2. Hemorrhagic fever with renal failure syndrome
(HFRS) occurs mainly in Europe and Asia and is
characterized by fever and renal failure associated
with hemorrhagic manifestations. Hemorrhagic
fever with renal failure syndrome is caused by an
airborne contact with secretions from rodent hosts
infected with the group of viruses belonging to the
genus Hantavirus of the family Bunyaviridae. In
Europe, hemorrhagic fever with renal failure
syndrome is caused by 3 hantaviruses: Puumala
virus (PUUV), carried by the bank vole (Myodes
glareolus); Dobrava virus (DOBV), carried by the
mouse (Apodemus flavicollis); and Saaremaa virus
(SAAV), carried by the striped field mouse
(Apodemus agrarius).
3. Hemorrhagic fever with renal failure
syndrome was initially recognized between
1913 and 1930 by Soviet scientists, who
described sporadic outbreaks of fever with
renal failure in the eastern Soviet Union. The
disease came to the attention of the Western
world in 1950, when the North American
soldiers serving with the United Nations
forces in Korea developed a febrile illness
associated with shock, hemorrhage, and
renal failure.
4. Pathogenesis
the pathogenesis is largely unknown, but findings
from several studies have suggested that immune
mechanisms play an important role. After the
infection, marked cytokine production, kallikrein-
kinin activation, complement pathway activation, or
increased levels of circulating immune complexes
occur. These components play an important role
during the febrile and hypotensive stages. Damage
to the vascular endothelium, capillary dilatation,
and leakage are clinically significant features of the
disease.
5. Transmission
Hantaviruses are carried and transmitted by rodents.
People can become infected with these viruses and
develop HFRS after exposure to aerosolized urine,
droppings, or saliva of infected rodents or after
exposure to dust from their nests. Transmission may
also occur when infected urine or these other
materials are directly introduced into broken skin or
onto the mucous membranes of the eyes, nose, or
mouth. In addition, individuals who work with live
rodents can be exposed to hantaviruses through
rodent bites from infected animals. Transmission
from one human to another may occur, but is
extremely rare.
6. Transmission of Hantaviruses
Chronically infected
rodent
Virus is present in
aerosolized excreta,
particularly urine
Horizontal transmission of infection by
intraspecific aggressive behavior
Virus also present in
throat swab and feces
Secondary aerosols, mucous
membrane contact, and skin
breaches are also sources of
infection
Courtesy of CDC
7. HFRS
A group of clinically similar diseases that
occur throughout Europe and Asia
Includes several diseases that formerly
had other names, including Korean
hemorrhagic fever, epidemic
hemorrhagic fever and nephropathia
epidemica
~15% fatality
8. The clinical features
The clinical features in hemorrhagic fever with
renal failure syndrome (HFRS) consist of a triad
of fever, hemorrhage, and renal insufficiency.
Other common symptoms during the initial
phase of the illness include headache, myalgia,
abdominal and back pain, nausea, vomiting,
and diarrhea.
Other symptoms include chills, dizziness,
increased thirst, costovertebral tenderness, and
flank pain.
10. Febrile Phase
3-5 days
Characterized by fever, chills
Headache, severe myalgia
(muscle pain), nausea
Blurred vision, photophobia,
eye pain caused by
movement
Flushing of face, V-area of the
neck and back
Petechiae (small red spots on
skin)
Abdominal pain and back
pain.
Thirst, edema,
hemoconcentration, postural
hypotension
11. Hypotensive phase
Hours to days
Blood pressure decrease, hypovolemia (decreased
blood volume), shock
Worsening of bleeding manifestations: petechiae,
epistaxis (nosebleed), gastrointestinal and
intracranial bleeding
Levels of urea and creatinine in blood rise,
proteinuria (excessive protein in urine)
Leukocytosis, thrombocytopenia (decreased # of
platelets)
12. Oliguric Phase
• 3-7 days
• Marked by decreased urine production due to
renal (kidney) dysfunction
• Hypervolemia (high blood volume) leading to
hypertension
• Blood electrolyte imbalance
• Continuation of hemorrhagic symptoms
• Severe complications: cardiac failure pulmonary
edema (swelling of lungs), and cerebral bleeding
13.
14. Diuretic Phase
Several days to several weeks
Beginning of recovery
3-6 liters of urine/ day; return to normal
renal activity
Anorexia, fatigue due to dehydration
15. Convalescent Phase
2-3 months
Progressive improvement in glomerular
filtration, renal blood flow, and urine
concentrating ability
16. Laboratory Studies
Enzyme-linked immunosorbent assay (ELISA) is useful
in detecting antihantaviral-specific immunoglobulin M
(IgM) early in the course of the illness.
Antihantaviral immunoglobulin G (IgG) titers may be
elevated for prolonged periods (as long as 10 y).
Blood findings usually reveals clinically significant
leukocytosis, an elevated or normal hematocrit level,
and thrombocytopenia.
Elevated levels of liver enzymes, BUN, and serum
creatinine can be observed.
Hyponatremia, hyperphosphatemia,
and hyperkalemia may occur during the oliguric phase.
Complement (C3) levels may be decreased; therefore,
hemorrhagic fever with renal failure syndrome should be
included in the differential diagnosis of
hypocomplementemic acute nephritic syndrome.
17. Imaging Studies
Advances in cross-sectional imaging have
allowed early diagnosis of the sequelae of HFRS.
In the kidneys, MRI T1-weighted imaging shows
a well-defined zone of low-signal intensity (blood
product deposition) in the subcortical medulla in
33% of cases, and, in 80% of cases, T2-
weighted images correlated with renal
histopathological findings of HFRS.
18. Radiographs of the abdomen may show
ascites (74%), paralytic ileus with intestinal
wall thickening (69%), retroperitoneal edema
(obscured psoas shadow [68%] and obscured
renal shadow [53%]), and kidney enlargement
(23%). In patients with pulmonary
involvement, chest radiography findings
include interstitial edema (14-44%),
subsegmental atelectasis (38%), pleural
effusion (6-32%), and cardiomegaly (6-21%).
19. Clinical Testing for HFRS
Thrombocytopenia (low platelet count) is
a signifier
Urine tests for albuminuria (abnormally
high amounts of the plasma protein
albumin in the urine)
Urine tests for microhematuria
(microscopic amounts of blood in the
urine)
20. Treatment
Treatment depends on the stage of the disease
and on the patient's hydration status and
hemodynamic condition.
Supportive therapy is the mainstay of care for
patients with hantavirus infections. Care includes
careful management of the patient’s fluid
(hydration) and electrolyte (e.g., sodium,
potassium, chloride) levels, maintenance of correct
oxygen and blood pressure levels, and appropriate
treatment of any secondary infections. Dialysis
may be required to correct severe fluid overload.
Intravenous ribavirin, an antiviral drug, has been
shown to decrease illness and death associated
with HFRS if used very early in the disease.