![Dosage regimen (for adults)
ADMINISTRATION
LOADING dose
(Day 1)
Day 1-4 Day 5-10
IV
17 mg/kg* (max
1000 mg per
dose)
17 mg/kg (max
1000 mg per
dose) 6 hourly
8 mg/kg (max
500 mg per
dose) 8 hourly
ORAL 2000 mg
1000 mg 6
hourly
500 mg 6
hourly
* If there appears to be a delay in beginning the treatment a loading dose of 30 mg /
kg [IV] (max 2 Gms) might be necessary as the loadingdose.](https://image.slidesharecdn.com/cchf-191101172015/85/Crimean-Congo-Hemorrhagic-Fever-39-320.jpg)
Crimean Congo Hemorrhagic Fever
- 1. CRIMEAN CONGO HEMORRHAGIC FEVER DR. BHAGWANA RAM JANGID PG RESIDENT DEPARTMENT OF PEDIATRICS
- 2. PART 1 INTRODUCTION HISTORICAL BACKGROUND GEOGHRAPHICAL DISTRIBUTION EPIDEMIOLOGY CLINICAL COURSE TRIAGE DIFFERENTIAL DIAGNOSIS LAB INVESTIGATION
- 3. INTRODUCTION It is a viral haemorrhagic fever caused by CCHF virus (Nairovirus genus ; bunyaviridae family). Primarily an animal disease, sporadic cases and outbreaks of CCHF affecting humans do occur. It’s tick born disease.
- 4. CCHF outbreaks constitute a threat to public health because of its Epidemic potential. High case fatality. Potential for nosocomial outbreaks. Difficulties in treatment and prevention.
- 5. Historical Background It was first described in the Crimea in 1944 when 200 Soviet military personnel were infected during world war II & given the name Crimean haemorrhagic fever. In 1967 peoples from Congo and Uganda were infected by similar virus thus the name Crimean Congo hemorrhagic fever. In India, the first laboratory confirmed case was reported on 19th January, 2011 in Gujarat
- 6. Geographical distribution Geographically this tick borne viral infection has been reported from different countries in South-east Europe Asia Middle East Africa
- 8. CCHF VIRUS Enveloped Single stranded –ve sense RNA virus. Glycoprotein spikes 8-10 nm in length. Helical nucleocapsid (200-3000 nm) Enter in cell using the cell surface protein Nucleolin.
- 9. VECTOR The Hyalomma species of tick (in gujarati it’s known as “itaddi”) are the most important vector for CCHF Virus. Other tick species vectors of CCHF Virus include Rhipicephalus, Ornithodoros, Boophilus, Dermatocentor, and Ixodes species. The ticks are also natural reservoir of CCHF virus. The ticks have 4 life stages (egg, larvae, nymph & adult). Both male & female can act as a vector. Transovarial & trans-stadial transmission.
- 11. RESERVOIR Ticks of the Hyalomma spp. also act as a reservoir. Wild animals & domestic ruminant animals such as Hares, rodents, camel, cattle, sheep and goats. Ostriches The most important source for acquisition of the virus by ticks is believed to be infected small vertebrates on which immature Hyalomma ticks feed. Domestic ruminant animals, such as cattle, sheep and goats, are viraemic for around one week after becoming infected.
- 12. HEDGEHOG
- 13. ENVIRONMENTAL FACTORS Ecological changes, poverty, social instability, poor health services, and absence of standard infection control practices have contributed to increased transmission of the CCHF virus. Highest incidence of the disease has been reported between March to May and again between August to October .
- 14. POPULATION AT RISK Agricultural workers, Slaughterhouse workers and veterinarians. Health care workers attending on suspect/ probable/ confirmed CCHF cases and not following contact precautions are at high risk of getting infection.
- 15. MODE OF TRANSMISSION Animal to Human Transmission • Human beings may acquire the CCHF virus by direct contact with blood or other tissues of infected livestock or they may become infected through a tick bite or crushing of infected tick. Human to Human Transmission • Humans can become infected if blood, body fluids and wastes from patients with the disease comes into contact with broken skin or mucous membranes, as occurs when medical care personnel sustain accidental needle stick injury.
- 18. Communicability: Highly infectious Susceptibility: Immunity after infection is probably lifelong.
- 19. CLINICAL FEATURES Course of this disease follows four distinct phases in humans Incubation phase Pre-hemorrhagic phase Hemorrhagic phase Convalescence phase
- 20. Incubation phase The length of the incubation period for the illness appears to depend on the mode of acquisition of the virus. Infection via tick bite: 1-3 days (max 9 days) Contact with infected blood or tissues : 5-6 days (max 13 days)
- 21. Pre-hemorrhagic phase Sudden onset of fever as high as 39-41°C, chills Severe headache, myalgia, rash Arthralgia, dizziness, photophobia. Back and abdominal pain. Additional symptoms such as Nausea, vomiting, diarrhea Loss of appetite. Neuropsychiatric manifestations like violent behavior, psychosis, change in mood and confusion etc.
- 22. Hemorrhagic phase In severe cases after 3-6 days of the onset of symptoms hemorrhagic manifestations occur. The spectrum of hemorrhages varies from petechiae & ecchymoses over skin and mucus membranes to serious intracranial bleed. Red eyes Bleeding manifestations like : Epistaxis, hematemesis, malena, hematuria, gum bleeds and intracerebral bleeds Jaundice Flushing of face Disseminated intravascular coagulation (DIC) Throat congestion Hepatorenal failure and Pulmonary failure Petechiae over palate Multiorgan dysfunction syndrome (MODS)
- 25. Convalescence phase The convalescence period begins in survivors about 10–20 days after the onset of illness. Labile pulse Xerostomia Tachycardia Poor vision Temporary or complete loss of hair Loss of hearing Polyneuritis Loss of memory Difficulty in breathing
- 28. CASE DEFINITION SUSPECTED CASE: A patient with abrupt onset of high fever >38.5°C and one of the following symptoms: severe headache, myalgia , nausea, vomiting, and/or diarrhea. AND/OR o History of insect (tick) bite within 14 days prior to the onset of symptoms; or o History of contact with tissues, blood, or other biological fluids from a possibly infected animal (e.g., abattoir workers, livestock owners, veterinarians) within 14 days prior to the onset of symptoms; or o History of exposure to a suspect, probable, or laboratory-confirmed CCHF case, within 14 days prior to the onset of symptoms (contacts of the patient including health care workers).
- 29. PROBABLE CASE: A probable CCHF case is defined as a suspected CCHF case fulfilling in addition the following criteria: Thrombocytopenia < 50,000/cmm AND Two of the following hemorrhagic manifestations: Hematoma at an injection site Hematemesis Petechiae Hemoptysis, Purpuric rash Gastrointestinal hemorrhage Epistaxis Gingival hemorrhage
- 30. CONFIRMED CASE: A confirmed CCHF case is defined as a case that fulfills the criteria for suspect/ probable CCHF and in addition is laboratory-confirmed with one of the following assays: Detection by RT-PCR of CCHF virus genome in a clinical specimen confirmed by sequencing of the PCR product. Detection by ELISA or IFA of specific IgM antibodies against CCHF virus or a 4-fold increase in specific IgG antibodies against CCHF virus in two specimens collected in the acute and convalescence phases.
- 32. Category A • Mild disease (fever < 38.50C, No systemic bleeding, Alanine Transaminase (SGPT) levels< 150 IU, Platelet count > 50,000). • These patients improve spontaneously in about day 10 of illness. Patient can be managed with supporting therapy and regular monitoring. • These patients do not require Ribavirin. Category B • The first 5 days of illness and are severely ill with high grade fever (> 38.50C), • local and systemic bleeding manifestations, • ALT/SGPT > 150 IU . AST/SGOT > 200 IU , platelets (< 50,000) or APTT > 60 sec. • These clinical path values are markers of poor prognosis if recorded during the first 5 days of illness and persons in this group should be treated as soon as possible with ribavirin. Category C • Patients first seen/recognized as CCHF after day 5 and are in comatose/terminal state with DIC and multi organ failure. Treatment with ribavirin is indicated but the prognosis is very poor.
- 33. DIFFERENTIAL DIAGNOSIS o Dengue Hemorrhagic Fever o Falciparum malaria o Leptospirosis o Typhoid Fever o Septicemic Plague o Rickettsial Infections o Meningococcemia o Viral Hepatitis o Other viral hemorrhagic fevers.
- 34. LABORATORY DIAGNOSIS CBC: Leukopenia with relative lymphocytosis & progressively worsening thrombocytopenia. Diagnostic methods: Detecting Antibodies The viral RNA or The Virus isolation.
- 35. There are no rapid diagnostic tests. ELISA-for IgG and IgM from 6th day of illness. IgM - upto four months IgG - upto five years. The virus may be isolated from blood or tissue specimens in the first five days of illness, and grown in cell culture. PCR and RT PCR-for detecting the viral genome
- 36. As CCHF virus is classified as risk group 4 virus and hence the clinical samples should be handled in specially- equipped, high biosafety level laboratories (BSL 3 plus or 4). ➢Ante-mortem: Blood sample: Serum/Plasma ➢Postmortem: Tissue sample (liver, spleen, bone marrow, kidney, Lung and brain)
- 38. TREATMENT The mainstay of treatment in CCHF is supportive in nature Maintenance of fluid and electrolyte balance. Maintenance of circulatory volume, and blood pressure. Platelet transfusion, PCV transfusion. Management of DIC, sepsis, shock and MODS Possible benefits with gammaglobulin obtained from immunization of horses.
- 39. Dosage regimen (for adults) ADMINISTRATION LOADING dose (Day 1) Day 1-4 Day 5-10 IV 17 mg/kg* (max 1000 mg per dose) 17 mg/kg (max 1000 mg per dose) 6 hourly 8 mg/kg (max 500 mg per dose) 8 hourly ORAL 2000 mg 1000 mg 6 hourly 500 mg 6 hourly * If there appears to be a delay in beginning the treatment a loading dose of 30 mg / kg [IV] (max 2 Gms) might be necessary as the loadingdose.
- 40. Dosage recommended for children ADMINISTRATION LOADING dose (Day 1) Day 1-4 Day 5-10 IV 17 mg/kg 17 mg/kg 6 hourly 8 mg/kg 8 hourly ORAL 30 mg/kg 15 mg/kg 6 hourly 7 mg/kg 6 hourly
- 41. RIBAVIRIN It is a member of the nucleoside anti metabolite drugs that interfere with duplication of viral genetic material. This is the only antiviral known to have some affect on the viruses causing VHF. Adverse effects : The most common side effect is mild to moderate haemolytic anaemia which is reversible. o iv use can cause pancytopenia & pancreatitis.
- 42. Contra-indications and precautions Ribavirin is contraindicated in patients with chronic anaemia and haemoglobin levels below 8 g/dl, and in patients with severe renal impairment (creatinine clearance <30 ml/min). Ribavirin is contraindicated for treatment in pregnant women. It can be given to pregnant women only if the benefit of ribavirin therapy appears to outweigh any fetal risk. Given the high risk of CCHF-related mortality both for pregnant women and foetuses, ribavirin still may be recommended.
- 43. New treatment strategies Interferons and interferon-stimulated antiviral proteins: MxA (interferon-induced GTPases) Antibodies to CCHF: Gammaglobulin obtained from immunisation of horses Development of monoclonal antibodies would allow better control Appropriate treatment of secondary infections should be instituted.
- 44. Post-exposure Prophylaxis Mucous membrane contact (kissing or sexual contact with a patient) Percutaneous injury in contact with the patients secretions, excretions, or blood. Exposed to hemorrhagic fever viruses (including CCHFV) in a bioterroristic attack Living or in cotact with the patients Who process laboratory specimens.
- 46. Indirect contact with case body fluids should be monitored for 14 days from the date of last contact with the patient or other source of infection by taking the temperature twice daily. If the patient develops a temperature of 38.5° C or greater, headache and muscle pains, he/she would be considered a probable case and should be admitted to hospital and started on ribavirin treatment.
- 47. THANK YOU uojkf= dh gkfnZd “kqHkdkeuk,a
Editor's Notes
- #30: any other hemorrhagic manifestation in the absence of any known precipitating factor for hemorrhagic manifestation.