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750 PART 5: Infectious Disorders

In a recent report, it was estimated that if as few as 10 persons were disturbances in regional circulation, and bleeding. Several of the hem-
initially infected by a covert biological attack with smallpox, within orrhagic fevers (Marburg, Ebola, Lassa, Junin, and Machupo viruses)
1 year as many as 224,000 persons would be infected if the disease went have been weaponized and experimented with for aerosol infectivity by
unchecked. Furthermore, a combination of quarantine (25% removal of the former Soviet Union, Russia, and the United States. Experimental
cases from society daily) and a mass vaccination program (reducing the infection of animals via aerosol is highly effective. However, aerosol
number of transmissions by 33%) would lead to halting of an epidemic infection of humans has never been documented, except in the case of
within 1 year, and the cumulative number of cases would be 4200. In hantavirus. However, these agents are highly infective by direct contact
order for this scenario to be feasible, it was estimated that over 9 million with needles, fluids, and tissues of infected persons. Important human
47
doses of vaccine would be necessary. 44,45 pathogens are:
Strict airborne and contact isolation in a negative pressure room is
of primary importance in dealing with a case of smallpox. However, • Arenaviruses: Lassa, Junin, and Machupo viruses that cause Lassa
this is only feasible in a small, contained outbreak. In a massive out- fever, Argentinean, and Bolivian hemorrhagic fevers, respectively.
break separate hospitals would need to be designated for those with • Bunyaviruses: Rift Valley fever (RVF) virus and Crimean-Congo hem-
complications or more severe forms of the disease. More likely, people orrhagic fever (CCHF) viruses cause RVF and CCHF. Hantaviruses
would have to be quarantined within their homes for routine sup- cause hemorrhagic fever renal syndrome (HFRS) and hantavirus
portive care. Patients requiring admission to the hospital in a scenario pulmonary syndrome (HPS).
like this would likely be critically ill. Keeping pace with fluid losses, • Filoviruses: Marburg and Ebola viruses.
electrolyte imbalances, and nutritional needs would be a major goal of • Flaviviruses: Dengue fever, Kyasanur forest disease, and Omsk hem-
therapy in these patients. This is especially true for patients with more orrhagic fever.
confluent rashes, as well as flat type and hemorrhagic type variants of
the disease. 40-42 VHF viruses target vascular endothelium, causing microvascular
Currently there is no definitive treatment of the disease. Cidofovir damage and derangement in vascular permeability. Common presenting
(currently FDA approved for treatment of cytomegalovirus retinitis) is complaints are fever, myalgias, and prostration. On examination patients
reportedly useful in preventing monkeypox and vaccinia in animals. It may have conjunctival injection, mild hypotension, flushing, and pete-
may have roles in postexposure prophylaxis and treatment of vaccinia chial hemorrhages. Bleeding is variable and generally not life threaten-
vaccination complications. This drug would possibly be made available ing, but it is an index of severity. Progression to shock and generalized
in a smallpox epidemic. 46 bleeding from the mucous membranes is often accompanied by neuro-
Vaccination is done with reconstituted lyophilized vaccinia. It is logical, hematopoietic, or pulmonary involvement. Hepatic involvement
applied with a bifurcated needle via 15 punctures at right angles into the is common; however, jaundice and frank hepatic failure is seen in a
skin overlying the deltoid without drawing blood. Successful vaccination small percentage patients with RVF, CCHF, Marburg, and Ebola hemor-
is confirmed by the appearance of a characteristic Jennerian pustule rhagic fevers, and yellow fever. Death is secondary to increased vascular
after a week, and this provides immunity for up to 10 years, and 20 years permeability, intravascular volume loss, and multiorgan failure. The
with revaccination. The vaccinee must understand that there is viable Working Group on Civilian Biodefense has concluded that CCHF and
vaccinia virus in the lesion from the moment the papule forms (2-5 days HFRS are unlikely to be employed as biowarfare agents, because they
after vaccination) until the scab dislodges (on days 14-21). The lesions are technically difficult to produce in large quantities. Dengue is also
should be covered as there is a risk of transmission to an unvaccinated an unlikely agent as it is not transmissible by aerosol, and only rarely
individual (“contact vaccinia”). 46 causes VHF. 47,48
A three-phase smallpox vaccination program was recently put forth Each virus has unique features that set it apart clinically. Lassa fever
by the U.S. government, under which medical and health care person- is endemic in West Africa, and has a high mortality in children and
nel are offered smallpox vaccination on a voluntary basis. The plan pregnant women. Hemorrhagic and neurologic complications are not
also calls for the creation of smallpox vaccination teams comprised pronounced and occur only in the severely ill. Case-fatality rates in
of health care workers and public health officials in each state. These hospitalized patients average 15% to 25%. In survivors deafness is a fre-
teams will assist in epidemiologic investigation and vaccination efforts quent sequela. In contrast, the South American arenaviruses (Argentine
during the first 7 to 10 days of an outbreak. Vaccination within 4 days and Bolivian hemorrhagic fevers) have prominent neurologic and hem-
of exposure will provide some protection from getting disease and will orrhagic manifestations. 47,48
decrease mortality. Recently it has been established that an increase in RVF is endemic in sub-Saharan Africa. Frank hemorrhagic disease
the dilution of the vaccine from 1 : 5 to 1 : 10 establishes immunity, and is seen in a minority of patients. Retro-orbital pain and blindness
this practice could substantially boost the availability of the vaccine to from retinitis occurs in 10%. In 1% of patients, fulminant disease with
the public. 46 hemorrhage, jaundice, and hepatitis develops, with a 50% fatality rate.
Contraindications for vaccination include immunosuppression, Fatal encephalitis occurs in <1%. Marburg and Ebola viruses produce
human immunodeficiency virus (HIV) infection, history of exfoliative prominent maculopapular rashes and DIC is a major component in
dermatologic conditions, and pregnancy. Complications of vaccina- their pathogenesis. Both are characterized by pronounced bleeding.
tion in order of frequency are infection, generalized vaccinia (usually Forty-one percent of patients manifest bleeding from puncture sites and
self-limited), eczema vacciniatum, postvaccinial encephalitis (with 10% mucous membranes; however, this form of bleeding does not distinguish
significant neurologic morbidity), and vaccinia gangrenosa (occurs in nonsurvivors from survivors. Pulmonary involvement is uncommon
immunosuppressed individuals and has a high fatality rate). Vaccinia and death usually results from multiorgan system failure and cardiovas-
immune globulin (VIG) is indicated for eczema vacciniatum, and vac- cular collapse. Fatality rates for Ebola and Marburg hemorrhagic fevers
cinia gangrenosa. 46 are 80% and 25%, respectively. 47-49
Routine laboratory tests in patients with VHFs are nonspecific, but
VIRAL HEMORRHAGIC FEVER the presence of early thrombocytopenia and coagulation abnormalities
should arouse suspicion. Definitive diagnosis of VHF is done by isola-
Viral hemorrhagic fever (VHF) is caused by a diverse group of RNA tion in cell culture or immunohistochemical staining of formalin-fixed
viruses that are transmitted to humans from their natural animal and tissues. These techniques should only be attempted under BSL 4 condi-
arthropod reservoirs. They produce clinical syndromes character- tions at the CDC or USAMRIID. In the field, viral identification can be
ized by fever, myalgias, prostration, increased vascular permeability, done safely following chemical inactivation with ELISA to detect viral

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