Hemorrhagic Smallpox

CDC Case Definition An illness with acute onset of fever >101°F followed by a rash characterized by firm, deep seated vesicles or pustules in the same stage of development without other apparent cause. Clinically consistent cases are those presentations of smallpox that do not meet this classical clinical case definition (1) hemorrhagic type, (2) flat type, and (3) variola sine eruptione. Laboratory criteria for diagnosis is (1) polymerase chain reaction (PCR) identification of variola DNA in a clinical specimen, or (2) isolation of smallpox (variola) virus from a clinical specimen (Level D laboratory only confirmed by variola PCR). 

A single case of disease by an uncommon agent (smallpox, some viral hemorrhagic fevers)... 

Biological Agents BACTERIA (Anthrax, Brucellosis, Cholera, Plague, Tularemia). VIRUSES (Crimean-Congo Hemorrhagic Fever, Rift Valley Fever, Smallpox, Venezuelan Equine Encephalitis (VEE), Viral Hemorrhagic Fever (Ebola)). TOXINS (Botulinum, Ricin, Staphylococcal Enterotoxin B (SEB), Trichothecene Mycotoxins/T-2). 

Viruses (smallpox, encephalitis, and hemorrhagic fevers like Ebola, Lassa and Rift Valley fevers)... 

This section addresses the viral forms of biological agents that would most likely be considered by terrorists. They include variola major (smallpox), Venezuelan equine encephalitis (encephalitis), Crimean Congo hemorrhagic fever, and Rift Valley hemorrhagic fever. 

Tiemo, P.M., Jr., Protect Yourself against Bioterrorism Everything You Need to Know about Anthrax, Plague, Botulism, Smallpox, Encephalitis, Cholera, Hemorrhagic Fevers, Ricin, and More, Pocket Books, New York, 2002. 

Second we have the issne of bioterrorism. There are many other potential threats smallpox, anthrax, tularemia, plague, a family of viral hemorrhagic fevers, among others. In addition, there are a limitless number of virulent bacteria that might be constructed employing the modem techniqnes of genetic engineering. 

The Variola major rash presents in four distinct ways, ordinary, modified, flat, and hemorrhagic. The type of rash presentation is probably associated with the strength of the immune response. Ordinary smallpox is most frequent, whereas the mild modified form, seen primarily in previously vaccinated patients, is uncommon. The most severe presentations, flat and hemorrhagic, are usually fatal but are fortunately rare. Smallpox infection can also occur without a rash. A mild but uncommon variation of variola infection, variola sine eruptione (meaning smallpox without a rash) occurs generally in previously vaccinated people and involves a febrile illness alone. Asymptomatic infections are also possible, yet rare. 

Flat-type refers to the characteristic lesions, which are flush with the skin rather than raised vesicles. In outbreaks in India, flat-type smallpox was responsible for between 5 and 10% of cases, with most of the flat-type cases (72%) occurring in children (25). Constitutional symptoms associated with the 3 day prodrome are more severe than in ordinary smallpox and continue after the rash develops. Patients have a high fever and appear toxic throughout the course of the illness. Oral lesions tend to be extensive, and the skin lesions evolve slowly. By the 7 or 8 day, the flat skin lesions appear buried in the skin. In comparison to ordinary smallpox, the vesicles contain little fluid and do not develop the characteristic umbilication. Unlike ordinary smallpox, flat-type smallpox lesions are soft and velvety in texture. The lesions may contain hemorrhages. Respiratory complications are common, and the prognosis for flat-type smallpox is grave. Most cases are fatal (25). 

In the early stages of a smallpox outbreak, perhaps before more typical cases appear, hemorrhagic smallpox can be confused with other conditions such as meningococcemia and leukemia, and flat (mahgnant) smallpox can be mistaken for hemorrhagic chickenpox. In some cases, the severe abdominal pain associated with the prodrome has prompted unnecessary surgical intervention (25). 

These are anthrax, smallpox, plague, botulism, tularemia, viral hemorrhagic fevers and ricin. They can disseminate and present a high risk on public health. Most of them require Level 4 Biosafety laboratories. 

Rash-maculop apul ar All rash syndromes typically accompanied by fever Rocky Mountain spotted fever, Scrub typhus, Epidemic typhus, Ebola/Marburg, Argentine hemorrhagic fever, Bolivian hemorrhagic fever, Dengue fever, Chikungunya fever, Tularemia (uncommon), Psittacosis (uncommon), Smallpox (early)... 

Cidofovir Treatment of Variola (Smallpox) in the Hemorrhagic Smallpox Primate Model and the IV Monkeypox Primate Model [252]... 

Huggins J W, Zwiers S H, Baker R O, et al. Cidofovir Treatment of Variola (Smallpox) in the Hemorrhagic Smallpox Primate Model and the IV Monkeypox Primate Model. Available http //www.who.int/csr/disease/smallpox/cidofovirtreatment/en/ index.html. 

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