Leptospirosis natural history, complications and prognosis: Difference between revisions

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{{Leptospirosis}}
{{Leptospirosis}}


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==Natural history==
== Overview ==
Leptospirosis is transported by the natural carriers such as feral, semi-domestic, farm and pet animals.<ref name="pmid11292640">{{cite journal| author=Levett PN| title=Leptospirosis. | journal=Clin Microbiol Rev | year= 2001 | volume= 14 | issue= 2 | pages= 296-326 | pmid=11292640 | doi=10.1128/CMR.14.2.296-326.2001 | pmc=88975 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11292640  }} </ref> Incubation period for leptospirosis varies between 3-20 days. The disease can cause wide range of symptoms from mild [[flu]]-like symptoms to severe disease with multi [[organ failure]] causing death. 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]].<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> The disease leptospirosis is poorly known and unaware of its natural history is mainly due to the wide range of non specific symptoms, subclinical nature of the disease in animals and non specific laboratory tests making the disease difficult to diagnose.<ref name="pmid16600656">{{cite journal| author=Vieira ML, Gama-Simões MJ, Collares-Pereira M| title=Human leptospirosis in Portugal: A retrospective study of eighteen years. | journal=Int J Infect Dis | year= 2006 | volume= 10 | issue= 5 | pages= 378-86 | pmid=16600656 | doi=10.1016/j.ijid.2005.07.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16600656  }} </ref> Outcome of the patient depends upon the [[pathogenic]] [[serovar]] and [[immunological]] status.
==Natural History==
Natural history of leptospirosis varies with each patient. It might be mild or asymptomatic, and go unrecognized or in some patients the illness may progress to [[kidney]] or [[liver failure]], [[aseptic meningitis]], life-threatening [[pulmonary hemorrhage]] and other syndromes.
===Acute Phase===
* Also known as septicemic phase or leptospiremic phase.
* Begins abruptly
* [[Bacteria]] are present in the [[blood]] and [[CSF]] of the patient
* Characterized by wide spectrum of nonspecific signs and symptoms such as [[fever]], [[chills]], [[headache]] and [[conjunctival]] suffusion making it very difficult to diagnose.<ref name="pmid16333189">{{cite journal| author=Bal AM| title=Unusual clinical manifestations of leptospirosis. | journal=J Postgrad Med | year= 2005 | volume= 51 | issue= 3 | pages= 179-83 | pmid=16333189 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16333189  }} </ref>
* Associate with severe [[myalgia]]
* Other less common findings include: [[Photophobia]], [[lymphadenopathy]], [[abdominal pain]], [[nausea]],  [[vomiting]], a transient [[rash]], [[sore throat]], [[coughing]] or [[chest pain]].
* Characterestic of  this phase also includes: Mild form of leptospirosis in ~90% cases which lasts several days to a week, followed by a brief  remission, during which the temperature drops and the symptoms disappear


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.  
===Immune phase===
* It is also known as leptospiruric phase.
* Circulating ([[IgM]]) [[antibodies]] are produced and leptospires are present in the [[urine]].
* Characterestic findings that differentiate from other febrile illnesses are [[myalgia]] and [[conjunctival]] suffusion.<ref name="pmid22843698">{{cite journal| author=Forbes AE, Zochowski WJ, Dubrey SW, Sivaprakasam V| title=Leptospirosis and Weil's disease in the UK. | journal=QJM | year= 2012 | volume= 105 | issue= 12 | pages= 1151-62 | pmid=22843698 | doi=10.1093/qjmed/hcs145 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22843698  }} </ref>
* [[Myalgia]] often involves in [[Calf muscle|calf]] muscles, less commonly involves [[abdominal]] and para-spinal [[muscles]].


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.
====Anicteric leptospirosis====
* More common but serious illness is uncommon.
* Most of cases present either subclinical or of very mild severity.
* Few cases present with a febrile illness of sudden onset.
* May progress to [[aseptic meningitis]] in ≤25% of patients and more common in younger age group than the patients with icteric leptospirosis.
* Mortality is very less when compared to icteric leptospirosis.
====Icteric leptospirosis====
* Rapidly progressive and severe form of leptospirosis([[Weil's disease]])
* In the severe form of leptospirosis [[renal failure]], [[hepatic failure]] and [[pulmonary hemorrhage]] can occur and associate with Icterohaemorrhagiae.<ref name="pmid11692294">{{cite journal| author=Katz AR, Ansdell VE, Effler PV, Middleton CR, Sasaki DM| title=Assessment of the clinical presentation and treatment of 353 cases of laboratory-confirmed leptospirosis in Hawaii, 1974-1998. | journal=Clin Infect Dis | year= 2001 | volume= 33 | issue= 11 | pages= 1834-41 | pmid=11692294 | doi=10.1086/324084 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11692294  }} </ref>
* Less common form of leptospirosis with incidence of 5%-10%
* [[Jaundice]] is not associate with [[Hepatocellular Disease|hepatocellular]] [[injury]], eventually [[Liver function tests|LFT]] returns to normal after recovery.
* High mortality rate with a range of 5%-15%.


==Complications==
==== Severe leptospirosis ====
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>[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.
Sever form of leptospirosis with [[organ failure]] including [[liver]] and [[kidney]] involvement is known as [[Weil's disease]].
* [[Hepatic]]: Mild to severe form of [[jaundice]] developed within 4-7 days after the initial clinical presentation that can progress to [[hepatic failure]] or [[hepatic encephalopathy]].
* [[Renal]]: Very common presentation involving [[kidneys]] is [[acute interstitial nephritis]], with cola colored [[urine]], [[oliguria]] or [[anuria]].
* [[Pulmonary]]:  Milder form of leptospirosis presents with [[cough]], [[chest pain]] and [[blood]] tinged [[sputum]], where as in severe form present with [[cough]], [[hemoptysis]], rapidly increasing [[breathlessness]] which may lead to [[respiratory failure]] and death. Hemorrhagic [[pneumonitis]] with [[interstitial]] and intra alveolar hemorrhage is the commonest cause of death in leptospirosis with case fatality rate of 0%-15%.
* [[Cardiovascular]]: [[Arrhythmias]] present with [[syncope]] and [[palpitations]].
* [[Nervous system]]: [[Meningitis]],  [[encephalitis]], focal defecits, [[spasticity]], [[paralysis]], [[Peripheral neuropathy|peripheral neuropathies,]] [[Nerve palsy|nerve palsies]] and [[Radiculopathy|radiculopathies]].


==Natural History, Complications & Prognosis==
Leptospirosis is transported by the natural carriers such as feral, semi-domestic and farm and pet animals.<ref name="pmid11292640">{{cite journal| author=Levett PN| title=Leptospirosis. | journal=Clin Microbiol Rev | year= 2001 | volume= 14 | issue= 2 | pages= 296-326 | pmid=11292640 | doi=10.1128/CMR.14.2.296-326.2001 | pmc=88975 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11292640  }} </ref> The disease leptospirosis is poorly known and unaware of its natural history is mainly due to the wide range of non specific symptoms, subclinical nature of the disease in animals, and non specific laboratory tests making the disease difficult to diagnose.<ref name="pmid16600656">{{cite journal| author=Vieira ML, Gama-Simões MJ, Collares-Pereira M| title=Human leptospirosis in Portugal: A retrospective study of eighteen years. | journal=Int J Infect Dis | year= 2006 | volume= 10 | issue= 5 | pages= 378-86 | pmid=16600656 | doi=10.1016/j.ijid.2005.07.006 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16600656  }} </ref>
===Natural History===
Natural history of leptospirosis varies with each patient. It might be mild or asymptomatic, and go unrecognized or in some patients the illness may progress to kidney or liver failure, aseptic meningitis, life-threatening pulmonary hemorrhage and other syndromes.
===Complications===
===Complications===
Complications of leptospirosis are associated with localization of pathogen(Leptospires) within the tissues during the immune phase, eventually present during the second week of the illness.
Complications of leptospirosis are associated with localization of [[pathogen]] (leptospires) within the [[tissues]] during the [[Immune|immune phase]], eventually present during the second week of the [[illness]].
* Pulmonary: Pulmonary hemorrhage<ref name="pmid16333187">{{cite journal| author=Salkade HP, Divate S, Deshpande JR, Kawishwar V, Chaturvedi R, Kandalkar BM et al.| title=A study of sutopsy findings in 62 cases of leptospirosis in a metropolitan city in India. | journal=J Postgrad Med | year= 2005 | volume= 51 | issue= 3 | pages= 169-73 | pmid=16333187 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16333187  }} </ref>
 
* Hematological: Thrombocytopenic purpura, Disseminated intravascular coagulation
'''Life threatening complications'''
* Neurological: Mild meningitis, encephalitis, radiculopathies, transverse myelitis, cranial nerve palsies and Guillain– Barre syndrome.<ref name="pmid16333189">{{cite journal| author=Bal AM| title=Unusual clinical manifestations of leptospirosis. | journal=J Postgrad Med | year= 2005 | volume= 51 | issue= 3 | pages= 179-83 | pmid=16333189 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16333189  }} </ref>
* [[Acute kidney injury]]
* [[Disseminated intravascular coagulation]]
* [[Gastrointestinal hemorrhage]]
* [[Hemorrhagic shock]]
 
'''Common Complications'''
* [[Pulmonary]]: Pulmonary hemorrhage<ref name="pmid16333187">{{cite journal| author=Salkade HP, Divate S, Deshpande JR, Kawishwar V, Chaturvedi R, Kandalkar BM et al.| title=A study of sutopsy findings in 62 cases of leptospirosis in a metropolitan city in India. | journal=J Postgrad Med | year= 2005 | volume= 51 | issue= 3 | pages= 169-73 | pmid=16333187 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16333187  }} </ref>
* [[Hematological]]: [[Thrombocytopenic purpura]], [[Disseminated intravascular coagulation]].
* [[Neurological]]: Mild [[meningitis]], [[encephalitis]], radiculopathies, [[transverse myelitis]], [[cranial nerve palsies]] and [[Guillain-Barre syndrome]].<ref name="pmid16333189">{{cite journal| author=Bal AM| title=Unusual clinical manifestations of leptospirosis. | journal=J Postgrad Med | year= 2005 | volume= 51 | issue= 3 | pages= 179-83 | pmid=16333189 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16333189  }} </ref>
* [[Cardiac]]: [[Myocarditis]], [[pericarditis]]<ref name="pmid2355200">{{cite journal| author=Watt G, Padre LP, Tuazon M, Calubaquib C| title=Skeletal and cardiac muscle involvement in severe, late leptospirosis. | journal=J Infect Dis | year= 1990 | volume= 162 | issue= 1 | pages= 266-9 | pmid=2355200 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2355200  }} </ref><ref name="pmid18262280">{{cite journal| author=Chakurkar G, Vaideeswar P, Pandit SP, Divate SA| title=Cardiovascular lesions in leptospirosis: an autopsy study. | journal=J Infect | year= 2008 | volume= 56 | issue= 3 | pages= 197-203 | pmid=18262280 | doi=10.1016/j.jinf.2007.12.007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18262280  }} </ref>
**[[Conduction System|Conduction]] abnormalities: [[First degree atrioventricular block]], widespread [[T-wave inversion]]<ref name="pmid18262280">{{cite journal| author=Chakurkar G, Vaideeswar P, Pandit SP, Divate SA| title=Cardiovascular lesions in leptospirosis: an autopsy study. | journal=J Infect | year= 2008 | volume= 56 | issue= 3 | pages= 197-203 | pmid=18262280 | doi=10.1016/j.jinf.2007.12.007 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18262280  }} </ref><ref name="pmid20790602">{{cite journal| author=Parsons M| title=Electrocardiographic Changes in Leptospirosis. | journal=Br Med J | year= 1965 | volume= 2 | issue= 5455 | pages= 201-3 | pmid=20790602 | doi= | pmc=1846500 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=20790602  }} </ref>
**[[Rhythm]] abnormalities: [[Atrial fibrillation]].
* [[Renal]]: [[Myositis]] '''→''' [[Rhabdomyolysis]] '''→''' [[Interstitial nephritis]] '''→''' [[Renal failure]]
* [[Pregnancy]]: [[Miscarriages]], active leptospirosis in [[fetus]]<ref name="pmid8399874">{{cite journal| author=Shaked Y, Shpilberg O, Samra D, Samra Y| title=Leptospirosis in pregnancy and its effect on the fetus: case report and review. | journal=Clin Infect Dis | year= 1993 | volume= 17 | issue= 2 | pages= 241-3 | pmid=8399874 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8399874  }} </ref><ref name="pmid7650320">{{cite journal| author=Carles G, Montoya E, Joly F, Peneau C| title=[Leptospirosis and pregnancy. Eleven cases in French Guyana]. | journal=J Gynecol Obstet Biol Reprod (Paris) | year= 1995 | volume= 24 | issue= 4 | pages= 418-21 | pmid=7650320 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=7650320  }} </ref>
'''Less Common Complications'''
* [[Cerebrovascular accident|Cerebrovascular]] accidents
* [[Rhabdomyolysis]]
* Acute [[acalculous cholecystitis]]
* [[Erythema nodosum]]
* [[Aortic stenosis]]
* [[Kawasaki syndrome]]
* [[Reactive arthritis]]
* [[Epididymitis]]
* [[Nerve palsy]]
* Male [[hypogonadism]]


===Prognosis===
===Prognosis===
The prognosis of leptospirosis depends upon several known and unknown factors, among which the type of pathogenic serovar and the host’s immune status are the important factors which determines the outcome.<ref name="pmid11292640">{{cite journal| author=Levett PN| title=Leptospirosis. | journal=Clin Microbiol Rev | year= 2001 | volume= 14 | issue= 2 | pages= 296-326 | pmid=11292640 | doi=10.1128/CMR.14.2.296-326.2001 | pmc=88975 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11292640  }} </ref> Most patients recover completely from leptospirosis, but the duration of recovery varies from months to years with or without late sequelae. The late sequelae may include neuropsychiatric problems such as paresis, paralysis, mood swings and depression etc. The major causes of death include renal failure, cardiopulmonary failure, and haemorrhage. Patients with risk factors such as old age and multiple underlying co-morbid conditions are often associated with more severe leptospirosis and increased mortality.
The prognosis of leptospirosis depends upon several known and unknown factors, among which the type of pathogenic [[serovar]] and the host’s immune status are the important factors which determines the outcome.<ref name="pmid11292640">{{cite journal| author=Levett PN| title=Leptospirosis. | journal=Clin Microbiol Rev | year= 2001 | volume= 14 | issue= 2 | pages= 296-326 | pmid=11292640 | doi=10.1128/CMR.14.2.296-326.2001 | pmc=88975 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11292640  }} </ref> Most patients recover completely from leptospirosis but the duration of recovery varies from months to years with or without late sequelae. The late sequelae may include [[neuropsychiatric]] problems such as [[paresis]], [[paralysis]], [[mood swings]] and [[depression]]. The major causes of death include [[renal failure]], [[cardiopulmonary]] failure and [[haemorrhage|hemorrhage]]. Patients with risk factors such as old age and multiple underlying co-morbid conditions are often associated with more severe leptospirosis and increased mortality.


==References==
==References==
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Venkata Sivakrishna Kumar Pulivarthi M.B.B.S [2]

Overview

Leptospirosis is transported by the natural carriers such as feral, semi-domestic, farm and pet animals.[1] Incubation period for leptospirosis varies between 3-20 days. The disease can cause wide range of symptoms from mild flu-like symptoms to severe disease with multi organ failure causing death. 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.[2] The disease leptospirosis is poorly known and unaware of its natural history is mainly due to the wide range of non specific symptoms, subclinical nature of the disease in animals and non specific laboratory tests making the disease difficult to diagnose.[3] Outcome of the patient depends upon the pathogenic serovar and immunological status.

Natural History

Natural history of leptospirosis varies with each patient. It might be mild or asymptomatic, and go unrecognized or in some patients the illness may progress to kidney or liver failure, aseptic meningitis, life-threatening pulmonary hemorrhage and other syndromes.

Acute Phase

Immune phase

  • It is also known as leptospiruric phase.
  • Circulating (IgM) antibodies are produced and leptospires are present in the urine.
  • Characterestic findings that differentiate from other febrile illnesses are myalgia and conjunctival suffusion.[5]
  • Myalgia often involves in calf muscles, less commonly involves abdominal and para-spinal muscles.

Anicteric leptospirosis

  • More common but serious illness is uncommon.
  • Most of cases present either subclinical or of very mild severity.
  • Few cases present with a febrile illness of sudden onset.
  • May progress to aseptic meningitis in ≤25% of patients and more common in younger age group than the patients with icteric leptospirosis.
  • Mortality is very less when compared to icteric leptospirosis.

Icteric leptospirosis

Severe leptospirosis

Sever form of leptospirosis with organ failure including liver and kidney involvement is known as Weil's disease.

Complications

Complications of leptospirosis are associated with localization of pathogen (leptospires) within the tissues during the immune phase, eventually present during the second week of the illness.

Life threatening complications

Common Complications

Less Common Complications

Prognosis

The prognosis of leptospirosis depends upon several known and unknown factors, among which the type of pathogenic serovar and the host’s immune status are the important factors which determines the outcome.[1] Most patients recover completely from leptospirosis but the duration of recovery varies from months to years with or without late sequelae. The late sequelae may include neuropsychiatric problems such as paresis, paralysis, mood swings and depression. The major causes of death include renal failure, cardiopulmonary failure and hemorrhage. Patients with risk factors such as old age and multiple underlying co-morbid conditions are often associated with more severe leptospirosis and increased mortality.

References

  1. ↑ 1.0 1.1 Levett PN (2001). "Leptospirosis". Clin Microbiol Rev. 14 (2): 296–326. doi:10.1128/CMR.14.2.296-326.2001. PMC 88975. PMID 11292640.
  2. ↑ Heuter, Kerry J.,Langston, Cathy E. (2003). "Leptospirosis: A re-emerging zoonotic disease". The Veterinary Clinics of North America. 33: 791–807.
  3. ↑ Vieira ML, Gama-Simões MJ, Collares-Pereira M (2006). "Human leptospirosis in Portugal: A retrospective study of eighteen years". Int J Infect Dis. 10 (5): 378–86. doi:10.1016/j.ijid.2005.07.006. PMID 16600656.
  4. ↑ 4.0 4.1 Bal AM (2005). "Unusual clinical manifestations of leptospirosis". J Postgrad Med. 51 (3): 179–83. PMID 16333189.
  5. ↑ Forbes AE, Zochowski WJ, Dubrey SW, Sivaprakasam V (2012). "Leptospirosis and Weil's disease in the UK". QJM. 105 (12): 1151–62. doi:10.1093/qjmed/hcs145. PMID 22843698.
  6. ↑ Katz AR, Ansdell VE, Effler PV, Middleton CR, Sasaki DM (2001). "Assessment of the clinical presentation and treatment of 353 cases of laboratory-confirmed leptospirosis in Hawaii, 1974-1998". Clin Infect Dis. 33 (11): 1834–41. doi:10.1086/324084. PMID 11692294.
  7. ↑ Salkade HP, Divate S, Deshpande JR, Kawishwar V, Chaturvedi R, Kandalkar BM; et al. (2005). "A study of sutopsy findings in 62 cases of leptospirosis in a metropolitan city in India". J Postgrad Med. 51 (3): 169–73. PMID 16333187.
  8. ↑ Watt G, Padre LP, Tuazon M, Calubaquib C (1990). "Skeletal and cardiac muscle involvement in severe, late leptospirosis". J Infect Dis. 162 (1): 266–9. PMID 2355200.
  9. ↑ 9.0 9.1 Chakurkar G, Vaideeswar P, Pandit SP, Divate SA (2008). "Cardiovascular lesions in leptospirosis: an autopsy study". J Infect. 56 (3): 197–203. doi:10.1016/j.jinf.2007.12.007. PMID 18262280.
  10. ↑ Parsons M (1965). "Electrocardiographic Changes in Leptospirosis". Br Med J. 2 (5455): 201–3. PMC 1846500. PMID 20790602.
  11. ↑ Shaked Y, Shpilberg O, Samra D, Samra Y (1993). "Leptospirosis in pregnancy and its effect on the fetus: case report and review". Clin Infect Dis. 17 (2): 241–3. PMID 8399874.
  12. ↑ Carles G, Montoya E, Joly F, Peneau C (1995). "[Leptospirosis and pregnancy. Eleven cases in French Guyana]". J Gynecol Obstet Biol Reprod (Paris). 24 (4): 418–21. PMID 7650320.
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