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CHAPTER 81: Biological Warfare 747

fluorescence staining for fraction 1 (F1) envelope antigen, phage lyses complain of cough and chest discomfort without having signs of pneu-
of cultures, or polymerase chain reaction (PCR) assay should confirm monia. Patients may have varying degrees of sore throat, abdominal
identification. Acute and convalescent serum titers for antibody to F1 pain, arthralgias, and myalgias. If untreated, anorexia, continued
antigen are retrospectively diagnostic. Chest radiographs in cases of weight loss, and debility occur over a period of weeks to months.
bubonic plague may show small transient unilateral infiltrates. However, Clinically the disease may present as either ulceroglandular (which
the presence of nodular or bilateral alveolar infiltrates in these patients includes glandular, oculoglandular, and pharyngeal), or pneumonic
is strongly associated with a more fulminant and fatal course. Primary (typhoidal) forms. 35
pneumonic forms of plague are associated with bilateral alveolar and Ulceroglandular tularemia accounts for about 85% of natural cases,
nodular infiltrates, with over half of them having pleural effusions. presenting as a cutaneous ulcer at the inoculation site within a few days
Cavitary lesions have also been noted to occur. 29,31,33 of the onset of symptoms. The tender ulcer usually measures 0.4 to 3 cm
Treatment requires the prompt administration of antibiotics, espe- in diameter, has raised edges, and is associated with regional lymph-
cially in the bacteremic and pneumonic forms. As the bacteria is capable adenopathy. Affected lymph nodes are also tender, and can become
of inducing an endotoxemia leading to DIC, septic shock, ARDS, and fluctuant and suppurate. A minority present with the glandular form
multiorgan failure, close observation of the patient and early resuscita- and no signs of skin involvement. The oculoglandular and pharyngeal
tive measures are warranted at the earliest sign of progression toward forms refer to the primary sites of inoculation, and are associated with
a more fulminant course. These patients require aggressive volume intense inflammation, edema, hemorrhage, and granulomatous disease
resuscitation, and may need mechanical ventilation as well as vasopres- of the inoculation site, as well as regional lymphadenopathy. Of interest
sor support. 29,31,33 is that the pharyngeal form of the disease is frequently associated with
Based on the Working Group on Civilian Biodefense’s recommenda- pneumonia. 34,35
tions for pneumonic plague, first-line therapy is with streptomycin 1 g Typhoidal tularemia refers to illness without lymphadenopathy or
IV or IM twice a day, or gentamicin 0.5 mg/kg IM or IV twice daily. signs of a portal of entry. It occurs in 15% of natural cases. It is likely
Alternate therapies are doxycycline 100 mg IV twice daily, ciprofloxacin that this is actually a primary pneumonic form of the disease, acquired
400 mg IV twice daily, or chloramphenicol 25 mg/kg IV four times daily. by inhalation of the organism. Onset is more abrupt, and patients
Therapy should be implemented in anyone exposed with a temperature are more toxic, with pronounced gastrointestinal symptoms such as
>38.5°C or a new cough. 28 abdominal pain, prostration, and watery diarrhea. Respiratory com-
In the setting of mass casualties where public health facilities may plaints and pneumonia are associated with 80% of cases. Pharyngitis,
be overwhelmed, first-line therapy recommendations for postexposure pleuritic chest pain, cough with minimal sputum production, and
prophylaxis in adults include doxycycline 100 mg orally twice daily, or bronchiolitis are common, while hemoptysis is uncommon. However,
ciprofloxacin 400 mg orally twice daily. Alternatively, chloramphenicol unlike both primary pneumonic plague and inhalational anthrax, the
25 mg/kg can be used. Currently no recommendations exist for vaccina- disease does not usually rapidly deteriorate to respiratory failure and
tion of public or health care providers in the postexposure setting. 29,31,33 death (see Table 81-3).
Patients with pneumonic forms of plague should be kept under respi- Both forms of tularemia are capable of causing pneumonia, ARDS, and
ratory droplet isolation protocols until they have received at least 48 septic shock, with the need for mechanical ventilation and vasopressor
hours of appropriate antibiotic therapy or shown improvement. Persons support, although only a handful of such cases exist in the postantibiotic
who have been exposed who refuse to take antibiotic prophylaxis but are literature. Interestingly, those that did had ulceroglandular forms of the
not symptomatic do not require isolation, but need to be watched and disease. Mortality is 35% in pneumonic forms of the disease without
treated at the first sign of cough or fever. The use of standard disposable therapy. With appropriate antibiotics fatalities would be <5%. However,
surgical masks is recommended. Microbiology lab personnel should be potential for widespread disability would be great. 34,35
aware of the potential of getting infected from handling samples during Initial laboratory tests are nonspecific. Moderate leukocytosis, eleva-
high-risk lab procedures, and BSL 3 precautions should be observed tions in lactate dehydrogenase, serum transaminases, and alkaline phos-
during such times. 29,31,33 phatase are common. CSF may show a small elevation in protein, low
glucose, and minimal increases in WBCs. Typically blood cultures are
TULAREMIA negative, owing to poor growth on standard media and a low index of
suspicion, and historically there is usually a delay of several days before
Tularemia is caused by a gram-negative, facultative intracellular bacte- identification. However, organisms have been recovered from blood,
rium, Francisella tularensis. It is a zoonotic disease of small mammals ulcers, conjunctival exudates, sputum, gastric washings, and pharyngeal
and is transmitted by arthropod vectors (primarily ticks). There are two exudates. Direct microscopic examination using fluorescent labeled
biovars of F tularensis. Biovar tularensis or type A is more common in antibodies provides a means of rapid diagnosis. Antigen detection, PCR,
the south-central and western United States, and is highly virulent to and ELISA are also used, and these methods are available at state and
rabbits and humans. Biovar palearctica or type B is more common in national reference labs through the LRN. Manipulation of cultures is a
Eurasia and less virulent to humans. The bacteria can survive for long well-known hazard to laboratory personnel, and should only be done
periods in soil, water, and animal carcasses. Organisms infect humans under BSL 3 containment. A fourfold increase in serum antibody is also
by direct contact with mucous membranes, broken skin, ingestion, or diagnostic, but given the fact that diagnostic levels cannot be obtained
inhalation. Hunters, animal handlers, and laboratory personnel work- until 10 or more days after the onset of illness, this information is mini-
ing with the bacteria are at greater risk for developing disease. Only 10 mally useful in managing an outbreak. 34,35
to 50 organisms are needed to cause infection in humans, via contact, In a large series of inhalation-acquired tularemia, 50% of the patients
inoculation, or inhalation. Theoretically, a biological attack with tulare- had chest x-ray abnormalities; 40% had infiltrates described as 2- to
mia would be with an aerosolized form. From the site of entry, bacteria 8-cm oval-shaped lesions with indistinct borders, mostly in the juxtahi-
are ingested by macrophages and transported to regional lymph nodes lar position; 21% had unilateral hilar adenopathy always associated with
where they multiply and disseminate. At the site of the entry, a predomi- other x-ray abnormalities; and 11% had pleural effusions. Pneumonia
19
nantly cell-mediated inflammatory reaction causes necrosis and granu- can occur in ulceroglandular disease, especially with the pharyngeal
loma formation. Granulomas are also formed at other target organs after form. Interstitial patterns, cavitary lesions, bronchopleural fistulae, and
dissemination. 34 frank ARDS have been reported on chest radiographs. 18,19 Pleural fluid
The incubation period is 3 to 5 days. Patients present with abrupt analysis shows a serosanguineous exudate with a lymphocytic predomi-
onset of fever, chills, headache, coryza, malaise, and weakness. A nance. Increased adenosine deaminase, lysozyme, and β -microglobulin
2
temperature-pulse deficit is noted in 42% of patients. Patients may occur similarly to tuberculous effusions. 34-36

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