Viral Hemorrhagic Fevers
Sections
Key Points
The causative agents are enveloped RNA viruses from four families cause hemorrhagic fevers: arenaviruses, filoviruses, bunyaviruses, and flaviviruses.
Viral hemorrhagic fevers are zoonotic infections.
Geographically limited to areas where their animal reservoirs reside, which include subtropical and tropical regions in Africa, Central and South America, South East Asia, and others.
Thus, changes to the environment can promote or reduce the spread of viral hemorrhagic fevers by widening or narrowing the ecological niches of the viral reservoirs and vectors.
Vaccine is available for Yellow Fever Virus.
Most viruses are prevented by avoidance of the animal reservoirs (via mosquito nets and rodent elimination) or, where possible, vaccination of the animals (especially when livestock are involved).
Furthermore, some of the viruses can be transmitted via infected human blood and tissues, so barrier nursing, thorough equipment disinfection, and other infectious disease precautions should be taken.
Viral outbreaks have been traced to hospitals where such precautions were not or could not be followed.
In most cases, treatment for viral hemorrhagic fever requires non-specific supportive care.
Timely diagnosis is also important, and is often made via serological tests.
Increased vascular permeability Hemorrhagic viral fevers are characterized by increased vascular permeability that leads to defective coagulation and organ damage.
The exact mechanisms leading to pathology varies by virus, and is not certain in some cases.
Generalized Pathogenesis of Viral Hemorrhagic Fevers
Our diagram is based on the pathogenesis of the Filoviruses, which includes Ebola virus and Marburg virus.
The enveloped RNA virus enters host cells, particularly macrophages and dendritic cells, and replicates within them. – Notice that by invading and taking over these cells of the innate immune system, the virus sabotages a key aspect of host defense.
The virus is disseminated to the organs via the blood.
Infection triggers the release of cytokines, nitric oxide, and other inflammatory chemical mediators that can damage tissues and alter vascular integrity. Some viruses even dampen immune responses that are specific to viral infections.
These immune responses and failures are key to the pathogenesis of viral hemorrhagic fevers.
Upon dissemination to the organs the virus replicates and damages the tissues; the liver and kidneys are often involved.
Vascular permeability increases and coagulation is defective; in some cases, disseminated intravascular coagulation can occur.
These events produce the symptoms of viral hemorrhagic fever.
– Be aware that the list of possible signs and symptoms is extensive, and varies by virus and severity of infection.
Be aware that some of these viruses cause other types of illness, and the case fatality rates we list are those specifically associated with viral hemorrhagic fevers.
Common Symptoms
Fever, headache, sore throat, abdominal pain, and vomiting are common in viral hemorrhagic fevers.
Plasma leakage can produce body cavity effusions; pleural and pericardial effusions can impair pulmonary and cardiac functions.
Increased bleeding often produces petechial or maculopapular rashes and ecchymosis
Bleeding may also occur in the internal organs, gums, conjunctiva, nose, and other mucous membranes.
Organ impairment, even failure, can occur as result of tissue damage and vascular dysfunction.
– Liver and kidneys are commonly involved.
– Liver involvement can lead to noticeable hepatic swelling and various degrees of jaundice (yellowing of the skin).
– Other organs, including the heart, lungs, and brain, can also be affected.
Onset of viral hemorrhagic fever symptoms is usually sudden.
When severe, multifocal organ necrosis, hypotension, shock, and death can occur.
Filoviruses
Ebola virus disease has a 50-90% case fatality rate.
Marburg virus disease has a 25% case fatality rate
Both are thought to be transmitted by fruit bats, and in human body fluids.
Specific signs and symptoms:
Petechial rash and ecchymosis.
Severe gastrointestinal symptoms, including abdominal pain, vomiting, and profuse diarrhea are also common.
Infection can produce multifocal lesions in the liver, lymphoid organs, and kidneys.
Death is usually caused by severe fluid loss and acid-base abnormalities.
Areneavirus
Lassa virus hemorrhagic fever is associated with a 1-15% case fatality rate.
Rodents are key reservoirs for the virus; they excrete the virus in their feces.
Specific signs and symptoms:
Unique in that symptoms often arise gradually rather than rapidly.
Lassa fever is associated with deafness (which may be temporary), face and neck edema, and chest effusions that can lead to respiratory distress.
Although many people recover, others experience a temporary remission that is followed by a return of symptoms and serious complications, including encephalitis and retinitis.
Lassa virus is associated with high rates of maternal death and fetal loss.
Treatment: Lassa virus fever can be treated with the antiviral Ribavirin.
Flaviviruses
Transmitted by mosquito vectors.
Yellow fever virus is associated with a 15-30% case fatality rate.
Preventable by vaccine.
Specific signs and symptoms:
Although most patients fully recover, 15-20% of patients enter the potentially fatal "intoxication" stage, which is associated with renal and hepatic failure and intense jaundice (hence the name "yellow" fever).
Dengue virus fever has a 1-5% case fatality rate; unlike Lassa virus, it is not preventable by vaccine, and can be transmitted in human bodily fluids.
Widespread in tropics & subtropics throughout SE Asia, Western Pacific, Africa, Mediterranean, and Americas.
Dengue hemorrhagic fever, also called Severe Dengue fever, is usually the result of a secondary Dengue infection (the first, or primary, infection may be mild or asymptomatic).
In Severe Dengue, the initial febrile state is followed by severe abdominal pain and vomiting, as well as hypothermia and other symptoms.
Cardiovascular dysfunction and dehydration can lead to Dengue Shock Syndrome and multiorgan failure.
Infants and the elderly seem to be at a higher risk for shock.
Bunyaviruses
Crimean-Congo hemorrhagic fever virus is associated with a 30-60% case fatality rate; the virus can be acquired from hard ticks or infected livestock.
Specific signs and symptoms:
Petechiae, ecchymosis, red throat, and sensory and mood changes are common.
Sensory and mood changes often manifest as photophobia, confusion, and agitation followed by depression.
Recovery tends to be slow.
Rift Valley fever virus is associated with a case fatality rate of 1%; it is transmitted via hard ticks and infected livestock.
Fatal hemorrhagic cases are associated with liver and renal failure.
People who work with livestock are at higher risk of infection. Fortunately, livestock vaccination can help prevent epidemics.
Old World Hantaviruses cause hemorrhagic fever with a 1-15% case fatality rate; they are transmitted by rodents.
The Hantaviruses are broadly categorized as "Old World" or "New World"; the Old World viruses, including Hantaan, Saaremaa, Seoul, Puumala, and Dobrava viruses, are associated with Hemorrhagic Fever with Renal Syndrome.
– Found in Europe and Asia.
Illness is characterized by acute kidney injury.
Tends to present in the following 5 phases (which may overlap): febrile, hypotensive, oliguric (low urine output), polyuric (high urine output), and convalescence.
Some survivors experience long term renal and/or cardiac complications.
Fatality rates are higher in the elderly.
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