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24 Cards in this Set

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Arbovirus Definition: “Arthropod-borne” virus

Virus cycles between _____ and ________ host

Only three arboviruses for which humans are a primary vertebrate host: (3)

Most other arboviruses that infect humans have other primary hosts (humans infected incidentally)
- Example?

Usual insect vectors: (3)
Viruses that are maintained in nature by a transmission cycle between susceptible vertebrate hosts and arthropods

Only three arboviruses for which humans are a primary vertebrate host: dengue, yellow fever, and Chkungunya viruses (possible explosive urban epidemics)

Most other arboviruses that infect humans have other primary hosts (humans infected incidentally)
- West Nile virus: birds

Usual insect vectors: mosquitoes, ticks, fleas
What is the number one mosquito borne arbovirus of the world?

What is the most clinically important form of this disease?
Dengue

Dengue Hemorrhagic Fever
Globally Important Arboviruses

Dengue Fever (DF) /Dengue Hemorrhagic Fever (DHF)

Transmitted by which type of mosquito?

Cycle?
Incubation?

If you don't have manifestation within __ weeks, you don't have dengue fever

How many serotypes?

Sequential infection can lead to ______ risk of ___

DF: Symptoms?
DHF: Symptoms?

Treatment?
- Transmitted by Aedes aegypti mosquito

Human-mosquito-human cycle: 2-10 day incubation

If you don't have manifestation within 2 weeks, you don't have dengue fever

4 serotypes of DV (DV1, DV2, DV3, and DV4)

Sequential infection can actually lead to augmented 2nd infection: increased risk of DHF

DF: “Breakbone fever” -- Fever, rash, HA, severe myalgia, arthralgia

DHF: Shock/DIC picture: DF + thrombocytopenia + bleeding

No treatment, (vaccine in clinical testing - phase I/II)
West Nile Encephalitis Virus - Epidemiology

Transmitted how?

Virus carried by?

Sign that virus is in area?
____ begin to die

Elderly or immunocompromised patients progress to ________ or ________
Mosquito transmitted

Migratory birds carry virus: hawks, jays, crows (in US virus kills birds - especially crows- not seen in old World)

~27,000 symptomatic human cases in US

Elderly or immunocompromised patients progress to aseptic meningitis or encephalitis
West Nile Virus Transmission

Cycle: Normally transmitted between _____ and ______

Can _________ be transferred to many types of mammals, including humans

Transmission occurs to humans from mosquitoes by _________

When ______ (type of bird) leave late summer/early fall, mosquitos start to infect humans
Normally between birds and mosquitoes

Can incidentally be transferred to many types of mammals, including humans

Transmission occurs to humans from mosquitoes by direct inoculation
West Nile Virus Epidemiology

~__ cases of meningoencephalitis per 140 infections

Higher risk in age > ___

Genetic susceptibility: CCR5-32, OAS1b

CCR5-32 deletion confers resistant to _____; but increased susceptibility for severe WNV infection
~1 case of meningoencephalitis per 140 infections

Higher risk in age > 55

Genetic susceptibility: CCR5-32, OAS1b

CCR5-32 deletion confers resistant to HIV; but increased susceptibility for severe WNV infection
Clinical Features of WNV Infection

- _-__ day (~_ weeks) incubation period post mosquito bite

- Typical case is ___(mild/severe?): (4) (symptoms last 3-6 days)

- Occasional ________ ____ (trunk>extremities) (rare in US cases)

- In elderly or patients with co-morbidities, may progress to (3)

- Virus infects and kills ________ _____ ______ neurons; may resemble _____

- Rare complications include (2)
- 5-15 day (2 weeks) incubation period post mosquito bite

- Typical case is mild: fever, HA, myalgia/arthralgia, anorexia (symptoms last 3-6 days)
- Sore throat and GI complaints (N/V/D) may occur

- Occasional maculopapular rash (trunk>extremities) (rare in US cases)

- In elderly or patients with co-morbidities, may progress to aseptic meningitis, encephalitis, flaccid paralysis

- Virus infects and kills anterior horn motor neurons; may resemble polio

- Rare complications include myocarditis and pancreatitis
West Nile Virus -Prognosis

- Recovery is usually ________ in __________ patients

- ____ (more/less) rapid recovery in adults compared to children, occasionally with residual deficits

- Of hospitalized patients, __% recovered but not to full functional level whereas __% recovered fully

- Most fatalities in patients > __ y.o.
- Recovery is usually complete in non-hospitalized patients

- Less rapid recovery in adults compared to children, occasionally with residual deficits

- of hospitalized patients, 50% recovered but not to full functional level whereas 40% recovered fully

- Most fatalities in patients > 50 y.o.
West Nile Virus Laboratory

Diagnosis:
- Serum Ig_ or paired Ig_ samples for immunoflourescence
a) Problem: cross reactivity with __________ ?

- Which lab is diagnostic?

Sensitivity
IgM (acute serum & CSF): __%
IgG (paired acute/convalescent sera): __% (basically, which is more sensitive?)

RT-PCR: ___ (high/low) sensitivity when viremic (short period)
Diagnosis

- Serum IgM or paired IgG samples for immunoflourescence
a) Problem: cross reactivity with other flaviviruses (St Louis, dengue, yellow fever - travel and vaccination history required)

- CSF IgM (Diagnostic for WNV)
- Serum or CSF RT-PCR for viral RNA

Sensitivity
IgM (acute serum & CSF): 70%
IgG (paired acute/convalescent sera): 90%

RT-PCR: high sensitivity when viremic (short period)

Nucleic acid based amplification assays
West Nile Encephalitis - Therapy and Vaccine

How do you treat West Nile Encephalitis?
All therapies are investigational

Vaccines: Investigational
- Killed (horses, birds - experimental)
- Chimeric Yellow Fever or Dengue strain
- Recombinant protein vaccine - E protein
- Attenuated Strain Vaccine - WNV 25

Vaccine issues: low frequency disease, side effects of immunization of large population
Chikungunya Virus

Chikungunya stands for

- Viral disease transmitted by?

- Virus Family? Genome?

- Causes? (symptoms)

- Treatment?

- Course?

- Mutations?
Chikungunya = contorted posture of patients with severe joint pain

- Viral disease transmitted by Aedes mosquitoes

- Member of Alphavirus family of RNA viruses (different from flavivirus)

- Causes a debilitating febrile illness (rash/joint pain/encephalitis)

- No vaccine/treatment

- Acute disease (lasts a few weeks); arthritis can take weeks/months to resolve due to long lasting inflammatory process

- Adaptive mutation (inc. amount of virus that replicates for longer period of time in mosquito host and inc. virulence in mammalian host) has led to explosive epidemics including recent disease in Italy

- Chikunugunya infection in returning US travelers

- Outbreaks: India, Indonesia, Malaysia, Singapore, Sri Lanka,Italy (1.3 million cases in India in 2006 alone)
Enterovirus Epidemiology

Family?

Envelope?

Serotypes?

Most infections are ____: manifestations = (2)

Some cause ____ disease: manifestations = (4)

Some cause chronic diseases: (3)
Belong to Picornaviridae family of RNA viruses

Non enveloped (important for why they spread easily)

Composed of more than 70 serotypes (1 set of Ab won’t protect as well as others)

Most enterovirus infections are mild
- Upper Respiratory Infection and febrile rash

Some cause severe disease: (heterogeneous)
- encephalitis, myocarditis, neonatal sepsis, polio

Some cause chronic diseases (heterogeneous)
-myocarditis, cardiomyopathy, neuromuscular disease
Enterovirus Epidemiology

Enterovirus epidemics predominate in _____ and _____(seasons?)

________ most likely to be affected

Most common age group: _-_ years old:
Due to: increased reporting bias; lack of cross-reactive immunity daycare exposure

Transmission mainly ____-____; also? (1)

Reservoirs?
Enterovirus epidemics predominate in summer and fall

Young children most likely to be affected

Most common age group: 1-4 years old

Due to: increased reporting bias; lack of cross-reactive immunity daycare exposure

Transmission mainly fecal-oral; also respiratory droplets

No non-human reservoirs
Epidemiology of Enterovirus Infections

One of the most important determinants is ___ - most primary infections occur during _________

_________ are most important for transmission cycle

_______ have more severe disease

Male:female ratio: ___ to ___

More prevalent in _________ and those living in _________
One of the most important determinants is age - most primary infections occur during childhood

children are most important for transmission cycle

Adults have more severe disease

Male predominance: 2 to 1 ratio

More prevalent in persons of low socioeconomic status and those living in urban areas
Steps in Enterovirus Pathogenesis

Describe the steps
Vaccines: Polio as a Model - Global Eradication

With global incidence declining, CDC recommends exclusive use of _____-______ vaccine only
- eliminates vaccine-associated paralytic poliomyelitis and shedding of vaccine virus

___ cases of paralytic polio in US since 1980
With global incidence declining, CDC recommends exclusive use of heat-killed vaccine only
- eliminates vaccine-associated paralytic poliomyelitis and shedding of vaccine virus

No cases of paralytic polio in US since 1980
________ are the main recognized cause of aseptic meningitis in children and adults of developed countries

What type of virus?

Suspect more during which sesons?

What associated symptoms should you look out for?

Diagnosis can be made with?
Enteroviruses are the main recognized cause of aseptic meningitis in children and adults of developed countries

Coxsackievirus group B: isolated from 62% of infants (< 3mo) with aseptic meningitis

Should be suspected as the causative agent of aseptic meningitis
during the summer and fall seasons

Rash may be present: Coxsackie A5, A9, A16; echovirus 4, 6,9

RT-PCR used in diagnosis
- Coxsackievirus B5
- Echoviruses 4, 6, 9 and 11
- Enterovirus 71: emerging
Enteroviruses and Respiratory Infections

Most frequently associated with URI (3)
- _________
- ________ (inflammation of upper airway, bark like a seal)
- ________ (can compromise airways)

Severity: URIs tend to be ___ and _____

Rarely, can cause lower respiratory tract infection, such as _______ ________?
Enteroviruses are a common cause of URI

Most frequently associated with URI
- common cold
- croup (inflammation of upper airway, bark like a seal)
- epiglottitis (can compromise airways)

URIs tend to be mild and self-limited

Rarely, can cause lower respiratory tract infection, such as interstitial pneumonia
Enteroviruses Cause Encephalitis

More severe and worse prognosis than ________: directly affects neurons

Manifestations? (3)

Can get ____ ________ syndrome:

Increased incidence of Enterovirus ___: clinically fare worse; this strain is more virulent; case fatality rate of CNS infection ranges from 7 to 31%
More severe and worse prognosis than meningitis: directly affects neurons

Altered mental status, focal neurologic signs, seizures

Can get acute cerebellar syndrome: polio, echoviruses, coxsackie A2 and A9

Increased incidence of Enterovirus 71: clinically fare worse; this strain is more virulent; case fatality rate of CNS infection ranges from 7 to 31%
Enteroviruses Cause Cardiac Disease

Acute Cardiac Disease
Which Enterovirus is main culprit?
Peak age group?

Chronic Cardiac Disease
Which type of heart disease?
Which group most common?
Virus isolated from specimen?
Possible mechanism?
Acute Cardiac Disease
Enteroviruses implicated as agent of viral myocarditis

Coxsackievirus B5 main culprit; other strains implicated

Peak age group: Young adults 20-39, increased males


Chronic Cardiac Disease
Implicated in sporadic dilated cardiomyopathy

Coxsackievirus B group most common

Virus not isolated from specimens

Possible immunopathogenic mechanism (mimicry?)
Enteroviruses Caues Eye Infections

What type of eye infection is most commonly caused by enteroviruses?

Symptoms?

Disease resolves in __ weeks?
Acute hemorrhagic conjuctivitis – most commonly caused by enteroviruses

Excessive lacrimation, pain, periorbital swelling,redness, possible visual impairment

Disease resolves in 1-2 weeks without sequelae

Also sporadic conjuctivitis and keratoconjuctivitis
Enteroviruses Cause Herpangina

Herpangina is?

Characteristic lesions on the?

May be as part of a constellation of ___-____-_____ disease: vesicular lesions of the hand, feet, mouth,

Several enteroviruses associated with herpangina: ?
Herpangina is a febrile illness of acute onset with fever and sore throat

Characteristic lesions on the anterior tonsils, soft palate, uvula, tonsils, and pharynx

May be as part of a constellation of hand-foot-and-mouth disease: vesicular lesions of the hand, feet, mouth,

Several enteroviruses associated with herpangina: coxsackie A/B, echoviruses, and enterovirus 71
Diagnosis of Enteroviral Infections

Std diagnostic tool?
RT-PCR of viral RNA from clinical specimen
Therapy for Enteroviral Infections

?
- There is no therapy
- Supportive care