Viral Hemorrhagic Fevers

(VHF)
 Viral Hemorrhagic Fever viruses
• Filoviruses Ebola Hemorrhagic fever (EHF)
Marburg virus

• Arenaviruse Lassa fever

“New World Arenaviruses”

• Bunyaviruses Rift Valley fever (RVF)

Hemorrhagic fever with renal syndrome (HFRS)
Crimean Congo Hemorrhagic fever (CCHF)
• Flaviviruses Yellow fever
Dengue fever
 Epidemiology
• These rodent viruses are geographically
widespread, with varying epidemiologic and
clinical presentations.
• Transmission to humans is through inhaltion
of infectious aerosols from rodent excrete and
bites.
• Insect vectors are involved in Congo Crimean
HF
 Clinical presentation
• Acute infection:
fever, myalgia, malaise; progression to prostration
• Small vessel involvement:
increased permeability, cellular damage
• Multisystem compromise (varies with pathogen)
• Hemorrhage may be small in volume
(indicates small vessel involvement,
thrombocytopenia)
• Poor prognosis associated with:
shock, encephalopathy, extensive hemorrhage
 Pathogenesis
• VHF syndrome is a constallation of findings
based on vascular instability and decreased
vascular integrity.
• An assault, direct or indirect, on the
microvascular leads to increased permeability
and(particularly when platelet function is
decreased) to actual disruption and local
hemorrhage
• In severe cases chock supervenes
• Direct damage to the vascular system, or
soluble mediators are thought to play a major
role
 Hantaanvirus Infections

• Acute infections caused by species

Hantaanvirus, transmitted to humans from
rodents, characterized either by acute renal
failure(nephritis) and hemorrhage or a
syndrome of acute noncardiogenic pulmonary
edema
 Hantaanvirus Infections

• Two major, sometimes overlaping syndromes

HFRS and HPS
• Four strains of the Hantaan virus, a
Bunyavirus, are involved in human disease. At
least nine viruses has been associated with
HFRS and HPS
• Viruses associated with HFRS are Hantaan,
Seul, Dobrava(Belgrade), Puumala.
 HFRS
• HF with renal failure
• A milder form of HFRS (nephropathia
epidemica) caused by Puumala virus is
common in Scandinvia:
Onset is sudden, with fever, headache,
backache, and abdominl pain.
On the 3rd to 4th day, conjunctival
hemorrhages, palatine petechiae, and truncal
petechial rush may appear
 HFRS

• Phases
– Febrile(toxic) 4-7 days
– Hypotensive
– Oliguric
– Polyuric
– Asthenic
Hantaanvirus Pulmonary Syndrome
(HPS)
• A flu like illness with acute onset.
• 2 to15 days later the patient develops acute
noncardiac pulmonary edema.
• Several patients have had a combination of
HFRS and HPS
• Elevated lactate levels are indicative of poor
prognosis.
• Patients who survive improve rapidly after 5 to
7 days.
Hantaanvirus Pulmonary Syndrome
CRIMEAN CONGO HEMORRHAGIC FEVER
(CCHF)
• Extensive geographic distribution
(Africa, Balkans, and western Asia)
• Transmission:
– Tick-borne (Hyalomma spp.)
– Contact with animal blood or products
– Person-to-person transmission
by contact with infectious body fluids
– Laboratory worker transmission
documented
• Mortality 15-40%
• Therapy: Ribavirin
Distribution of CCHF virus
 CCHF

• Ticks spread this Bunyavirus from domestic

animals to man in Asia and Africa.
• As a brief febrile illness rather then variably
severe haemorrhagic disease including
jaundice, disseminated intravascular
coagulation and thrombocytopenia may
develop.
• Diagnosis is serological.
• Treatment is supportive.
 CCHF
• Presentation occurs after 2-3 weeks of
incubation with a febrile illness, followed by a
hypotensive phase in which there may be
hemorrhagic features and renal failure (hence
HFRS).
• Patients often have blurred vision and an
erythematous blanching rash.
• Other presentations involve acute nephritis.
• There may be person-to-person spread and
isolation is therefore necessary.
• Treatment is supportive.
 PREVENTION OF CCHF

• DEET repellents for skin

• Permethrin repellents for clothing –
(0.5% permethrin should be applied to clothing ONLY)
• Check for and remove ticks at least twice daily.
• If a tick attaches, do not injure or rupture the tick.
Remove ticks by grasping mouthparts at the skin
surface using forceps and apply steady traction.
 Ebola and Marburg Fevers

• The filoviruses that cause these diseases are

endemic in Central and East Africa.
• The primary animal source of these infections
is uncertain. Ebola occurs in explosive
outbreaks in Sudan and Zaire and is spread
from person to person, particularly
nosocomially by contaminated syringes.
• Marburg virus has been spread from vervet
monkeys and their organs used in tissue
culture.
 Ebola and Marburg Fevers

• Acute infection is associated with high level of

circulating virus, and viral antigen.
• Clinical improvement takes place when viral
titers decrease concomitantly with the onset of
virus-specific immune response, as detected by
ELISA or fluorescent antibody test.
• In fatel cases there is little evidence of an
antibody response
 Ebola and Marburg Fevers
• Clinical disease in both infections involves an
incubation period of one-two weeks, acute
fever, myalgia and headaches and then
gastrointestinal problems together with
haemorrhagic features and shock. There is a
high mortality.
• Treatment requires supportive care in
appropriate isolation facilities. Interferon and
convalescent serum have been tried to little
effect.
 Lassa Fever
• This zoonotic arenavirus is carried in
otherwise healthy multimammate rats
(Mastomys natalensis).
• It was first described in West Africa, but the
geographical range of the host extends
throughout Africa south of the Sahara, and
foci of human disease have been described as
far south as Mozambique.
 Lassa Fever
• Spread to man occurs when rodent urine
contaminates household foodstuffs.

• Transmission from patients to hospital staff may

occur by direct contact with body fluids, and by
needle stick injury.

• Pathology includes widespread interstitial

hemorrhages.

• There is a hepatitis with areas of hepatic necrosis,

renal tubular necrosis, pneumonitis and a broad
spectrum of other tissue pathologies.
 Lassa Fever
• Presentation occurs 4-14 days after exposure.
• The majority of indigenous human cases are mild.
Pregnant women and expatriates are particularly
likely to progress to severe disease.
• Fever, back and retrosternal chest pains and
generalized myalgia are followed by an ulcerative
pharyngitis, facial oedema and hypotension.

• In severe cases a notable finding is elevated liver

enzymes.
• The disease can be confirmed by serology or by virus
isolation in special facilities.
 Lassa Fever

• Supportive treatment requires the correction

of hypovolaemia, anaemia and electrolyte
disturbance, the appropriate management of
renal failure and the consideration of specific
therapy. The latter may include immune
convalescent serum and intravenous ribavirin.
• In the absence of a vaccine, control depends
upon reducing rodent exposure.
 Lassa Fever
• In West Africa normal barrier nursing procedures, the
avoidance of needle stick injury and other body fluid
contamination are enough to prevent spread of
infection to staff and other patients.
• However, the possibility of nosocomial spread and
the severity of the disease have led to the use of much
more stringent precautions for cases imported into
western nations. These include the use of isolation
tents, chemical treatment of all body fluids and
special arrangements for laboratory investigations
 VHF: Differential Diagnosis

• Febrile tropical illnesses:

– Malaria
– Typhoid fever
– Bacterial gastro-enteritis
– Rickettsial diseases
 VHF: Supportive therapy

• Rule out or treat febrile illnesses:

malaria, rickettsia, leptospirosis, typhoid, dysentery
• Early hospitalization
• Distant medical evacuation associated with high mortality
• Cautious sedation and analgesia
• Careful hydration
• Pressors, cardiotonic drugs
• Support of coagulation system