Leptospirose magnified 200 times with dark-field microscope
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Leptospirosis (also known as Weil's disease, canicola fever, canefield fever, nanukayami fever or 7-day 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. It was first described by Adolph Weil in 1886 when he reported an "acute infectious disease with enlargement of spleen, jaundice and nephritis". The pathogen, Leptospira-genus bacteria was isolated in 1907 from post mortem renal tissue slice.
Though being recognised among the world's most common zoonosis, leptospirosis is a relatively rare bacterial infection in humans. The infection is commonly transmitted to humans by allowing fresh water that has been contaminated by animal urine to come in contact with unhealed breaks in the skin, eyes or with the mucous membranes.
Leptospirose magnified 200 times with dark-field microscope
Except for tropic areas, leptospirosis cases have a relatively distinct seasonality with most of them occurring August through September (in the Northern
Leptospirosis is caused by a spirochaete bacterium called leptospira interrogans that has at least 4 different serovars of importance in the United States causing disease (icterohaemorrhagiae, canicola, pomona, grippotyphosa). There are other (less common) infectious strains. It should be however noted that 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 seemingfully more useful from 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. Rats, raccoons, possums, voles, skunks, mice and even infected Dogs may serve as hosts. Dogs may lick the urine of an infected animal off the grass, or drink from an infected puddle. There have even been reports of "house Dogs" getting leptospirosis apparently from licking the urine of infected mice that entered the house. There is a direct correlation between the amount of rainfall and the incidence of leptospirosis.
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 bacteria dissemination in convalescence are extremely rare in humans. Leptospirosis is common among watersport enthusiasts in certain areas as prolonged immersion in water is known to promote the entry of the bacteria.
In animals, the incubation period (time of exposure to first symptoms) is anywhere from 2 to 20 days. One should strongly suspect leptospirosis and include it as part of a differential diagnosis if the whites of the Dog's eyes appear jaundiced (even slightly yellow), but the absence of jaundice does not rule out leptospirosis, and its presence could indicate hepatitis or liver pathology other rather than leptospirosis. Vomiting, failure to eat or drink, reduced urine output, unusually dark or brown urine, lethargy, and other such symptoms are also indications of the disease.
In humans, leptospiral infection causes a wide range of symptoms, and some infected persons may have no symptoms at all. Because of the wide range of symptoms the infection is often wrongly diagnosed. This leads to a lower registered number of cases than there really are. Symptoms of leptospirosis include high fever, severe headache, chills, muscle aches, and vomiting, and may include jaundice, red eyes, abdominal pain, diarrhea, and/or a rash. The symptoms in humans appear after 4-14 day incubation period.
Complications include meningitis, respiratory distress and renal interstitial tubular necrosis, which results in renal failure and often liver failure (this severe form of the disease is known as Weil's disease). Cardiovascular problems are also possible. Approximately 5-50% of severe leptospirosis cases are fatal, however, such cases only constitute about 10% of all registered incidents.
The natural course of leptospirosis falls into 2 distinct phases, septicemic and immune. During a brief period of 1-3 days between the 2 phases, the patient shows some improvement.
First stage: This stage is called the septicemic or leptospiremic stage because the organism may be isolated from blood cultures, cerebrospinal fluid (CSF), and most tissues.
During this stage, which lasts about 4-7 days, the patient develops a nonspecific flulike illness of varying severity.
It is characterized by fever, chills, weakness, and myalgias, primarily affecting the calves, back, and abdomen.
Other symptoms are sore throat, cough, chest pain, hemoptysis, rash, frontal headache, photophobia, mental confusion, and other symptoms of meningitis.
Because of the abrupt nature of the onset, the patient often can tell exactly when the symptoms started.
During the 1-3 day period of improvement that follows the first stage, the temperature curve drops and the patient may become afebrile and relatively asymptomatic. The fever then recurs, indicating the onset of the second stage when clinical or subclinical meningitis appears.
Second stage: This stage is called the immune or leptospiruric stage because circulating antibodies may be detected or the organism may be isolated from urine; it may not be recoverable from blood or CSF.
This stage occurs as a consequence of the body's immunologic response to infection and lasts 0-30 days or more.
Disease referable to specific organs is seen. These organs include the meninges, liver, eyes, and kidney.
Nonspecific symptoms, such as fever and myalgia, may be less severe than in the first stage and last a few days to a few weeks.
Many patients (77%) experience headache that is intense and poorly controlled by analgesics; this often heralds the onset of meningitis.
Anicteric disease: Aseptic meningitis is the most important clinical syndrome observed in the immune anicteric stage.
Meningeal symptoms develop in 50% of patients. Cranial nerve palsies, encephalitis, and changes in consciousness are less common. Mild delirium also may be seen.
Symptoms may be nonspecific, and a viral etiology may be suspected.
Meningitis usually lasts a few days, but occasionally it can last 1-2 weeks.
Death is extremely rare in the anicteric cases.
Icteric disease: Leptospires may be isolated from the blood for 24-48 hours
after jaundice appears. Abdominal pain with diarrhea or constipation (30%),
hepatosplenomegaly, nausea, vomiting, and anorexia also are seen.
Uveitis (2-10%) can develop early or late in the disease and has been reported to occur as late as 1 year after initial illness. Iridocyclitis and chorioretinitis are other late complications that may persist for years. These symptoms first manifest 3 weeks to 1 month after exposure. Subconjunctival hemorrhage is the most common ocular complication of leptospirosis, occurring in as many as 92% of patients. Leptospires may be present in the aqueous humor.
Renal symptoms such as azotemia, pyuria, hematuria, proteinuria, and oliguria are seen in 50% of patients with leptospirosis. Leptospires may be present in the kidney.
Pulmonary manifestations occur in 20-70% of patients.
Adenopathy, rashes, and muscular pain also are seen.
Clinical syndromes are not specific to the serotype, although some manifestations may be seen more commonly with some serotypes.
Often, the serovar helps determine some of the more characteristic clinical manifestations, but any leptospiral serovar can lead to the signs and symptoms seen with this disease. For example, jaundice is seen in 83% of patients with L icterohaemorrhagiae infection and in 30% of patients infected with L pomona. A characteristic pretibial erythematous rash is seen in patients with L autumnalis infection. Similarly, GI symptoms predominate in patients infected with L grippotyphosa. Aseptic meningitis commonly occurs in those infected with L pomona or L canicola. Weil syndrome.
This severe form of leptospirosis primarily manifests as profound jaundice, renal dysfunction, hepatic necrosis, pulmonary dysfunction, and hemorrhagic diathesis.
It occurs at the end of the first stage and peaks in the second stage, but the patient's condition can deteriorate suddenly at any time. Often the transition between the stages is obscured.
o Fever may be marked during the second stage.
o Criteria to determine who will develop Weil disease are not well defined.
o Pulmonary manifestations include cough, dyspnea, chest pain, bloodstained sputum, hemoptysis, and respiratory failure.
o Vascular and renal dysfunctions accompanied by jaundice develop 4-9 days after onset of disease, and the jaundice may persist for weeks.
o Patients with severe jaundice are more likely to develop renal failure, hemorrhage, and cardiovascular collapse. Hepatomegaly and tenderness in the right upper quadrant may be present.
o Oliguric or anuric acute tubular necrosis may occur during the second week due to hypovolemia and decreased renal perfusion.
o Multi-organ failure, rhabdomyolysis, adult respiratory distress syndrome, hemolysis, splenomegaly (20%), congestive heart failure, myocarditis, and pericarditis also may occur. o Weil syndrome carries a mortality rate of 5-10%. The most severe cases of Weil syndrome, with hepatorenal involvement and jaundice, carry a case-fatality rate of 20-40%. Mortality rate is usually higher for older patients.
Leptospirosis may present with a macular or maculopapular rash, abdominal pain
mimicking acute appendicitis, or generalized enlargement of lymphoid glands
resembling infectious mononucleosis. It also may present as aseptic meningitis,
encephalitis, or fever of unknown origin.
Leptospirosis should be considered when a patient has a flulike disease with aseptic meningitis or disproportionately severe myalgia.
On infection the microorganism can be found in blood for the first 7 to 10 days (invoking serologicaly 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 ferments are performed. The later reveal a moderate elevation of transaminases. Diagnosis of leptospirosis is confirmed with tests such as Enzyme-Linked Immunosorbent Assay (ELISA) and PCR. It should be noted that serological testing is laborious and expensive, thus underused 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 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 like certain dwelling areas, seasonality, contact with stagnant water (swimming, working on flooded meadows, etc) and|or rodents in the medical history support the leptospirosis hypothesis and serve indictaions for specific tests (if available).
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 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.
Supportive therapy measures (esp. in severe cases) include detoxication 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 administraion 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.
Improper treatment greatly reduces the survival rate. A patient with leptospirosis SHOULD be treated at a specialized medical institution and MUST remain hospitalized untill proper resolution of organ(s) failure and clinical infection.
In a study of 38 Dogs diagnosed and properly treated for leptospirosis published in the February 2000 issue of the Journal of the American Veterinary Association, the survival rate for the dialysis patients was slightly higher than the ones not put on dialysis, but both were in the 85% range (plus or minus). Of the Dogs in this study that did not die, most recovered adequate kidney function, although one had chronic renal problems.
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