FMMS PRIMER ON BIOTERRORISM

Anthrax

• Description: a spore forming gram-positive rod, which can cause disease by inhalation, inoculation, or ingestion of spores, which, upon reversion to regular bacterial forms, produce potent “edema” and “lethal” toxins.
• The pneumonic, or inhalational, form starts 1-6 days after exposure with, fever, myalgias cough and fatigue, which after a brief improvement, progress to an abrupt respiratory distress and shock. There are no specific physical findings, but the chest x-ray may show a widened mediastinum, with or without effusion, but mostly without, infiltrates, because the disease is primarily a mediastinitis. Fifty percent have associated meningitis.
• Diagnosis: widened mediastinum on CXR, Gram-positive rods may be found on gram stains of CSF or buffy coats, and positive blood cultures later in the illness.
• Treatment: IV doxycycline or quinolones (supernormal doses) for 4 weeks, plus vaccination.
• Prophylaxis: avoid inhalation of contaminated material, doxycycline or Ciprofloxacin x 8 weeks plus vaccination (3 doses).
• Pediatrics: doxycycline or penicillin.
• Isolation: Standard. No person-to-person transmission of inhalation anthrax.
• Inoculation (cutaneous) anthrax may appear in conjunction with inhalation cases. Local tissue destruction results in the formation of a black eschar or ulcer with (+/-severe) surrounding edema. Some develop septicemia.
• Gastrointestinal anthrax occurs when large numbers of spores are ingested. It may present with nausea and vomiting, abdominal pain, bloody diarrhea +/- ascites, which progresses to an acute abdomen. The toxins destroy the mesenteric lymph nodes and the circulation to the small bowel.

Plague

• Description: Yersinia pestis is a gram-negative rod, which causes disease in two forms.
• The pneumonic form begins 2-3 days after inhalation of an aerosol, either from an infected patient or from a bioterrorist aerosol source, with sudden onset of myalgias, high fevers, headache and cough with bloody sputum. Within one day it progresses to a fulminant pneumonia with dyspnea, stridor, cyanosis, septic shock with DIC and hepatocellular damage. The chest x-ray has consolidation /infiltrates. Six percent have associated meningitis.
• The bubonic form would probably not be used as a bioagent.
• Diagnosis: cultures and gram stains of blood, sputum, CSF and lymph node aspirates. Immunoassays available.
• Treatment: gentamicin, doxycycline or chloramphenicol (for meningitis).
• Prophylaxis: doxycycline.
• Isolation: mandatory for at least the first 48 hours of treatment.
• Pediatric: doxycycline or trimethoprim/sulfa for prophylaxis but gentamicin or chloramphenicol for treatment.

Tularemia

• Description: Tularemia is caused by Francisella tularensis, a small, fastidious Gram-negative bacillus. Human infections can occur via aerosols, contaminated food or water, from arthropod bites, or through skin exposure.
• The incubation period can be as short as 24 hours, but can be up to 14 days or longer. Sporadic cases of tularemia occur in most parts of the USA, and tularemia is endemic among small animals in California. Although the infectious dose of F. tularensis is very low, there is no evidence for person-to-person transmission of infection.
• Each route of infection produces a different clinical picture. Clinical or radiographic features cannot differentiate tularemia pneumonia from other serious bacterial pneumonias. The usual result of inhalation is pneumonia with hilar adenopathy and/or pleural effusions in about 1/3 of cases. High fever, chills, rigors, sore throat, myalgias (elevated CPK in some) and a non-productive cough are common. There may be pulse-temperature dissociation. Untreated, the mortality of tularemia pneumonia may reach 50%. Ingestion is more likely to cause exudative tonsillitis and supporative cervical adenitis.
• Diagnosis is difficult because the bacteria are fastidious and grow slowly, they may not grow out of sputum on standard blood agar, or the laboratory may not recognize them. Rapid diagnostic tests are not available. Blood and pleural fluid cultures may be positive. Aspirates of enlarged lymph nodes will also yield the pathogen. Serology can be used for retrospective diagnosis. A four-fold titer increase or a titer above 1:160 is diagnostic, but this usually takes 10-14 days to develop.               
  
• Treatment is with parenteral gentamicin 5mg/kg qd, or doxycycline 100 mg, or chloramphenicol 15mg/kg q 6h, or erythromycin 500 mg q. 8h. Because this organism can be drug-resistant, in vitro susceptibility testing should guide subsequent treatment. Doxycycline or fluoroquinolones can be used for prophylaxis in people who were likely exposed but not yet ill. There is no available vaccine. Contaminated surfaces can be cleaned with 10% bleach and then wiped with 70% alcohol. Cloths and skin can be washed with soap and water.