These viruses are presented in alphabetical order. They are listed in Table 46–1 in terms of their nucleic acid and presence of an envelope.
Table 46–1Minor Viral Pathogens ||Download (.pdf) Table 46–1 Minor Viral Pathogens
Herpes B virus, poxviruses of animal origin (cowpox virus, monkeypox virus)
BK virus, human bocavirus
Borna virus, Cache Valley virus, Crimean-Congo hemorrhagic virus, hantaviruses, Heartland virus, Hendra virus, Jamestown Canyon virus, Japanese encephalitis virus, Lassa fever virus, Lujo virus, lymphocytic choriomeningitis virus, Nipah virus, Powassan virus, spumaviruses, Tacaribe complex of viruses (e.g., Junin and Machupo viruses), Whitewater Arroyo virus
Astrovirus, Sapporo virus
Astrovirus is a nonenveloped RNA virus similar in size to poliovirus. It has a characteristic five- or six-pointed star appearance in the electron microscope. It causes watery diarrhea, especially in children. Most adults have antibodies against astrovirus, suggesting that infection occurs commonly. No antiviral drugs or preventive measures are available.
BK virus is a member of the polyomavirus family. Polyomaviruses are nonenveloped viruses with a circular, double-stranded DNA genome. BK virus and JC virus (see Chapter 44) are the two polyomaviruses that infect humans.
BK virus infection is widespread as determined by the presence of antibody and is typically acquired in childhood, and infection is not associated with any disease at that time. It does, however, cause nephropathy and graft loss in immunosuppressed renal transplant patients. Asymptomatic shedding of BK virus in the urine of immunocompromised patients and pregnant women in the third trimester occurs. There is no antiviral therapy effective against BK virus.
Borna virus is an enveloped virus with a nonsegmented, single-strand, negative-polarity RNA genome. It has the smallest genome of any virus with this type of RNA and is the only virus of this type to replicate in the nucleus of the infected cell. DNA sequences homologous to the Borna virus genome are integrated into human cellular DNA. It is a neurotropic virus known to infect regions of the brain such as the hippocampus.
Borna is the name of a town in Germany where the virus caused a disease in horses in 1885. It is primarily a zoonotic virus causing disease in domestic animals, such as cattle, sheep, dogs, and cats. In humans, Borna virus often causes fatal encephalitis. In addition, there is evidence that it is associated with human psychiatric diseases characterized by abnormal behavior, such as bipolar disorder.
This virus was first isolated in Utah in 1956 but is found throughout the Western Hemisphere. It is a bunyavirus transmitted by Aedes, Anopheles, or Culiseta mosquitoes from domestic livestock to people. It is a rare cause of encephalitis in humans. There is no treatment or vaccine for Cache Valley virus infections.
CRIMEAN-CONGO HEMORRHAGIC VIRUS
Crimean-Congo hemorrhagic virus (CCHV) causes Crimean-Congo hemorrhagic fever (CCHF), which is characterized by fever, hemorrhage into the skin (ecchymoses) and gastrointestinal tract, and severe liver necrosis. Death often occurs due to shock and multiorgan failure. A broad spectrum of disease occurs, from mild flulike symptoms to severe hemorrhagic fever. There is no antiviral drug therapy and no vaccine.
CCHV is an enveloped, negative-polarity RNA virus that is a member of the bunyavirus family. It is transmitted most often by the bite of ticks of the genus Hyalomma. Nosocomial transmission also occurs.
Hantaviruses are members of the bunyavirus family. The prototype virus is Hantaan virus, the cause of Korean hemorrhagic fever (KHF). KHF is characterized by headache, petechial hemorrhages, shock, and renal failure. It occurs in Asia and Europe but not in North America and has a mortality rate of about 10%. Hantaviruses are part of a heterogeneous group of viruses called roboviruses, which stands for “rodent-borne” viruses. Roboviruses are transmitted from rodents directly (without an arthropod vector), whereas arboviruses are “arthropod-borne.”
In 1993, an outbreak of a new disease, characterized by influenzalike symptoms followed rapidly by acute respiratory failure, occurred in the western United States, centered in New Mexico and Arizona. This disease, now called hantavirus pulmonary syndrome, is caused by a hantavirus (Sin Nombre virus) endemic in deer mice (Peromyscus) and is acquired by inhalation of aerosols of the rodent’s urine and feces. It is not transmitted from person to person. Very few people have antibody to the virus, indicating that asymptomatic infections are not common.
The diagnosis is made by detecting viral RNA in lung tissue with the polymerase chain reaction (PCR) assay, by performing immunohistochemistry on lung tissue, or by detecting IgM antibody in serum. The mortality rate of hantavirus pulmonary syndrome is very high, approximately 35%. Between 1993 and December 2009, a total of 534 cases of hantavirus pulmonary syndrome have been reported in the United States. Most cases occurred in the states west of the Mississippi, particularly in New Mexico, Arizona, California, and Colorado, in that order.
There is no effective drug; ribavirin has been used but appears to be ineffective. There is no vaccine for any hantavirus.
This virus was first recognized as a human pathogen in 2012, when it caused fever, thrombocytopenia, and leukopenia in two men in the state of Missouri. It is a member of the bunyavirus family. It is transmitted by the bite of the Lone Star tick, Amblyomma. There is no antiviral treatment or vaccine for this virus.
This virus was first recognized as a human pathogen in 1994, when it caused severe respiratory disease in Hendra, Australia. It is a paramyxovirus resembling measles virus and was previously called equine morbillivirus. The human infections were acquired by contact with infected horses, but fruit bats appear to be the natural reservoir. There is no treatment or vaccine for Hendra virus infections.
This virus (monkey B virus or herpesvirus simiae) causes a rare, often fatal encephalitis in persons in close contact with monkeys or their tissues (e.g., zookeepers or cell culture technicians). The virus causes a latent infection in monkeys that is similar to herpes simplex virus (HSV)-1 infection in humans.
Herpes B virus and HSV-1 cross-react antigenically, but antibody to HSV-1 does not protect from herpes B encephalitis. The presence of HSV-1 antibody can, however, confuse serologic diagnosis by making the interpretation of a rise in antibody titer difficult. The diagnosis can therefore be made only by recovering the virus. Acyclovir may be beneficial. Prevention consists of using protective clothing and masks to prevent exposure to the virus. Immune globulin containing antibody to herpes B virus should be given after a monkey bite.
Human bocavirus (HBoV) is a parvovirus isolated from young children with respiratory tract infections. Antibody to HBoV is found in most adults worldwide. A description of this virus was first reported in 2005, and its precise role in respiratory tract disease has yet to be defined.
Jamestown Canyon virus (JCV) is a member of the bunyavirus family that causes encephalitis. It is transmitted by mosquito bite, most commonly by Aedes species. JCV circulates widely among deer in North America, but human disease is rare. In the United States, cases are primarily in the northeastern and midwestern states. There is no antiviral treatment or vaccine for JCV infections.
JAPANESE ENCEPHALITIS VIRUS
This virus is the most common cause of epidemic encephalitis in rural areas of Asia. The disease is characterized by fever, headache, nuchal rigidity, altered states of consciousness, tremors, incoordination, and convulsions. The mortality rate is high, and neurologic sequelae are severe and can be detected in most survivors. The disease occurs throughout Asia but is most prevalent in Southeast Asia. The rare cases seen in the United States have occurred in travelers returning from that continent. American military personnel in Asia have been affected.
Japanese encephalitis virus is a member of the flavivirus family. It is transmitted to humans by certain species of Culex mosquitoes endemic to Asian rice fields. There are two main reservoir hosts—birds and pigs. The diagnosis can be made by isolating the virus, by detecting IgM antibody in serum or spinal fluid, or by staining brain tissue with fluorescent antibody. There is no antiviral therapy. Prevention consists of an inactivated vaccine and personal protection against mosquito bites. Immunization is recommended for individuals living in areas of endemic infection for several months or longer.
Lassa fever virus was first seen in 1969 in the Nigerian town of that name. It causes a severe, hemorrhagic fever characterized by multiorgan involvement. The disease begins slowly with fever, headache, vomiting, and diarrhea and progresses to involve the lungs, heart, kidneys, and brain. A petechial rash and gastrointestinal tract hemorrhage ensue, followed by death from vascular collapse. The fatality rate is approximately 20%.
Lassa fever virus is a member of the arenavirus family, which includes other infrequent human pathogens such as lymphocytic choriomeningitis virus and certain members of the Tacaribe group. Arenaviruses (“arena” means sand) are united by their unusual appearance in the electron microscope. Their most striking feature is the “sandlike” particles on their surface, which are ribosomes. The function, if any, of these ribosomes is unknown. Arenaviruses are enveloped viruses with surface spikes, a helical nucleocapsid, and single-stranded RNA with negative polarity.
The natural host for Lassa fever virus is the small rodent Mastomys, which undergoes a chronic, lifelong infection. The virus is transmitted to humans by contamination of food or water with animal urine. Secondary transmission among hospital personnel also occurs. Asymptomatic infection is widespread in areas of endemic infection.
The diagnosis is made either by isolating the virus or by detecting a rise in antibody titer. Ribavirin reduces the mortality rate if given early, and hyperimmune serum, obtained from persons who have recovered from the disease, has been beneficial in some cases. No vaccine is available, and prevention centers on proper infection control practices and rodent control.
Lujo virus is an arenavirus that causes a hemorrhagic fever similar to Lassa fever. This virus emerged in Zambia in 2008 and caused an outbreak in which four of the five infected patients died. The one survivor was treated with ribavirin. The identification of this virus was made by sequencing the viral RNA from the liver and serum of patients. The animal reservoir and mode of transmission are unknown, but other arenaviruses are transmitted by rodent excreta.
LYMPHOCYTIC CHORIOMENINGITIS VIRUS
Lymphocytic choriomeningitis virus is a member of the arenavirus family. It is a rare cause of aseptic meningitis and cannot be distinguished clinically from the more frequent viral causes (e.g., echovirus, Coxsackie virus, or mumps virus). The usual picture consists of fever, headache, vomiting, stiff neck, and changes in mental status. Spinal fluid shows an increased number of cells, mostly lymphocytes, with an elevated protein level and a normal or low sugar level.
The virus is endemic in the mouse population, in which chronic infection occurs. Animals infected transplacentally become healthy lifelong carriers. The virus is transmitted to humans via food or water contaminated by mouse urine or feces. There is no human-to-human spread (i.e., humans are accidental dead-end hosts), although transmission of the virus via solid organ transplants has occurred. In 2005, seven of eight transplant recipients who became infected died. Diagnosis is made by isolating the virus from the spinal fluid or by detecting an increase in antibody titer. No antiviral therapy or vaccine is available.
This disease is the prototype used to illustrate immunopathogenesis. If immunocompetent adult mice are inoculated, meningitis and death ensue. If, however, newborn mice or X-irradiated immunodeficient adults are inoculated, no meningitis occurs despite extensive viral replication. If sensitized T cells are transplanted to the immunodeficient adults, meningitis and death occur. The immunodeficient adult mice, who are apparently well, slowly develop glomerulonephritis. It appears that the mice are partially tolerant to the virus in that their cell-mediated immunity is inactive, but sufficient antibody is produced to cause immune complex disease.
Marburg virus and Ebola virus are similar in that they both cause hemorrhagic fever and are members of the filovirus family; however, they are antigenically distinct. Marburg virus was first recognized as a cause of human disease in 1967 in Marburg, Germany. The common feature of the infected individuals was their exposure to African green monkeys that had recently arrived from Uganda. As with Ebola virus, the natural reservoir of Marburg virus is unknown, although bats are suspected. Ebola virus is described in Chapter 39.
Marburg hemorrhagic fever begins with a constellation of symptoms some of which are fever, headache, sore throat, myalgia, arthralgia, epigastric pain, vomiting, and diarrhea. Later, bleeding into the skin and gastrointestinal tract occurs, followed by shock and disseminated intravascular coagulation leading to multiorgan failure. The hemorrhages are the result of both severe thrombocytopenia and death of endothelial cells. Marked lymphopenia occurs. The mortality rate associated with this virus can be up to 90%.
In 2005, an outbreak of hemorrhagic fever caused by Marburg virus killed hundreds of people in Angola. No cases of disease caused by Marburg virus occurred in the United States prior to 2008. However, in that year, a U.S. traveler became ill after visiting a cave in Uganda inhabited by fruit bats. He returned to the United States, where he was diagnosed with Marburg hemorrhagic fever. He recovered without sequelae.
The diagnosis is made by PCR assay or detecting a rise in IgM antibody titer. No antiviral therapy or vaccine is available. As with Ebola virus, secondary cases among medical personnel have occurred; therefore, stringent infection control practices must be instituted to prevent nosocomial spread.
Nipah virus is a paramyxovirus that causes encephalitis, primarily in the South Asian countries of Bangladesh, Malaysia, and Singapore. The fatality rate is approximately 70%. The natural reservoir appears to be fruit bats. People who have contact with pigs are particularly at risk for encephalitis, and some human-to-human transmission occurs. In general, paramyxoviruses are transmitted by saliva or sputum and that is likely to be the natural mode of transmission. Exposure to body fluids also transmits the virus. There is no treatment or vaccine for Nipah virus infections.
Powassan virus is a flavivirus that causes severe encephalitis with significant sequelae. It is transmitted by Ixodes ticks, and rodents are the reservoir. It is the only flavivirus transmitted by ticks.
It is named for the town of Powassan, Ontario, Canada, where one of the first cases occurred. Most cases in the United States occur in Minnesota and Wisconsin. There are typically 0 to 10 cases in the United States each year. The diagnosis can be made by PCR or serologic tests. There is no antiviral drug or vaccine.
POXVIRUSES OF ANIMAL ORIGIN
Four poxviruses cause disease in animals and also cause poxlike lesions in humans on rare occasions. They are transmitted by contact with the infected animals, usually in an occupational setting.
Cowpox virus causes vesicular lesions on the udders of cows and can cause similar lesions on the skin of persons who milk cows. Pseudocowpox virus causes a similar picture but is antigenically distinct. Orf virus is the cause of contagious pustular dermatitis in sheep and of vesicular lesions on the hands of sheepshearers.
Monkeypox virus is different from the other three; it causes a human disease that resembles smallpox. It occurs almost exclusively in Central Africa. In 2003, an outbreak of monkeypox occurred in Wisconsin, Illinois, and Indiana. In this outbreak, the source of the virus was animals imported from Africa. It appears that the virus from the imported animals infected local prairie dogs, which then were the source of the human infection. None of those affected died. In Africa, monkeypox has a death rate of between 1% and 10%, in contrast to 50% for smallpox. There is no effective antiviral treatment. The vaccine against smallpox appears to have some protective effect against monkeypox.
Any new case of smallpox-like disease must be precisely diagnosed to ensure that it is not due to smallpox virus. There has not been a case of smallpox in the world since 1977,1 and smallpox immunization has been allowed to lapse.
For these reasons, it is important to ensure that new cases of smallpox-like disease are due to monkeypox virus. Monkeypox virus can be distinguished from smallpox virus in the laboratory both antigenically and by the distinctive lesions it causes on the chorioallantoic membrane of chicken eggs.
Sapporo virus is a calicivirus that causes acute gastroenteritis. The main symptoms are vomiting and diarrhea, especially in young children. It is transmitted by ingestion of food or water contaminated with human feces. There is no antiviral drug or vaccine. It is named after Sapporo, Japan, the city where it was first isolated. It is a member of the sapovirus group of viruses which are non-enveloped, single-stranded, positive polarity RNA viruses.
Spumaviruses are a subfamily of retroviruses that cause a foamy appearance in cultured cells. They can present a problem in the production of viral vaccines if they contaminate the cell cultures used to make the vaccine. There are no known human pathogens.
TACARIBE COMPLEX OF VIRUSES
The Tacaribe complex contains several human pathogens, all of which cause hemorrhagic fever.
The best known are Sabia virus in Brazil, Junin virus in Argentina, and Machupo virus in Bolivia. Hemorrhagic fevers, as the name implies, are characterized by fever and bleeding into the gastrointestinal tract, skin, and other organs. The bleeding is due to thrombocytopenia. Death occurs in up to 20% of cases, and outbreaks can involve thousands of people. Agricultural workers are particularly at risk.
Similar to other arenaviruses such as Lassa fever virus and lymphocytic choriomeningitis virus, these viruses are endemic in the rodent population and are transmitted to humans by accidental contamination of food and water by rodent excreta. The diagnosis can be made either by isolating the virus or by detecting a rise in antibody titer. In a laboratory-acquired Sabia virus infection, ribavirin was an effective treatment. No vaccine is available.
This virus is the cause of a hemorrhagic fever/acute respiratory distress syndrome in the western part of the United States. It is a member of the arenavirus family, as is Lassa fever virus, a cause of hemorrhagic fever in Africa (see earlier in this chapter). Wood rats are the reservoir of this virus, and it is transmitted by inhalation of dried rat excrement. This mode of transmission is the same as that of the hantavirus, Sin Nombre virus (see earlier in this chapter). There is no established antiviral therapy, and there is no vaccine.