Intracellular localization of Crimean-Congo Hemorrhagic Fever
Crimean-Congo Hemorrhagic Fever - WUR · The attack and the infection rates of Crimean Congo...
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1 Crimean-Congo Hemorrhagic Fever Onder Ergonul, MD, MPH Marmara University, School of Medicine Infectious Diseases Department Istanbul, Turkey 29 November 2008, Lelystad, Netherlands
Transcript of Crimean-Congo Hemorrhagic Fever - WUR · The attack and the infection rates of Crimean Congo...
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Crimean-Congo Hemorrhagic Fever
Onder Ergonul, MD, MPH
Marmara University, School of Medicine
Infectious Diseases DepartmentIstanbul, Turkey
29 November 2008, Lelystad, Netherlands
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Crimean-Congo Haemorrhagic Fever Geographic Distribution
Country at risk (serological evidence + vector)
Country with low risk (presence of vector)
50 to 200 cases per year
5 to 49 cases per year
50° North limit for the geographic distribution of genus Hyalomma ticks
Pierre Formenty, et al. In Ergonul & Whitehouse, CCHF, Springer, 2007
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CCHF in Europe and the neighborhood
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casesdeath
The Number of the CCHF cases in Turkey
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Incidence rate per 100 000: 2003, 2004, 2005 and 2006.
Vatansever, Z, et al. In: CCHF. Ergonul & Whitehouse, Springer, 2007
İstanbul’da Saptanan Olguların Geldikleri Yerlere Göre Dağılımı
2006 yılı, toplam 10 olgu
Midilli K, Gargılı A, Ergönül Ö, et al. BMC Infect Dis 2007
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Produced by Dr.Şebnem ErenErgonul O. Lancet ID 2006; 6: 203-214
Fig 2: Geographical correlation of genotypes (Hewson, In: Ergonul & Whitehouse)
Africa 1
Europe 1
Asia 2
Asia 1
Africa 3
Africa 2
Europe 2
S Genotypes
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Vatansever Z. In: Ergonul & Whitehouse, Crimean-Congo Hemorrhagic Fever: A Global Perspective, Springer, 2007
H. marginatum spp. (MaxEnt algorithm)
Vatansever, Z, et al. In: CCHF. Ergonul & Whitehouse, Springer, 2007
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Vatansever Z. In: Ergonul & Whitehouse, Crimean-Congo Hemorrhagic Fever: A Global Perspective, Springer, 2007
14‐26 days 4‐20 days(110‐120 days)
9‐14 days
30‐90 days
• Stable local foci in the nature• Virus is circulated between ticks and wild/domestic animals• Foci expand after ecological changes
NotificationNotification afterafter humanhuman casescases......
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The Course of Infection in animals
• No clinical symptoms– Not known in veterinary medicine
• Viremia– Lasts for 7-10 days in mammals
Seropositive and/or PCR+ Animals in Turkey
• Cattle• Sheep• Wild boars• Hares• Ground feeding birds
– Partridges etc.
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Trends of monthly mean temperature in Sivas
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Climate Change
Global warming is too global.However, the climate effects!
Agustin Estrada-Pena
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Agustin Estrada-Pena
Clinical Features
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The Suspected Case
1. Individuals, who had fever, myalgia, malaise, diarrhea, and
2. History of being in endemic area– Tick exposure history and/or– Residency or travel to CCHF endemic
region
The probable casePatients who had leukopenia, thrombocytopenia, elevated AST, ALT, and LDH levels.
Confirmed caseCCHF IgM of PCR positivity in the blood or body fluids of the patient.
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The attack and the infection rates of Crimean Congo Hemorrhagic The attack and the infection rates of Crimean Congo Hemorrhagic Fever Virus Infection in an endemic regionFever Virus Infection in an endemic regionÖnder Ergönül, Herve Zeller, Şirin Menekşe, Aysel Çelikbaş, Şebnem Eren, Nurcan Baykam, Başak Dokuzoğuz
ECCMID 2006, NiceECCMID 2006, Nice
Conclusions
One of every fıve persons living in endemic area, andone of two persons with tick bite history in endemicarea acquire the disease. The infection and attackrates are very high compared to other diseases.
55 individualsin endemic region,
30 dealing withhusbandry
19 individualswith historyof tick bite
IgG (+)8 /19 with tick bite history6 / 35 without tick bite history
6 individualswithout history of tick bite
11 patients
ResultsThe infection rate 0.27 (15/55)
The infection rate 0.42 among the individuals, who had the history of tick bite(p=0.046).
The attack rate 0.2 (11/55).
Ergonul O. Lancet ID 2006; 6: 203-214
PLTs
Incubation3-7 days
Prehemorrhagic period1-7 days
Hemorrhagic period2-3 days
Convelescence
Bleeding from various sites(hematemesis, melena, etc.)somnolence
AST
ALT
WBCs
Fatalityhappens
Polymerase Chain Reaction: The first 9 days
Myalgia, Fever,Nausea-vomitingDiarrhea
7 d 10 d
days
DIC
IgM (7 days-4 months) and IgG (7 days-5 years)
viremia
The Clinical Course of Crimean-Congo Hemorrhagic Fever
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The Predictors of FatalityViral factorsHigh viral loadshown by recent studies for many VHFs
Cevik, et al. CID 2007
Host factorsCytokines: TNF alfa, IL1, IL6
Ergonul, et al. JID 2006
Why The Case Fatality Rates Are Different?
1) Different strains 2) Co-existent infections3) Host factors2) Health care facility
• Access• Quality
3) Public awareness
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Pathogenesis
• Capillary fragility– “capillary toxicosis”, Soviet scientists– Infection of endothelium
• Coagulopathy• Multiple host induced mechanisms
– Massive apoptosis of lymhocytes– Induction of proinflammatory cytokines– Dysregulation of coagulation cascade– DIC
Geisbert TW, Nature Med 2004 10: 110-121
Geisbert TW, Nature Med 2004
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J Infect Dis 2006; 193: 941-4
3/4 (50)19/40 (48)PCR positivity
0/4 (0)27/40 (68)IgG positivity
¼ (25) 37/40 (93)IgM positives
Patients diedn=4
Patients survivedn=50
Antibody production is weaker among fatal cases
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Bone marrow aspiration smear, stained with Wright, showing hemophagocytosis
A) phagocytosis of an erythrocyte and nuclear remnants by a macrophage.
B) phagocytosis of platelets by a macrophage.
Karti SS, et al. Emerg Infect Dis 2004
Am J Hematol 2007
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CCHFRift ValleyHanta
BunyaviridaeSouth America HFLassa Fever
Arenaviridae
Ribavirin: Only Drug for VHFs
PLTs
Incubation3-7 days
Prehemorrhagic period1-7 days
Hemorrhagicperiod
2-3 days
Convelescence
AST and ALT
Fatality
7 d 10 d days
DisseminatedIntravascularCoagulationviremia
EARLYPHASE
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Therapeutic options in disease course: Ribavirin could be more effective in early phase
CYTOKINES
Ergonul O. Treatment of CCHF, Antivir Res 2008
The Role of Ribavirin in CCHF
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Confounders in Ribavirin use
1. Severity 2. Number of Days from onset of symptoms
1. Prehemorhagic2. Hemorhagic
3. Ineffective application: GIS symptoms in oral use (hematemesis)
4. Duration of treatment5. Inclusion criteria
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Health Care Workers infected by CCHF
182008112006-32005
552003Moritania
122002
012002Albania
17421950-1974Bulgaria
?31994
171984
11 (?)2003Turkey
3288TOTAL
241976Pakistan
251979 United Arabic
Emirates
221979Iraq
?51967South Africa
fatalinfectedYearCountry
Case Management
Suspected case Clinical symptomsHistoryBiochemical tests
Preventive measures Isolation of the patientEducation of the HCWsUse or barrier precautions
Confirmation of dgx PCRELISA
Decision for tx Definition of severity criteria and ribavirin useDifferential diagnosis and doxycyclineHematologic supportRespiration support
Follow-up No recurrenceHCWs
Ergönül O. Lancet Infect Dis 2006
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Vatansever Z, In: Ergonul & Whitehouse, Crimean-Congo Hemorrhagic Fever: A Global Perspective, Springer, 2007
Tick removal: What is the best way?
Vaccination experience is limited to BulgariaEfficacy: We need more clarity
Dr. Nikolai Kalvatchev
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Bulgarian ExperiencePassive simultaneous transfer of two different specific immunoglobulin preparations,
“CCHF-bulin” (for intramuscular use) “CCHF-venin” (for intravenous use),
prepared from the plasma of CCHF survivor donors (Vassilenko et al., 1990).
Only 7 patients
Turkish Experience on CCHF1. Acceleration phase of the epidemic curve:
Every year, more cases than a year ago.2. Dissemination of the cases to the west.3. More HCWs have been effected.
1. Protection of HCWs2. Infection Control in Hospitals
4. Debate on ribavirin use: RCT?5. Personal protection
1. How to remove ticks?2. Repellents, permethrine
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“I was tired, and what was the use? I musthave examined the stomachs of a thousandmosquitoes by this time. But the Angel of Fate fortunately laid his hand on my head”
Sir Ronald Ross, 1857-1932
How long should we wait?
Thank you
