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| {{DiseaseDisorder infobox |
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| Name = Leptospirosis |
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| Image = Lepto-klein.JPG |
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| Caption = Leptospirose magnified 200 times with dark-field microscope |
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| DiseasesDB = 7403 |
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| ICD10 = {{ICD10|A|27| |a|20}} |
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| ICD9
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| OMIM = 607948 |
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| MedlinePlus = 001376 |
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| eMedicineSubj = med |
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| eMedicineTopic = 1283 |
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| eMedicine_mult = {{eMedicine2|emerg|856}} {{eMedicine2|ped|1298}} |
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| MeshName = Leptospirosis |
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| MeshNumber = C01.252.400.511 |
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| }}
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| __NOTOC__ | | __NOTOC__ |
| {{Leptospirosis}} | | {{Leptospirosis}} |
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| | {{CMG}};{{AE}}{{VSKP}} |
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| {{About1|Leptospira}} | | {{About1|Leptospira}} |
| {{CMG}}
| | '''For patient information on this page, click [[Leptospirosis (patient information)|here]]''' |
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| {{SK}} Cane cutter's fever; Harvest fever; Infection due to Leptospira; Japanese autumnal fever; Queensland fever; Rice-field worker's disease; Seven day fever; Spirochaetal jaundice; Spirochetal jaundice | | {{SK}} Cane cutter's fever; Harvest fever; Infection due to Leptospira; Japanese autumnal fever; Queensland fever; Rice-field worker's disease; Seven day fever; Spirochaetal jaundice; Mud fever; Swamp fever; Cane field fever; Fort Bragg fever; Tibial fever; Haemorrhagic jaundice; Spirochetosis; Canicola fever; Rat Catcher’s yellows disease; Swineherds disease |
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| ==[[Leptospirosis overview|Overview]]== | | ==[[Leptospirosis overview|Overview]]== |
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| ==Diagnosis== | | ==Diagnosis== |
| [[Leptospirosis history and symptoms| History and Symptoms]] | [[Leptospirosis physical examination | Physical Examination]] | [[Leptospirosis laboratory findings|Laboratory Findings]] | [[Leptospirosis CT|CT]] | [[Leptospirosis other imaging findings|Other Imaging Findings]] | [[Leptospirosis other diagnostic studies|Other Diagnostic Studies]] | | [[Leptospirosis history and symptoms| History and Symptoms]] | [[Leptospirosis physical examination | Physical Examination]] | [[Leptospirosis laboratory findings|Laboratory Findings]] | [[Leptospirosis other imaging findings|Other Imaging Findings]] | [[Leptospirosis other diagnostic studies|Other Diagnostic Studies]] | [[Leptospirosis criteria]] |
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| ==Treatment== | | ==Treatment== |
| [[Leptospirosis medical therapy|Medical Therapy]] | [[Leptospirosis surgery|Surgery]] | [[Leptospirosis primary prevention|Primary Prevention]] | [[Leptospirosis secondary prevention|Secondary Prevention]] | [[Leptospirosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Leptospirosis future or investigational therapies|Future or Investigational Therapies]] | | [[Leptospirosis medical therapy|Medical Therapy]] | [[Leptospirosis primary prevention|Primary Prevention]] | [[Leptospirosis cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Leptospirosis future or investigational therapies|Future or Investigational Therapies]] |
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| ==Case Studies== | | ==Case Studies== |
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| ==Related Chapters== | | ==Related Chapters== |
| * [[Stomach]] | | * [[Leptospira]] |
| * [[Gastroenteritis]]
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| * [[Infection]]
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| ==Overview==
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| '''Leptospirosis''' (also known as '''Weil's disease''', '''canicola fever''', '''canefield fever''', '''nanukayami fever''', '''7-day fever''' and many more<ref name=NORD>[http://children.webmd.com/Weil-Syndrome Weil Syndrome<!-- Bot generated title -->]</ref>) is a [[infectious disease|bacterial]] [[zoonotic]] disease caused by [[spirochaete]]s of the [[genus]] ''[[Leptospira]]'' that affects [[human]]s and a wide range of animals, including mammals, birds, amphibians, and reptiles. It was first described by [[Adolf Weil (physician)|Adolf Weil]] in 1886 when he reported an "acute infectious disease with [[splenomegaly|enlargement of spleen]], [[jaundice]] and [[nephritis]]". ''Leptospira'' was first observed in 1907 from a [[post mortem]] [[kidney|renal tissue]] slice.<ref>Stimson AM (1907). "Note on an organism found in yellow-fever tissue." ''Public Health Reports'' '''22''':541.</ref>
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| Though being recognised among the world's most common [[zoonosis|zoonoses]], 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]], [[eye]]s or with the [[mucous membrane]]s. Outside of [[Tropics|tropical]] areas, leptospirosis cases have a relatively distinct seasonality with most of them occurring August-September/February-March.
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| ==Where is leptospirosis found?==
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| Leptospirosis occurs worldwide but is most common in temperate or tropical climates. It is an occupational hazard for many people who work outdoors or with animals, for example, farmers, sewer workers, veterinarians, fish workers, dairy farmers, or military personnel. It is a recreational hazard for campers or those who participate in outdoor sports in contaminated areas and has been associated with swimming, wading, and whitewater rafting in contaminated lakes and rivers. The incidence is also increasing among urban children.
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| ==Causes==
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| [[Image:Leptospira scanning micrograph.jpg|300px|left|thumb|[[Scanning electron microscope]] of a number of Leptospira sp. bacteria atop a 0.1 µm [[polycarbonate]] filter]]
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| Leptospirosis is caused by a spirochaete bacterium called ''[[Leptospira]]'' spp. that has at 5 different [[serovar]]s of importance in the United States causing disease (icterohaemorrhagiae, canicola, pomona, grippotyphosa, and bratislava).<ref name=VCNA>{{cite journal|author=Heuter, Kerry J.,Langston, Cathy E.|title=Leptospirosis: A re-emerging zoonotic disease|journal=The Veterinary Clinics of North America|year=2003|volume=33|pages=791-807}}</ref> There are other (less common) infectious strains. It should however be 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 seemingly more useful from diagnostic and epidemiologic standpoint at the moment (which may change with further development and spread of technologies like [[PCR]]).
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| Leptospirosis is transmitted by the urine of an infected animal, and is contagious as long as it is still moist. Although rats, mice and voles are important primary hosts, a wide range of other mammals including dogs, deer, rabbits, hedgehogs, cows, sheep, raccoons, possums, skunks, and even certain marine mammals are also 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, gulleys 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.
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| Leptospirosis is also transmitted by the semen of infected animals<ref name="lept">{{cite journal | author=Kiktenko VS| title=Leptospirosis infection through insemination of animals.| journal=J Hyg Epidemiol Microbiol Immunol.| year=1976| volume=21| issue=2| page=207-213| url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=987112&dopt=Abstract}}</ref>. Abattoir workers can contract the disease through contact with infected blood or body fluids.
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| 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 watersport enthusiasts in specific areas as prolonged immersion in water is known to promote the entry of the bacteria. Occupational risk factors include [[veterinarian]]s, slaughter house workers, farmers, and sewer workers. An outbreak in an inner city environment has been linked to contact with rat urine.<ref name=VCNA>{{cite journal|author=Heuter, Kerry J.,Langston, Cathy E.|title=Leptospirosis: A re-emerging zoonotic disease|journal=The Veterinary Clinics of North America|year=2003|volume=33|pages=791-807}}</ref>
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| ==How do people get leptospirosis?==
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| Outbreaks of leptospirosis are usually caused by exposure to water contaminated with the urine of infected animals. Many different kinds of animals carry the bacterium; they may become sick but sometimes have no symptoms. Leptospira organisms have been found in cattle, pigs, horses, dogs, rodents, and wild 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, especially with mucosal surfaces, such as the eyes or nose, or with broken skin. The disease is not known to be spread from person to person.
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| ==How long is it between the time of exposure and when people become sick?==
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| The time between a person's exposure to a contaminated source and becoming sick is 2 days to 4 weeks. Illness usually begins abruptly with fever and other symptoms. Leptospirosis may occur in two phases; after the first phase, with fever, chills, headache, muscle aches, vomiting, or diarrhea, the patient may recover for a time but become ill again. If a second phase occurs, it is more severe; the person may have kidney or liver failure or meningitis. This phase is also called Weil's disease.
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| The illness lasts from a few days to 3 weeks or longer. Without treatment, recovery may take several months.
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| ==Symptoms==
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| In animals, the [[incubation period]] (time of exposure to first [[symptom]]s) is anywhere from 2 to 20 days. In dogs, the liver and kidney are most commonly damaged by leptospirosis. [[Vasculitis]] can occur, causing [[edema]] and potentially [[disseminated intravascular coagulation]] (DIC). [[Myocarditis]], [[pericarditis]], [[meningitis]], and [[uveitis]] are also possible sequelae. <ref name=VCNA>{{cite journal|author=Heuter, Kerry J.,Langston, Cathy E.|title=Leptospirosis: A re-emerging zoonotic disease|journal=The Veterinary Clinics of North America|year=2003|volume=33|pages=791-807}}</ref> One should strongly suspect leptospirosis and include it as part of a [[differential diagnosis]] if the sclerae of the dog's eyes appear [[jaundice]]d (even slightly yellow), though the absence of jaundice does not eliminate the possibility of leptospirosis, and its presence could indicate [[hepatitis]] or other liver pathology rather than leptospirosis. [[Vomit]]ing, fever, failure to eat, reduced urine output, unusually dark or brown urine, and [[lethargy]] are also indications of the disease.
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| In humans, leptospiral infection causes a wide range of [[symptom]]s, and some infected persons may have no symptoms at all. Leptospirosis is a '''biphasic disease''' that begins with flu-like symptoms (fever, chills, [[myalgia]]s, intense headache). The first phase resolves and the patient is asymptomatic briefly before the second phase begins that is characterized by meningitis, liver damage (causing jaundice), and renal failure. Because of the wide range of symptoms the infection is often [[misdiagnosis|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 [[vomit]]ing, and may include [[jaundice]], red eyes, [[abdominal pain]], [[diarrhea]], and/or a [[rash]]. The symptoms in humans appear after a 4-14 day incubation period.
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| ==Complications==
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| Complications include [[meningitis]], respiratory distress and renal interstitial tubular necrosis, which results in [[renal failure]] and often [[liver failure]] (the severe form of this disease is known as '''Weil's disease''', though it is sometimes named '''Weil Syndrome'''<ref name=NORD /><ref>[http://www.medterms.com/script/main/art.asp?articlekey=23871 Weil syndrome definition - Medical Dictionary definitions of popular medical terms easily defined on MedTerms<!-- Bot generated title -->]</ref>). 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.
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| ==Diagnostics==
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| [[Image:Leptospirosis in kidney.jpg|thumb|left|Kidney tissue, using a [[silver stain]]ing technique, revealing the presence of ''Leptospira'' bacteria]]
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| 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 [[microbial culture | 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 later 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.
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| [[Diagnosis]] of leptospirosis is confirmed with tests such as [[Enzyme-Linked Immunosorbent Assay]] (ELISA) and [[Polymerase chain reaction|PCR]]. Serological testing, the MAT (microscopic agglutination test), is considered the [[Gold standard (test)|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.
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| [[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 [[fever]]s, [[hepatitis]] of various [[etiology|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 (medicine)|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 as indications for specific tests (if available).
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| Leptospira can be cultured in [[Ellinghausen-McCullough-Johnson-Harris medium], which is incubated at 28 to 30ºC.<ref>{{cite journal|title=Gellan gum as a substitute for agar in leptospiral media|author=Rule PL, Alexander AD|journal=J Clin Microbiol|volum=23|issue=3|pages=500–504|year=1986|pmid=3754265}}</ref> 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.
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| ==Differentiating Leptospirosis from other Diseases==
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| The table below summarizes the findings that differentiate [[Leptospirosis]] from other conditions that cause [[fever]], [[diarrhea]], [[nausea]] and [[vomiting]]:
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| {| style="border: 0px; font-size: 90%; margin: 3px;" align=center
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| ! style="background: #4479BA; width: 120px;" | {{fontcolor|#FFF|Disease}}
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| ! style="background: #4479BA; width: 550px;" | {{fontcolor|#FFF|Findings}}
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Ebola]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" | Presents with [[fever]], [[chills]] [[vomiting]], [[diarrhea]], generalized [[pain]] or [[malaise]], and sometimes [[Internal bleeding|internal]] and external [[bleeding]], that follow an [[incubation period]] of 2-21 days.
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Typhoid fever]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" | Presents with [[fever]], [[headache]], [[rash]], gastrointestinal symptoms, with [[lymphadenopathy]], relative [[bradycardia]], [[cough]] and [[leucopenia]] and sometimes [[sore throat]]. [[Blood]] and [[stool culture]] can confirm the presence of the causative bacteria.
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| | style="padding: 5px 5px; background: #DCDCDC;" |'''[[Malaria]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |Presents with acute [[fever]], [[headache]] and sometimes [[diarrhea]] (children). A [[blood smear]]s must be examined for malaria parasites. The presence of [[parasites]] does not exclude a concurrent viral infection. An [[antimalarial]] should be prescribed as an [[empiric therapy]].
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Lassa fever]]'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |Disease onset is usually gradual, with [[fever]], [[sore throat]], [[cough]], [[pharyngitis]], and [[facial edema]] in the later stages. [[Inflammation]] and exudation of the [[pharynx]] and [[conjunctiva]] are common.
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Yellow fever]] and other [[Flaviviridae]] '''
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| | style="padding: 5px 5px; background: #F5F5F5;" | Present with [[hemorrhage|hemorrhagic]] complications. [[Epidemiological]] investigation may reveal a pattern of disease [[transmission]] by an insect vector. Virus isolation and serological investigation serves to distinguish these [[viruses]]. Confirmed history of previous [[yellow fever]] [[vaccination]] will rule out [[yellow fever]].
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''[[Shigellosis]] & other bacterial enteric infections'''
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| | style="padding: 5px 5px; background: #F5F5F5;" | Presents with [[diarrhea]], possibly [[Dysentery|bloody]], accompanied by [[fever]], [[nausea]], and sometimes [[toxemia]], [[vomiting]], [[cramps]], and [[tenesmus]]. [[Stool]]s contain [[blood]] and mucous in a typical case. A search for possible sites of bacterial infection, together with cultures and [[blood smear]]s, should be made. Presence of [[leucocytosis]] distinguishes bacterial infections from [[viral infections]].
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| | style="padding: 5px 5px; background: #DCDCDC;" | '''Others'''
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| | style="padding: 5px 5px; background: #F5F5F5;" |[[Viral Hepatitis]], [[rheumatic fever]], [[typhus]], and [[mononucleosis]]
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| |}
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| ==Treatment==
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| 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 [[vaccine]]s; 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 [[asymptomatic carrier|carrier]] state.
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| Supportive therapy measures (esp. in severe cases) include [[detoxication]] and normalization of the [[Electrolyte#Physiological importance|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). [[Corticosteroid]]s 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.
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| ===Antimicrobial regimen===
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| *1. '''Severe''' <ref>{{cite book | last = LastName | first = FirstName | title = Human leptospirosis guidance for diagnosis, surveillance and control | publisher = World Health Organization | location = Geneva | year = 2003 | isbn = 9241545895 }}</ref> <ref>{{cite book | last = Bartlett | first = John | title = Johns Hopkins ABX guide : diagnosis and treatment of infectious diseases | publisher = Jones and Bartlett Learning | location = Burlington, MA | year = 2012 | isbn = 978-1449625580 }}</ref>
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| :* Preferred regimen: [[Penicillin]] 1.5 MU IV q6h for 5-7 days
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| *2. '''Less severe'''
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| :* Preferred regimen (1): [[Amoxycillin]]
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| :* Preferred regimen (2): [[Ampicillin]]
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| :* Preferred regimen (3): [[Doxycycline]] 100 mg IV/PO q12h/bid for 5-7 days
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| :* Preferred regimen (4): [[Erythromycin]]
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| :* Preferred regimen (5): [[Ceftriaxone]] 1 g IV q24h for 5-7 days
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| :* Preferred regimen (6): [[Cefotaxime]]
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| :* Preferred regimen (7): [[Quinolone]] PO
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| ==Research==
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| Leptospirosis: a zoonotic disease of global importance. Lancet Infect Dis. 2003 Dec;3(12):757-71
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| Bharti AR, Nally JE, Ricaldi JN, Matthias MA, Diaz MM, Lovett MA, Levett PN, Gilman RH, Willig MR, Gotuzzo E, Vinetz JM; Peru-United States Leptospirosis Consortium.
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| In the past decade, leptospirosis has emerged as a globally important infectious disease. It occurs in urban environments of industrialised and developing countries, as well as in rural regions worldwide. Mortality remains significant, related both to delays in diagnosis due to lack of infrastructure and adequate clinical suspicion, and to other poorly understood reasons that may include inherent pathogenicity of some leptospiral strains or genetically determined host immunopathological responses. Pulmonary haemorrhage is recognised increasingly as a major, often lethal, manifestation of leptospirosis, the pathogenesis of which remains unclear. The completion of the genome sequence of Leptospira interrogans serovar lai, and other continuing leptospiral genome sequencing projects, promise to guide future work on the disease. Mainstays of treatment are still tetracyclines and beta-lactam/cephalosporins. No vaccine is available. Prevention is largely dependent on sanitation measures that may be difficult to implement, especially in developing countries.
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| 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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| ==Can leptospirosis be prevented?==
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| The risk of acquiring leptospirosis can be greatly reduced by not swimming or wading in water that might be contaminated with animal urine.
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| Protective clothing or footwear should be worn by those exposed to contaminated water or soil because of their job or recreational activities.
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| ==See also==
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| * Marine Mammal Center
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| ==References==
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| <references/>
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| ==External links== | | ==External links== |
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| *[http://www.leptoinfo.com leptoinfo.com - A website for Dog Owners and Veterinary Professionals dedicated to sharing information on Leptospirosis in Canada] | | *[http://www.leptoinfo.com leptoinfo.com - A website for Dog Owners and Veterinary Professionals dedicated to sharing information on Leptospirosis in Canada] |
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