Hantaviruses are negative-sense, single-stranded RNA viruses that are primarily transmitted to humans through contact with infected rodent droppings and urine. They cause two serious diseases: Hemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS). HFRS presents with fever, abdominal pain, bleeding, and kidney failure, while HPS causes rapid onset pulmonary edema leading to respiratory distress. Diagnosis involves virus isolation from patient samples or serological detection of antibodies. There is no vaccine and treatment focuses on supportive care.
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Hantavirus
1. HANTAVIRUS
PRESENTER: Dr. Paripurna Baruah, 2nd YR PGT, Deptt. Of Microbiology
MODERATOR: Dr. Chimanjita Phukan, Assoc. Professor, Deptt. Of Microbiology
2. CLASSIFICATION
NEGATIVE SENSE
SINGLE STRANDED
RNA VIRUSES
SEGMENTED GENOME
ORTHOMYXOVIRIDAE
BUNYAVIRIDAE
(approx. 300 distinct
viruses)
ORTHOBUNYAVIRUS
NAIROVIRUS
HANTAVIRUS
PHLEBOVIRUS
TOSPOVIRUS
ARENAVIRIDAE
MONOPARTITE (-)
SENSE GENOME
3. STRUCTURE
Bunyaviruses are spherical or
pleomorphic, 80 to 120 nm
enveloped particles.
External features of the virions
include a distinct bila- minar
membrane, approximately 5 nm
thick, and a fringe of surface
projections approximately 5–10 nm
long, comprised of the viral envelope
glycoproteins, G1 and G2
The genome is made up of a triple-
segmented, circular, single-stranded,
negative-sense RNA, 11–19 kb in
overall size.
Virion particles contain three
circular, helically symmetric
nucleocapsids about 2.5 nm in
diameter and 200–3000 nm in
length.
Replication occurs in the cytoplasm,
and an envelope is acquired by
budding into the Golgi.
7. ■ Viruses of the family Bunyaviridae are maintained in nature in a complex life cycle,
usually involving an arthropod vector and a vertebrate host. The exceptions are
viruses of the genus Hantavirus, which are maintained by chronic infection of
rodents and other small mammals.
■ Hantaviruses, perhaps like other members of the family, represent an excellent
example of co-evolution of the virus with a specific vertebrate host. As information
about each of the genetically unique hantaviruses accumulates, it is increasingly
apparent that each virus is specifically linked to a particular species of rodent host.
8. ■ The viruses are found worldwide and cause two serious and often fatal human
diseases:
– HEMORRHAGIC FEVER WITH RENAL SYNDROME
– HANTAVIRUS PULMONARY SYNDROME.
■ It is estimated there are 100,000–200,000 cases of hantavirus infections annually
worldwide.
■ There are several distinct hantaviruses, each associated with a specific rodent host.
■ The virus infections in rodents are lifelong and without deleterious effects. Transmission
among rodents seems to occur horizontally, and transmission to humans occurs by
inhaling aerosols of rodent excreta (urine, feces, saliva).
■ The presence of hantavirus-associated diseases is determined by the geographic
distribution of the rodent reservoirs.
9. ■ There is a strong occupational association with the risk of hantaviral infection,
farmers, woodcutters, soldiers, and others with significant rural exposure being
most often infected.
■ Hantaviral infections are seasonal.
■ They occur frequently in warmer months when recreational activities and outdoor
work bring people into close contact with infected rodents. Infections caused by
hantaan and Puumala virus peak in prevalence also in late fall and early winter in
Asia and Europe, respectively. In cold seasons, the rodents seek shelter in homes
and sheds, infecting not only male workers, but also children and women.
10. the Hantaan-like
viruses
Murinae rodents (Old
World mice and rats)
Sin Nombre- like
viruses
Sigmodontinae
rodents (New World
mice and rats)
Puumala-like
viruses
Arvicolinae rodents
(lemmings and
voles)
13. ■ HEMORRHAGIC FEVER WITH RENAL SYNDROME (HFRS) has long been recognized
clinically in Asia, Russia, and Scandinavia, but the etiology of the syndrome has been
known only since the late 1970s.
■ It was not until 1978, however, that the causative agent, hantaan virus, was isolated
from the lungs of the striped fieldmouse, Apodemus agrarius.
■ The most severe form of HFRS occurs in Asia and is caused by prototype hantaan virus.
It is associated with a case-fatality rate of approximately 5 percent, although this may
be much higher in certain rural areas.
14. ■ Abrupt onset of fever, chills, malaise, myalgia, headache, dizziness, and anorexia
after a variable incubation period of 2–42 days, but most often of 2–4 weeks.
•severe abdominal and back pain
• nausea and vomiting,
• tenderness over the lower back,
• flushing of face, neck and chest,
•injection of conjunctivae, palate, and pharynx.
• Petechia on the axillae, face, neck, chest, and soft
palate,
•hemorrhages into the conjunctivae
•Normal/ slightly elevated white blood cell counts,
decreased platelets and rising hematocrit
• Proteinuria may appear towards the end of this phase
of the disease
15. ■ Defervescence occurs after 3–7 days
■ start of the hypotensive phase,
■ several hours to a few days.
■ tachycardia, falling arterial pressure, and narrowing pulse pressure, mental
changes and, in severe cases, classic shock.
•Bleeding tendencies continue
• Leukocytosis, thrombocytopenia, and prolonged bleeding times
are seen;
•there are high levels of proteinuria and oliguria begins.
•About one-third of the fatalities occur during this phase.
16. ■ The oliguric phase follows and lasts for 3–7 days,
■ blood pressure returns to normal or is slightly elevated due to rela- tive
hypervolemia.
•elevated serum creatinine and blood urea nitrogen and other
evidence of renal failure
•Rash and facial flushing disappear during this phase.
• Severe hemorrhagic manifestations,
• gastro- intestinal or CNS bleeding being especially serious.
•Almost half the deaths occur during this phase, often due to
•pulmonary edema or infection,
•electrolyte imbalance,
•late shock,
•hemorrhage into the brain.
17. ■ Clinical recovery begins during the diuretic phase, with the normalization of
clotting and return of renal function. For the next few hours or days there is
diuresis, with outputs of 3–6 liters daily.
•Specific therapy is not available, and careful
supportive care is essential to improving survival.
•Care must be consistent with the phase of the
disease, careful attention being paid to fluid
management.
•Recent studies have demonstrated that ribavirin is
efficacious in treating HFRS if administered early in
the course of illness
18. ■ Other Old World hantaviruses cause diseases similar to, though generally less
severe than, classic hantaan virus infections.
■ These include Puumala virus, the cause of nephropathia epidemica of western
Europe, Scandinavia, and the western portions of Russia.
■ Nephropathia epidemica may follow the same phases as classic HFRS, but is fatal
in less than 1 percent of cases.
19. HEMORRHAGIC FEVER WITH RENAL
SYNDROME
acute viral infection that causes an interstitial nephritis that can lead to acute renal
insufficiency and renal failure in severe forms of the disease.
HFRS
Severe form of
the disease
5% case fatality
Hantaan virus
Asia
Dobrava virus
Balkan region
Moderately
severe form of
disease
Seoul virus
China
Americas
Nephropathia
epidemica
<1% case fatality
Puumala virus
Eurasia
20. HANTAVIRUS PULMONARY SYNDROME
■ Hantavirus pulmonary syndrome was first recognized in 1993, when an outbreak
of an apparently new and highly fatal form of severe respiratory illness occurred in
southwestern USA.
■ It was caused by a previously unknown hantavirus, later named Sin Nombre virus
(also reported as Four Corners or Muerto Canyon virus).
21. ■ More than 2000 cases of HFRS occurred among United Nations troops during the
Korean War, but Hantaan virus was not isolated until 1976 in Korea from a rodent,
Apodemus agrarius.
■ HFRS is treated using supportive therapy. Prevention depends on rodent control
and protection from exposure to rodent droppings and contaminated material.
22. HANTAVIRUS PULMONARY SYNDROME
■ In 1993, an outbreak of severe respiratory illness occurred in the United States,
now designated the hantavirus pulmonary syndrome (HPS).
■ It was found to be caused by a novel hantavirus (Sin Nombre virus).
■ This agent was the first hantavirus recognized to cause disease in North America
and the first to cause primarily an adult respiratory distress syndrome.
■ Since that time, numerous hantaviruses have been detected in rodents in North,
Central, and South America.
23. ■ The deer mouse (Peromyscus maniculatus) is the primary rodent reservoir for Sin
Nombre virus. Deer mice are wide- spread, and about 10% of those tested show
evidence of infection with Sin Nombre virus.
■ HPS is generally severe, with reported mortality rates of 30% or greater. This case-
fatality rate is substantially higher than that of other hantavirus infections.
■ The disease begins with fever, headache, and myalgia followed by rapidly
progressive pulmonary edema, often leading to severe respiratory compromise.
There are no signs of hemorrhage.
24. Based on a study on the 17 patients originally described by
Duchin et al (1994)
76%
76%
71%
SYMPTOMS
COUGH/ DYSPNOEA GASTROINTESTINAL HEADACHE
100%
100%
50%
SIGNS
TCHYPNOEA TACHYCARDIA HYPOTENSION
25. ■ This disease was seen to be rapidly progressive with high case fatality, killing 13 of
the 17 patients described in this study.
■ Predictors of death included increase in hematocrit and partial thromboplastin
time, and all deaths occurred with profound hypotension.
■ In another study done by Zaki et al in 1995, post mortem was done in all 44 fatal
cases, to find
– Multiorgan involvement with generalized vascular congestion.
– Viral antigens were abundantly distributed in endothelial tissue of lungs,
lymphoid follicles of spleen and also lymph node follicles.
26. ■ Treatment has been:
– prompt hospitalization,
– aggressive clinical management
– early pulmonary support.
■ Ribavirin, which can be efficacious in the treatment of HFRS patients, has been
administered to hantavirus pulmonary syndrome patients, but at present there are
insufficient data to indicate efficacy clearly.
28. SPECIMEN
■ Blood collected during the acute phase of the disease may yield the virus.
■ Serum is collected for serological diagnosis.
■ Autopsy tissue.
29. ISOLATION
■ Tissue culture
■ inoculation of suckling mice
■ cell cultures of mammalian or insect origin have been often used with
considerable success.
30. DIAGNOSTIC TESTS
■ Diagnosis is based on demonstration of the specific virus causing infection, by isolation, by
detection of viral antigen or nucleic acids, or by acquisition of antibody specific for the infecting
virus.
■ Routine serological techniques such as
– hemagglutination inhibition,
– complement fixation,
– immunofluorescent antibody assays,
– neutralization tests in mice or cell culture
■ have been used to demonstrate rising or falling titres of antibody in paired sera from patients.
■ These techniques are generally time consuming and expensive, and do not offer a definitive
diagnosis soon enough to influence clinical management.
31. ■ Recently, more rapid diagnostic procedures have been developed that can offer a
presumptive diagnosis within a few hours of receipt of a single acute serum sample.
■ With enzyme immunoassays, viral antigen may be detected directly, or virus-specific
IgM antibody demonstrated, generally in time to influence clinical management.
■ For example, patients with HFRS due to hantaan virus are often positive for IgM
antibodies at the time of hospital admission.
■ Direct detection of viral nucleic acid, most often through reverse transcriptase-
polymerase chain reaction amplification, and subsequent sequencing or endonuclease
digestion of amplified products, has recently been applied for diagnosis.
■ However, the value of the technique is limited by the need for specially designed
primers and very careful laboratory techniques to minimize the risk of contamination
(Grankvist et al. 1992; Feldmann et al. 1993; Nichol et al. 1993).
■ At present, these techniques are limited to research or reference laboratories and not
widely available.
32. References
■ Duchin, J.S., Koster, F.T., et al. 1994. Hantavirus pulmonary syndrome: a clinical description of 17
patients with a newly recognized disease. N Engl J Med, 330, 949–55.
■ Zaki, S.R., Greer, P.W., et al. 1995. Hantavirus pulmonary syndrome. Pathogenesis of an emerging
infectious disease. Am J Pathol, 146, 552–79.
■ Grankvist, O., Juto, P., et al. 1992. Detection of nephropathia epidemica virus RNA in patient
samples using a nested primer-based polymerase chain reaction. J Infect Dis, 165, 934–7.
■ Feldmann, H., Sanchez, A., et al. 1993. Utilization of autopsy RNA for the synthesis of the
nucleocapsid antigen of a newly recognized virus associated with hantavirus pulmonary
syndrome. Virus Res, 30, 351–67.
■ Nichol, S.T., Spiropoulou, C.F., et al. 1993. Genetic identification of a novel hantavirus associated
with an outbreak of acute respiratory illness in the southwestern United States. Science, 262,
914–17.