II. Epidemiology
- No natural source of Smallpox remains as of 1977
- Biological Weapon potential
- Outbreaks historically occurred in winter
- Same time as Varicella Zoster Virus and Measles
III. History
- British first used Smallpox as Biological Weapon
- French and Indian Wars 1754-1767
- Distributed contaminated blankets to Native Americans
- Edward Jenner demonstrated efficacy of Vaccine 1796
- Found milkmaids who had Cowpox did not get Smallpox
- Initiated Cowpox inoculation which prevented Smallpox
- Eradication of Smallpox completed in 1977
- Smallpox Vaccination discontinued
- United States: 1972
- Worldwide: 1980
- Most labs destroyed Variola virus samples by 1999
- Smallpox Vaccination discontinued
IV. Pathophysiology
- Variola Virus is a brick-shaped 200 nm member of Orthopoxvirus genus
- Cowpox is also a member of Orthopoxviruses
V. Types
- Standard Smallpox (90% of cases)
- Variola major (much more severe, lethal form)
- Variola Minor
- Severe variants
- Hemorrhagic Smallpox (more common in pregnant women)
- Malignant Smallpox
VI. Transmission
- Contagious only after onset of rash
- Infectious for first 7 to 10 days after rash
- Infectivity wanes after scabs form
- Only very low dose (few virions) needed for infection (highly contagious)
- Pandemic can be caused by 100 active cases
- Direct contact with oropharyngeal droplets or aerosols
- Contaminated clothing or linen
- Person to person transmission
- No animal or Insect hosts
VII. Symptoms
- Incubation Period of 7 to 17 days (usually 12-14 days)
- Viral prodrome (2-3 days before rash)
- High fever
- Rigors
- Malaise
- Myalgia
- Headache
- Backache
- Abdominal Pain
- Vomiting
VIII. Signs: Rash
- Timing
- Onset of rash within 2-4 days of fever
- Location
- Initial: Oropharynx, face (centrifugal)
- Next: Arms (esp. Forearms)
- Next: Remainder of extremities including legs
- Next: Palms and soles
- Later: Trunk
- Typical Smallpox Characteristics
- Initial: Maculopapular
- Next: Vesicles or Oral Ulcers within 1-2 days
- Next: Round, tense and embedded Pustules
- Next: Crusts or scabs form by 8-9 days of rash
- Last: Scars form with Sebaceous Gland destruction
- Hemorrhagic Smallpox Characteristics
- Initial: Dusky erythema
- Next: Petechiae
- Next: Hemorrhaging from skin and mucus membranes
- Malignant Smallpox Characteristics
- Initial: Slow confluence of lesions
- Next: Soft, flattened, velvety Vesicles form
- Next: Reddish fine-grained Skin Coloration
- Contrasts: No formation of Pustules or scabs
IX. Differential Diagnosis
-
Varicella Zoster Virus (features of VZV listed)
- No lesions on palms or soles in VZV
- VZV with minimal prodrome; fever onset with rash
- Stages of maturation much faster in VZV
- Rash develops rapidly
- Scab forms within 7 days of rash
- Scab separates within 14 days of rash
- Trunk more involved in VZV than face or extremities
-
Meningococcemia
- Contrast with Hemorrhagic or Malignant Smallpox
- Severe Acute Leukemia
- Contrast with Hemorrhagic or Malignant Smallpox
X. Labs: Used to identify epidemic
- Throat swab for PCR (preferred) or ELISA
- Obtain samples from possible source
- Open Vesicle with scalpel and dab with cotton swab
- Obtain scab sample with forceps
- Send sample in sealed Vacutainer (tape top)
- Encase Vacutainer in second, water proof container
- Send samples to high-containment labs (BL-4)
- Smallpox rapidly identified under electron microscopy
XI. Management: Emergently reduce transmission risk
- Patient Isolation at facility (home is preferred)
- Negative pressure room
- High-efficiency particulate air filtration
- Deceased patients should be cremated
- Vaccinate mortuary workers
- Protect all medical facility personnel
- Medical care by recently vaccinated persons only
- Immunize all hospital employees
- Furlough non-immunized employees
- Infectious precautions (Gloves and Mask)
- Contact public health immediately
- Decontamination
- Laundry in biohazard bags, autoclave, then launder
- Waste in biohazard bags and incinerate
- Room Decontamination per protocol
- Identify and immunize contacts of infection source
- Household or face-to-face contact with febrile source
- Isolate if fever >101 within 17 days of exposure
- Forced quarantine may be necessary
XII. Management: Medical
- See Prevention below (include Postexposure Prophylaxis)
- Symptomatic and supportive care
- Tecovirimat (TPOXX)
- Indicated in severe Vaccinia
- Dose: 600 mg orally twice daily for 14 days
- Interrupts virus transmission between cells
- Other agents with benefit
XIII. Prognosis
- Variola major: 30% to 50% mortality rate in unvaccinated patients
- Variola Minor: 1-2% mortality rate
- Hemorrhagic Smallpox: Uniformly fatal by day 6 of rash
- Malignant Smallpox: Frequently fatal
XIV. Prevention
- Pre-exposure Smallpox Vaccination
- Immunity wanes after 5-10 years
- Those vaccinated 30 years ago are likely susceptible
- Routine Smallpox Vaccination stopped in U.S. 1972
-
Post-exposure Prophylaxis
- Vaccinia Immune Globulin 0.6 ml/kg IM
- Must be given within 3 days (ideally within 24 hours)
-
Smallpox Vaccination
- Must be given within 4 days of exposure (before symptoms) to be effective
- Contraindicated in pregnancy (risk of fetal Vaccinia) unless benefits outweight risks
- Vaccinia Immune Globulin 0.6 ml/kg IM
- Variola Immunoglobulin (Vaccinia immune globulin)
- High risk patients, given within first 7 days
- Give in combination with post-exposure Vaccination
- Dose: 100 mg/kg IM
-
Cidofovir
- May be efficacious if used within 2 days of exposure
- Indicated in significant exposure during pregnancy
XV. References
- Seeyave (2015) Crit Dec Emerg Med 29(5): 13-21
- Wilson (1991) Harrison's IM, McGraw-Hill, p. 709-11
- Breman (1998) N Engl J Med 339:556-9 [PubMed]
- Henderson (1999) JAMA 281:2127-37 [PubMed]
- Rathjen (2021) Am Fam Physician 104(4): 376-85 [PubMed]
Images: Related links to external sites (from Bing)
Related Studies
Definition (MSHFRE) | Maladie virale bénigne survenant chez les vaches laitières due au cowpox virus, se manifestant par des éruptions cutanées localisées principalement au niveau de la mamelle et des trayons. L'homme peut se contaminer lors de la traite d'un animal infecté. |
Definition (MSH) | A mild, eruptive skin disease of milk cows caused by COWPOX VIRUS, with lesions occurring principally on the udder and teats. Human infection may occur while milking an infected animal. |
Concepts | Disease or Syndrome (T047) |
MSH | D015605 |
ICD9 | 051.01 |
ICD10 | B08.010 |
SnomedCT | 154344005, 266193008, 70090004 |
English | Cow Pox, Pox, Cow, yaba, cowpox, cowpox (diagnosis), Cow pox, Cowpox [Disease/Finding], cow pox, Cowpox (disorder), Cowpox |
French | Cow-pox, Vaccine, Cowpox |
Italian | Malattia vaccinica, Vaiolo bovino |
Spanish | Vacuna, Viruela Bovina, Cowpox, viruela vacuna (trastorno), viruela vacuna, Vaccinia, Viruela Vacuna |
Swedish | Kokoppor |
Japanese | ギュウトウ, 牛痘 |
Czech | kravské neštovice, Kravské neštovice, Nepravé neštovice |
Finnish | Lehmärokko |
Russian | KOROV'IA OSPA, OSPA KOROV, КОРОВЬЯ ОСПА, ОСПА КОРОВ |
Croatian | KRAVLJE BOGINJE |
Polish | Ospa krowia |
Hungarian | Tehénhimlő, tehén himlő |
Norwegian | Kukopper |
Portuguese | Cowpox, Vacínia, Varíola Bovina |
Dutch | koepokken, Koepokken, Pokken, koe- |
German | Kuhpocken |
Ontology: Poxviridae (C0032868)
Definition (NCI) | A family of double-stranded DNA viruses infecting mammals, birds and insects. Contains two subfamilies: chordopoxvirinae, poxviruses of vertebrates, and entopoxvirinae, poxviruses of insects. |
Definition (MSH) | A family of double-stranded DNA viruses infecting mammals (including humans), birds and insects. There are two subfamilies: CHORDOPOXVIRINAE, poxviruses of vertebrates, and ENTOMOPOXVIRINAE, poxviruses of insects. |
Definition (CSP) | family of dsDNA viruses; replication occurs in the cytoplasm with inclusion bodies; natural host range is narrow; transmission is by several routes including airborne, fomites, direct contact and mechanically by arthropods. |
Concepts | Virus (T005) |
MSH | D011212 |
SnomedCT | 424976006, 243567005 |
English | Poxviruses, Family: Poxvirus group, Family Poxviridae, Poxvirus group, Family Poxviridae (organism), pox virus, poxviruses, poxvirus, virus pox, pox viruses, poxviridae, Poxvirus group (organism), Poxviridae, Poxvirus |
Swedish | Poxviridae |
Spanish | grupo Poxvirus, familia Poxviridae (organismo), familia: grupo Poxvirus, familia Poxviridae, Poxviridae, grupo Poxvirus (organismo) |
Czech | Poxviridae |
Finnish | Rokkovirukset |
Russian | POKSVIRUSY, OSPY SVINEI VIRUS, POXVIRIDAE, ОСПЫ СВИНЕЙ ВИРУС, ПОКСВИРУСЫ |
Japanese | ポックスウイルス科 |
Italian | Poxvirus, Poxviridae |
Croatian | Not Translated[Poxviridae] |
Polish | Poxviridae |
French | Poxvirus, Poxviridae |
Norwegian | Not Translated[Poxviridae] |
German | Pockenviren |
Dutch | Pokkenvirussen, Poxviridae |
Portuguese | Poxviridae |
Ontology: Smallpox (C0037354)
Definition (MSHFRE) | Maladie infectieuse hautement contagieuse, souvent mortelle, due à un orthopoxvirus. Elle est caractérisée par une fièvre bi-phasique, une éruption caractéristique au niveau de la peau. La vaccination a réussi à éradiquer la variole dans le monde. (Dorland, 28ème éd.) |
Definition (MEDLINEPLUS) |
Smallpox is a disease caused by the Variola major virus. Some experts say that over the centuries it has killed more people than all other infectious diseases combined. Worldwide immunization stopped the spread of smallpox three decades ago. The last case was reported in 1977. Two research labs still keep small amounts of the virus. Experts fear bioterrorists could use the virus to spread disease. Smallpox spreads very easily from person to person. Symptoms are flu-like. They include
There is no treatment. Fluids and medicines for pain or fever can help control symptoms. Most people recover, but some can die. Those who do recover may have severe scars. The U.S. stopped routine smallpox vaccinations in 1972. Military and other high-risk groups continue to get the vaccine. The U.S. has increased its supply of the vaccine in recent years. The vaccine makes some people sick, so doctors save it for those at highest risk of disease. NIH: National Institute of Allergy and Infectious Diseases |
Definition (MSH) | An acute, highly contagious, often fatal infectious disease caused by an orthopoxvirus characterized by a biphasic febrile course and distinctive progressive skin eruptions. Vaccination has succeeded in eradicating smallpox worldwide. (Dorland, 28th ed) |
Concepts | Disease or Syndrome (T047) |
MSH | D012899 |
ICD9 | 050.9, 050 |
ICD10 | B03 |
SnomedCT | 186505008, 266193008, 154344005, 67924001, 47452006 |
English | Variola, Variolas, Smallpox, unspecified, smallpox (variola), variola, smallpox, smallpox (diagnosis), Smallpox NOS, Smallpox [Disease/Finding], variola major, Small pox, smallpox disease, Smallpox NOS (disorder), Smallpox, Classical smallpox, Smallpox (disorder), Smallpox, NOS, Variola, NOS, Ordinary smallpox, small pox |
Dutch | pokken, niet-gespecificeerd, Pokken1, pokken, Pokken, Variola |
French | Variole, non précisée, Variole |
German | Pocken, unspezifisch, Blattern, Pocken, Variola |
Italian | Vaiolo non specificato, Variola, Vaiolo |
Portuguese | Varíola NE, Varíola |
Spanish | Viruela no especificada, viruela, SAI (trastorno), viruela, SAI, variola, viruela (trastorno), viruela, viruela clásica, viruela clásica (trastorno), Viruela, Variola |
Japanese | 痘瘡、詳細不明, トウソウショウサイフメイ, トウソウ, 小痘瘡, 天然痘, 疱瘡, 乳痘, アラストリム, 痘瘡 |
Swedish | Smittkoppor |
Czech | variola, Variola, Pravé neštovice, blíže neurčené, neštovice pravé, pravé neštovice |
Finnish | Isorokko |
Russian | OSPA, OSPA KAFROV, OSPA BELAIA, OSPA NATURAL'NAIA, ALASTRIM, VARIOLA MINOR, АЛАСТРИМ, ОСПА, ОСПА БЕЛАЯ, ОСПА КАФРОВ, ОСПА НАТУРАЛЬНАЯ |
Korean | 마마 |
Croatian | VARIOLA |
Polish | Ospa prawdziwa, Alastrim |
Hungarian | Variola vera, nem meghatározott, variola vera |
Norwegian | Variola, Kopper |
Ontology: Vaccinia (C0042214)
Definition (MSHFRE) | Réactions cutanées et parfois généralisées, secondaires à une vaccination contre la variole |
Definition (MSH) | The cutaneous and occasional systemic reactions associated with vaccination using smallpox (variola) vaccine. |
Concepts | Disease or Syndrome (T047) |
MSH | D014615 |
SnomedCT | 111852003 |
English | Vaccinias, vaccinia, vaccinia (diagnosis), Vaccinia [Disease/Finding], Vaccinia (disorder), Vaccinia, NOS, Vaccinia |
Swedish | Vaccinia |
Czech | vakcínie, Vakcínie |
Finnish | Vaccinia |
Russian | OSPOVAKTSINA, ОСПОВАКЦИНА |
Spanish | Infección por el virus vaccinia, vaccina, vaccinia (trastorno), vaccinia, variola vaccina, Vaccinia |
French | Virus de la vaccine, Vaccine |
Italian | Vaccinia, Pustola vaccinica |
Dutch | vaccinia, Vaccinia |
Japanese | ワクシニア, ワクシニア |
Portuguese | Vaccinia, Vacínia |
Polish | Ospa poszczepienna, Krowianka |
Hungarian | vaccinia |
Norwegian | Vaccinia |
German | Vaccinia |
Ontology: Orthopoxvirus (C0206580)
Definition (NCI_CDISC) | Any viral organism that can be assigned to the genus Orthopoxvirus. |
Definition (NCI) | A genus of poxviruses that cause generalized infections with a rash in mammals. Orthopoxviruses are enveloped, double standed DNA viruses. |
Definition (MSH) | A genus of the family POXVIRIDAE, subfamily CHORDOPOXVIRINAE, comprising many species infecting mammals. Viruses of this genus cause generalized infections and a rash in some hosts. The type species is VACCINIA VIRUS. |
Concepts | Virus (T005) |
MSH | D018155 |
SnomedCT | 29724001 |
LNC | LP14832-7, MTHU002049 |
English | Orthopoxvirus, Genus Orthopoxvirus (organism), Orthopoxvirus (organism), Genus Orthopoxvirus, orthopoxvirus, orthopoxviruses, Orthopoxviruses, ORTHOPOXVIRUS, Genus: Vaccinia subgroup, Vaccinia subgroup virus, Vaccinia subgroup, Orthopoxvirus, NOS, Vaccinia subgroup, NOS |
Swedish | Ortopoxvirus |
Spanish | género Orthopoxvirus (organismo), género Orthopoxvirus, ortopoxvirus (organismo), Orthopoxvirus, ortopoxvirus, subgrupo del virus de la vaccinia, subgrupo del virus vacunal |
Czech | Orthopoxvirus |
Finnish | Ortopoxvirus |
Russian | ORTOPOKSVIRUS, ОРТОПОКСВИРУС |
Croatian | Not Translated[Orthopoxvirus] |
Polish | Orthopoxvirus |
Japanese | オルソポックスウイルス, オルトポックスウイルス, オルトポックスウイルス属 |
French | Orthopoxvirus |
German | Orthopoxvirus |
Italian | Orthopoxvirus |
Dutch | Orthopoxvirus, Virus, Orthopox- |
Portuguese | Orthopoxvirus |
Ontology: Variola major (C1812609)
Concepts | Disease or Syndrome (T047) |
ICD9 | 050.0 |
SnomedCT | 266193008, 154344005, 47452006 |
Dutch | variola major |
French | Variole majeure |
German | Variola major |
Italian | Variola major |
Portuguese | Varíola major |
Spanish | Viruela mayor, variola mayor (trastorno), variola mayor |
Japanese | 大痘瘡, ダイトウソウ |
English | variola major, variola major (diagnosis), Variola major, Variola major (disorder) |
Czech | Variola major |
Hungarian | Variola major |