Viral Hemorrhagic Fevers (VHFs) PDF

VIRAL HAEMORRHAGIC FEVERS (VHFs)  Viral hemorrhagic fevers (VHF): Intro: group of infections caused by a group of viruses from different viral families that produce a clinical syndrome of severe, life-threatening diseases characterized by febrile illness, bleeding disorders (h...

VIRAL HAEMORRHAGIC FEVERS (VHFs)  Viral hemorrhagic fevers (VHF): Intro: group of infections caused by a group of viruses from different viral families that produce a clinical syndrome of severe, life-threatening diseases characterized by febrile illness, bleeding disorders (haemorrhage), and multisystem organ failure The liver is most often severely damaged  Viral hemorrhagic fevers (VHF): Intro: Haemorrhage may occur depending on the virus VHF is severe multi-system syndrome characterized by diffuse vascular damage VHFs are of public health importance ✓due to high case fatality rate ✓possibility of human-to-human transmission. ✓difficulties in diagnosing and treating.  Causative agents VHF are zoonotic and transmitted to humans by bites of infected arthropods (ticks, mosquitoes), or from contact with infected bats, rodents and other animals. VHFs are caused by 4 ssRNA families of viruses 1. Arenaviridae are generally associated with rodent as reservoirs e.g. Lassa Fever Virus and South American HF Viruses. 2. Bunyaviridae with >300 virus species, the most important pathogens are Crimean-Congo virus (CCHF) and Hantavirus. Rift Valley fever virus (RVFV), RVF is commonly observed in domesticated animals (cattle, buffalo, sheep, goats, and camels)  Hantavirus is transmitted by rodents and with two forms of clinical presentations- Hemorrhagic fever with renal syndrome (HFRS) Hantavirus Pulmonary Syndrome (HPS). 3. Filoviridae Marburg virus Ebola virus; they cause severe haemorrhagic fever in humans and primates 4. Flaviviridae are enveloped ssRNA viruses, Yellow Fever Virus Dengue Fever virus are transmitted by mosquitos and Kyasanur Forest disease virus are transmitted ticks  Humans are dead-end hosts for most of the VHF, but are definitive hosts in urban yellow fever, phlebotomus fever, chikungunya, Zika and dengue. Infection may spread from person to person through direct contact with infected patient’s blood, secretions and excretions. Animal reservoirs are generally rodents, but domestic livestock, monkeys, bats and other primates may serve as intermediate hosts. They are lethal viruses and could be used for bioterrorism.  Virology Dengue fever and Henipavirus infections (Nipah and Hendra virus) are sometimes categorized as VHFs, although bleeding is rare in these infections Survival of virus is dependent on an animal or insect host as natural reservoir Viruses usually restricted to particular geographic areas, yet cases have been reported far from endemic regions.  Viral Hemorrhagic Fever Agents Virus Virus/Syndrome Geographic Reservoir or Human-human Family occurrence Vector transmission? Arenaviridae Junin (Argentine HF) S.America Rodents Lassa Fever – yes, (new world/old via body fluids; Machupo (Bolivian HF) S.America world) others – not usually Guanarito (Venezuelan HF) S. America Sabia (Brazilian HF) S. America Lassa (Lassa Fever) West Africa Lujo (lujo HF) S. Africa Flaviridae Yellow Fever Tropical Africa, Mosquitoes Yellow Fever – blood Latin America infective up to fifth day of illness; Dengue Fever Tropical areas Kyasanur Forest Disease India Ticks Others - No Omsk HF Siberia  Viral Hemorrhagic Fever Agents Virus Family Virus/Syndrome Geographic Reservoir or Human-human occurrence Vector transmission? Bunyaviridae Congo-Crimean HF Crimea, parts of Ticks CCH Fever–yes, Africa, Europe & through body Asia fluids; Rift Valley Fever Africa Mosquitoes Rift Valley Fever, Hantaviruses Diverse- Africa, Rodents Hantaviruses – no (Hemorrhagic Renal Syndrome/ Hantavirus Pulmonary Syndrome) Filoviridae Ebola HF Africa Fruit bats Yes, body fluid Marburg HF Africa transmission  Arenaviridae Transmission Virus transmission and amplification in rodents is both vertical & horizontal Virus are shed through urine, feaces, and other body fluids Human infection is by −Contact with excreta of rodents −Contaminated materials −Aerosol transmission −Animal contact with abraded skin of human Human to human transmission also occur  Arenaviridae Epidemiology Have worldwide distribution but those causing haemorrhagic fevers are restricted to – Africa: Lassa is endemic - South America: Junin, Machupo, Guanarito, and Sabia ❖Agricultural and domestic exposure are the most common Case fatality: 5 – 35% Explosive nosocomial outbreaks can occur with Lassa and Machupo  Arenaviridae in Humans Incubation period typically is between 10–14 days Disease onset begins with fever and malaise for 2–4 days. Most patients of lassa fever virus will recover following this stage but latin America Arena viruses (LAHF) will typically progress to severe stages symptoms Severe stages incuding hemorrhagic stage of the disease quickly follows with hemorrhage, leukopenia, thrombocytopenia, Neurologic signs  Filoviridae The Filoviridae (Ebola and Marburg viruses) responsible for some of the most lethal VHFs. The genus Ebolavirus is comprised of 6 distinct species Zaire ebolavirus, Sudan ebolavirus, Bundibugyo ebolavirus (Uganda), Taï Forest ebolavirus (Ivory Coast) Reston ebolavirus (USA & Italy respectively), Bombali ebolavirus (in bat in Serra Leone) Each with different mortality rate.  Marburg virus Genus- Marburgvirus with a single species of virus- Murburg Marburgvirus Phylogenetic analysis based on genome sequences data suggest the single species has at least 5 lineages. Four are closely related with nucleotide sequences differing between 0-7.8% The 5th lineage has nucleotide divergence of up to 21%. The sequences have been classified into 2 major lineages Marburg (Musoke, Popp, Angola, Ci67) Ravn viruses  Filoviridae Transmission Reservoir for Ebola not confirmed but mostly pointing to fruit bat Intimate contact is main means of transmission of filoviruses to humans. Nosocomial transmission is a major problem of outbreaks in Africa −Exposure to infectious tissues, excretions, and hospital wastes Aerosol transmission observed in primates but not a major means of transmission in humans  Filoviridae Epidemiology Marburg , reservoir is the Rousettus aetypticus. Many a time, found coinfecting with the Ravn virus -Africa Case fatality – 24-88% averaging 50% in outbreaks Ebola - Sudan, Zaire, Bundibugyo and Tai eboloa – Africa Case fatality – 53-88% Ebola Reston – isolated from macaques from Philippines marked first finding of filo viruses outside Africa The pattern of disease of humans in nature is relatively unknown except for major epidemics. Transmission via needle-stick or injecting equipment usually associated with severe disease, rapid deterioration and maybe high death rate  Filoviridae in Humans Most severe hemorrhagic fever Incubation period: 2- 21 days Abrupt onset- Fever, chills, malaise, and myalgia The patient rapidly deteriorates and progresses to multisystem failure Hemorrhage and DIC Death around day 7–11 Painful recovery Survivors often plagued with arthralgia, uveitis, psychosocial disturbances, and orchitis for weeks following the initial fever  Filoviridae in Animals Filoviruses cause severe haemorrhagic fever in non-human primates with mortality as high as ~82% but non-pathogenic to humans −It has same clinical course as other filoviruses in humans  Flaviviridae Group of arbovirus mostly transmitted by arthropods vectors 1648 : Yellow Fever described 17th–20th century- there were Yellow Fever and Dengue outbreaks 1927: Yellow Fever virus isolated 1943: Dengue virus isolated 1947 - Omsk Hemorrhagic Fever virus isolated 1957: Kyasanur Forest virus isolated  Flaviviridae Transmission Arthropod vector of yellow Fever virus is Aedes aegypti −Sylvatic cycle −Urban cycle Kyasanur Forest Virus is transmitted by Ixodid tick From infected rats, shrews , squirrels Omsk Hemorrhagic Fever virus is transmitted by ixodid tick from rodent to rodent −Muskrat are epizootic hosts and human contact with their urine, feaces or blood could course infection −Alkhumra virus closely related to OHFV and reservoir is cow, camel, sheep  Flaviviridae Epidemiology Yellow Fever Virus – Africa and Americas but activity is intermittent and localized Case fatality rate – varies but may reach 50% Dengue Virus – Asia, Africa, Australia, and Americas Incidence on the rise due to spread of A. aegyptae Case fatality rate – 1-10% Kyasanur Forest virus confined to Karnataka (Mysore) state – India Case fatality rate – 3–5% Omsk Hemorrhagic Fever virus – Europe Case fatality rate – 0.5–3%  Flaviviridae in Humans Yellow Fever Incubation period is between 3 to 6 days, The clinical manifestations can range from mild to severe signs with a short remission period Severe Yellow Fever begins abruptly with fever, chills, severe headache, lumbosacral pain, generalized myalgia, anorexia, nausea and vomiting, and minor gingival hemorrhages. A period of remission may occur for 24 hours followed by an increase in the severity of symptoms. Death usually occurs on n day 7 – 10.  Flaviviridae in Humans Dengue Hemorrhagic Fever Incubation period 5 to 7 days Dengue virus will cause a mild flu-like illness upon first exposure. If the person is then infected by a different sero-type, dengue hemorrhagic fever can occur. The disease can begin as normal dengue fever but quickly progress to a hemorrhagic syndrome. Rapid shock ensues but can be reversed with appropriate treatment.  Flaviviridae in Humans Kyasanur Forest Disease is characterized by fever, headache, myalgia, cough, bradycardia, dehydration, hypotension, gastrointestinal symptoms, and hemorrhages. Recovery is uncomplicated with no lasting sequelae. Omsk Hemorrhagic Fever presents like the KFD however hearing loss, hair loss, neuropsychiatric complaints are commonly reported following recovery (lasting sequelae.)  Flaviviridae circulation in Animals Yellow Fever virus Is maintained in non-human primates with varying clinical signs which may be an unapparent infection or a severe hemorrhagic illness depending on species Dengue virus Has been isolated from non-human primates but causes no clinical symptoms Kyasanur Forest Disease Virus May cause viremia in livestock but show no clinical symptoms Omsk Hemorrhagic Fever Virus Maintained in rodents but causes no clinical symptoms  Mode of transmission - Yellow Fever – Aedes mosquito (A. aegypti, A. africanus, A. simpsoni, A. furcifer, A. luteocephalus, and A. albopictus (Asian tiger mosquito) - Dengue Fever – mosquito (Aedes aegypti), may be through sex but chances extremely rare as explained by researcher Annelies Wilder- Smith - Omsk HF/Kyasanur FD: Tick bite No confirmed reported cases of person to-person transmission in YF, DENV, Omsk or Kyasanur forest diseases.  Yellow Fever cycles 3 cycles for yellow fever: -Jungle -Urban -intermediate  Yellow Fever Clinical presentation The majority of persons infected with yellow fever virus have no illness or only mild illness Initial symptoms Fever, chills, severe headache, back pain, muscle aches, nausea, fatigue. Faget’s sign may be seen Most symptomatic patients develop only this stage, In 15% of symptomatic patients develop severe form after short period of symptom remission (Toxic shock phase). Toxic phase - fever returns with initial symptoms PLUS Coagulopathy & hemorrhage (hematemesis), Jaundice, Hypotension, shock, metabolic acidosis, Arrhythmias, Confusion, seizures, and coma can occur.  Mortality rate: 5-10% (20-50%) in epidemics and hospitalized patients). Vaccine is available and indicated for travels to endemic area in Africa or South America. Immunity in 10 days in 80%- 100%% of people vaccinated Protection for 30-35 years. No need for booster No specific treatment available.  Dengue Fever Described as “breakbone fever” Endemic throughout Americas, Asia & Africa Vector – A. aegypti & A. albopictus. Virus replicates in mosquitos. Very Rare in blood transfusion, organs transplant &Vertical transmission  Dengue Fever The most prevalent mosquito-borne viral disease in the world. 1/3 of world populations are exposed (400 million cases yearly) >100 countries have endemic dengue transmission. First attenuated vaccine developed in 2015 by Sanofi Pasteur for people in endemic areas. No specific treatment.  Four Dengue Virus Serotypes (DEN 1,2,3,4) All can cause severe & fatal infection Infection with one serotype gives No cross immunity to other types but life long immunity to the same type, However, more predisposition to DHF/DSS if infected by another serotype. Humans are main reservoir but monkeys are also suspected! Clinical Manifestations of disease Undifferentiated fever Classic Dengue Fever Dengue Hemorrhagic Fever Dengue Shock Syndrome  Classic Dengue Fever Acute febrile illness Severe Hemorrhage mainly retro-ocular; Myalgia & arthralgia – often severe (breakbone fever); Nausea & vomiting > 50%; diarrhea (30%) Rash (50%) of variable appearances; maculopapular, petechial, or erythematous  Dengue Hemorrhagic Fever (DHF): Most serious form of dengue virus infection WHO estimates 500,000 cases /year Mortality ≈ 10% WHO 4 diagnostic criteria for DHF - Fever (2-7 days) -Hemorrhagic manifestations -Thrombocytopenia (Low platelet counts