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734 PART 5: Infectious Disorders

VHFs are identified in North America, mostly in travelers. Dengue
• Clues to LF are insidious onset, sore throat, chest pain, cervico- fever (DF) is often diagnosed in travelers, but severe DF is not common.
3-7
facial edema, high maternal mortality and fetal loss during preg- Yellow fever (YF) is occasionally reported in travelers even though most of
nancy, and irreversible deafness. those at risk of exposure are immunized. Lassa fever (LF) and filovirus
8,9
• Clues to filovirus (Marburg and Ebola) infections are a rash HF have been reported in travelers. 10-15 Such travel-associated infections
around the fifth day, severe bleeding, jaundice, person-to-person may increase in the future due to increased high-risk “adventure” travel to
transmission in community outbreaks and nosocomial settings, remote areas of the world where VHF viruses are prevalent.
and a very high mortality rate. Acquisition of VHF in the United States occurs. Dengue is present
• A delayed-onset rash is characteristic of dengue, filoviruses, and LF. on US territory. 16,17 Significant rates of Seoul hantavirus infection are
reported in rats trapped in US cities and at-risk human populations
• Jaundice and liver failure are typical of YF, CCHF, RVF, and filo- have evidence of prior infection. 18-20 Lab accidents and person-to-person
https://kat.cr/user/tahir99/
virus HF. transmission of VHF viruses have occurred in Western countries. 21,22
• Bleeding is often severe with CCHF, filoviruses, South American Rift Valley fever could be introduced into Europe or the United States.
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VHFs, and Hantaan virus–associated HFRS, but only rarely so in Bioterrorism is a significant threat with VHF pathogens listed on the
dengue and LF. group A bioterrorism agent list. The manifestations of VHFs depend
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• Neurological complications are seen in South American HF, KFD, on the specific pathogens, but with significant overlap (Table 80-2).
Alkhurma HF, and a small minority of RVF virus infection. Physicians should consider the diagnosis of VHF in the appropriate set-
• Acute kidney injury is typical in HFRS and YF, and also seen in HCPS. ting and recognize the severity of illness, the need to implement specific
• Ribavirin is proven effective in Lassa fever and HFRS, and may be measures to prevent spread, and the potential benefits of ribavirin.
effective in South American HF and CCHF. ■ FLAVIVIRIDAE

VHF-causing Flaviviridae include dengue and YF, which are highly
prevalent over wide geographic areas, and three geographically restricted
INTRODUCTION
infections: Omsk hemorrhagic fever, Kyasanur forest disease, and
Viral hemorrhagic fever (VHF) starts with a nonspecific febrile pro- Alkhurma HF.
drome associated with protean manifestations, followed by widespread
endovascular insult, viral immunosuppression, multiorgan damage, Dengue Fever and Dengue Hemorrhagic Fever
hemorrhagic complications, and shock. The mortality rate depends on The Pathogen and the Life Cycle Dengue virus (DENV) is an enveloped positive-
the pathogen, the inoculum size, and host factors. strand RNA flavivirus. Its genome encodes three structural proteins
VHF viruses belong to four families of enveloped, single-stranded and seven nonstructural proteins. There are four serotypes (DENV-1,
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RNA viruses: Flaviviridae, Arenaviridae, Filoviridae, and Bunyaviridae DENV-2, DENV-3, and DENV-4) and multiple genotypes.
(Table 80-1). They infect humans through exposure to animals (zoo- DF is an urban disease. DENV is transmitted from person to person
nosis), or through the bite of an arthropod vector. Person-to-person through the bite of Aedes mosquitoes. Aedes aegypti, the most impor-
transmission occurs with some viruses both in community and in health tant vector of DF, is broadly distributed in the tropical and subtropical
care settings. The geographic distribution of VHFs is limited by the dis- regions of the world and is well adapted to survival within and around
tribution of the arthropod vector or the natural reservoir. 1,2 urban homes where its larvae infest water-filled artificial containers.
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TABLE 80-1 Etiology and Epidemiology of Viral Hemorrhagic Fevers
Pathogens
Geographic
Family Genus Virus Disease Distribution Common Modes of Human Infection Reservoir
Flaviviridae Flavivirus Dengue viruses DHF, DSS, severe Asia, America, and Aedes mosquitoes especially Aedes Human reservoir (sylvatic cycle)
(DENV-1-4) dengue Africa, mostly urban aegypti in cities
Yellow fever virus (YFV) Yellow fever South America Human infected accidentally when enter- Sylvatic/jungle cycle between monkeys
ing the jungle or in the African savanna and mosquitoes
Sub-Saharan Africa Human epidemics in cities infested with African savanna cycle between tree hole
the peridomestic Aedes aegypti Aedes and monkeys
Urban cycle between Aedes aegypti
and people
Omsk HF virus (OHFV) Omsk HF Siberia, Russia Tick bite Hard ticks (Dermacentor reticulatus)
Exposure to muskrats and their skins
Kyasanur Forest disease Kyasanur Forest South India Tick bite Hard ticks (Haemaphysalis spinigera)
virus (KFDV) disease
Alkhurma virus (ALKV) Alkhurma HF Saudi Arabia Tick bite; butchering of camels and Soft ticks (Ornithodoros savignyi)
sheep; drinking unpasteurized milk
Egypt
Arenaviridae Arenavirus Lassa virus (LASV) Lassa Fever West Africa Aerosol of urine or direct contact with Multimammate rat (Mastomys natalensis)
rodent; person-to-person transmission
Lujo virus Lujo virus HF Zambia Single natural infection with Probably rodent
person-to-person transmission
(Continued)

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