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CHAPTER 80: Viral Hemorrhagic Fevers 739
Diagnosis LASV IGM and LASV antigen are detected by ELISA early. was 87% sensitive and 88% specific for the diagnosis of AHF. Proteinuria
Real-time-PCR is limited by strain variations. LASV can be isolated above 1 g/L was highly specific but not sensitive (44%). 76
from the blood, body fluids, or tissues when grown in Vero cell cultures Diagnosis RT-PCR, IgM, Junin Ag detection, and viral isolation help con-
in a BSL-4 level laboratory. 67 firm the diagnosis.
Management of Lassa Fever In a randomized study performed in Sierra Leone, Management Convalescent serum used within 8 days of onset decreases
intravenous ribavirin (loading dose 2 g followed by 1 g q6h for 4 days then mortality from 16.5% to 1.1%, but in 10% of recipients causes a transient,
500 mg q6h for 6 days) was highly effective if started within 7 days of late neurologic syndrome. 76,77 Ribavirin is effective when started early. 79
onset of LF. The mortality in cases associated with high AST was reduced
from 55% to about 5%. Oral ribavirin was also effective, but intravenous Vaccine A live, attenuated Junin virus vaccine is used in Argentina. In
convalescent plasma was not. Ribavirin is useful even when started later. a randomized trial in agricultural workers, its efficacy was 95% with
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minor adverse effects. The vaccine has been provided to more than
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Infection Control and Prevention of Nosocomial Transmission LASV is a BSL-4 agent: 250,000 persons. 75
Laboratory testing should be limited to essential tests and all laboratory
specimens require BSL-4 handling. LASV is classified as a category A Infection Control and Prevention of Nosocomial Transmission JUNV is a BSL-4 agent
bioterrorism agent. The CDC and local Department of Health should and is classified as category A bioterrorism agent. JUNV causes person-
be notified for assistance with the diagnostic workup, management, and to-person transmission in nosocomial outbreaks through direct contact
infection control. with blood and body fluid, and barrier nursing appears highly effective.
LASV has caused nosocomial transmission in West Africa but not Bolivian Hemorrhagic Fever (Machupo Virus)
in developed countries. Person-to-person transmission in nosocomial
cases involved direct contact with blood and body fluid or large particle Pathogen and Epidemiology Bolivian hemorrhagic fever (BHF) was first recog-
inhalation, not aerosol transmission. Patients should be placed on con- nized in 1959 in the Beni Department of Bolivia, an agricultural region
tact and airborne isolation precautions, and barrier nursing techniques near the Amazon River. Machupo virus (MACV) was named after a
should be used. Investigation of contact is warranted, and persons at local river. The reservoir is a field rodent that lives in and around rural
high risk of exposure may benefit from postexposure prophylaxis with houses and in fields. Trapping the rodents stopped the first outbreak.
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oral ribavirin. 11 More outbreaks have been reported recently. Humans are infected by
aerosols of rodent excreta. Person-to-person transmission and nosoco-
Lujo Virus Hemorrhagic Fever: Lujo arenavirus caused a nosocomial mial spread have been described. 75,82
outbreak in South Africa in 2008, resulting in HF in five patients, Clinical Manifestations, Diagnosis, Management, and Prevention All South American
four of whom died. The index patient was infected in Zambia and HF have similar clinical findings. RT-PCR, IgM, Ag detection, and viral
evacuated to South Africa. During the flight, nebulization, suction- isolation help confirm the diagnosis. Ribavirin appears effective in BHF. 83
ing, and manual ventilation resulted in infection of a paramedic. Two The Junin vaccine protects against Machupo virus challenge in guinea
nurses and one cleaner were infected at the South African hospital. pigs and nonhuman primates. Rodent control is highly effective in pre-
Only after the fifth patient became ill were barrier precautions imple- venting outbreaks.
mented. There were no further cases. The fifth patient received riba-
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virin and survived. The clinical presentation of Lujo virus infection Venezuelan Hemorrhagic Fever (Guanarito Virus)
appears similar to LF. 65 Pathogen and Epidemiology In 1989, an outbreak of HF was recognized in the
municipalities of Guanarito and Guanare in the Portuguesa state in north-
South American Hemorrhagic Fevers western Venezuela. Guanarito virus (GTOV) was identified as the cause of
The Pathogens and their Life Cycle The New World arenaviruses are Junin, Venezuelan hemorrhagic fever (VHF). The reservoir is a rodent. Sporadic
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Machupo, Guanarito, Sabiá, and Chapare viruses. All have a rodent cases are recognized in the 9000 km endemic region. 84,85 The emergence
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reservoir and the clinical presentations are similar. Severe hemor- of HF is related to deforestation and human invasion of rodent habitat and
rhagic and neurologic complications are much more common in South is more common in adult men during November to January.
American HF than in LF.
Clinical Manifestations, Diagnosis, and Management The case-fatality rate is high
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Argentine Hemorrhagic Fever (Junin Virus) (33%). RT-PCR, IgM, Ag detection, and viral isolation help confirm
Pathogen and Epidemiology Argentine hemorrhagic fever (AHF) was identi- the diagnosis. Ribavirin is likely effective in Venezuelan HF.
fied in 1955 around Junin, a town located in north central Argentina. Chapare Hemorrhagic Fever: Chapare virus–associated HF was first
Junin virus (JUNV) was isolated. The endemic area initially limited to a recognized in 2003 in rural Bolivia in an area near Cochabamba,
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16,000 km area of Pampas around Junin has increased to 150,000 km Bolivia, outside the known Machupo HF endemic zone. Chapare virus
of rich farmland. Field rodents are the reservoir. Infection is through is closely related to Sabiá virus. The reservoir is unknown. 74
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exposure to aerosols of rodent body fluids or excreta. Before immuni-
zation campaigns, there were 100 to 800 cases annually. Agricultural Brazilian Hemorrhagic Fever
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workers are exposed from March to June when harvesting corn and soy- Pathogen and Epidemiology Sabiá virus (SABV) was first isolated in 1990 in an
bean. Person-to-person transmission occurs. Nosocomial transmission agricultural engineer infected in Sabiá, a village near São Paulo, Brazil.
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is due to exposure to the blood and tissues of infected patients. The patient was admitted 12 days after onset of a febrile illness, and was
Clinical Manifestations Most infections are symptomatic. After an incuba- found to have oral erythema, conjunctival petechiae, leukopenia, and
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tion of 5 to 21 days, there is insidious onset of fever, headache, myalgia, elevated AST. She developed severe bleeding and neurological com-
back pain, gastrointestinal symptoms, retroorbital pain, photophobia, plications, and died on the fourth admission day. The autopsy showed
and dizziness. Physical examination may show trunk and cervicofa- diffuse pulmonary hemorrhages, hepatic congestion with focal necrosis,
cial flushing, periorbital edema, conjunctival injection, oral erythema, and massive gastrointestinal bleeding. A laboratory technician was
and cervical adenopathy. Gingival and vaginal bleeding is common. infected and developed a severe febrile illness with headache, myalgias,
Neurologic symptoms (irritability, lethargy, and tremor of the hand and sore throat, conjunctivitis, nausea, vomiting, diarrhea, epigastric pain,
tongue) and axillary petechiae may develop. and bleeding gums, but survived. In 1994, a Yale researcher working
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The neurological-hemorrhagic phase starts 8 to 12 days after onset in in a BSL-3 laboratory was infected while centrifuging infected Vero
20% to 30% of patients. Severe hemorrhagic manifestations and severe cells containing Sabiá virus: Transmission most likely occurred through
neurological complications are characteristic. The case-fatality rate of aerosols. After an incubation of about 8 days, there is insidious onset
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untreated, recognized cases is 10% to 30%. The association of a platelet of a febrile illness associated with myalgia, headache, conjunctival injec-
count below 100,000/mm and a white cell count below 2500 cells/mm tion, sore throat, nausea, vomiting, diarrhea, epigastric pain, bleeding
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