Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne viral disease characterized by fever and hemorrhage. It is caused by the CCHF virus and transmitted primarily through ticks of the genus Hyalomma. The virus infects a range of animals and is found across parts of Africa, Asia, and Europe. Most human cases result from tick bites, with 10,000 cases reported annually. While many infections are mild, the disease can progress to include hemorrhage, organ failure, and death in around 30% of cases. Treatment focuses on supportive care, while ribavirin's efficacy is uncertain.

1. Crimean-Congo
Hemorrhagic Fever
Gaby Falakha, MD
Pediatrician & Neonatologist

2. INTRODUCTION
 Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease
transmitted by ticks and characterized by fever and hemorrhage.
 It was first described in Soviet soldiers in the Crimea in 1944 and was
named Crimean fever.
 In 1956, the virus was isolated from a child in Congo, with similar
symptoms and was named Congo virus.
 The causative agent of both illnesses was shown to be the same virus,
which was subsequently termed CCHF virus.
 CCHF infects a range of animals
 Humans are the only known host that develops disease.

3. Hemorrhagic fever viruses
Family Disease Vector Geographic Distribution
Filoviridae Ebola Unknown Africa
Filoviridae Marburg Unknown Africa
Arenaviridae Lassa Rodent West Africa
Arenaviridae New World Arenaviridae Rodent Americas
Bunyaviridae CCHF Tick Africa, Central Asia, Eastern
Europe, Middle east
Bunyaviridae Rift valley fever Mosquito Africa, Saudi Arabia, Yemen
Bunyaviridae Hemorrhagic fever with
renal syndrome
Rodent Asia, Balkans, Europe, Eurasia
Flaviviridae Dengue Mosquito Africa, Asia, Pacific America
Flaviviridae Yellow Fever Mosquito Africa, Tropical Americas
Flaviviridae Omsk Tick Central Asia
Flaviviridae Kyasanur Tick India

4. Hemorrhagic fever viruses
Family Disease Vector Geographic Distribution
Filoviridae Ebola Unknown Africa
Filoviridae Marburg Unknown Africa
Arenaviridae Lassa Rodent West Africa
Arenaviridae New World Arenaviridae Rodent Americas
Bunyaviridae CCHF Tick Africa, Central Asia, Eastern
Europe, Middle east
Bunyaviridae Rift valley fever Mosquito Africa, Saudi Arabia, Yemen
Bunyaviridae Hemorrhagic fever with
renal syndrome
Rodent Asia, Balkans, Europe, Eurasia
Flaviviridae Dengue Mosquito Africa, Asia, Pacific America
Flaviviridae Yellow Fever Mosquito Africa, Tropical Americas
Flaviviridae Omsk Tick Central Asia
Flaviviridae Kyasanur Tick India

5. EPIDEMIOLOGY
 Each year, more than
10,000 human cases are
reported from southeastern
Europe and western Asia.
 Estimated 500 deaths/year
 The primary means of
transmission to humans is
tick bites.

6. Geography and season
 CCHF is endemic in parts of Africa, the Middle East, Asia, and southeastern Europe.
 CCHF virus (CCHFV) has been observed in over 30 countries, including in Africa (Democratic
Republic of Congo, South Africa, Nigeria, Senegal, Uganda, Tanzania, Mauritania, Kenya), Asia
(Pakistan, Afghanistan, Tajikistan, Uzbekistan, Kazakhstan, China), the Middle East (Iran, Iraq,
United Arab Emirates, Saudi Arabia, Oman), and southeastern Europe (the Russian Federation,
Bulgaria, Albania, Kosovo, Turkey, Greece, and Spain)
 Emergence of CCHF in India was reported in 2011, and CCHF in Spain was first reported in
2016.
 In the Northern Hemisphere, transmission of CCHFV is common between May and September,
with a peak incidence in June and July. In Pakistan, CCHF has biannual peaks between March
and May and between August and October.
 In Turkey, there is peak transmission in early summer months and a strong association with
living at altitude greater than 836.5 m.

7. VIROLOGY
 CCHF virus (CCHFV) is a member of the Nairovirus genus within the
family Bunyaviridae, which contains negative-stranded,
enveloped RNA viruses.
 The genome of CCHFV has three segments, which are small (S),
medium (M), and large (L).
 Based on the CCHFV S-segment sequences, CCHFV strains have seven
clades in different geographical locations. Balkan strains are closely
related to Turkish and southwestern Russian strains.
 Cross-border movements of livestock may have contributed to the
insertion of new clades into countries and spread of the disease.
 Wild birds have also been shown to have the capacity to carry ticks
containing CCHFV to different geographic areas.

9. Ticks
 CCHFV is primarily transmitted via hard-bodied Hyalomma
ticks of the family Ixodes, particularly Hyalomma
marginatum.
 The geography of CCHF infection reflects the distribution
of Hyalomma ticks, which have a northern geographic limit
of 48° north latitude.
 CCHFV has also been isolated from Rhipicephalus,
Boophilus, and Dermacentor spp, which may also transmit
the virus.
 The most common viral reservoirs are domestic livestock
(sheep, goat, cow, and pig), which are infected by adult
ticks.

10. Ticks
 Larvae and nymphs tend to feed on rodents, hares,
hedgehogs, and ground-dwelling birds, which serve as
amplifying hosts for the virus.
 Hyalomma ticks have a two-year life cycle, and blood meals
are required for development at each life cycle stage.
 Ticks can remain attached for 2 to 13 days; after completion
of feeding, the ticks detach from the host and begin to search
for new hosts.
 The virus begins to multiply within 36 hours of attachment
 It does not have the ability to survive outside the host but
may persist in infected body fluids such as blood, stool, or
vomit.

11. Four Life Stages
1. Egg
2. Larva
3. Nymph
4. Adult
• Eggs are laid in spring and hatch as larvae 2-4
weeks later
• Larvae feed on mice, birds and other small
animals
• Nymph feed on small animals in the spring
and summer
• Adults feed on large animals
• In spring adult female lay their eggs
Ticks must take a blood meal in order to molt to
the next life stage
1
2
3
4

13. Four Life Stages
1. Egg
2. Larva
3. Nymph
4. Adult
• Ticks can become infected at any life-
cycle stage during feeding on a
viremic animal or during co-feeding
with an infected tick, and mammals
likely act as important amplification
hosts for the virus.
Ticks can transmit disease during
the three last life-cycle stages.

14. Ticks
 Ticks survive most readily in relatively warm, dry habitats.
 Tick density increases markedly following a preceding mild winter and in the setting of
diminished rainfall; these conditions are associated with increased numbers of human
CCHF cases.
 Environmental factors associated with CCHF infection include livestock grazing at the edge
of forests and presence of scrub and herbaceous vegetation

16. Transmission
 CCHF is transmitted via ticks, direct contact with blood or other bodily fluids of infected
animals, nosocomial transmission, and vertical transmission.
 CCHF is most commonly transmitted via tick bites or crushing ticks with bare fingers.
 Ticks can attach to all sites of the human body
 Transmission can also occur via direct contact with blood or other bodily fluids of livestock
 In a large epidemiologic study including more than 1800 cases of CCHF:
1. 69 % of patients reported a history of tick bite or tick contact
2. 62 % reported close contact with animals
3. 10 % had history of direct contact with animal body fluids or tissue
 The risk of community-based transmission to close contacts and relatives of patients with
CCHF is low.

17. Transmission
 Nosocomial transmission of CCHFV has been described.
 The risk is highest during later stages of disease, which are associated with higher viral
loads as well as diarrhea, vomiting, and hemorrhage.
 Direct contact with blood and body fluids, needle-stick injuries, and splash exposures are
common causes of nosocomial transmission.
 Health care personnel are also at risk of infection during aerosol-generating procedures.
 Mother-to-child (vertical) transmission of CCHFV has been described; in such cases, fetal
prognosis may be guarded. Thus far, breastfeeding has not been associated with CCHFV
transmission. The role of sexual transmission is uncertain
 The risk of laboratory exposure to CCHFV while processing blood samples is low if routine
laboratory procedures are followed

18. Risk groups
 Individuals at risk for CCHFV infection include agricultural workers, individuals in rural
areas engaged in animal husbandry, abattoir workers, veterinarians, leather factory
workers in areas with high tick density, campers and hikers, hunters, soldiers, health care
workers, and travelers to endemic areas
 In high-risk populations, the sero-prevalence of CCHFV infection is 10 to 14 percent.
 Data are insufficient regarding the risk of CCHFV infection in immunocompromised hosts.

19. Risk groups
 Individuals at risk for CCHFV infection include agricultural workers, individuals in rural
areas engaged in animal husbandry, abattoir workers, veterinarians, leather factory
workers in areas with high tick density, campers and hikers, hunters, soldiers, health care
workers, and travelers to endemic areas
 In high-risk populations, the sero-prevalence of CCHFV infection is 10 to 14 percent.
 Data are insufficient regarding the risk of CCHFV infection in immunocompromised hosts.

20. CLINICAL MANIFESTATIONS
 The spectrum of clinical manifestations ranges from subclinical illness (88%) to acute
infection with hemorrhage and multi-organ failure.
 The incubation period ranges from 1 to 13 days; it correlates with viral load and the type
of transmission.
 The incubation period following tick bite is typically one to three days
 The incubation period following contact with blood and body fluids is typically three to
seven days.
 Relatively short incubation periods have been described in cases due to nosocomial
infection during later stages of disease, which are associated with high viral loads as well
as diarrhea, vomiting, and hemorrhage.

21. CLINICAL MANIFESTATIONS
 Clinical manifestations of CCHF include sudden onset of
fever, headache, malaise, myalgia, sore throat, dizziness,
conjunctivitis, photophobia, abdominal pain, nausea, and
vomiting.
 Rales are generally associated with pulmonary hemorrhage.
 Ocular findings include sub-conjunctival and retinal
hemorrhage, which may occur in the absence of visual
complaints.
 Other clinical findings include tachycardia, hepatomegaly,
lymphadenopathy, and confusion.
One case series including more than 1600
patients with CCHF
Fatigue 92%
Fever 89%
Myalgia 70%
Headache 68%
Nausea 65%
Vomiting 43%
Diarrhea 25%
Hemorrhage 23%

22. Hemorrhagic phase
 Petechial rash
 Ecchymosis and large bruises
 Hematemesis
 Melena
 Epistaxis
 Hematuria
 Hemoptysis
 Bleeding from other sites

24. DIFFERENTIAL DIAGNOSIS
1. Other viral hemorrhagic fevers: Dengue, Ebola, Marburg, Lassa, and yellow fever.
2. Malaria
3. Rickettsia infection
4. Q fever
5. Brucellosis
6. Leptospirosis
7. Viral hepatitis
8. Meningococcemia
In addition, noninfectious entities in the differential diagnosis include:
1. Idiopathic thrombocytopenic purpura (ITP)
2. Acute leukemia

25. TREATMENT
 There is no proven antiviral treatment for CCHF infection.
 Ribavirin has been studied in vitro, in animal models, and in some patients; it has not
been shown to reduce viral load or mortality in humans, and its clinical efficacy is
controversial.
 Management of CCHF consists of supportive care; in severe cases, blood product
replacement is warranted.
 Patients with CCHF should be managed in a health care center with appropriate facilities
for diagnosis, treatment, and prevention of disease, including isolation precautions.
 Data are insufficient to support routine use of steroids, intravenous immunoglobulin, or
plasma exchange.
 Use of hyper-immunoglobulin (prepared from the plasma of donors with antibody
against CCHF) requires further study.

26. Evaluation of antiviral efficacy of
Ribavirin, Arbidol, and Favipiravir (T-705) in a mouse model for
Crimean-Congo hemorrhagic fever
 Favipiravir is approved in Japan for the treatment of influenza virus infections but has
shown promise against other highly pathogenic RNA viruses, including Ebola and Lassa.
 Two studies have evaluated Favipiravir against CCHF in vivo.
 In a study by Oestereich et al., Favipiravir treatment was effective in suppressing viral
replication and preventing mortality following CCHF infection, even when treatment was
started after 48 hours
 Favipiravir and Ribavirin could synergistically inhibit CCHF in vitro, allowing lower doses of
both drugs to be used in vivo with clinical efficacy, suggesting that combination therapies in
humans may be effective in treating CCHF while reducing unwanted side effects
Oestereich L, Rieger T, Neumann M, et al.:. PLoS Negl Trop Dis. 2014; 8(5): e2804.

27. The host inflammatory response contributes to disease severity in
Crimean-Congo hemorrhagic fever virus infected mice
 In cell culture, CCHFV is sensed by the cytoplasmic RNA sensor retinoic acid-inducible gene I (RIG-I)
molecule and its adaptor molecule mitochondrial antiviral signaling (MAVS) protein.
 MAVS initiates both type I interferon (IFN-I) and pro-inflammatory responses.
 MAVS-deficient mice were not susceptible to CCHFV infection when IFN-I signaling was active and
showed no signs of disease.
 When IFN-I signaling was blocked by antibody, MAVS-deficient mice lost significant weight, but were
uniformly protected from lethal disease, whereas all control mice succumbed to infection.
 Treatment of mice with an anti-TNF-α neutralizing antibody also conferred partial protection in a
post-virus exposure setting.
May 19, 2022 https://doi.org/10.1371/journal.ppat.1010485

28. Convalescent phase
 10-20 days after illness onset
 Generalized weakness
 Tachycardia
 Other nonspecific symptoms
 Recovery usually complete but slow, may take up to one year

29. PROGNOSIS
 The mortality rate varies among countries and ranges from 2 to 80 percent.
 Mortality rates in endemic countries are approximately 4 to 20 percent.
 CCHF is a notifiable disease in Turkey and Iran, and both countries have active
surveillance and detection systems.
 Between 2002 and 2015, 9787 cases were reported to the Ministry of Health in Turkey,
with a mortality rate of 4.8 percent.

30. PROGNOSIS
 Hemorrhage (particularly
gastrointestinal bleeding and hematuria)
 Impaired consciousness
 Central nervous system involvement
 Diarrhea
 Splenomegaly
 Thrombocytopenia, leukocytosis
 Increased SGPT and SGOT
 Decreased fibrinogen levels with a
prolonged activated partial
thromboplastin time.
 In addition, CCHFV RNA level >107
copies/mL is an important indicator for
mortality (positive predictive value 80
percent, sensitivity 89 percent,
specificity 93 percent)
Independent predictors of mortality include:

31. Environmental cleaning
 CCHF virus can be inactivated by disinfectants including:
 1% sodium hypochlorite (household bleach)
 70% alcohol
 2% glutaraldehyde
 Hydrogen peroxide
 Per-acetic acid
 The virus is susceptible to high temperature at 56°C (133°F) for 30 minutes or 60°C (140°F)
for 15 minutes.
 Areas contaminated with CCHFV can be disinfected with an approved hospital disinfectant
or bleach.
 Housekeeping staff should use personal protective equipment when cleaning.

32. 1. Avoid tick-infested areas.
2. Wear light colored clothing for easy finding of ticks on clothes.
3. Wear protective clothing (long sleeves, long pants).
4. Tuck your pant legs into your socks so that ticks cannot crawl
up inside of your pant legs.
5. Use chemical repellent with DEET (on skin) and acaricides (tick
killer) on boots and clothing.
1
2
3
4
5
Reducing risk of tick-to-human transmission
Food safety
Do not consume unpasteurized milk
Virus usually inactivated in meat by post-slaughter acidification
Virus also killed by cooking

33. • Use fine-tipped tweezers (or a thread).
• Grab the tick as close as possible to the skin. DO NOT twist
or jerk the tick.
• Gently pull straight up until all parts of the tick are
removed.
• Wash hands with soap and water.
• Apply antiseptic on tick bite or clean with soap and water.
• NEVER crush a tick with your fingers.
Safe Removal of Ticks

34. CCHF in Iraq
 CCHF is endemic in Iraq with
recurrent outbreaks since it was
first reported in 1978.
 Since week 19 2021, 45 suspected
cases and 9 associated deaths were
reported among which 7 cases and
5 deaths were laboratory
confirmed.
 The 2021 cases peaked in week 27
(4 cases) and 38 (4 cases)
Weekly Epidemiologic Monitor; Volume 14; Issue no 49; 05 December 2021

35. CCHF in Iraq
 Most of the current cases have been reported
from Thi Qar (10 cases), Ninewa (2 cases), Erbil (3
cases), Baghdad (3 cases), Bable (2 cases), Diyala
(1 case) and Al Anbar (1 case).
 More males than females have been affected at a
ratio of 1.2 : 1.
 No cases have been detected amongst health care
workers
 CCHF is endemic in Iraq with recurrent outbreaks
since it was first reported in 1978.
Age (years) Distribution of CCHF
cases in 2021
9-15 4
16-25 13
26-45 13
46-65 8
>65 6
Weekly Epidemiologic Monitor; Volume 14; Issue no 49; 05 December 2021

37. Crimean-Congo fever kills eight people in Iraq so far
By Al Mayadeen English. May 9th, 2022
• Eight people have died so far this year in Iraq after an unusually
high number of cases of Crimean-Congo hemorrhagic fever
• At least 40 cases of the disease were detected in different parts of
the country this year
• Iraq normally records up to 20 cases a year, which result in one or
two deaths.
• 23 of the cases, five of which resulted in death, were recorded in
the southern Iraqi Province of Thi Qar.
• Half of the infected have recovered.
Workers in Iraq spraying cattle with a
disinfectant in order to stop the disease from
spreading (The National)

38. Iraq: 1st Crimean-Congo hemorrhagic fever case reported
in Erbil
 To date, Iraq has seen 56 CCHF cases through May 10.
 The Director General of Erbil Health, Dlovan Muhammad Saleh, said: “the first case of
hemorrhagic fever was recorded in Erbil.” He added, “A 17-year-old is infected, and he is
now under medical care.”
 Twelve people have died so far this year in Iraq from Crimean-Congo hemorrhagic fever
and another 56 people are infected
Newsdesk May 11th, 2022

39. Take home message
 Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease transmitted by ticks and
characterized by fever and hemorrhage.
 CCHFV is most commonly transmitted via ticks or direct contact with bodily fluids of infected
animals; nosocomial transmission can also occur.
 Clinical manifestations of CCHF include sudden onset of fever, headache, malaise, myalgia, sore
throat, dizziness, conjunctivitis, photophobia, abdominal pain, nausea, and vomiting. In severe
cases, hemorrhagic manifestations may follow.
 The diagnosis of CCHF should be suspected in patients presenting with fever and bleeding who have
relevant geographic and epidemiologic risk factors. Diagnostic tools include PCR and serology.
 Management of CCHF consists of supportive care
 Patients with CCHF should be managed in a health care center with appropriate facilities for
management and prevention of infection.
 Prevention of CCHF consists of avoiding tick exposure and avoiding contact with animal bodily fluids.