Zoonotic and vector-borne diseases from A to Z
Anaplasmosis is a bacterial infection that is spread to people by the bite of a tick. It was previously called human granulocytic ehrlichiosis (HGE) and has more recently been called human granulocytic anaplasmosis (HGA). Symptoms include fever, headache, chills, and muscle aches. Anaplasmosis is treatable with antibiotics. No human cases have been diagnosed in Washington state, but cases have been diagnosed in dogs.
Anisakiasis is an infection with the marine fish Anisakis roundworm (Anisakis simplex). People can get infected when they ingest the immature stages of the worm (larvae) in raw or undercooked infected fish in dishes such as sushi, sashimi, ceviche, and pickled herring. Symptoms usually occur within hours of eating and may include nausea, vomiting, diarrhea, and abdominal pain. If the larvae pass into the bowel, symptoms mimicking Crohn's disease may occur after 1-2 weeks. In some cases the larvae migrate from the stomach to other tissues and severe allergic reactions can occur. The larvae can be killed by cooking fish to 140ºF (60ºC) for 10 minutes, freezing fish at -4ºF (-20ºC) for at least 7 days, or blast freezing fish to -31ºF (-35ºC) for 15 hours.
- Anisakiasis, CDC
Avian (or bird) influenza refers to diseases caused by avian influenza A viruses that occur naturally among wild aquatic birds worldwide and can infect domestic poultry. Currently, there are several avian influenza viruses circulating among domestic poultry that are infecting people in Asia, the Middle East and Africa, The spread of avian influenza viruses from one ill person to another has been reported very rarely. However, because of the possibility that avian influenza could change and gain the ability to spread easily between people, monitoring for human infection is extremely important for public health. Since it would be a new virus to people, no one would be immune, and a pandemic could occur. Human influenza pandemics originating from avian influenza viruses have happened several times in the 20th century, including 1918, 1957, and 1968.
Babesiosis is an infection with a microscopic Babesia parasite that is spread to people by tick bites. Symptoms can range from none or very mild to fever, headache, body ache, nausea and fatigue. Because the parasite infects the red blood cells it can cause anemia. Babesiosis can be treated successfully. There have been a few cases of babesiosis reported in people in WA state.
See cat scratch disease.
See raccoon roundworm.
Brucellosis is a bacterial infection that can affect goats and other livestock such as sheep and cows and wild ruminants such as deer, elk and bison. Brucellosis causes abortion or stillbirth in animals. Brucellosis is rare in livestock in the U.S. but common in many other countries. People most often get infected from direct contact with the placenta and other discharges from animals that are giving birth. Infected animals can shed the Brucella bacteria in milk and in vaginal fluids after abortion or birth. People can also get infected from consuming unpasteurized milk and other dairy products from infected animals. Symptoms in people vary, but serious disease can occur. Dogs can also get brucellosis but the dog type rarely spreads to people.
See Herpesvirus B.
Campylobacteriosis is an infection of the intestines caused by a bacterium called Campylobacter. The bacteria are commonly found in the feces of infected animals and in food products contaminated with the bacteria during processing or preparation. Raw or undercooked chicken is one of the most common sources of human infection.
Cat scratch disease is a bacterial disease caused by Bartonella henselae. People with weak immune systems are at increased risk of getting seriously ill with cat scratch fever. Young cats and kittens are most likely to be the source of human infection and about 40% of cats carry these bacteria at some point in their lives. The infection, which rarely causes disease in cats, is transmitted between cats by fleas. Infected flea droppings on the cat's fur or claws are the source of human infections, which are spread from the cat to a person by a cat bite, scratch or lick. Cat scratch fever can be prevented by practicing effective flea control and by avoiding cat bites or scratches.
Coccidioidomycosis is caused by infection with the fungus Coccidioides. The fungus is present in the soil in the southwestern US, but has recently been found in south-central Washington and cases have occurred in Washington state. People and animals can get infected when breathing in the fungal spores. Symptoms include fever, fatigue, cough, difficulty breathing, headache, night sweats, muscle aches, and rash. Infection may be asymptomatic. Treatment is with antifungals. The infection is not spread between people and animals, but is included here because it affects both people and animals.
Cryptococcus gattii is a fungus found in the environment in the Pacific Northwest. People and animals can get infected when breathing in the fungal spores. The infection can affect the lungs, central nervous system, or both. Treatment is with antifungals. The infection is not spread between people and animals, but is included here because it affects both people and animals.
Cryptosporidiosis is caused by infection with a tiny parasite called Cryptosporidium parvum. The parasite produces cysts (eggs), which are passed in the stool of infected people or animals. The cysts can survive for 2 – 6 months in moist environments and are commonly found in lakes and streams. The parasite is spread by the fecal-oral route. People and animals can get infected when drinking contaminated water or eating contaminated food, or by direct contact with infected persons or animals. About 50% of dairy calves are infected and shed cysts. Infection can cause diarrhea and abdominal cramps. The disease is self-liming in healthy people, but can be prolonged and more serious in persons with weakened immune systems.
Dipylidium is tapeworm of cats and dogs. People become infected when they accidentally swallow a flea infected with tapeworm larvae; most reported cases involve children. Dipylidium infection is easily treated in humans and animals.
- Dipylidium Infection, CDC
Escherichia coli (E. coli) comprise a large group of bacteria that live in the guts of animals and people. Most are harmless but some can cause disease. One particular strain called E. coli O157:H7 can cause serious disease in people. The E. coli O157:H7 bacteria are shed in the stool of infected animals and people. People can get infected when they eat food or drink water or milk contaminated by the bacteria. Infection with E. coli O157:H7 can cause diarrhea and in some cases a severe complication called hemolytic uremic syndrome (HUS). HUS damages the kidneys and blood vessels and is more common in young children and the elderly.
Fish tank granuloma is an infection caused by Mycobacterium marinum. These bacteria are widespread in aquatic environments and often occur in aquarium fish or food fish raised under crowded conditions. Before chlorination, outbreaks of mycobacteriosis occurred in contaminated swimming pools. People can get infected through direct contact with contaminated water sources, including aquarium water. The bacteria enter through breaks in the skin. The infection can cause skin lesions, usually on the fingers or hands. Skin lesions may heal or in some cases may persist for months. In persons with weakened immune systems, the bacteria may cause joint and bone infections. To prevent infection persons who clean aquariums should wear gloves and wash their hands thoroughly afterwards.
- Mycobacterium marinum, CFSPH, Iowa State University
Giardia are tiny parasites that may infect the intestines of people and many types of animals. The infection may have no symptoms, or there may be mild to severe symptoms including watery foul-smelling diarrhea, stomach cramps, gas, fever, nausea, vomiting, and headache. People are the primary source of giardia infection for other people, but some infections may be spread between animals and humans. Giardia parasites have been found in dogs, cats, ruminants like goats and cows, and wild animals. The parasite is transmitted by contact with feces from an infected person or animal, or by drinking water from contaminated sources. Beavers may be a source of contamination of lake or stream water.
Hantavirus Pulmonary Syndrome (HPS) is a severe illness caused from exposure to the droppings or urine of deer mice that carry the virus. About 1- 5 hantavirus cases are reported each year in Washington State and about one third of the cases have been fatal. It is important to take precautions when cleaning an enclosed space such as a shed, cabin or trailer where mice have nested or rodent droppings are present.
Herpes B virus is carried by a high percentage of macaque monkeys. While symptomatic human infection with B virus is rare, the consequences may be severe with a mortality rate of about 70% in untreated cases and the potential for life-long disability in survivors. Most B virus cases have been associated with occupational exposure (a bite, scratch or splash to mucous membrane) to macaque monkeys used in research. However, there is the potential for exposure of travelers to free-living macaques which frequent tourist sites in many parts of the world, or to macaques kept as pets. [Note: Monkeys are not suitable pets. Private possession of monkeys and other primates is illegal in Washington and many other states.]
A person bitten, scratched or exposed to body fluids from a monkey should thoroughly wash the bite or scratch or flush exposed membranes, such as the eye. A health care provider or public health authority should be contacted promptly regarding treatment and possible use of antiviral medication to prevent B virus infection.
Leptospirosis is a disease caused by bacteria called Leptospira that infects both humans and a wide range of animals. It occurs worldwide but is more common in temperate and tropical areas of the world. Some people infected with leptospirosis will have no symptoms at all, and some people will become severely ill. Some wild and domestic animals, such as rodents, raccoons, cattle, pigs, and dogs, carry the Leptospira bacteria and pass them in their urine. Soil or water contaminated with infected urine are the most common causes of human infection but the disease can also be spread by direct contact with urine from an infected animal. The disease can have a high fatality rate in dogs but early diagnosis and treatment improves the chances for recovery.
Listeriosis is a rare but serious disease of humans caused by infection with the bacterium Listeria monocytogenes; it is usually acquired by eating or drinking foods contaminated with the germ. Unpasteurized milk products and cold cuts are some of the most common sources of listeriosis. Infected cattle and goats can also spread the infection to humans when the infection causes them to abort and the placental remains are heavily contaminated. Listeria is especially hazardous to pregnant women and can result in miscarriage, stillbirth or illness or death in newborn infants. Older adults and people with weakened immune systems are also at higher risk of serious consequences of Listeria infection.
Lyme disease is caused by a bacterium called Borrelia burgdorferi, which is transmitted by the bites of infected ticks. Ticks become infected by feeding on infected rodents and deer. It is the most common tick-borne disease in the US. Infections acquired in Washington state appear to be rare, but the disease is a concern in the Eastern and Midwestern states, and in some areas of California and Oregon. The first symptom is usually an expanding red rash which starts at the site of the tick bite. Fever, headache, muscle aches and joint pain may also occur. If it goes untreated, later symptoms can include recurring rash, joint pain, heart disease and nervous system disorders.
Lymphocytic choriomeningitis is caused by infection with the LCM virus. LCMV occurs worldwide and the primary host of LCMV is the common house mouse. Pet rodents can become infected after being in contact with wild house mice infesting pet stores or homes. Pregnant women are most at risk from LCMV infection, which can cause birth defects and mental retardation in the unborn baby.
Monkeypox is a disease caused by a virus found in monkeys and other animals such as rats, mice and rabbits. It was first discovered in laboratory monkeys in 1958 and in people in 1970. In June 2003, monkeypox was found in several people in United States who likely got sick after contact with infected pet prairie dogs. People get monkeypox from an animal with the virus if they are bitten or if they touch the animal's body fluid or blood. The disease can also spread from person to person through respiratory droplets produced from sneezing or coughing. In Africa, monkeypox kills between one and ten percent of people who get it, but this percentage is likely lower in the United States. There is no specific treatment for monkeypox but there is a vaccine available that lowers the risk of getting the disease.
- Monkeypox, CDC
Orf is a common disease worldwide in goats and sheep. It is also called "sore mouth" or "scabby mouth." It is caused by a virus (parapoxvirus) that causes blisters to form on the lips, muzzle, and in the mouth. Later the blisters become crusty scabs. It is especially common in young animals and may cause them to have difficulty nursing or feeding. Most animals recover completely within a month, but may get reinfected. Orf lesions may resemble foot-and-mouth disease, which is a very serious animal disease that has not occurred in the U.S. since 1929. Due to concern about foot and mouth disease, the WA State Department of Agriculture investigates possible cases of orf in goats and sheep to be sure that the animal does not have foot-and-mouth disease (see link below).
People can get infected via direct contact with an infected animal or by touching contaminated equipment such as halters, buckets or fences in the animal's environment. The virus penetrates through small lesions in the skin. People most often get infections on their fingers where blisters form in 3-7 days. The sores may be painful and can last for two months. A lab test to diagnose the infection is available at the Centers for Disease Control and Prevention. A healthcare provider would need to contact the local health department for information about testing. There is no specific treatment and people do not infect other people. Activities that may put people at risk of infection include bottle feeding or shearing sheep or goats, petting infected animals, handling contaminated equipment, and being bitten by an infected animal.
- Frequently Asked Questions About Sore Mouth Infection (Orf Virus), CDC
- Foot-and-mouth disease: A Foreign threat to Washington livestock, WA State Dept. of Agriculture
Rat bite fever is a bacterial disease. The bacteria are carried by rats and are part of the normal flora of their mouth and nose. People can get infected through bites or scratches by rats. Up to 10% of rat bites may result in rat bite fever. Other animals such as mice, gerbils, squirrels, cats and dogs can also get infected and may or may not get sick with rat bite fever, and can spread it. Rat bite fever is thought to be rare in the U.S. Persons who handle rats as part of their work or children who live in rat infested areas are at higher risk of this disease.
Staphylococcus aureus (also called 'staph') is a bacterium that is commonly found on human skin and inside the nose. It can colonize (live on) the skin without causing any illness or it can cause disease ranging from mild to serious. Some staph bacteria are resistant to certain antibiotics. Methicillin-resistant S. aureusbacteria (MRSA) are resistant to methicillin and related antibiotics. Other antibiotics can be used to treat a MRSA infection, but treatment may take longer. MRSA is spread by close contact with infected people or through items such as contaminated towels, soaps, sheets and clothes. About 85% of MRSA infections happen in healthcare settings and the rest in the community. MRSA infections have been reported in dogs, cats, horses, cattle, sheep, rabbits, and chickens. Dogs, cats, horses and other animals can also be MRSA carriers without symptoms of infection. MRSA can be spread between humans and animals.
Plague is a serious infection of humans caused by a germ called Yersinia pestis. It is usually caused by the bite of a flea that has fed on an infected wild animal, such as a rat, chipmunk or prairie dog. It usually causes large sores and abscesses in the glands of the arms and legs. Plague is treatable with antibiotics. Since 1907 there has only been one case of human plaque reported in Washington State in 1984. Dogs, and especially cats, can also become infected and can spread the disease to their human companions. Ongoing surveillance of wildlife (primarily coyotes) since 1975 has found that an average of 3% of tested animals had been exposed to plaque from eating plaque infected rodents. No animals have tested positive since 2002.
Psittacosis is the term for the disease in people caused by the bacteria Chlamydophila psittaci. It most often causes pneumonia, but other organs may also be affected. Infection usually occurs when a person inhales dried droppings or nasal secretions from infected cockatiels, parakeets, and other parrot-like birds. The same disease in birds is termed 'avian chlamydiosis'.
Avian chlamydiosis is a relatively common disease found in parrot-like (psittacine) birds. When the disease is transmitted to people, it is called 'psittacosis'. Washington State has regulations in place to help reduce the risk of zoonotic transmission of the disease by requiring pet shops and bird breeders to take certain measures to control the disease in birds and prevent its spread to people.
- Psittacosis, PHSKC
- Psittacosis and Chlamydiosis, NASPHV
- WA Administrative code (WAC) 246-100-201: Birds – Measures to prevent psittacosis
- Notifiable Conditions: Psittacosis, WA State Dept. of Health
Q fever is a disease caused by a type of bacterium named Coxiella burnetii. It is primarily a disease of cattle, sheep, and goats although other livestock and pets can also get Q Fever. The disease in people ranges from asymptomatic to severe. Most animals have no symptoms but infection may cause abortion in sheep and goats. Infection in people occurs by inhaling dust contaminated with dried placental material, birth fluids, as well as urine and feces from infected animals. The risk of infection is greatest close to the source of bacteria, but there have been cases of infection even several miles away. Accidentally inhaling contaminated milk is a less common way of getting infected.
- Q Fever, PHSKC
- Q fever, MMWR article
- Q fever: Coordinated Public Health and Animal Health Response, NASPHV
Baylisascaris, an intestinal raccoon roundworm, can infect a variety of other animals including humans. Symptoms of infection in people depend on how many eggs are ingested and where in the body the larvae migrate (travel to). Once inside the body, eggs hatch into larvae and cause disease when they travel through the liver, brain, spinal cord, or other organs. Ingesting a few eggs may cause few or no symptoms, while ingesting large numbers of eggs may lead to serious symptoms. Symptoms of infection may take a week or so to develop. If a person is suspected of having swallowed soil contaminated by raccoon droppings, consult a health care provider immediately as preventative medication may be indicated. Be sure to report the concern about recent exposure to raccoon feces to your doctor.
Ringworm is a skin disease that can affect people and many kinds of animals. It is not caused by a worm at all, but rather by fungus that can grow in the skin. Ringworm on a person's head usually shows as a bald patch of scaly skin and elsewhere it can cause a red, ring-shaped rash that may be itchy. Dogs and cats, especially kittens, can have ringworm and spread it to people or other animals by direct contact with the pet's fur. Spores of the ringworm fungus can survive for a long time on carpet, furniture and other surfaces and cause infections. People can also get ringworm from other people and their personal items like combs.
- Ringworm, CFSPH, Iowa State University
RMSF is a bacterial infection that is spread to people by the bite of an infected tick. Symptoms include fever, headache, abdominal pain, muscular pain, and a rash may develop. RMSP is treatable with antibiotics, but can be very serious or even fatal without treatment. RMSF is rare in WA state.
Salmonellosis is an infection of the intestines caused by a group of bacteria called Salmonella. The bacteria are shed in the stool of infected animals and humans. Infection can happen when a person eats food or drinks water or milk that has been contaminated with Salmonella bacteria. Salmonella bacteria have also been found in tropical fish and home aquariums. Infection with Salmonella can cause serious disease especially in children younger than 5 years of age, the elderly, and persons with weakened immune systems.
Chicks and ducklings frequently harbor Salmonella bacteria in their droppings. The disease caused by Salmonella is called 'salmonellosis'. Since the 1990s 45 Salmonella outbreaks have been linked to live poultry. One of the largest affected over 22 residents of Washington and Oregon, with half the patients younger than 13 years old. The disease is often much more serious in children, especially those under 5 years old, as well as the elderly, and persons with weakened immune systems.
Salmonellosis is a bacterial infection of the intestines caused by a group of bacteria called Salmonella. The bacteria are shed in the stool of infected animals and humans. Infection can happen when a person eats food or drinks water or milk that has been contaminated with Salmonella bacteria. Infection with Salmonella can cause serious disease especially in children younger than 5 years of age, the elderly, and persons with weakened immune systems.
- Salmonellosis, PHSKC
Owl pellets are the coughed-up fur and bones of small animals and birds eaten by owls. Because the skeletons of these small animals are preserved almost intact, picking owl pellets apart to view them is a common and rewarding activity for grade school and middle school science classes. The problem is that because owls and their prey are often carriers of a germ called Salmonella, the pellets can contain Salmonella germs, too. The hands and tables of the students can become contaminated with Salmonella germs while handling the pellets and students can swallow the germs and become sick with diarrhea, vomiting and fever. Owl pellets that have been heat-treated to kill the germs are safe, however, and should be used by science classes. If your child will be learning with owl pellets in school, check with the teacher to make sure the pellets have been heat-treated so they are safe.
Reptiles (turtles, snakes, anoles, iguanas, geckos, and chameleons) and amphibians (frogs, salamanders, newts, toads) frequently carry Salmonella bacteria in their intestines. Even though the reptile usually doesn't appear ill, the infection can spread to people. Illness is most severe in children younger than 5 years of age, the elderly, and people with weakened immune systems.
Salmonellosis is a bacterial infection of the intestines caused by a group of bacteria called Salmonella. The bacteria are shed in the stool of infected animals and humans. Infection can happen when a person eat food or drink water or milk that has been contaminated with Salmonella bacteria. Infection with Salmonella can cause serious disease, especially in children younger than 5 years of age, the elderly, and persons with weakened immune systems.
Seoul virus is a type of hantavirus that does not cause hantavirus pulmonary syndrome. People that become infected with this virus often exhibit relatively mild or no disease but some will develop a form of hemorrhagic fever with renal syndrome (HFRS) with death in approximately 1-2% of cases (1 to 2 persons in 100 people). Seoul virus is spread to people by infected pet and wild rats, specifically the brown and Norway rats. Seoul virus is found worldwide. People become infected with the virus after coming into contact with urine, droppings, or saliva of infected rodents, or by breathing in contaminated urine, droppings or nesting material that has been stirred up in the air. Seoul virus is not spread from person to person.
More information about prevention of Seoul virus, especially for rat owners and breeders:
An infection with a type of fungus, sporotrichosis can be spread to people from the skin of infected animals or by getting dirt into scratches and cuts. The bacteria, called Sporothrix scheneckii, causes open sores in animals that can spread the disease to people. Dogs, horses and cats can become infected, but most human infections come from contact with cats, such as being scratched by an infected cat. The infection is treatable in both humans and animals.
Streptococcus equi subsp. zooepidemicus (S. zooepidemicus) is a bacteria that can be commonly found in the respiratory tract of horses that may or may not show signs of infection. This bacteria rarely causes human illness and is usually associated with eating or drinking unpasteurized dairy products or with direct horse contact, but has also been linked to contact with guinea pigs or ill dogs. Older persons might have an increased risk for infection with S. zooepidemicus, and infections can be severe and cause a broad range of symptoms. S. zooepidemicus may also cause infections in domestic animals such as cattle, pigs, guinea pigs, dogs, and cats.
Swine influenza is a respiratory disease of pigs caused by type A influenza viruses. Swine viruses do not usually infect people. However, sporadic human infections with swine influenza viruses have occurred. Since 2011 a number people have been infected with a swine influenza virus (H3N2v) after contact with pigs at fairs. Spread of swine influenza virus to people most likely happens through droplets from infected pigs sneezing or coughing. Illness is most severe in pregnant women, children younger than 5 years of age, the elderly, and people with weakened immune systems.
See Dipylidium Infection (Dog and Cat Flea Tapeworm).
Tick-borne relapsing fever is a disease caused by bacteria called Borrelia. The bacteria are spread by soft (argasid) ticks that are infected with the bacteria from feeding on infected wild rodents. The disease is characterized by relapsing (recurrent) periods of fever and other symptoms lasting for 2 to 7 days, disappearing for about 4 to 14 days, and then reoccurring. This cycle may go on for weeks if treatment is not started.
Toxocariasis is a disease affecting people caused by parasitic Toxocara roundworms commonly found in the intestine of dogs and cats. Although most people infected with Toxocara have no symptoms, the parasite is capable of causing blindness and other serious illness. It is likely that toxocariasis is under-diagnosed. A recent study showed that transmission of Toxocara is most common in young children and youth and that about 14% of the U.S. population is infected. Children become infected as they tend to play in (and sometimes eat) soil or sand that has been contaminated with dog or cat feces.
- Toxocara infection, CDC
Toxoplasmosis is a common disease found in birds and mammals across North America. The infection is caused by a protozoa parasite called Toxoplasma gondi and affects 10 to 20 out of every 100 people in North America by the time they are adults. The concern is greatest for pregnant women because the growing fetus can become infected with the toxoplasmosis parasite. This can happen if the mother is infected with the parasite while pregnant or before she becomes pregnant. Infection in the unborn child early in pregnancy can result in miscarriage, poor growth, early delivery or stillbirth. If a child is born with toxoplasmosis he/she can experience eye problems, hydrocephalus (water on the brain), convulsions or mental disabilities.
Tularemia is a bacterial disease caused by Francisella tularensis and is most commonly found in wild animals (e.g. wild rodents, squirrels, rabbits, hares and beavers). People and their pets can become ill from tularemia by coming into contact with infected dead or ill animals through animal bites and exposure to contaminated blood or raw meat. Tularemia can also be transmitted by the bite of an infected arthropod (e.g. ticks, biting flies), exposure to contaminated water or soil and inhalation of bacteria. Although rare in WA state 1 to 10 cases of tularemia in people are reported every year. Prevent exposures to tularemia: don't handle dead or ill animals; avoid animal bites, tick and deer fly bites; and avoid direct bare-hand contact with blood and raw meat from wild animals. Don't drink untreated water in areas where tularemia is known to occur in wild animals.
- Tularemia, CDC
- WA State. Dept. of Health Notifiable Conditions: Tularemia
- Ticks and Tick-borne diseases in Washington, WA State Dept. of Health
West Nile virus is spread by mosquitoes. It was first found in Africa in 1937, but it did not appear in the U.S. until 1999. After being discovered in New York, where it killed birds at a zoo and infected people, it spread westward across the U.S. and Canada. In 2006, West Nile virus was detected in King County for the first time. West Nile virus has now become established in Washington State. Wild birds become infected with West Nile virus and mosquitoes spread the virus to other birds and to humans. People with the virus may have no symptoms, or they may have illness ranging from mild to severe. In the severe forms, West Nile virus affects the nervous system and may result in disability, paralysis or death. Horses are also at high risk of contracting and dying from West Nile virus, a vaccine is available for horses.
Yersiniosis is a disease caused by infection with a bacterium called Yersinia enterocolitica. Infection can cause fever, abdominal pain and diarrhea that may last from 1 to 3 weeks. Young children are more likely than adults to become sick. The bacterium is spread by the fecal-oral route from infected people or animals or by eating pork that is undercooked or by drinking contaminated milk. Usually people get sick from infected pigs, but other animals such as cats, dogs, horses, cows, rodents and rabbits can also carry this disease.