HEMORRHAGIC FEVERS
 The viral HF syndrome is a constellation of findings
based on vascular instability and decreased vascular
integrity
 Cutaneous flushing and conjunctival suffusion are
examples of common, observable abnormalities n the
control of local circulation
 Hemorrhage is inconstant and in most cases an
indication of widespread vascular damage
 In some viral HF syndromes, specific organs may be
particularly impaired:
 HF with renal syndromes- Kidney
 Hantavirus pulmonary syndrome- Lungs
 Yellow fever- Liver
 Pathogenesis of HF is poorly understood
 Acute phase in most cases of HF is associated with
ongoing virus replication and viremia
 Exceptions are the Hantavirus and dengue HF/dengue
shock syndrome, in which the immune response plays a
major pathogenic role
 All begin with abrupt onset of fever and myalgia
 On initial PE, there is conjunctival suffusion, muscle
or abdominal tenderness to palpation, borderline or
postural hypotension, petechiae and periorbital
edema
 Petechiae is often best visualized in the axilla
 Hemoconcentration is most marked in hantavirus
diseases and DHF/DSS
 Poor prognostic signs:
- Shock
- Multifocal bleeding
- CNS involvement
 One of the major diagnostic clues is travel to an
endemic area
 Early recognition is important due to need for virus-
specific therapy and supportive measures including:
- prompt, atraumatic hospitalization
- fluid therapy
- cardiotonic drugs
- pressors to maintain BP at a level that will
support renal perfusion
- treatment of secondary bacterial infections
- replacement of clotting factors and platelets
- DIC should only be treated if clearly evident
 Available evidence suggests that HF patients have
decreased cardiac output and respond poorly to fluid
loading
 Differential Diagnosis:
- malaria
- shigellosis
- typhoid
- leptospirosis
- relapsing fever
- rickettsial diseases
LASSA FEVER
 Cause endemic and epidemic dsease in Nigeria, Sierra
Leone, Guinea, and Liberia
 More widely distributed in West Africa
 Spread to humans via: small particle aerosols from
chronically infected rodents and may be acquired
during capture and eating of these animals
 Also, thru close person-to-person contact
 Virus is often present in urine during convalescence and
suspected to be present in seminal fluid early in
recovery
 Nosocomial spread is uncommon
 All ages and both sexes are affected
 Incidence is highest in dry season but transmission
takes place year round
 Average case has gradual onset (among the HF agents,
only the arenaviruses are typically associated with a
gradual onset) that gives way to more severe
constitutional symptoms and prostration
 Bleeding is seen in only 15-30% of cases
 Maculopapular rash is often noted in light skinned
Lassa patients
 Effusions are common
 Fetal death rate is 92% in the last trimester
 WBC are normal or slightly elevated
 Platelet counts are normal or somewhat low
 Deafness coincides with clinical improvement in 20% of
cases and is permanent and bilateral in some
 Fatal outcome if with:
- high serum conc. Of AST
- high level viremia
 Patients with AST level of >150 IU/mL should be
treated with IV ribavirin (an antiviral nucleoside
analogue)
 Only major SE of ribavirin is reversible anemia that
doesn’t require transfusion
SOUTH AMERICAN HF SYNDROMES (Argentine, Bolivian,
Venezuelan, and Brazilian)
 Clinically similar to one another but epidemiology
differs
 Transmission by: person to person contact or
nosocomial but rare
 The basic disease resembles Lassa fever with 2 marked
differences:
1. Thrombocytopenia (often marked) is the rule and
quite common
2. CNS dysfunction is much more common than in
Lassa fever and is often manifest by marked confusions,
tremors of upper extremities and tongue and cerebellar
signs
 Argentine HF is readily treated with convalescent phase
plasma given within the first 8 days of illness
 In the absence of passive antibody therapy, IV ribavirin
in the dose recommended for Lassa fever is likely
effective in all South American HF syndromes
 Avoid intimate contacts for several weeks after
recovery
 A safe, effective, live attenuated vaccine exists for
Argentine HF
RIFT VALLEY FEVER
 Mosquito borne Rift Valley fever virus is also a pathogen
of domestic animals
 Maintained in nature by transovarial transmission in
floodwater Aedes mosquitoes and presumably also has a
vertebrate amplifier
 Virus is infectious when transmitted by contact with
blood or aerosols from domestic animals or their
abortuses
 Slaughtered meat is not infectious
 Anaerobic glycolysis in post mortem tissues results in
an acidic environment that rapidly inactivates the
Bunyaviridae such as Rift Valley Fever virus and
Crimean Congo HF virus
 Most infections are manifested as the fibrile-myalgic
syndromes
 No proven therapy
 Only supportive care need be given
 Epidemic disease is [revented by vaccination of live
stock

CRIMEAN-CONGO HF
 This severe syndrome has a wide geographic
distribution, potentially being found wherever
ticks of the genus Hyalomma occur
 Veterinary serosurveys are the most effective
mechanism of for the surveillance of virus
circulation in a region
 Human infection acquired via a tick bite or during
the crushing of an infected tick
 Domestic animals don’t become ill but do develop
viremia
 Thus, there s danger of the infection at the time
of slaughter
 Causes extensive liver damage
 Clinical lab values show:
- DIC
- Elevated AST, CPK, and bilirubin
 Patients with fatal cases develop leukocytosis
 Thrombocytopenia is more marked
 Clinical experience shows ribavirin is efficacious
and should be used
HF with renal syndrome
 First to be identified as an HF
 Widely distributed in Europe and Asia
 In Europe, most often caused by Puumala virus (rodent
reservoir, the bank vole)
 In Asia, by Hantaan virus (rodent reservoir, the striped
field mouse)
 Most cases occur in rural residents and vacationers,
exception is the Seoul virus diseases
 Human infections is acquired primarily through
aerosols of rodent urine
 Patients with Hantavirus diseases are not infectious
 HF with renal syndrome is the most important form of
HF today
 Severe classic Hantaan disease has 4 stages: F-HOP
 FEBRILE period: abrupt onset of fever, headache,
myalgia, thirst
 HYPOTENSIVE phase: falling BP; relative bradycardia;
lab findings include leukocytosis with a left shift,
atypical lymphocytosis, proteinuria, vascular leakage
causing hemoconcentration, and renal tubular necrosis;
kinin activation is marked; rising hematocrit levels
reflects increasing vascular leakage
 OLIGURIC phase: continuing hemorrhage; oliguria
persisting for 3-10 days before renal function returns
 POLYURIC stage: As renal function returns, there is
danger of dehydration and electrolyte abnormalities
 Mainstays of therapy are management of shock,
reliance on pressors, modest crystalloid infusion, IV
use of human serum albumin, and treatment of renal
failure with prompt dialysis
 IV ribavirin has reduced mortality and morbidity in
severe cases
 Puumala virus, the most common cause of HF with
renal syndrome (former name—nephropathia
epidemica)
 Dominant features of infections with Puumala viruses
are: fever, abdominal pain, proteinuria, mild oliguria,
and sometimes blurring of vision or glaucoma ff. by
polyuria and hyposthenuria in recovery
 Diagnosis is readily made by IgM-capture ELISA
HANTAVIRUS PULMONARY SYNDROME
 Causative viruses are hantaviruses of a distinct
phylogenetic lineage that is associated with the rodent
subfamily Sigmodontinae
 Sin nombre virus chronically infects the deer mouse
and is the most important virus causing Hantavirus
pulmonary syndrome in the United States
 Disease is linked to rodent exposure and particularly
affects rural residents in dwellings permeable to
rodent entry
CLINICAL FINDINGS:
 Prodrome: (3-4 days; range 1-11 days) fever,
myalgia, dizziness, vertigo, malaise, nausea,
vomiting, abdominal pain
 Patients are usually recognized as the
cardiopulmonary phase begins
 Cardiopulmonary phase: tachycardia, hypotension,
tachypnea, early signs of pulmonary edema
 Final phase: rapid decompensation with
hypoxemia, resp. failure, low cardiac output,
myocardial depression, increased pulmonary
vascular permeability, shock
 Goal of management is to prevent severe hypoxemia by
oxygen therapy, and if needed, intubation and intensive
respiratory management
LAB FINDINGS:
 Thrombocytopenia (important early clue), atypical
lymphocytes, and a left shift, often with
lymphocytosis; hemoconcentration; hypoalbuminemia;
and proteinuria
 IgM testing of acute phase serum can yield positive
results, even during the prodromal stage
 RT_PCR of blood clots or tissue usually gives a positive
result in the first 7-9 days of illness
PROGNOSIS:
 Most pts who survive for 48 hrs recover with residua
 Mortality rates are approx. 30-40% despite optimal
management
YELLOW FEVER
 Causes a typical HF syndrome with prominent hepatic
necrosis
 Pts are viremic for 3-4 days and can have jaundice,
hemorrhage, black vomit, anuria, and terminal delirium
 Albuminuria is usually noted and may be marked
 Urban yellow fever can be prevented by control of the
mosquito vector Aedes aegypti
 The continuing sylvatic cycle requires vaccination of all
visitors to areas of potential transmission
DENGUE HEMORRHAGIC FEVER/DENGUE SHOCK SYNDROME
 Previous infection with a heterologous dengue virus
serotype may elicit nonprotective antibodies and
enhanced disease if pts are reinfected
 DHF is marked by bleeding tendencies
 DSS is more serious because of vascular permeability
leading to shock
 Period of shock lasts only 1-2 days and most patients
respond promptly to close monitoring, oxygen
administration, and infusion of crystalloid or—in severe
cases--colloid
 In severe cases, frank shock occurs with cyanosis,
hepatomegaly, ascites and pleural effusions, and GI
bleeding
 Control of Aedes aegypti, the mosquito vector, is key
to control disease
 Macrophage or monocyte infection is central to
pathogenesis of dengue fever and to the origin of
DHF/DSS
 Induction of vascular permeability and shock depends
on multiple factors, include the ff:
- presence of enhancing or neutralizing
antibodies
 - age (risk decreases considerably after age
12)
- sex (F>M)
- race
- nutritional status (malnutrition is
protective)
- sequence of infection
- infecting serotype (Type 2 is more
dangerous than other serotypes)
 DHF is identified by detection of bleeding tendencies
(tourniquet test, petechiae) or overt bleeding in the
absence of underlying causes such as pre-existing GI
lesions