Download Rotavirus

Medical Virology
Lecture 03/04
Viruses associated with
gastrointestial tract infections
Enterovirus of picornaviridae & acute gastroenterities virus
Youjun Feng
Center for Infection & Immunity, Zhejiang University School of Medicine
[email protected]
Viruses infected through gastrointestinal tract
Enteroviruses of picornaviridae
Acute gastroenteritis viruses
• Polioviruses
• Rotavirus
• Coxsackieviruses
• Calicivilus
• Echoviruses
• New enteroviruses
Norovirus
Sapovirus
• Astrovirus
• Enteric adenovirus
Parenteral disease
Viral gastroenteritis/viral
diarrhea
Enterovirus of picornaviridae
PICORNAVIRUSES
Small RNA Viruses
icosahedral symmetry
Non-enveloped
+ strand RNA
+ Strand RNA is infectious, serves as mRNA
Most are very cytolytic to cells
PICORNAVIRUSES
Members
Virus
Disease
Enterovirus
Poliovirus
Poliomyelitis
Coxsackie Virus A
Herpangina, Hand Foot and Mouth disease
Coxsackie B
Myocarditis, Pericarditis
Echovirus
other Enterovirus
Rhinovirus
100 serotypes
Heparnavirus Hepatitis A virus
Common Cold
Hepatitis
Enterovirus of picornaviridae
parenteral disease
DISEASE MECHANISMS
Transmission route:
Fecal-oral
Season:
summer
DISEASE MECHANISMS
Viremia
Enterovirus of picornaviridae
Poliovirus
Poliovirus
Members
Serotypes
Disease
Poliovirus
Coxsackie Virus A
Coxsackie B
Echovirus
other Enterovirus
1-3
1-22, 24
1-6
1-9, 11-27, 29-34
Poliomyelitis
Herpangina, Hand Foot
and Mouth disease
Myocarditis, Pericarditis
Poliovirus & poliomyelitis
Poliovirus & poliomyelitis
In spinal paralysis one or more limbs
may be affected or complete flaccid
paralysis may occur.
Iron lung
•
•
In bulbar paralysis cranial nerves and the
respiratory center in the medulla are
affected leading to paralysis of neck and
respiratory muscles.
no sensory loss
Polio vaccines
Decline in Poliomyelitis
World Polio Map
World Polio Map
World Polio Map
Current situation
In 2011, only four countries (Afghanistan, India, Nigeria and
Pakistan) remain polio-endemic, down from more than 125
in 1988.
In 2012, only three countries (Afghanistan, Nigeria and
Pakistan) remain polio-endemic, down from more than 125
in 1988.
Current situation
http://www.who.int/csr/don/2011_09_01/en/index.html
Enterovirus of picornaviridae
Coxsackieviruses
Echoviruses &New Enteroviruses
Other enteroviruses & diseases
PATHOGENESIS
Fecal-Oral route trasmission
Spread in the body like polioviruses
Disease Associations
Paralytic Disease
Meningitis Enc
ephalitis
Undifferentiated febrile illness
Hand foot mouth disease.
Herpangina
Epidemic Pleurodynia (Bornholm disease)
Myocarditis
Respiratory Infections
Rubelliform rashes.
Neonatal Infection
Conjunctivitis
Pancreatitis/Diabetes
Exanthems
- Rubelliform rashes
- EV leading cause in summer & fall. All types of rash
Herpangina/
•Herpangina – usually coxackie A
• acute onset, fever, sore throat,
dysphagia
• lesions – posterior pharynx
• no gingivitis
Hand-foot-and-mouth disease
• Hand-foot-and-mouth
Hand food and mouth disease(HFMD)
disease:
•
mostly coxackie A 14, HEV71
– fever, malaise, sore throat,
vesicles on bucal mucosa,
tongue, hands, feet, buttocks
•
highly infectious
•
resolution – 1w
Typical lesions around the
Mouth of an 11 month old male
Management and Prevention
• no specific antiviral therapy
available
• no vaccine available mainly because
of the multiplicity of serotypes
Viruses infected through gastrointestinal tract
Enteroviruses of picornaviridae
Acute gastroenteritis viruses
•
Polioviruses
•
Rotavirus
•
Coxsackieviruses
•
Calicivilus
•
Echoviruses
•
New enteroviruses
parenteral disease
Norovirus
sapovirus
•
Astrovirus
•
Enteric adenovirus
viral gastroenteritis/viral
diarrhea
Viruses infected through gastrointestinal tract
rotavirus
Rotavirus Pathogenesis
• Universal disease
– All children are exposed and acquire
antibodies by age 5
• Leading cause of severe dehydrating
diarrhea in infants and young children
• Sudden onset of watery diarrhea, fever
and vomiting
• Recovery in 4-5 days
Rotavirus Transmission
• Fecal-oral?
– Improvements in water, sanitation, hygiene
have not decreased incidence
Diagnosis
• Rapid diagnosis - antigen detection in stool by
ELISA (uses a monoclonal antibody).
• Electron microscopy
Rotavirus vaccines
• Wyeth - Rotashield (Sept. 1998)
– Live, oral, tetravalent
– human/simian re-assortant viruses
– withdrawn in 1999 due to increased
incidence of intus-susception
• Merck - Rotateq (Feb. 2006)
– Live, oral, penta-valent
– Bovine/human re-assortant viruses
Rotavirus vaccines
• GSK - Rotarix; not yet available in U.S.
– Live, oral, attenuated, human
– Mono-valent
– Cross-protective, replicates well in GI
Treatment and prevention
• Treatment
Supportive - rehydration (oral / intravenous)
Antiviral agents not known to be effective
• Prevention of spread
Hand washing with good technique
Disinfection of surfaces, toilets, toys
Norwalk virus
•First discovered in Norwalk, Ohio
•Has been at the root of several epidemics or outbreaks of
gastroenteritis across North America in hospital emergency rooms,
schools and even on cruise ships
•There is a group of similar or related viruses that are referred to as
Norwalk-like viruses or agents.
•Can infect people of any age and usually cause profuse watery diarrhea,
vomiting and fatigue.
•The infection lasts a few days and there is no specific treatment.
•Most of the time, it spreads form one person to another through direct
or indirect contact with infected feces or vomit.
•The infection develops within 1-2 days after contact with an infected
person.
SUMMARY
1. Know the common viruses infected through
gastrointestial tract: Enterovirus of
picornaviridae and acute gastroenteritis virus.
2. Understand the properties of picornaviruses.
3. Master the clinical findings as a result of
rotavirus infection.
Self control questions
1.Each of the following statements regarding rotavirus is correct EXCEPT:
(A)the infection mainly affects children younger than 3 years
(B)it is a major cause of death in children in developing countries
(C)a high viral concentration is necessary for a efficient transfer of the virus
(D)in the northern hemisphere the virus is transmitted during the winter/spring
season
2.Each of the following statements regarding norovirus is correct EXCEPT:
(A)the infection mainly affects younger children and older people as well
(B)epidemics occur every 2 to 3 years
(C)the first line diagnostics is the detection of the virus by PCR from fecal
samples
(D)a vaccine is available that protects people from norovirus infection
3. Each of the following statements regarding the mode of action of the viruses/bacteria is
correct EXCEPT:
A. noroviruses possess an enzyme that inhibits proteinsynthesis of the host cell
B. rotaviruses induce cell death (apoptosis) thereby causing diarrhea
C. Shigella produces a N-glycosidase that has a specificity for 28S ribosomal RNA and upon
this action stops protein synthesis of the host cell
D. Vibrio cholerae ADP-ribosylates G-proteins and thereby activates an adenylate cyclase
which indirectly affects the efflux of water
4. Each of the following statements regarding the treatment of severe diarrhea is correct
EXCEPT:
A. if possible glucose should be given the oral way at a concentration of 20g/L
B. Chloride and bicarbonate losses should be included in the glucose/electrolyte solution to
compensate anionic loss
C. sodium and potassium losses should be included in the glucose/electrolyte solution to
compensate cationic loss
D. coca cola contains all the electrolytes and the glucose to compensate the loss of glucose
and electrolytes that are lost during diarrhea
5. Each of the following statements regarding the infectious dose of the viruses/bacteria is
correct EXCEPT:
A.
B.
C.
D.
noroviruses have an infectious dose lower than 100 particles
rotaviruses have an infectious dose higher than 1000 particles
campylobacter requires 1000 to 10.000 particles to become infective
Vibrio cholerae requires > 1.000.000 particles to become infective
6. Please describe the general properties of picornaviruses.
7. What are the clinical findings as a result of rotavirus infection versus Norwalk virus
infection?
8. What causes poliomyelitis? What is the route of infection? What is the global
situation of the disease? How about the vaccine?