Crimean–Congo

Hemorrhagic fever
Dr.T.V.Rao MD
 What is Viral
Hemorrhagic Fever?
• Severe multisystem syndrome
• Damage to overall vascular system
• Symptoms often accompanied by
hemorrhage
• Rarely life threatening in itself
• Includes conjunctivitis, petechia, echymosis
Virology of Hemorrhagic fevers
• They are all RNA viruses
• They are all zoonotic (natural reservoir is an
arthropod or other animal host)
• Disease is restricted to habitat of the host
• Humans become infected by contact with
host
• Some viruses can be transmitted from
human to human
Classification of Prominent
Hemorrhagic Fevers
 Bunyaviridae History
• 1930: Rift Valley Fever – Egypt
• Epizootic in sheep
• 1940s: CCHF - Crimean peninsula

Center for Food Security and Public

2004
Health Iowa State University -
• Hemorrhagic fever in agricultural
workers
• 1951: Hantavirus – Korea
• Hemorrhagic fever in UN troops
• 5 genera with over 350 viruses
 Bunyaviridae Transmission
• Arthropod vector
• Exception – Hantaviruses
• RVF – Aedes mosquito

Center for Food Security and Public

2004
Health Iowa State University -
• CCHF – Ixodid tick
• Hantavirus – Rodents
• Less common
• Aerosol
• Exposure to infected animal tissue
 Bunyaviridae in Animals
• RVF
• Abortion – 100%
• Mortality rate
• >90% in young
• 5-60% in older
animals
• CCHF
• Unapparent infection in
livestock
• Hantaviruses
• Unapparent infection in
rodents
 Transmission of Disease

• CCHFV usually circulates between asymptomatic

animals and ticks in an enzootic cycle. This virus has been
found in at least 31 species of ticks, including seven
genera of the family Ixodidae (hard ticks). Members of
the genus Hyalomma seem to be the principal vectors.
Transovarial, transstadial and venereal transmission occur
in this genus. Hyalomma marginatum marginatum is
particularly important as a vector in Europe, but CCHFV
is also found in Hyalomma anatolicum anatolicum and
other Hyalomma spp.
 What is Crimean-Congo hemorrhagic fever?

• Crimean-Congo hemorrhagic
fever (CCHF) is caused by
infection with a tick-borne virus
(Nairovirus) in the family
Bunyaviridae. The disease was
first characterized in the Crimea
in 1944 and given the name
Crimean hemorrhagic fever. It
was then later recognized in
1969 as the cause of illness in
the Congo, thus resulting in the
current name of the disease.
 What is Crimean-Congo
hemorrhagic fever
• Crimean-Congo
hemorrhagic fever (CCHF)
is caused by infection with
a tick-borne virus
(Nairovirus) in the family
Bunyaviridae. The disease
was first characterized in
the Crimea in 1944 and
given the name Crimean
hemorrhagic fever. It was then
later recognized in 1969 as the cause of illness
in the Congo, thus resulting in the current
name of the disease.
 Taxonomical character of
CCHF
• The antigenic characterization of the virus is, on the
other hand, far better established than its position in
the International Committee on Taxonomy of Viruses
(ICTV) scheme. Exhaustive and continued efforts by
hemagglutination inhibition (HI), complement
fixation (CF) and agar gel diffusion and precipitation
(AGDP) tests have shown the virus to be antigenically
related to no other viruses except: to Hazara with
which it constitutes the CCHF group,
Crimean-Congo hemorrhagic fever caused by
Member of Nairovirus

• CCHFV is a member of the Nairovirus genus of the

family Bunyaviridae. Other genera within the family
include Orthobunyavirus, Hantavirus, Phlebovirus,
and Tospovirus. According to the most recent report
from the International Committee on the Taxonomy
of Viruses, there are seven recognized species in the
genus Nairovirus containing 34 viral strains. The most
important Serogroups are the CCHF group, which
includes CCHFV, and Hazara virus, which has not
been demonstrated to be pathogenic to human
 CCHF is a Tick borne Disease
• CCHF spreads to humans either by tick-bites,
or through contact with viraemic animal
tissues during and immediately post-slaughter.
CCHF outbreaks constitute a threat to public
health services because of its epidemic
potential, its high case fatality ratio (10-40%),
its potential for nosocomial outbreaks and the
difficulties in treatment and prevention.
 Crimean–Congo hemorrhagic fever
• Crimean–Congo hemorrhagic fever (CCHF) is a
widespread tick-borne viral disease, a zoonosis of
domestic animals and wild animals, that may affect
humans. The pathogenic virus, especially common in
East and West Africa, is a member of the
Bunyaviridae family of RNA viruses. Clinical disease is
rare in infected mammals, but commonly severe in
infected humans, with a 30% mortality rate.
Outbreaks of illness are usually attributable to
handling infected animals or people.
CCHF endemic in …..
• CCHF is endemic in all
of Africa, the Balkans,
the Middle East and in
Asia south of the 50°
parallel north, the
geographic limit of the
genus Hyalomma, the
principal tick vector.
Global distribution and phylogenetic relationships
of Crimean-Congo hemorrhagic fever virus
(CCHFV) strains
 Taxonomical Name …
• The International Committee on Taxonomy of Viruses
proposed the name Congo-Crimean hemorrhagic
fever virus, but the Soviets insisted on Crimean–
Congo hemorrhagic fever virus. Against all principles
of scientific nomenclature based on priority of
publication, it was adopted as the official name in
1973 in possibly the first instance of a virus losing its
name to politics and the Cold War. However, since
then Congo-Crimean or just Congo virus
 How is CCHF spread and how do
humans become infected?

Ixodid (hard) ticks, especially

those of the genus, Hyalomma,
are both a reservoir and a vector
for the CCHF virus. Numerous
wild and domestic animals, such
as cattle, goats, sheep and hares,
serve as amplifying hosts for the
virus. Transmission to humans
occurs through contact with
infected animal blood or ticks.
HUMAN CONTACT CAN SPREAD THE
DISEASE
• CCHF can be transmitted
from one infected human
to another by contact with
infectious blood or body
fluids. Documented
spread of CCHF has also
occurred in hospitals due
to improper sterilization of
medical equipment, reuse
of injection needles, and
contamination of medical
supplies.
Who are Who are at Risk
• People at most risk for
CCHF include livestock
workers, people who
herd animals, and people
who work in
slaughterhouses in
endemic
areas. Additionally if
health care workers in
endemic areas have
unprotected contact with
infectious blood or body
fluids, they are at high
risk.
The disease starts with short
Incubation period
• Incubation period
– 3-7 days
• Hemorrhagic
Fever - 3–6 days
following clinical
signs
 Pathophysiology
• The target organ is the vascular bed.
• Dominant clinical features are due to micro
vascular damage and changes in vascular
permeability
• In most cases of viral hemorrhagic fever, the
coagulopathy is multifactorial, including:
• hepatic damage
• disseminated intravascular coagulation
• primary marrow injury to megakaryocytes
 How the disease manifests
• Typically, after a 1–3 day incubation period following
a tick bite (5–6 days after exposure to infected blood
or tissues), flu-like symptoms appear, which may
resolve after one week. In up to 75% of cases,
however, signs of hemorrhage appear within 3–5
days of the onset of illness in case of bad
containment of the first symptoms: first mood
instability, agitation, mental confusion and throat
petechia, then soon nosebleeds, bloody urine and
vomiting, and black stools.
 Symptoms
• Fever, fatigue, dizziness, myalgia's, and
prostration
• Signs of bleeding range from only conjunctival
hemorrhage, mild hypotension, flushing, and
petechiae to shock and generalized mucous
membrane hemorrhage and evidence of
pulmonary, hematopoietic, and neurologic
dysfunction
• Renal insufficiency is proportional to
cardiovascular compromise except in
Hemorrhagic Fever and Renal Syndrome in which
it is an integral part of the disease
Hemorrhagic disorders are cause of
Morbidity and Mortality
• As the illness
progresses, large areas
of severe bruising,
severe nosebleeds, and
uncontrolled bleeding at
injection sites can be
seen, beginning on about
the fourth day of illness
and lasting for about two
weeks
Can lead to Major Organ Failure
• The liver becomes
swollen and painful.
Disseminated
intravascular
coagulation may occur
as well as acute kidney
failure and shock, and
sometimes acute
respiratory distress
syndrome.
How is Crimean-Congo hemorrhagic
fever diagnosed?
• Laboratory diagnosis of
CCHF can be made by
finding a positive
serological test result,
evidence of viral antigen in
tissue by
immunohistochemical
staining and microscopic
examination, or
identification of viral RNA
sequence in blood or
tissue, in a patient with a
clinical history compatible
with CCH
 Virological Diagnosis
• Crimean-Congo hemorrhagic
fever can be diagnosed by
isolating CCHFV from blood,
plasma or tissues. At autopsy,
the virus is most likely to be
found in the lung, liver,
spleen, bone marrow, kidney
and brain. CCHFV can be
isolated in a variety of cell
lines including SW-13, Vero,
LLC-MK2 and BHK-21 cells.
RT- PCR is a sensitive tool in
Diagnosis
• Crimean-Congo
hemorrhagic fever is often
diagnosed by RT-PCR on
blood samples. This
technique is highly
sensitive. However, due to
the genetic variability in
CCHFV strains, a single set
of primers cannot detect all
virus variants, and most RT-
PCR assays are either
designed to detect local
variants or lack sensitivity.
 Serological Tests are easier to
use
• Crimean-Congo
hemorrhagic fever can
also be diagnosed by
serology. Tests detect
CCHFV-specific IgM, or a
rise in IgG titers in paired
acute and convalescent
sera. IgG and IgM can
usually be found with
indirect
immunofluorescence or
ELISA after 7-9 days of
illness
 Outbreaks leads to Mortality
• In documented
outbreaks of CCHF,
fatality rates in
hospitalized patients
have ranged from 9%
to as high as 50%.
• CCHF - Africa, Eastern
Europe, Asia
• 30% case fatality rate
 Prevention and Control
• Protective clothing
• Disposable gowns, gloves,
masks and shoe covers,
protective eyewear when
splashing might occur, or if
patient is disoriented or
uncooperative
• WHO and CDC
developed manual
• “Infection Control for
Viral Hemorrhagic Fevers
In the African Health
Care Setting”
Prevention and Control
• Anyone suspected of
having a VHF must use
a chemical toilet
• Disinfect and dispose of
instruments
• Use a 0.5% solution of
sodium hypochlorite
(1:10 dilution of bleach)
 How to Prevent CCHF
• Agricultural workers and others working with animals
should use insect repellent on exposed skin and clothing.
Insect repellants containing DEET (N, N-diethyl-m-
toluamide) are the most effective in warding off ticks.
Wearing gloves and other protective clothing is
recommended. Individuals should also avoid contact with
the blood and body fluids of livestock or humans who
show symptoms of infection. It is important for healthcare
workers to use proper infection control precautions to
prevent occupational exposure.
 Health care workers can be at risk
• Avoiding contact with
blood and body fluids
of humans or animals,
especially those who
have symptoms of
infection is also
important. Health care
workers need to be
sure to use proper
sanitation methods
 Ribavirin in experimental use
• Prevalence needs to be
measured in animals and in
at-risk humans in endemic
areas; and a useful animal
model needs to be
developed. Further
research is needed to
determine the efficacy of
specific treatment with
ribavirin and other antiviral
drugs, and develop a safe
and effective vaccine for
human use.
Prophylactic Methods to
prevent include
• Prophylactic treatment
with ribavirin has
occasionally been used
after high-risk exposures.
Safe burial practices,
including the use of 1:10
liquid bleach solution as
a disinfectant, have been
published
Control of Tick Bites is priority
in Prevention
• Measures to avoid tick bites include tick repellents,
environmental modification (brush removal, insecticides),
avoidance of tick habitat and regular examination of clothing
and skin for ticks. Clothing should be chosen to prevent tick
attachment; long pants tucked into boots and long-sleeved
shirts are recommended. Acaricides can be used on livestock
and other domesticated animals to control ticks, particularly
before slaughter or export.
 How to Prevent Outbreaks

• Agricultural workers and others working with animals

should use insect repellent on exposed skin and
clothing. Insect repellants containing DEET (N, N-
diethyl-m-toluamide) are the most effective in warding
off ticks. Wearing gloves and other protective clothing
is recommended. Individuals should also avoid contact
with the blood and body fluids of livestock or humans
who show symptoms of infection. It is important for
healthcare workers to use proper infection control
precautions to prevent occupational exposure.
 Follow the Universal Precautions
while caring Patients
• Strict universal
precautions are
necessary when caring
for human patients.
These recommendations
include barrier nursing,
isolation and the use of
gloves, gowns, face-
shields and goggles with
side shields.
Laboratory Workers to be
cautious …
•Laboratory
workers must
follow
stringent
biosafety
precautions.
Yet no Safe and Effective Vaccine
• An inactivated, mouse-
brain derived vaccine
against CCHF has been
developed and is used
on a small scale in
Eastern Europe.
However, there is no
safe and effective
vaccine widely
available for human
use.
• Programme created by Dr.T.V.Rao
MD for e-learning for awareness to
Medical and Public Health personal
in the developing world
• Email
• doctortvrao@gmail.com