, other mammals
* Human Disease: usually mild, with flu-like sx; typically few days, no long term effects
* severe disease: West Nile encephalitis, meningitis
95
Ebola Virus Disease
What is the clinical course
* Day 0-1
* mild fever, decreased appetite, headache
* drink and eat, ambulating
* Day 2-3
* fever, headache
* decreased appetite, nausea, diarrhea 2-3 bm/day, epig pain, hiccups
* ambulating but severe lethargy, lassitude
* Day 4-9
* fever, headache, myalgias, arthralgias
* d, v (up to 10 l/day), bloody diarrhea, emesis
* pulse weak, fast, falling urine output
* little to no ambulation
* delirium, wide-eyed stare, seizures
* Terminal phase: Day 10-12
* fever and GI sx subside
* confusion and delirium worsen to comatose
* oliguric/anuric
* both gradual and sudden deaths
