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
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, especiallythose of the genus, Hyalomma,are both a reservoir and a vectorfor the CCHF virus. Numerouswild and domestic animals, suchas cattle, goats, sheep and hares,serve as amplifying hosts for thevirus. Transmission to humansoccurs through contact withinfected 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, myalgias, 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.
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