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Biodefense Reference Library
Foreign Animal and Zoonotic Disease Center
 
One Medicine: One Health (Zoonotic Disease) Online Course

Presented by

Stephen M. Apatow, Director of Research and Development 
Humanitarian Resource Institute Biodefense Reference Library
Foreign Animal and Zoonotic Disease Center
[Vitae][Email]

ZOONOTIC DISEASES
VIRAL

CONTAGIOUS ECTHYMA

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Orf, Contagious pustular dermatitis, Contagious Pustular Stomatitis, Ecthyma Contagiosum) 

AGENT:
Genus Parapoxvirus of Family Poxviridae. 
RESERVOIR AND INCIDENCE
Sheep and goats worldwide. 
TRANSMISSION:
Crusted areas on muzzle, eyelids, oral cavity, feet, or external genitalia are laden with virus. Transmitted easily from animals to man by contact. The virus is highly resistant to adverse environments and persists for many years. 
DISEASE IN ANIMALS:
Necrosis in the skin and mucous membranes of the gastrointestinal and urogenital tracts. Intense pain can interfere with eating. 
DISEASE IN MAN:
Large painful nodules usually distributed on the hands. Weeping red surfaces. These resolve with minimum scarring 1-2 months later. 
DIAGNOSIS:
Diagnosis is made by a history of contact with sheep, goats, or wild ungulates; by EM demonstration of the poxvirus in the lesion; cell culture; or serologically. 
PREVENTION/CONTROL:
Wear rubber gloves when handling infected sheep and when working in an environment near infected sheep. 

MONKEY POX

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.
Centers for Disease Control: Monkeypox: Updates/Advisories 
Humanitarian Resource Institute: Monkeypox:  Biodefense and Epidemiological Tracking
AGENT:
Orthopoxvirus Disease in humans is indistinguishable from smallpox, (Variola) i.e., serologic & clinical syndrome. 
RESERVOIR AND INCIDENCE
Animals: Nine reported outbreaks in captive NHP's, primarily rhesus and cynomolgus. Has also been reported in languors, baboons, chimpanzees, orangutans, marmosets, gorillas, gibbons, and squirrel monkeys. The virus has been isolated from a wild squirrel. Man: The first human case of Monkey Pox was reported in 1970. Between 1970 and 1986, over 400 cases had been reported from tropical rain forested areas of West and Central Africa. 
TRANSMISSION:
Transmission can be via direct contact, aerosol, ingestion, or parenteral administration. Person to person transmission can occur. 
DISEASE IN NONHUMAN PRIMATES:
Usually exhibit a high morbidity and low mortality. Clinical signs may be inapparent or an animal may exhibit fever, lymphadenopathy, and cutaneous eruptions of the extremities, trunk, lips, or face. Cynos seem to be most severely affected. Death is uncommon except in infant monkeys. 
DISEASE IN MAN:
Signs in man include fever, sore throat, headache, and a vesiculopustular rash of peripheral distribution which clears up in 5 to 25 days. Severe complications include bronchopneumonia, vomiting, and diarrhea. Case fatality rate 10-15%. Although the disease is not common in man it is important from the standpoint of differentiating it from smallpox. 
DIAGNOSIS:
Based on progression of lesions, histopathology and virus isolation. On histological examination epidermal cells contain eosinophilic cytoplasmic and intranuclear inclusions. ELISA 
TREATMENT:
Symptomatic. 
PREVENTION/CONTROL:
Sanitation, isolation. Vaccination with vaccinia virus is protective in both man and nonhuman primates. 

YABAPOX

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.
AGENT:
Poxvirus 
RESERVOIR AND INCIDENCE
Affects mangabeys, rhesus, cynos, vervets, stumptails, and patas monkeys. Latent infection in African species that can infect Asian primates and U.S. born African primates. 
TRANSMISSION:
Need further clarification of the epidemiology of this disease. Role of insect vectors has not been determined. Aerosol transmission has been proven experimentally. *Transmission to humans from monkeys has not been recorded. The virus can affect man usually after accidental skin puncture. 
DISEASE IN NONHUMAN PRIMATES:
Subcutaneous benign tumors (Histiocytomas) that may reach several cm. in diameter. They usually regress spontaneously in 3 to 6 weeks. 
DISEASE IN MAN:
Lesions similar to those seen in monkeys 
PREVENTION/CONTROL:
Usual care should be exercised by animal handlers, including wearing of protective clothing. 

TANAPOX

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Benign Epidermal Monkeypox, BEMP) 

AGENT:
Tanapox virus. 
RESERVOIR AND INCIDENCE
Monkeys. In 1966 23 human cases were reported in the U.S. among personnel who worked with monkeys affected at 3 primate centers. A serologic study carried out on 263 monkeys of Asian origin (Macaca) revealed a 15% rate; in 55 African Green Monkeys, the rate was 76%. 
TRANSMISSION:
Aerosols or vectors. Human cases in the laboratory have resulted from contamination of abrasions or scratches. 
DISEASE IN NONHUMAN PRIMATES:
Lesions occur primarily on the face, consisting of raised areas with a central scab. Papules ulcerate, scab and heal. 
DISEASE IN HUMANS:
There is a fever for a few days, with headache and prostration and a single skin vesicle. Cytoplasmic inclusions are seen in skin lesions. Within 3 weeks of onset, the lesion spontaneously regresses. 
DIAGNOSIS:
EM of skin scrapings or viral isolation. 
TREATMENT:
Symptomatic. 
PREVENTION/CONTROL:
Mosquito control. Asian and African monkeys should be housed separately. Wear protective clothes. 

HERPESVIRUSES

There are more than 35 Herpesviruses of NHPs most of which are NOT zoonotic. 

HERPES B

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Herpesvirus simiae, Simian B Disease) 

AGENT:
Double-stranded DNA Virus. Direct zoonosis. For each Herpesvirus there exists a host for which the virus is almost uniformly fatal and reservoir hosts in which the virus exists in subclinical or latent infection. a. H. suis latent in swine, fatal in cattle. b. H. simplex I latent in man, fatal in Aotus, Gibbon, Marmoset (especially). c. H. saimiri I latent in Saimiri sciureus, fatal in Marmosets, Aotus (also known as Herpes T, Herpes M, Herpes Tamarinus). d. H. saimiri II latent in Saimiri sciureus, fatal in Marmosets, Aotus (this is an oncogenic virus, causing Malignant Melanoma of Reticulum Cell Type). e. H. simiae latent in rhesus and other macaques, fatal in man (also known as Herpes B Virus). f. Liverpool Vervet Monkey Virus: reservoir host ???, fatal in Cercopithecus aethiops. The Herpesviruses are serologically distinct but do share some antigenic properties. Herpes B Virus has been shown to have some antigenic relationship to Herpesvirus simplex by serum neutralization tests. However, antibody from Herpesvirus simplex does not confer immunity to Herpes B Virus. 
RESERVOIR AND INCIDENCE
Incidence of infection of the reservoir host is normally high but you rarely see clinical disease. Clinical disease is usually confined to the very young or to the immunologically compromised. On occasion lethal infection occurs in the reservoir host: in humans, generalized Herpes simplex is often fatal in infants; in swine, Herpes suis is fatal in piglets. Natural infection does not result in elimination of the virus or in immunity but produces a latent infection or carrier, which always makes vaccination of reservoirs impractical. Herpesvirus B was first described in 1934 by Sabin/Wright. The virus was recovered from a laboratory worker who had been bitten 18 days previously by an apparently healthy rhesus. Since 1934, there have been 24 reported cases, all fatal, except four. Of the four, only one is reasonably free of severe neurological deficits. (Patients have remained in coma for as long as 40 months prior to succumbing to the disease.) Incubation is considered to be 10-20 days from exposure to the virus; however, in the Pensacola cases, clinical disease occurred within 4-5 days of exposure. Contact with macaques does not constitute exposure. The susceptibility of man to clinical B infection is low although mortality is high. 
TRANSMISSION:
direct contact, including sexual transmission, aerosols, and fomites. 
THE DISEASE IN NHP:
The reservoir hosts for Herpesvirus simiae are monkeys of the genus Macaca. Monkeys incriminated include M. mulatta (rhesus), M. fascicularis (cyno), M. fuscata (Japanese macaque), and M. arctoides (Stump-tail macaque). B virus may produce mild cold-sore type lesions, primarily at mucocutaneous junctions, mucous membranes, and tongue. But, it has been demonstrated that infection is not confined to the mouth but can also be found in the genitalia. These lesions are similar to those caused by Herpesvirus simplex I in man. Two factors have been associated with antibody increases with age; 80-100% of imported adult rhesus may have antibody compared to 20% imported juveniles. The second factor was type of caging. Animals housed together had significantly higher titers than individually-caged animals. Clinical disease may develop at the time of primary infection but it is not known if lesions invariably follow infection. However, periodic shedding of the virus may occur without the presence of visible lesions. Once a monkey is infected with B Virus, it should be considered infective for life. 
THE DISEASE IN MAN:
Human infection is characterized by encephalitis with diplopia; nystagmus, patch paresthesia of head, neck and upper extremities. Acute abdominal pain, fever and diarrhea have also been observed prior to neurologic symptoms. Patients may also have a vesicular rash and/or keratoconjunctivitis. The histopathological changes resemble those of fatal, systemic Herpesvirus simplex in infants: encephalitis, myelitis and foci of necrosis in liver, spleen, lymph nodes and adrenals. The case fatality rate is 70%. 
DIAGNOSIS:
ELISA and viral isolation. 
TREATMENT:
Acyclovir. 
PREVENTION/CONTROL:
Control includes personal hygiene, protective clothing and common sense in handling monkeys. The virus is susceptible to oxidizing agents, soap, and water. Guidelines for prevention and treatment have been developed. The reader is referred to the reference by Holmes, GP, et al for further details. Emphasis can not be too strong concerning the use of protective clothing when entering a room with macaques. A perfectly healthy monkey may be lethal to you. 

Arthropod borne ARBOVIRUSES:

Centers for Disease Control:  Arboviral Encephalitides

Perspectives

Arthropod-borne viruses, i.e., arboviruses, are viruses that are maintained in nature through biological transmission between susceptible vertebrate hosts by blood feeding arthropods (mosquitoes, psychodids, ceratopogonids, and ticks). Vertebrate infection occurs when the infected arthropod takes a blood meal. The term 'arbovirus' has no taxonomic significance. Arboviruses that cause human encephalitis are members of three virus families: the Togaviridae (genus Alphavirus), Flaviviridae, and Bunyaviridae. 

All arboviral encephalitides are zoonotic, being maintained in complex life cycles involving a nonhuman primary vertebrate host and a primary arthropod vector. These cycles usually remain undetected until humans encroach on a natural focus, or the virus escapes this focus via a secondary vector or vertebrate host as the result of some ecologic change. Humans and domestic animals can develop clinical illness but usually are "dead-end" hosts because they do not produce significant viremia, and do not contribute to the transmission cycle. Many arboviruses that cause encephalitis have a variety of different vertebrate hosts and some are transmitted by more than one vector. Maintenance of the viruses in nature may be facilitated by vertical transmission (e.g., the virus is transmitted from the female through the eggs to the offspring). 

Arboviral encephalitides have a global distribution, but there are four main virus agents of encephalitis in the United States: eastern equine encephalitis (EEE), western equine encephalitis (WEE), St. Louis encephalitis (SLE) and La Crosse (LAC) encephalitis, all of which are transmitted by mosquitoes. Another virus, Powassan, is a minor cause of encephalitis in the northern United States, and is transmitted by ticks. A new Powassan-like virus has recently been isolated from deer ticks. Its relatedness to Powassan virus and its ability to cause disease has not been well documented. Most cases of arboviral encephalitis occur from June through September, when arthropods are most active. In milder (i.e., warmer) parts of the country, where arthropods are active late into the year, cases can occur into the winter months. 

The majority of human infections are asymptomatic or may result in a nonspecific flu-like syndrome. Onset may be insidious or sudden with fever, headache, myalgias, malaise and occasionally prostration. Infection may, however, lead to encephalitis, with a fatal outcome or permanent neurologic sequelae. Fortunately, only a small proportion of infected persons progress to frank encephalitis. 

Experimental studies have shown that invasion of the central nervous system (CNS), generally follows initial virus replication in various peripheral sites and a period of viremia. Viral transfer from the blood to the CNS through the olfactory tract has been suggested. Because the arboviral encephalitides are viral diseases, antibiotics are not effective for treatment and no effective antiviral drugs have yet been discovered. Treatment is supportive, attempting to deal with problems such as swelling of the brain, loss of the automatic breathing activity of the brain and other treatable complications like bacterial pneumonia. 

There are no commercially available human vaccines for these U.S. diseases. There is a Japanese encephalitis vaccine available in the U.S. A tick-borne encephalitis vaccine is available in Europe. An equine vaccine is available for EEE, WEE and Venezuelan equine encephalitis (VEE). Arboviral encephalitis can be prevented in two major ways: personal protective measures and public health measures to reduce the population of infected mosquitoes. Personal measures include reducing time outdoors particularly in early evening hours, wearing long pants and long sleeved shirts and applying mosquito repellent to exposed skin areas. Public health measures often require spraying of insecticides to kill juvenile (larvae) and adult mosquitoes. 

Selection of mosquito control methods depends on what needs to be achieved; but, in most emergency situations, the preferred method to achieve maximum results over a wide area is aerial spraying. In many states aerial spraying may be available in certain locations as a means to control nuisance mosquitoes. Such resources can be redirected to areas of virus activity. When aerial spraying is not routinely used, such services are usually contracted for a given time period. 

Financing of aerial spraying costs during large outbreaks is usually provided by state emergency contingency funds. Federal funding of emergency spraying is rare and almost always requires a federal disaster declaration. Such disaster declarations usually occur when the vector-borne disease has the potential to infect large numbers of people, when a large population is at risk and when the area requiring treatment is extensive. Special large planes maintained by the United States Air Force can be called upon to deliver the insecticide(s) chosen for such emergencies. Federal disaster declarations have relied heavily on risk assessment by the CDC. 

Laboratory diagnosis of human arboviral encephalitis has changed greatly over the last few years. In the past, identification of antibody relied on four tests: hemagglutination-inhibition, complement fixation, plaque reduction neutralization test, and the indirect fluorescent antibody (IFA) test. Positive identification using these immunoglobulin M (IgM) - and IgG-based assays requires a four-fold increase in titer between acute and convalescent serum samples. With the advent of solid-phase antibody-binding assays, such as enzyme-linked immunosorbent assay (ELISA), the diagnostic algorithm for identification of viral activity has changed. Rapid serologic assays such as IgM-capture ELISA (MAC-ELISA) and IgG ELISA may now be employed soon after infection. Early in infection, IgM antibody is more specific, while later in infection, IgG antibody is more reactive. Inclusion of monoclonal antibodies (MAbs) with defined virus specificities in these solid phase assays has allowed for a level of standardization that was not previously possible. 

Virus isolation and identification have also been useful in defining viral agents in serum, cerebrospinal fluid and mosquito vectors. While virus isolation still depends upon growth of an unknown virus in cell culture or neonatal mice, virus identification has also been greatly facilitated by the availability of virus-specific MAbs for use in IFA assays. Similarly, MAbs with avidities sufficiently high to allow for specific binding to virus antigens in a complex protein mixture (e.g., mosquito pool suspensions) have enhanced our ability to rapidly identify virus agents in situ. While polymerase chain reaction (PCR) has been developed to identify a number of viral agents, such tests have not yet been validated for routine rapid identification in the clinical setting. 

Mosquito-borne encephalitis offers a rare opportunity in public health to detect the risk of a disease before it occurs and to intervene to reduce that risk substantially. The surveillance required to detect risk is being increasingly refined by the potential utilization of these new technologies which allows for rapid identification of dangerous viruses in mosquito populations. These rapid diagnostic techniques used in threat recognition can shorten public health response time and reduce the geographic spread of infected vectors and thereby the cost of containing them. The Arbovirus Diseases Branch of NCID's Division of Vector-Borne Infectious Diseases has responsibility for CDC's programs in surveillance, diagnosis, research and control of arboviral encephalitides. 

La Crosse Encephalitis

La Crosse (LAC) encephalitis was discovered in La Crosse, Wisconsin in 1963. Since then, the virus has been identified in several Midwestern and Mid-Atlantic states. During an average year, about 75 cases of LAC encephalitis are reported to the CDC. Most cases of LAC encephalitis occur in children under 16 years of age. LAC virus is a Bunyavirus and is a zoonotic pathogen cycled between the daytime-biting treehole mosquito, Aedes triseriatus, and vertebrate amplifier hosts (chipmunks, tree squirrels) in deciduous forest habitats. The virus is maintained over the winter by transovarial transmission in mosquito eggs. If the female mosquito is infected, she may lay eggs that carry the virus, and the adults coming from those eggs may be able to transmit the virus to chipmunks and to humans. 

Historically, most cases of LAC encephalitis occur in the upper Midwestern states (Minnesota, Wisconsin, Iowa, Illinois, Indiana, and Ohio). Recently, more cases are being reported from states in the mid-Atlantic (West Virginia, Virginia and North Carolina) and southeastern (Alabama and Mississippi) regions of the country. It has long been suspected that LAC encephalitis has a broader distribution and a higher incidence in the eastern United States, but is under-reported because the etiologic agent is often not specifically identified. 

LAC encephalitis initially presents as a nonspecific summertime illness with fever, headache, nausea, vomiting and lethargy. Severe disease occurs most commonly in children under the age of 16 and is characterized by seizures, coma, paralysis, and a variety of neurological sequelae after recovery. Death from LAC encephalitis occurs in less than 1% of clinical cases. In many clinical settings, pediatric cases presenting with CNS involvement are routinely screened for herpes or enteroviral etiologies. Since there is no specific treatment for LAC encephalitis, physicians often do not request the tests required to specifically identify LAC virus, and the cases are reported as aseptic meningitis or viral encephalitis of unknown etiology. 

Also found in the United States, Jamestown Canyon and Cache Valley viruses are related to LAC, but rarely cause encephalitis. 

Eastern Equine Encephalitis

Eastern equine encephalitis (EEE) is also caused by a virus transmitted to humans and equines by the bite of an infected mosquito. EEE virus is an alphavirus that was first identified in the 1930's and currently occurs in focal locations along the eastern seaboard, the Gulf Coast and some inland Midwestern locations of the United States. While small outbreaks of human disease have occurred in the United States, equine epizootics can be a common occurrence during the summer and fall. 

It takes from 4-10 days after the bite of an infected mosquito for an individual to develop symptoms of EEE. These symptoms begin with a sudden onset of fever, general muscle pains, and a headache of increasing severity. Many individuals will progress to more severe symptoms such as seizures and coma. Approximately one-third of all people with clinical encephalitis caused by EEE will die from the disease and of those who recover, many will suffer permanent brain damage with many of those requiring permanent institutional care. 

In addition to humans, EEE virus can produce severe disease in: horses, some birds such as pheasants, quail, ostriches and emus, and even puppies. Because horses are outdoors and attract hordes of biting mosquitoes, they are at high risk of contracting EEE when the virus is present in mosquitoes. Human cases are usually preceded by those in horses and exceeded in numbers by horse cases which may be used as a surveillance tool. 

EEE virus occurs in natural cycles involving birds and Culiseta melanura, in some swampy areas nearly every year during the warm months. Where the virus resides or how it survives in the winter is unknown. It may be introduced by migratory birds in the spring or it may remain dormant in some yet undiscovered part of its life cycle. With the onset of spring, the virus reappears in the birds (native bird species do not seem to be affected by the virus) and mosquitoes of the swamp. In this usual cycle of transmission, virus does not escape from these areas because the mosquito involved prefers to feed upon birds and does not usually bite humans or other mammals. 

For reasons not fully understood, the virus may escape from enzootic foci in swamp areas in birds or bridge vectors such as Coquilletidia perturbans and Aedes sollicitans. These species feed on both birds and mammals and can transmit the virus to humans, horses, and other hosts. Other mosquito species such as Ae. vexans and Culex nigripalpus can also transmit EEE virus. When health officials maintain surveillance for EEE virus activity, this movement out of the swamp can be detected, and if the level of activity is sufficiently high, can recommend and undertake measures to reduce the risk to humans. 

Western Equine Encephalitis

The alphavirus western equine encephalitis (WEE) was first isolated in California in 1930 from the brain of a horse with encephalitis, and remains an important cause of encephalitis in horses and humans in North America, mainly in western parts of the USA and Canada. In the western United States, the enzootic cycle of WEE involves passerine birds, in which the infection is inapparent, and culicine mosquitoes, principally Cx. tarsalis, a species that is associated with irrigated agriculture and stream drainages. The virus has also been isolated from a variety of mammal species. Other important mosquito vector species include Aedes melanimon in California, Ae. dorsalis in Utah and New Mexico and Ae. campestris in New Mexico. WEE virus was isolated from field collected larvae of Ae. dorsalis, providing evidence that vertical transmission may play an important role in the maintenance cycle of an alphavirus. 

Expansion of irrigated agriculture in the North Platte River Valley during the past several decades has created habitats and conditions favorable for increases in populations of granivorous birds such as the house sparrow, Passer domesticus, and mosquitoes such as Cx. tarsalis, Aedes dorsalis and Aedes melanimon. All of these species may play a role in WEE virus transmission in irrigated areas. In addition to Cx. tarsalis, Ae. dorsalis and Ae. melanimon, WEE virus also has been isolated occasionally from some other mosquito species present in the area. Two confirmed and several suspect cases of WEE were reported from Wyoming in 1994. In 1995, two strains of WEE virus were isolated from Culex tarsalis and neutralizing antibody to WEE virus was demonstrated in sera from pheasants and house sparrows. During 1997, 35 strains of WEE virus were isolated from mosquitoes collected in Scotts Bluff County, Nebraska.

Human WEE cases are usually first seen in June or July. Most WEE infections are asymptomatic or present as mild, nonspecific illness. Patients with clinically apparent illness usually have a sudden onset with fever, headache, nausea, vomiting, anorexia and malaise, followed by altered mental status, weakness and signs of meningeal irritation. Children, especially those under 1 year old, are affected more severely than adults and may be left with permanent sequelae, which is seen in 5 to 30% of young patients. The mortality rate is about 3%. 

St. Louis Encephalitis

In the United States, the leading cause of epidemic flaviviral encephalitis is St. Louis encephalitis (SLE) virus. SLE is the most common mosquito-transmitted human pathogen in the U.S. While periodic SLE epidemics have occurred only in the Midwest and southeast, SLE virus is distributed throughout the lower 48 states. Since 1964, there have been 4,437 confirmed cases of SLE with an average of 193 cases per year (range 4 - 1,967). However, less than 1% of SLE viral infections are clinically apparent and the vast majority of infections remain undiagnosed. Illness ranges in severity from a simple febrile headache to meningoencephalitis, with an overall case-fatality ratio of 5-15 %. The disease is generally milder in children than in adults, but in those children who do have disease, there is a high rate of encephalitis. The elderly are at highest risk for severe disease and death. During the summer season, SLE virus is maintained in a mosquito-bird-mosquito cycle, with periodic amplification by peridomestic birds and Culex mosquitoes. In Florida, the principal vector is Cx. nigripalpus, in the Midwest, Cx. pipiens pipiens and Cx. p. quinquefasciatus and in the western United States, Cx. tarsalis and members of the Cx. pipiens complex. 

Powassan Encephalitis

Powassan (POW) virus is a flavivirus and currently the only well documented tick-borne transmitted arbovirus occurring in the United States and Canada. Recently a Powassan-like virus was isolated from the deer tick, Ixodes scapularis. Its relationship to POW and its ability to cause human disease has not been fully elucidated. POW's range in the United States is primarily in the upper tier States. In addition to isolations from man, the virus has been recovered from ticks (Ixodes marxi, I. cookei and Dermacentor andersoni) and from the tissues of a skunk (Spiligale putorius). It is a rare cause of acute viral encephalitis. POW virus was first isolated from the brain of a 5-year-old child who died in Ontario in 1958. Patients who recover may have residual neurological problems. 

Venezuelan Equine Encephalitis

Like EEE and WEE viruses, Venezuelan equine encephalitis (VEE) is an alphavirus and causes encephalitis in horses and humans and is an important veterinary and public health problem in Central and South America. Occasionally, large regional epizootics and epidemics can occur resulting in thousands of equine and human infections. Epizootic strains of VEE virus can infect and be transmitted by a large number of mosquito species. The natural reservoir host for the epizootic strains is not known. A large epizootic that began in South America in 1969 reached Texas in 1971. It was estimated that over 200,000 horses died in that outbreak, which was controlled by a massive equine vaccination program using an experimental live attenuated VEE vaccine. There were several thousand human infections. A more recent VEE epidemic occurred in the fall of 1995 in Venezuela and Colombia with an estimated 90,000 human infections. Infection of man with VEE virus is less severe than with EEE and WEE viruses, and fatalities are rare. Adults usually develop only an influenza-like illness, and overt encephalitis is usually confined to children. Effective VEE virus vaccines are available for equines.

Enzootic strains of VEE virus have a wide geographic distribution in the Americas. These viruses are maintained in cycles involving forest dwelling rodents and mosquito vectors, mainly Culex (Melanoconion) species. Occasional cases or small outbreaks of human disease are associated with there viruses, the most recent outbreaks were in Venezuela in 1992, Peru in 1994 and Mexico in 1995-96. 

Other Arboviral Encephalitides

Many other arboviral encephalitides occur throughout the world. Most of these diseases are problems only for those individuals traveling to countries where the viruses are endemic. 

Japanese Encephalitis

Japanese encephalitis (JE) virus is a flavivirus, related to SLE, and is widespread throughout Asia. Worldwide, it is the most important cause of arboviral encephalitis with over 45,000 cases reported annually. In recent years, JE virus has expanded its geographic distribution with outbreaks in the Pacific. Epidemics occur in late summer in temperate regions, but the infection is enzootic and occurs throughout the year in many tropical areas of Asia. The virus is maintained in a cycle involving culicine mosquitoes and waterbirds. The virus is transmitted to man by Culex mosquitoes, primarily Cx. tritaeniorhynchus, which breed in rice fields. Pigs are the main amplifying hosts of JE virus in peridomestic environments. 

The incubation period of JE is 5 to 14 days. Onset of symptoms is usually sudden, with fever, headache and vomiting. The illness resolves in 5 to 7 days if there is no CNS involvement. The mortality in most outbreaks is less than 10%, but is higher in children and can exceed 30%. Neurologic sequelae in patients who recover are reported in up to 30% of cases. A formalin-inactivated vaccine prepared in mice is used widely in Japan, China, India, Korea, Taiwan and Thailand. This vaccine is currently available for human use in the United States, for individuals who might be traveling to endemic countries. 

Tick-Borne Encephalitis

Tick-borne encephalitis (TBE) is caused by two closely related flaviviruses which are distinct biologically. The eastern subtype causes Russian spring-summer encephalitis (RSSE) and is transmitted by Ixodes persulcatus, whereas the western subtype is transmitted by Ixodes ricinus and causes Central European encephalitis (CEE). The name CEE is somewhat misleading, since the condition can occur throughout much of Europe. Of the two subtypes, RSSE is the more severe infection, having a mortality of up to 25% in some outbreaks, whereas mortality in CEE seldom exceeds 5%. 

The incubation period is 7 to 14 days. Infection usually presents as a mild, influenza-type illness or as benign, aseptic meningitis, but may result in fatal meningoencephalitis. Fever is often biphasic, and there may be severe headache and neck rigidity, with transient paralysis of the limbs, shoulders or less commonly the respiratory musculature. A few patients are left with residual paralysis. Although the great majority of TBE infections follow exposure to ticks, infection has occurred through the ingestion of infected cows' or goats' milk. An inactivated TBE vaccine is currently available in Europe and Russia. 

West Nile Encephalitis

WNV is a flavivirus belonging taxonomically to the Japanese encephalitis serocomplex that includes the closely related St. Louis encephalitis (SLE) virus, Kunjin and Murray Valley encephalitis viruses, as well as others. WNV was first isolated in the West Nile Province of Uganda in 1937 (2). The first recorded epidemics occurred in Israel during 1951-1954 and in 1957. Epidemics have been reported in Europe in the Rhone delta of France in 1962 and in Romania in 1996 (3-5). The largest recorded epidemic occurred in South Africa in 1974 (6).

An outbreak of arboviral encephalitis in New York City and neighboring counties in New York state in late August and September 1999, was initially attributed to St. Louis encephalitis virus based on positive serologic findings in cerebrospinal fluid (CSF) and serum samples using a virus-specific IgM-capture enzyme-linked immunosorbent assay (ELISA). The outbreak has been subsequently confirmed as caused by West Nile virus based on the identification of virus in human, avian, and mosquito samples. See also these MMWR articles Outbreak of West Nile-Like Viral Encephalitis -- New York, 1999. MMWR, 1999:48(38);845-9 and Update: West Nile-Like Viral Encephalitis -- New York, 1999. MMWR, 1999:48(39);890-2. A recent outbreak WN encephalitis occurred in Bucharest, Romania in 1996.

The virus that caused the New York area outbreak has been definitively identified as a strain of WNV. The genomic sequences identified to date from human brain, virus isolates from zoo birds, dead crows, and mosquito pools are identical. SLE and West Nile viruses are antigenically related, and cross reactions are observed in most serologic tests. The isolation of viruses and genomic sequences from birds, mosquitoes, and human brain tissue permitted the discovery of West Nile virus in North America and prompted more specific testing. The limitations of serologic assays emphasize the importance of isolating the virus from entomologic, clinical, or veterinary material. 

Although it is not known when and how West Nile virus was introduced into North America, international travel of infected persons to New York or transport by imported infected birds may have played a role. WNV can infect a wide range of vertebrates; in humans it usually produces either asymptomatic infection or mild febrile disease, but can cause severe and fatal infection in a small percentage of patients. Within its normal geographic distribution of Africa, the Middle East, western Asia, and Europe, WNV has not been documented to cause epizootics in birds; crows and other birds with antibodies to WNV are common, suggesting that asymptomatic or mild infection usually occurs among birds in those regions. Similarly, substantial bird virulence of SLE virus has not been reported. Therefore, an epizootic producing high mortality in crows and other bird species is unusual for either WNV or SLE virus. For both viruses, migratory birds may play an important role in the natural transmission cycles and spread. Like SLE virus, WNV is transmitted principally by Culex species mosquitoes, but also can be transmitted by Aedes, Anopheles, and other species. The predominance of urban Culex pipiens mosquitoes trapped during this outbreak suggests an important role for this species. Enhanced surveillance for early detection of virus activity in birds and mosquitoes will be crucial to guide control measures. 

Related: 

Murray Valley Encephalitis

Murray Valley encephalitis (MVE) is endemic in New Guinea and in parts of Australia; and is related to SLE, WN and JE viruses. Inapparent infections are common, and the small number of fatalities have mostly been in children.

YELLOW FEVER

Centers for Disease Control and Prevention: National Center for Infectious Diseases 
yellow fever

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Black Vomit) 

AGENT:
RNA virus, Family Togaviridae, (Group B Arbovirus) 
RESERVOIR AND INCIDENCE
All primates susceptible; major Public Health problem in Central and S. America and Africa. 
TRANSMISSION:
Mosquito vector: Aedes and Hemagogues.
DISEASE IN NONHUMAN PRIMATES:
There is high fever and vomiting, with jaundice, oliguria, and generalized hemorrhages. Microglobular fatty degeneration of liver cells occurs with disruption of the hepatic lobule and necrosis of midzonal liver cells, producing so called "Councilman" bodies. Degeneration and necrosis of the kidney tubules occurs. There are hemorrhages in tissues. 
DISEASE IN MAN:
Most cases have fever, severe headache and backache, jaundice and albuminuria, followed by full recovery with a week, but in severe cases there is a second episode of fever, prostration, jaundice, renal failure and generalized hemorrhages. Microglobular fatty degeneration of liver cells occurs with disruption of the hepatic lobule and necrosis of midzonal liver cells, producing so called "Councilman" bodies. Degeneration and necrosis of the kidney tubules occurs. There are hemorrhages in tissues. The case fatality rate among indigenous populations of endemic regions is <5%, but may exceed 50% among nonindigenous groups and in epidemics. 
DIAGNOSIS:
Virus isolation or serology. 
TREATMENT:
Consists of limiting food to high-carbohydrate, high-protein liquids, IV glucose and saline, analgesics and sedatives, and saline enemas. 
PREVENTION/CONTROL:
Monkeys should originate from a yellow fever free area, or be maintained in a double-screened mosquito-proof enclosure, or have been immunized against yellow fever. For humans, mosquito control, vaccination, and adherence to PHS quarantine standards. 

HANTAVIRUS PULMONARY SYNDROME

Centers for Disease Control and Prevention: National Center for Infectious Diseases
hantavirus pulmonary syndrome

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

INTRODUCTION:
On May 14, 1993, the New Mexico Department of Health was notified of 2 persons who had died within 5 days of each other. Their illnesses were characterized by abrupt onset of fever, myalgia, headache, and cough, followed by the rapid development of respiratory failure. Tests for Yersinia pestis and other bacterial and viral pathogens were negative. After additional persons who had recently died following a similar clinical course were reported by the Indian Health Service, the health services of Arizona, Colorado and Utah were contacted to seek other possible cases. Blood and tissue specimens were sent to the Centers for Disease Control and Prevention (CDC). The results were negative except for signals for the Puumala hantavirus. Relying on molecular and immunological research performed by the Army, the National Institutes of Health, and the CDC itself, by June 9th, the CDC was able to prove that a new hantavirus was the culprit (1). As of November 5th, laboratory evidence of acute hantavirus infection had been confirmed in 42 persons. Twenty-six (62%) of these persons have died. Most cases were in the Southwest but some have been reported as far afield as North Dakota and California (1). This paper presents a brief overview of hantavirus infections with primary focus on Hantavirus Pulmonary Syndrome (HPS) and recommended laboratory precautions to reduce the risk of accidental exposure. Other detailed reviews are available elsewhere (2-7). 
AGENT:
Isolation of the first recognized hantavirus (Hantaan virus) was reported from the Republic of Korea in 1978. The genus Hantavirus is a member of the family Bunyaviridae. Hantaviruses are further divided into genotypes. Representative viruses in each genotype are the Hantaan virus, the Seoul virus, the Puumala virus, and the Prospect Hill virus. Additional groups exist. Hantaan, Puumala, and Seoul viruses are known human pathogens; Prospect Hill has not been associated with disease. The causative agent of HPS represents a previously unidentified genotype. Since the 1930s, epidemic and sporadic hantavirus-associated disease has been described throughout Eurasia, especially in Scandinavia and Northeastern Asia. In the 1950s, thousands of United Nations military personnel were infected with hantavirus during the Korean conflict; more recently, transmission has been documented among United States military personnel training in the Republic of Korea. Hantaviruses have been isolated from rodents in the United States, and serological studies have documented human infections with hantaviruses. However, acute disease associated with infection by pathogenic hantaviruses has not previously been reported in the Western Hemisphere (8). Previously called the Four Corners Virus and Muerto Canyon Virus, the causative genotype for HPS is now called Sin Nombre Virus. 
DISEASE IN HUMANS:
The clinical manifestations previously associated with hantavirus infections have been characterized by hemorrhagic features and by renal involvement. In HPS, however, onset of illness has been characterized by a prodrome consisting of fever, myalgia, and variable respiratory symptoms followed by the abrupt onset of acute respiratory distress. Other symptoms reported during the early phase of illness have included headache and gastrointestinal complaints. Hemoconcentration and thrombocytopenia have developed in a majority of the cases. The hospital course has been characterized by bilateral pulmonary infiltration, fever, hypoxia, and hypotension; recovery in survivors has been without sequelae. It is important to note that no defined set of symptoms and signs reliably distinguishes HPS from other forms of noncardiogenic pulmonary edema or adult respiratory distress syndrome (9). Postmortem examination has routinely revealed serous pleural effusions and heavy edematous lungs. Microscopic findings have included interstitial infiltrates of mononuclear cells in the alveolar septa, congestion, septal and alveolar edema with or without mononuclear cell exudate, focal hyaline membranes, and occasional alveolar hemorrhage. Large mononuclear cells with the appearance of immunoblasts have been found in red and periarteriolar white pulp of the spleen, hepatic portal triads, and other sites. Hantavirus antigens, localized primarily in endothelial cells, have been detected in most organs, with marked accumulations in the lungs (9). The incubation period for the known pathogenic hantaviruses, although highly variable, generally range from 2 to 4 weeks (8). Based on reported cases, the incubation period for HPS appears to be one to three weeks (10). 
RESERVOIRS:
Rodents are the primary reservoir hosts with each hantavirus appearing to have a preferential rodent host. The epidemiological characteristics of outbreaks of human disease and the severity for the infection are determined mainly by the rodent host. Available data strongly supports the deer mouse (Peromyscus maniculatus) as the primary reservoir of the newly recognized hantavirus (11). Serologic evidence of infection has also been found in pi¤on mice (P. truei) and the brush mice (P. boylii). Other rodent species that have tested positive so far include the house mouse (Mus musculus), the harvest mouse (Reithrodontomys sp.), the rock squirrel (Spermophalus variegatus), the white-throated wood rat (Neotoma albigula), and the western chipmunk (Tamias spp.). P. maniculatus is highly adaptable and is found in different habitats, including human residences in rural and semirural areas, but generally not in urban centers (12). The wood mouse or striped field mouse (Apodemus sp.) associated hantaviruses also cause severe human disease with mortality rates between 3 and 7%. Rattus associated disease is less severe and asymptomatic infections may be more common. The most benign form of hantaviral disease (HVD), also called Nephropathia epidemica and first described in Scandinavia, is caused by a hantavirus that infects voles (Clethrionomys species). Infected voles and human disease occur throughout western Europe (13). The hantaviruses have been identified in other animals. At the International Symposium on Hemorrhagic Fever with Renal Syndrome (HFRS), Leningrad, 5-10 May 1991, the presence of hantaviral antigen was reported in 13 species of birds in eastern parts of the former U.S.S.R. (13). The CDC is also investigating whether other animals, particularly those that prey on rodents, may carry the virus. The impetus for this research is a 1987 study suggesting that cats, which tested positive for two other hantaviruses-the Hantaan and Seoul types-may help transmit the virus to humans in China. As for the HPS virus, so far CDC scientists have identified one infected nonrodent species (aside from humans): the desert cottontail (Sylvilagus auduboni). But virologists think most nonrodents are "dead-end" hosts that shed little virus and are unlikely to infect people (14). Laboratory rats, which were a reservoir of hantavirus, have been responsible for several outbreaks of HVD among animal caretakers and laboratory workers at research institutions in Korea, China, the former Soviet Union, Japan, Scandinavia, the U.K., France, the Netherlands and Belgium (13). Transmission of Hantavirus from laboratory reared mice and rats has not been documented in the United States. 
TRANSMISSION:
Susceptibility of rodents may vary depending on the combination of rodent species and virus strains; however, Hantaviruses do not cause apparent illness in their reservoir hosts (15). In rodents, the virus is detected primarily in the lung and kidney, where it persists despite the presence of serum antibodies. Infected rodents shed large quantities of virus in saliva, urine, and feces for many weeks, but the duration and period of maximum infectivity are unknown. Although the main route of transmission is aerosolization, the demonstrated presence of infectious virus in saliva of infected rodents and the marked sensitivity of these animals to hantaviruses following inoculation suggests that biting may also be an important mode of transmission among rodents (12). Arthropod vectors are not known to have a role in the transmission of hantaviruses. Domestic animals may bring infected rodents into contact with humans (12). Human infection may occur when infective saliva or excreta are inhaled as aerosols produced directly from the animal. Transmission may also occur when dried materials contaminated by rodent excreta are disturbed, directly introduced into broken skin, introduced onto the conjunctivae, or, possibly, ingested in contaminated food or water. Persons have also become infected after being bitten by rodents (12). Person-to-person transmission has not been associated with any of the previously identified hantaviruses nor with the recent outbreak in the Southwest (16). In the current epidemic, known hantavirus infections of humans have occurred primarily in adults and are associated with domestic, occupational, or leisure activities that bring humans into contact with infected rodents, usually in a rural setting. Cases have been epidemiologically associated with the following situations: Planting or harvesting field crops Occupying previously vacant cabins or other dwellings Cleaning barns and other outbuildings Disturbing rodent-infested areas while hiking or camping Inhabiting dwellings with indoor rodent populations Residing in or visiting areas in which the rodent population has shown an increase in density (12). In Europe, isolation of hantaviruses from immunocytomas and ascites tumors has highlighted additional risks from working with persistently infected rodents. Tumors, passaged over the years in hantavirus-infected laboratory rats, transfer the virus when implanted in hantavirus-free rats. Since, in rodents, hantaviruses are not transmitted vertically but horizontally, the use of caesarian section and foster mother techniques have been recommended for laboratories breeding rodent colonies. Before implantation, tumors should be checked for the presence of the hantaviruses (this precaution should be followed by laboratory workers in the U.S. importing tumors, organs, or live rodents from hantavirus endemic areas) (12). 
DIAGNOSIS:
The CDC in consultation with the Council of State and Territorial Epidemiologists has developed screening criteria for HPS (9). Cases meeting the screening criteria should be reported to the CDC through state health departments. These criteria are: Potential case-patients must have one of the following: a febrile illness (temperature ò101 oF [ò38.3 oC]) occurring in a previously healthy person characterized by unexplained adult respiratory distress syndrome, or bilateral interstitial pulmonary infiltrates developing within 1 week of hospitalization with respiratory compromise requiring supplemental oxygen, OR an unexplained respiratory illness resulting in death in conjunction with an autopsy examination demonstrating noncardiogenic pulmonary edema without an identifiable specific cause of death. Potential case-patients are to be excluded if they have any of the following: a predisposing underlying medical condition (e.g., severe underlying pulmonary disease, solid tumors or hematologic malignancies, congenital or acquired immunodeficiency disorders, or medical conditions [e.g., rheumatoid arthritis or organ transplant recipients] requiring immunosuppressive drug therapy [e.g., steroids or cytotoxic chemotherapy]). an acute illness that provides a likely explanation for the respiratory illness (e.g., recent major trauma, burn, or surgery; recent seizures or history of aspiration; bacterial sepsis; another respiratory disorder such as respiratory syncytial virus in young children; influenza; or legionella pneumonia). Confirmed case-patients must have the following: at least one specimen (i.e., serum and/or tissue) available for laboratory testing for evidence of hantavirus infection. AND in a patient with a compatible clinical illness, diagnosis is confirmed when any of the following criteria are met: IgM antibodies to hantavirus antigens, fourfold or greater increase in immunoglobulin G titers to hantavirus antigens in paired serum specimens, a positive immunohistochemical stain for hantavirus antigen in tissues, or positive polymerase chain reaction (PCR) for hantavirus ribonucleic acid. Currently, diagnosis of the HPS strain of Hantavirus in animals is in its infancy. IFA based tests offered by national research laboratories may be used for screening; however, false negatives can occur depending on the antigen used. PCR remains the method of choice for strain identification. Presently, one laboratory (Rockefeller University Laboratory Animal Research Center, [212]327-8522) offers this service with more, hopefully, coming on line in the future (17). 
TREATMENT:
Supportive care and meticulous monitoring of vital signs and fluid balance are the basis for therapy. Severe hypoxia and overhydration should be avoided or prevented. Pressors or cardiotonic drugs should be employed to maintain perfusion without excessive fluid administration (9). In one controlled study involving HFRS, intravenous administration of the antiviral drug ribavirin was effective in treating severe cases of hantavirus infection when administered early in the course of illness (8). The effectiveness of using ribavirin to treat HPS has not been established, yet. 
PREVENTION AND CONTROL:
Hantaviruses have lipid envelopes that are susceptible to most disinfectants (e.g., dilute hypochlorite solutions, detergents, ethyl alcohol (70%), or most general-purpose household disinfectants). How long these viruses survive after being shed in the environment is uncertain (12). The reservoir hosts of the hantavirus in the southwestern United States also act as hosts for the bacterium Yersinia pestis, the etiology agent of plague. Although fleas and other ectoparasites are not known to play a role in hantavirus epidemiology, rodent fleas transmit plague. Control of rodents without concurrent control of fleas may increase the risk of human plague as the rodent fleas seek an alternative food source. Thus, eradicating the reservoir hosts of hantaviruses is neither feasible nor desirable. Once the virus has been cultured, it might be possible to develop a vaccine against the HPS strain. However, currently, the best available approach for disease control and prevention is risk reduction through environmental hygiene practices that deter rodents from colonizing the home and work environment (12). No restriction of travel to areas affected by this outbreak is considered necessary; however, activities that may disrupt rodent burrows or result in contact with rodents or aerosolization or rodent excreta should be avoided. Laboratory workers practicing universal precautions while processing routine clinical materials (such as blood, urine, and respiratory specimens) are not considered to be at increased risk for hantavirus infection. However, laboratory-acquired infections have occurred among persons who handled infected wild or laboratory rodents. Therefore, laboratory work that may result in propagation of hantaviruses should be conducted in a special facility (biosafety level 3) (8). Recommendations for laboratory animal facilities housing wild-caught rodents include: Access to rooms should be restricted to only those individuals who have a legitimate need to be in the room. Colony should be serologically screened for the agent. Animals should be housed and handled under standard microisolation techniques. Biological safety cabinets should be used and not laminar flow workbenches. Until the status of the colony can be ascertained, individuals working with the rodent should: a. Obtain a baseline serum sample. The serum should be stored at -20oC. b. Insure that all persons involved are informed of the symptoms of the disease and given detailed guidance on prevention measures. c. Seek immediate medical attention if a febrile or respiratory illness develops within 45 days of the last potential exposure. The attending physician should be informed of the potential occupational risk of hantavirus infection. d. Wear an half-face air-purifying (or negative-pressure) respirator or powered air-purifying respirator with HEPA filter when handling rodents or their cages. Respirators are not considered protective if facial hair interferes with the face seal. Respirators should be fitted by trained personnel in accordance with OSHA standards. e. Wear rubber or plastic gloves when handling rodents or cages. Gloves should be washed and disinfected before removing them. f. Wear dedicated outer garments (disposable, if possible), rubber boots or disposable shoe covers and protective goggles. Personal protective gear should be decontaminated upon removal. If not disposable, they should be laundered on site using hot water and detergent. Machine-dry using a high setting. If no laundry facilities are available, non-disposable items should be immersed in liquid disinfectant until they can be washed. All potentially infective waste material (including respirator filters, bedding, caging, disposable protective garments, and used disposables such as syringes, gauze, etc.) should be placed in autoclavable plastic bags and sterilized. Needles, scalpels, pipettes, and other sharp materials should be placed in puncture proof containers and sterilized. Spread from feral rodents was postulated as the cause of one source of contamination (18). Therefore, facilities and individual rooms should be vermin-proof to prevent accidental egress and ingress of rodents. All openings greater than ¬ inch should be screened or sealed. Carcasses should be placed in a plastic bag and disposed as biohazard waste or incinerated. Since feral rodents may transmit the disease, it is recommended that Hantavirus testing be included in animal health monitoring programs. Why the Current Epidemic? Because of the rodent connection with this disease, medical investigators and public health officials sought ecological information on the deer mouse and other native rodent species. Anecdotal information from residents in the afflicted areas suggested that rodents were exceptionally abundant last winter, and scientists speculated that, if true, the increased potential for rodent-human contact and disease transmission might account for the sudden epidemic. Biologists with the Sevilleta, New Mexico Long-Term Ecological Research (LTER) site have long-term data on rodent communities in the region. At the request of the CDC and the New Mexico Health Department, LTER researchers provided detailed demographic analyses from 1989-1993 for the 22 rodent species inhabiting the area. The LTER data showed tenfold population increases in various Peromyscus species and wood rats (Neotoma spp.) during the spring of 1993. Population increases occurred simultaneously in grasslands, desert-shrublands, and woodlands. Comparisons of the rodent data to the region's climatological data indicated that rodent population dynamics is associated with above-average precipitation during the winter of 1992-93, in turn leading to abundant food sources (19). 

References

  1. Marshall, E. 1993. Hantavirus outbreak yields to PCR. Science. 262:832-836. 
  2. LeDuc, J. W., J. E. Childs, and G. E. Glass. 1992. The Hantaviruses, etiologic agents of hemorrhagic fever with renal syndrome. Annu Rev Public Health. 13:79-98. 
  3. Niklasson, B. S. 1992. Hemorrhagic fever with renal syndrome, virological and epidemiological aspects. Pediatr Nephrol. 6(2):201-204. 
  4. Cosgriff, T. M. and R. M. Lewis. 1991. Mechanisms of disease in hemorrhagic fever with renal syndrome. Kidney Int Suppl. 35:S72-79. 
  5. Tkachenko E. A. and H. W. Lee. 1991. Etiology and epidemiology of hemorrhagic fever with renal syndrome. Kidney Int Suppl. 35:S54-61. 
  6. Beaty, B. J. and C. H. Calisher. 1991. Bunyaviridae--natural history. Curr Top Microbiol Immunol. 169:27-78. 
  7. Gonzalez-Scarano, F., M. J. Endres, and N. Nathanson. 1991. Bunyaviridae: Pathogenesis. Curr Top Microbiol Immunol. 169:217-249. 
  8. 1993. Emerging infectious diseases. Outbreak of acute illness. Wkly Epidemiol Rec. 68(25):186-8. 
  9. 1993. Emerging infectious diseases. Update: Hantavirus Disease. MMWR. 42(29, 31, and 42). 
  10. Sands, L. 1993. Guidelines for 
    11. DIAGNOSIS:
    and treatment of unexplained adult respiratory distress syndrome. Arizona Department of Health Services. 
  11. Nichol, S. T., C. F. Spiropoulou, S. Morzunov, et al. 1993. Genetic identification of a Hantavirus associated with an outbreak of acute respiratory illness. Science. 262:914-917. 
  12. 1993. Hantavirus infection-Southwestern United States: interim recommendations for risk reduction. MMWR. 42(RR-11). 
  13. McKenna, P., G. VanDerGroen, G. Hoofd, et al. 1992. Eradication of hantavirus infection among laboratory rats by application of caesarian section and a foster mother techniques. J Infect. 25:181-190. 
  14. Stone, R. 1993. The mouse-pi¤on nut connection. Science. 262:833. 
  15. Kawamura, K., X. K. Zhang, J. Arikawa, et al. 1991. Susceptibility of laboratory and wild rodents to Rattus or Apodemus-type hantaviruses. Acta Virol. 35:54-63. 
  16. Hughes, J. M., C. J. Peters, M. L. Cohen, et al. 1993. Hantavirus pulmonary syndrome: an emerging infectious disease. Science. 262:850-851. 
  17. Morse, S. 1994. Personal communication. 
  18. Wong, T. W., Y. C. Chan, E. H. Yap, et al. 1988. Serological evidence of Hantavirus infection in laboratory rats and personnel. Int J Epidemiol. 17(4):887-890. 
  19. Dybas, C. 1993. NSF-funded researchers find rodent population explosion may be behind hantavirus epidemic in southwest. NSF Bulletin #93-59. 

HEMORRHAGIC FEVER WITH RENAL SYNDROME [HFRS]

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Korean Hemorrhagic Fever, Nephropathia Epidemica, Epidemic Hemorrhagic Fever, Hemorrhagic Nephrosonephritis) 

AGENT:
Bunyaviridae family, Hantaan virus genus 
RESERVOIR AND INCIDENCE
Recognized originally in troops serving in the Korean war. Named Hantaan after river in endemic area of Korea. Isolated in 1978 in Apodemus agrarius, then adapted to tissue culture and laboratory rats. Serologic mapping indicates that Hantaviruses have infected large numbers of people in the region from Japan across central and north Asia to the Scandinavian Peninsula, and southward in Europe to the Balkans. Other Hantaviruses have been identified in urban rats captured in major Asian and Western cities, including the USA and Brazil. Hosts of hantavirus are wild Rodents Several antigenic subtypes exist, each associated with a single rodent species: Apodemus species - Striped field mouse - A. agrarius (Korea) associated with KHF. Domestic Rattus norvegicus and Rattus rattus in Korea and Domestic Rattus norvegicus in the U.S. had virus similar to prototype Hantaan virus yet distinct from it. Microtus pennsylvanicus: the meadow vole. Reservoir for Prospect Hill virus, most recently isolated Hantavirus. Isolated at NIH and named for Prospect Hill in Frederick, MD where the vole was captured that yielded the first isolate. No human disease associated with this so far but antibody has been identified among mammalogists in the U.S.(1982). Cletheronomys glareolus: the bank vole. Reservoir for Puumala virus, cause of Nephropathia epidemica (NE), a mild form of HFRS found in Scandinavia, Western Soviet Union and much of Europe. 
TRANSMISSION:
Aerosol transmission from rodent excreta is presumed. Virus is present in urine, feces and saliva of persistently infected asymptomatic rodents; highest virus concentration is found in the lungs. Human to human transmission does not occur. 
DISEASE IN RODENTS:
Chronic, ASYMPTOMATIC infection. Following infection, rodent is viremic for about 1 week when virus is disseminated throughout the body. After viremia antigen is usually abundant in the lungs, spleen and kidneys. Antibody is produced and persists but does not diminish the abundance of antigen expressed in organs. 
DISEASE IN MAN:
Symptoms begin with the sudden onset of fever which lasts 1-2 weeks, accompanied by prostration, anorexia, generalized pains, conjunctivitis, proteinuria and hypotension, possibly followed by hemorrhages and hematuria with renal failure. Case fatality rate is 7%. 
DIAGNOSIS:
Serology using indirect immunofluorescence or ELISA. 
TREATMENT:
IV ribavirin 
PREVENTION/CONTROL:
Although most US commercial animal breeders have eliminated these viruses through barrier breeding and caesarean derivation, small suppliers and producers of select inbred strains may be at risk of infection. Be aware of potentially infected animals when receiving shipments from Japan, Belgium or other countries which may have the agent present in lab. animals (where virus-free certification cannot be provided). Animals should be serologically tested in advance of shipment. Test all rodent tissues, tumors, cell lines received from source that cannot provide virus free certification. Education and awareness of potential problem. Exclude rodents from housing and other buildings in endemic areas. 

OTHER HEMORRHAGIC FEVERS

Centers for Disease Control and Prevention: National Center for Infectious Diseases
arenavirus infections

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Arenaviruses) All have natural persistent infection in rodents with humans being accidental hosts. Route of transmission to humans is generally thought to occur thru contamination of food, water, or air by rodent feces or urine or by inoculation of skin abrasions. Humans are infected primarily through infected rodents invading human habitats. Contact with infected rodent feces has produced disease in laboratory personnel. 

DIAGNOSIS:
By serology or virus isolation. Control is to reduce opportunity for exposure to infected rodents. 1. JUNIN VIRUS: produces Argentinian hemorrhagic fever There is an illness of 1-2 weeks with insidious onset of fever, malaise, rigors, fatigue, headache, vomiting, constipation or diarrhea, conjunctival congestion, retro-orbital pain, epistaxis, petechial hemorrhages beneath skin, palate and gums. Edema of the upper body is possible. In severe cases hematemesis and melena, encephalopathy, bradycardia and hypertension occur. Case fatality rate 5-30%. Several hundred cases reported each year in Argentina. Associated with at least 3 different cricetine rodent species in Argentina 2. MACHUPO VIRUS: produces Bolivian Hemorrhagic fever Signs and case fatality rate like Junin virus. Case #s have been decreasing rapidly since initiation of rodent control programs in 1975. Associated with Calomys callosus (Bolivia). 3. LASSA FEVER: Serologically related to Lymphocytic Choriomeningitis, Machupo, and Junin virus. Fever has insidious onset over 2-3 days and may persist for up to 4 weeks, with malaise, headache and generalized aching and sore throat. Vomiting and diarrhea, possibly edema of face and neck, lymphadenopathy with hemorrhages and renal failure occurs in the second week. The prostration is out of proportion to fever. Often there is a maculopapular rash. Occurs in large areas in West Africa. Documented man to man transmission. Found in common rodent Mastomys natalensis, multimammate rat (West Africa). 

LYMPHOCYTIC CHORIOMENINGITIS - LCM

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.
AGENT:
Arenavirus Of many latent viruses present in mice, only LCM naturally infects humans. LCM can easily be transmitted from animals to humans. Isolated by Armstrong and Lillie during investigation of a St. Louis Encephalitis outbreak in 1933. 
RESERVOIR AND INCIDENCE
Worldwide in wild mice (M. musculus). This disease is principally confined to the eastern seaboard and northeastern states in the U.S. Wild mice infect the lab mouse. Mouse and hamster are the only species in which long term, asymptomatic infection is known to exist. *LCM virus is present in experimental mouse tumors which is a second source of infection for humans. This was first recognized in a transplantable leukemia of C58 mice. The disease can also be transmitted to laboratory animals via inoculation of infected tissue culture cells. The infection also occurs in guinea pigs, rabbits, rats, canines, swine, and primates. 
TRANSMISSION:
Infection in mice is maintained by congenital infection followed by lifelong carriage and excretion of virus in saliva, urine, and feces. Human infections are probably from contaminated food and dust, the handling of dead mice, and mouse bites. Bloodsucking arthropod vectors such as ticks, lice, and mosquitos may transmit the disease. Person to person transmission does not occur. 
DISEASE IN ANIMALS:
The clinical signs of LCM depend on the host's resistance and age when infected, although the various categories of the disease are not always clearly delineated. Animals infected in utero or during the first 48 hours postpartum may develop a transient viremia but recover completely within a few weeks. Other animals similarly infected may develop a persistent tolerant infection (PTI) that continues asymptomatically for 6 or more months. Animals infected after the first few days, when the virus will be recognized as foreign, often overcome the infection completely, but an acute, usually fatal syndrome can develop. Signs of acute infection in mice continue for 1-2 weeks and include decreased growth, rough hair coat, hunched posture, blepharitis, weakness, photophobia, tremors, and convulsions. The terminal stage of the PTI, which occurs over several weeks to 5 to 12 month old mice, is characterized by weight loss, blepharitis, and impaired reproductive performance and runted litters. The important necropsy signs are microscopic. Visceral organs, including the liver, kidneys, lungs, pancreas, blood vessels, and meninges, are infiltrated by lymphocytes. A glomerulonephritis of probable immune complex origin is a characteristic feature of terminal PTI. 
DISEASE IN MAN:
The features may include influenza-like illness for up to 2 weeks, possibly with orchitis. Sometimes meningitis, paralysis and coma follow. Joint pains occur during convalescence. 
DIAGNOSIS:
CF or virus isolation. 
PREVENTION/CONTROL:
Serologic monitoring Infection can be eradicated by cesarean derivation prevent wild mice from entering facilities control ectoparasites and roaches Restrict flow of traffic into and out of LCM infected colonies Protective clothing and proper care when handling infected animals or tissues. Basic hygienic practices Screen tissue culture cell lines and murine tumor lines and animals periodic serologic testing of high risk personnel

CALIFORNIA ENCEPHALITIS/LA CROSSE ENCEPHALITIS

Centers for Disease Control and Prevention: Division of Vector-Borne Infectious Diseases
La Crosse encephalitis

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(USA) (Tahyna virus [Europe]) A mild, febrile, viral disease which occasionally causes severe encephalitis. It is transmitted by mosquitoes from small wild mammals, mainly in summer, to persons frequenting woodland areas of the USA and Canada, and certain European countries such as Yugoslavia and the USSR. The causative agents are the California encephalitis group of viruses (Bunyaviridae). There is no vaccine. 

RESERVOIR AND MODE OF TRANSMISSION:
The virus cycles amongst small wild animals (e. chipmunks, squirrels, rabbits and hares) and a variety of mosquito species. The infection can be maintained independently over several years by transovarial transmission in the mosquito. Humans are accidental hosts infected by mosquito bite during occupational or recreational activities in wooded areas. Accidental infections from laboratory accidents have occurred. 
INCUBATION PERIOD:
Humans. 5-15 days. Animals. Unknown. 
CLINICAL FEATURES:
Humans. Symptoms lasting about 5-10 days range from fever and headache with nausea and vomiting to fits and signs of aseptic meningitis, encephalitis and neurological sequelae. Animals. Unknown but assumed subclinical. 
PATHOLOGY:
Humans. Encephalitis. Animals. Unknown. 
DIAGNOSIS:
:Humans. The virus may sometimes be isolated from blood or rarely, from cerebrospinal fluid. Serologic tests of blood or cerebrospinal fluid may be diagnostic in specific types of encephalitis (by demonstrating virus-specific IgM or a fourfold change in complement-fixing or neutralizing antibodies). Animals. Impracticable. 
PROGNOSIS:
In humans, fatality is rare but neurological defects may persist. Animals. Thought to be subclinical. 
PREVENTION:
Humans. Prevent mosquito bites. Control the mosquito vector. Apply laboratory safety procedures. Animals. Impracticable. 
TREATMENT:
Humans. Vigorous symptomatic therapy. Such measures include reduction of intracranial pressure (Mannitol), monitoring of intraventricular pressure, the control of convulsions, maintenance of the airway, administration of oxygen, and attention to adequate nutrition during periods of prolonged coma. Animals. Not applicable. 
LEGISLATION:
Humans. Acute encephalitis is notifiable in many countries, including the USA and the UK. Animals.None. 

MARBURG VIRUS

Centers for Disease Control and Prevention: National Center for Infectious Diseases
Marburg virus infection

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(African Hemorrhagic Fever, Green or Vervet Monkey Disease) 

AGENT:
Agent is classified as a Filovirus. It is an RNA virus, superficially resembling rhabdoviruses but has bizarre branching and filamentous or tubular forms shared with no other known virus group on EM. 
RESERVOIR AND INCIDENCE
An acute highly fatal disease first described in Marburg, Germany in 1967. Brought to Marburg in a shipment of infected African Green Monkeys from Uganda. 31 people were affected and 7 died in 1967. Exposure to tissue and blood from African Green monkeys (Cercopithecus aethiops) or secondary contact with infected humans led to the disease. No disease occurred in people who handled only intact animals or those who wore gloves and protective clothing when handling tissues. A second outbreak was reported in Africa in 1975 involving three people with no verified contact with monkeys. Third and fourth outbreaks in Kenya 1980 and 1987. Natural reservoir is unknown. Monkeys thought to be accidental hosts along with man. Antibodies have been found in African Green monkeys, baboons, and chimpanzees. 100% fatal in experimentally infected African Green Monkeys, Rhesus, squirrel monkeys, guinea pigs, and hamsters. 
TRANSMISSION:
Direct contact with infected blood or tissues or close contact with infected patients. Virus has also been found in semen, saliva, and urine. 
DISEASE IN NONHUMAN PRIMATES:
No clinical signs occur in green monkeys, but the disease is usually fatal after experimental infection of other primate species. Leukopenia and petechial hemorrhages throughout the body of experimentally infected monkeys, sometimes with GI hemorrhages. 
DISEASE IN MAN:
5-7 day incubation period. Headache, fever, muscle pain, vomiting, diarrhea, hemorrhagic diathesis, Conjunctivitis, photophobia, skin rash, and jaundice. Leukopenia, thrombocytopenia, proteinuria. Shock and death in 25% of cases. Hemorrhages throughout the body on post mortem examination. 
DIAGNOSIS:
IFA, ELISA, Western blot, EM, or virus isolation. 
TREATMENT:
Supportive Possibly immune serum 
PREVENTION/CONTROL:
Strict quarantine on newly imported, wild-caught primates. Naturally infected monkeys should become ill or die within several weeks. Hygiene, sanitation, and protective clothing Isolation of human patients with prevention of sexual intercourse until semen is free of virus. 

EBOLA

Centers for Disease Control and Prevention: National Center for Infectious Diseases
Ebola hemorrhagic fever

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(African Hemorrhagic Fever) 

AGENT:
Similar to Marburg morphologically similar but antigenically distinct. Both are RNA Filoviruses and have bizarre branching and filamentous or tubular forms shared with no other known virus group. 
RESERVOIR AND INCIDENCE
Reservoirs unknown. Monkeys are probably accidental hosts, along with humans. First recognized in 1976 in Northern Zaire and Southern Sudan, 500 cases with 350 deaths reported. 
TRANSMISSION:
Person-to-person transmission occurs by direct contact with infected blood, secretions, organs or semen. Nosocomial infections have been frequent; all Zaire cases acquired from contaminated syringes and needles died. 
DISEASE IN MAN:
Fever, headache, malaise, followed by chest discomfort, diarrhea, and vomiting. Case fatality rate is 50-90%. 
DIAGNOSIS:
IFA, ELISA, Western blot, EM, or virus isolation. 
TREATMENT:
Supportive Possibly immune serum 
PREVENTION/CONTROL:
Strict quarantine on newly imported, wild-caught primates. Naturally infected monkeys should become ill or die within several weeks. Hygiene ,sanitation, and protective clothing Isolation of human patients with prevention of sexual intercourse until semen is free of virus. 

RABIES

Centers for Disease Control and Prevention: National Center for Infectious Diseases
rabies

Office International des Epizooties
Rabies: Manual of standards Diagnostic Tests and Vaccines 2000

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Hydrophobia, Lyssa) 

AGENT:
Rhabdovirus which causes an acute almost invariably fatal disease. 
RESERVOIR AND INCIDENCE
Worldwide distribution (few countries are exceptions) Primary reservoirs vary geographically, eg. foxes, bats, raccoons, skunks, dogs, cats, cattle, and others. In the U.S. and Canada, wildlife rabies most frequently involves skunks, raccoons, and bats. There has been a progressive epizootic among raccoons in the eastern U.S. for over a decade. Involve wild and domestic species. Mostly wild species involved, only 10% of cases are in domestic animals 16 cases have been confirmed in nonhuman primates, including chimpanzees, cebus, cynos, and squirrel monkeys. All source countries of NHP's have endemic rabies. In Germany, Paarman described 25 Avian cases of Rabies involving 11 chickens, 2 geese, 1 duck, 1 sparrow, 1 owl, 1 crow, 3 hawks, 1 kite, 1 magpie, and 4 buzzards with Negri bodies observed in only three. In the U.S., the Great Horned Owl may shed the virus in its droppings after consuming an infected skunk. Rodents and lagomorphs are unlikely to have rabies. In the U.S., rabies has been reported 13 times in ferrets since 1958, most often in pet ferrets acquired from pet shops. 
TRANSMISSION:
Virus laden saliva via bite, scratch, or abrasion Tissues and fluids in the laboratory Rabid dogs shed virus in saliva 5-7 days before showing signs. Cat does so for only 3 days before signs. Aerosol transmission has been documented in the laboratory and in caves where bats roost (requires a high concentration of suspended viral particles). Animals showing signs of rabies are usually shedding large amounts of virus. 
DISEASE IN ANIMALS:
Rabid animals of all species exhibit typical signs of CNS disturbance, with minor variations peculiar to carnivores, ruminants, bats, and man. The clinical course, particularly in dogs, can be divided into 3 phases: the prodromal, the excitative, and the paralytic. The term "furious rabies" refers to animals in which the excitative phase is predominant, and "dumb or paralytic rabies" to those in which the excitative phase is extremely short or absent and the disease progresses quickly to the paralytic phase. In any animal, the first sign is a change in behavior, which may be indistinguishable from a GI disorder, injury, foreign body in the mouth, poisoning, or an early infectious disease. Temperature change is not significant, and driveling may or may not be noted. Animals usually stop eating and drinking and may seek solitude. Frequently, the urogenital tract is irritated or stimulated as evidenced by frequent urination, erection in the male, and sexual desire. After the prodromal period of 1-3 days, animals either show signs of paralysis or become vicious. Carnivora, pigs, and occasionally, horses and mules bite other animals or people at the slightest provocation. Cattle butt any moving object. The disease progresses rapidly after the onset of paralysis, and death is virtually certain within 10 days of the first signs. Rabid domestic cats and bobcats attack suddenly, biting and scratching viciously. Rabid foxes frequently invade yards or even houses, attacking dogs and people. The irrationality of behavior that can occur is demonstrated in the fox that attacks a porcupine; finding a fox with porcupine quills can, in most cases, support a diagnosis of rabies. Rabid foxes and skunks are responsible for most pasture cattle losses, and have attacked cattle in barns. The rabid raccoon is characterized by its loss of fear of man, its frequent aggression and incoordination, and its activity during the day, being predominantly a nocturnal animal. In urban areas, they often attack domestic dogs. Bats flying in the daytime are probably rabid. 
DISEASE IN MAN:
There is usually a history of animal bite. Pain appears at the site of the bite, followed by paresthesias. The skin is quite sensitive to changes of temperature, especially air currents. Attempts at drinking cause extremely painful laryngeal spasm, so that the patient refuses to drink (hydrophobia). The patient is restless and behaves in a peculiar manner. Muscle spasm, laryngospasm, and extreme excitability are present. Convulsions occur. Large amounts of thick tenacious saliva are present. 
DIAGNOSIS:
Consider Rabies as a possible problem in any wild caught or random-source laboratory animal of unknown vaccination history showing central nervous system signs or symptoms. Virus isolation from body fluid or tissue Fluorescent antibody (FA) staining of tissues, including cornea, frozen skin, mucosal scrapings, as well as brain. Highly specific & rapid. Can now detect different strains (ie skunk vs raccoon origin) via monoclonal antibody analysis which is specific for one antigenic focus on the viral particle. The identifiable strains correlate well with species and geographic distributions observed. This allows identification of source and is an important epidemiologic tool. (5 strains have been isolated from terrestrial animals; 2 skunk, 1 raccoon, 1 gray fox, 1 red fox, More than 5 have been isolated from bats.) 
TREATMENT:
This very severe illness with an almost universally fatal outcome requires skillful intensive care with attention to the airway, maintenance of oxygenation, and control of seizures. 
PREVENTION/CONTROL:
Virus is destroyed rapidly at greater than 50 C and survives no more than a few hours at room temperature (Can persist for years in frozen tissues) Vigorous first aid for bite wounds. Consult Health Authority if suspected exposure. Postexposure immunization: Up to 50% of human rabies immune globulin is infiltrated around the wound; the rest is administered IM. Human Diploid Cell Vaccine (HDCV) is given as 5 injections IM at days 0, 3, 7, 14, and 28. Control disease in domestic animals by vaccination and enforced animal control measures. Discourage keeping of wild animals as pets. Discourage the vaccination of wild animal pets for rabies. Vaccination of high risk personnel. 

HEPATITIS A

Centers for Disease Control and Prevention: National Center for Infectious Diseases
hepatitis A

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Infectious hepatitis, Epidemic hepatitis, Epidemic jaundice) 

AGENT:
Family Picornaviridae, Genus enterovirus 
RESERVOIR AND INCIDENCE
More than 200 cases of hepatitis A virus infection in humans have been associated with nonhuman primates, principally chimpanzees but also woolly and patas monkeys, Celebes apes, siamangs, and gorillas. Man, and, rarely captive chimpanzees are the reservoir host; less frequently, certain other nonhuman primates. An enzootic focus has been identified in Malaysia, but there is no suggestion of transmission to man. 
TRANSMISSION:
Although transmission of the virus may occur by contaminated needles, it is usually by the fecal-oral route. Nonhuman primates acquire the disease from man. 
DISEASE IN NONHUMAN PRIMATES:
Usually do not show clinical signs, although malaise, vomiting, and jaundice have been reported. Disease is detected by elevated liver enzymes or diagnostic liver biopsies. Usually a self-limiting disease. 
DISEASE IN MAN:
Fever, malaise, anorexia, headache, muscle pain, abdominal discomfort, and jaundice. Liver enzymes are elevated along with LDH, bilirubin, and alkaline phosphatase. Morbidity is variable and mortality is 0.6% Development of antibody confers lifelong immunity. 
DIAGNOSIS:
RIA or ELISA 
TREATMENT:
Bed rest, IV fluids if dehydrated. 
PREVENTION/CONTROL:
Strictly quarantine newly arrived chimps and allow only limited human contact for at least 45-60 days. Protective clothing (gown, gloves, & mask) Routine disinfection of equipment and personal hygiene. Administer immune serum to handlers of newly imported chimpanzees (0.02ml/kg) every 3 mos. or 0.06 ml/kg every 4 months. Vaccine being developed. 

MEASLES

Centers for Disease Control and Prevention: National Center for Infectious Diseases 
measles

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Rubeola, Morbilli) 

AGENT:
Family Paramyxoviridae, Genus Morbillivirus. The same genus contains the viruses of Canine Distemper and Bovine Rinderpest. 
RESERVOIR AND INCIDENCE
Man is the only known reservoir. New world monkeys are more resistant than old world monkeys but exhibit high mortality when infected. 
TRANSMISSION:
Virus is excreted from the mucous membranes of the eye and pharynx and later from the respiratory and urinary tracts. Virus is shed in the prodromal phase and continues through the exanthematous phase. Highly contagious! Can spread from man to monkey, monkey to monkey, man to man, and monkey to man. 
DISEASE IN NONHUMAN PRIMATES:
Many infections occur subclinically. Rash, fever, facial edema, giant cell pneumonia, conjunctivitis, nasal discharge. 
DISEASE IN MAN:
Incubation period 10-14 days. Conjunctivitis Koplik spots - bluish white spots on buccal mucosa 2-3 days after onset Leukopenia Rash in mouth, cheeks, neck, chest, and body. Can be complicated by middle ear infection, bronchopneumonia, encephalitis Fetal risk if contracted during pregnancy. The mortality rate in children in the U.S. is 0.2%, but may be as high as 10% in developing countries. 
DIAGNOSIS:
Clinical signs, serology, histopath. 
TREATMENT:
Bed rest, acetaminophen, saline eye sponges, nose drops. Vitamin A (400,000 IU/day) has been shown to reduce pediatric morbidity and mortality. 
PREVENTION/CONTROL:
Vaccinate personnel working with nonhuman primates (Live attenuated measles vaccine) if they do not have: 1. a titer to rubeola (HI >1:4 protective) 2. confirmed history of previous vaccination 3. confirmed prior disease Live attenuated measles vaccine can be given to macaques but causes disease and death in marmosets and owl monkeys. 

CYTOMEGALOVIRUS DISEASE

Centers for Disease Control and Prevention: National Center for Infectious Diseases
Cytomegalovirus infection

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

Most cytomegalovirus infections in healthy individuals are asymptomatic, with the virus remaining (exact cells of latency are not known). However the virus is isolable from up to 25% of salivary glands, 10% of uterine cervices, and 1% of neonatal urine samples. Seroprevalence increases with age and the number of sexual partners; detectable antibody is present in the serum of most homosexual men. Transmission is sexual, congenital, through or transplantation, and person-to-person (e.g., day care centers). Severe disease occurs primarily in the immunocompromised, especially those with AIDS and transplant patients. 

DISEASE IN MAN:
A. Classification: There are three recognizable syndromes. 1. Perinatal disease and cytomegalovirus inclusion disease-Intrauterine infection of infants whose mothers had a primary infection during pregnancy results in a neonatal syndrome of jaundice, hepatosplenomegaly, thrombocytopenia, periventricular central nervous system calcifications, mental retardation, motor disability, and purpura. 
DIAGNOSIS:
Confirmed by viruria within the first week after birth or serum IgM antibodies to cytomegalovirus. Hearing deficits occur in over 15% and mental retardation in up to 30%. Neonatally acquired disease may resemble mononucleosis; while it is often asymptomatic, neurologic deficits may ensue later in life. 2. Acute acquired cytomegalovirus infection--This syndrome, akin to EBV-associated infectious mononucleosis, is characterized by fever, malaise, myalgias and arthralgias (but not pharyngitis or respiratory symptoms), atypical lymphocytes, and abnormal liver function tests. Unlike EBV-associated infectious mononucleosis, the heterophil antibody is not found. Transmission can be by sexual contact, by milk, by respiratory droplets (probably) among nursery or day care center attendants, and by (usually massive) transfusions of blood. 3. Disease in immunocompromised hosts-Tissue and bone marrow transplant patients are at increased risk for CMV infection, especially in the first I 00 days after allograft transplantation. HIV-infected patients may have a variety of CMV manifestations. Cytomegalovirus is itself immunosuppressive and may worsen manifestations of HIV infection, including Pneumocystis carinii pneumonia. a. CMV retinitis-Retinitis due to CMV infection occurs primarily in AIDS patients. Screening for visual symptoms may be helpful, but ophthalmologic documentation of neovascular, proliferative lesions ("pizza-pie" retinopathy) is required for diagnosis. b. Gastrointestinal and hepatobiliary CMV-Serious gastrointestinal CMV disease occurs in AIDS and after organ transplantation, cancer chemotherapy, or steroid therapy. Esophagitis presents with odynophagia; small bowel disease may mimic inflammatory bowel disease or may present as ulceration or perforation. Colonic CMV disease causes diarrhea, hematochezia. abdominal pain, fever, and weight loss. Pancreatitis, when not due to pentamidine, didanosine, or (less often) zalcitabine is often due to cytomegalovirus; hepatobiliary involvement often includes other pathogens, including Cryptosporidium. Diagnosis is by mucosal biopsy that shows characteristic CMV histopathologic findings of intranuclear ("owl's eye") and intracytoplasmic inclusions. c. Pulmonary CMV-Pulmonary CMV infection occurs in about 15% of bone marrow transplant recipients: the mortality rate is 80-90% in this group. CMV seronegative blood products should be used in seronegative recipients of seronegative transplants. High-titer CMV immunoglobulins may be effective in preventing CMV pneumonia in the seronegative recipients. d. Neurologic CMV-Polyradiculopathy and encephalitis have been reported but are not common. When they do occur, there is often concomitant retinitis, which may be subclinical. Prolonged ganciclovir may be helpful, and treatment should be continued indefinitely. 
DIAGNOSIS:
Cytomegalovirus is isolable from urine, cervical secretions, semen, saliva, blood, and other tissues, but virus isolation is most useful when combined with pathologic findings, including large cells with intranuclear and intracytoplasmic inclusions that resemble owl's eyes: cultures alone are of little use in diagnosing AIDS-related cytomegalovirus infections. Retinitis among aids patients is diagnosed clinically. The acute mononucleosis syndrome is associated with a lymphocytosis, often 2 weeks after the fever. Serologic tests (IFA and the anticomplement immunofluorescent antibody [ACIF]) are useful primarily in seroepidemiologic studies. In AIDS patients, titers may be depressed, and seroconversions are seldom documented, with most seroconversions having occurred in the past. Antigen detection by virus technology (including the polymerase chain reaction technique) must be interpreted in the context of clinical and pathologic findings. 
TREATMENT:
Two antiviral agents with efficacy against cytomegalovirus are ganciclovir, given in a dosage of 5 mg/kg IV every 12 hours for 14-21 days (maintenance: 5-7 mg/kg/day for 5 days each week, with dose reduction for renal impairment); and foscarnet, given as a loading dose of 20 mg/kg IV and then 60 mg/kg every 8 hours over 2 weeks (maintenance: 120 mg/kg/day). The induction phase is essential for AIDS patients with cytomegalovirus disease involving critical parts of the retina; for less critical areas, maintenance therapy can be used from the outset. Both agents are effective in preventing progression of retinitis, and ganciclovir is useful in cytomegalovirus colitis; treatment is usually lifelong in patients with AIDS. Complications include neutropenia with ganciclovir (preventing concomitant zidovudine therapy) and renal impairment with foscarnet (often manageable with hydration).
CONTROL:
Cytomegalovirus hyperimmune globulin given to seronegative bone marrow or renal transplant recipients may be prophylactic. Limiting transfusions, using products filtered to remove leukocytes, and selecting cytomegalovirus-seronegative donors are all important in reducing the rate of cytomegalovirus transmission.

INFLUENZA

Centers for Disease Control: Influenza: Updates/Advisories 
Humanitarian Resource Institute: Influenza:  Biodefense and Epidemiological Tracking

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Swine and Equine Influenza, Fowl Plague) 

AGENT:
The causative agent is influenza type A (Orthomyxoviridae). 
RESERVOIR AND INCIDENCE
Humans, wild and domestic birds, horses and pigs are reservoirs of influenza viruses, which appear to be species specific. Convalescent carriers act as reservoir hosts between epidemics. Antigenic shift is probably required before animal virus becomes epidemic in humans. Sporadic human infections with swine and avian strains have been reported. Human cases of influenza have occurred from contamination by aerosols from infected ferrets and vice versa. 
TRANSMISSION:
Transmission is by inhalation of droplets produced by coughing and sneezing, especially in crowded, enclosed spaces. 
DISEASE IN ANIMALS:
Fever has a sudden onset followed by anorexia, coughing, respiratory distress and mucoid nasal discharge, with rapid recovery. There is consolidation in the lung. Copious mucopurulent exudate fills the bronchioles. 
DISEASE IN HUMANS:
Typical symptoms include fever, chills, headache, myalgia, malaise, coryza, pharyngitis and cough with full recovery within two weeks, although viral or secondary bacterial pneumonia may develop, especially in the elderly. 
DIAGNOSIS:
Virus isolation, CF or HI serology. 
TREATMENT:
Bed rest, analgesics, and cough mixtures. Amantadine decreases duration by 50%. Antibiotics are reserved for bacterial complications. Ribavirin aerosol has helped severely ill patients. 
PREVENTION/CONTROL:
Polyvalent human influenza vaccine provides partial immunity (about 85% efficacy) for a few months to one year. The vaccine's antigenic configuration changes yearly and is based on prevalent strains of the preceding year. Chemoprophylaxis with amantadine will markedly reduce the attack rate among exposed individuals if begun immediately and continued for 10 days. Vaccinate horses annually. Prohibit imports of live poultry and poultry meat from countries where fowl plague occurs. 

SEVERE ACUTE RESPIRATORY SYNDROME (SARS)

World Health Organization: Severe Acute Respiratory Syndrome (SARS)
U.S. Centers for Disease Control: Severe Acute Respiratory Syndrome (SARS)

SARS, an atypical pneumonia of unknown aetiology, was recognized at the end of February 2003. The World Health Organization (WHO) is co-ordinating the international investigation with the assistance of the Global Outbreak Alert and Response Network and is working closely with health authorities in the affected countries to provide epidemiological, clinical and logistical support as required. 

PREVENTION/CONTROL:

WHO biosafety guidelines for handling of SARS specimens: 25 April 2003

NEWCASTLE DISEASE

Office International des Epizooties
Newcastle disease: Manual of standards Diagnostic Tests and Vaccines 2000

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

(Pseudo Fowl Pest) 

AGENT:
Newcastle disease virus, family Paramyxoviridae 
RESERVOIR AND INCIDENCE
The natural reservoir is wild and domesticated birds. 
TRANSMISSION:
Transmission is by inhalation of infectious aerosols. Intensive conditions favor spread by contact, on inanimate objects and airborne between poultry houses. Human infections occur mainly amongst laboratory workers and those who work with infected chickens or who give live vaccine, especially by aerosol. 
DISEASE IN ANIMALS:
In poultry, respiratory and nervous signs occur, including gasping and coughing; also drooping of wings, twisting of the head and neck; inappetence and paralysis. Egg production ceases. Petechial hemorrhages are characteristic, especially in the preventricular mucosa. Necrosis of the intestinal mucosa give a "bran" like appearance. Congestion and mucoid exudate appears in the lungs and bronchi. 
DISEASE IN HUMANS:
Usually symptoms are confined to painful conjunctivitis lasting a few days, but fever and influenza-like symptoms for up to 3 weeks may follow. 
DIAGNOSIS:
Virus isolation or ELISA. 
TREATMENT:
Symptomatic. 
PREVENTION/CONTROL:
Hygienic precautions are needed when handling infected birds. Avoid inoculation injuries and ensure laboratory safety. Maintain strict hygiene in poultry sheds and quarantine of imported live birds, prohibit importation from infected countries, sterilization of, or prohibition on, waste food fed to poultry. Vaccination of poultry. 
 

OTHER SPECULATIVE VIRAL ZOONOSES:

ROTAVIRUS:

Centers for Disease Control and Prevention: National Center for Infectious Diseases
rotavirus

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

Rotaviruses cause gastroenteritis in animals and humans. They are not strictly species-specific, and experimental cross-infections with human or animal rotaviruses in several animal species have been confirmed. The finding of serotypes common to man and various animal species might indicate that some serotypes can infect both. However, the natural occurrence of cross-infections between species and the possible role of animals in the epidemiology of the disease in humans are still unknown. 

RETROVIRUSES:

Disease Overview: Institutional Animal Care and Use Committee, University of California, Santa Barbara.

The human immunodeficiency viruses (HIVs)-acquired immunodeficiency syndrome (AIDS) or HAIDS pandemic originated from lentiviruses of nonhuman primates (thus qualifying as a zoonosis) that moved into humans in Africa. The HAIDS patients eventually die of opportunistic infections, all potentially zoonotic. The HAIDS infection remained parochial, first endemically and then epidemically, until the African urbanization that occurred in each of the countries postindependence. The latter included wars and the massive movement of soldiers (virologically naive) from the American continent to Africa and back. The HAIDS viral ecology coincided with African swine fever (ASF) in the Americas. Haiti became the focal point for both infections. Some infected Haitians also became, together with some infected drug addicts in the United States, a source of contaminated human blood for transfusions and production of plasma derivatives. 
 

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