Viral Hemorrhagic Fevers

YELLOW FEVER
 Viral Hemorrhagic Fevers
Viral hemorrhagic fevers refer to a group of
illnesses that are caused by several distinct
families of viruses.
In general, the term "viral hemorrhagic fever"
is used to describe a severe multisystem
syndrome (multisystem in that multiple organ
systems in the body are affected).
Characteristically, the overall vascular
system is damaged, and the body's ability to
regulate itself is impaired.
These symptoms are often accompanied by
hemorrhage (bleeding); however, the
bleeding is itself rarely life-threatening. While
some types of hemorrhagic fever viruses can
cause relatively mild illnesses, many of these
viruses cause severe, life-threatening
disease.
 Symptoms:
Fever, nausea, vomiting, flushed face,
constipation, stomach discomfort,
headache, muscle pains, restlessness and
irritability--can lead to jaundice and black,
coffee-ground vomit
 Flaviviridae
(dengue, yellow fever,
Groupe TBE)

Viral Haemorrhagic Fevers

Arenaviridae
(Lassa, Junin, Machupo, Guanarito)

Envelopped
RNA viruses

Bunyaviridae
Filoviridae (CCHF, RVF,
(Ebola, Marburg) Hantaviruses)
Family Genus VIRUS DISTRIBUTION
Flaviviridae Flavivirus Yellow Fever Africa South America
Dengue 1,2,3,4. Tropical areas

Omsk HF Russia
Alkhurma Saudi Arabia

Kyasanur Forest HF India

Bunyaviridae Phlebovirus Rift Valley Fever Africa, Saudi Arabia

Nairovirus Crimean-Congo HF Africa, Eurasia

Hantavirus Hantan Dobrava Puumala Eurasia

Sin Nombre, Andes Americas
 The features of viral families
They are all RNA viruses, and all are covered, or enveloped,
in a fatty (lipid) coating.
Their survival is dependent on an animal or insect host, called
the natural reservoir.
The viruses are geographically restricted to the areas where
their host species live.
Humans are not the natural reservoir for any of these viruses.
Humans are infected when they come into contact with
infected hosts. However, with some viruses, after the
accidental transmission from the host, humans can transmit the
virus to one another.
Human cases or outbreaks of hemorrhagic fevers caused by
these viruses occur sporadically and irregularly. The
occurrence of outbreaks cannot be easily predicted.
With a few noteworthy exceptions, there is no cure or
established drug treatment for VHFs.
 YELLOW FEVER
(also called yellow jack, black vomit, or
sometimes American Plague)
Yellow fever — acute arboviral infectious disease,
which characters by fever, hard intoxication,
thrombohaemorrhagic syndrome, affection of liver and
kidneys.

The “yellow” in the name is explained by the

jaundice that affects some patients, causing
yellow eyes and yellow skin.
 Morphology of Yellow fever virus
(YFV)
Virus classification
Group:
Group IV ((+)ssRNA)
Family:Flaviviridae
Genus:Flavivirus
Type species
Yellow fever virus

YFV is one of the

smallest RNA viruses
isolated
 Epidemiology
Human infection is begun
after deposition of viral
particles through the skin
in infected arthropod
saliva.
Mosquitos are the
primary vector in
transmission of the
disease from forest
monkeys to humans and
in person-to-person
transmission.
Types of Yellow fever
There are three types of transmission cycles for Yellow Fever :
sylvatic, intermediate and urban.

1. Slyvatic (or Jungle) Yellow Fever: Monkeys can be the bearer

of the Yellow Fever virus, and when bitten by the aedes mosquito,
the infected mosquito can transmit the disease to humans.
2. Intermediate Yellow Fever: In rural areas of humid and semi
humid savannahs in Africa, due to increased contact humans and
infected mosquitoes, small-scale epidemics of Yellow Fever maybe
occur. This is the most common type of outbreaks seen in Africa in
recent years. This can shift to urban epidemic if the conditions are
suitable, if the infected mosquito is present and where people are not
vaccinated.
3. Urban Yellow Fever: Large epidemics can occur when migrants
introduce the virus into areas with high population density. The
aedes aegypti mosquito carries the virus from person to person.
These outbreaks can be severe if spread to a large geographical area.
Geographic distribution
 Pathogenesis
After infection the virus first replicates locally,
followed by transportation to the rest of the body
via the lymphatic system.
Following systemic lymphatic infection the virus
proceeds to establish itself throughout organ
systems, including the heart, kidneys, and the
parenchyma of the liver; high viral loads are also
present in the blood. Necrotic masses
(Councilman bodies) appear in the cyytoplasm
of hepatocytes.
 Symptoms
The incubation period is 3 to 6 days.
There are two disease phases:

period of infection (acute phase)

period of remission
period of intoxication (toxic phase)
 Period of infection
fever,
muscle pain (with prominent backache),
headache,
shivers,
loss of appetite, and nausea or vomiting.
The high fever is often paradoxically associated
with a slow pulse (known as Faget’s sign).
After 3 or 4 days most patients improve
and their symptoms disappear.
 Period of remission
This period is from several hours to 1-2
days.
The temperature decreases
The state of health of patients normalize.
 Period of intoxication
Toxic phase develops within 24 hours.
Fever reappears,
Jaundice
abdominal pain with vomiting.
Bleeding can occur from the mouth, nose,
eyes, and stomach.
blood appears in the vomit and feces.
Kidney function deteriorates; this can
range from abnormal protein levels in the
urine (proteinuria) to complete kidney
failure with no urine production (anuria).
Half of the patients in the "toxic phase" die
within 14 days.
 Laboratory diagnostic
Examination of serum for
isolation of virus,
Demonstration of viral genome
by polymerase chain reaction, or
by antigen detection by
monoclonal antibody-enzyme
immunoassay.
Serological methods (especially
IgM enzyme immunoassay)
RFC,
 Laboratory diagnostic
The blood analysis: leukopenia,
thrombocytopenia, in atoxic phase –
leukocytosis.
The urine analysis: proteinuria,
hematuria.
Postmortem diagnosis may be
accomplished by histopathological
examination of the liver(midzonal
necrosis and eosinophilic
degeneration of hepatocytes
(Councilman bodies)), with or without
immuno-cytochemical analysis to
detect yellow-fever viral antigen.
 Treatment
There is no true cure for yellow fever.
Treatment is symptomatic and supportive only.
Fluid replacement, fighting hypotension and
transfusion of blood derivates is generally
needed only in severe cases.
In cases that result in acute renal failure, dialysis
may be necessary.
A fever victim needs to get a lot of rest, fresh air,
and drink plenty of fluids.
 Prevention
The yellow fever vaccine is a live-virus
vaccine that has been used for several
decades. The vaccine requires only one
shot. If a person is in a yellow fever endemic
area for more than 10 years, he or she will
need a booster shot.
Prevent exposure by getting vaccinated prior
to travel to high-risk areas and through the
use of DEET-containing mosquito repellents
 The Yellow Fever Vaccine
After receiving the yellow fever vaccine, you
should receive an International Certificate of
Vaccination (yellow card) that has been
validated by the vaccination center. This
certificate becomes valid 10 days after
vaccination and lasts for 10 years. You will need
this card as proof of vaccination to enter certain
countries. Please make sure you discuss your
travel itinerary with your doctor or nurse before
you receive your yellow fever vaccination.
 CRIMEAN-CONGO
HEMORRHAGIC FEVER
Crimean-Congo hemorrhagic fever
(CCHF) is a viral disease caused by the
Nairovirus.
 Etiology
Family Bunyaviridae
Genus Nairovirus
Virus Crimean-Congo
HF - RNA virus
Virions have the
spherical form of 92-96
nm in diameter.
The virus is opened in 1945 by
M.P.Chumakovym in the Crimea.
 Epidemiology
Humans become
infected by being
bitten by ticks,
principally of the
genus Hyalomma, or
by crushing ticks,
often while working
with domestic animals
or livestock.
Mechanism of transmission
Contact with blood, secretions, or excretions of
infected animals or humans may also transmit
infection. Even in epidemics, cases do not show
narrow clustering and person-to-person spread
is rare, though possible through contact with
infectious blood or bodily fluids. CCHF would
probably be delivered by aerosol if used as a
biological warfare agent biological warfare agent
(BW agent).
In areas with endemic CCHF, the disease may
occur most often in the spring or summer.
CCHF is endemic in eastern Europe, particularly in the
Soviet Union. However, it may occur in other parts of
Europe, especially around the Mediterranean. CCHF has
been recognized in northwest China (39), Central Asia,
and the Indian subcontinent and may occur in the Middle
East and throughout much of Africa.
 Clinical symptoms
The incubation period for CCHF is about 2-9
days. The incubation period following contact
with infected blood or tissues is usually 5 to 6
days, with a documented maximum of 13
days.
There are 2 stages in current of disease:
Initial stage
The heat period
 Initial stage
fever and chills 3-12 days
after tick exposure,
headache,
myalgia, arthralgia,
lumbar and abdominal
pain,
nausea and vomiting,
delirium, and prostration.
Sore throat, conjunctivitis,
jaundice, photophobia, and
various sensory and mood
alterations may develop.
 The heat period
petechial rash
hemorrhagic diathesis,
large ecchymoses,
bleeding from needle-
puncture sites, and
hemorrhage from multiple
other sources.
bleeding from nasal, gastric,
intestinal, uterine and renal
membranes.
Fatal cases are associated
with extensive hemorrhage,
coma, and shock.
Death is usually due to shock,
blood loss or intercurrent
infection.
The mortality is about 15 to 30 per cent,
but may be as high as 40 to 80 per cent in
hospital or nosocomial outbreaks. In those
patients who recover, improvement
generally begins on the ninth or tenth day
after onset of illness.
Convalescence in survivors is prolonged
with asthenia, dizziness, and often hair
loss.
 Laboratory Diagnostic
requires isolating the virus from blood during the first
week of disease.
detecting rising antibody titer by IFA, complement
fixation,
detectable antigen by rapid enzyme-linked
immunosorbant assay (ELISA) testing of acute serum
samples. IgM ELISA antibodies occur early in
recovery.
Polymerase chain reaction has recently been used in
diagnosing CCHF.
Nonspecific laboratory abnormalities include
progressive neutropenia, lymphopenia,
thrombocytopenia, and anemia. Hyperbilirubinemia
and elevated liver enzymes are common.
 Treatment
Ribavirin 30 mg/kg (initial dose); then 16 mg/kg
each 6 h x 4 d; then 8 mg/kg each 8 h x 6 d
Immune sera have also been used for
therapeutic purposes several times, but its value
has not been demonstrated.
Patients with suspected or confirmed CCHF
should be isolated and cared for using barrier
nursing techniques. Because of several well-
defined outbreaks within hospitals, protective
measures for medical personnel are an issue.
 Prevention
No vaccine is available.
An inactivated mouse-brain vaccine is
used on a small scale in Eastern Europe,
but there is no safe and effective vaccine
widely available for human-use.
Chikungunya fever
Chikungunya fever is a viral disease
caused by alphavirus.

The disease was first described by Marion

Robinson and W.H.R. Lumsden in 1955.
 Morphology

The Chikungunya virus (CHIKV) is

a positive-sense, single-stranded
RNA virus from
Family Togaviridae
Genus Alphavirus.
Chikungunya fever is endemic in Central Africa, south and south-eastern
Asia. This was the cause of the actual plague in the Indian Ocean and a
threat to the Mediterranean coast at present, requiring urgent meetings of
health officials in France, Italy, and Spain.
 Epidemiology

Humans become infected by

being bitten by Aedes
aegypty mosquito
Mechanism of transmission-
transmissive.
Reservoir of viruses in Aedes aegypty mosquito
nature is a patient at the
virusemia’s period.
 Clinical symptoms

fever (39 °C),

a petechial or maculopapular rash usually
involving the limbs and trunk,
arthralgia or arthritis,
headache,
conjunctival infection,
slight photophbia.
The fever typically lasts for two days and
abruptly comes down.
 Dermatological manifestations:

Maculopapular rash
Nasal blotchy erythema
Freckle-like pigmentation
Pigmentation on face
Lichenoid eruption and
hyperpigmentation in
photodistributed areas
Multiple aphthous-like
ulcerus over scrotum, crural
areas and axilla.
Lympoedema in acral
distribution
(bilateral/unilateral)
Multiple ecchymotic spots
(Children)
Vesiculobullous lesions
(infants)
Subungual hemorrhage
Photo urticaria
Acral urticaria
 Pedal oedema (swelling of legs) is
observed in many patients, the cause of
which remains obscure as it not related to any
cardiovascular, renal or hepatic abnormalities.
 Laboratory diagnostic
Virus isolation (by inoculation of
mosquito cell culture, mosquito,
mammalian cell culture or
suckling mice).
ELISA (virus-specific IgM
antibodies).
Haemagglutination inhibition (HI)
antibodies appear with the
cessation of viremia. All patients
will be positive by day 5 to 7 of
illness.
 Treatment
There is no specific treatment for Chikungunya.

Treatment is symptomatic—rest, fluids, and

ibuprofen, naproxen, acetaminophen, or
paracetamol may relieve symptoms of fever and
aching.
Chloroquine Phosphate (250 mg/day) .
Infected persons should be protected from further
mosquito exposure (staying indoors and/or under a
mosquito net during the first few days of illness) so
that they can’t contribute to the transmission cycle.
 Preventation

No vaccine.
Infected persons should limit further
exposure to mosquito bites, stay indoors
and under a mosquito net.
Dengue fever (alternative disease names
Breakbone fever) is a flu-like illness spread
by the bite of an infected mosquito.

Dengue hemorrhagic fever is a severe,

often fatal, complication of dengue fever.
 Etiology

Group:Group IV ((+)ssRNA)
Family: Flaviviridae
Genus: Flavivirus
Species: Dengue virus

There are four known serotypes:

DEN-1,
DEN-2,
DEN-3,
DEN-4.
 Risk factors for dengue
hemorrhagic fever include
A person's age
Immune status,
Persons who were previously infected with
one or more types of dengue virus are
thought to be at greater risk for developing
dengue hemorrhagic fever if infected
again.
100 endemic countries throughout the Americas,
South-east Asia, the western Pacific islands, Africa
and the Eastern Mediterranean.
EPIDEMIOLOGY
 EPIDEMIOLOGY
The viruses are
transmitted via the bite of
various day-feeding
mosquitoes of the
subgenus Stegomyia.
The principal vector is
Aedes aegypti.
Once infected, a
mosquito remains
infective for life.
 Pathogenesis and pathophysiology :
There are two main pathophysiologic changes
occur:
 (a) Vascular permeability increases which results in
plasma leakage, leading to hypovolaemia and shock.
 (b) abnormal haemostasis, due to vasculopathy,
thrombocytopenia and coagulapathy, leading to various
haemorrhagic manifestations.
The severity of DHF as compared with dengue fever
may be explained by the enhancement of virus
multiplication in macrophages by heterotypic antibodies
resulting from a previous dengue infection. There are
evidences suggesting that cell mediated immune response
may also be involved in the pathogenesis of DHF.
 Clinical symptoms
The incubation period is
usually 5-6 days but may
vary from 3 to 10 days.
Infants and youths often
experience an
undifferentiated febrile
disease with rash.
Older children and adults
may have a mild febrile
syndrome but more
typically experience high
fever, severe headache,
pain behind the eyes,
muscle and joint pains and
rash.
DHF is characterized by
high fever,
haemorrhagic phenomena,
enlarged liver and circulatory
failure.
A sudden onset of fever is the
first indication of DHF,
accompanied by facial flush and
other symptoms of dengue
fever.
The fever persists for 2-7 days
and can reach 41° C, followed
by febrile convulsions and
haemorrhagic phenomena.
If disease untreated,
the patient may go into
shock (DSS) with a
rapid, weak pulse,
followed by signs of
circulatory failure such
as cool, blotchy skin.
Without proper
treatment, the patient
may die within 12-24
hours.
 Laboratory diagnostic:
Virus isolation by infection of
new-born mice with blood or
infected mosquitoes
Detection of antigens or
antibody to the agent in the
blood (serology)
ELISA is available
Thrombopenia
Raised hematocrit
 Treatment
There is no specific treatment treatment for
dengue.
Persons with dengue fever should rest and drink
plenty of fluids. They should be kept away from
mosquitoes for the protection of others. Dengue
hemorrhagic fever is treated by replacing lost
fluids. Some patients need transfusions to
control bleeding.
 Prevention
There is no vaccine to prevent
dengue.
1. Prevent mosquito bites :
 Protect yourself from the bite -wear
full sleeve cloths and long dresses
to cover the limbs.
 Use repellents - care should be
taken in using repellents on young
children and elders.
 Use mosquito nets to protect
babies., old people and others who
may rest during the day.
 To tighten all water containers
regularly.
2. Prevent the multiplication of
mosquitoes :
Mosquitoes which spread dengue live and
breed in stagnant water in and around house.
 Drain out the water from desert / window air
coolers (when not in use), tanks, barrels,
drums, buckets etc.
 Remove all objects containing water (e.g.
plant saucers, etc.) from the house.
 All stored water containers should be kept
covered all times.
 Collect and destroy discarded containers in
which water collect, e.g. bottles, plastic
bags, tins, tyres etc.
 Ebola virus
Ebola viral disease – acute viral
infectious from group of hemorrhagic
fever with characteristic symptoms such
as headache, myalgia, petechial skin
rash, bloody diarrhea and shock.
The virus is named after the Ebola River
Valley in the Democratic Republic of the
Congo (formerly Zaïre), near the site of
the first recognized outbreak in 1976.
 Virus classification
Group:Group V ((-)ssRNA)
Order:Mononegavirales
Family:Filovirus
Genus:Ebolavirus
Type species
Zaïre Ebolavirus
Species
Reston Ebolavirus
Sudan Ebolavirus
Ivory Coast Ebolavirus
Bundibugyo Ebolavirus
 Epidemiology
There is a strong suspicion that the disease is a
zoonosis. In the natural reservoir cycle of the virus is
unknown, but may be monkeys.
The disease occurs in all age groups with predominance
in adults.
The mechanism of transmission of infection in these
outbreaks was mainly by direct contact with infected
blood, by very close and prolonged contact with an
infected patient, or by inoculation by accident or through
the use of a contaminated syringe and needle.
Exceptionally, unusual nosocomial transmission creates
an amplifying cycle and causes epidemics.
 Clinical symptoms
The incubation period is about 4 to 10days.
severe frontal and temporal headache,
high fever
generalized pains, particularly in the back.
bradycardia.
prostration
severe watery diarrhoea
weight loss
Dehydration,
knife-like chest and pleuritic pain
a very dry (rather than sore) throat,
accompanied by cough.
exhaustion,
nausea,
dizziness
On white skin a
characteristic, non-
itching, maculopapular
rash appears between days
5 and 7, last 3 or 4days,
and is followed by a fine
desquamation.
On black skin the rash,
often described as being
“like measles” is not so
obvious and can often
only be recognized later
with the appearance of
skin desquamation.
Severe bleeding (between
days 5 and 7).
haematemesis, melaena,
and sometimes the passage
of fresh blood in the stools.
also bleeding from the nose,
gums, and vagina, and
subconjunctival
haemorrhages.
Petechiae and bleeding from
needle puncture sites are
also very common.
Death generally occurred
between days 7 and 16,
usually preceded by severe
blood loss and shock.
 Laboratory diagnostic
Methods of diagnosis of Ebola include testing saliva and urine samples.

1. Clinical blood analysis: 2. Biochemical

A leucopenia which was investigations:
followed by a increased levels of
leucocytosis; aspartate transaminase and
a low erythrocyte alanine transaminase.
sedimentation rate; Serum alkaline
A considerable phosphatase and creatinine
thrombocytopenia was phosphokinase remained
recorded from about day normal.
3 onwards; Creatine and urea
a abnormal platelet increased only in cases of
aggregation. anuria.
3. Electrocardiographic changes were compatible with a
myocarditis or other damage to the myocardium.
4. Microbiological diagnostics:
the isolation of the virus.
Immunofluorescent staining techniques.
Immunoelectron microscopy
Polymerase chain reaction on serum,
Enzyme immunoassay on tissue sections,
Immunofluorescence on impressions of postmortem liver.
Immunofluorescence test.

Ebola Green Flourescent

 Ebola Reston Tissue Culture

human liver tissue infected with the Ebola virus

 Treatment
There is no specific therapy.

The use of specific therapy in the form of

convalescent plasma been successful.
 Prevention
No vaccine is yet available.