CHILDREN DISEASES – PICORNAVIRIDAE (POLIO) AND VARICELLA ZOSTER pdf
1. CHILDREN DISEASES –
PICORNAVIRIDAE (POLIO) AND
HERPESVIRIDAE (CHICKENPOX)
PRESENTED BY GABRIEL FIOSSI ASSAGBA
AND YOLANDA LINDSAY MABUTO
VIROLOGY SS2016
2. TAXONOMY
• Single stranded
• Naked
• Positive sense
• Smallest known virus
http://what-when-how.com/wp-content/uploads/2011/05/tmp2499_thumb1.jpg
3. CLASSIFICATION
Order: Picornavirales
Family: Picornaviridae
Genus:
• Hepatovirus
• Hepatitis A virus
• Cardiovirus
• Cardiovirus A
• Apthovirus
• Foot-and-mouth
disease virus
• Parechovirus
• Human parechovirus
• Ljungan virus
• Enterovirus
• Enterovirus A
• Enterovirus B
• Enterovirus C
• Enterovirus D
• Enterovirus E
• Enterovirus F
• Enterovirus G
• Enterovirus H
• Enterovirus J
• Rhinovirus A
• Rhinovirus B
• Rhinovirus C
4. HISTORY
• 2000 Egyptian depictions of a young man with an
BC atrophied limb believed to represent poliomyelitis
• 1789 First clinical descriptions of poliomyelitis
• 1890 Description of infantile paralysis
• 1897 Foot-and-mouth disease virus (FMDV) was discovered
• 1908 Polio virus isolated
• 1949 Identification of 3 Polio serotypes and viral replication in
culture developed
• 1952 Polio epidemic in the United States with over 21,000
paralytic cases
• 1955 The development of Salk vaccine
• 1961 The development of Sabin vaccine
• 1988 Global polio eradication initiative by WHO
• 1989 Identification of the polio receptor CD155
https://en.wikipedia.org/wiki/History_of_poliomyelitis
http://www.microbiologybook.org/lecture/images/polioem.jpg
5. VIRION
• Morphology spherical
• Envelope no
• Diameter (nm) 27–30
• Structural components core, capsid
• Additional information simple, small virus
acid stable and insensitive
to inorganic solvents
http://viralzone.expasy.org/all_by_protein/97.html
6. GENOME
• Nucleic acid RNA
• Strandness single-stranded
• Polarity positive sense
• Configuration linear
• Segments 1
• Size (kb) 7.1 – 8.9
• Transcription units 1
• Additional information RNA serves as both genome
and viral mRNA
7. GENOME
Viral Protein (VPg)
P1 region: Structural proteins
P2 and P3: Non structural protein
associated with
replication
IRES: Direct translation of
polyprotein
http://viralzone.expasy.org/all_by_species/33.html
8. REPLICATION STRATEGY
• Entry mechanism receptor binding (CD 155)
endocytic pathway
• Site of transcription cytoplasm
• Site of genome replication cytoplasm
• Replication intermediate double stranded RNA
• Site of virion assembly cytoplasm
• Egress mechanism lysis
10. POLIOVIRUS SEROTYPES
• Serotypes: Poliovirus 1, 2 and 3
• Structure: Slight differences in capsid protein
• Occurrence:
http://www.polioeradication.org/mediaroom/newsstories/Three-Years-with-No-Wild-Poliovirus-Type-3/tabid/526/news/1312/Default.aspx
11. EPIDEMIOLOGY
Reservoir : human
Transmission: faecal – oral route
oral – oral route
Temporal pattern: seasonal in temperate climates but less in
tropical climates
Incubation period: between 3 – 35 days
Prone areas: poor sanitation and overcrowding
http://sphweb.bumc.bu.edu/otlt/MPH-Modules/PH/Polio/Polio_NEW2.html
12. PATHOGENESIS
http://polioandprevention.blogspot.de/
Viremic phase
The virus replicates in the oropharyngeal and intestinal mucosa
Virus spreads to tonsils and multiplies in Peyer`s patches, cervical and
mesenteric nodes
Virus is absorbed into bloodstream and spreads to internal organs and lymph
nodes
No further spread of the virus
Asymptomatic or mild
Febrile undifferentiated illness
Neurologic phase
Virus spreads to spinal
cord and brain Paralysis
Alimentary phase
Lymphatic phase
13. CLINICAL MANIFESTATIONS
Outcomes of Polio Infection
Outcome Proportion of cases
No symptoms 72%
Abortive poliomyelitis 24%
Nonparalytic aseptic
meningitis
1–5%
Paralytic poliomyelitis 0.1–0.5%
Spinal polio
Bulbospinal polio
Bulbar polio
79% of paralytic cases
19% of paralytic cases
2% of paralytic cases
14. ABORTIVE POLIOMYELITIS
• Mild non specific illness
• Lasts for about 2 – 3 days
• Symptoms include:
• Fever
• Headaches
• Vomiting
• General discomfort
• Complete recovery in a week
• Does not affect the CNS
http://poliocta5.weebly.com/signs-and-symptoms.html
15. NONPARALYTIC ASEPTIC MENINGITIS
• Nonparalytic illness
• Lasts between 2 – 14 days
• Symptoms include:
• Symptoms of abortive poliomyelitis
• Stiffness and pain of neck and back
• Abnormal reflexes
• Problems with swallowing
• Does not involve CNS
http://poliocta5.weebly.com/signs-and-symptoms.html
16. PARALYTIC POLIOMYELITIS
• Most severe form of poliomyelitis
• Begins with 2 – 3 days of minor illness
• Starting with symptoms of Abortive
poliomyelitis and Aseptic meningitis
• Loss of reflexes
• Severe muscle aches or weakness
• Flaccid paralysis
• Paralysis beyond six months is permanent
http://www.glogster.com/fishblitz/polio/g-6kvh3qdu797kikdo5nl9ea0
17. SPINAL POLIO
• More common (79%)
• Paralysis is flaccid and asymmetrical
• Normally affects the extremities
• Paralysis ranges from mild to quadriplegia
• Lethality
• Children: 2 – 5%
• Adults: 10 – 30%
http://www.premiumtimesng.com/news/headlines/178845-fact-check-jonathan-health-minister-lied-about-polio-eradication-in-nigeria.html
18. BULBOSPINAL POLIO
• Affects the diaphragm
• Leads to paralysis of arms and legs
• May affect swallowing and heart
functions
• Patients are sustained using artificial
ventilator
https://regionreporter.wordpress.com/2014/02/19/vaccine-preventable-illness-affected-many-lives/
19. BULBAR POLIO
• Involves the nerves in the bulbar
region
• Symptoms:
• Difficulty in breathing, speaking and
swallowing
• Facial and tongue weakness
• Pulmonary oedema and shock may occur
• May be fatal
https://en.wikipedia.org/wiki/Corticobulbar_tract
21. POSTPOLIO SYNDROME
• Slowly progressive muscular atrophy with evidence of ongoing
motor nerve damage
• 15–30 years after recovery
• 25–50% of people who have previously survived
https://www.pinterest.com/tttheroux/post-polio-syndrome/
22. DIAGNOSIS
• Laboratory Diagnosis:
• Viral isolation from stool sample or pharynx
• Cerebrospinal fluid analysis
• Increased levels of polio antibodies from serological tests
https://www.youtube.com/watch?v=iKGGuQlSyEs
23. TREATMENT
• There is no cure for polio
• Treatment is usually supportive focused on the relief of symptoms
and preventing complications
• These normally include:
• Antibiotics to prevent infection of weakened muscles
• Analgesics for pain
• Moderate exercise
• Nutritious diet
http://www.buffalovalley.org/treatment.html
24. PREVENTION
• Vaccination
• There are two vaccines available :
• Inactivated Polio Vaccine (1955) • Oral Polio Vaccine (1961)
http://www2.cedarcrest.edu/academic/bio/hale/bioT_EID/lectures/poliovaccines.html
http://www.polioplace.org/people/albert-b-sabin-md
25. VACCINE DERIVED POLIO VIRUS (VDPV)
• Mutated strains from Oral Polio Vaccine
• Rarely cause paralysis
• Estimated occurrence is 1 in 27 million
Types :
1. circulating vaccine-derived poliovirus (cVDPV)
2. immunodeficiency-related vaccine-derived poliovirus (iVDPV)
3. ambiguous vaccine-derived poliovirus (aVDPV)
• Risk factors are low immunization rates, poor sanitation, high population
densities
• Management:
• Immunization and surveillance in areas of outbreak
• The Trivalent to Bivalent Oral Polio Vaccine Switch - Between 17 April and 1 May,
2016
26. POLIO ERADICATION
• World wide effort to eradicate all cases of polio infection started in
1988 led by WHO, UNICEF, Rotary Foundation and partnered by Bill
and Melinda Gates Foundation
• Nearly $10 billion raised and donated to eradication cause
• 2.5 billion children have been immunized since its inception
• It is projected that the world will save $50 billion when polio is
eradicated
http://elbiruniblogspotcom.blogspot.de/2012/03/cdc-global-health-polio-our-progress.html
27. POLIO ERADICATION
TWO LAST REMAINING COUNTRIES WITH WILD POLIO CASES
http://outbreaknewstoday.com/afghanistan-reports-1st-polio-case-of-2015/
28. OBSTACLES TO POLIO ERADICATION
• Lack of basic sanitation services
• Lack of basic health infrastructure
• Effects of civil war and internal strife
• Maintenance of potency of the live vaccine in extremely hot and remote
areas
• Opposition and aid workers killings
• Unfounded myths about Polio vaccine
29. MYTHS OF THE POLIO VACCINE
• USA was using the vaccine to sterilize local population in Pakistan
leading to Taliban attacks on vaccination workers
• Northern Nigeria that the vaccine makes girls sterile
• Infection of people with HIV/AIDS through vaccination
• Polio vaccine spreads cancer
https://www.pinterest.com/geraldvanderhof/vaccination
30. NEWS
Summary
• Number of polio cases
reduced with last reported
case in 2013
• Attributed to effective
surveillance and prompt
response to reports
• Effective use of resources
and accountability of results
• Implementation of strategies
in Ebola outbreak in 2014
https://jid.oxfordjournals.org/content/213/suppl_3/S65.full
33. CLASSIFICATION
Order-Family-Subfamily-Genus-Species
Order: Herpesvirales
Family: Herpesviridae
Subfamily
Alphaherpesvirinae
• Simplexvirus
o Human herpesvirus 1 (HSV-1)
o Human herpesvirus 2 (HSV-2)
• Varicellovirus
o Human herpesvirus 3 (VZV)
Betaherpesvirinae
• Cytomegalovirus
o Human herpesvirus 5 (HSV-5)
• Roseolovirus
o Human herpesvirus 6 (Roseola virus)
o Human herpesvirus 7 (Roseola virus)
Gammaherpesvirinae
• Lymphocryptovirus
o Human herpesvirus 4 (Epstein-Barr virus)
• Rhadinovirus
o Human herpesvirus 8 (Kaposi’s sarcoma-associated
herpesvirus)
http://en.m.wikipedia.org/wiki/File:Herpesviridae_EM_PHIL_2171_lores.jpg
34. HISTORY
• 1867 Herbeden distinguished between small pox and varicella
• 1888 Von Bokay suggested varicella and herpes zoster were caused
by same agent
• 1892 Von Bokay further suggests infectious aetiology and pathogenic
relationship between them
• 1911 Aragao saw the first particles with light microscopy
• 1919 Paschen first described the elementary bodies
• 1925 Kundratitz inoculated children with herpes zoster fluids
• 1933 Amies confirms Paschen´s description of VZV
• 1943 Ruska first described appearance of VZV with electron microscopy
• 1943 Garland discovers herpes zoster caused by VZV reactivation
35. HISTORY
• 1952 Weller and Stoddard confirmed one causal agent for both diseases
• 1974 Hilleman made the advent of the live attenuated vaccine virus
• 1981 Merck licensed the “Oka” strain of VZV in the United States
• 1986 Complete nucleotide sequence of VZV determined
• 1988 Varicella vaccine was licensed for use in Japan and Korea
• 1995 Varicella vaccine developed and introduced in the USA
• 2005 A combination vaccine containing attenuated measles, mumps,
rubella and varicella virus (MMRV)
• 2006 Vaccine for herpes zoster licensed
• 2012 Injuries and deaths reported following varicella vaccination
37. GENOME
• Nucleic acid DNA
• Strandness double-stranded
• Configuration linear
• Segments 1
• Size (kb) >152
• Transcription units 86
• Additional information DNA can isomerize
38. GENOME
TRL Terminal repeat long
UL Unique long region
IRL Internal repeat long
IRs Internal repeat short
US Unique Short
TRS Terminal Repeat
http://journals.cambridge.org/fulltext_content/ERM/ERM7_15/S146239940500966Xsup005.htm
• US region can orientate either of two directions
• Two isomers of the genome in infected cells
39. VZV GENES AND THEIR LOCATION AND FUNCTION
ORF VIRION LOCATION PREDICTED FUNCTION
4 Tegument Transactivator
9 Tegument Complex with gE
10 Tegument Transactivator
11 Tegument RNA binding
14 Envelope gC
20 Capsid Capsid assembly protein
21 Capsid Nucleocapsid protein
23 Capsid Small capsid surface protein
40 Nucleocapsid Capsid assembly protein
Adapted from David M. Knipe. P. Mowley. Field’s virology volume 2 6th edition
40. REPLICATION STRATEGY IN PRIMARY INFECTION
• Entry mechanism fusion of viral envelope with
plasma membrane
• Site of transcription nucleus
• Site of genome replication nucleus
• Site of virion assembly nucleus
• Egress mechanism vesicular transport from nuclear
membrane to extracellular space
LYTIC
41. REPLICATION STRATEGY IN LATENCY
• Circular viral genome in nucleus
• Reactivation into primary cycle
42. REPLICATION STRATEGY IN LATENCY
• Circular viral genome in nucleus
• Reactivation into primary cycle
• Immunosuppression
Reactivation by
www.netanimations.net/Moving_Animated_Quuestion_Marks_And_Exclamation_Point_Gif_Animations.htm
43. REPLICATION STRATEGY IN LATENCY
• Circular viral genome in nucleus
• Reactivation into primary cycle
• Immunosuppression
• Stress
Reactivation by
http://mercedeskaygold.com/stressed/
45. PATHOGENESIS OF VARICELLA
INOCULATION T CELL VIREMIA
PRIMARY SKIN
INFECTION
RETROGRADE
TRANSPORT
http://www.nature.com/nrmicro/journal/v12/n3/images/nrmicro3215-f1.jpg
49. CLINICAL MANIFESTATIONS
• Varicella (Chickenpox)
• Pruritic vesicular rash throughout body
(begins scalp, face or trunk)
• Red bumps to draining blisters then scabs
• Fever, malaise, headache and abdominal
pain
• Complication: Varicella pneumonia
• Herpes zoster (Shingles)
• Vesicular rash restricted to dermatomal
distribution
• Reactivation from latency
(Immunocompromised patients and elderly)
• Complication: Post-Herpetic Neuralgia
(PHN)
http://img.webmd.com/dtmcms/live/webmd/consumer_assets/site_images/media/medical/hw/n5551347.jpg
http://www.craigzuckerman.net/portfolio/shingles-moderate/
50. OTHER DISEASES AND COMPLICATIONS
• Neonatal varicella
• Congenital varicella
• Meningitis
• Hepatitis
• Pancreatitis
• Bacterial superinfection
51. EPIDEMIOLOGY
Occurrence: worldwide
Incidence: 15 -16 per 1000 (VZV)
1.5 – 3.0 per 1000 (HZ)
Reservoir: human
Transmission: airborne, direct contact with lesion
Temporal pattern: differs between temperate and tropical climate
tropical areas more adults affected
Incubation period: 10 – 21 days
Risk factors: immunocompromised people
pregnant women
unvaccinated individuals
52. DIAGNOSIS
• Differential
• Differentiated from rashes caused by
other pathogens
• Laboratory
• Detection of Varicella IgG antibodies with ELISA
• Viral isolation in culture
• Viral DNA detection by PCR and DFA
• Immunohistochemical staining
https://s3.amazonaws.com/lowres.cartoonstock.com/medical-chicken_pox-disease-illness-bug-virus-bfrn547_low.jpg
53. TREATMENT
• Vidarabine and Human leukocyte interferon
• Reduced duration of viral replication
• Acyclovir
• Valacyclovir and Famciclovir
• Inhibitor of VZV DNA polymerase
• Higher specificity
• Few adverse effects
• Better clinical efficacy
http://www.kaefproduk.com/pic/ACYCLOVIR-200-10X10-393.jpg
54. VACCINATION FOR VARICELLA
• Live attenuated virus vaccines
• Varivax and ProQuad (MMRV)
• CDC recommends shots at 12 months old and booster dose 4-6 years
• Lifelong, at least 10-20 years
• Reported Complications
• shock, seizures, chickenpox and encephalitis
• Effectiveness 95%
• 1995 FDA showed 70-80%
• 2002 CDC study 44% against disease of
any severity
• 86% moderate or severe disease http://www.shinglesexpert.org/wp-content/uploads/Varivax-Shingles-vaccine-500x414.jpg
55. PREVENTION
• Passive antibody prophylaxis
• High dose intravenous immunoglobulin
within 48 hours of exposure
• Antiviral prophylaxis
• Acyclovir during the incubation period
• Vaccination
https://s3.amazonaws.com/lowres.cartoonstock.com/children-doctor-ill-sick-unwell-childhood_illnesses-kscn2020_low.jpg
56. VACCINATION FOR HERPES ZOSTER
• Live attenuated virus vaccine
• Zostavax
• CDC recommends shots for individuals aged 60 years and older
• Protection up to 3 years
• Reported Complications
• 1-5% mild chickenpox
• Effectiveness
• Incidence reduction 51.3%
• PHN reduction 66.5%
• Pain and severity reduction 61.1%
http://cdn2.hubspot.net/hub/519118/hubfs/zoztavax.jpg?t=1464028653105&width=485
57. ERADICATION
Successful eradication requires
• Human host as ONLY reservoir
• Availability of vaccine
• Vaccination of 95% of the world population
• Availability of diagnostics tools with sufficient
specificity and sensitivity
http://www.lebtech.net/2545-thickbox_default/virus-eradication.jpg
58. NEWS
SUMMARY
• Compared CD4+ T cells response to VZV
proteins before and after HZ
vaccination
• After vaccination the T cell response
diversified
• T cells prior vaccination identify ORF
59,12,62,18 proteins
• After vaccination wider range of viral
proteins recognized ORF
40,67,9,59,12,62,18
• Two fold increase in responsiveness
I.F: 5.997
https://jid.oxfordjournals.org/content/212/7/1022.full?sid=b14025b8-e00c-4661-9130-f5ea6bb583ad
61. REFERENCES
• David M. Knipe. P. Mowley. Field’s virology volume 2 4th edition chapter 78&79
• "Varicella – Zoster Virus: Everything You Need To Know." Herpes Treatment Box. Herpestreatmentbox.com. Web. 8 May 2016.
• Gross G , Doerr HW (eds): Herpes Zoster. Monogr Virol. Basel, Karger, 2006, vol 26, pp 1-8
• "Varicella." World Health Organization. WHO, 4 Apr. 2015. Web. 8 May 2016
• "Historical Background." Virus. Web. 08 May 2016. <https://virus.stanford.edu/herpes/History.html>.
• Bhalla, P., G. Forrest, M. Gershon, Y. Zhou, P. Larussa, S. Steinberg, and A. Gershon. "Disseminated, Persistent, and Fatal Infection Due to the
Vaccine Strain of Varicella-Zoster Virus in an Adult Following Stem Cell Transplantation." Clinical Infectious Diseases (2014): 1068-074. Print.
• Zerboni, L., N. Sen, S. Oliver, and A. Arvin. "Molecular Mechanisms of Varicella Zoster Virus Pathogenesis." Nature Reviews Microbiology
(2014): 1-29. Web.
• Marin, M., and S. Bialek. "Varicella (Chickenpox)." Centers for Disease Control and Prevention. 10 July 2015. Web.
• Wood, M. "History of Varicella Zoster Virus." National Center for Biotechnology Information. U.S. National Library of Medicine PubMed, Oct.
2000. Web. 10 May 2016.
• "Varicella Zoster (Chickenpox)." National Vaccine Information Center. Web. <http://www.nvic.org/Vaccines-and-Diseases/Chickenpox.aspx>.
• Arvin, A. "Varicella-Zoster Virus." Clinical Microbiology Reviews 9.3 (1996): 361-81. Web.
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• “Varicella Zoster Virus (VZV).” Am J Transplant 2009 December, 9 (Suppl 4): S115: doi10.111/j.1600-6143.2009.02901.x
• First slide image from https://microbewiki.kenyon.edu/images/thumb/c/cd/Varicella-
zoster_virus_enhanced_by_an_electron_microscope.jpg/400px-Varicella-zoster_virus_enhanced_by_an_electron_microscope.jpg
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• http://poliocta5.weebly.com/signs-and-symptoms.html
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• http://viralzone.expasy.org/all_by_species/33.html
• http://viralzone.expasy.org/all_by_protein/97.html
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