Transcript Crimean-Congo Hemorrhagic Fever Virus

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Crimean-Congo haemorrhagic fever (CCHF) virus is a RNA virus
of geneus Nairovirus, from the Family Bunyaviridae. The disease it
caused is called CCHF because it was first discovered in Crimea
in 1994, so Crimean was given as part of the name; also, in 1956,
the same pathogen caused a similar illness in Congo, so then the
combination of the two places resulted the final term CCHF and
CCHF virus.
The virus is mainly seen in East and West Africa, but has also been
endemic in many areas in Asia and Eastern Europe. In recent
years, outbreaks have emerged from new places like Pakistan,
Albania and Iran as well.
CCHF is a tick-borne virus (mainly by argasid or ixodid ticksspecifically by Hyalomma, Dermacentor, Amblyomma and
Rhipicephalus species). The virus causes zoonostic diseases--from
both domestic and wild animals to humans.
This disease can create approximately 30% of mortality in all
infected individuals ( human infections are not as frequent as
animals).
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Alternative Disease Names
• Congo Fever
• Central Asian hemorrhagic fever
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Genome*Structure
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Circular, negative sense, ss RNA.
Monomeric
Segmented into 3 segments: large, medium, and small
17,100-22,800 nucleotides (complete genome)
Enveloped
Virion: spherical
Replicates in the cytoplasm
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Currently, the entry pathway and replication mechanisms for
Crimean-Congo hemorrhagic fever virus (CCHFV) is still poorly
understood.
To provide a general understanding, the raplicaiton strategy for its
genus Nairovirus is summarized below:
• Nairovirus enters host cells by receptor-mediated endocytosis—attachment by
their Gn-Gc glycoprotein dimers.
• The nucleic acids are released in the cytoplasm of the host cells, where
replication also takes place.
• When virions are assembled, they exist the cells via budding.
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Recent advance in research has provided some insights into
CCHFV:
• CCHFV utilizes clathrin-dependent endocytosis
• drugs that interfere with the formation of clathrincoated pits or the acidification
of endosomes can prevent entry of virus and release of the viral genome
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Cholesterol depletion can limit CCHFV infection
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Hyalomma tick
Hyalomma tick serves as the most common vector for CCHF
virus. It transmits the disease to a livestock (mainly
ruminants or ostriches) through biting, then when people
butcher (in contact with the blood) or eat the infected
animals, they become infected as well. Illness will show after
the viral incubation of three days. The transmission can be
both horizontal and vertical.
In the ticks—the females can pass the virus to their eggs,
which will develop and grow into the new adult ticks with
the virus.
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virus is found around the world and can
use small mammals like hare, hedgehogs
and rats as reservoirs. Ticks serve as the
vectors to transmit the virus to domestic
animals like sheep, cows and goats and then
infect humans. Although there could be high
titer of virus-concentration in the animals'
blood, the animals do not show any illness,
so it's difficult to realize if the animals are
infected.
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After exposure to the virus, like by a tick bite, the virus incubates in
the body first for up to three days. Then after approximately a week,
the infected hosts show initial flu-like symptoms including fever,
chills, severe headache, lumbar/abdominal/muscular pain, nausea,
anorexia, fatigue, red eyes/throats, fatigue, vomiting, malaise and
photophobia (being sensitive to light).
During this time, but at least after three to five days, 75% of the cases
reveal acute respiratory distress syndrome as well as the onset of
hemorrhagic symptoms—beginning as a petechial rash, which are
skin lesions that are like broken blood vessels underneath the skin or
bruises.
The rash can appear both in the internal and external mucosal linings.
Patients at this state can develop extreme mood swings, agitation,
aggressiveness and mental confusion.
At the later stage of the infection, blood can be observed in saliva,
nose, stool, urine, vomit; also black stool can be seen in certain
patients.
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Some infected individuals can develop painful and enlarged
liver (hepatomegaly), enlarged lymph node
(lymphadenopathy) and swollen abdomen (abdominal
organs/tissues)
In severe CCHF, acute kidney failure occurs due to
disseminated intravascular coagulation—a type of vascular
collapse that can cause death; patients have very low white
blood cell count.
However, this only happens in less than half of infected
individuals (and only in the second week of infection). For
individuals who survive after the second week of exposure,
they will recover but the recovery time is very long (years).
Coma, lethargy (extreme drowsiness), depression, lassitude
and low blood pressure can accompany in the acute CCHF
phase.
Retrieved from Centers for Disease Control, Dr. B. E.
Henderson, Public Health Image Library #2136
Retrieved from Centers for Disease Control, Dr. B. E. Henderson,
Public Health Image Library #2137
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Observation of obvious symptoms like bleeding from various places from
the body
Checking for tick bites
Leukopenia, Thrombocytopenia
ELISA (enzyme-linked immunoassay)
• --can detect antibodies such as IgM and IgG levels in the suspected
individuals’ serum—but this test has to wait at least a week postexposure in order to perform (false-negative).
• IgG concentration is stable and remains high for a long period of
time—up to five years but IgM level decreases after approximately
four months—but during which, there is sufficient amount that is
enough for diagnosis purposes.
Immunofluorescence assay (EIA) is commonly used to detect antigens
from the viral particles residing in cells or infected tissues.
Safely equipped laboratories should be utilized to perform any of these
diagnosis tests.
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Immunodeficient or malnourished individuals may not
mount an adequate humoral immune response, so for
these people, serological tests are not quite effective.
Viral load tests should be done instead—to directly
observe their blood or tissues for the presence of viruses.
If the viral load is low in the blood, for better observation,
a few virus can be extracted and grow in enriched broth
or plates with cell cultures for a few days, then use RTPCR (CCHFV is a RNA virus) to detect viral nucleic acids.
Differential diagnosis should accompany the tests
described before to help eliminate other viral
diseases, which cause very similar symptoms that
can interfere with the identification of CCHF virus.
 The viruses that can also cause hemorhagic fever
or many similar illneses are: Argentinian
hemorrhagic fever virus, Dengue fever virus,
Ebola hemorrhagic fever virus, Lassa fever virus,
Marburg fever virus, Yellow fever virus and Rift
valley fever virus.
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Currently, there is still no specific treatments available for CCHF
Also, no effective and safe vaccine for humans
There is a small portion of mouse brain-derived vaccines used in Europe (but
is not recommended by many countries and is not commercially available).
However, symptoms can be treated for decreasing discomfort and prolonging
life
• Utilizing painkillers to ameliorate various pain from lesions or bleeding
• anti-inflammation drugs to decrease swelling of infected sites, tissues and
liver
• antibiotics to treat secondary bacteria infections.
• Blood transfusion to filter out the virus under strict and careful
management is recommended and usually required in later stage of acute
infection.
• Common antiviral drug like riboflavin can be applied along with other
treatments—usually during outbreaks.
• For those who recovered, their blood now contains immunity against CCHF
virus, so can be used to passively immunize other individuals, but so far
this strategy is only occasionally utlized due to safety reasons.
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Chemicals like acaricides can be used in livestock
production industries to kill ticks and control their spread.
Workers should wear protective clothes and gloves if
working in endemic areas. Farmers, slaughterhouse workers
and veterinarians should be cautious in handling animal
blood or secretions that can be infectious.
Residents who live near/in endemic areas should protect
themselves by being sprayed with repellents, like DEET and
permethrin (insecticide) to avoid ticks sticking to skin,
clothes and/or hair.
Doors, windows, and screens can be sprayed with more
concentrated and harsher insecticides to prevent ticks’ entry
into residential areas.
In the hospitals, nosocomial infections by CCHF often
occur as well, so CCHF patients are usually isolated.
 CCHF is highly infectious and even sometimes
surgeons who operate on CCHF patients can
become infected.
 Sharps (needles), patients' blood specimens and
body wastes should be decontaminated before
disposal and handled carefully by healthcare
workers (wearing gloves at all times and washing
hands frequently before and after contacting of
potential infectious materials (this virus can survive
in the environment and reside on fomtes).
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The virus is widespread and is capable of maintaining a very stable number in the
vectors (ticks) and reservoirs for a long period of time
Therefore, the vectors and animals can be used to cause outbreaks in humans in
targeted areas during a biological attack.
Mortality is high, so it can be used to kill large numbers
Since the animals (reservoirs) do not demonstrate apparent symptoms (but
reproductivity can be comprimised), the sign of an outbreak is difficult to identify,
so prevention is hard to take place. Once an outbreak occurs, a huge amount of
people are already infected by infected animals and ticks. It can take a long time to
stop the outbreak.
A favored characteristic of a biological weapon.
The virus caused heath damage in people and low productivity in livestocks can
lead to economic lose
To fight against CCHF in a bio-attack, ticks control is crucial (acaricides). Domestic
animals should be monitored and regularly tested and report any irregular
behaviors or sign to the authorities.
If the virus is detected, the animals should be isolated immediately from other
healthy ones to minimize the spread and possible economic lose.
Common disinfectants, formulated solutions, and dry heat (56°C for 30 min) and UV
light can all effectively kill the virus. Areas that breed animals or process animal
products should be routinely sanitized to ensure the safety and health of both
animals and humans (and prevent bio-attack).