Variola Virus Variola Virus

Presented by Megan ElinePresented by Megan Eline

Orthopox CharacteristicsOrthopox Characteristics

Belongs to Orthopoxidae Family

Very large, brick-shaped virus.

300 X 200 nm in size.

dsDNA genome (200 kbp).

Virus particle is enveloped and contains

filamentous nucleocapsid

What is Smallpox?What is Smallpox?

A serious, A serious, contagious, often contagious, often fatal disease caused fatal disease caused by the variola virus.by the variola virus.

2 Clinical forms:2 Clinical forms:– Variola majorVariola major– Variola minorVariola minor

Pustules

Early History of SmallpoxEarly History of Smallpox

Origin is uncertain, but believed to have Origin is uncertain, but believed to have

originated in Africa, which then spread to India originated in Africa, which then spread to India

and China.and China.

Smallpox reached Europe between the 5th and 7th Smallpox reached Europe between the 5th and 7th

centuries centuries

Epidemics occurred in the North American Epidemics occurred in the North American

colonies in the 17th and 18th centuries colonies in the 17th and 18th centuries

EpidemiologyEpidemiology

The first recorded smallpox epidemic was in 1350 BC The first recorded smallpox epidemic was in 1350 BC during the Egyptian-Hittite war. during the Egyptian-Hittite war.

In the London epidemic of 1857-1859, there were 14,244 In the London epidemic of 1857-1859, there were 14,244 deaths; in the 1863-1865 outbreak - 20,059 deathsdeaths; in the 1863-1865 outbreak - 20,059 deaths..

Japan-1892 their records showed 165,774 cases with Japan-1892 their records showed 165,774 cases with 29,979 deaths.29,979 deaths.

In the Philippines between 1917 and 1919, 162,503 In the Philippines between 1917 and 1919, 162,503 reported cases and 71,453 deaths.reported cases and 71,453 deaths.

In the 20th century alone, an estimated 300 million In the 20th century alone, an estimated 300 million people died from the disease. people died from the disease.

Smallpox gets defeatedSmallpox gets defeated

Last known case in the United States was in 1949.Last known case in the United States was in 1949.

Last known naturally occurring case in the world Last known naturally occurring case in the world was in Somalia in 1977.was in Somalia in 1977.

Except for laboratory stockpiles, the virus has Except for laboratory stockpiles, the virus has been eliminated.been eliminated.

Dr. Edward JennerDr. Edward Jenner

Observed that farmers who Observed that farmers who caught cowpox never caught cowpox never caught smallpox.caught smallpox.

1798 he introduced cowpox 1798 he introduced cowpox vaccination for smallpox. vaccination for smallpox.

James Phipps was the first James Phipps was the first person to receive the person to receive the vaccine and he did not vaccine and he did not become infected. become infected.

SymptomsSymptoms

Fever (101°-104°F)Fever (101°-104°F)

MalaiseMalaise

Head and body achesHead and body aches

Occasional vomitingOccasional vomiting

RashesRashes

PustulesPustules

TransmissionTransmission

Humans are the only natural hosts.Humans are the only natural hosts. To survive, the virus must pass from person To survive, the virus must pass from person

to person.to person. Inhaled droplets of air or aerosols enters Inhaled droplets of air or aerosols enters

through respiratory mucosal route.through respiratory mucosal route. Direct or prolonged face-to-face contact Direct or prolonged face-to-face contact

required with infected person.required with infected person. Bodily fluids or contaminated objects.Bodily fluids or contaminated objects.

Replication Process Replication Process (Lytic Cycle)(Lytic Cycle)

Binding to cell receptors and penetration of host Binding to cell receptors and penetration of host cell.cell.

Uncoating of protein coat.Uncoating of protein coat. Gene expression and transcription.Gene expression and transcription. Genome replication (occurs in the cytoplasm).Genome replication (occurs in the cytoplasm). Assembly and release of new virions.Assembly and release of new virions. Replication occurs in ~12 hours. Replication occurs in ~12 hours.

Variola Virus Replication Variola Virus Replication

Infection ProcessInfection Process

Incubation Period (7-17 days)Incubation Period (7-17 days)

– No symptoms occurring.No symptoms occurring.– Virus replicates in lymph nodes.Virus replicates in lymph nodes.– Not contagious.Not contagious.

Prodrome Period (2-4 days)Prodrome Period (2-4 days)– Initial symptoms occurring.Initial symptoms occurring.– Virus replicates in spleen, bone marrow, & lymph Virus replicates in spleen, bone marrow, & lymph

nodes.nodes.– Sometimes contagious.Sometimes contagious.

Early Rash (4 days)Early Rash (4 days)

– Small red spots on tongue and in mouth.Small red spots on tongue and in mouth.

– Spots develop into sores.Spots develop into sores.

– Most contagious phase!!!Most contagious phase!!!

– Rash appears on skin & spreads over body within Rash appears on skin & spreads over body within

24 hours.24 hours.

– Fever develops.Fever develops.

Third day - raised bumps appear.Third day - raised bumps appear. Fourth day bumps fill up with a thick, opaque Fourth day bumps fill up with a thick, opaque

fluid.fluid.– Fever increases and remains high until scabs form. Fever increases and remains high until scabs form.

Pustular Rash (5 days)Pustular Rash (5 days)

– Pustules form.Pustules form.– Contagious.Contagious.

Pustules and Scabs (~5 days)Pustules and Scabs (~5 days)

– Pustules form a crust and scabPustules form a crust and scab

– By the end of second week after rash appears, most sores are By the end of second week after rash appears, most sores are scabbed over.scabbed over.

– Contagious.Contagious. Resolving Scabs (~6 days)Resolving Scabs (~6 days)

– Scabs fall off and leave scars.Scabs fall off and leave scars.

– Contagious.Contagious.

Scabs ResolvedScabs Resolved– Once the last scab has fallen off, the person is no longer Once the last scab has fallen off, the person is no longer

contagious. contagious.

Diagnostic TestsDiagnostic Tests

Routine viral cultures.Routine viral cultures.

Variola PCR targets the hemagglutin gene.Variola PCR targets the hemagglutin gene.

Electron Microscopy.Electron Microscopy.

PrognosisPrognosis

Variola major fatality rate is 30%.Variola major fatality rate is 30%.– Hemorrhagic & flat smallpox have >90% Hemorrhagic & flat smallpox have >90%

fatality rate.fatality rate.

Variola minor fatality rate is <1%.Variola minor fatality rate is <1%.

Preventative Measures Preventative Measures

Smallpox vaccine provides a Smallpox vaccine provides a high level of protection high level of protection against the disease for about against the disease for about five years. Without the five years. Without the vaccine, it is nearly vaccine, it is nearly impossible to prevent impossible to prevent infection. infection.

Contains live vaccina virus.Contains live vaccina virus.

Does not contain smallpox Does not contain smallpox and does not cause and does not cause smallpox.smallpox.

More Preventative MeasuresMore Preventative Measures

•Good hand hygiene.

•Isolation of suspected smallpox patients.

•Keep sites covered with gauze.

Smallpox as a Biological Smallpox as a Biological Weapon Weapon

Smallpox was used as a biological weapon during the French-Smallpox was used as a biological weapon during the French-Indian wars in the United States (1754-1767), when British Indian wars in the United States (1754-1767), when British soldiers gave the Indians blankets that had been used by soldiers gave the Indians blankets that had been used by

smallpox patients.smallpox patients.

Japan considered the use of smallpox as a biological weapon in World War II.

Smallpox is currently contained in two high security labs Smallpox is currently contained in two high security labs (United States and Russia).(United States and Russia).

Rated among the most dangerous of all potential biological Rated among the most dangerous of all potential biological weapons. weapons.

Shared modes of protection against poxvirus infection by Shared modes of protection against poxvirus infection by attenuated and conventional smallpox vaccine virusesattenuated and conventional smallpox vaccine viruses

Trying to develop a safer vaccine due to a more Trying to develop a safer vaccine due to a more immunocompromised population of individuals (ie. AIDS, immunocompromised population of individuals (ie. AIDS, chemotherapy for cancer, organ transplant).chemotherapy for cancer, organ transplant).

Used modified vaccinia Ankara and NYVAC replication-Used modified vaccinia Ankara and NYVAC replication-deficient vaccinia virusesdeficient vaccinia viruses

If vaccine is present at time of virulent strain, then the If vaccine is present at time of virulent strain, then the antibody is sufficient to protect the host and T cells are not antibody is sufficient to protect the host and T cells are not necessary. necessary.

If no prior immunity, then T cells and antibodies must If no prior immunity, then T cells and antibodies must both respond. T cells are more efficient & clear infection both respond. T cells are more efficient & clear infection better than antibodies. better than antibodies.

QUIZ!!!!QUIZ!!!!

When is smallpox the When is smallpox the most most contagious?contagious? Name 3 symtoms of smallpox.Name 3 symtoms of smallpox. T or F Humans are not the only natural T or F Humans are not the only natural

hosts of the variola virus.hosts of the variola virus. When was the last known case of When was the last known case of

smallpox in the United States? smallpox in the United States?

ResourcesResources

www.cdc.gov.www.cdc.gov. The New Mexico Epidemiology Report,Volume The New Mexico Epidemiology Report,Volume

2003, Number 4. 2003, Number 4. Ward, Brian., Epidemic. New York, Dorling

Kindersley Publishing, Inc., 2000 Prescott, Lansing M., John P. Harley, Donald A.

Klein, Microbiology, New York, McGraw-Hill 2002 http://dermatology.about.com/cs/smallpox/a/

smallpoxhx.htm www.aafp.org/afpwww.aafp.org/afp/ 20030901/889.html/ 20030901/889.html

Resources ContinuedResources Continued

http://www.whale.to/v/smallpox1.htmlhttp://www.whale.to/v/smallpox1.html httphttp://://wwwwww..cnncnn..comcom/HEALTH/library/DS/00424./HEALTH/library/DS/00424.htmlhtml cidrap.umn.edu/cidrap/content/bt/smallpox/cidrap.umn.edu/cidrap/content/bt/smallpox/

biofacts/smllpx-summary.htmlbiofacts/smllpx-summary.html www.pnas.org.www.pnas.org. http://dermatology.about.com/cs/smallpox/a/

smallpoxhx.htm wwwwww..aafpaafp..orgorg//afpafp/ 20030901/889./ 20030901/889.htmlhtml