Leptospirosis

Leptospirosis (also known as Weil's syndrome, canicola fever, canefield fever, nanukayami fever, 7-day fever, Rat Catcher's Yellows, Fort Bragg fever, black jaundice, and Pretibial fever) is caused by infection with bacteria of the genus Leptospira and affects humans as well as other animals.
Leptospirosis is among the world's most common diseases transmitted to people from animals. The infection is commonly transmitted to humans by allowing water that has been contaminated by animal urine to come in contact with unhealed breaks in the skin, the eyes, or the mucous membranes. Because urine has a natural disinfecting effect and leptospirosis is one of the very few bacteria that can survive in such an environment, it is one of very few urine transmitted diseases. It also only persists outside a host in a warm, wet environment. As such, outside of tropical areas, leptospirosis cases have a relatively distinct seasonality with most cases occurring in spring and autumn where conditions are most favorable.
==Causes and transmission==
Leptospirosis is caused by a spiral shaped bacterium called Leptospira spp. There are at least five strains (Icterohaemorrhagiae, Canicola, Pomona, Grippotyphosa, and Bratislava).of importance in the United States and Canada, all of which cause disease in dogs.
There are other less common infectious strains. Genetically different leptospira organisms may be identical serologically and vice versa. Hence, an argument exists on which basis strains should be identified - by their common genetics or their common serology. The traditional serologic system is seemingly more useful from a diagnostic and epidemiologic standpoint at the moment (which may change with further development and spread of technologies like polymerase chain reaction (PCR).
Leptospirosis is transmitted by the urine of an infected animal and is contagious as long as it is still moist. Although rats, mice, and moles are important primary hosts, a wide range of other mammals including dogs, deer, rabbits, hedgehogs, cows, sheep, raccoons, opossums, skunks, and certain marine mammals are able to carry and transmit the disease as secondary hosts. Dogs can contract the disease by licking the urine of an infected animal off the grass or soil or drinking from an infected puddle.
There have been reports of house bound dogs contracting leptospirosis apparently from licking the urine of infected mice that entered the house. The type of habitats most likely to carry infective bacteria are muddy riverbanks, ditches, gullies, and muddy livestock rearing areas where there is regular passage of either wild or farm mammals. There is a direct correlation between the amount of rainfall and the incidence of leptospirosis, making it seasonal in temperate climates and year-round in tropical climates. Leptospirosis is also transmitted by the semen of infected animals.
Humans become infected through contact with water, food, or soil containing urine from these infected animals. This may happen by swallowing contaminated food or water or through skin contact. The disease is not known to be spread from person to person and cases of bacterial dissemination in convalescence are extremely rare in humans. Leptospirosis is common among water-sport enthusiasts in specific areas as prolonged immersion in water is known to promote the entry of the bacteria. Surfers and whitewater paddlers are at especially high risk in areas that have been shown to contain the bacteria, and can contract the disease by swallowing contaminated water, splashing contaminated water into their eyes or nose, or exposing open wounds to infected water.
===At risk occupations===
Occupations at risk include veterinarians, slaughterhouse workers, farmers, sewer maintenance workers, waste disposal facility workers, land surveyors, and people working on derelict buildings. Slaughterhouse workers may contract the disease through contact with infected blood or body fluids. Rowers are also sometimes known to contract the disease.
==Signs and symptoms==
Leptospiral infection in humans causes a range of symptoms, and some infected persons may have no symptoms at all. Leptospirosis has two distinct phases, the first of which begins with flu-like symptoms (fever, chills, myalgias, intense headache). The first phase resolves, and the patient is briefly asymptomatic until the second phase begins. This is characterized by meningitis, liver damage (causing jaundice), and renal failure. The infection is often wrongly diagnosed due to the wide range of symptoms. This leads to a lower registered number of cases than probably exist.
Symptoms of leptospirosis may also include muscle aches, vomiting, conjunctivitis, abdominal pain, diarrhea, and rash. Initial presentation may resemble pneumonia. The symptoms in humans appear after a 4–14 day incubation period. More severe manifestations include meningitis, extreme fatigue, hearing loss, respiratory distress, azotemia, renal interstitial tubular necrosis, which results in renal failure and occasionally liver failure (the severe form of this disease is known as Weil's disease, though it is sometimes named Weil Syndrome). Cardiovascular problems are also possible.
The incubation period in animals is anywhere from 2-20 days. In dogs the liver and kidney are most commonly damaged by leptospirosis. In addition, there are recent reports of a pulmonary form of canine leptospirosis associated with severe hemorrhage in the lungs similar to the human pulmonary hemorrhagic syndrome. Vasculitis may occur, causing edema and potentially DIC. Myocarditis, pericarditis, meningitis, and uveitis are also possible.
In veterinary medicine, one should strongly suspect leptospirosis and include it as part of a differential diagnosis if the sclera of the dog's eyes appear jaundiced (even slightly yellow). However, the absence of jaundice does not eliminate the possibility of leptospirosis, and the presence of jaundice could instead indicate hepatitis or other liver pathology rather than leptospirosis. Vomiting, fever, failure to eat, reduced urine output, unusually dark or brown urine, and lethargy are also indications of the disease.
==Diagnosis==
On infection the bacteria can be found in blood and CSF for the first 7 to 10 days (invoking serologically identifiable reactions) and then moving to the kidneys. After 7 to 10 days the bacteria can be found in fresh urine. Hence, early diagnostic efforts include testing a serum or blood sample serologically with a panel of different strains.
Kidney function tests (BUN and creatinine) as well as blood tests for liver functions are performed. The latter reveal a moderate elevation of transaminases. Brief elevations of AST, ALT, and gamma-glutamyltransferase (GGT) levels are relatively mild. These levels may be normal, even in children with jaundice.
Diagnosis of leptospirosis is confirmed with tests such as enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). The MAT (microscopic agglutination test), a serological test, is considered the gold standard in diagnosing leptospirosis. As a large panel of different leptospira need to be subcultured frequently, which is both laborious and expensive, it is underused, mainly in developing countries.
The differential diagnosis list which includes leptospirosis is very large due to its diverse symptoms. For forms with middle to high severity, the list includes dengue fever and other hemorrhagic fevers, hepatitis of various etiologies, viral meningitis, malaria, and typhoid fever. Light forms should be distinguished from influenza and other related viral diseases. Specific tests are a must for proper diagnosis of leptospirosis.
Under circumstances of limited access (e.g., developing countries) to specific diagnostic means, close attention must be paid to the medical history of the patient. Factors such as certain dwelling areas, seasonality, contact with stagnant contaminated water (bathing, swimming, working on flooded meadows, etc.) or rodents in the medical history support the leptospirosis hypothesis and serve as indications for specific tests (if available).
Leptospira can be cultured in Ellinghausen-McCullough-Johnson-Harris medium, which is incubated at 28 to 30°C. The median time to positivity is three weeks with a maximum of three months. This makes culture techniques useless for diagnostic purposes, but they are commonly used in research.
==Treatment==
Doxycycline may be used as a prophylaxis 200–250 mg once a week, to prevent infection in high risk areas. Treatment is a relatively complicated process comprising two main components: suppressing the causative agent and fighting possible complications. Effective antibiotics include cefotaxime, doxycycline, penicillin, ampicillin, and amoxicillin. Human therapeutic dosage of drugs is as follows: doxycycline 100 mg orally every 12 hours for 2 weeks or penicillin 1–1.5 MU every 4 hours for 1 week. In dogs, penicillin is most commonly used to end the leptospiremic phase (infection of the blood), and doxycycline is used to eliminate the carrier state.
Supportive therapy measures (especially in severe cases) include detoxification and normalization of the hydroelectrolytic balance. Glucose and saline solution infusions may be administered; dialysis is used in serious cases. Elevations of serum potassium are common and if the potassium level gets too high special measures must be taken. Serum phosphorus levels may likewise increase to unacceptable levels due to renal failure.
Treatment for hyperphosphatemia consists of treating the underlying disease, dialysis where appropriate, or oral administration of calcium carbonate, but not without first checking the serum calcium levels (these two levels are related). Corticosteroid administration in gradually reduced doses (e.g., prednisolone starting from 30–60 mg) during 7–10 days is recommended by some specialists in cases of severe hemorrhagic effects. Organ specific care and treatment are essential in cases of renal, liver, or heart involvement.
==Prevention==
Human vaccines are available in a few countries, including Cuba and China. Animal vaccines are only for a few strains. Dog vaccines are effective for at least one year. Currently, no human vaccine is available in the U.S..
==Epidemiology==
Annual rates of infection vary from 0.02 per 100,000 in temperate climates to 10 to 100 per 100,000 in tropical climates.
==History==
The disease was first described by Adolf Weil in 1886 when he reported an "acute infectious disease with enlargement of spleen, jaundice, and nephritis". Leptospira was first observed in 1907 from a post mortem renal tissue slice. In 1908, Inada and Ito first identified it as the causative organism and in 1916 noted its presence in rats.
Leptospirosis was postulated as the cause of an epidemic among Native Americans along the coast of present-day Massachusetts that occurred immediately before the arrival of the Pilgrims in 1620 and killed most of the native population. Earlier proposals included plague, yellow fever, smallpox, influenza, chickenpox, typhus, typhoid fever, trichinellosis, meningitis, and a combined infection of hepatitis B with the delta agent. The disease may have been brought to the New World by Europeans and spread by the high-risk daily activities of the Native Americans.
Before Weil's characterization in 1886, the disease known as infectious jaundice was very likely the same as Weil's disease, or severe icteric leptospirosis. During the Egyptian campaign, Napoleon's army suffered from what was probably infectious jaundice. Infectious jaundice occurred among troops during the American Civil War.
It was also reported among troops at Gallipoli and other battles of World War I, where the sodden conditions of trench warfare favored infection. Terms used in early 20th century descriptions of leptospirosis include the pseudo-dengue of Java, seven-day fever, autumn fever, Akiyama disease, and marsh or swamp fever. L. icterohaemorrhagiae was identified as the causative agent in pre-World War II outbreaks in Japan, which were characterized by jaundice and a high mortality rate.
In October 2010 British rower Andy Holmes died after contracting Weil's Disease. His death has raised awareness of the disease among the public and medical professionals.
==On the series==
===Locked In===
Gregory House stumbled upon Lee when he was at another hospital where they were both patients in the emergency room. The attending physician thought that Lee was brain dead, but House realized that Lee was still conscious and had locked-in syndrome. He was finally able to confirm this when he got Lee to blink in response to questions.
The attending at the hospital thought that the locked-in syndrome was the result of Lee's bicycle accident. However, House was not convinced - people who fall off bicycles put their hands out to brace themselves, and Lee had no injuries to the parts of the hands and arms he would have used. He figured that the locked-in syndrome caused the accident, not the other way around.
House realized that infections can cause injury to the brainstem, which results in locked-in syndrome. However, cancer and stroke also had to be part of the differential.
House managed to have Lee transferred to Princeton-Plainsboro. His next symptom was blood in the urine, a possible sign of kidney failure. House arranged a biopsy of a lesion in Lee's brain. The biopsy was consistent with a number of infections and unfortunately the biopsy itself caused further brain damage, leaving Lee unable to blink.
After establishing a brain computer interface, the team ruled out coronavirus, Epstein-Barr virus, malaria, and rotavirus after realizing that Lee had been lying about his employment, they searched the workplace where he had been working as a janitor and found cadmium. They gave him chelation for cadmium poisoning, but he developed ulcerative keratitis, which ruled it out.
The doctors once again turned to the loss of the patient's myelin. However, this could be caused by either an infection or an autoimmune condition. However, Lee managed to communicate to the doctors that he had an itch in his left foot. This pointed to liver failure and sclerosing cholangitis. However, while they were preparing for a biopsy to confirm, Kutner noted that Thirteen had a rash on her wrist where Lee's urine had spilled on it by accident. Kutner realized that the basement Lee had been staying in had rodents which could have carried leptospirosis, which he transmitted to Thirteen through his urine, causing her rash. They examined Lee's skin and found a bad scratch on his finger that could have allowed the bacteria entry. They ran tests on the rats in the basement to confirm, then successfully treated Lee for the condition.
===Other mentions===
*In The Social Contract, the team suspects that Nick Greenwald might have contracted leptospirosis from dogs when they find out his wife is involved in a dog rescue operation.
*In Sleeping Dogs Lie, as they realize a dog might be the source of the disease, House rules out leptospirosis as a diagnosis for Hannah when Allison Cameron suggests it because Hannah doesn't have conjunctivitis and her creatinine levels are normal.
*In Family, when the team found an abandoned well, they thought Matty may have drunk from it and become infected with leptospirosis. However, Matty had only taken a sip months before and the team realized that the disease would have progressed more quickly. 
*When they did an environmental scan on James Sidas' apartment, Chris Taub found signs of mice and thought Sidas might have leptospirosis. However, Chase rejected the idea because Sidas had no fever.
*In Larger than Life, they realize Jack has an infection and House orders treatment for leptospirosis because he doesn't think there is enough time to wait for blood cultures and leptospirosis is common in subway tunnels due to the presence of rodents and moisture.
*In Gut Check, one of the first tests House runs on Bobby Hatcher is for leptospirosis because Bobby was coughing up blood.
==Links==
*Leptospirosis at Wikipedia - this article was largely developed from the text at Wikipedia.
*Leptospirosis at NIH MedicinePlus
*Leptospirosis at World Health Organization
*Leptospirosis Information Center
*Leptospirosis at the Government of Canada travel site
*Leptospirosis at CDC
*Leptospirosis at Medicine Net
*Hoax Slayer - Can you get leptospirosis from rat pee on a soda can? Luckily, it's very unlikely.
This article was the featured article for May, 2013.
Category:Infections
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