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718 PART 5: Infectious Disorders

complications in DHF. 54,57,59 Other modalities, including intravenous control department, as public health interventions and outbreak investi-
immunoglobulins, pentoxifylline, and activated factor VII, have also gation will be paramount to reduce spread of disease. If exposure to an
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been proposed for use but data continue to be very limited. 54,57,59 HCW occurs, there is no specific postexposure prophylaxis, and infec-
■ EBOLA/MARBURG tion control and occupational health should be involved with potential
quarantine measures for exposed individuals.
distributed viruses found worldwide, including Ebola and Marburg ■ HANTAVIRUS
The hemorrhagic fever viruses include wide number of geographically
viruses, Rift Valley fever, Crimean Congo hemorrhagic fever, Lassa Hantaviruses are part of a larger genus that contains over 20 viral
fever, yellow fever, and dengue fever. 61,62 Ebola and Marburg viruses species. 73,74 They make up two severe acute febrile illnesses: hemor-
are in the family Filoviridae. Although any of the many VHF can cause rhagic fever with renal syndrome (HFRS, found in the Old World) and
severe disease in a traveler, Marburg and Ebola virus serve as a classic hantavirus cardiopulmonary syndrome (HPS, found in the New World).
template for VHFs and will be largely discussed here. Marburg virus Particularly, HPS was classified when cases of severe acute febrile respi-
has a single species while Ebola has four different species that vary in ratory illness were seen in the Southwestern United States. 73,74 In North
virulence in humans. Transmission appears to occur through contact America, disease was originally reported mostly in the Southwest and
with nonhuman primates and infected individuals. 62,63 Settings for trans- California, though more recently, cases have been reported in other
mission have occurred in vaccine workers handling primate products, parts of the United States, Canada, Europe, China, Chile Argentina, and
nonhuman primate food consumption, nosocomial transmission, and other parts of South America. Cyclical outbreaks tend to occur largely
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laboratory worker exposure. The use of VHF in bioterrorism has also in relation to the rodent population change. Symptoms initially begin
been postulated, largely based on its high contagiousness in aerosolized with a fever, chills, and myalgias in a prodromal phase. There is a lack of
primate models. The exact reservoir for the virus was initially felt to be upper respiratory symptoms as disease progresses rapidly to dry cough,
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with wild primates, but recently bats have been labeled as the reservoir, respiratory failure, and ARDS, shock, coagulopathy, and arrhythmias.
passing the infection onto nonhuman primates in the wild. The clinical Resolution can also occur rapidly. 75,76 Notably, thrombocytopenia with
manifestations of both Marburg and Ebola virus are similar in presenta- an immunoblast predominant leukocytosis is characteristic of the early
tion and pathophysiology, with morality being the only major difference cardiopulmonary phase. Diagnosis is by serologic testing of IgM in
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between them. Initial incubation period after exposure to the virus is early disease and IgG in later disease through public health laboratories.
5 to 7 days, with clinical disease beginning with the onset of fever, chills, Clinical contact with rodents in an endemic area with a leukocytosis
malaise, severe headache, nausea, vomiting, diarrhea, and abdominal and thrombocytopenia should aid the diagnosis. Treatment is mainly
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pain. 65-67 Disease onset is abrupt, and over the next few days, symptoms supportive, with extracorporeal membrane oxygenation being used in
and signs worsen to include prostration, stupor, and hypotension. Shortly some case. Ribavirin has been effective in HFRS, but not HPS. Mortality
thereafter, impaired coagulation occurs with increased conjunctival and remains at roughly 20%. 75,76 Transmission of hantavirus occurs through
soft tissue bleeding. In some cases, more massive hemorrhage can occur contact with rodent material when the virus is aerosolized. 75,76 This
in the gastrointestinal and urinary tract, and in rare instances, alveolar mostly occurs in indoor settings where dead rodent and rodent feces are
hemorrhage can occur. 65-67 The onset of maculopapular rash on the arms present. Direct live rodent contact has not been implicated in transmis-
and trunk also appears classic and may be a very distinctive sign. Along sion, and no human-to-human transmission has been documented with
with the bleeding and hypotension, multiorgan failure occurs eventually HPS. Cases appear mostly to be isolated North America, with a spring
leading to death. Reports of outbreaks and cases have largely occurred in to early summer cyclical pattern. 75,76 The amount and extent of the expo-
developing countries where critical care resources are more limited, thus sure change based on the rodent reservoir population. Hantavirus is a
experience with mechanical ventilation and the development of ARDS is reportable disease to public health officials.
not well documented. Case fatality rates have reached 80% to 90% in the
recent outbreak of Marburg outbreak in Angola, but Ebola case fatality
rates appear lower at 50%. 62,63 The diagnosis of VHF becomes extremely RICKETTSIAL DISEASES
alert and involve the public health department, and institute infection ■ ROCKY MOUNTAIN SPOTTED FEVER
important in order to initiate supportive care before the onset of shock,
control measures. 8,61,68 However, diagnosis is difficult outside of the Rocky Mountain spotted fever (RMSF) is a potentially lethal, but curable
endemic area. VHF should be suspected in cases of an exposed labora- tick-borne disease. The clinical spectrum of human infection ranges
tory worker, an acutely ill traveler from an endemic area (ie, central from mild to fulminant disease. The causative agent, Rickettsia rickettsii,
Africa), or in the presence of some classic clinical findings with increas- is a gram-negative, obligate intracellular bacterium with a tropism for
ing cases within the community suggesting a bioterror attack. Outside of vascular endothelial cells. 78,79 Infection leads to direct vascular injury that
travel or laboratory exposure, the presence of a high fever, malaise and may contribute to increased vascular permeability. Activation of clotting
joint pain, conjunctival bleeding and bruising, confusion, and progres- factors ensues. The host response, which is secondary to vascular injury,
sion to shock and multiorgan failure should raise suspicion of VHF, par- can lead to a variety of clinical manifestations such as interstitial pneu-
ticularly if multiple cases are presenting in the community. Laboratory monitis, myocarditis, and encephalitis. RMSF occurs throughout the
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diagnosis includes antigen testing by enzyme-linked immunosorbent United States, in Canada, Mexico, Central America, and in parts of South
assay or viral isolation by culture, but these tests are only performed America (Bolivia, Argentina, Brazil, and Colombia) and is the most com-
by the CDC currently. 8,61,68-71 As no specific therapy is available, patient mon rickettsial infection in the United States. The seasonal distribution
management includes supportive care, including a lung-protective of RMSF parallels the activity of the transmitting ticks, which serve as
strategy with low-tidal-volume ventilation if ARDS occurs as part of the the vector and reservoir for rickettsia. Many patients have a history of
disease course. 8,61,68-71 In a few cases in a Zaire outbreak in 1995, whole tick exposure before the onset of illness. 78,80,81 However, up to one-third
blood with IgG antibodies against Ebola may have improved outcome, of patients do not report a history of a tick bite, since the inoculation site
although analysis showed these patients were likely to survive anyhow. is generally painless and often obscured by hair or a skin fold. The tick
Although transmission appears to spread by droplet route, airborne transmits infection to humans during feeding. After the tick has been
precautions are recommended with respiratory protection with an N-95 attached to the host for 6 to 10 hours, rickettsiae are released from the
or PAPR and placement of the patient in a respiratory isolation room. salivary glands of the ticks. In addition, humans may become infected
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Equipment should be dedicated to that individual, and all higher risk by contact with tick tissues or fluids during the process of tick removal.
procedures should be done with adequate, full PPE. Any suspected case Infected patients become symptomatic 2 to 14 days after being bitten
of VHF should immediately involve public health officials and infection by an infected tick, with most clinical cases occurring between 5 and

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