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

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Bunyaviridae History

• 1930: Rift Valley Fever – Egypt

• Epizootic in sheep

•1940s: CCHF - Crimean peninsula

•Hemorrhagic fever in agricultural workers

•1951: Hantavirus – Korea

•Hemorrhagic fever in UN troops

•5 genera with over 350 viruses

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Bunyaviridae Transmission

• Arthropod vector

• Exception – Hantaviruses

• RVF – Aedes mosquito

•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 beenfound in at least 31 species of ticks, including sevengenera of the family Ixodidae (hard ticks). Members ofthe genus Hyalomma seem to be the principal vectors.Transovarial, transstadial and venereal transmission occurin this genus. Hyalomma marginatum marginatum isparticularly important as a vector in Europe, but CCHFVis also found in Hyalomma anatolicum anatolicum andother 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