2Smallpox as a Bioterrorism Agent Last reported case in Minnesota in 1947Eradicated in 1977Intelligence reports indicate virus has been stolenPotential for use as bioweaponHigh (30%) case fatality rateSmall infectious dose ( organisms)Much secondary spread; 10 to 20-fold increase each generation
3Variola Virus Orthopoxvirus Infects only humans in nature Rapidly inactivated by UV light, chemical disinfectants, heatOther orthopoxviruses that infect humans are vaccinia, cowpox and monkeypox.Culture needed to differentiate variola from other orthopoxviruses.Rapidly inactivated by bleach and Lysol.No evidence strains with different virulence. Severe disease a result of host factors.
4Smallpox Clinical Presentations Variola majorSevere illnessCase fatality rate of >30%Variola minorLess severeCase fatality of <1%Variola major the only type known until end of 19th century. Occurred in Asia and parts of Africa. Last case in Bangladesh in 1975.Variola minor first described in South Africa in Predominant type in Americas and 20th century Africa. Last case in Somalia in 1977.
5Clinical Presentations of Variola Major Ordinary (>90% of cases in unvaccinated people)Modified (mild; occurs in previously vaccinated people)Flat (uncommon; usually fatal)Hemorrhagic (uncommon; usually fatal)Types based on nature and evolution of skin lesions. The relative vigor of the immune response probably determined clinical presentation. On evidence of different strain of virus causing different presentations.
6Modified Smallpox Occurs in previously vaccinated persons Prodrome may be less severeNo fever during evolution of rashSkin lesions evolve more quicklyRarely fatalMore easily confused with chickenpox
7Flat Smallpox Severe prodrome Fever remains elevated throughout course of illnessExtensive enanthemSkin lesions soft and flat, contain little fluidMost cases fatal
8Hemorrhagic Smallpox Prolonged severe prodrome Fever remains elevated throughout course of illnessEarly or late hemorrhagic signsBleeding into skin, mucous membranes, GI tractUsually fatal
9Smallpox Complications Bacterial infection of skin lesionsArthritisRespiratoryEncephalitisDeath30% overall for ordinary smallpox40%-50% for children <1 year>90% for flat and hemorrhagic smallpox
10Smallpox Prodrome Incubation period 12 days (range 7-19 days) Prodrome abrupt onset of fever >101oFmalaise, headache, muscle pain, nausea, vomiting, backachelasts 1-4 days
11Smallpox RashEnanthem (mucous membrane lesions) appears approx. 24 hours before skin rashMinute red spots on the tongue and oral/pharyngeal mucosaLesions enlarge and ulcerate quicklyVirus titers in saliva highest during first week of exanthem
12Smallpox RashExanthem (skin rash) appears 2-4 days after onset of feverFirst appears as macules, usually on the faceLesions appear on proximal extremities, spread to distal extremities and trunkVesicles often have a central depression (“umbilication”)Pustules raised, round, firm to the touch, deeply embedded in the skin
13Smallpox RashLesions in any one part of the body are in same stage of developmentMost dense on face and distal extremities (centrifugal distribution)Lesions on palms and soles (>50% of cases)
23Smallpox Differential Diagnosis Varicella (chickenpox)VacciniaMonkeypoxCowpoxHerpes zosterDrug-induced rashesErythema multiformeCoxsackie virusHerpes Simplex VirusSecondary syphilisMolluscum contagiosum (esp. HIV patients)Scabies and insect bitesImpetigoContact dermatitisMany eruptive illnesses could be misdiagnosed as smallpox. Key differential diagnoses of smallpox are varicella (chickenpox), vaccinia, monkeypox, cowpox, and disseminated herpes zoster. Drug-induced rashes can also be confused with smallpox but can be diagnosed by a careful history taking and examination. Sulfonamides can cause severe vesicular and bullous rashes.A morbilliform (resembling measles) rash on the face due to measles virus (rare in the U.S.) or coxsackievirus (hand, foot and mouth disease)* may be confused with early smallpox. Lesions associated with secondary syphilis vary in size and distribution and a differentiating feature is that the papules do not evolve. Patients with AIDS may have widespread molluscum (soft tumors or papular epidermal growths) lesions.*Hand, foot and mouth disease in humans is a different disease than foot and mouth disease which is a disease primarily of cloven hooved animals.
24Smallpox (Variola) Febrile prodrome Centrifugal distribution (most dense on face, then extremities, less on trunk)Synchronous lesions (appear during a 1-2 day period and evolve at the same rate)Rash maculopapular, then vesicular, and later pustularLesions firm to touch, deeply embedded in skinLesions on palms and soles
25Chickenpox (Varicella) Fever with onset of rashCentripetal distribution (greater concentration of lesions on the trunk rather than the face and extremities)Lesions appear in crops every few days and develop at different stages: papules, vesicles, pustules, and scabsLesions are more superficial and will burst if probedNot on palms and soles
27Lesions same stage and deeply embedded in skin Lesions in different stages and more superficial
28Most lesions have formed scabs Scabs not yet formedMost lesions have formed scabs
29Smallpox Major Criteria Febrile prodrome 1-4 days before rash onset; fever of >101 F, and at least 1 additional symptom*Rash lesions deep, firm/hard, round and well circumscribedOn any one part of the body lesions in same stage of development*Prostration, headache, backache, chills, vomitingor severe abdominal pain
30Smallpox Minor Criteria Greatest concentration of lesions on face and distal extremitiesLesions first appeared on oral mucosa/palate, face, forearmsPatient appears toxic or moribundLesions evolve from macules to papules to pustules over daysLesions on palms and soles
31Risk of Smallpox by Clinical History and Examination High riskfebrile prodrome andclassic smallpox lesions andsame stage of developmentModerate risk1 major OR > 4 minor criteriaLow riskno febrile prodrome orfebrile prodrome and < 4 minor criteria
33POSSIBLE CASE OF SMALLPOX REPORT TO MDH IMMEDIATELY:orA possible case of smallpox is a public health emergency. If a case of smallpox is suspected, call MDH immediately, at any time, for consultation and specific directions regarding proper sample collection.
34Smallpox Clinical Treatment Strict airborne and contact isolationSupportive care is the mainstay of smallpox therapyEnsure adequate fluid intakeAlleviate pain, feverAggressive treatment of secondary infectionsAntiviral therapy is experimental (Cidofovir)Vaccination of contacts up to 4 days post-exposure can prevent/attenuate clinical symptomsVaccine may be beneficial up to 4 days postexposureThis offers some protection against acquiring infection and significant protection against a fatal outcome
35Infection ControlStrict adherence to Standard, Airborne, and Contact PrecautionsAirborne:Closed door, negative pressure rooms with > 6 air exchanges per hour. Exhaust outside or through HEPA filtration.Caregivers must wear NIOSH respiratory protection when entering rooms (N95 masks preferred because PAPRs difficult to clean).
37Smallpox Information on the Web American Academy of Dermatology:CDC smallpox:Center for Civilian Biodefense Strategies: biodefense.orgCenter for Infectious Disease Research and Policy:IDSA Website.MDH: