INFECTIOUS DISEASE

TURKISH

 

VIROLOGY - CHAPTER  TWENTY TWO

VIRAL DISEASES TRANSMITTED BY VERTEBRATES OR FOR WHICH THE RESERVOIR OR VECTOR IS UNCLEAR

Dr. Margaret Hunt
Professor Emerita
University of South Carolina School of Medicine

VIRAL DISEASES TRANSMITTED BY RODENTS

Note: Rodents can be infected by rabies virus although they are rarely, if ever, involved in transmission to humans. Rabies is the subject of a separate chapter.

ARENAVIRUS FAMILY

All of the above arenaviruses (and other arenaviruses causing hemorrhagic fever not listed here) have a rodent vector. The arenavirus-associated hemorrhagic fevers have a high case-fatality rate (5 - 35%). The arenaviruses seem to establish persistent infections easily in certain rodents, which get a viremia and a viruria, and shed virus in urine, stools and saliva. Humans are thought to acquire infection from contact with contaminated materials, contaminated food, or aerosolized droppings, nesting materials, etc. Disease in humans often show the following: dehydration, hemoconcentration, hemorrhage, shock syndrome, cardiovascular collapse. In 1999-2000, there were reports of three deaths apparently due to a North American arenavirus (Whitewater Arroyo).  It is not clear if there are other unrecognized cases of this virus or what the case fatality rate is.  

Lymphochoriomeningitis is acquired from close contact with rodents or rodent contaminated materials or in rodent breeding facilities. Infections are frequently asymptomatic. Clinical infections are not usually fatal, but there may be some long-term complications. It is not associated with hemorrhagic fever, but can cause meningitis, encephalitis, myelitis.

The incubation period of LCMV infection is usually between 8 and 13 days. A characteristic biphasic febrile illness then follows. The initial phase, which may last as long as a week, typically begins with any or all of the following symptoms: fever, malaise, anorexia, muscle aches, headache, nausea, and vomiting. Other symptoms that appear less frequently include sore throat, cough, joint pain, chest pain, testicular pain, and parotid (salivary gland) pain. Following a few days of remission, the second phase of the disease occurs, consisting of symptoms of meningitis (for example, fever, headache, and a stiff neck) or characteristics of encephalitis (for example, drowsiness, confusion, sensory disturbances, and/or motor abnormalities, such as paralysis). LCMV has also been known to cause acute hydrocephalus, which often requires surgical shunting to relieve increased intracranial pressure. In rare instances, infection results in myelitis (inflammation of the spinal cord) and presents with symptoms such as muscle weakness, paralysis, or changes in body sensation.  (CDC)

CASE REPORTS

Lymphocytic choriomeningitis deaths from an Arenavirus infection

The hantavirus genus differs from other members of Bunyaviridae in that members are transmitted by rodents (rather than arthropods). Each hantavirus is only transmitted by a limited number of genera/species of rodent. Infected rodents can spread virus via saliva, urine (they get a viruria) or droppings. When fresh urine, droppings or recently contaminated nesting material is swept up or disturbed, the virus can be aerosolized and inhaled. Some of these viruses can cause severe disease, but even for these viruses many infections are sub-clinical, or very mild and never diagnosed.

Associated with hemorrhagic fever with renal syndrome (HFRS)

Hemorrhagic fever with renal syndrome (formerly known as Korean Hemorrhagic Fever) has a case-fatality rate of about 7%. Other members of the Hantaviruses which cause HFRS (hemorrhagic fever with renal syndrome) tend to have a lower fatality rate. Transmission appears to be via inhalation of, or contact with, rodent urine, droppings or saliva.

HFRS has an incubation time of about two weeks to a month. First, there is a febrile phase for up to a week. This is typified by fever but other symptoms include general malaise, nausea, pain and other flu-like symptoms. This is followed by the hypotensive phase of a few days (lower platelet count, tachycardia and hypoxemia). The third phase, the oliguric phase, also lasts a few days and is characterized by protein in the urine (proteinuria) and renal failure. Finally, there is the diuresis phase of days to weeks typified by excessive urination. The patient then usually recovers.

Associated with severe pulmonary syndrome

There is a group of Hantaviruses found in North and South America that is transmitted by rodents to humans (by inhalation or contact with excreta) and which causes Hantavirus Pulmonary Syndrome (HPS) rather than hemorrhagic fever. 

These HPS viruses have a high case fatality rate of about 36%. The viruses are widely distributed throughout the the Americas but relatively rarely cause human disease - about 380 known cases so far in the US. Initial symptoms often include fever, myalgia, nausea, vomiting and a cough; this may progress to dizziness and shortness of breath as lungs fill with fluid, followed by acute respiratory distress. There are a several Hantaviruses that have been associated with this syndrome, one of the best known of the United States HPS-associated viruses is Sin Nombre virus.

In 2012, there was an outbreak of Hantavirus pulmonary syndrome at Curry Village in Yosemite National Park in California. The infected persons stayed in tent cabins at the village which may have been accessible to mice. Of the first eight patients, three died.

Although Hantavirus came to the public’s attention in 1993 in the Four Corners region of the southwest of the United States, the virus has been around for much longer in human disease. It probably broke out in 1993 because there were ideal conditions for an increase in the deer mouse population thereby causing more human-mouse contact and spread of the virus. Once the virus was discovered, it was possible to look for similar viruses in stored tissue samples from patients who had experienced similar symptoms and the earliest case of HPS was found in a 38-year-old Utah man who contracted a similar disease in 1959.

The disease is not restricted to the Four Corners region since a bridge inspector in Louisiana who had not been in the Four Corners region developed HPS. This patient had been infected by a different Hantavirus, called Bayou virus, carried by the rice rat (Oryzomys palustris). Another Hantavirus that has caused human infection, called the Black Creek Canal virus, is carried by the cotton rat (Sigmodon hispidus) while in New York, the Hantavirus New York-1, appears to be carried by the white-footed mouse (Peromyscus leucopus). More recently, cases of HPS have been discovered in Argentina, Brazil, Canada, Chile, Paraguay, and Uruguay, making it a pan-hemispheric disease.
 
The virus has never been reported to spread by person-to-person contact in the United States; however, in 1996 there may have been person-to-person Hantavirus transmission in Argentina.

 

HPS Case Definition

 

Deer Mouse Habitat in North America. The deer mouse is found throughout North America, preferring woodlands, but also appearing in desert areas CDC

Cotton Rat Habitat in North America. The cotton rat is found in the southeastern US and down into Central and South America. It inhabits overgrown areas with shrubs and tall grasses.
CDC

Rice Rat Habitat in North America. The rice rat prefers marshy areas and is semi-aquatic. It is found in the southeastern US and Central America
CDC

White-footed Mouse Habitat in North America. The white-footed mouse is found throughout southern New England and the Mid-Atlantic and southern states, the midwestern and western states, and Mexico. It prefers wooded and brushy areas, although it will sometime inhabit more open ground 
CDC
 

  Transmission electron micrograph of a virus that causes Hantavirus pulmonary syndrome (Sin Nombre virus).
CDC/Cynthia Goldsmith  csg1@cdc.gov 

  New World Hanatviruses
CDC

  Map of the United States and adjacent areas showing distribution of Peromyscus maniculatus and location of hantavirus pulmonary syndrome cases 
CDC

Radiographic Progression of HPS in the Lungs
CDC

Hantavirus Pulmonary Syndrome Clinical Progression
CDC

  Hantavirus Pulmonary Syndrome  Common Laboratory Findings 
CDC

Histopathology of hanatvirus pulmonary syndrome  Other Organs
CDC 

Using immunohistochemical (IHC) technique, this photomicrograph is actually an enlargement of PHIL 12727, from a human central nervous system (CNS) tissue specimen, which revealed some of the cytoarchitectural histopathologic changes associated with a Nipah virus infection.
CDC/ Brian W.J. Mahy, BSc, MA, PhD, ScD, DSc

HENIPAVIRUSES

Hendra and Nipah viruses (Paramyxoviruses, negative strand RNA viruses)

These two similar paramyxoviruses have their natural reservoir in and are spread by fruit bats (Flying foxes: genus Pteropus).

Nipah virus was first discovered in Malaysia and Singapore in 1999 when it caused fever and headache after a few days and, in some cases, respiratory disease. The respiratory symptoms include a very loud cough. This was followed by confusion, coma and encephalitis. Sequelae of the infection include convulsions. There were 257 confirmed cases of Nipah virus in the 1999 Malaysia outbreak and about 40% of patients died. They were all adult males, who were in close contact with infected pigs. The name Nipah comes from the name of their village.

Nipah virus outbreaks have also occurred in India and Bangladesh. 

Hendravirus (equine morbillivirus) is named after the Hendra area of Brisbane, Australia, where it was first discovered in 1994. It caused respiratory disease (severe flu-like symptoms) and neurological problems in both horses and three humans. One of the three humans infected had delayed encephalitis and two died of the infection. It appears that the humans caught the virus as a result of direct contact with infected horses.

Diagnosis of both viruses is by ELIZA (to detect antibodies in the patients) and RT-PCR (to detect the virus directly). Virus can also be isolated from throat swabs or cerebro-spinal fluid.

There are no useful drugs to treat infected patients although ribavirin has been shown to work against the virus in the laboratory. In 2012, it was shown that a soluble form of the Hendravirus glycoprotein can protect moneys from challenge with Nipah virus which may lead to a vaccine against both viruses. It is planned to use a veterinary vaccine first in Australia, thereby targeting the spread to humans.

• Nipah Virus and Lychee fruits

Ebola Virus
CDC

Transmission electron micrograph of Marburg virus. Virions are often seen bent into sixes and hairpin configurations.    CDC/Dr. Erskine Palmer 

VIRAL DISEASES IN WHICH THE RESERVOIR OR VECTOR IS UNCLEAR

VIRUS DISEASES WITH UNKNOWN RESERVOIR / VECTOR
Envelope	Symmetry	Genome	Size*
Filoviridae family
yes	helical	single strand negative sense
* Relative size adapted from White and Fenner , Medical Virology, 1994

EBOLA AND MARBURG VIRUSES

Ebola and Marburg viruses cause hemorrhagic fevers and have a case-fatality rate which can be as high as 60-90% for certain strains of the viruses. These viruses occur in Africa, but the natural reservoir is unknown. They occasionally infect humans, but the means by which this occurs is usually not clear. 

Patients have severe hemorrhages and there is a lot of virus present, so stringent barrier nursing techniques are needed to prevent further spread. There have been a few cases where humans have been infected by apparently healthy laboratory monkeys.

Ebola virus, which is named after a river in the Democratic Republic of the Congo, infects humans and other primates and was first identified in 1976. The virus is a negative strand RNA filovirus

Disseminated intravascular coagulation (DIC) leading to tissue ischemia and eventual depletion of clotting factors is a typical feature of filovirus infections. Currently several anti-clotting agents are being tested for their effectiveness at preventing the DIC in animal models.

• More on Ebola virus and hemorrhagic fever

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This page last changed on Wednesday, November 23, 2016
Page maintained by Richard Hunt