01Approach to the Critical Patient/attcp67

Immediate isolation and infection control

›Isolation priority

›Single-patient room with closed door on arrival for any suspected CCHF case

›Contact and droplet precautions minimum

›Airborne infection isolation room if aerosol-generating procedures anticipated

›PPE requirement for stable suspected case

›Fluid-resistant gown

›Face shield and surgical mask

›Double gloves

›PPE requirement for confirmed or unstable case with active bleeding or vomiting

›Impermeable gown and apron

›PAPR or N95 respirator

›Double gloves and boot covers

Hemorrhagic shock and resuscitation

›Hemodynamic threats

›Active hemorrhage with hemodynamic compromise

›SBP < 90 mmHg

›MAP < 65 mmHg

›Shock physiology

›Tachycardia

›Altered mental status from hypoperfusion

›Avoid IM injections and invasive procedures

›Minimise line insertions to essential access only

›Pressure dressings over venipuncture sites

›Resuscitation targets

›IV crystalloid resuscitation first-line

›Normal saline or Ringer's lactate

›Titrate to MAP >= 65 mmHg

02History/hx66

Exposure history

›Tick exposure

›Tick bite from Hyalomma species

›Incubation period 1 to 14 days after tick bite, typically 3 to 7 days

›Identified in 68% of confirmed cases

›Tick crushing with bare hands during manual removal

›Contact with tick haemolymph

›Rural residence in 87% of cases in large Turkish cohort

›Outdoor activities in endemic areas

›Hiking, camping, picnicking in spring and summer

›Peak tick activity April through October

›Animal and occupational exposure

›Livestock contact

›Farmers, herders, and veterinarians highest risk

›Slaughterhouse workers with blood or tissue contact of viraemic animals

›Healthcare occupational exposure

›Contact with blood or body fluids of infected patient

›Nosocomial transmission well documented

›Blood or body fluid splash OR 4.2 for healthcare worker infection

›Funeral exposure

›Contact with deceased CCHF patient

›Cultural funeral practices in endemic regions

›Travel history

›Travel to or residence in endemic regions

›Turkey, Iran, Pakistan, Afghanistan

›Balkans, Central Asia, Africa

›Spain as emerging European endemic area

03Physical Exam/exam62

Vital signs and general

›Vital sign pattern

›High fever

›39 to 41 degrees Celsius during prehemorrhagic and hemorrhagic phases

›Hypothermia may signal terminal deterioration

›Heart rate

›Tachycardia common in active disease

›Resting HR > 96 bpm independent risk factor for severe disease in children

›Bradycardia during convalescence or ribavirin-associated

›Blood pressure

›Hypotension sign of haemorrhagic shock

›SBP < 90 mmHg as escalation trigger

›Oxygen saturation

›Reduced with pulmonary haemorrhage or effusion

›Baseline room air value essential

Skin and mucous membrane findings

›Haemorrhagic skin signs

›Petechiae

›Early hemorrhagic phase finding

›Dependent and pressure areas initially

›Ecchymoses

›Progression from petechiae

›Injection site and trauma sites

›Large hematomas

›Spontaneous or at venipuncture sites

›Sign of severe coagulopathy

›Facial and mucosal signs

›Facial flushing and hyperemia

04Differential Diagnosis/ddx62

Life-threatening viral hemorrhagic fevers

›Other viral hemorrhagic fevers

›Ebola virus disease

›Sub-Saharan African exposure

›ICD-10 A98.3

›Human-to-human transmission dominant

›Marburg virus disease

›Central and East African exposure

›ICD-10 A98.3

›High case fatality rate comparable to CCHF

›Lassa fever

›West African exposure

›ICD-10 A96.2

›Rodent contact rather than tick exposure

›Rift Valley fever

›African and Arabian Peninsula exposure

›Mosquito vector rather than tick

›Hantavirus infection

›Hemorrhagic fever with renal syndrome

›Rodent contact via aerosolised excreta

›Prominent renal failure early

Non-viral differentials

›Bacterial causes

›Meningococcemia

›ICD-10 A39.2

›Purpura fulminans pattern

›No tick exposure

›Leptospirosis

05Laboratory Tests/lt70

Core hematologic labs

›Complete blood count

›Thrombocytopenia

›Hallmark finding of CCHF

›Platelet cutoff < 21.5 x 10 to the power 9 per litre has 82% sensitivity and specificity for confirmed CCHF

›Monitor 1 to 2 times daily for nadir

›Leucopenia

›Common in early disease

›Lymphocyte count < 1.19 x 10 to the power 9 per litre is early marker with AUC 0.976

›Lymphopenia as early indicator

›Identified before other haematologic changes

›High diagnostic value in ED presentation

›Coagulation panel

›DIC screen

›Prolonged PT and aPTT

›Elevated D-dimer

›Low fibrinogen

›Fibrinogen level

›Component of SSI severity score

›Hypofibrinogenemia in HLH complication

Metabolic and organ function

›Hepatic panel

›Transaminases

›AST disproportionately elevated relative to ALT

›Elevation correlates with disease severity

›Component of SSI scoring

›LDH and CK

›Elevated early in disease

06Diagnostic Tests/dt94

Scoring Systems

›SSI severity scoring index

›Components of SSI score

›Platelet count threshold

›Active bleeding presence

›Fibrinogen level

›aPTT prolongation

›Somnolence

›Clinical utility

›Developed specifically for CCHF severity stratification

›Higher scores correlate with mortality and need for ICU

›Guides ribavirin and corticosteroid use decisions

›Swanepoel criteria for severe disease

›Severity markers

›Platelet count < 20 x 10 to the power 9 per litre

›WBC > 10 x 10 to the power 9 per litre

›AST or ALT > 200 IU/L

›PT or aPTT > 60 seconds

›Fibrinogen < 1 g/L

›Predictive value

›Presence of 5 or more criteria predicts fatal outcome

›Used to stratify aggressive vs conservative management

›Viral load as prognostic marker

›High viral load

›Associated with severe and fatal disease

›Quantitative RT-PCR used in reference centres

›Not widely available for bedside decision-making

MRI

›MRI head indications

›Altered mental status with negative CT

›Cerebral vasculitis or encephalitis evaluation

›Microbleeds not detectable on CT

›Suspected CCHF encephalitis

›T2 FLAIR hyperintensities in some cases

›DWI sequences for restricted diffusion

›Practical limitations

›Unstable patient is absolute contraindication

›Availability in endemic regions often limited

›MRI cardiac indications

›Suspected myocarditis

›Gadolinium late enhancement pattern

›Elevated troponin with wall motion abnormalities

›Not first-line in acute hemorrhagic phase

CT

›CT head

›Indications

›Altered mental status or neurologic deterioration

›Suspected cerebral haemorrhage

›Headache with focal deficits

›Findings in CCHF

›Intracerebral haemorrhage

›Subarachnoid blood

›Cerebral oedema in severe cases

›CT abdomen and pelvis

›Indications

›Intra-abdominal haemorrhage assessment

›Hepatosplenomegaly quantification

›Suspected portal vein thrombosis

›Contrast considerations

›IV contrast when renal function permits

›Non-contrast acceptable for haemorrhage detection

›CT chest

›Indications

›Haemoptysis with respiratory compromise

›Pleural effusion characterisation

›Pulmonary haemorrhage extent

›Findings

›Ground glass opacities from pulmonary haemorrhage

›Pleural effusion

›Pulmonary oedema pattern

Ultrasound

›Abdominal ultrasound

›Hepatosplenomegaly assessment

›Hepatomegaly in 20 to 40% of cases

›Splenomegaly in 14 to 23% of cases

›Serial measurements for progression

›Free fluid detection

›Intraperitoneal haemorrhage

›Ascites in hepatic failure

›Portal vein assessment

›Portal vein thrombosis as rare but documented complication

›Doppler flow assessment

›Cardiac POCUS

›Echocardiographic findings

›Reduced LVEF more common in fatal cases

›Pericardial effusion

›Segmental wall motion abnormalities

›Indications for formal echo

›Troponin elevation

›Persistent tachycardia or arrhythmia

›Haemodynamic instability unexplained by haemorrhage

›Pleural assessment

›Pleural effusion identification

›More sensitive than CXR for small effusions

›Bilateral or unilateral assessment

›Procedural guidance

›Ultrasound-guided thoracentesis when drainage required

›Reduces complication risk in coagulopathic patient

07Disposition/dispo42

Admission and isolation requirements

›All confirmed or suspected CCHF cases require hospital admission

›No outpatient management for confirmed or high-suspicion cases

›Rapid platelet decline can be fatal within hours

›Isolation facility required

›Notification requirements at time of admission

›Public health authority immediate notification

›Contact tracing initiation

›ICU admission indications

›Active haemorrhage

›Requiring ongoing blood product transfusion

›Haemodynamic instability

›DIC with multiorgan failure

›Hepatorenal insufficiency

›Thrombocytopenia with CNS haemorrhage

›Altered mental status

›Somnolence or coma

›Seizures

›ICU required in approximately 8% of cases in large cohort

Contact tracing and post-exposure prophylaxis

›Contact identification

›Healthcare contacts

›All staff who cared for patient before isolation

›Monitor for 14 days after last exposure

›Household contacts

›Family members with potential body fluid exposure

›Funeral attendees with body contact

›Post-exposure prophylaxis

08Treatment/t93

Supportive care

›Fluid and electrolyte management

›IV crystalloid resuscitation

›Normal saline first-line

›Ringer's lactate acceptable alternative

›Titrate to haemodynamic targets

›Fluid and electrolyte monitoring

›Daily electrolytes including potassium

›Input and output balance

›Avoid fluid overload with myocarditis risk

›Blood product replacement

›Platelet transfusion

›For severe thrombocytopenia with active bleeding

›Threshold guided by clinical bleeding not count alone

›Platelet < 20 x 10 to the power 9 per litre with haemorrhage

›Packed red blood cells

›Active haemorrhage with haemodynamic compromise

›Haemoglobin threshold individualised by clinical state

›Fresh frozen plasma

›DIC with prolonged coagulation times and bleeding

›10 to 15 mL per kg

›Cryoprecipitate

›Fibrinogen < 1.5 g/L with bleeding

›Preferred over FFP for fibrinogen replacement

›GI and ulcer prophylaxis

›H2 blockers for peptic ulcer prophylaxis

›Ranitidine 150 mg orally twice daily or IV equivalent

›Reduces GI haemorrhage risk during hemorrhagic phase

›Proton pump inhibitor alternative

›Omeprazole 40 mg IV or orally daily

›For high-risk GI bleed patients

Antiviral therapy

›Ribavirin

›Dosing protocol

›Loading dose 30 mg/kg IV or orally once

›Days 1 to 4: 15 mg/kg every 6 hours

›Days 5 to 10: 7.5 mg/kg every 8 hours

›Efficacy evidence

›Meta-analysis showed 1.7-fold reduction in mortality

›2018 Cochrane review found insufficient reliable evidence for certainty

›Most effective when started within 96 hours of symptom onset

›Monitoring during ribavirin

›Haemolytic anaemia: weekly CBC

›Arrhythmia risk: continuous cardiac monitoring

›Liver function tests

›Bone marrow suppression monitoring

›Dose adjustment

›Reduce with renal impairment

›Creatinine clearance guides dosing

›Contraindications and cautions

›Pregnancy: teratogenic risk, balance against high maternal mortality

›Haemolytic anaemia risk requiring monitoring

›Drugs to avoid

›Aspirin and NSAIDs

›Worsen platelet dysfunction

›Increase GI haemorrhage risk

›Anticoagulants

›Avoid unless specific indication such as portal vein thrombosis

›Risk of fatal haemorrhage

›Intramuscular injections

›Risk of haematoma at injection site

›Use IV or oral routes only

Adjunctive therapy

›Corticosteroids

›Indication

›Severe or haemorrhagic cases

›Suspected HLH complication

›Evidence

›Approximately 2.3-fold mortality reduction when combined with ribavirin

›Class IIb recommendation based on observational data

›Dosing

›Prednisolone 1 to 2 mg/kg orally daily or

›Methylprednisolone 1 mg/kg IV daily

›Duration guided by clinical response

›Intravenous immunoglobulin

›Role

›Experimental indication

›Some evidence of benefit in case series

›Not standard of care

›Convalescent plasma

›Passive immunotherapy approach

›Limited availability in non-endemic settings

›Case reports of benefit in severe disease

Infection control interventions

›Environmental decontamination

›Dedicated patient equipment

›Single-patient use where possible

›Sodium hypochlorite disinfection of surfaces

›Autoclaving of reusable items

›Linen and waste management

›Double-bagged biohazard disposal

›High-level disinfection for soiled linen

›Staff exposure management

›Post-exposure prophylaxis for high-risk exposures

›Oral ribavirin 500 mg every 6 hours for 5 days

›Start within 48 hours of exposure

›Monitor for 14 days post-exposure

09Special Populations/sp65

Pregnancy

›Pregnancy-specific risks

›High maternal and fetal mortality

›CCHF in pregnancy associated with poor obstetric outcomes

›Spontaneous abortion, stillbirth, premature delivery reported

›Vertical transmission possible

›Haemorrhage risk amplified

›Placental haemorrhage

›Postpartum haemorrhage risk

›Physiologic changes affecting assessment

›Baseline thrombocytopenia of pregnancy may confound interpretation

›Altered pharmacokinetics for ribavirin dosing

›Treatment modifications in pregnancy

›Ribavirin

›Teratogenic in animal models, Category X in first trimester

›Some guidelines recommend use in severe CCHF given high maternal mortality risk

›Shared decision-making with patient and obstetric team

›Blood product management

›Aggressive platelet and FFP replacement

›Obstetric team involvement for delivery planning

›Avoidance of ribavirin for 6 months before conception after treatment

›Both male and female patients

›Contraception counselling at discharge

Geriatric

›Age-related risk modifications

›Age >= 50 years as mortality risk factor

›OR 3.1 for mortality in multivariate analysis

›Reduced physiologic reserve

10Background/b79

Epidemiology

›Global distribution

›Most geographically widespread tick-borne viral disease

›Endemic across Africa, Eastern Europe, Middle East, and Asia

›Emerging in new European regions including Spain

›Autochthonous cases confirmed in Spain reported in NEJM 2017

›High-burden countries

›Turkey accounts for large proportion of reported cases

›Iran, Pakistan, Afghanistan, and Balkans major endemic foci

›New endemic territory as Hyalomma tick range expands northward

›Case demographics

›Male sex predominance

›65.7% of cases male in large Turkish cohort

›Occupational exposure as dominant driver

›Rural residence

›87% of cases in rural settings

›Agricultural and animal husbandry occupations at highest risk

›Seasonal distribution

›Peak incidence spring and summer corresponding to tick activity

›April through October highest risk period

›Mortality data

›Case fatality rate 10 to 40% overall

›As low as 5% with high-quality supportive care

›Paediatric mortality approximately 2%

›Adult mortality 5 to 13% with treatment

›Subclinical infection common

›Many infections are asymptomatic or mild

›Seroprevalence exceeds reported case rates in endemic regions

Pathophysiology

›Viral entry and replication

›Causative agent

›Nairovirus genus, Bunyaviridae family

›CCHF virus negative-sense RNA virus

›Tick vector Hyalomma species transmits during feeding

›Viraemic phase

›High viral load in blood during first 7 to 10 days

›Endothelial tropism with direct cell injury

›Monocyte and macrophage infection driving cytokine dysregulation

›Haemorrhagic mechanism

›Thrombocytopenia

›Bone marrow suppression from viral infection

›Platelet consumption in DIC

›Immune-mediated platelet destruction possible

›Coagulopathy

›DIC from endothelial damage and cytokine storm

›Hepatitis reducing clotting factor production

›Fibrinolysis activation

›Vascular permeability

›Cytokine-mediated endothelial dysfunction

›Capillary leak contributing to oedema and haemorrhage

›HLH complication

›Mechanism

›Uncontrolled macrophage activation from viral trigger

›Hyperferritinaemia, hypertriglyceridaemia, hypofibrinogenaemia

›Hemophagocytosis in bone marrow

›Clinical recognition

›Markedly elevated ferritin in context of severe CCHF

›Worsening cytopenias beyond expected disease pattern

Therapeutic Considerations

›Ribavirin evidence base

›Mechanism of action

›Nucleoside analogue inhibiting viral RNA polymerase

›Reduces viral replication and load

›Evidence quality

›2018 Cochrane review: insufficient high-certainty evidence

›Meta-analysis: 1.7-fold reduction in mortality

›Observational studies support early initiation

›Timing principle

›Greatest benefit when initiated within 96 hours of symptom onset

›2.4-fold increase in mortality odds per day of treatment delay

›Corticosteroid rationale

›Anti-inflammatory benefit

›Reduces cytokine-mediated endothelial injury

›Specific indication for HLH complication

›Combined therapy outcome

›Approximately 2.3-fold mortality reduction with ribavirin plus corticosteroid combination

›Class IIb observational evidence

›Supportive care primacy

›Cornerstone of management per Lancet Infectious Diseases 2023 systematic review

›Crystalloid resuscitation

›Blood product replacement guided by serial CBC and coagulation

›Prevention of iatrogenic haemorrhage from procedures

11Patient Discharge Instructions/pdi43

copy discharge instructions

›What you had and what to expect

›Crimean-Congo Hemorrhagic Fever is a serious viral infection spread by tick bites

›Recovery takes 2 to 4 weeks after discharge

›Fatigue, hair loss, and muscle weakness may persist for weeks to months

›Gradual return to normal activities as tolerated

›Your blood counts and liver tests will continue to improve

›Follow-up blood tests are essential to confirm recovery

›Do not donate blood for at least 6 months

›Medications

›Complete your full course of any medications prescribed

›Do not stop early even if feeling better

›Take with food to reduce stomach upset

›Avoid aspirin and ibuprofen and all anti-inflammatory drugs

›These increase bleeding risk

›Acetaminophen is safe for pain or fever

›If you received ribavirin, avoid pregnancy for 6 months

›Use effective contraception during this period

›This applies to both male and female patients

›Warning signs to return to emergency immediately

›Any new bleeding

›Nosebleeds that do not stop

›Blood in urine or stool

›Vomiting blood

›Unusual bruising or large hematomas

›Fever returning after discharge

›Temperature above 38.5 degrees Celsius

›Neurologic changes

12References/r38

Guidelines and key sources

›Systematic reviews and meta-analyses

›Rigby I et al. Standard of Care for Viral Haemorrhagic Fevers: Systematic Review of Clinical Management Guidelines. Lancet Infectious Diseases 2023

›PMID 36758568

›Supports crystalloid resuscitation and blood product replacement as cornerstone

›Johnson S et al. Ribavirin for Treating Crimean Congo Haemorrhagic Fever. Cochrane Database of Systematic Reviews 2018

›Insufficient high-certainty evidence for ribavirin efficacy

›Meta-analysis supports 1.7-fold mortality reduction

›Arab-Bafrani Z et al. Efficacy of Ribavirin Therapy in CCHF. Journal of Antimicrobial Chemotherapy 2019

›PMID 31369086

›2.4-fold increase in mortality per day of ribavirin delay

›Landmark cohort and review articles

›Ergönül O. Crimean-Congo Haemorrhagic Fever. Lancet Infectious Diseases 2006

›PMID 16554245

›Key epidemiology and mortality risk factor data

›Dokuzoguz B et al. Severity Scoring Index for CCHF and Impact of Ribavirin and Corticosteroids. Clinical Infectious Diseases 2013

›PMID 23946218

›SSI scoring system and corticosteroid combination evidence

›Negredo A et al. Autochthonous CCHF in Spain. New England Journal of Medicine 2017

›Confirmed European emergence of CCHF

›Infection control and public health

›Siegel JD et al. 2007 Guideline for Isolation Precautions. American Journal of Infection Control 2007

›PMCID PMC7119119

›PPE and isolation standards applicable to CCHF

›CDC Yellow Book 2025. Post-Travel Evaluation to Rule Out Viral Special Pathogen Infection

›CDC Category C bioterrorism agent classification

›Travel medicine guidance for returning travellers

›Ergönül O et al. Post-exposure Prophylaxis for CCHF Among Healthcare Workers. Emerging Infectious Diseases 2018

Evidence & Review