More Diseases That Affect Horses and Humans

Diseases that occur in horses and humans are the subject of several CEH studies

Diseases that can be spread from animals to humans under normal conditions are known as zoonotic diseases. They can be spread in several different ways including, 1) ingestion of a parasite shed from an infected animal as in Cryptosporidiosis, 2) being bitten by a common vector such as ticks or mosquitoes as in Lyme disease, 3) direct contact of infected tissues or fluids as in rabies or vesicular stomatitis, and 4) direct contact with a bacterial or fungal organism as in Salmonella or coccidioidomycosis ("valley fever"). Research conducted on these diseases in horses often benefits human medicine as well.

Lyme Disease

Lyme disease is caused by a bacterial organism (Borrelia burgdorferi) and it is spread by ticks. The ticks belong to the Ixodes family and are primarily found on deer. Lyme disease is more common in humans and dogs but also occurs in horses. The symptoms vary but usually a horse with Lyme disease will show an unexplained reluctance to move, as if sore all over, and/or a transitory lameness that can not be ascribed to any specific cause. Joint swelling may also be apparent in some horses. Reports of secondary complications include nervous system disorders such as seizures or signs of encephalitis (head pressing, walking in circles, blindness), eye problems such as "moon blindness," and reproductive disorders.

The bacterial organism, Borrelia burgdorferi, which causes Lyme disease.

In humans, the clinical symptoms of Lyme disease vary drastically between patients and can be difficult to diagnose. In 60-80 percent of human patients, an early sign of Lyme disease is a slowly expanding red skin rash following a tick bite. Secondary complications include abnormalities of the musculoskeletal, nervous or cardiovascular systems such as arthritis, irregular heartbeat and brain/spinal cord complications.

Lyme disease can be effectively treated with various antibiotics, however, diagnosis can be tricky. Lyme disease in horses is diagnosed by checking the blood for specific antibodies and a clinical evaluation. The blood test, however, has limitations because it does not differentiate between infection and mere exposure to the organism. Research to develop better diagnostic tests in horses has a direct application to human medicine.

Equine and Human Granulocytic Ehrlichiosis

The light colored Ehrlichia organism (arrow)is tucked within the darker ring of a white blood cell from a horse.

The same tick that spreads Lyme disease appears to be the culprit in another disease of humans and horses, granulocytic ehrlichiosis. This condition, which mimics Lyme disease, was once thought to be two separate diseases. Through equine research headed by the UC Davis Center for Equine Health’s Dr. John Madigan, it was found that both conditions, Equine Granulocytic Ehrlichiosis (EGE) and Human Granulocytic Ehrlichiosis (HGE), were caused by a bacterial organism called Ehrlichia equi (E. equi).

The clinical signs of EGE in horses include fever, depression, jaundice, limb swelling, incoordination, low white blood cell count and a decreased number of blood platelets. In humans, the clinical signs of HGE mimic the flu and include fever, headache, shaking, chills and nausea.

EGE and HGE are easily treated in the early stages using tetracycline antibiotics. If not treated quickly with appropriate antibiotics, the organism may spread throughout the body causing significant damage to internal organs and possible death in both horses and humans. Using blood tests, diagnosis of EGE and HGE is made by the identification of E. equi in the white blood cells.

UC Davis researchers developed a PCR (polymerase chain reaction) test that is highly sensitive and specific for detecting E. equi in blood samples from affected horses. The equine research helped to identify ticks as the vector of this disease in both humans and horses and has been used as a model for diagnosis and treatment of EGE/HGE.

For more information, visit the HGE/EGE web site.

Potomac Horse Fever
Potomac horse fever (PHF) or equine monocytic ehrlichiosis is a disease caused by a bacterial organism called Ehrlichia risticii (E. equi). In horses, the clinical signs of PHF include fever, lethargy, diarrhea and occasionally, mild colic. Laminitis (founder) can be a serious complication that limits a horse’s future performance.

The larvae of flukes (parasites harbored by snails) are being studied for their role in the spread of Potomac Horse Fever.

Until recently, researchers did not know how horses were being exposed to this organism. Dr. John Madigan and his research team have recently identified freshwater snails and the larvae of flukes (parasitic flatworms harbored by the snails) as possible carriers of this disease. This research is exciting because until now, it was thought that PHF was spread by ticks. Though more research is underway, prevention may be as simple as keeping horses away from the streams, ponds and other aquatic habitats where these snails and flukes reside.

Freshwater snails appear to be the possible carriers of Potomac Horse Fever.

Dr. Madigan’s research team also identified E. risticii as the disease causing organism for the "Shasta River crud," a disease reported in horses living near California’s Shasta and Klamath rivers. The first cases of Potomac horse fever were identified in 1979, but the Shasta River illness has been reported for at least 25 years and causes the same clinical signs as PHF. When researchers compared the DNA of the disease-causing organism, they found that it was the same disease.

The disease causing agent of PHF is closely related to another bacterial organism associated with an aquatic habitat, Neorickettsia helminthoeca, which causes "salmon poisoning," a fatal condition in dogs that eat infected salmon, as well as Ehrlichia sennetsu, an agent of human illness in Japan and Malaysia. The disease in humans causes signs of chronic mononucleosis and occurs in people that have waded in particular waterways.

Potomac horse fever currently is treated with tetracycline antibiotics, however, the success rate of treatment varies depending on the severity of the infection and the timing of the treatment. Diagnosis of PHF is based on the history, clinical findings and the knowledge of E. risticii activity in the immediate area. Accurate, reliable diagnostic testing for PHF is currently unavailable. Through the CEH, UC Davis researchers have developed diagnostic tests utilizing polymerase chain reaction (PCR) testing to meet this need. The PCR test is currently being used for research purposes with the intent that it will be utilized for standard diagnostic testing. This PCR test has also identified new strains of PHF and it was determined that the current vaccines are not effective in preventing infection by these new strains.

The equine research on the mode of transmission and diagnostic testing will have a direct application to the two related diseases in humans and dogs. For more information, visit the equine monocytic ehrlichia web site .

Equine Encephalomyelitis
There are three strains of equine encephalomyelitis and each is caused by a virus that is spread by mosquitoes. Eastern and western equine encephalomyelitis (EEE and WEE) occur in the United States and Venezuelan equine encephalomyelitis (VEE) occurs in Central and South America and occasionally, in parts of the United States. In general, infected horses develop fever, loss of appetite, depression, elevated heart rate, abnormalities in white blood cell counts and diarrhea (in VEE). The horses become unresponsive or irritable and exhibit head-pressing, leaning on walls or fences, compulsive circling and in some cases, blindness. Death is usually preceded by coma and convulsions. Horses that survive often have residual neurologic defects.

Humans can become infected with the EEE virus, the WEE virus and some subtypes of the VEE virus. The clinical signs in people vary from a mild flu-like illness to severe brain disease. Deaths have been reported primarily in children and the elderly.

Dr. Laura Kramer, an associate research virologist with the UC Davis Center for Vector-Borne Diseases, provided the following information regarding encephalomyelitis in California.

"The numbers of epizootic (disease that affects many species of animals) incidences of equine encephalitis cases during the 1930s and 1940s devastated agricultural production in the Central Valley and culminated in the discovery of western equine encephalomyelitis (WEE) virus as the causative agent. Research quickly developed an effective vaccine and in Kern County from 1943-1952, only 168 cases of equine encephalomyelitis which resulted in a 29 percent fatality rate were reported by veterinarians, attesting to the efficacy of prevention by vaccination. All cases occurred from May to October in horses that were reportedly unvaccinated. Few cases have been recognized in recent years. WEE, like several other arthropod-borne viruses, is transmitted in nature by the mosquito, Culex tarsalis, in a cycle involving wild birds as reservoir hosts. A secondary cycle involving Aedes mosquitoes and rabbits may develop during summer, but the infection of humans and domestic animals, including horses, is accidental and a dead end for the virus.

"In the past decade, there has been increasing public awareness of newly emerging diseases which present a threat to equines and man In 1992, the 12th International Symposium on New and Emerging Infectious Diseases was held at the UC Davis School of Veterinary Medicine. At this symposium, one topic of discussion was arthropod-borne viral infections which have the potential to become serious problems in California. Researchers determined that of the cases of equine encephalitis in California during 1965-1978, five arboviruses (viruses transmitted by insects such as mosquitoes and flies) in addition to WEE were implicated as causative agents, including St. Louis encephalitis (SLE). Additional arboviral infections of equines have been documented, but currently there is no indication that these cause clinical illness.

"Arboviruses have also caused epidemics in California, the largest of which was centered in the San Joaquin Valley in 1952 with 375 WEE and 45 SLE confirmed cases. Expanded preventive mosquito control, water management projects on the western slope of the Sierra Nevadas, and improved agricultural irrigation methods have essentially eliminated WEE and SLE as a significant cause of human illness in California. There is little evidence that mosquito-borne arboviruses other than WEE and SLE are the cause of a significant number of human cases in California. However, to date, the causative agents of 95 percent of aseptic meningitis and viral encephalitis cases are not diagnosed, and the possible role of one or more vector-borne viruses as the causative agents of these diseases remains an important issue."

Leptospirosis
Leptospirosis is primarily a water-borne illness caused by leptospires (spiral shaped bacteria belonging to the spirochete group). Rodents act as the major reservoirs of the bacteria. Current CEH research headed by Dr. Rance LeFevbre of the UC Davis Center for Vector-Borne Diseases is focused on the diagnosis and treatment of recurrent uveitis or "moon blindness," a complication of leptospirosis in horses.

Recurrent uveitis, or moon blindness, is a leading cause of blindness in horses. The blindness is caused by the severe inflammatory processes that occur inside the horse’s eyes. As the name of the disease implies, recurrent uveitis typically occurs multiple times which increases the chances for damage to the eye and eventual vision impairment. The clinical signs mimic trauma or injury to the eye and include watering of one or both eyes, constricted pupils, red and swollen membranes, and the cornea (transparent outer coating of the eye) may become opaque and cloudy. The condition is very painful and often, the horse is very sensitive to light. Currently, treatment of recurrent uveitis is basically designed to relieve the discomfort associated with the condition using a topical steroid, oral pain killers and topical atropine to dilate the pupil.

Typical cloudy appearance of the eye of a horse with moon blindness caused by leptospirosis.	Moon blindness is very painful and often, the eye is very sensitive to light which causes the horse to squint.

The cause of this disease is attributed to a variety of infectious agents and/or immune system hyper-reactivity. Published reports since the early 1950’s have implicated leptospirosis in recurrent uveitis. Previous UC Davis studies positively identified leptospiral infection as a cause of moon blindness in horses. The next step is to determine if horses can be successfully cured of leptospiral infections with antibiotics and to determine if the pathologic events that lead to blindness can be halted. Dr. LeFevbre’s current research is aimed at 1) developing laboratory tools with which to provide reliable and routine diagnosis of leptospiral induced equine recurrent uveitis, 2) providing an effective antibiotic treatment for resolving this disease in horses, and 3) designing an effective vaccine for the prevention of this disease in horses.

Due to the ubiquitous distribution of leptospires in nature, horses throughout the world have been diagnosed with equine recurrent uveitis. Thus, all horses are at risk for the disease. Leptospires can survive in water sources for prolonged periods of time. Horses can contract leptospirosis from drinking troughs, urine contaminated grass, hay, or grain, or from other infected horses.

Human cases of leptospirosis are relatively rare in the United States. Most cases are reported in developing countries where water contaminated exposure is common. The symptoms, including uveitis, are virtually identical in both humans and animals. Other symptoms include flu-like ailments, septicemia, meningitis, liver and kidney problems with potential failure of one or both organs, abortion and occasionally death. Individuals most at risk are veterinarians, dairy workers, meat processing workers, sewage workers, etc. The equine research on recurrent uveitis has the potential to be used in human medicine as well.

Center for Vector-Borne Diseases
In response to the growing public concern regarding diseases which are transmitted by vectors such as ticks and mosquitoes, the UC Davis School of Veterinary Medicine established the Center for Vector-Borne Diseases (CVBD). This program, formerly known as the Arbovirus Research Unit, was previously affiliated with the School of Public Health at UC Berkeley. In addition to arboviruses (viruses transmitted by insects such as mosquitoes and flies), the CVBD addresses disease agents transferred by other species such as ticks (Lyme disease), deer mice (Hantavirus), raccoons (rabies) or fleas (Bubonic plague). This center brings together the activities and complementary strengths of the School of Veterinary Medicine, the School of Medicine and the College of Agricultural and Environmental Sciences. The faculty members associated with this center have expertise in vector-borne veterinary and human infectious diseases and in public health entomology and are building a strong multi-disciplinary program of research and teaching.

The CVBD focuses primarily on California problems such as Lyme disease, ehrlichiosis, urine typhus, western and St. Louis encephalitis and babesiosis (piroplasmosis in the horse) which are some of the diseases emerging in the state as environmental and demographic changes take place. In addition, the CVBD also focuses on world-wide research efforts designed to offer better strategies for protecting human health, animal industries and foreign trade from vector-borne diseases that occur in developing countries in tropical areas of the world.

The co-directors of the CVBD are Dr. Rance LeFebvre, a professor of veterinary medicine and authority on Lyme disease, and Dr. Tom Scott, one of the nation’s most distinguished medical entomologists and director of the UC Davis Mosquito Research Laboratory. For more information, contact the CVBD at (530) 754-6087 or by FAX (530) 754-6360.

Center for Comparative Medicine
In June of this year, the University of California Davis celebrated the opening of the Center for Comparative Medicine (CCM). The CCM is a cooperative, interdisciplinary research and teaching center, co-sponsored by the UC Davis Schools of Medicine and Veterinary Medicine, to further the understanding of persistent infectious diseases common to humans and animals.

Society faces immediate problems in regard to persistent infectious diseases which are becoming more urgent as world population grows, people are living longer, and infectious and zoonotic (transmissible from animals to man) diseases are emerging at an increasing rate. Persistent infections/diseases including viral (e.g. acquired immune deficiency syndrome virus, cytomegaloviurs, papilloma viruses, etc.), bacterial (e.g. Lyme disease, ehrlichiosis, tuberculosis, etc.), and parasitic (e.g. malaria, babesiosis, metazoan parasitism, etc.) are shared by humans and animals or induced by closely related agents in humans and animals. The investigation of these diseases which have a substantial impact on society will benefit humans and animals alike.

The CCM’s research mission is to investigate host-agent interactions and to develop intervention strategies for persistent infectious diseases common to humans and animals. The CCM’s teaching mission is to promote academic excellence in comparative medical research.

The director of the CCM is Dr. Stephen Barthold, a world renowned comparative pathologist, a laboratory animal pathologist and director of an National Institutes of Health funded Lyme disease program. For more information, contact the CCM at (530) 752-7913 or by FAX (530) 752-7914 or visit its web site.