viruses associated with gastrointestial tract infections medical virology lecture 03/04 youjun feng...

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Viruses associated with gastrointestial tract infections Medical Virology Lecture 03/04 Youjun Feng Center for Infection & Immunity, Zhejiang University School of Medicine [email protected] .cn Enterovirus of picornaviridae & acute gastroenterities virus

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Viruses associated withgastrointestial tract infections

Medical VirologyLecture 03/04

Youjun Feng

Center for Infection & Immunity, Zhejiang University School of Medicine

[email protected]

Enterovirus of picornaviridae & acute gastroenterities virus

Viruses infected through gastrointestinal tract

Enteroviruses of picornaviridae Acute gastroenteritis viruses

Polioviruses

Coxsackieviruses

Echoviruses

New enteroviruses

Parenteral disease

• Rotavirus

• Calicivilus

NorovirusSapovirus

• Astrovirus

• Enteric adenovirus

Viral gastroenteritis/viraldiarrhea

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

Members

Enterovirus

Virus

Poliovirus

Disease

Poliomyelitis

Rhinovirus

Heparnavirus

Coxsackie Virus A

Coxsackie B

Echovirus

other Enterovirus

100 serotypes

Hepatitis A virus

Herpangina, Hand Foot and Mouth disease

Myocarditis, Pericarditis

Common Cold

Hepatitis

PICORNAVIRUSES

Enterovirus of picornaviridae

parenteral disease

DISEASE MECHANISMS

Transmission route:Fecal-oral

Season:

summer

Viremia

DISEASE MECHANISMS

Enterovirus of picornaviridae

Poliovirus

Poliovirus

DiseasePoliomyelitis

Herpangina, Hand Foot

and Mouth disease

Myocarditis, Pericarditis

Serotypes1-3

1-22, 24

1-6

1-9, 11-27, 29-34

MembersPoliovirus

Coxsackie Virus A

Coxsackie B

Echovirus

other Enterovirus

Poliovirus & poliomyelitis

Poliovirus & poliomyelitis

In spinal paralysis one or more limbsmay be affected or complete flaccid

paralysis may occur.

In bulbar paralysis cranial nerves and therespiratory center in the medulla areaffected leading to paralysis of neck andrespiratory muscles.

no sensory loss

Iron lung

Polio vaccines

Decline in Poliomyelitis

World Polio Map

World Polio Map

World Polio Map

In 2011, only four countries (Afghanistan, India, Nigeria and

Pakistan) remain polio-endemic, down from more than 125

in 1988.

Current situation

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 AssociationsParalytic Disease

Meningitis Encephalitis

Undifferentiated febrile illnessHand foot mouth disease.

HerpanginaEpidemic Pleurodynia (Bornholm disease)

MyocarditisRespiratory InfectionsRubelliform rashes.Neonatal Infection

ConjunctivitisPancreatitis/Diabetes

Exanthems- Rubelliform rashes

- EV leading cause in summer & fall. All types of rash

•Herpangina – usually coxackie A• acute onset, fever, sore throat,

dysphagia• lesions – posterior pharynx• no gingivitis

Herpangina/

• Hand-foot-and-mouth

disease:

mostly coxackie A 14, HEV71

– fever, malaise, sore throat,vesicles on bucal mucosa,tongue, hands, feet, buttocks

highly infectious

resolution – 1w

Hand-foot-and-mouth disease

Hand food and mouth disease(HFMD)

Typical lesions around theMouth of an 11 month old male

Management and Prevention

• no specific antiviral therapyavailable

• no vaccine available mainly becauseof the multiplicity of serotypes

Viruses infected through gastrointestinal tract

Enteroviruses of picornaviridae Acute gastroenteritis viruses

Polioviruses

Coxsackieviruses

Echoviruses

New enteroviruses

parenteral disease

Rotavirus

Calicivilus

Norovirussapovirus

Astrovirus

Enteric adenovirus

viral gastroenteritis/viraldiarrhea

Viruses infected through gastrointestinal tract

rotavirus

Rotavirus Pathogenesis

• Universal disease– All children are exposed and acquire

antibodies by age 5

• Leading cause of severe dehydratingdiarrhea in infants and young children

• Sudden onset of watery diarrhea, feverand 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 byELISA (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 increasedincidence 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

• TreatmentSupportive - rehydration (oral / intravenous)Antiviral agents not known to be effective

Treatment and prevention

• Prevention of spreadHand washing with good techniqueDisinfection of surfaces, toilets, toys

•First discovered in Norwalk, Ohio

•Has been at the root of several epidemics or outbreaks ofgastroenteritis 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 asNorwalk-like viruses or agents.

Norwalk virus

•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 director indirect contact with infected feces or vomit.

•The infection develops within 1-2 days after contact with an infectedperson.

SUMMARY

1. Know the common viruses infected throughgastrointestial tract: Enterovirus ofpicornaviridae and acute gastroenteritis virus.

2. Understand the properties of picornaviruses.

3. Master the clinical findings as a result ofrotavirus infection.

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/springseason

Self control questions

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 fecalsamples(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 iscorrect EXCEPT:

A. noroviruses possess an enzyme that inhibits proteinsynthesis of the host cellB. rotaviruses induce cell death (apoptosis) thereby causing diarrheaC. Shigella produces a N-glycosidase that has a specificity for 28S ribosomal RNA and upon

this action stops protein synthesis of the host cellD. 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 correctEXCEPT:

A. if possible glucose should be given the oral way at a concentration of 20g/LB. Chloride and bicarbonate losses should be included in the glucose/electrolyte solution to

compensate anionic lossC. sodium and potassium losses should be included in the glucose/electrolyte solution to

compensate cationic lossD. coca cola contains all the electrolytes and the glucose to compensate the loss of glucose

and electrolytes that are lost during diarrhea

6. Please describe the general properties of picornaviruses.

7. What are the clinical findings as a result of rotavirus infection versus Norwalk virusinfection?

8. What causes poliomyelitis? What is the route of infection? What is the globalsituation of the disease? How about the vaccine?

A. noroviruses have an infectious dose lower than 100 particlesB. rotaviruses have an infectious dose higher than 1000 particlesC. campylobacter requires 1000 to 10.000 particles to become infectiveD. Vibrio cholerae requires > 1.000.000 particles to become infective

5. Each of the following statements regarding the infectious dose of the viruses/bacteria iscorrect EXCEPT: