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Definition of Leptospirosis
Leptospirosis (also known as Weil’s disease, Weil’s syndrome, canicola fever, canefield fever, nanukayami fever, 7-day fever, Rat Catcher’s Yellows, Fort Bragg fever, and Pretibial fever) is a bacterial zoonotic disease caused by spirochaetes of the genus Leptospira that affects humans and a wide range of animals, including mammals, birds, amphibians, and reptiles.
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.
Though recognised among the world’s most common zoonoses, leptospirosis is a relatively rare bacterial infection in humans. 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 with most of them occurring August–September/February–March.
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 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 exists. Symptoms of leptospirosis include high fever, severe headache, chills, muscle aches, and vomiting, and may include jaundice, red eyes, abdominal pain, diarrhea, and rash. The symptoms in humans appear after a 4–14 day incubation period.
The incubation period (time of exposure to first symptoms) in animals is anywhere from 2 to 20 days. In dogs the liver and kidney are most commonly damaged by leptospirosis. Vasculitis may occur, causing edema and potentially disseminated intravascular coagulation (DIC). Myocarditis, pericarditis, meningitis, and uveitis are also possible sequelae. One should strongly suspect leptospirosis and include it as part of a differential diagnosis if the sclerae of the 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.
Scanning electron micrograph of a number of Leptospira sp. bacteria atop a 0.1 µm polycarbonate filter
Leptospirosis is caused by a spirochaete bacterium called Leptospira spp. that has at least 5 serovars of importance in the United States and Canada causing disease in dogs (Icterohaemorrhagiae, Canicola, Pomona, Grippotyphosa, and Bratislava). There are other (less common) infectious strains. Genetically different leptospira organisms may be identical serologically and vice versa. Hence, an argument exists on the basis of strain identification. 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 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, possums, skunks, and certain marine mammals are able to carry and transmit the disease as secondary hosts. Dogs may lick the urine of an infected animal off the grass or soil, or drink from an infected puddle. There have been reports of “house 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. Slaughterhouse workers may contract the disease through contact with infected blood or body fluids.
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. Occupations at risk include veterinarians, slaughterhouse workers, farmers, sewer workers, and people working on derelict buildings. Rowers are also sometimes known to contract the disease.
Kidney tissue, using a silver staining technique, revealing the presence of Leptospira bacteria
On infection the microorganism can be found in blood 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. It is also possible to culture the microorganism from blood, serum, fresh urine and possibly fresh kidney biopsy. 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 PCR. Serological testing, the MAT (microscopic agglutination 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.
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 anamnesis 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 3 months. This makes culture techniques useless for diagnostic purposes, but is commonly used in research.
Leptospirosis treatment is a relatively complicated process comprising two main components: suppressing the causative agent and fighting possible complications. Aetiotropic drugs are antibiotics, such as cefotaxime, doxycycline, penicillin, ampicillin, and amoxicillin (doxycycline can also be used as a prophylaxis). There are no human vaccines; animal vaccines are only for a few strains, and are only effective for a few months. 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. Doxycycline 200–250 mg once a week is administered as a prophylaxis. 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 (esp. 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.
Doxycycline may be used to prevent infection in adventure travelers to high risk areas.
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