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Leptospira magnified 200 times with dark-field microscope
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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:290) 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 that transmits from animals to people (zoonosis). 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 with the mucous membranes. Outside of tropical areas, leptospirosis cases have a relatively distinct seasonality—most cases occur in spring and autumn.
Doxycycline may be used 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 or penicillin. 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.
Signs and symptoms
Leptospiral infection in humans causes a range of symptoms, and some infected persons may have no symptoms at all. Leptospirosis is a biphasic disease that begins with flu-like symptoms (fever, chills, myalgias, intense headache). The first phase (mild leptospirosis) resolves, and the patient is briefly asymptomatic until the second phase (severe leptospirosis) begins. 90 percent of the disease is mild leptospirosis and without any specific treatment and the rest develop to severe leptospirosis. This is characterized by heart affected, liver damage (causing jaundice), renal failure with same signs and symptons; brain affected, meningitis of the outer layer of the brain, encephalitis of brain tissue with same same signs and symptons; and lung affected as the most serious and life-threatening of all leptospirosis complications. The infection is often incorrectly diagnosed due to the nonspecific symptoms.
Signs and symptoms of leptospirosis include high fever, severe headache, chills, muscle aches, and vomiting, and may include jaundice, red eyes, 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, and 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.
Incubation (time of exposure to first symptoms) in animals is anywhere from 2 to 20 days. In dogs, leptospirosis most often damages the liver and kidney. In addition, recent reports describe a pulmonary form of canine leptospirosis associated with severe hemorrhage in the lungs—similar to human pulmonary hemorrhagic syndrome. Vasculitis may occur, causing edema and potentially disseminated intravascular coagulation (DIC). Myocarditis, pericarditis, meningitis, and uveitis are also possible sequelae.
Leptospirosis should be strongly suspected and included as part of a differential diagnosis if the sclerae of a dog's eyes appear jaundiced (even slightly yellow). The absence of jaundice does not eliminate the possibility of leptospirosis, and its presence could 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.
Other (more common) lethal infectious strains exist. Genetically different leptospira organisms may be identical serologically and vice versa. Hence, some argue about strain identification. The traditional serologic system currently seems more useful from a diagnostic and epidemiologic standpoint—but this 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 the urine is still moist. Rats, mice, and moles are important primary hosts—but a wide range of other mammals including dogs, deer, rabbits, hedgehogs, cows, sheep, raccoons, opossums, skunks, and certain marine mammals carry and transmit the disease as secondary hosts. In Africa, the banded mongoose has been identified as a carrier of the pathogen, likely in addition to other African wildlife hosts. Dogs may lick the urine of an infected animal off the grass or soil, or drink from an infected puddle.
House-bound domestic dogs have contracted leptospirosis, apparently from licking the urine of infected mice in 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 wild or farm mammals. The incidence of leptospirosis correlates directly with the amount of rainfall, making it seasonal in temperate climates and year-round in tropical climates. Leptospirosis also transmits via the semen of infected animals.
Humans become infected through contact with water, food, or soil that contains urine from these infected animals. This may happen by swallowing contaminated food or water or through skin contact. The disease is not known to spread between humans, and bacterial dissemination in convalescence is extremely rare in humans. Leptospirosis is common among water-sport enthusiasts in specific areas, as prolonged immersion in water promotes 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 who work on derelict buildings. Slaughterhouse workers can contract the disease through contact with infected blood or body fluids. Rowers, kayakers and canoeists also sometimes contract the disease.
On infection the microorganism can be found in blood and Cerebrospinal fluid (CSF) for the first 7 to 10 days (invoking serologically identifiable reactions) and then moving to the kidneys. After 7 to 10 days the microorganism 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 (blood urea nitrogen and creatinine) as well as blood tests for liver functions are performed. The latter reveal a moderate elevation of transaminases. Brief elevations of aspartate aminotransferase (AST), alanine aminotransferase (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 must be subcultured frequently, which is both laborious and expensive, it is underused, especially in developing countries.
Differential diagnosis list for leptospirosis is very large due to diverse symptomatics. 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 is commonly used in research.
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 US.
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 1 week 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 hydro-electrolytic balance. Glucose and salt 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). Corticosteroids 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 haemorrhagic effects. Organ specific care and treatment are essential in cases of renal, liver, or heart involvement.
Annual rates of infection vary from 0.02 per 100,000 in temperate climates to 10 to 100 per 100,000 in tropical climates.
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 syndemic infection of hepatitis B virus 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.
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- The Leptospirosis Information Center
- U.S. Disease Control and Prevention Center page on Leptospirosis
- Leptonet.net – the Leptospirosis information portal
- International Leptospirosis Society page
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- Leptoinfo.com – A website for Dog Owners and Veterinary Professionals dedicated to sharing information on Leptospirosis in Canada