FMMS PRIMER ON BIOTERRORISM

General Discussion

• Viral agents proposed for use as biologic weapons include Smallpox (variola virus), Venezuelan Equine Encephalitis Virus, and the multiple agents causing viral hemorrhagic fevers, typified by Ebola.
• General characteristics of these viruses include:
  • Initial presentation with non-specific flu-like symptoms.
  • Pathogenesis secondary to direct cytopathic effect, immune-complex deposition, or other processes often resulting in vascular injury and end-organ failure.
  • Vaccination most effective prophylaxis but few vaccines generally available for proposed agents.
  • Few antiviral agents have proven efficacy or are available.

Smallpox – Variola virus

• Declared eradicated 1980 by WHO, known stockpiles of virus still remain at the CDC in Atlanta and at the Institute for Viral preparations in Moscow and possibly at other sites in the world. In the USA, civilian vaccination programs ended in the early 1980’s while the military stopped in 1989.
• Virus is spread by aerosol with incubation period averaging ~12 days (7-19days).
• Clinical symptoms begin with abrupt onset of malaise, fevers, rigors, headache, emesis, backache, and delirium (15%) followed 2-3 days later by onset of rash on face, hands, forearms, and legs then spreading centrally with lesions progressing from macules to papules to pustular vesicles. Lesions typically are in the same stage of development.
• Patients are highly infectious during the initial respiratory phase and remain so until all eschars are off.  Mortality is about 30% in unvaccinated population. Mortality is lower in vaccinated individuals, but no civilians have maximal protection because vaccination ceased 30 years ago.
• Characteristics differentiating the Rashes of Variola and Varicella:

• Clinical diagnosis of Varicella virus infection (i.e. chickenpox) is adequate if the clinical presentation is typical.  Atypical or unusually severe cases of Varicella should prompt consideration of laboratory testing to confirm the diagnosis of Varicella; the exclusion of Varicella, either via rapid diagnostic testing for Varicella antigen or viral culture should suggest the possibility of a pox virus infection or another alternate diagnoses.
• Treatment: Cidofovir and other antivirals but none are proven effective. Isolation: Airborne.
• Vaccination within 3 days of exposure will prevent  disease and within 5 days life-saving. CDC has 12 – 14 million doses of vaccine. Oral vaccine in development.

Equine Encephalitis Viruses

• Togaviridae, all can be infectious by aerosol, easily produced and stable. VEE studied as a weapon by USA. Susceptibility is high (90-100%) with ~ 100% of those infected develop acute disease.
• Incubation period of 1-6 days followed by acute febrile illness with malaise, myalgias, fevers, rigors, severe headache, and photophobia x 24-72 hours followed by nausea, emesis, cough, sore throat, and diarrhea. 0.5-4% will develop encephalitis with altered mental status.
• Diagnosis on clinical and epidemiological grounds. Exam is non-specific. Lab often with leukopenia and lymphopenia, increased AST, and lymphocytic pleocytosis in CSF. Confirmation provided by viral isolation (throat, serum, CSF), serology (IgM available) and PCR.
• Treatment is supportive, mortality < 1% (increased at extremes of life), vaccine is experimental. Isolation: Airborne.

Viral Hemorrhagic Fevers

• Caused by various RNA viruses, usually with an animal reservoir. All are potentially infectious by aerosol with high morbidity and mortality.
  • Arenaviridae: Lassa, Argentine, Bolivian, Venezuelan, and Brazilian
  • Bunyaridae: Rift Valley Fever, Congo-Crimean, Hantaviruses
  • Filoviradae: Ebola, Marburg
  • Flaviviridae: Yellow Fever
• All hemorrhagic fever viruses can cause capillary leak syndromes.
• Incubation period 5-10 days (Filoviradae) followed by malaise, fever, myalgias, prostration, conjunctival injection, petechiae, ecchymoses, shock, diffuse hemorrhage, neurologic dysfunction and pulmonary collapse. Increased LFT’s and renal dysfunction poor prognosis.
• Diagnosis based on clinical and epidemiologic parameters. Definitive diagnosis: serology, PCR, and viral isolation.
• Treatment is largely supportive, avoiding ASA/antiplatelet drugs, Ribavirin (Lassa, CCHF, HFRS, and RVF). Vaccine available for Yellow Fever, Argentine, Bolivian, and Rift Valley Fever. Isolation = Airborne.

Influenza Virus

• As several of the bioagents may produce febrile, respiratory symptoms/signs, during the annual influenza season in Fresno-Madera (December - March), the clinician should consider performing specific, diagnostic tests for the presence of influenza virus or antigen. Several rapid diagnostic tests are commercially available and can be performed on sputum samples. Viral isolation is also available and may assist in the management of these patients and others in the community (i.e. use of specific anti-influenza medications and vaccine optimization).