Viral Hemorrhagic Fever (VHF): Slideshow

Viral hemorrhagic fever (VHF) refers to a diverse group of viral pathogens that are characterized clinically by fever and a bleeding diathesis. Manifestations may include flushing of the face and chest, petechiae, mucosal and gastrointestinal bleeding, frank bleeding, malaise, edema, hypotension, myalgias, headache, vomiting, and diarrhea. In extreme cases, shock and death may occur because of circulatory instability due to increased vascular permeability and diffuse hemorrhage. Image courtesy of the Centers for Disease Control and Prevention.

Several viral infections are responsible for causing VHF. These viruses are often transmitted by arthropods, especially mosquitoes. Sometimes the infection may be spread from person to person through direct contact with infected patients, their blood, or their secretions and excretions. Animal reservoirs are generally rodents, but domestic livestock, monkeys, and other primates may also serve as intermediate hosts. Image courtesy of Wikimedia Commons.

The distinct enveloped RNA viruses that cause most VHF cases are members of 4 families: Arenaviridae, Bunyaviridae, Filoviridae, and Flaviviridae. Although the reservoirs for these viruses are not in the United States, cases have been reported in this country in travelers who have visited an endemic region. Due to the increasing threat of bioterrorism, these highly infectious and potentially lethal viruses are of increasing concern.

Lassa fever is caused by a single-stranded zoonotic RNA virus of the Arenaviridae family. First described in 1969, infection occurs in West Africa and is named after the town in Nigeria where the first cases were observed. The "multimammate rat" of the genus Mastomys is a common village rodent and is a host for the virus. The virus is spread to humans by direct contact with infectious rodent urine and droppings. Transmission can occur through cuts and sores, as well as by inhalation of infectious particles. Person-to-person transmission can occur through contact with infectious blood, tissue, secretions, and excretions, but not through casual contact such as skin to skin. Image on left courtesy of the Centers for Disease Control and Prevention. Image on right courtesy of Wikipedia Commons.

The incubation period is 1-3 weeks. Signs and symptoms include fever, retrosternal pain, sore throat, back pain, cough, abdominal pain, vomiting, diarrhea, conjunctivitis, facial swelling, proteinuria, and mucosal bleeding. Neurologic problems include hearing loss, tremors, and encephalitis. Most infections are subclinical, with more than 80% of people infected with Lassa virus having no observable symptoms; for the rest, it is a severe, multisystem disease. When associated with occasional epidemics, the case fatality rate has reached 50%. The first imported case of Lassa fever in more than 20 years occurred in New Jersey in 2004.

Ribavirin may be an effective treatment for Lassa fever. It is most effective when given early in the course of the illness (usually within first 7 days). Use of ribavirin for postexposure prophylaxis is controversial. Prevention of infection depends largely on control of the rodent population, although results of studies are mixed. In addition, patients require considerable supportive care, intravenous fluids, and careful monitoring. Image courtesy of Wikipedia Commons.

Crimean-Congo hemorrhagic fever (CCHF) is caused by the Nairovirus in the family Bunyaviridae. It was first characterized in the Crimea in 1944 and recognized in 1969 in the Congo. CCHF is found in Eastern Europe (particularly in the former Soviet Union), throughout the Mediterranean, in Northwestern China, Central Asia, Southern Europe, Africa, the Middle East, and India. The principal host vector is the Hyalomma tick. Cattle, goats, sheep, and hares serve as amplifying hosts for the virus. Transmission to humans occurs through contact with infected animal blood or infected ticks. Person-to-person transmission may occur, resulting in nosocomial outbreaks. Image on left courtesy of the World Health Organization. Image on right courtesy of the Centers for Disease Control and Prevention.

The onset of CCHF is sudden, with initial signs and symptoms including headache, high fever, back, joint and abdominal pain, and vomiting. Conjunctival injection, facial flushing, oropharyngeal erythema, and palatal petechiae may be observed. Jaundice may occur, as may changes in mood and sensory perception in severe cases. As the illness progresses, evidence of bleeding may be seen and includes cutaneous ecchymoses, epistaxis, and uncontrolled bleeding at injection sites. Among hospitalized patients, mortality ranges from 9% to as high as 50%. The image on the right shows ecchymoses encompassing left upper extremity 1 week after onset of CCHF. Ecchymoses often are accompanied by hemorrhage in other locations: epistaxis, puncture sites, hematemesis, melena, and hematuria. Image on left courtesy of Wikimedia Commons.

Yellow fever is an anthroponotic infection (vector-borne person to person) caused by the yellow fever virus, a flavivirus. Infection occurs in tropical regions of Africa and in parts of Central and South America and is vectored by Aedes mosquitoes. It is a very rare cause of illness in US travelers. The last epidemic of yellow fever in North America occurred in New Orleans in 1905. There are 2 kinds of yellow fever: forest-acquired and urban. Forest-acquired yellow fever is mainly a disease of monkeys and is spread via infected mosquitoes to monkeys in the tropical rainforest. Human infection occurs via mosquito bites after the mosquito has fed on infected monkeys. Urban yellow fever, however, is the most common cause of yellow fever outbreaks and epidemics. In such cases, mosquitoes live among humans in cities, towns, and villages and spread the virus among susceptible humans. The presence of infectious mosquitoes is facilitated by larval growth in discarded tires, flower pots, oil drums, and water-storage containers. Images courtesy of the Centers for Disease Control and Prevention.

Vaccination against yellow fever is recommended before travel to the Amazon forest. For those who acquire clinical illness, there is a 3- to 6-day incubation period. Illness ranges in severity from a self-limited febrile illness to severe hepatitis and hemorrhagic fever. Symptoms of severe infection include high fever, chills, headache, myalgias, vomiting, and backache. After a brief remission, symptoms may renew and severe infection can lead to shock, bleeding, and kidney and liver failure. Hepatic involvement results in jaundice, thus giving yellow fever its name. Mortality ranges from 15% to more than 50%. Image courtesy of Wikimedia Commons.

Dengue fever (DF) is viral illness transmitted by mosquitoes. It is found in tropic and subtropic regions, including the Indonesian archipelago, northeastern Australia, South and Central America, Southeast Asia, and Sub-Saharan Africa. DF is caused by a flavivirus and has 4 described serotypes. Infection is transmitted to humans by mosquitoes. Most infections are self-limited and influenzal in nature. Other manifestations include dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Images courtesy of the Centers for Disease Control and Prevention.

Classic DF manifests as fever, rash, severe headaches, chills, and muscle and joint pain. Disease severity increases in children and the elderly. DF is the most common mosquito-borne virus in the world, causing up to 100 million infections and 25,000 deaths each year. DHF and DSS are more severe manifestations, usually seen in those previously infected with another dengue serotype. Findings include irritability, restlessness, and increased sweating, followed by a shock-like state and hemorrhage. Shown in this image is a child with DHF or DSS presenting as severely hypotensive and with disseminated intravascular coagulation. This patient has morbilliform exanthem of dengue fever. Note islands of sparing characteristics for dengue. Dengue viruses are primarily transmitted by Aedes aegypti mosquitoes (top left) an invasive, domestic species with tropical and subtropical worldwide distribution that originated in Africa. Aedes albopictus (bottom left) is another important mosquito vector of dengue and is originally from Asia. Images on left courtesy of the Centers for Disease Control and Prevention.

The natural habitat of the Aedes mosquito is rain-filled cavities (such as in trees), bamboo internodes, and leaf-axils of plants. In urban environments, examples of aquatic habitats include rain-filled cavities such as large discarded containers, pots, and open septic tanks, as shown in this image. Image courtesy of the Centers for Disease Control and Prevention.

Ebola virus hemorrhagic fever (HF) is named after a river in the Democratic Republic of the Congo (formerly Zaire) in Africa where it was first recognized in 1976 and has appeared sporadically since its initial recognition. The incubation period for Ebola HF ranges from 2 to 21 days. Within a week, a raised rash, often hemorrhagic (bleeding), spreads over the body. Typically there is bleeding from the mucous membranes (eg, mouth, nose, eyes, and rectum). This image shows treatment of patients with Ebola HF during outbreak of the disease in 1995 in Kikwit, Democratic Republic of the Congo, as well as an Ebola HF prevention poster used during the Kikwit outbreak. Images courtesy of the Centers for Disease Control and Prevention.

This 1976 photograph of 2 nurses in Kinshasa, Zaire, shows a patient, Mayinga N'Seka, who was treated and later died in Ngaliema Hospital in Kinshasa. The virus is 1 of 2 members of a family of RNA viruses called the Filoviridae. Four of the 5 identified subtypes have caused disease in humans: Ebola-Zaire, Ebola-Sudan, Ebola-Ivory Coast, and Ebola-Bundibugyo. The fifth, Ebola-Reston, has caused disease in nonhuman primates. Human infection with Ebola-Reston has been recorded, but infection is usually asymptomatic. It is not understood why some recover from Ebola HF and others do not. Ebola is found only in certain parts of Africa. No cases in the United States have ever been reported. Image courtesy of Wikimedia Commons.

A hospital isolation ward in Gulu, Uganda, during the October 2000 outbreak. Infections with Ebola virus are acute. The reservoir of Ebola is thus far unknown, but it is hypothesized that human infection occurs via contact with an infected animal. Once a patient is infected, the virus can be transmitted from direct contact with the blood and/or secretions of an infected person and through contact with objects, such as needles, that have been contaminated with infected secretions. Nosocomial transmission occurs frequently during Ebola HF outbreaks. Image courtesy of Wikimedia Commons.

Closely related to Ebola is Marburg HF virus. Marburg HF has been reported in Uganda, Zimbabwe, the Democratic Republic of the Congo, Kenya, and Angola. Cases of Marburg HF outside Africa are rare but have been reported in Europe. The incubation period is 5-10 days. The onset of the disease is sudden and is marked by fever, chills, headache, and myalgias. Around the fifth day after the onset of symptoms, a maculopapular rash, most prominent on the trunk (chest, back, stomach), may occur. Nausea, vomiting, chest pain, sore throat, abdominal pain, and diarrhea can occur. Extreme symptoms include jaundice, pancreatitis, severe weight loss, delirium, shock, liver failure, massive hemorrhage, and multiorgan dysfunction. Recovery from Marburg hemorrhagic fever may be prolonged and accompanied by orchitis, recurrent hepatitis, transverse myelitis, or uveitis. Images courtesy of the Centers for Disease Control and Prevention.

The African fruit bat (Rousettus aegyptiacus) may serve as the reservoir host of the Marburg virus. Fruit bats infected with Marburg virus do not show obvious signs of illness. Similar to Ebola virus, the first transmission to humans is not always known. Person-to-person transmission of Marburg occurs as with Ebola. The case fatality rate for Marburg hemorrhagic fever is between 23% and 25%. Images courtesy of Wikipedia Commons.

Marburg or Ebola HF symptoms often appear similar to other infectious diseases, such as malaria or typhoid fever. Antigen-capture enzyme-linked immunosorbent assay (ELISA) testing, IgM-capture ELISA, polymerase chain reaction, and virus isolation can be used to confirm a case of Marburg HF. Image courtesy of Wikipedia Commons.

Treatment for VHFs include supportive care consisting of maintenance of appropriate fluid and electrolyte balance, oxygenation and blood pressure, and treatment of any other complicating infections. This includes balancing the patient's fluids and electrolytes, maintaining oxygen status and blood pressure, replacing lost blood and clotting factors, and treating for any complicating infections. Image courtesy of Wikipedia Commons.

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For more information, see the following resources:

• eMedicine, Dermatology: Viral Hemorrhagic Fevers
• eMedicine, Pediatrics: General Medicine: Viral Hemorrhagic Fevers
• eMedicine, Emergency Medicine: CBRNE - Viral Hemorrhagic Fevers
• eMedicine, Infectious Diseases: Yellow Fever
• eMedicine, Infectious Diseases: Ebola Virus
• Centers for Disease Control and Prevention: Viral Hemorrhagic Fevers

Contributor Information

Author
Anusuya Mokashi, MD
Resident
Department of Diagnostic Radiology
Staten Island University Hospital
New York, NY

Disclosure: Anusuya Mokashi, MD, has disclosed no relevant financial relationships.

Editor
Michael Stuart Bronze, MD
Professor, Stewart G. Wolf Chair in Internal Medicine
Department of Medicine
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma

Disclosure: Michael Stuart Bronze, MD, has disclosed no relevant financial relationships.