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CHAPTER 81: Biological Warfare 749

of 97 days. Aspiration pneumonia was presumed to occur in 29% of hemorrhagic manifestations and rapid progression to death even before
patients, all of whom received mechanical ventilation. Patients generally any skin lesions could be discerned. Variola sine eruptione was seen in
regained respiratory muscle strength later than in other muscle groups. vaccinated persons and was characterized by a 48-hour period of febrile
Death from sepsis and shock were related to aspiration or ventilator- illness. Unfortunately the various types cannot be distinguished until
associated pneumonia. 39 they start to manifest. 40,41
Definitive diagnosis of botulism is by mouse neutralization ( bioassay), The classical type of disease begins acutely with prodromal symp-
where type-specific antitoxin is used to protect mice against toxin in toms, followed by an enanthema of the tongue, mouth, and oropharynx.
a patient’s serum. Serum should be obtained prior to administration The next day a discrete centrifugal rash, characterized by 2- to 3-mm
of antitoxin, as it may interfere with the assay. Results may take up to reddish macules, begins on the face, hands, and forearms. These lesions
2 days. Gastric, stool, and vomitus samples can also be used. Samples progress to become papules and then vesicles of 3 to 5 mm in size, and
should be handled under BLS 2 conditions at a level B lab. 37,39 spread centrally to cover the whole body by the fourth to seventh day.
The mainstays of therapy are administration of antitoxin, ventilatory By the eighth day pustules of 4 to 6 mm are formed. Over the next 5
assistance, and supportive care. Patients presenting with foodborne to 8 days, the pustules become larger and have a central depression
botulism should be given activated charcoal and then antitoxin when (umbilicated). Later they become flattened and more confluent. During
available. Currently an equine botulinum antitoxin that provides passive this phase of rash another fever spike occurs. By the 13th day the lesions
immunity against types A, B, and E toxins is available from the CDC start to crust and over the ensuing week start to scab and separate, leav-
through state and local health departments. Prompt administration ing depressed depigmented lesions. The rash is typically more peripher-
limits the severity of disease, but does not reverse existing paralysis. An ally distributed and homogeneous in stage when compared to the rash
investigational heptavalent antitoxin against types A through G is avail- of chickenpox. Secondary infections of the rashes were reportedly not
able in the United States Army for other toxin types. Unlike organophos- common. Complications of the disease included panophthalmitis and
phate poisoning, atropine is not indicated and would possibly exacerbate secondary infection causing blindness in 1%, arthritis in 2% of children,
symptoms. 37,39 and encephalitis in 1%. Bronchitis was occasionally reported; however,
Patients unable to handle oropharyngeal secretions should be placed pneumonia was rare. 40,41
in reverse Trendelenburg position with frequent pulmonary and oropha- Death from the classic type of disease was reported to be most
ryngeal toilet to avoid aspiration. Patients with clinical signs of respiratory common during the second week. The fatality rate in the classic type
failure require endotracheal intubation and mechanical ventilation. It is seems directly related to the degree of confluence among the lesions.
important to recognize that patients remain conscious throughout and This may have direct bearing on the degree of fluid sequestration and
may require sedation to relieve anxiety. Aminoglycosides, clindamycin, protein loss during the vesicular and pustular stage. Renal failure,
and steroids should be avoided, as they may worsen muscle atrophy and electrolyte imbalance, protein loss, and metabolic derangements were
exacerbate neuromuscular blockade and myopathy. 37,39 reportedly similar to those of burn victims and likely accounted for the
Postexposure prophylaxis with antitoxin is currently neither rec- majority of the morbidity of shock, infection, and death. 42
ommended nor practical. Exposed persons who are not symptomatic The two most dreaded forms of the disease are the hemorrhagic and
should be watched closely and given antitoxin if symptoms develop. flat types. Hemorrhagic type has a predilection for pregnant women.
Vaccination against botulinum toxin using a multivalent toxoid is advo- There was no difference in incidence between vaccinated and unvac-
cated only for military personnel and laboratory workers who may be at cinated individuals. It was characterized by a shorter more severe
great risk. Decontamination is not required, as the agent is not dermally prodromal phase and marked prostration. Diffuse hemorrhagic lesions
active. However, the possible use of a nerve agent should be considered (likely due to DIC) occurred in all mucous membranes and skin, lead-
in a scenario with many patients presenting with muscular weakness, ing to sloughing of these surfaces. Pulmonary edema and hemoptysis
and dealt with appropriately with decontamination (see Table 81-4). 37,39 were common. Patients were reportedly conscious until the very end
and death often occurred within a week. Flat type disease was rare in
SMALLPOX vaccinated individuals. The prodromal fever was present throughout
the eruptive phase of the disease, and patients were extremely toxic in
Smallpox vaccination ceased in 1980, after the disease was declared appearance. Mucous membrane sloughing was also characteristic. 40-42
eradicated by the WHO. This has left a civilian population under the It is likely that the vast majority of practicing clinicians would not
age of 30 totally susceptible. If the virus were ever intentionally released, be able to recognize smallpox in its early stages, by which time it would
its properties like high person-to-person transmission, viability outside already be too late to prevent its spread. The differential diagnosis of the
its human host, and high fatality rate would cause colossal damage. 40,41 disease is quite vast, but the most common misdiagnosis would be that of
Smallpox is caused by the variola virus of the orthopoxvirus family. chickenpox. Chickenpox has a less pronounced prodromal illness, a more
Smallpox is highly infectious and person-to-person spread occurs by centripetal rash, asynchronous evolution of the rash, quicker scab formation
inhalation of expectorated respiratory droplet nuclei and by direct (1 week), and a fatality rate of <1%. Other illnesses that can be confused
contact of the mucous membranes. Fomites such as contaminated linen with smallpox are monkeypox, various cutaneous drug reactions, atypical
43
of infected patients have also been responsible for spread. The incuba- measles, and molluscum contagiosum. Cases of hemorrhagic and flat type
tion period is 12 to 14 days. Following deposition on the upper airway smallpox would be difficult to diagnose clinically, and would likely be mis-
mucosa, the virus is transported to regional lymph nodes and then other diagnosed as severe meningococcemia, DIC from other diseases, Stevens-
lymphoid tissues. The virus then spreads systemically and localizes in Johnson syndrome, or a filovirus hemorrhagic fever. 40-42
small vessels of the dermis and oropharyngeal mucosa. This prodromal Notification of local, state, and national public health authorities is of
phase lasts for 3 days, and is marked by high fever, rigors, malaise, the utmost importance, as the diagnosis of smallpox is an international
vomiting, headache, and backache. 40,41 public health emergency. Specimens should be sent to state and national
The clinical manifestations of smallpox are of five types. The clas- health authorities using the LRN, under BSL 4 precautions. 40-42
sic or ordinary type accounted for 90% of cases with a fatality rate of Demonstration of the characteristic brick-shaped virus under elec-
30%. Modified type occurred in 25% of unvaccinated and 2% of vac- tron microscopy is confirmatory for an orthopoxvirus, and aggregations
cinated cases with rare fatalities. Flat type occurred in 7% of cases and of variola virus particles called Guarnieri bodies can be found under
was characterized by slow evolution of flat, soft focal skin lesions and light microscopy. However, none of these tests are capable of discrimi-
severe systemic toxicity. It had a fatality rate of 95% and 33% in the nating variola from other orthopoxviruses. Definitive diagnosis is by
unvaccinated and vaccinated, respectively. Hemorrhagic type was almost isolation of the virus on chorioallantoic membrane culture and further
uniformly fatal, occurring in 3%, and was characterized by diffuse testing with PCR. 40-42

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