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740 PART 5: Infectious Disorders

gums, and later gastrointestinal bleed. Leukopenia, thrombocytopenia, Zaire Ebola RNA was detected by RT-PCR in three species of African
and proteinuria are present. One patient treated with intravenous ribavi- tree-roosting fruit bats. 92,101
rin improved within 48 hours. Diagnosis relies on the techniques used Pathogenesis of Filovirus Hemorrhagic Fevers EBOV infects a number of cell types,
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with other American HF viruses. including monocytes, macrophages, and dendritic cells. Hepatocellular
■ FILOVIRIDAE necrosis results in decreased synthesis of coagulation proteins. Adreno-
Filoviridae are filamentous, enveloped, negative-sense, single-stranded cortical necrosis leads to adrenal insufficiency, hypotension, and hypo-
volemia. There is severe depletion of lymphocytes. EBOV induces the
RNA viruses with a unique morphology: Virions have a uniform diameter production of proinflammatory mediators and reactive radicals. 88,102,103
but highly variable length and shapes, such as branching. The genome is Disseminated intravascular coagulation, vasodilation, and increased
nonsegmented. There are two genera: Ebolavirus and Marburgvirus. Lake endothelial permeability lead to shock and multiorgan failure. EBOV
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Victoria marburgvirus is the single species in the genus Marburgvirus. evades interferon responses. 104
https://kat.cr/user/tahir99/
Four African ebolaviruses and Reston ebolavirus are the five species in the Clinical Manifestations of Marburg and Ebola Hemorrhagic Fever Filoviruses cause severe
genus Ebolavirus. Filoviruses cause HF with a very high mortality. Fruit VHFs with a high-case fatality rate. MHF is associated with a case fatality
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bats are likely the reservoir. 91-93 rate of 25% to 90%. EHF case fatality rates depend on the specific virus:
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Marburg Hemorrhagic Fever BEBOV (42%), SEBOV (42%-65%), or ZEBOV (57%-90%). 95,105
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The Pathogen Lake Victoria marburgvirus (MARV) causes Marburg HF The incubation period ranges from 3 to 13 days. There is a sudden
(MHF). Its genotypes differ by up to 21% at the nucleotide level. MARV onset of fever, myalgia, headache, vomiting, diarrhea, abdominal pain,
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was identified in 1967 in Marburg, Germany, among scientists who had shortness of breath, sore throat, and conjunctival injection. Neurological
handled the tissues of African green monkeys imported from Uganda. symptoms may be prominent and weight loss is rapid. Severe hemor-
This outbreak also caused laboratory-associated cases in Frankfurt, rhagic complications involve multiple sites. A rash, pronounced on the
Germany, and Belgrade, Yugoslavia. MARV infected 25 laboratory trunk, buttocks, and upper arms, is detected in 25% to 52% of patients
personnel ( primary cases). There were six secondary cases due to blood on day 5 to 7 of illness. Injected conjunctivae and pharynx, lymphade-
exposure among hospital staff. The mortality rate was 25%. A prolonged nopathy, tender hepatomegaly, and abdominal tenderness are charac-
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outbreak was identified in Durba, Democratic Republic of Congo: cases teristic. Laboratory tests show thrombocytopenia, initially leukopenia
occurred in miners who worked in a gold mine infested with bats, in their and lymphopenia, and later leukocytosis with elevated granulocytes and
household contacts and in exposed health care workers. The case mortal- atypical lymphocytes. High transaminases predict a poor outcome.
ity was 83% and the outbreak ceased only when the mine was flooded. Complications include multiorgan failure and disseminated intravas-
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An outbreak in northern Angola included 252 cases with 90% mortality. 94 cular coagulation. Severe hypotension, shock, and coma are typical. The
median survival in fatal cases is 9 days. Patients who are alive on day 14
Epidemiology of MHF Cave-dwelling bats are likely the reservoir: MARV was have a 75% survival rate. Convalescence may be complicated by orchitis,
detected by RT-PCR in Egyptian fruit bats (Rousettus aegyptiacus) in prolonged hepatitis, transverse myelitis, uveitis, or parotitis.
Gabon and cave roosting bats in the gold mine epidemiologically linked
to the Durba outbreak of MHF in miners. 96,97 Diagnosis of Filovirus Infection Filoviruses require BSL-4 facilities and are cate-
MARV rarely infects travelers. MHF was diagnosed in 2008 in a gory A bioterrorism agents. The CDC special pathogens branch performs
Dutch woman who was exposed in the “Python Cave” (Maramagambo virus isolation, Ag capture ELISA, IgM and IgG ELISA, and RT-PCR.
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Forest, Queen Elizabeth Park, western Uganda) infested with Egyptian Quantitative RT-PCR assay is sensitive and effective for field testing.
fruit-eating bats. In 2008, an American woman was infected during Management of Filovirus Hemorrhagic Fever The management of MHF and EHF
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a trip to Uganda where she visited the same cave. Person-to-person is supportive. Patients are managed in a pressure-negative room with an
14
transmission is through direct contact with blood or body fluids, but anteroom in the ICU. Strict isolation and strict barrier nursing proce-
transmission by droplets and aerosols is possible. dures are effective in preventing transmission.
Ebola Hemorrhagic Fever ■ BUNYAVIRIDAE
The Pathogens Four African ebolaviruses cause Ebola HF (EHF): Zaire Bunyaviridae are enveloped single-stranded RNA viruses with a
ebolavirus, Sudan ebolavirus, Côte d’Ivoire ebolavirus, and Bundibugyo trisegmented RNA genome. The genera Orthobunyavirus, Phlebovirus,
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ebolavirus. Reston ebolavirus is present in the Philippines but is not Nairovirus, and Hantavirus include a number of VHF-causing viruses:
pathogenic. 89,98 In 1976, two outbreaks of EHF occurred in southern Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, severe
Sudan and northern Zaire (Democratic Republic of the Congo). Ebola fever with thrombocytopenia syndrome virus, and the hantaviruses
virus was named after a local river. Sudan ebolavirus (SEBOV) caused associated with HFRS.
284 cases with a mortality rate of 53%. Zaire ebolavirus (ZEBOV) caused
318 cases with a mortality rate of 88%. In 1994, Côte d’Ivoire ebolavirus Crimean-Congo Hemorrhagic Fever: An epidemic of Crimean hemor-
(CIEBOV) caused a single case of HF in an ethnologist exposed to a rhagic fever involved about 200 Soviet military troops in the Crimea
dead chimpanzee. In 2007, Bundibugyo ebolavirus (BEBOV) caused in 1944. The virus was isolated in 1967 and found to be identical
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an outbreak in Uganda, with 131 cases and a mortality rate of 40%. to the Congo virus, which had been isolated from a febrile patient
Reston ebolavirus (REBOV) was identified in 1989 at a quarantine in 1956 in the Belgian Congo (Democratic Republic of the Congo).
facility in Reston, Virginia, in Cynomolgus monkeys imported from The pathogen was renamed Crimean-Congo hemorrhagic fever virus
the Philippines. REBOV caused later cases in Cynomolgus monkeys (CCHFV). 107
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in the Philippines, some of which were exported to Italy (1992) and The Pathogen and Life Cycle CCHFV belongs to the genus Nairovirus. Nucleic
the USA (1996). Five healthy animal handlers serocoverted. REBOV is acid sequence analysis demonstrates great antigenic variation. The
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lethal for monkeys but is not pathogenic to humans. In 2008, REBOV natural life cycle includes Hyalomma marginatum ticks, which feed on
was identified in healthy pigs and antibody detected in pig handlers in wild or domestic mammals and ground-feeding birds. The ticks are
the Philippines. 99,100 present in most of Africa and large parts of Eurasia south of the 50°
Epidemiology of Ebola Hemorrhagic Fever Outbreaks are initiated by a single or a parallel North.
few initial zoonotic human infections likely through exposure to bats, Epidemiology The geographic distribution of CCHF includes more than
followed by sustained person-to-person transmission in community 30 countries of Africa, Europe, and Asia. The incidence and the area of
settings or hospitals. Person-to-person transmission requires direct distribution are increasing. 108-112 Infections are acquired through ticks,
contact with patients, their body fluids, or their soiled clothes or linens. exposure to blood or tissues of infected livestock, and direct contact

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