Hemorrhagic fever with renal syndrome (HFRS)
This disease is known as HFRS, epidemic hemorrhagic fever, Korean
hemorrhagic
fever,
epidemic
nephritis
nephropathica,
epidemic
Balkan
hemorrhagic fever.
HFRS occurs mainly in Europe, Asia and characterized by fever and renal
failure and hemorrhagic manifestations.
First this disease was recognized between 1913 and 1930 by soviet scientists
during sporadic outbreaks of fever with renal syndrome in the eastern Soviet
Union. Later disease occurs in North America, Korea, Europe.
Etiology.The disease is caused by the arbovirus, genus hantavirus, it is RNA
virus, lipid envelope, deactivating one’s ordinary disinfectants. The severity of
illness depends on the type of infecting virus and on the geographic distribution.
Korean hemorrhagic fever is a severe type of HFRS observed in Asia and
caused by hantavirus.
Balkan hemorrhagic fever is a severe type of HFRS and caused by Dobsava
virus, observed in Balkan continent.
Nephropathia epidemica is a mild borne of HFRS, which occurs in Europe,
China and caused by the Puumala virus.
Epidemiology.HFRS is caused by an airborne contact with secretions from
rodent hosts, infected with the group of viruses. The severity of this disease
depends on the type of virus and on the geographic distribution.
-Korean HF is transmitted by the infected apodemus agrarius (field mouse)
and is a severe form of HFRS. This disease is observed in Asia.
- Balkan HF is a severe type of HFRS caused by the Dobrava virus, and
transmitted by the infected apodemus flavicollis (yellow-necked field mouse), it
occurs in Balkan continent . Severe form
- HFRS due to Seoul virus is transmitted by the infected Rattus rattus (black
rat) or the Rattus norvegiculis (urban rat) and it is mild or moderate form of the
disease.
- nephropathia epidemica is a mild form of HFRS observed in Europe caused
by the Puumala virus and transmitted by the infected clethrionomys glareolus
(European bank vole).
Inoculation of the microorganism into human in the natural body is by
aerogenic route, by contact and alimentary route. Sporadic cases of HFRS are
registered during all year, predominantly in human. Group disease occurs
predominantly in summer and autumn.
Pathogenesis.The immune mechanisms play an important role in HFRS
pathogenesis. The cytokine production, complement pathway activation or an
increase in circulating complexes occur and play an important role during febrile
and hypotensive stages. Damage of the vascular endothelium, leakage, capillary
dilation is significant features of the disease.
Nitric oxide productions increase in the active phase of disease. In the
kidneys venous stage with serous – hemorrhagic edema development causes
degenerative changes in the epithelium cells and appearing of fibrin into kidneys
caniculla.
So serous-hemorrhagic nephritis in both kidneys and acute destructive and
obstructive hydronephrosis may develop.
Clinical manifestation.The incubation period in HFRS may range from 1 to
2 weeks in average, but may last until to 8 weeks. The disease may range from
mild to severe subclinical infection are especially common among children. The
onset of disease is sudden
Symtoms:
. Initially infancy headache, abdominal pain, fever chills, nausea.
Hushing of the face, inflammation or redness of cyst or rash, later – low
blood pressure, vascular leakage, acute kidney values.
The severity of the disease is associated with type of HFRS agent.
Hantavirus and Dobravas virus infection are usually severe, Seoul, Searemaa,
Rumula virus infections are usually moderate course of disease can include five
stages.
1.
Febrile stage lasts about 4-6 days. The asset of disease is abrupt with
high fever up to 40C. The patient complaints are headache, chills, abdominal, back
pain and malaise. During examination of patients can be revealed blushing of the
face, neck, chest, petechiae on the soft palate, axilla. Subconjunctival hemorrhage
bradycardia may be noted.
2.
The hypotensive stage lasts from a few hours to 2 days. It is
characterized by decreasing of the blood pressure, tachycardia, acute abdominal
pain, convulsion or purposeless movements. Blood examination in this stage may
reveal the changes of coagulation profile such as elevation of the prothrombin
time, activation of partial thromboplastin time, prolongation of bleeding time.
3.
The oliguria stage lasts about 3 to 6 days. The main signs in this stage
are oliguria, elevation of the blood pressure, tendency to bleeding, edema
(including pulmonary edema) thrombocytopenia. Anuria may be preserved then.
4.
The diuretic stage lasts 2-3 weeks and is characterized by increasing
of the diuresis (until 3 to 6 litters daily) rapid signs of dehydration and severe
shock in some cases. The main signs of previous stage disappear in many cases.
5.
The convalescent stage lasts for as long as 3 to 6 months. The main
signs of hemorrhagic fever with renal syndrome begin to disappear from the
second week of disease, glomerular filtration rate normalizes during 3 to 6 months.
The renal tubular concentrating capacity recovers many mouths.
Diagnostics.Diagnosis of HFRS is based on the geographic distribution of
the disease, epidemiological and clinical data, laboratory evaluations.
Blood picture abnormalities revealed are the following: leucocytosis,
thrombocytopenia, elevation of hematocrit; prolonged bleeding time, elevation of
prothrombin time, activation of thromboplastin time in hypo stage; elevation of
live enzymes, blood urea nitrogen; hematuria, proteinuria can be evident;
hypernatremia, hyperphasphatemia, hyperpotassemia.
Serological tests can help in diagnosis. Enzymes linked immunosorbent
assay is useful for section of antibodies. For field rise in titer IgM for 1 week
against Hantaviruses are evident.
Hantavirus antigen can be detected in different tissues, in microvasculature
by immunohistochemical methods.
Treatment.The treatment depends on the stage of the disease, status of
hydration and overall hemodynamic patient’s condition.
A low sodium diet with restriction of fluid during, diuretics oliguria stage is
recommended. Dialysis is indicated if the patient is oliguric for a prolonged time
with no response to diuretics and renal failure is rapid with electrolyte abnormality
and worsening fluid
Maintaining fluid and electrolyte balance is mandatory in the acute disease.
Early and effective fluid therapy is the cornerstone in the renal failure. The use of
vasoactive agents and albumin is recommended in shock period:
excessive administration of fluid can lead to extravasation due by vascular
leak, especially during the febrile and hypotensive stages. In oliguric stages
diuretic is recommended
.
Dialysis is indicated if the patient is oliguric for a prolonged time with no
response to diuretics and renal failure is rapid with electrolyte abnormality and
worsening fluid.
Corticosteroids, prednisolone, hydrocortisone inhibitors of proteolysis
(contrical), vitamins (C, P) other symptomatic drugs can be used
. Ribaverin intravenous that is indicated within 4 days of illness can reduce
morbidity and used only in some countries.
Antihypertensive agent, vasoactive drugs, colloids or diuretics may be
needed to control hypertension, treat shock, to induce diuresis.
After discharging from the hospital patients must be examined in outpatient
department during 3 to 6 months.
Ebola hemorrhagic fever
Ebola hemorrhagic fever is an acute virus quarantine dangerous disease
which is characterized by severe course, pronounced hemorrhagic syndrome and
high mortality rate.
Etiology.Ebola hemorrhagic fever is caused by four or five viruses classified
in the genus Ebola virus family Filoviridae . They are Zaire Ebola virus ( Ebo-z),
Sudan Ebola virus (Ebola-s) , Ebola Ivory Coast ( EBOCI), Bundibugon Ebola
virus ( BDBV). The filth Reston virus is thought to be a pathogenic for humans, it
is pathogenic for monkeys.
Ebola virus has different forms, the virions are tubular and variable in shape
and may appear as “U”, “6” coiled, circular or branched shape. The virions are
generally 80mm in diameter, can be up do 1400 mm long. This virus is RWAcontaining microorganism complexed with the proteins NP, LVP 30 and VP35. In
the so- called matrix space of microorganism the viral proteins VP 40 and VP 24
are colaced.
This virus is highly infectious, can change very quickly, is not resistant to
damaged factors of the external environment (ph.humidity, insulation) all Ebola
virus subtypes are originated from Africa, except subtype Reston, which is from
Philippines.
Epidemiology.The reservoirs of infection in EHF are chimpanzees, spiders,
sold ticks, fluid bats, monkeys, gorillas, plants, fruit bats. The sick patients are
dangerous for other people. The mechanisms of transmission are the following:
•
Through the close contact with infected animal blood and cell cultures
•
Through the contact with blood and discharges of infected human
(semen feces, vomitus, mucus, urine)
•
Through inhalation of infected small particle aerosols
Humans can be infected with different routes: by air –droplets,contact
injections or sometimes sexually.
The susceptibility to this disease is high, immunity is stable, secondary
disease is rare (about 5 %).
In 7 to 10% of the population in endemic areas have antibody to Ebola
virus.First cases of EHF was first discovered in 1976 near the Ebola, rivers in what
is now the Democratic Republic of the Congo, now Zaire.
Pathogenesis.The portal entries for Ebola viruses are mucous membranes
and skin. After infection the virus lead to the lymph nodes and spleen with
following virus replication there and intensive virusemia development.
About 1 week after infection the begins attaching blood and lives cells. If the
pathological process will progress the virus can destroy vital organs such as the
liver, kidneys, leading to massive internal bleeding. As a result of primary toxic
effect of the virus and autoimmune reaction the decreasing of thrombocytes
production damaging of vessels epithelium in internal organs with necrotic foci
and hemorrhage are noted. The main changes are located in the liver, spleen,
lymph nodes, kidneys, brain, ovaries. In fatal cases non-effective immune response
could be due to immunosuppressive amino acid sequence in filovirus glucoprotein.
Clinical manifestation.The incubation period is 3to 10 days, ranges from 2
to 21 days. The onset of EHF is abrupt with high fever (39-40C), frontal and
temporal headache, myalgia, arthralgias, abdominal pain, nausea, vomiting.
The chest pain, cough, pharyngitis can be noted too. These early symptoms
are easily mistaken for typhoid fever, malaria, influenza or various bacterial
infection.
Later disease may process to cause more serious symptoms. On 2-3 days of
the disease blood vomiting, diarrhea, dark or bloody feces, lethargy, change in
menation are noted. An enanthema of the palate and tonsils, cervical
lymphadenopathy has revealed during the first week of illness. The maculopapular
rash begins on the 5-7 day on the face, neck and spreads centrifugally to the
extremities. A line desquamation of the affected skin, especially on the palms and
soles appears 4-5 days later.
Hemorrhagic syndrome, which occurs on 3-5 day of disease is the most
common. Epistaxis, hematemesis, petechia, purpura, ecchymosis, bleeding
erosions in mucosa of mouth, bleeding from needle- puncture sites are
characteristics. In severe cases gastrointestinal, renal, vaginal and / or conjunctival
bleeding develop in sick patients.
Somnolence, delirium, coma, hypotension, tachycardia, paresthesia, crams
can be pronounced. During the first weak the temperature remains, around 40 0 C,
decreasing by lysis, for the second week, only to increase again on 12-14 days. On
the 2-nd week splenomegaly, hepatomegaly, edema scrotum or labia.
Complications.Myocarditis, pancreatitis, orchitis (which lead to testicular
atrophy).
Mortality rate is high (range from 50-90%). The cause of death is usually
due to hypovolemia shock or organ failure often accompany by DVS and liver
failure (on the 8-16 day of illness). Recovery is often protracted over 3 to 4 weeks’
period. During their period loss of hai , intermittent abdominal pain , poor appetite,
prolonged psychotic disturbances have been later – transverse myelitis and uveitis
have been reported.
Diagnostics.Laboratory findings in EHV include leucopenia ( low as
1000/ul) from the first day of disease with neutrophilia
by the fourth day ;
thrombocytopenia ( often with fewer than 10000 cells/ul) on 6-12 days; elevation
of transaminase levels ( sat > alt ) . Fatal cases may include evidence of
disseminated intravascular coagulation.
Specific diagnostics requires isolation of the Ebola virus or detection of
serological evidence of infection in paired serum samples. Viremia coincides with
the febrile stage of disease; virus has been isolated from tissue, urine,semen, treat,
rectal swabs. These investigations may be done only in specialized high – security
laboratories ELISA, PSR.
Treatment.The therapy of EHF is supportive. The administration of
convalescent –phase serum from recovered patient has been proposed. Interferon,
in DI S – heparin, replacement of coagulation factors and platelets can be used.
Prevention.The patients must be isolated in special department with strong
regime. The prevention of EHV includes:
•
Proper sterilization of injection equipment
•
Protect from body fluids during dealing with cadavers
•
Routine barrier nursing precautions, strict isolation, respiratory
protection
•
Extensive quarantine precautions
•
Producing of effective vaccine for humans
Marburg hemorrhagic fever
Marburg hemorrhagic fever (MHF) is acute zoonotic disease with high
mortality rate, pronounced intoxication and universal capillary toxicosis.
Marburg virus is known after outbreaks of hemorrhagic fever in Germany in
1967 year.
Etiology.The agent of this disease is Marburg virus family Filaviridae. The
viral parts are polymorphic ( as threats, spirals, or oval forms) 790 mm long and 80
mm diameter. This microorganism contains negative one threading RNA and
lipoprotein. There are 7 proteins in the virions. The protein contents of Marburg
virus mimic Ebola virus but strain specific antigens in Marburg virus is
concentrates in areas of 6 p protein and group specific antigens- in areas of Np
protein. Hemagglutinin and hemolysin didn't revealed in Marburg virus. This
microorganism is resistant to external environment factors.
Epidemiology.The source of MHF virus is monkeys predominantly African
marmosets. The mechanisms of transmission are by contact, aerosols, ardiphicial.
The routers of transmission are by air – droplets, by contact, by injections. The
MHF virus can be in blood, nasopharyngeal mucus, urine, sperm during 3 months.
The human infection is possible in primary contact with blood and organs of
monkeys through damaged skin (in injections, cuts), through the conjunctiva
sexual mechanism of transmission was described too.
The susceptibility to Marburg virus is high. Secondary cases of MHF are
absent. The immunity after disease is stable. Jason depending characteristics of
their disease didn't described.
MHF occurs in the central and West Africa and south of this Continent.
Pathogenesis.The portals entry of MHF are damaged skin, mucous
membranes of mouth and eyes.
The primary replication of MHF happens in mononuclear cells and
macrophages later viremia which is accompanied by suppression of the immune
system
function
develops.
Together
with
generalized
microcirculation
disturbances. These changes lead to revealing of DIS and polyorganic
disturbances. In the lungs, myocardial, liver, kidneys, spleen, suprarenal glands
and other organs can have revealed foci of necrosis and hemorrhages.
Clinical manifestation.The incubation period in MHF is 3-16 days. The
onset of disease is acute with pronounced intoxication. The fever is high during 2
weeks, which is accompanied by headache, myalgia, predominantly in lumbar –
sacral area.
During examination in initial period conjunctivitis, enanthems, vesicular –
erosive changes in month bradycardia can revealed. To us of muscles has been
increased and muscles is painful.
On 3-4 days vomiting and watery diarrhea appear which can lead to
dehydration.
On 5-6 days’ maculopapular eruptions with following desquamation is
possible.
On 6-7 days’ hemorrhagic manifestations (such as skin hemorrhages, nasal,
gastrointestinal and other hemorrhages), signs of hepatitis, myocarditis, damaging
of kidneys are noted.
The damaging of central nervous system can be done. Adynamia,
meningismus are characteristics for CNS damaging at the end of first week signs of
toxic shock and dehydration can be pronounced.
The patient’scondition become worse on the 8-10 days and 15-17 days after
onset of the disease. The fatal outcomes can be in these days. Generally, mortality
rate in MHF ranges from 25-50. The reasons of death are edema of lungs and
brain, hypovolemic shock, acute renal insufficiency, DTS syndrome development.
In the favorable outcomes in convalescent period appearing of long diarrhea,
asthenic syndrome sign, psychic abnormalities, balding can be noted.
Complication.Complication
of
MHF
are
hepatitis,
orchids,shock, uveitis, sometimes pneumonia and psychosis.
myocarditis,
Diagnostics.Clinical diagnostics
is difficult because pathognomonic
symptoms of MHF is absent. Epidemiological data (stay in places with natural foci
of MHF), contact with green marmosets, contact with patients and results of
serological virological, electron – microscopic investigations.
Specific investigations mimic Ebola hemorrhagic fever diagnostics
(revealing of the virus culture, PCR, IFA, NA, CFT and others).
In fatal outcomes electron microscopic investigation or NYF assay for
revealing of virus are used.
Blood picture investigation revealed the following changes: anemia,
anisocytosis,
poikilocytosis,
thrombocytopenia.Elevation
of
leucocytosis,
the
sniff
transaminase
level;
to
the
the
signs
left,
of
hypocoagulation and metabolic acidosis.
Treatment.The patients with MHF must be hospitalized with strong regime
in department of hospital. Diet is 4 without exception of the protein and sodium
chloride. Pathogenetic therapy is the main management. The aims of this therapy
are dehydration, treatment of toxic shock and hemorrhagic syndrome.
Reconvalescent serum, interferon, plasmapheresis can be used.
Prognosis serious with 25% in average fatality rate or prolonged
convalescent period.