5/28- 5 Arboviruses: Toga, Flavi, Bunya, Arena, Filo Flashcards
What three families are comprised in Arboviruses?
- Togaviridae
- Flaviviridae
- Bunyaviridae
T/F: Once arboviruses are spread to humans by arthropods (e.g. mosquitos), they can be transferred human-to-human
False. Humans are typically dead-end hosts
Clinical syndromes of arboviral infections?
CNS disease:
- Encephalitis/meningoencephalitis
- Aseptic meningitis
Febrile illnesses (+/- rash)
“Hemorrhagic diseases”
Asymptomatic (unrecognized infxn)
Arthropod vectors
- Mosquitos
- Ticks
- Flies
Most viruses are spread most efficiently by 1/limited number of insect species (but may be spread by others)
Worldwide Distribution of Major Arboviral Encephalitides: know the North American and then Japanese Encephalitis (vaccine preventable)
Learn
Do arboviruses have seasonal fluctuations?
Yes. Early summer/fall when mosquitoes at peak level
Symptoms of encephalitis
- Fever, HA, vomiting, confusion, seizures
- Minimally stiff neck (differentiates from meningitis)
- With recovery, a proportion will have residual neurologic damage (varies with virus)
Two structural surface glycoproteins of Togaviridae?
E1
E2
Two genera of Togaviridae
- Alphavirus (Group A arboviruses)
- Rubivirus = rubella
Alphavirus classification by __?
Antigenic
Different thypes of antigenic classifications (4)?
- Antigenic complex: very closely related but distinct
- Species level: individual agents, antigenically related but easily separable (>4x diffs between homo/hetero titers of both sera)
- Antigenic serotypes: (>4x diffs between homo/hetero titers of one but not both sera)
- Antigenic varieties- special tests to distinguish
New world alphavirus antigenic complexes
- Eastern equine encephalitis virus (EEEV)
- Western equine encephalitis virus (WEEV)
- Venezuelan equin encephalitis virus (VEEV)
Old world alphavirus antigenic complexes
- Semliki Forest virus (SFV)
- Middleburg virus (Africa)
- Ndumu virus (Africa)
- Barmah Forest virus (Sindbis virus is old world although in WEEV antigenic complex)
Clinical syndromes of new world alphaviruses? old world?
New:
- Encephalitis
- Aseptic meningitis
Old:
- Febrile illness
- Rash
- Arthritis
Semilki Forest virus group includes?
Chikungunya = important one
(Africa and Asia; now also in C/S America and Florida) (pic B)
Also:
- SFV (Africa/Asia)
- O’nyong-nyong (Africa)
- Mayaro (Central/South America)
- Ross River (Australia/Oceania)
WEEV group includes?
- Sindbis (Europe, Asia, Africa, Australia)
How many people with Chikungunya develop clinical symptoms?
72-97%
Incubation period of Chikungunya?
3-7 days (range 1-12 days)
Clinical symptoms of Chikungunya?
Mainly fever and polyarthralgia
- Fever: abrupt onset, typically > 39’C (>102.2’F)
- Joint pain: sever, debilitating, multiple joints, bilateral, symmetric, most common in hands/feet
Also:
- Headache
- Myalgia
- Arthritis
- Conjunctivitis
- Nausea/vomiting
- Maculopapular rash
- Mortality rare (occurs mostly in older adults)
Resolution of acute symptoms with Chikungunya?
Typically resolve 7-10 days
Recovery phase of Chikungunya may involve?
- Some pts may have relapse of rheumatologic symptoms (polyarthralgia, polyarthritis, tenosynovitis, Raynaud’s) in months following acute illness
- Persistent joint pain for months to years in some
Diagnosis of Alphavirus infxn?
- Epidemiology (travel/exposure)
- Serology is primary means for New World (ELISA)
- Viremia in some old world viruses (e.g. Chikungunya) so isolation during initial illness
Treatment/prevention of alphavirus?
- Supportive (no antiviral therapy)
- Prevent by avoiding/controlling mosquitoes
- Investigational inactivated and live attenuated (e.g. VEE) vaccines for high risk individuals
T/F: Rubella is not an arbovirus
True; rubella is spread person-to-person
Symptoms of Rubella
- Mild febrile exanthem in children and adults
Infection when in pregnancy commonly results in congenital Rubella? Symptoms?
1st trimester especially
- Cataracts
- Deafness
- Cardiac abnormalities
Treatment/prevention of Rubella?
Vaccine preventable
What is the composition of Flaviviridae envelope?
Lipid
Three genera of Flaviviridae?
- Flavivirus
- Pestivirus
- Hepacivirus
Clinical syndromes of flavivirus?
- CNS dz (encephalitis, aseptic meningitis)
- Fever, arthralgia, rash
- Hemorrhagic fever
Flavivirus tick-borne viruses
- Kyasanur Forest dz (Haemaphysalis ticks)
- Omsk Hemorrhagic fever (Dermacentor ticks; also Culex, Aedes mosquitoes)
- Powassan virus (Ixodes ticks)
- Tick-borne encephalitis (Ixodes ticks)
Flavivirus mosquito-borne viruses
- Japanese encephalitis virus group
- Dengue virus group
- Yellow fever virus group
- Others
Flavivirus with no known arthropod vecto
Rio Bravo group
Japanese Encephalitis Virus Group includes?
- JEV
- Murray Valley encephalitis virus
- St. Louis encephalitis virus
- West Nile virus
When is the peak of Japanese Encephalitis virus?
Late summer/early fall
What is the age distribution of JEV infxn?
Bimodal: young and old
Incubation period of JEV?
4-14 days
What percentage of JEV infected show symptoms? Mortality of JEV?
1:300 symptomatic to non 10-35% mortality
Diagnosis of JEV
IgM ELISA
Prevention of JEV?
Inactivated vaccine
West Nile spread in US (2014)
Human infxn everywhere but Maine, Vermont, New Hampshire
Non-human infxn everywhere but Maine
How many infected with West Nile are asymptomatic?
70-80% subclinical with West Nile
How many infected develop West Nile fever? Sx?
20%
- Headache
- Arthralgias
- Vomiting
- Body aches
- Rash
- Diarrhea
How many infected with West Nile develop encephalitis/meningitis? Sx?
< 1%
- Aseptic meningitis
- Encephalitis
- Poliomyelitis- syndrome
Endemic areas of yellow fever?
Symptoms of yellow fever?
Undifferentiated febrile illness (resembles many other fevers)
Classic yellow fever:
- Fever, vomiting, epigastric pain
- Prostration, dehydration
- Scleral icterus
- Renal and hepatic abnormalities
- Hemorrhagic tendency GI bleeding- black vomitus
Phases of clinical yellow fever
Phase 1: nonspecific febrile illness
- Viremic pt but diagnosis difficult
Period of Remission
- Brief clinical improvement
- 3-4th day after onset
Phase 2: “intoxication”
- Hepatic and renal dysfunction
- Bleeding
Mortality rate for severe yellow fever?
50%
Prevention of yellow fever?
Efficacy?
Risks?
Live attenuated vaccine (17D strain)
- Grown in embyronated chicken eggs
- Protective immunity in > 90% at 10 days, > 99% at 30 days
- Very safe, but rare cases of yellow fever-like syndrome, post-vaccinal encephalitis, death (avoid in immunocompromised) Mosquito eradication, prevention of biting
How many serotypes of Dengue virus?
- 4 serotypes (possibly 5) of Dengue fever can cause severe and fatal dz
- Each serotype provides lifetime immunity and short-term cross-immunity
- Genetic variation within serotypes
- Some genetic variants within each serotype appear to be more virulent/have greater epidemic potential
Worldwide distribution of Dengue fever?
Clinical syndromes of Dengue (broad)?
- Undifferentiated fever
- Classic dengue fever
- Dengue hemorrhagic fever
- Dengue shock syndrome (rash)
Vector of Dengue fever?
Aedes aegypti mosquito
Diagnosis of Flavivirus?
- Serology (primary)
- RT-PCR
- Culture
Prevention/Treatment of Flavivirus?
Supportive (except Hep C…) Prevention:
- Vector control
- Vaccination (JEV, yellow fever, others not licensed in US)
T/F: Bunyaviridae is non-segmented?
False; it is tripartitie (3 segments)
Structural proteins of Bunyaviridae?
2 external glycoproteins:
- G1
- G2
Nucleocapsid protein (N)
Large transcriptase protein (L)
Four human genera of Buyaviridae?
- Bunyavirus
- Hantavirus
- Nairovirus
- Phlebovirus
Byunavirus genus includes? Geography?
California serogroup (Aedes triseriatus)
- California encephalitis (W. US, Canada)
- La Crosse (MW/E. US)– especially pediatric pops
- Jamestown Canyon (N. America)
- Tahyna (Europe)
Bunyamwera
Incubation period of California serogroup (Aedes triseriatus)?
3- 7 days
What does Nairovirus cause?
Crimean- Congo Hemorrhagic Fever
- Febrile illness followed by multi-organ failure
What is the vector for Nairovirus? Geography?
Tick-borne (Hyalomma)
Africa/Middle East/E Europe/Asia
Incubation of Nairovirus?
3-6 days
What does Phlebovirus cause?
Rift Valley fever
- Fever, myalgia, malaise encephalitis
Vector for Phlebovirus? Geography?
Sandfly fever viruses Endemic in sub-Saharan Africa
Transmission of Phlebovirus?
Potential for nosocomial spread
(aerosol; direct contact?)
Incubation of Phlebovirus?
2-6 days
Hantavirus causes what?
Hemorrhagic fever with renal syndrome (HFRS)
- Hantaan fever
- Seoul virus Hantavirus pulmonary syndrome (HPS)
- Sin nombre virus
- Flu-like illness followed by cap leak syndrome
- Most frequent: fever, myalgia, nausea/vomiting, cough
- Other: dizziness, arthralgia, SOB (later in course)
- Rare: rhinorrhea, sore throat
- Seen on chest x-ray: bilateral interstitial infiltrates (mod-rapid progression), bilateral alveolar infiltrates, or pleural effusion (hemorrhage not a major part of clinical syndrome)
Transmission of Hantavirus?
- 2ndary aerosols, mucous membrane contact, skin breaches…
- Virus present in aerosolized rodent excreta, particularly urine
- Horizontal transmission of infxn by intraspecific aggressive behavior
- Chronically infected rodent
New World Hantaviruses with geographic distribution
Diagnosis of Hantavirus
- Serologic (ELISA, HAI, Neutralization)– primary
- Antigen detection
- Culture (RVF, CCHF)
Prevention and treatment of Hantavirus
- Vector avoidance
- Vaccine (RVF- indicated, not licensed)
- Treatment is supportive (Ribavirin in HFRS, possibly in CCHF)
Arenaviridae unique genetic feature?
Ambisense
T/F: Arenaviridae is non-segmented
False; it is bipartite (2 segments- L and S)
Is Arenaviridae DNA or RNA?
RNA
Two serologic groups of Arenaviridae?
- Old world: LCM, Lassa fever
- New world: Junin fever, others
What is this?
Lass virus
What are the important Arenaviridae viruses associated with human dz?
- Lassa
- LCMV
(Also: Junin, Machupo, Guanarito, Sabia, LCMV)
Transmission of Arenavirus?
- Natural infxn of rodents
- Aerosolization of rodent excretions
- Nosocomial spread by contact with blood/body fluids
- Solid organ transplants
Symptoms of LCM?
Hemorrhagic fever
- N/V/D
- Pulmonary edema
- Capillary leak/bleeding
Endemic areas for Lassa fever?
- West Africa (Nigeria, Liberia, Sierra Leone, Guinea)
Infections and deaths due to Lassa fever?
300,000-500,000 infxns/year 5,000 deaths
Transmission of Lassa fever?
- Rodent-to-human (“multimammate rat, Mastomys species-complex)
- Secondary human-to-human transmission with the potential for nosocomial outbreaks with high cast fatality
Diagnosis and Treatment and Prevention of Lassa fever?
Diagnose:
- Serology
- Antigen detection
- RT-PCR
- Culture
Treatment:
- Ribavirin for lassa fever
- Convalescent serum also used
Prevention:
- No vaccines
- Rodent control
Two genera of Filoviridae?
- Marburgvirus
- Ebolavirus
Species of ebola?
- Zaire
- Sudan
- Bundibugyo
- Tai Forest
- Reston
What is this?
Ebola virus
Transmission of Filovirus?
Reservoir is fruit bats Infection seen after contact w/ infected primates or infected persons
What dz does Filovirus cause? time frame?
Hemorrhagic fever
Acute onset (typ 8-10 days after exposure, range 2-21 d)
- Fever, chills, myalgia, malaise, weakness
- GI Sx: vomiting, diarrhea, abdominal pain
- Miscarriage
- Hemorrhage is late sign (<50% of cases)
Diagnosis of Filovirus?
- Antigen detection (primary)
- EM
- Cell culture (BSL-4 agent)
- Serology
- RT-PCR
Treatment of Filovirus?
- Supportive
- Vaccines under development
Sequelae in survivors of Filovirus?
- Arthralgia/myalgia (frequent, severe, persistent)
- Prolonged asthenia
- Malnutrition
- Mental health issues
- Hearing loss
- Cardiac injury (e.g. myocarditis)
- Hearing loss
- Cerebral complications (e.g. seizures, encephalopathy)
- Ocular problems