1. FOUR
CORNERS
DISEASE
Dr.R.Jayaprada

2. OVERVIEW
 History
 Organism
 Epidemiology
 Transmission
 Disease in Humans
 Prevention and Control

3. INTRODUCTION
 Two major outbreaks of disease led to the discovery of
hantaviruses in the Old and New Worlds.
 The first outbreak occurred during the Korean War (1950 to
1953), where in more than 3,200 United Nations troops fell ill
with Korean hemorrhagic fever, which is commonly referred
to as hemorrhagic fever with renal syndrome (HFRS).
 The second outbreak of disease occurred in the Four
Corners region of the United States in 1993 and was initially
referred to as Four Corners disease, which is now called
hantavirus pulmonary syndrome (HPS) or hantavirus
cardiopulmonary syndrome (HCPS).

4. FOUR CORNERS OUTBREAK
 The converging point of Colorado,
Utah, Arizona, and New Mexico‘s
state borders became the location
of the 1993 Four Corners Outbreak
of Hantavirus Pulmonary Syndrome
(HPS).
 The Navajo tribal belief is such that
mice were responsible for bringing
seeds to the earth, allowing
humans to survive.
 Mice are thought of as the
―landlords of the world‖ and are
highly respected in Navajo culture.

5. HISTORY
 In May 1993, an outbreak of an unexplained pulmonary illness
occurred in the southwestern United States, in an area shared
by Arizona, New Mexico, Colorado and Utah known as "The
Four Corners".
 A young, physically fit Navajo man suffering from shortness of
breath was rushed to a hospital in New Mexico and died very
rapidly.

6. The mysterious illness
 A native Indian Health physician began to notice an outbreak
of an unexplained illness that caused death among normal
healthy young adults
 After calling his colleagues, he discovered that 10 people had
already died of a similar respiratory disease
 Autopsies did not reveal any sign of viral pneumonia, influenza
or any other common disease that attacked the lungs
 Although this disease was not specific to the Navajo people, to
the media, the disease became known as the ―Navajo disease‖
 When the number of cases doubled to about 20 victims, the
CDC was called in

7. CDC
 In May 1993, the CDC was called in to investigate the case.
 The CDC, using immunofluorescent techniques and their virus
library, was able to positively identify this new virus as a relative of
the hantavirus strains that were found on the Eurasian continent
 However, scientists were skeptical for 3 reasons
 The only hantaviruses known were on the Eurasian continent
 The diseases caused by the Eurasian hantavirus strain did not
cause respiratory failure
 The new virus in the ―four corners‖ appeared to be 5 times as
lethal as the strain in Europe!

8. HISTORY
 HPS was first recognized as a HANTAVIRUS DISEASE.
 32 of the 53 people were infected & died.
 A warm winter allowed for an increase in the host population.
 Outbreak was caused by the SIN NOMBRE STRAIN(SNV, in
Spanish, "Virus sin Nombre", for "nameless virus").
 30% of the mice in that area carried this strain.

9. FOUR CORNERS OUTBREAK
 Winter and spring 1993
 Drought for several years followed by snow and rain
 Vegetation blossomed and rodent population grew
tenfold
 Virus was isolated 1 month after the first report of cases and
named as Muerto Canyon virus, then Four Corners virus, and
finally Sin Nombre Virus (SNV –―virus without a name‖).

10. FOUR CORNERS OUTBREAK
 Newly emerging virus has been present since 1959.
 38 year old Utah man that had died from an illness
compatible with hanta in 1959.
 Researchers located his lung tissue and utilizing current
technology, were able to isolate SNV in 1994.
 The earliest case of HPS to be confirmed by IHC with direct
visualization of hanta viral antigens in postmortem tissue
involved a patient who died in 1978.

11. HISTORY
 Hantavirus disease outbreaks have occurred as far back as
American Civil War times.
 There are records of a hemorrhagic fever syndrome (HFRS)
during World War I and II.
 First outbreaks of hantavirus causing HFRS were reported in
Russia in 1913 and 1932.
 Japanese troops in Manchuria reportedly had cases in 1932
and cases referred to as Nephropathia Epidemica (NE) in
Sweden appeared in 1934.
 Western medicine diagnosed Korean Hemorrhagic Fever
(KHF) during the Korean War in the 1950‘s.

12. HISTORY
 1951-1954: Korean War
 3,200 U.N. troops develop disease
 Hantaan River separated N. & S. Korea
 1977
 Hantaan agent was isolated and characterized
 1990: 94% of serum samples from soldiers in 1950‘s had
antibodies
 1979
 Seoul virus found in Japan and Europe

13. HISTORY
 Its original name was "Four Corners virus" or "Navajo Flu",
but the name was changed after local residents raised
objections.
 Its rodent host, the Deer mouse (Peromyscus maniculatus),
was first identified by Terry Yates, a professor at the
University of New Mexico.

14. HISTORY
 1951-1954: HEMORAGIC FEVER WITH RENAL FAILURE FIRST RECOGNIZED
AS A PATHOGEN AFTER AN OUTBREAK IN HANTAAN KOREA.
 1977: DISEASE ISOLATED AND NAMED AFTER HANTAAN RIVER.
 1978: IT WAS CONFIRMED THAT THE VIRUS IS CARRIED BY RODENTS.
 1981: FIRST SUCCESSFUL PROPAGATION OF VIRUS IN CELL CULTURE.
 1993: OUTBREAK OF HPS IN FOUR CORNER REGION OF
COLORADO, NEW MEXICO, ARIZONA AND UTAH.

15. RECENT CASES
 May 2003: Montana
 Three cases
 Two deaths
 Contracted virus from rodents in home
 First cases since fall of 2001
 Overall cases in Montana
 Virus first appeared in state in 1993
 20 cases
 5 deaths

16. ORGANISM

17. BUNYAVIRIDAE
 Genus Human disease
 Bunyavirus LaCrosse encephalitis, others
 Phlebovirus Rift Valley fever, sandfly fever
 Nairovirus Crimean-Congo hemorrhagic fever
 Tospovirus Plant virus, no known human disease
 Hantavirus -Hemorrhagic fever with renal syndrome
 -Hantavirus pulmonary syndrome

18. HANTA VIRUS GENUS
 Hantavirus Similarities
 RNA viruses
 Lipid membrane
 Tri-segmented genome
 Hantavirus Differences
 Hantavirus transmitted through aerosolized rodent urine,
feces and saliva.
 Others genera transmitted through arthropod vectors.

19. IMPORTANT SPECIES OF HANTA
 The genus Hanta contains at least four species—
 1.Hantaan virus causing the severe HFRS in the Far East,
North Asia and Russia,
 2.Seoul virus causing a milder type of disease and probably
present worldwide,
 3.Puumala virus responsible for Nephropathia epidemica in
Northern and Eastern Europe, and
 4.Prospect Hill virus isolated from voles in the USA, which
has not been associated with human illness.

20. INTRODUCTION
 Hantaviruses belong to the bunyaviridae family of viruses.
 Hanta viruses are rodent borne diseases transmitted from
humans to humans in aerosolized urine/ saliva & occasionally
by bite.
 International committee on taxonomy of viruses recognized
30 species in the genus Hanta virus (of which 21 are
pathogenic to humans).

21. TAXONOMY
 Rodent borne Hantaviruses are divided into 3 groups based
on the taxonomic assignment of their principal hosts
belonging to families muridae & cricetidae.
FAMILY SUBFAMILY PRINICIPAL HOST
MURIDAE Murinae old world rats &
mice
Cricetidae Arvicolinae Voles & Lemmings
Cricetidae Sigmodontinae
New world rats &
Mice
Cricetidae Neotominae

22. TAXONOMY

23. ASSOCIATION WITH DISEASE
 Murine rodents are the principal hosts of Hanta virus
associated with severe HFRS.
 Voles are the principal hosts of Puumula virus, which is the
cause for relative mild form of HFRS called Nephropathia
epidemica.
 Sigmodontinae & Neotominae rodents the principal hosts of
Hanta virus Known to cause HPS.

24. Molecular Biology of Hantavirus
Physical Properties
Structure
Genetics
Replication Cycle
Pathogenesis

25. DESCRIPTION OF THE AGENT
 Spherical
 Enveloped, ss negative
sense RNA virus.
 Virions 80-120nm in diameter
with a characteristic square
grid-like structure.
 Helical nucleocapsid.
 Genome consists of three
RNA segments: L, M, and S.
 NO matrix protein.
 Lipid bilayer.

27. DESCRIPTION OF THE AGENT
 Spikes protrude from the lipid bilayer envelope.
 Spikes consists of glycoproteins Gn & Gc (formerly G1 &G2
respectively).
 Virion contains ribonucleocapsid--SS RNA complexed with
nucleocapsid protein- L protein.
 Genomes of Hanta virus consists of trisegmented negative
sense Linear ss RNA.
 Three segments:
 Large (L) codes for viral polymerase
 Medium (M) codes for G1 and G2 glycoproteins
 Small (S) codes for nucleocapsid

28. STRUCTURAL PROTEINS
 Membrane Glycoproteins
 Nucleocapsid Protein
 Viral Polymerase

29. Membrane
glycoproteins
(G1 and G2) Polymerase (L)
Nucleocapsid
proteins (N)

30. Membrane Glycoproteins
 G1: 64-67kDa
 G2: 54 kDa, highly conserved
 Integral membrane proteins
 G1-G2 heterodimers form 8 nm projections on
virion surface
 Cysteine-rich
 Contain asparagine-linked sugar groups
 Important in cell entry and pathogenesis

31. Nucleocapsid Protein
 48 kDA
 Complexes with genomic vRNA in virus, as well as
with cRNA after infection, but not with mRNA
 Necessary for virus replication and packaging

32. Viral Polymerase
 247 kDA
 RNA-dependent RNA polymerase (RdRp)
 Complexed with ribonucleocapsids in virion
 Endonuclease activity to cleave host mRNA
 Transcriptase activity for making cRNA and mRNA
from vRNA
 Helicase activity to unwind vRNA during
transcription

33. Genomic Organization
 Tripartite negative sense genome
 Small (S) segment, 1.7-2.1kb, codes for N nucleocapsid
protein
 Medium (M) segment, 3.6-3.7kb, codes for G1 and G2
glycoproteins
 Large (L) segment, 6.5 kb, codes for L polymerase
protein

34. Sin Nombre Virus
• Circular single stranded; RNA
• Total genome 10500-22700 nucleotides long
• 100 (80-120) nm in diameter
• Surface projections of envelope distinct; spikes (of
about 10 nm).
• Reservoir for Sin Nombre virus is deer mice

35. Viral Replication
 Receptor mediated endocytosis
 Occurs in cytoplasm
 Budding at Golgi apparatus or cell membrane

36. Hantavirus Replication Cycle
 Attachment
 Entry and Uncoating
 Primary Transcription
 Translation
 Genome Replication
 Secondary Transcription
 Virion Assembly
 Virion Release

38. Attachment
 Viral G1 and G2 glycoproteins interact with cell
surface receptors
 Pathogenic hantavirus bind β3 integrins
 Non-pathogenic hantaviruses bind β1 receptors

39. Virion Assembly
 Membrane-bound G1 and
G2 peptides are
transported to Golgi
apparatus and
carbohydrates are
attached by N-linked
glycosylation
 vRNA complexes with N
nucleocapsid protein,
forms looped panhandle
structure, and complexes
with polymerase

40. Virion Release
Two Mechanisms
 Nucleocapsid complexes  G1 and G2 embed
bud into the Golgi into cell membrane
membrane with G1 and through Golgi
G2 embedded
vesicles
 Virion particle is formed
 Virions bud from cell
inside Golgi apparatus
membrane, not
 Virions are transported to
through Golgi
cell membrane by vesicles
apparatus
and released by exocytosis

41. Old World & New World Hantavirus
 Hantaviruses are commonly referred to as Old World and
New World hantaviruses due to the geographic distribution
of their rodent reservoirs and the type of illness (HFRS or
HPS) that manifests upon transmission to humans.

42. Old World Hantavirus vs New World Hantavirus
 Found mostly in Europe and  Discovered in the ―four
Asia corners in America
 Carried by rodents  Carried by rodents
 Causes HFRS  Causes HPS
 Targets the kidney  Targets the lungs
 Mortality rate is <10-15%  Mortality rate is 50-60%
 Vaccine exists for these  Vaccine does not exist for
strains these strains

43. HANTA VIRUSES IN THE OLD WORLD
Serotype Host Location
Hantaan Apodemus agrarius Asia, Far
(striped field mouse) East
Russia
Dobrava A. agrarius, A. flavicollis Europe
(yellow neck mouse) Balkans
Seoul Rattus norvegicus, R. rattus Worldwide
(Norway brown rat, roof
rat)
Puumala Clethrionomys glareolus Europe
(red bank vole)

44. HANTA VIRUSES IN THE NEW WORLD
Serotype Host Location
Sin Nombre Peromyscus Central &
maniculatus (deer West U.S.,
mouse) Canada
Monongahela Peromyscus Eastern U.S.,
maniculatus (deer Canada
mouse)
New York Peromyscus leucopus Eastern U.S.,
(white-footed mouse) Canada
Bayou Oryzomys palustris SE U.S.
(rice rat)
Black Creek Sigmodon hispidus SE U.S.
Canal (cotton rat)

45. HANTA VIRUSES IN THE NEW WORLD
Serotype Host Location
Andes Oligoryzomys Argentina/Ch
longicaudatus (long- ile
tailed pygmy rice rat)
Oran O. longicaudatus NW Argentina
Lechiguanas O. flavescens Central
Argentina
Hu39694 Unknown Central
Argentina
Laguna Negra Calomys laucha Paraguay/
Bolivia
Juquitiba Unknown Brazil

46. DISTRIBUTION OF NEW AND OLD WORLD
HANTAVIRUSES

47. Epidemiology and Rodent Hosts
 Each strain of hantavirus has a specific rodent host
 Hantavirus species appear to have co-evolved
with host rodent species
 Rodents carrying hantavirus are asymptomatic

48. EPIDEMIOLOGY
 Hantan virus ,prototypical member of genus Hanta virus is the
cause of a severe form HFRS endemic in Korea, China and
Eastern Russia.
 Dobrava- Belgrade virus is an agent of Severe form of HFRS in
the Balkans Greece and Russia
 Seoul Virus is endemic in Asia, Europe and America
 Puumala viurs is endemic in Europe and Scandinivea
 Saaremaa virus – in Europe .
 Amur virus – Eastern Russia.
 SinNOmbre virus is the major cause of HPS in North America .
 Andes virus is the major cause of HPS inSouth America

49. Geographical representation of approximate
hanta viral disease incidence by country per year.
Jonsson C B et al. Clin. Microbiol. Rev. 2010;23:412-441

50. Transmission
Vectors
 Transmitted via aerosolized rodent urine, feces, and saliva
 Deer mouse (Peromyscus maniculatus)
 Cotton rat (Sigmodon hispidus)
 White-footed mouse (Peromyscus leucopus)
 Striped field mouse (Apodemus agrarius)
 Bank vole (Clethrionomys glareolus)
 Rat (Rattus)

51. Deer Mouse Cotton Rat House Rat (Mus musculus)
Rice Rat White Footed Mouse

54. Hantavirus and Host Cells
 Virus replication typically halts host macromolecule
synthesis
 Hantavirus replication does not affect host cell‘s natural
functions
 Hantavirus release does not require host cell lysis
 Hantavirus is able to establish a persistent infection in rodent
host cells

55. Integrins
 Hetero dimeric receptors composed of α and β subunits
 Present on endothelial cells, macrophages, and platelets –
cells affected by Hantavirus infection
 Normally involved in regulation of endothelial cell adhesion,
platelet aggregation, Ca++ channel activation, and
extracellular matrix interactions, including cell migration

56. β3-Integrins
 Required for infection by pathogenic Hantaviruses
 β1 integrins are used by non-pathogenic strains
 Attachment of G1/G2 proteins of viroid to integrin
initiates endocytosis, but also activates the
receptor
 Variation in virus G1/G2 protein may account for
severity of disease

57. Hantavirus Infection
Pathogenesis
 Binding of Hantavirus glycoproteins to β3 integrin causes
disruption of vascular integrity
 Capillaries become more permeable
 Arteriole vasoconstriction and vasodilatation are disrupted
 Binding to platelet receptors affects clotting and platelet
function

58. Immune Reaction
 Immune system activated against Hantavirus epitopes
 Virus epitopes expressed on surface of host cells triggers
cytotoxic T-cell attack on host tissues
 Symptoms are consistent with inflammatory response

59. Clinical Presentation
of Hantavirus Infection
Three different clinical manifestations of hantavirus infection
caused by different viral strains
Hemorrhagic fever with renal syndrome (HFRS)
 Found in Europe and Asia
Nephropathia Epidemica (NE)
 Found in Europe
Hantavirus pulmonary syndrome (HPS)
 Found in north and south America

60. MAJOR DIFFERENCE B/N HFRS & HPS
 HFRS HPS
 Retroperitoneum is the Lungs & thoracic cavity are the
major site of the vascular major sites of vascular leaks in
leak in HFRS. HPS.

61. Stages of Hemorrhagic Fever with Renal Syndrome
(HFRS)
1)Incubation (4-40 days)
2)Febrile Phase (3-5 days):Characterized by fever, chills,
headache, severe myalgia (muscle pain), nausea
3)Hypotensive Phase (hours to days): Decrease in blood pressure,
hypovolemia (decreased blood volume), shock
4)Oliguric Phase (3-7 days):Marked by decreased urine
production due to renal (kidney) dysfunction

62. Stages of Hemorrhagic Fever with Renal
Syndrome (HFRS)
Recovery:
5)Diuretic Phase (2-21 days):Beginning of recovery, 3-6 liters of
urine/ day; return to normal renal activity
6)Convalescent Phase (2-3 months):
Progressive improvement in glomerular filtration, renal blood
flow, and urine concentrating ability

64. Clinical Testing for
HFRS
 Thrombocytopenia (low platelet count) is a signifier
 Urine tests for albuminuria (abnormally high amounts
of the plasma protein albumin in the urine)
 Urine tests for microhematuria (microscopic amounts
of blood in the urine)

65. Problems Diagnosing HFRS
 Early symptoms resemble influenza
 More serious symptoms of hypotensive phase have
acute onset

66. PATHOLOGY
 In HFRS, pathology findings are:
 1.Effusions in the body cavities,
 2.Retroperitoneal edema,
 3.Enlarged, congested & hemorrhagic kidneys.

67. Nephropathia Epidemica (NE)
 Puumala hantavirus strain
 Common mild form of HFRS in Europe
 Similar sequence of symptoms as HFRS, but much
milder
 Only 6% of serologically confirmed cases require
hospitalization

68. HPS
 1993 four corners outbreak
 Cases found in almost all parts of the Americas
 ~50% fatality

70. Stages of Hantavirus Pulmonary Syndrome (HPS)
1)Incubation (4-30 days)
2)Febrile phase (3-5 days): Characterized by fever, myalgia,
malaise, headache, dizziness, anorexia, nausea, vomiting,
and diarrhea.
3)Cardiopulmonary phase ( 4-24 hours): Presentation and rapid
progression of shock and pulmonary edema (4-24h non-
productive cough and tachypnea (shortness of breath)
4)Diuretic phase
5)Convalescent phase: Results in chronic decreased small-
airway volume and diminished alveolar diffusing capacity

71. HPS Radiographic Findings
 Bilateral interstitial infiltrates
 Moderate to rapid progression
 Bilateral alveolar infiltrates
 Pleural effusion
 Normal heart size

72. Clinical Testing for HPS
 Many lab tests and radiographs appear normal
 Serological tests more effective
 ELISA IgM capture assay, using either SNV, Laguna
Negra, or Andes antigens are used in all countries that
have previously detected cases
 Immunofluorescent test for the presence of antibodies
 Blood analysis also may find thrombocytopenia with
platelet count less than 150,000 mm in 98% of cases

73. PATHOLOGY
 In HPS, pathology findings are:
 1.Copious amounts of frothy fluid in bronchi & other airways,
 2.Edematous lungs &
 3.Pleural effusions.

74. LABORATORY DIAGNOSIS

75. COLLECTION,TRANSPORT & STORAGE OF
SPECIMENS
 SPECIMENS:
 Blood, Serum, Urine, CSF, Respiratory secretions.
 Specimens are collected during acute phase of illness.
 Precautions must be taken while handling the specimens of
Hanta virus.
 1)Sera from HFRS/ HPS patients should be handled at BSL-2.
 2) Potentially infectious tissue specimens should be handled at
BSL-2 using BSL-3 practices.
 Blood, Serum/plasma samples for serology should be strored at
4º C & sent to lab on ice packs.
 Samples for RNA isolation & subsequent testing by RT PCR are
stored continuously at -70º C.

76. LABORATORY DIAGNOSIS
 1.Direct detection—a. Microscopy.
b. Antigen detection.
c. Nucleic acid detection.
 2.Virus isolation.
 3.Serologic tests.
 4.Identification– a. Serologic methods.
b. Genetic methods.
 5.Typing Systems.—Sequence analysis.

77. DIRECT DETECTION
 Microscopy : It has limited diagnostic value.
 Electron microscopic examination of autopsy tissues from HFRS & HPS
patients showed more number of HANTA viral inclusion bodies
containing mature intact virions.
 Antigen detection : Immunohistochemistry: can test formalin fixed tissues
with specific monoclonal (murine) and polyclonal antibodies
retrospective diagnosis.
 Nucleic acid detection : By RT PCR, Nested PCR, real time RT PCR.
 Use of genus specific Oligonucleotide primers that anneal to regions of
‗S‘& ‗M‘ genomic segments confirms genotype of the infecting virus.
 Exponential production of product that may be sequenced for viral
characterization .

78. VIRUS ISOLATION
 Virus isolation is not commonly used for diagnosis of Hanta
viral infections in humans.
 Vero E6 cell line (ATCC CRL-1586) is used to isolate hanta virus
from blood, urine, tissue samples of HFRS patients and from
serum &urine of patients with Andes virus HPS.
 A monolayer cell cultures of Vero E6 cells are inoculated with
a crude / clarified tissue homogenate & maintained under a
fluid overlay for 10-14 days.

79. VIRUS ISOLATION
 Hanta viruses are neither cytopathic in cultured cells nor
pathogenic in laboratory rodents.
 Detection of infection in cultured cells & in tissues of
laboratory rodents is by an indirect method i.e
 1.Fluorescent antibody testing for viral antigen.
 2.RT PCR assay for Hantavirus specific RNA.

80. SEROLOGIC TESTS
 Detection of circulating immunoglobulins.
 Usually there is a robust immune response by the time symptoms
are present (24hours –within one week of infection)
 IgM present 3-6 months after infection.
 IgG can be detected for years post infection.
 IgG & IgM responses are directed first against nucleocapsid
protein, then against the glycoproteins.
 Neutralizing antibodies appear during acute phase of HFRS &
HPS—Reactive against glycoproteins Gn & Gc.
 IgG against Gn is more specific than anti nucleocapsid protein
IgG.

81. SEROLOGIC TESTS
 Methods to detect antibodies against hanta viruses in serum/ plasma are;
 1.High particle density agglutination.
 2.Indirect Immunofluorescence assay.
 3. Immunoprecipitation.
 4.RadioImmunoassay.
 5.Haemagglutination inhibition.
 6.Plaque & Focus reduction Neutralization -Foci of infected cells(viral
antigen in focus) is revealed by IHC staining/ Chemiluminescence.
 7.Western Immunoblotting-*using recombinant antigens and isotype
specific conjugates for IgM/IgG differentiation.
 8.µ capture (IgM) ELISA.
 9.IgG ELISA.

82. IgM Capture ELISA
 Highly sensitive in detecting antiHantavirus IgM, but not
specific for virus.
 It uses a Hanta virus infected cell lysate as test antigen.
 Uninfected cell lysate as control.
 Appropriate positive & negative control.

83. Treatment of
Hantavirus Infection
 General care, alleviation of symptoms
 Ribavirin (HFRS)
 ECMO (HPS).
 Hyper immune (Neutralizing ) serum.

84. GENERAL CARE
HFRS HPS
 General treatment for  General treatment for
renal failure pulmonary pathology
 Hydration  Administration of
 Dialysis oxygen

85. THERAPY
Aggressive supportive care
 Fluid management
 Hemodynamic monitoring
 Ventilatory support
 Peritoneal dialysis
 Pressor agents (blood pressure support)
 Inotropic agents (cardiac support)
 Increases cardiac muscle contractility
 Broad spectrum antibiotic therapy until HPS is proven
(to cover for differential diagnoses)
 Intravenous ceftriaxone or aminoglycoside
 Doxycycline

86. Ribavirin
 Administered intravenously
 Shown to be effective
against Hemorrhagic Fever
with Renal Syndrome
 Not shown to be effective
against Hantavirus
Pulmonary Syndrome
causing strains

87. ECMO-Takes over the function of heart and lungs while the patient
recovers from initial cause of pulmonary/cardiac failure
 Three components:
 1)membrane artificial
lung that adds oxygen
and removes carbon
dioxide
 2) roller pump that
moves the patient‘s
deoxygenated blood to
the membrane and back
into the body
 3) heat exchanger that
warms the blood back to
body temperature

88. PREVENTION & CONTROL
 Vaccines
 Hygiene

89. VACCINES
 No WHO approved vaccines are available.
 Inactivated vaccines have been developed in Asia & used
locally in Korea for protection of humans against HFRS.
 Inactivated vaccines are prepared from brains of suckling rats/
mice or from cell cultures infected with Hantaan virus/ seoul
virus.----Hantavax, commercially produced in S.korea.
 STRATAGIES for development of new Hanta virus vaccines
include:
 1.Recombinant nonpathogenic viruses,
 2. Rodent/ cell culture derived inactivated virus.
 3. Naked DNA
 4.E. Coli expressed truncated nucleocapsid as an immunogen

90. PREVENTION & CONTROL
 Rodent Control - control measures should be
aimed at reducing contact between humans and
rodents.
 Prevent aerosolization of virus from rodent
excrement
 Dampen surfaces with detergent before cleaning
 General hygiene