VHF.pdf

Viral haemorrhagic fevers Viral haemorrhagic fevers (VHFs) are zoonoses caused by several different viruses like Lassa fever, Ebola fever, Marburg fever, Yellow fever, Dengue, Crimean–Congo haemorrhagic fever, Rift Valley fever, Kyasanur fever, Bolivian and Argentinian haemorrhagic fever and Haemorr...

Viral haemorrhagic fevers Viral haemorrhagic fevers (VHFs) are zoonoses caused by several different viruses like Lassa fever, Ebola fever, Marburg fever, Yellow fever, Dengue, Crimean–Congo haemorrhagic fever, Rift Valley fever, Kyasanur fever, Bolivian and Argentinian haemorrhagic fever and Haemorrhagic fever with renal syndrome (Hantaan fever) Crimean-Congo hemorrhagic fever INTRODUCTION  Crimean-Congo hemorrhagic fever (CCHF) is a zoonotic disease transmitted by ticks and characterized by fever and hemorrhage.  CCHF infects a range of animals; humans are the only known host that develops disease. EPIDEMIOLOGY  In 2022, Iraq reported a surge of over 200 infections during the first half of the year.  In the Northern Hemisphere, transmission of CCHFV is common between May and September, with a peak incidence in June and July. 1   The most common viral reservoirs are domestic livestock (sheep, goat, cattle, and pig), which are infected by adult ticks.  Ticks can remain attached for 2 to 13 days; after completion of feeding, the ticks detach from the host and begin to search for new hosts. The virus begins to multiply within 36 hours of attachment.  The virus does not have the ability to survive outside the host but may persist in infected body fluids such as blood, stool, or vomit. Transmission to humans  CCHF is transmitted via ticks,  direct contact with blood or other bodily fluids of infected animals,  nosocomial transmission,  and vertical transmission.  The risk of community-based transmission to close contacts and relatives of patients with CCHF is low.  Relatives and caregivers should avoid direct contact with infected patients and their blood/bodily fluids, wear gloves and protective clothes, and wash hands regularly.  Personal items such as razors or toothbrushes should not be shared.  Nosocomial transmission of CCHFV has been described.  The risk is highest during later stages of disease, which are associated with higher viral loads as well as diarrhea, vomiting, and hemorrhage. 2   Health care personnel are also at risk of infection during aerosol-generating procedures.  Transmission between patients sharing the same hospital room has occurred, likely due to contact with infected blood or body fluids  breastfeeding has not been associated with CCHFV transmission.  The role of sexual transmission is uncertain  The risk of laboratory exposure to CCHFV while processing blood samples is low if routine laboratory procedures are followed. Risk factors  Agricultural workers,  individuals in rural areas engaged in animal husbandry, abattoir workers,  veterinarians,  leather factory workers in areas with high tick density,  campers and hikers,  hunters,  soldiers,  health care workers,  and travelers to endemic areas VIROLOGY CCHF virus (CCHFV) is a member of the Nairovirus family within the Bunyavirus order, which contains negative-stranded, enveloped RNA viruses. 3 CLINICAL MANIFESTATIONS  Subclinical illness (88 percent)  Acute infection with hemorrhage and multiorgan failure.  The incubation period ranges from 1 to 13 days; it correlates with viral load and the type of transmission. Clinical manifestations of CCHF include  sudden onset of fever,  Headache,  Malaise,  Myalgia,  Sore throat,  Dizziness,  Conjunctivitis,  Photophobia,  Abdominal pain,  Nausea, and vomiting  Hepatomegaly,  Lymphadenopathy,  And confusion.  The initial period of nonspecific symptoms generally lasts up to seven days and is followed by either recovery or progression to severe disease. The convalescence period in recovering patients generally lasts up to four weeks with no long-term sequelae.  In severe cases, hemorrhagic manifestations are observed; these include:  petechiae 4  ecchymoses 5  Epistaxis, and gum bleeding  Pulmonary hemorrhage,  Intra-abdominal bleeding,  Hematuria, 6   Melena, and  Vaginal bleeding (heavy menstrual bleeding or early menstrual bleeding) can also occur.  Severe disease is thought to be due to an exaggerated proinflammatory cytokine response ("cytokine storm"), causing endothelial cell activation and increased vascular permeability, resulting in  Hypotension,  Shock,  Multiple organ failure, and  Death.  Laboratory findings may include:  Thrombocytopenia,  leukopenia,  hyperbilirubinemia  elevated transaminases  prolongation of international normalized ratio, prothrombin time, and activated partial thromboplastin time.  Anemia is observed in some cases.  In the setting of multiorgan failure,  elevated blood urea nitrogen,  creatinine, and  creatine phosphokinase may be present.  Patients with disseminated intravascular coagulation have decreased fibrinogen levels and increased fibrin- degradation products. 7  DIAGNOSIS  Clinical: the diagnosis of CCHF should be suspected in patients presenting with fever and bleeding who live in endemic area or visited an endemic area in the previous 2 weeks or had been bitten by tick or had contact with animals or their body fluids. Diagnostic tools  RT-PCR  specific immunoglobulin (Ig)M and IgG by ELISA.  Specific IgM positivity in a single sample indicates current infection, and seroconversion or fourfold rise of CCHFV IgG antibody levels in paired sera confirm recent or current infection.  CCHFV can be cultured in cell culture; this requires biosafety level 4 laboratories and is only used for research purposes. DIFFERENTIAL DIAGNOSIS The differential diagnosis depends on the geographic region and includes:  Other viral hemorrhagic fevers  Malaria  Rickettsial infection  Q fever  Brucellosis  Leptospirosis 8  Relapsing fever  Viral hepatitis  Meningococcemia  In addition, noninfectious entities in the differential diagnosis include:  Idiopathic thrombocytopenic purpura (ITP)  Acute leukemia TREATMENT  ribavirin is given intravenously (100 mg/kg, then 25 mg/kg daily for 3 days and 12.5 mg/kg daily for 4 days) when Lassa fever or South American haemorrhagic fevers are suspected.  There is no proven antiviral treatment for CCHF infection.  Ribavirin it has not been shown to reduce viral load or mortality in Crimean–Congo haemorrhagic fever and its clinical efficacy is controversial.  Management of CCHF consists of supportive care; in severe cases, blood product replacement is warranted.  Patients with CCHF should be managed in a health care center with appropriate facilities for diagnosis, treatment, and prevention of disease, including isolation precautions.  Data are insufficient to support routine use of steroids, intravenous immunoglobulin, or plasma exchange. 9   Use of hyperimmunoglobulin (which is prepared from the plasma of donors with antibody against CCHF) requires further study.  Hyperimmunoglobulin can decrease viral load via direct neutralization, although viral strain variability may be an important determination in the use of this therapy. Supportive care  Careful attention should be paid to fluid balance and electrolytes.  Mechanical ventilation  Hemodialysis  vasopressor, and inotropic agents may be needed.  Acetaminophen may be used for fever and pain management;  Nonsteroidal antiinflammatory drugs should be avoided as these agents can adversely affect normal clotting.  Platelet transfusion is warranted to maintain platelet count >50,000/mm3 in the setting of bleeding and for patients with platelet count 50,000/mm3 and normal coagulation tests (international normalized ratio, prothrombin time, and activated partial thromboplastin time).  If possible, a negative blood polymerase chain reaction for viral hemorrhagic fever should also be documented. 11 Postexposure management The exposed individual should undergo a two-week period of monitoring for symptoms or signs of CCHF, including daily temperature measurement and weekly assessment of complete blood count measurement; no quarantine is required. Development of a febrile illness during the monitoring period should prompt diagnostic testing. The role of ribavirin for prevention of clinical illness when given as postexposure prophylaxis is uncertain. PROGNOSIS  The mortality rate varies among countries and ranges from 2 to 80 percent.  Mortality rates in endemic countries are approximately 4 to 20 percent.  Most patients with CCHF live in rural areas and may have limited or delayed access to health care facilities, which may be associated with adverse outcomes. Independent predictors of mortality include presence of  Hemorrhage (particularly gastrointestinal bleeding and hematuria)  Impaired consciousness  Central nervous system involvement,  Diarrhea  Splenomegaly  Thrombocytopenia  Leukocytosis, 12   Increased alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase  decreased fibrinogen levels with a prolonged activated partial thromboplastin time  Viral load >107 copies/mL PREVENTION Prevention consists of  avoiding tick exposure and avoiding contact with animal bodily fluids.  Restricted areas should be established for slaughtering.  To reduce the risk of human infection during slaughtering, animals should be quarantined for 14 days before slaughtering.  All butchers and slaughters should be educated for preventive measures.  There is no approved vaccine for use in humans or animals. Reference:  Uptodate, 5 October 2022 13