Hemorrhagic fevers

1. Hemorrhagic fevers By abhinay sharma bhugoo Ml-610 23.10.11

2. Viral Hemorrhagic Fevers • Viral hemorrhagic fevers refer to a group of illnesses that are caused by several distinct families of viruses. • In general, the term "viral hemorrhagic fever" is used to describe a severe multisystem syndrome. • Characteristically, the overall vascular system is damaged, and the body's ability to regulate itself is impaired. • These symptoms are often accompanied by hemorrhage (bleeding); however, the bleeding is itself rarely life-threatening. • While some types of hemorrhagic fever viruses can cause relatively mild illnesses, many of these viruses cause severe, life-threatening disease.

3. Atlanta, Georgia: Electron Micrograph: Ebola virus causing African Hemorrhagic Fever. (Courtesy of the National Archives, 82-424)

4. Hosts and Vectors • Viruses associated with most VHFs are zoonotic. This means that these viruses naturally reside in an animal reservoir host or arthropod vector. • They are totally dependent on their hosts for replication and overall survival. • For the most part, rodents and arthropods are the main reservoirs for viruses causing VHFs, for example, the multimammate rat, cotton rat, deer mouse, house mouse, and other field rodents. • Arthropod ticks and mosquitoes serve as vectors for some of the illnesses. However, the hosts of some viruses remain unknown -- Ebola and Marburg viruses are well-known examples.

5. Common Features in HFV • They are all RNA viruses, and all are covered, or enveloped, in a fatty (lipid) coating. • Their survival is dependent on an animal or insect host, called the natural reservoir. • The viruses are geographically restricted to the areas where their host species live. • Humans are not the natural reservoir for any of these viruses. Humans are infected when they come into contact with infected hosts. However, with some viruses, after the accidental transmission from the host, humans can transmit the virus to one another. • Human cases or outbreaks of hemorrhagic fevers caused by these viruses occur sporadically and irregularly. The occurrence of outbreaks cannot be easily predicted. • With a few noteworthy exceptions, there is no cure or established drug treatment for VHFs.

6. Overview • Organism • History • Epidemiology • Transmission • Disease in Humans • Disease in Animals • Prevention and Control

7. The Organisms

8. Viral Hemorrhagic Fever • Viruses of four distinct families • Arenaviruses • Filoviruses • Bunyaviruses • Flaviviruses • RNA viruses • Enveloped in lipid coating

9. Classification

13. Arenaviridae Junin virus Machupo virus Guanarito virus Lassa virus Sabia virus

14. Arenaviridae History • First isolated in 1933 • 1958: Junin virus - Argentina • First to cause hemorrhagic fever • Argentine hemorrhagic fever • 1963: Machupo virus – Bolivia • Bolivian hemorrhagic fever • 1969: Lassa virus – Nigeria • Lassa fever

15. Virus transmission and amplification occurs in rodents Shed virus through urine, feces, and other excreta Human infection Contact with excreta Contaminated materials Aerosol transmission Person-to-person transmission Arenaviridae Transmission

16. Arenaviridae Epidemiology • Africa • Lassa • South America • Junin, Machupo, Guanarito, and Sabia • Contact with rodent excreta • Case fatality: 5 – 35% • Explosive nosocomial outbreaks with Lassa and Machupo

17. Arenaviridae in Humans • Incubation period • 10–14 days • Fever and malaise • 2–4 days • Hemorrhagic stage • Hemorrhage, leukopenia, thrombocytopenia • Neurologic signs

18. Bunyaviridae Rift Valley Fever virus Crimean-Congo Hemorrhagic Fever virus Hantavirus

19. Bunyaviridae History • 1930: Rift Valley Fever – Egypt • Epizootic in sheep • 1940s: CCHF - Crimean peninsula • Hemorrhagic fever in agricultural workers • 1951: Hantavirus – Korea • Hemorrhagic fever in UN troops • 5 genera with over 350 viruses

21. Arthropod vector Exception – Hantaviruses RVF – Aedes mosquito CCHF – Ixodid tick Hantavirus – Rodents Less common Aerosol Exposure to infected animal tissue Bunyaviridae Transmission

22. Bunyaviridae Epidemiology • RVF - Africa and Arabian Peninsula • 1% case fatality rate • CCHF - Africa, Eastern Europe, Asia • 30% case fatality rate • Hantavirus - North and South America, Eastern Europe, and Eastern Asia • 1-50% case fatality rate

23. Bunyaviridae Humans • RVF • Incubation period – 2-5 days • 0.5% - Hemorrhagic Fever • CCHF • Incubation period – 3-7 days • Hemorrhagic Fever - 3–6 days following clinical signs • Hantavirus • Incubation period – 7–21 days • HPS and HFRS

24. Bunyaviridae Animals • RVF • Abortion – 100% • Mortality rate • >90% in young • 5-60% in older animals • CCHF • Unapparent infection in livestock • Hantaviruses • Unapparent infection in rodents

25. Overview in time • 1930’s: virus isolated Kenya • 1950-1951: outbreak in Kenya • 1977-1978: outbreak in Egypt • 1987: outbreak in Senegal • 1997-1998: outbreak in Kenya • Largest reported • 89.000 human cases-478 deaths • 2000-2001: outbreak in Saudi Arabia and Yemen

27. RVF Signs and symptoms • Incubation period: 2-6 days • Flu like symptoms • Fever, headache, myalgia, nausea, vomiting • Recovery 4-7 days • Severe Symptoms • Retinopathy (0.5-2%) • Hemorrhagic fever (<1%) • Encephalitis (<1%) • Overall mortality 1%

30. Distribution of Rift Valley Fever in Africa. Blue, countries with endemic disease and substantial outbreaks of RVF; green, countries known to have some cases, periodic isolation of virus, or serologic evidence of RVF.

31. Hemorrhagic Fever with Renal Syndrome (HFRS)

32. What is hemorrhagic fever with renal syndrome? • Hemorrhagic fever with renal failure syndrome (HFRS) occurs mainly in Europe and Asia and is characterized by fever and renal failure associated with hemorrhagic manifestations. • caused by an airborne contact with secretions from rodent hosts infected with the group of viruses belonging to the genus Hantavirus of the family Bunyaviridae. • In Europe, hemorrhagic fever with renal failure syndrome is caused by 3 hantaviruses: Puumala virus (PUUV), carried by the bank vole (Myodes glareolus); Dobrava virus (DOBV), carried by the mouse (Apodemus flavicollis); and Saaremaa virus (SAAV), carried by the striped field mouse (Apodemus agrarius).

33. History • Hemorrhagic fever with renal failure syndrome was initially recognized between 1913 and 1930 by Soviet scientists, • The disease came to the attention of the Western world in 1950, when the North American soldiers serving with the United Nations forces in Korea developed a febrile illness associated with shock, hemorrhage, and renal failure. • In 1993, in the southwestern United States, an outbreak of respiratory illness caused by the Sin Nombre virus, which belongs to the genus Hantavirus, occurred and was described as the Hantavirus pulmonary syndrome (HPS).

34. pathogenesis • The pathogenesis is largely unknown, but findings from several studies have suggested that immune mechanisms play an important role. • Damage to the vascular endothelium, capillary dilatation, and leakage are clinically significant features of the disease.

35. How do humans get HFRS? • Hantaviruses are carried and transmitted by rodents. • after exposure to aerosolized urine, droppings, or saliva of infected rodents or after exposure to dust from their nests. • Transmission may also occur when infected urine or these other materials are directly introduced into broken skin or onto the mucous membranes of the eyes, nose, or mouth • Transmission from one human to another may occur, but is extremely rare.

36. Which rodents carry the hantaviruses that cause HFRS in humans? • Rodents are the natural reservoir for hantaviruses • striped field mouse (Apodemus agrarius), the reservoir for both the Saaremaa and Hantaan virus; • the brown or Norway rat (Rattus norvegicus), the reservoir for Seoul virus; • the bank vole (Clethrionomys glareolus), the reservoir for Puumala virus; • and the yellow-necked field mouse (Apodemus flavicollis), which carries Dobrava virus.

37. What are the symptoms of HFRS? • The clinical features in hemorrhagic fever with renal failure syndrome (HFRS) consist of a triad of fever, hemorrhage, and renal insufficiency. • Other common symptoms during the initial phase of the illness include headache, myalgia, abdominal and back pain, nausea, vomiting, and diarrhea. • The disease may range from mild to severe. Subclinical infections are especially common in children.

38. The average incubation period varies from 4-42 days. The disease is characterized by fever, hemorrhagic manifestations, and (if severe) hypovolemic shock. • The disease has 5 progressive stages: febrile, hypotensive, oliguric, diuretic, and convalescent. • Individual patients can completely skip stages.

39. Febrile phase: Symptoms include fever, chills, sweaty palms, diarrhea, malaise, headaches, nausea, abdominal and back pain, respiratory problems such as the ones common in the influenzavirus, as well as gastro-intestinal problems. These symptoms normally occur for three to seven days and arise about two to three weeks after exposure.[8]

40. Hypotensive phase: This occurs when the blood platelet levels drop and symptoms can lead to tachycardia and hypoxemia. This phase can last for 2 days. • Oliguric phase: This phase lasts for three to seven days and is characterised by the onset of renal failure and proteinuria occurs.

41. Diuretic phase: This is characterized by diuresis of three to six litres per day, which can last for a couple of days up to weeks. • Convalescent phase: This is normally when recovery occurs and symptoms begin to improve.

42. How is HFRS treated? • Supportive therapy is the mainstay of care for patients with hantavirus infections. • Care includes careful management of the patient’s fluid (hydration) and electrolyte (e.g., sodium, potassium, chloride) levels, maintenance of correct oxygen and blood pressure levels, and appropriate treatment of any secondary infections. Dialysis may be required to correct severe fluid overload. Intravenous ribavirinhas been shown to decrease illness and death associated with HFRS if used very early in the disease.

43. Is HFRS ever fatal? • Depending upon which virus is causing the HFRS, death occurs in less than 1% to as many as 15% of patients. Fatality ranges from 5-15% for HFRS caused by Hantaan virus, and it is less than 1% for disease caused by Puumala virus.

44. How is HFRS prevented? • Rodent control is the primary strategy for preventing hantavirus infections.

45. Filoviridae Marburg virus Ebola virus

46. Filoviridae History • 1967: Marburg virus • European laboratory workers • 1976: Ebola virus • Ebola Zaire • Ebola Sudan • 1989 and 1992: Ebola Reston • USA and Italy • Imported macaques from Philippines • 1994: Ebola Côte d'Ivoire

48. Epidemic Outbreaks of Marburg • Out breaks occured in Kenya, South Africa, Democratic Republic of Congo. • Recent outbreak in Angola in 2005

49. Filoviridae Transmission • Reservoir is UNKNOWN • Bats implicated with Marburg • Intimate contact • Nosicomial transmission • Reuse of needles and syringes • Exposure to infectious tissues, excretions, and hospital wastes • Aerosol transmission • Primates

50. Filoviridae Epidemiology • Marburg – Africa • Case fatality – 23-33% • Ebola - Sudan, Zaire and Côte d'Ivoire – Africa • Case fatality – 53-88% • Ebola – Reston – Philippines • Pattern of disease is UNKOWN