children diseases – picornaviridae (polio) and varicella zoster pdf

CHILDREN DISEASES PICORNAVIRIDAE (POLIO) AND HERPESVIRIDAE (CHICKENPOX)

PRESENTED BY GABRIEL FIOSSI ASSAGBA AND YOLANDA LINDSAY MABUTO

VIROLOGY SS2016

TAXONOMY

Single stranded Naked Positive sense Smallest known virus

http://what-when-how.com/wp-content/uploads/2011/05/tmp2499_thumb1.jpg

CLASSIFICATIONOrder: PicornaviralesFamily: PicornaviridaeGenus: 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

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

VIRION

Morphology spherical Envelope no Diameter (nm) 2730 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

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

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

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


Attachment Penetration Uncoating Replication Encapsidation RNA synthesis Cell lysis

http://www.mdpi.com/1999-4915/7/8/2832/htm

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

EPIDEMIOLOGY

Reservoir : human

Transmission: faecal oral routeoral 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

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 virusAsymptomatic or mild

Febrile undifferentiated illness

Neurologic phase

Virus spreads to spinal cord and brain Paralysis

Alimentary phase

Lymphatic phase

CLINICAL MANIFESTATIONS

Outcomes of Polio InfectionOutcome Proportion of cases

No symptoms 72%

Abortive poliomyelitis 24%

Nonparalytic asepticmeningitis 15%

Paralytic poliomyelitis 0.10.5%

Spinal polioBulbospinal polio

Bulbar polio

79% of paralytic cases19% of paralytic cases2% of paralytic cases

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

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


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

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

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/

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

TRAGIC SITUATION IN 1950s

POSTPOLIO SYNDROME

Slowly progressive muscular atrophy with evidence of ongoingmotor nerve damage

1530 years after recovery 2550% of people who have previously survived

https://www.pinterest.com/tttheroux/post-polio-syndrome/

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

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

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

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

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

POLIO ERADICATION

TWO LAST REMAINING COUNTRIES WITH WILD POLIO CASEShttp://outbreaknewstoday.com/afghanistan-reports-1st-polio-case-of-2015/

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

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

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

HERPESVIRIDAE VARICELLA (CHICKENPOX)

http://www.turbosquid.com/3d-models/varicella-zoster-virus-3d-model/493482

TAXONOMY

Double-stranded Enveloped

http://what-when-how.com/wp-content/uploads/2011/05/tmp2499_thumb1.jpg

CLASSIFICATIONOrder-Family-Subfamily-Genus-SpeciesOrder: HerpesviralesFamily: Herpesviridae Subfamily Alphaherpesvirinae

Simplexviruso Human herpesvirus 1 (HSV-1)o Human herpesvirus 2 (HSV-2)

Varicelloviruso 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 (Kaposis sarcoma-associated herpesvirus)

http://en.m.wikipedia.org/wiki/File:Herpesviridae_EM_PHIL_2171_lores.jpg

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 Paschens description of VZV 1943 Ruska first described appearance of VZV with electron microscopy 1943 Garland discovers herpes zoster caused by VZV reactivation

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

VIRION

Morphology icosahedral Envelope yes Diameter (nm) 120-180 Structural components core, capsid, envelope, tegument Additional information capsid surrounded by amorphous

tegument envelope contains viral glycoproteins

http://sigmadiagnosticsinc.comhttp://edoc.hu-berlin.de/dissertationen/gutzeit-cindy-2009-11/HTML/image001.jpg

GENOME

Nucleic acid DNA Strandness double-stranded Configuration linear Segments 1 Size (kb) >152 Transcription units 86 Additional information DNA can isomerize

GENOME

TRL Terminal repeat longUL Unique long region IRL Internal repeat longIRs Internal repeat shortUS Unique ShortTRS 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

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. Fields virology volume 2 6th edition

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

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



Immunosuppression Stress

Reactivation by

http://mercedeskaygold.com/stressed/


http://www.nature.com/nrmicro/journal/v12/n3/images/nrmicro3215-f1.jpg

Attachment to cellglycosaminoglycans

Endocytosis Uncoating Replication

Nucleus DNA into nucelocapsid Budding Virion assembly

Nucleus Release

Transported to cell surface

PATHOGENESIS OF VARICELLA

INOCULATION T CELL VIREMIA PRIMARY SKIN INFECTION

RETROGRADETRANSPORT

http://www.nature.com/nrmicro/journal/v12/n3/images/nrmicro3215-f1.jpg

PATHOGENESIS OF VARICELLA

LATENCYDORSAL

GANGLIAREACTIVATION

ANTEROGRADETRANSPORT

RETROGRADETRANSPORT

REACTIVATEDSKIN INFECTIONHerpes Zoster


VZV Herpes zoster(shingles)Varicella(chickenpox)

Diseases caused by VZV


VZV Herpes ZosterVaricella

Primary Infection Reactivationfrom latency

Diseases caused by VZV

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/

OTHER DISEASES AND COMPLICATIONS

Neonatal varicella Congenital varicella Meningitis Hepatitis Pancreatitis Bacterial superinfection

EPIDEMIOLOGYOccurrence: worldwideIncidence: 15 -16 per 1000 (VZV)

1.5 3.0 per 1000 (HZ)Reservoir: humanTransmission: airborne, direct contact with lesionTemporal pattern: differs between temperate and tropical climate

tropical areas more adults affectedIncubation period: 10 21 daysRisk factors: immunocompromised people

pregnant womenunvaccinated individuals

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

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

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

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

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

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

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 responsivenessI.F: 5.997

https://jid.oxfordjournals.org/content/212/7/1022.full?sid=b14025b8-e00c-4661-9130-f5ea6bb583ad

http://refutationstoantivaccinememes.org/

Paramyxoviridae

REFERENCES David M. Knipe. P. Mowley. Fields 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. .

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. .

Arvin, A. "Varicella-Zoster Virus." Clinical Microbiology Reviews 9.3 (1996): 361-81. Web.

Jeffrey I. Cohen, M.D. The Varicella-Zoster Virus Genome. Curr Top Microbiol Immunol . 2010 ; 342: 114. doi:10.1007/82_2010_10

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

D. M. Knipe, P. M. Howley, D. E. Griffin, R. A. Lamb, M. A. Martin, B. Roizman and S. E. Straus, Eds . Fields Virology, Fourth Edition, Volumes 1 and 2. Lippincott Williams and Wilkins, Philadelphia (2001)

Ryan, Kenneth, and Ray, C. George, Sherris Medical Microbiology, 4th Edition, McGraw-Hill, 2004, pp 541


http://emedicine.medscape.com/article/967950-overview#showall

http://www.healthline.com/health/poliomyelitis#Symptoms4

http://www.who.int/topics/poliomyelitis/en/

http://polioandprevention.blogspot.de/

https://www.youtube.com/watch?v=VKBf3M-KJ4s

http://viralzone.expasy.org/all_by_species/33.html

http://viralzone.expasy.org/all_by_protein/97.html

http://www.microbiologybook.org/virol/picorna.htm

http://www.picornaviridae.com/index.html

http://web.stanford.edu/group/virus/picorna/2004flynn/Picornaviridae2.htm#_Polio_Virus_Profile

https://en.wikipedia.org/wiki/Picornavirus

http://www.picornaviridae.com/enterovirus/enterovirus.htm

http://www.mdpi.com/1999-4915/7/8/2832/htm

http://www.polioeradication.org/polioandprevention/thevirus/vaccinederivedpolioviruses.aspx

http://www.who.int/features/qa/64/en/

http://outbreaknewstoday.com/afghanistan-reports-1st-polio-case-of-2015/

http://www.polioeradication.org/Polioandprevention/Thevaccines/Oralpoliovaccine(OPV).aspx

https://regionreporter.wordpress.com/2014/02/19/vaccine-preventable-illness-affected-many-lives/

http://www.newworldencyclopedia.org/entry/Poliomyelitis

CHILDREN DISEASES PICORNAVIRIDAE (POLIO) AND HERPESVIRIDAE (CHICKENPOX)TAXONOMY CLASSIFICATIONHISTORYVIRIONGENOMEGENOMEREPLICATION STRATEGYREPLICATION STRATEGYPOLIOVIRUS SEROTYPESEPIDEMIOLOGYPATHOGENESISCLINICAL MANIFESTATIONSABORTIVE POLIOMYELITISNONPARALYTIC ASEPTIC MENINGITISPARALYTIC POLIOMYELITISSPINAL POLIOBULBOSPINAL POLIOBULBAR POLIOTRAGIC SITUATION IN 1950sPOSTPOLIO SYNDROMEDIAGNOSISTREATMENTPREVENTIONVACCINE DERIVED POLIO VIRUS (VDPV)POLIO ERADICATIONPOLIO ERADICATIONOBSTACLES TO POLIO ERADICATIONMYTHS OF THE POLIO VACCINENEWS HERPESVIRIDAE VARICELLA (CHICKENPOX)TAXONOMYCLASSIFICATIONHISTORYHISTORYVIRIONGENOMEGENOMEVZV GENES AND THEIR LOCATION AND FUNCTIONREPLICATION STRATEGY IN PRIMARY INFECTIONREPLICATION STRATEGY IN LATENCYREPLICATION STRATEGY IN LATENCYREPLICATION STRATEGY IN LATENCYREPLICATION STRATEGYPATHOGENESIS OF VARICELLA PATHOGENESIS OF VARICELLA CLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONSCLINICAL MANIFESTATIONSOTHER DISEASES AND COMPLICATIONSEPIDEMIOLOGYDIAGNOSISTREATMENTVACCINATION FOR VARICELLAPREVENTIONVACCINATION FOR HERPES ZOSTERERADICATIONNEWSSlide Number 59Slide Number 60REFERENCESSlide Number 62Slide Number 63

children diseases – picornaviridae (polio) and varicella zoster pdf

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