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Smallpox: A Brief Overview


The last naturally occurringcase of smallpox was reportedin Somalia in October 1977.Despite the eradication ofsmallpox, the causative agent,variola virus, remains in existence.1,2

The last naturally occurringcase of smallpox was reportedin Somalia in October 1977.Despite the eradication ofsmallpox, the causative agent,variola virus, remains in existence.1,2As a result of waning or nonexistenthuman immunity to this organism,claims of clandestine viral stockpiles,and purported efforts by theformer Soviet Union to create aweapon from the agent, variola virusis considered a possible biowarfareand bioterrorism agent. This virus isextremely infectious by aerosol route,is readily transmissible from personto person, is stable, and produces relativelyhigh mortality. Moreover, theimpact of its use would be compoundedby the inadequacy of current vaccinestockpiles in the United States.3,4In addition, there is concern that theclosely related monkeypox virus,which is not under strict surveillance,might be employed as a weapon.EPIDEMIOLOGYThe most recent outbreaks ofvariola major carried mortality ratesof 30% in nonimmunized persons and3% in immunized persons. In 10% ofcases, smallpox assumes either of 2highly fatal and less specific pictures:hemorrhagic disease accompaniedby a diffuse erythematous rash thatevolves into petechiae and hemorrhages,and a malignant form accompaniedby papules that coalesce andnever become pustular. Both of thesevariant pictures would be much lesseasily recognized by most practitioners.Fewer skin lesions develop inpersons with variola minor or withpreexisting partial immunity.CLINICAL COURSEAfter an incubation period of 12to 14 days (range, 7 to 17 days), clinicalmanifestations of smallpox beginabruptly with fever, malaise, rigors,vomiting, headache, and backache.Delirium and abdominal pain occur ina minority of patients. Some patientsexhibit an erythematous rash at thisstage.4-6 After 2 to 3 days, a maculopapulareruption appears on the face,hands, forearms, and oropharyngealmucosa; it later spreads centripetally.Lesions progress within a few daysfrom macules to papules to vesiclesand then to pustular vesicles; 8 to 14days after onset of the illness, scabsform, with subsequent formation ofpigmented depressed scars.Unlike varicella lesions--withwhich smallpox lesions might easilybe confused (see Photo Essay, page176h)--smallpox lesions remain synchronizedduring the course of theillness and are more deeply seatedin the dermis; in addition, there is agreater abundance of lesions on theface and extremities than on thetrunk.PREVENTIVE MEASURESPersons with suspected smallpoxand their close contacts must beplaced in strict quarantine with respiratoryisolation for 17 days. Thevirus is shed in oropharyngeal secretionsprimarily after the onset of theexanthem.4-6 While mucous membranesecretion of the virus diminishesafter the first few days of theeruptive lesions, the virus can be recoveredfrom scabs throughout theillness period.All exposed persons and theircontacts should receive the vacciniaviral vaccine as soon as possible.Some protection against disease maybe achieved if the vaccine is givenwithin a few days of exposure. Thecurrent supply of vaccinia vaccineand vaccinia immune globulin, whichwould be needed for those with postvaccinationcomplications and thoseat risk, is potentially inadequate; however,this problem is currently beingaddressed.The duration of protective immunityfollowing primary vaccinationis probably less than 15 years;following revaccination, it may last30 years. Current efforts are focusedon the evaluation of possibleantiviral agents, such as cidofovirand its derivatives, in the treatmentof variola infections.DIAGNOSTIC ISSUESConfirmation of the diagnosisof smallpox is crucial; PCR andELISA are the most useful assays.Virions and Guarnieri bodies maybe seen with electron and light microscopy,respectively, but thesefindings do not distinguish betweenvariola and the other orthopoxviruses.Monkeypox, which is still endemicin areas in Africa, can producea clinically indistinguishabledisease, although person-to-personspread is less common than withsmallpox.3,7,8 Monkeypox may alsobe an attractive and tractableweapon.5 Any suspicion of smallpoxshould prompt immediate notificationof public health authorities.


REFERENCES:1. Preston R. The bioweaponeers. The New Yorker.March 9, 1998:52-65.
2. Henderson DA. The looming threat of bioterrorism.Science. 1999;283:1279-1282.
3. Breman JG, Henderson DA. Poxvirus dilemmas–monkeypox, smallpox, and biologic terrorism.N Engl J Med. 1998;339:556-559.
4. Henderson DA, Inglesby TV, Bartlett JG, et al.Smallpox as a biological weapon: medical and publichealth management. JAMA. 1999;281:2127-2137.
5. US Army Medical Research Institute for InfectiousDiseases. Medical Management of Biological CasualtiesHandbook. 3rd ed. Frederick, Md: USAMRIID; 1998.
6. Franz DR, Jahrling PB, Friedlander AM, et al.Clinical recognition and management of patients exposedto biological warfare agents. JAMA. 1997;278:399-411.
7. Centers for Disease Control and Prevention.Human monkeypox–Kasai Oriental, DemocraticRepublic of Congo, February 1996–October 1997.MMWR. 1997;46:1168-1171.
8. Cohen J. Is an old virus up to new tricks? Science.1997;277:312-313.

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