Page 1010 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 80: Viral Hemorrhagic Fevers 741

with blood or body fluids of infected persons. Agriculture workers, Africa was seen in Saudi Arabia and Yemen in 2000, and in the Comoros
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veterinarians, abattoir workers, hikers, and campers are at increased Islands in 2006. 119,124-126 RVF could be introduced to Europe and North
risk. Health care workers may be infected through blood exposure. 107,113 America through the trade of livestock or airplane transport of infected
Nosocomial transmission is common in endemic regions. Mother-to- mosquitoes. RVF could then persist in North America as the vectors are
child transmission is reported. present and the climate is favorable. 23
Clinical Presentation Infection is often asymptomatic. After a short incuba- Clinical Presentation During outbreaks, most infections are mild. After a
tion (3-7 days), the “prehemorrhagic period” starts with a sudden onset short incubation (2-7 days), there is acute onset of a febrile prodrome
of high fever, myalgia, back pain, abdominal pain, headache, vomiting, (fever, chills, headache, photophobia, retroocular pain, myalgia, arthral-
diarrhea, with conjunctivitis, bradycardia, hypotension, and flushing gia, vomiting, rash) with conjunctival injection, epigastric tender-
of the face and upper trunk. The “hemorrhagic period” starts around ness, flushing, epistaxis, and scattered petechiae. Patients defervesce
day 3 to 5 and is mild to severe. Hepatomegaly and splenomegaly occur and improve within 4 to 7 days. A minority of patients develop VHF.
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in one-third of admitted patients. Cerebral hemorrhage, massive liver Bleeding and icteric hepatitis are typical of severe HF, and epigastric
necrosis, and progression to shock are associated with poor prognosis. pain, liver tenderness, and encephalopathy are common. Some develop
Laboratory tests show severe thrombocytopenia, elevated transami- hepatorenal syndrome or shock. A Saudi study of 683 patients admit-
nases, and disseminated intravascular coagulopathy. Mortality ranges ted to the hospital with laboratory-confirmed RVF showed an overall
from 5% to 30% in hospitalized patients. Predictors of severe outcome mortality of 14%, jaundice in 18%, neurological manifestations in
at day 5 of illness include thrombocytopenia below 20,000/mm , white 17%, hemorrhagic manifestations in 7%, and ocular abnormalities in
3
count above 10,000/mm , AST above 200, and coagulopathy. Patients 1%. Useful laboratory findings include elevated transaminases (98%),
3
with hematemesis, melena, or somnolence have a poor prognosis. 107,114 thrombocytopenia (38%), and elevated creatinine (27%). Bleeding,
Pathogenesis The pathogenesis of CCHF is not well understood. Patients neurological manifestations, and jaundice are associated with a high
who die have a high viral load and weak antibody responses. High levels mortality rate (45%-65%). 125
of interleukin-10, γ-interferon, and tumor necrosis factor alpha are Encephalitis appears in a minority of patients after initial clinical
associated with high viral load and poor outcome. 115 improvement. 125,127 Retinitis is seen in about 1% of infections, but its
Diagnosis RT-PCR and antigen-capture ELISA are used. IgM or IgG manifestations are delayed by 4 weeks in most cases. It can be unilateral
ELISA may be detected late in the course of illness. Viral isolation or bilateral and involves the macular and perimacular retina. Acutely,
requires a BSL-4 laboratory. hemorrhages and exudates are seen near the macula, and scarring leads
to a partial or total loss of central vision.
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Management Treatment with ribavirin appears effective when used during
the first 4 days but efficacy has not been proven in randomized Diagnosis ELISA for RVF virus antigen and RVF IgM detection, RVF
trials. Supportive treatment with fresh frozen plasma and platelets is RT-PCR, RVF virus isolation, and RVF-specific immunohistochemical
important. Prevention of nosocomial transmission involves using testing are available.
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universal precautions, strict isolation, and barrier nursing precautions. Pathogenesis Important features of RVF HF are a fulminant, icteric hepa-
Postexposure prophylaxis with oral ribavirin is reasonable for high-risk titis with diffuse necrosis of hepatocytes, bleeding associated with DIC,
exposures. and neuroinvasion. Death may be related to bleeding, liver failure, renal
failure, DIC, or encephalitis. 120
Rift Valley Fever: Rift Valley fever (RVF) was first identified in 1930
as a mosquito-borne epizootic affecting sheep in the Rift Valley of Infection Control, Therapy, and Prevention Nosocomial transmission has not been
Kenya, East Africa, along with mild febrile illness in humans. The Rift reported and universal precautions should be sufficient. Treatment is
Valley fever virus (RVFV) was soon isolated. 117 supportive.
An RVFV modified live virus (Smithburn strain) is broadly used in
The Pathogen and Life Cycle The RVF Phlebovirus is transmitted to humans and parts of Africa to vaccinate cattle and sheep. Vaccination should not be
animals (cattle, sheep, goats) by mosquitoes. Floodwater Aedes mcintoshi
are the reservoir in Africa: Females lay infected drought- resistant eggs in performed during epizootics; however, needles are used to immunize mul-
tiple animals. Several human vaccine candidates are being developed.
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ground depressions (damboes) where they survive for years. After very
Epidemics in the population are more likely when a large proportion
heavy or prolonged rains, flooding induces the eggs to hatch and a new of people are not immune, and specific weather and geography condi-
RVF outbreak commences when A mcintoshii females feed on animals 118
and humans. Other mosquitoes amplify transmission, resulting in large tions are present. Geographic information system (GIS) technology
can predict impending outbreaks, and early immunization of livestock
epizootics and human epidemics. Epizootics are associated with great 124
numbers of abortions, fetal malformation, and neonatal deaths in cattle and mosquito control may prevent large outbreaks.
and sheep. Severe Fever with Thrombocytopenia Syndrome: Severe fever with throm-
Other modes of human infection involve direct contact with infected bocytopenia syndrome (SFTS) was first recognized in rural areas of
animals (blood, body fluids, tissues) and exposure to aerosols (amniotic the Hubei and Henan provinces of central China in 2009. The clinical
fluid aerosols and laboratory accidents). 118,119 RVFV can be transmit- presentation includes fever, gastrointestinal symptoms, thrombocyto-
ted through aerosol when poor biosafety procedures are followed. penia, and leukopenia. The mortality is high (30%). The pathogen is
120
Exposure to animal products is more likely to be associated with severe a novel Phlebovirus, termed severe fever with thrombocytopenia syn-
disease probably due to a large inoculum. 121,122 drome virus (SFTSV). The virus is also referred to as Huaiyangshan
129
Epidemiology RVFV is endemic throughout sub-Saharan Africa. Intermit- virus (HYSV) and the illness as Huaiyangshan HF (HYSHF). 130
tent epidemics infect thousands of individuals and are associated with Like other Bunyaviridae, SFTSV has a trisegmented, single-stranded
large epizootics. The distribution of RVF has been enlarging. In the RNA genome. Haemaphysalis longicornis ticks, widely distributed
130
thirties RVF was described in Kenyan sheep, with only self- limited in eastern Asia and the Pacific, are the vector and feed on a variety of
febrile illness in humans. Afterward, recurrent epizootics affected cattle domestic and wild animals. 129
and sheep in East Africa. RVF was recognized as an important human After an incubation of 5 to 14 days, there is sudden onset of high fever,
pathogen in the fifties when large outbreaks in South Africa caused headache, myalgias, and gastrointestinal symptoms. Some individuals
significant morbidity and mortality due to retinitis, encephalitis, and develop severe neurological symptoms, multiorgan abnormalities, and
VHF. 123,124 RVF was introduced to new parts of Africa (Egypt in the bleeding complications. 129,131,132 Labs show thrombocytopenia, leukopenia,
seventies, West Africa in the eighties, and East Africa recently). The proteinuria, hematuria, and elevated transaminases, lactate dehydroge-
mortality rate in recent outbreaks was 1% to 2%. Extension outside nase, and creatinine.
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