this is a very serious hemorrhagic virus even if, it is very rare in our settings , we should be aware of it and sometime include it in our differential of renal failure with hemorrhagic fever or cardiopulmonary stuffs.

1. INFECTIOUS DISEASES: HANTAVIRUS
TOPIC : HEMORRHAGIC FEVER WITH RENAL
SYNDROME.
By MURAGIJEYEZU Emmanuel.
University of Rwanda

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. Epidemiology
• 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 Africa.
• 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.

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

18. 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.

19. • 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 .

20. 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.

21. 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.

22. • 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

23. 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 .

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

25. 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.

26. 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.

27. 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