3. Introduction
• CCHF → caused by infection with→ tick borne virus nairovirus
• Belongs to family Bunyaviridae
• Disease→ characterized in Crimean in 1944 thus given the name
Crimean hemorrhagic fever
• Later recognized in 1969→cause of illness in Congo
• Thus resulting in the current name of the disease
• Disease found in different areas of the globe like Eastern Europe,
throughout the Mediterranean, in northwestern China, central Asia,
southern Europe, Africa, the Middle East, and the Indian subcontinent
4.
5. Transmission
• Ixodid ticks from genus→Hyalomma
• Are both considered as vector and reservoir for CCHF virus
• Wild and domestic animals like cattle, goats, sheep and hares
• Acts as amplifying hosts for the virus
• Transmission to humans occurs through the contact with infected animal
or ticks
• While it is transmitted to other human is by contact through infected
blood or body fluids
• Also occurred in hospitals due to improper sterilization of medical
equipment, reuse of injection needles, and contamination of medical
supplies.
6.
7. Genome Structure
• Has 3 –ive strands of RNA
• It includes the S, M , and L segments
• S segment codes for a nucleoprotein
• M segment codes for a glycoprotein precursor
• L segment codes for RNA polymerase
12. Immune Response
• Replicating CCHFV delays substantially the IFN response, possibly by
interfering with the activation pathway of IRF-3
• CCHFV can impair innate immune system
• Causes a delay in adaptive immune response, which is critical for
clearance of CCHFV
13. Partial Activation of Macrophages and DC,s
• Macrophages and DC,s plays imp role at very early stage of infection
• Influential role in the initiation and control of adaptive immune system
by releasing proinflammatory cytokines and chemokines
• However in vivo and invitro studies shows that these cells gains the
partial ability to mature to act as APC,s
• This results in the lack of upregulation of MHC II complex
14. Delayed Induction of INF,s
• CCHF→one of the IFN sensitive virus
• However CCHF delays the production→ IFN,s preventing the antiviral
effect
• In a recent study it was shown that administration of IFN before the
infection significantly decreases the virus titers
• But after infection it showed no decrease in virus titers
• So IFN,s are inefficient in controlling viral replication in the infected cell
• MxA protein also plays significant role by inhibition of viral replication
• So it is suggested that the MxA protein may be induced insufficiently or
too late to prevent the progression of the disease in CCHF infected
patients.
15. Depletion in NK cells and Lymphocytes
• Part of innate immune response against viruses
• Helps in detection and lysis of infected cells
• NK, B and T cells increase in numbers on the initial time of infection
• But decreased significantly on the third day regardless of the activation
• Increase in production is due to early cytokine production
• Later uncontrolled apoptosis of lymphocytes results in lymphocyte
depletion
• Therefore disruption of both innate and adaptive immune response
happens
• Lead towards the inability in controlling virus replication
16. Treatment
• Primarily supportive
• Careful attention to fluid balance and correction of electrolyte
abnormalities, oxygenation and hemodynamic support, as well as
appropriate treatment of secondary infections
• Ribavirin is somewhat provides treatment against virus
17. Vaccine
• Since 1970s several trials have been terminated due to high toxicity
• Somewhat efficacious CCHF vaccine is an inactivated antigen
preparation
• Currently used in Bulgaria
• Alternatively, many scientists appear to believe that treatment of CCHF
with ribavirin is more practical than prevention
• In 2011, a Turkish research team led by Erciyes University successfully
developed the first non-toxic preventive vaccine
• Passed the clinical trials.
• This vaccine is pending approval by the US FDA
