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Hantavirus
- 1. HANTAVIRUS PRESENTER: Dr. ParipurnaBaruah, 2nd YR PGT, Deptt. Of Microbiology MODERATOR: Dr. Chimanjita Phukan, Assoc. Professor, Deptt. Of Microbiology
- 2. CLASSIFICATION NEGATIVE SENSE SINGLE STRANDED RNAVIRUSES SEGMENTED GENOME ORTHOMYXOVIRIDAE BUNYAVIRIDAE (approx. 300 distinct viruses) ORTHOBUNYAVIRUS NAIROVIRUS HANTAVIRUS PHLEBOVIRUS TOSPOVIRUS ARENAVIRIDAE MONOPARTITE (-) SENSE GENOME
- 3. STRUCTURE Bunyaviruses are sphericalor 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.
- 5. G1 and G2 glycoproteins Carbohydrate Transmembranedomains of G1 and/or G2 Bilaminar lipid envelope N protein Ribonucleocapsids (L, M, S) L protein 80–120 nm
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- 7. ■ Viruses ofthe 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 virusesare 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 isa 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)
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- 13. ■ HEMORRHAGIC FEVERWITH 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 onsetof 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 occursafter 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 oliguricphase 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 recoverybegins 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 OldWorld 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 WITHRENAL 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 than2000 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 deermouse (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 astudy 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 diseasewas 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 hasbeen: – 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.
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- 28. SPECIMEN ■ Blood collectedduring 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 ■ Diagnosisis 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, morerapid 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.