Page 1011 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

742 PART 5: Infectious Disorders

Person-to-person transmission was documented in two outbreaks family members have been reported, and the risk of transmission is
when family members were taking care of an ill relative in the hospital, greater when people share the same bed or exposure to blood is docu-
likely due to direct contact with blood or respiratory secretions. 131,132 mented. Direct contact, aerosol from saliva/respiratory secretions,
Diagnosis is confirmed by detection of SFTS RNA by RT-PCR or serol- and sexual contact might lead to such transmission. Clinically, ANDV
ogy (IgG by ELISA). causes more severe hemorrhagic, renal, hepatic, and muscular impair-
ment than SNV does. Hemorrhagic manifestations due to DIC appear
Hantaviruses: Like other Bunyaviridae, hantaviruses are enveloped, late in the course.
negative-sense, single-stranded RNA viruses with a genome divided in
three segments. They are maintained in nature by a specific rodent and Diagnosis Hantavirus antibody (both IgM and IgG) is detectable shortly
after the onset of the prodrome. RT-PCR detects hantavirus early in the
excreted in the rodent urine, saliva, and respiratory secretions. The dis-
tribution of the rodent reservoir explains their restricted distribution and course, but hantavirus RNA rapidly drops after onset of the cardiopul-
monary phase.
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rural predominance. Seoul virus is an exception as its reservoir is Rattus
norvegicus, the brown rat, present worldwide in urban environments. Management Management is supportive with intubation and lung-
People get infected when inhaling infectious aerosols of rodent urine, protective low-tidal-volume ventilation. Ribavirin does not appear
saliva, or respiratory secretions. Occasionally other modes of transmis- effective, maybe because patients present when the cardiopulmonary
sion are significant, such as rodent bite, wound contamination, mucosal phase has already begun and viral replication is already decreasing.
exposure, or ingestion of contaminated food. Person-to-person trans- Hemorrhagic Fever with Renal Syndrome: Recognized during the Korean
mission is frequently reported with Andes virus. Of the numerous
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hantaviruses in rodents, at least 20 are pathogenic to humans. 134,135 War (1950-1953), Korean hemorrhagic fever caused more than 3000 cases
in United Nations troops. Hantaan virus isolated in 1978 was named after a
Hantaviruses are divided into Old World and New World hantaviruses.
New World hantaviruses cause the hantavirus cardiopulmonary syn- South Korean river. The first virus in the genus Hantavirus is the prototype
dromes (HCPS). The most important pathogens are Sin Nombre virus in of severe HFRS. The Korean striped field mouse is the reservoir. In China,
North America and Andes virus in South America. Both are associated at least 1.2 million cases of HFRS due to Hantaan virus and Seoul virus
were reported from 1950 to 1997, leading to 40,000 deaths. In Europe,
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with a high fatality rate (25%-40%). 145
Old World hantaviruses are responsible for hemorrhagic fever with most HFRS cases are caused by Puumala virus.
renal syndrome (HFRS), prevalent in Eurasia and identified in Africa. Pathogens Hantaan virus (HTNV) causes a severe HFRS. The reservoir is
Hantaan, Seoul, Dobrava, and Puumala viruses are the most common in the Korean striped field mouse (Apodemus agrarius koreae), widespread
Eurasia. Seoul virus is found worldwide. in China, South Korea, and Russia. 146
The separation between HCPS and HFRS may not be absolute. 20,136 Amur virus (AMRV), related to HTNV, also causes a severe HFRS.
The reservoir, Apodemus peninsulae, is present in South Korea, Russia,
Hantavirus Cardiopulmonary Syndrome: New World hantaviruses as and China.
human pathogens were identified in 1993, when an outbreak of febrile Dobrava-Belgrade virus (DOBV) is prevalent in the Balkans where it
illness followed by the rapid onset of severe respiratory distress and causes a severe HFRS. The reservoir is Apodemus flavicollis, the yellow-
cardiogenic shock was identified in the southwestern US four-corner necked forest mouse.
region. Sin nombre virus (SNV) was isolated and the syndrome named Saaremaa virus (SAAV), related to DOBV, causes a mild HFRS in the
hantavirus pulmonary syndrome. The deer mouse (Peromyscus manicu- Baltic countries and Eastern Europe. The reservoir is the striped field
latus) is the reservoir. There had been a great increase in the numbers mouse (Apodemus agrarius).
of deer mice before the outbreak. People got infected not only outdoors Puumala virus (PUUV) causes nephropathia epidemica, a mild HFRS
but also indoors when cleaning buildings infested with deer mice. with mortality below 1%. The rodent reservoir, Myodes glareolus, is
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This was not a new disease: Stored lung tissue from 1959 showed infec- present throughout Europe.
tion. SNV has been identified in at least 30 US states. During 1993 Seoul virus (SEOV) infects Rattus norvegicus, the Norwegian brown
138
to 2009, more than 500 cases were reported. At least 14 hantaviruses rat, distributed in urban centers worldwide. 147,148 SEOV causes a mild
139
cause HPS in America. In North America, SNV and New York virus HFRS, with a mortality rate of 1% to 2%. In the USA, the seroprevalence
(NYV) cause HCPS, but Monongahela virus (MGLV), Black Creek of Seoul virus may be greater than 50% in Norwegian rats, and below
Canal virus (BCCV), and Bayou virus (BAYV) cause renal failure with 1% in exposed homeless populations and intravenous drug users. 18,19
HCPS. At least nine hantaviruses cause HPS in South America such as Laboratory rats can be chronically infected.
Andes, Araraquara, and Juquitiba viruses. Andes virus is associated with Pathogenesis HFRS-causing hantaviruses infect endothelial, renal tubular,
person-to-person transmission. 134,140,141 and follicular dendritic cells. The infection results in increased vascular
Pathogenesis New World hantaviruses infect the lung microvascular endo- permeability with leakage of plasma in the tissues and the retroperi-
thelium. They induce major microvascular leakage, with rapid develop- toneal space. The kidneys are large and edematous; pathology shows
ment of low-pressure pulmonary edema. tubular dilation and infiltrates.
Clinical Manifestations HCPS is characterized by a long incubation (2-5 weeks), Clinical Manifestations Infection through inhalation is followed after a 2- to
followed by the acute onset of a febrile prodrome (myalgia, headache, 4-week incubation by sudden onset of a febrile prodrome with associ-
back pain, abdominal pain, and diarrhea) with thrombocytopenia. ated manifestations (headache, myalgia, abdominal pain, back pain,
Patients present to the hospital late, with symptoms of cough and vomiting, cough, flushing of face and neck, injection of conjunctiva and
shortness of breath. The rapid development of low-pressure, bilateral pharynx), epistaxis, petechiae, and a retroperitoneal high-protein effu-
pulmonary edema and pleural effusions leads to respiratory failure. The sion that is highly characteristic of HFRS. Labs show low-grade DIC,
peripheral blood shows a characteristic tetrad: thrombocytopenia, neu- thrombocytopenia, and proteinuria.
trophilic leukocytosis, hemoconcentration, and reactive immunoblasts. A hypotensive phase may follow. As the fever improves, the patient
A low cardiac index associated with high systemic vascular resistance has ongoing vomiting and increasing back pain. The urine output
leads to cardiogenic shock, a major cause of death. Patients who sur- decreases. Labs show leukocytosis, immunoblasts, hemoconcentration,
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vive the first few days improve but often develop polyuria and have a thrombocytopenia, and abnormal urine (proteinuria, hematuria, leuko-
prolonged convalescence. cyturia, and casts). Cardiogenic shock may develop.
Andes virus (ANDV) causes HCPS in Chile, Argentina, and An oliguric phase follows. Severe hemorrhage (hemoptysis, GI
Bolivia. Outbreaks due to person-to-person transmission between bleed, hematuria) and acute oliguric renal failure are typical. HTN and
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