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Hantavirus

1. INFECTIOUS DISEASES: HANTAVIRUS TOPIC : HEMORRHAGIC FEVER WITH RENAL SYNDROME. By LOMURIA GODFREY MANDELA Metropolitan International university

2. GENERAL INTRODUCTION HANTAVIRUS is genus of more than 20 known species of rodent-borne viruses , the family Bunyaviridae. 11 spp are associated with human diseases. Only Two major forms of syndrome are known : 1 ) Hemorrhagic fever with renal syndrome ( HFRS) found in old world. 2) Hantavirus cardiopulmonary syndrome (HCPS, also called HPS) found in new world.

3. HANTAVIRUS They are single-stranded, negative-sense RNA genomes that are divided into three segments: The L, or large segment, encodes a replicative enzyme, RNA-dependent RNA polymerase; The M (middle) segment encodes the envelope glycoproteins G1 and G2, and The S segment encodes the nucleocapsid protein N.

4. Cont… The envelope glycoproteins G1, G2 may mediate attachment to cells via the beta-3-integrin cell-surface molecule , which is found on endothelial cells and platelets throughout the body . Tissue tropism especially to renal tubules This the key for the whole pathogenesis.

5. Species and severity Severe form :Dobrava , hantaan viruses Intermediate form :Seoul virus Mild form :puumala , vole-borne virus Sangassou virus

6. HEMORRHAGIC FEVER WITH RENAL SYNDROME. TRIAD : FEVER , HEMORRHAGE AND RENAL FAILURE In addition to history of rodents contact.

7. HFRS were recognized between 1913 and 1930 by Soviet scientists, who described sporadic outbreaks of fever with renal failure in the eastern Soviet Union . in 1950 -1953, when the North American soldiers in Korea developed a febrile illness associated with shock, hemorrhage, and renal failure . 3000 soldiers infected , 10% died of diseases. History

8. WHO removed confusion. In an attempt to avoid confusion, these diseases are now collectively referred to by the World Health Organization as "hemorrhagic fever with renal syndrome" (HFRS). epidemic hemorrhagic fever, hemorrhagic nephrosonephritis, Songo fever , Korean hemorrhagic fever, and nephropathia epidemica

9. E pidemiology Approximately 150,000 to 200,000 cases of HFRS are hospitalized each year world wide, with most of the cases occurring in the developing countries. The case fatality rate of HFRS varies from < 3% to 12% depending on the viruses. Only one case was reported from A frica. To our search no case in Rwanda.

10. GEOGRAPHICAL DISTRIBUTION

11. TRANSMISSION TO Human . Through contact with infected rodent excreta (urine , saliva , feces , dead body or blood ) Being inhalation , Mucosa contact or bite

12. PATHOGENESIS EARLY INFECTION: after contact with the virus they are taken up in phagocytes and transported to draining lymph nodes. The viruses establish infection in the regional nodes and disseminate primarily to distant organs. The viruses replicate principally in vascular endothelial cells and then establish a secondary viremia through tissue tropism.

13. Cell entry : the viruses use beta-3 integrins to enter endothelial cell. dysregulation of endothelial cell . Increased vascular permeability and loss of maintenance of vascular integrity, central role in the disease progress is immune mediated through activation of pro inflammatory mediators TNF , IL1,6,8 and high NO.

14. Patho cont….. Damage to vascular endothelium Initiation of tubular and interstitial damage by cytokines and other humoral factors (such as TNF, IL 1 ), causing acute tubulo-interstitial nephritis. This is corroborated by the increased expression of cytokines in the peritubular areas. The correlation of urinary excretion of interleukin-6 with the amount of proteinuria (eg, severity of damage). congestion and dilatation of the medullary vessels, hemorrhage into the medullary tissues, interstitial edema, and tubular cell necrosis and degeneration.

15. Clinical features A 2- to 3-week incubation period is followed by a protracted clinical course. The hallmark triad of HFRS comprise of: fever , hemorrhage and renal failure. Typical phases : febrile period , hypotension, oliguria , Diuresis and convalescence phase.

16. DIFFERENTIAL DIAGNOSIS Viral hemorrhagic fevers (dengue fever,…) Leptospirosis DIC Malaria Hemolytic uremic syndrome Sepsis Scrub typhus

17. DIAGNOSIS tests history with the previous rodent exposure and physical examination should give us the high suspicion of the disease. The diagnostic test should include exclusion tests for others : FBC , LFTS ( LDH ,Transaminase enzymes , coagulation factors , albumin ) Renal functional test ( urea , creatinine, electrolytes ) which may reveal hemoconcentration and elevation in lactate dehydrogenase, serum lactate, and increased hepatocellular enzymes , thrombocytopenia and leukocytosis (as high as 90,000 cells/mcL ), uremia ,electrolytes imbalance . Rarely Cardiac enzymes (CK-MB, troponin) , CXR if respiratory signs.

18. SEROLOGY TESTS : ELISA test detection of antibodies against viral antigens IgG and IgM. IgM in HFRS patient rise simultaneously with the onset of clinical symptoms and will reach the maximum 7-11 days after initial symptoms, in convalescent phase the level of IgM decline then the level of IgG increase which persist for long time . A plaque reduction neutralization test : The gold standard serologic assay and distinguishes between the different Hantavirus species. This should be performed in a laboratory with appropriate biosafety (level 3). RT-PCR of a blood clot collected .

19. MANAGEMENT. Currently , there is no specific therapy available for both HFRS . The cornerstone of treatment is supportive management . Including early admission to an ICU where blood and tissue oxygenation, cardiac output, central blood pressure and cerebral pressure can be monitored . Maintaining fluids balance is very important; it must be carefully monitored according to the patient's fluid status, amount of urinary output , and kidney function. Usually one or two haemodialysis sessions are needed for HFRS treatment.

20. Cont.. Ribavirin shows antihantaviral effect both in vitro and in vivo . Ribavirin is often used in treatment of HFRS in China and clinical trials there have shown that Ribavirin therapy can significantly reduce the mortality and the risk of entering the oliguric phase and experiencing hemorrhage. Ribavirin is included in the WHO Model List of Essential Medicines for HFRS treatment in 2007 . No clinical benefit of corticosteroid in treatment of HFRS.

21. Antihypertensive agents Diuretics ( furosemide ) ACE-inhibitor Beta blockers Colloids Vasopressors ( dopamine ) Transfusion if Hb < 7g/dl Nutrition ( salt and fluid restriction) Patient education Early referral

22. surgical If the clinical presentation involves extravasation of plasma in the abdomen (suggestive of acute abdomen and subsequent development of paralytic ileus), occasionally, exploratory laparotomy. Renal rupture, which rarely occurs, requires surgical management. A pediatric nephrologist should perform renal biopsy if necessary .

23. Complications Chronic renal failure Anemia Stroke Thrombocytopenia HUS Pulmonary edema Superinfection. IVH (intraventricular hemorrhage)

24. Prognosis The prognosis of HFRS depends severity of illness and on the causative strain in which hantaan virus and dobrava virus are the common cause of severe HFRS, with a mortality rate of 3% up to 12%. convalescence within 3—6 months if patient managed conservatively well.

25. Prevention Control of rodents in houses and avoidance of exposure to rodent excreta in rural settings. Vaccines are being studied in animals and some countries like korea are using the vaccine in military campoos.

26. My library 1.kasper et al “Harrison principles of internal medicine 19ed pdf ”. 2.Maxine A. Papadikas et al “current medical diagnosis and treatment 2015 54ed pdf ”. 3. Dispatches Hantavirus “Transmission in the United States” Vol. 3, No. 3, July–September 1997 , Emerging Infectious Diseases. 4. Sinasi Salman, MD “ Uremic Bleeding: Pathophysiology, Diagnosis, and Management” C l i n i c a l R e v i e w A r t i c l e . 5. Gerald B appel MD “ Renal involvement with hantavirus infection (hemorrhagic fever with renal syndrome)” up to date .com 2013. 6.Brian H jelly MD “Epidemiology and diagnosis of hantavirus infection” up to date .com 2013. 7. . Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 18, No. 12, December 2012 .   8. www.medscape.com

27. THANK YOU FOR YOUR KIND ATTENTION

28. METROPOLITAN INTERNATIONAL UNIVERSITY NAME: LOMURIA GODFREY MANDELA COURSE: DIPLOMA IN CLINICAL MEDICINE REGISTRATION NUMBER: 23B/DCM/012/UMR COURSE UNIT: MICROBIOLOGY II LECTURER’S NAME: MADAM LINDA