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Weil's Disease

Leptospirosis

Weil's disease is a severe and potentially life-threatening zoonotic infection caused by Leptospira, a spirochetal bacterial pathogen. Fever, constitutional symptoms, gastrointestinal irritation and muscle ache progressing to hepatorenal failure, pulmonary dysfunction, and involvement of other organs is the typical clinical presentation. Clinical criteria and microbiological studies are needed to make the diagnosis.


Presentation

Leptospirosis is a widely recognized infection caused by a spirochetal bacteria, Leptospira spp., and virtually any region of the world is considered to be endemic for this infection [1] [2] [3] [4]. These microbial organisms are responsible for chronic renal infections in a range of animal hosts (livestock, medium-sized mammals, rodents, bats, amphibians and various other), who excrete them through urine and contaminate soil, water or even food, which are the primary sources of human exposure [1] [2] [5]. After the acquisition of Leptospira through abraded or damaged skin/mucosal membranes when in contact with contaminated water or soil, the mean incubation period is about 7-14 days (ranging from 2-30 days) [2] [4] [5] [6]. Although the clinical presentation can be quite variable, fever accompanied by chills, myalgia, headaches, meningismus, a nonproductive cough and gastrointestinal complaints (diarrhea, nausea, vomiting and abdominal pain) are seen in the majority of cases [2] [3] [6] [7]. In approximately 10% of patients, a severe form of leptospirosis develops and the term Weil's disease is used to describe the life-threatening organ dysfunction that is encountered, primarily involving the liver and the kidneys [2] [3] [4] [5]. Acute kidney injury (AKI) manifesting as oliguria, or even anuria in the setting of renal failure, together with jaundice, are hallmarks of Weil's disease [2] [4] [5] [6]. In addition, thrombocytopenia and several other factors contribute to hemorrhagic episodes, most frequently in the pulmonary system (presenting as hemoptysis), whereas epistaxis, petechiae, ecchymoses, melena or hematemesis can also develop [2]. Multiorgan failure, acute respiratory distress syndrome (ARDS), circulatory collapse and altered consciousness may all ensue in Weil's disease, which is why mortality rates reach up to 30%, especially in the absence of early recognition and proper therapy [3] [6]. Moreover, older patients and those who suffer from loss of consciousness are at a significantly higher risk for fatal outcomes [2] [3].

Fever
  • Weil disease; Icterohemorrhagic fever; Swineherd's disease; Rice-field fever; Cane-cutter fever; Swamp fever; Mud fever; Hemorrhagic jaundice; Stuttgart disease; Canicola fever Galloway RL, Stoddard RA, Schafer IJ. Leptospirosis.[medlineplus.gov]
  • As fever still remained and was followed by jaundice, decreasing hemoglobin, increasing bilirubin with abnormal value of liver enzymes; other causes of disease were investigated.[ncbi.nlm.nih.gov]
  • Acute undifferentiated fever, i.e., acute fever without an obvious focus of infection, is the most common clinical presentation of both leptospirosis and scrub typhus ( 11 ).[doi.org]
Chills
  • Technical Information for Leptospirosis Clinical Features Symptoms of leptospirosis include fever, headache, chills, muscle aches, vomiting/diarrhea, cough, conjunctival suffusion, jaundice, and sometimes a rash.[web.archive.org]
  • \ ˈvī(ə)lz-, ˈwī(ə)lz- \ Medical Definition of Weil's disease : a severe form of leptospirosis that is characterized by jaundice, chills, fever, muscle pain, shortness of breath, and chest pain and that is caused by a spirochete of the genus Leptospira[merriam-webster.com]
  • In 90% of cases, leptospirosis only causes mild flu-like symptoms, such as headache, chills and muscle pain. However, in some cases the infection is more severe and can cause life-threatening problems, including organ failure and internal bleeding.[web.archive.org]
  • SYMPTOMS Symptoms may include fever, headaches, chills, severe muscle pain in the calves and thighs, vomiting, diarrhoea and bloodshot eyes.[hellandback.ie]
Hunting
  • "Diseases such as leptospirosis that have been around for a very long time are often overlooked amid the hunt for the next newly emerging disease," Alexander said.[sciencedaily.com]
  • High‐risk activities include freshwater swimming, rafting, kayaking, canoeing, fishing, hunting, and trail biking. The 3% to 5% risk of development of photodermatitis in doxycycline‐treated persons should be taken under consideration.[dx.doi.org]
High Fever
  • Symptoms Symptoms begin between 3 and 21 days after exposure, with an influenza-like illness with severe headache, high fever, tiredness, chills, muscle aches and vomiting.[hnbc.org.uk]
  • Symptoms: high fever, severe headache, chills, muscle aches, and vomiting. Also may include jaundice, red eyes, abdominal pain, diarrhea, or a rash.[web.archive.org]
Anemia
  • Severe Weil's syndrome complicated by hemolytic anemia. Int J Infect Dis 2010; 14:e181-2. 6. Baytur YB, Lacin S, Koyuncu FM, et al. Weil's syndrome in pregnancy. Eur J Obstet Gynecol Reprod Biol 2005; 119:132-3. 7.[doi.org]
Hemoptysis
  • Pericorneal reddening, Photophobia Iridocyclitis Retro orbital pain, Rash O looks like a heart for bradycardia Weil's disease mnemonic "WEILS" Wet due to hemorrhage E is to remind me of epistaxis and other hemorrhagic manifestations like petechiae, hemoptysis[medicowesome.com]
  • Desmopressin therapy for massive hemoptysis associated with severe leptospirosis. Am J Respir Crit Care Med. 2003;167:726-28. Kishor KK, Rao PV, Bhat KR, et al. Pancreatitis in Weil’s disease. Trop Doct. 2002;32:230-31.[rarediseases.org]
  • In addition, thrombocytopenia and several other factors contribute to hemorrhagic episodes, most frequently in the pulmonary system (presenting as hemoptysis), whereas epistaxis, petechiae, ecchymoses, melena or hematemesis can also develop.[symptoma.com]
  • Geoff Heffner, Coughing and Hemoptysis, Textbook of Small Animal Emergency Medicine, (229-233), (2018).[doi.org]
  • Pulmonary involvement ranges from 20% to 70% and may manifest with cough, chest pain, dyspnea, hemoptysis, hemorrhage, and adult respiratory distress syndrome.[dx.doi.org]
Vomiting
  • Other symptoms may include: conjunctivitis, vomiting, diarrhea, stomach pain, jaundice, cough, and rarely a skin rash.[web.archive.org]
  • Signs included vomiting in 9 patients, haemorrhages in 6, and renal function was impaired in 6. Creatine phosphokinase levels were found above normal limits in 75% of the cases.[ncbi.nlm.nih.gov]
  • Symptoms of leptospirosis (Weils disease) are a flu like illness with persistent and severe headache leading to vomiting and should be reported to your doctor immediately. Make sure you tell the Dr that you might have been in contact with rat urine.[ukmalt.com]
  • Safety Executive publishes information on Leptospirosis at this weblink: ROSPA (The Royal Society for the Prevention of Accidents) has some excellent guidance at this link: sease.aspx Symptoms: Flue/Fever Muscular Pains/Aches Loss of Appetite Sickness/Vomiting[cambridgecanoeclub.org.uk]
Nausea
  • Although the clinical presentation can be quite variable, fever accompanied by chills, myalgia, headaches, meningismus, a nonproductive cough and gastrointestinal complaints (diarrhea, nausea, vomiting and abdominal pain) are seen in the majority of cases[symptoma.com]
  • Symptoms can take 2 to 26 days (average 10 days) to develop, and may include: Dry cough Fever Headache Muscle pain Nausea, vomiting, and diarrhea Shaking chills Less common symptoms include: Abdominal pain Abnormal lung sounds Bone pain Conjunctivitis[medlineplus.gov]
  • Infection with the bacterium causes an illness which has similar symptoms to flu – temperature, muscle aches and nausea. In mild cases these symptoms can be easily treated and patients will likely recover in a few weeks.[rya.org.uk]
Abdominal Pain
  • Although the clinical presentation can be quite variable, fever accompanied by chills, myalgia, headaches, meningismus, a nonproductive cough and gastrointestinal complaints (diarrhea, nausea, vomiting and abdominal pain) are seen in the majority of cases[symptoma.com]
  • Symptoms can take 2 to 26 days (average 10 days) to develop, and may include: Dry cough Fever Headache Muscle pain Nausea, vomiting, and diarrhea Shaking chills Less common symptoms include: Abdominal pain Abnormal lung sounds Bone pain Conjunctivitis[medlineplus.gov]
  • Later symptoms may include jaundice, eye redness, abdominal pain and diarrhoea. Severe cases can cause failure of kidneys or liver. The disease can be fatal – do not ignore symptoms.[hnbc.org.uk]
Jaundice
  • Abstract Two patients are described with Weil's disease as a rare cause of jaundice. We discuss some features that can lead to early diagnosis.[ncbi.nlm.nih.gov]
  • Severe leptospirosis characterised by profound jaundice is referred to as Weil's disease.[ncbi.nlm.nih.gov]
  • Other symptoms may include: conjunctivitis, vomiting, diarrhea, stomach pain, jaundice, cough, and rarely a skin rash.[web.archive.org]
  • Abstract A case of fulminant leptospirosis is presented, manifesting as rapid progression from acute undifferentiated febrile illness to refractory shock, jaundice, renal failure and massive pulmonary hemorrhage.[ncbi.nlm.nih.gov]
Hepatomegaly
  • Hepatomegaly. Kidney dysfunction (leptospiral nephropathy) is usual, sometimes with life-threatening acute kidney injury with signs of uraemia and disturbance of consciousness.[patient.info]
Red Eye
  • See a GP if you might have been exposed to infected pee and you have: a very high temperature, or feel hot and shivery a headache feeling and being sick aching muscles and joints red eyes loss of appetite These are symptoms of leptospirosis.[nhs.uk]
  • Symptoms of Weils disease typically manifest between three days and three weeks after contact with contaminated water and consist of muscle pains, severe headaches, high temperatures, red eyes, nausea, skin rashes and sometimes hallucinations.[injury-compensation-zone.co.uk]
  • The flu-like illness may resolve without treatment but, in some cases, an immune phase follows with a return of fever, jaundice, red eyes, abdominal pain, diarrhoea, or a rash.[patient.info]
  • Also may include jaundice, red eyes, abdominal pain, diarrhea, or a rash. If the disease is not treated, the patient could develop kidney damage, meningitis, liver failure, and respiratory distress. In rare cases death occurs.[web.archive.org]
Myalgia
  • Abstract A 44-year-old black male presented with fever, myalgia and weakness. He had elevated blood urea nitrogen, creatine phosphokinase and serum glutamic-oxaloacetic transaminase.[ncbi.nlm.nih.gov]
  • The most common presentation involved fever, malaise and myalgia. Conjunctival congestion was found in 75% of the cases and jaundice was encountered in 90% of the cases.[ncbi.nlm.nih.gov]
  • We describe a case of a 53 year old man presenting with myalgia and fever in whom the diagnosis of leptospirosis was not initially considered.[ncbi.nlm.nih.gov]
  • Myalgia and jaundice were recorded in all patients. Signs included vomiting in 9 patients, haemorrhages in 6, and renal function was impaired in 6. Creatine phosphokinase levels were found above normal limits in 75% of the cases.[ncbi.nlm.nih.gov]
  • The patients with thrombocytopenia had higher frequencies of dehydration (53% vs. 35.3%, p 0.001), epistaxis (5.7% vs. 0.8%, p 0.033), hematemesis (13% vs. 4.6%, p 0.006), myalgia (91.5% vs. 84.5%, p 0.038), hematuria (54.8% vs. 37.6%, p 0.011), metabolic[ncbi.nlm.nih.gov]
Petechiae
  • […] conjunctival) Pericorneal reddening, Photophobia Iridocyclitis Retro orbital pain, Rash O looks like a heart for bradycardia Weil's disease mnemonic "WEILS" Wet due to hemorrhage E is to remind me of epistaxis and other hemorrhagic manifestations like petechiae[medicowesome.com]
  • In addition, thrombocytopenia and several other factors contribute to hemorrhagic episodes, most frequently in the pulmonary system (presenting as hemoptysis), whereas epistaxis, petechiae, ecchymoses, melena or hematemesis can also develop.[symptoma.com]
  • The disease is characterized by jaundice, fever, oliguria, headache, myalgia, haemorrhagic tendencies with purpura or petechiae, and enlargement of liver and spleen. The illness lasts from 4 to 9 days.[whonamedit.com]
  • Purpura, petechiae, epistaxis, minor haemoptysis and other signs of bleeding are common. Other symptoms include fever, vomiting, abdominal pain, skin rashes, conjunctival haemorrhage, and uveitis.[patient.info]
Purpura
  • The disease is characterized by jaundice, fever, oliguria, headache, myalgia, haemorrhagic tendencies with purpura or petechiae, and enlargement of liver and spleen. The illness lasts from 4 to 9 days.[whonamedit.com]
  • Haug Browse recently published Learning/CME Learning/CME View all learning/CME CME Case 3-2019: A 70-Year-Old Woman with Fever, Headache, and Progressive Encephalopathy Caplacizumab Treatment for Acquired Thrombotic Thrombocytopenic Purpura Randomized[nejm.org]
  • Purpura, petechiae, epistaxis, minor haemoptysis and other signs of bleeding are common. Other symptoms include fever, vomiting, abdominal pain, skin rashes, conjunctival haemorrhage, and uveitis.[patient.info]
Epistaxis
  • The patients with thrombocytopenia had higher frequencies of dehydration (53% vs. 35.3%, p 0.001), epistaxis (5.7% vs. 0.8%, p 0.033), hematemesis (13% vs. 4.6%, p 0.006), myalgia (91.5% vs. 84.5%, p 0.038), hematuria (54.8% vs. 37.6%, p 0.011), metabolic[ncbi.nlm.nih.gov]
  • […] through animal urine Occipital headache Suffusion (conjunctival) Pericorneal reddening, Photophobia Iridocyclitis Retro orbital pain, Rash O looks like a heart for bradycardia Weil's disease mnemonic "WEILS" Wet due to hemorrhage E is to remind me of epistaxis[medicowesome.com]
  • In addition, thrombocytopenia and several other factors contribute to hemorrhagic episodes, most frequently in the pulmonary system (presenting as hemoptysis), whereas epistaxis, petechiae, ecchymoses, melena or hematemesis can also develop.[symptoma.com]
  • Purpura, petechiae, epistaxis, minor haemoptysis and other signs of bleeding are common. Other symptoms include fever, vomiting, abdominal pain, skin rashes, conjunctival haemorrhage, and uveitis.[patient.info]
  • The more severe manifestations were fever, headache, epistaxis, jaundice, and skin lesions.[web.archive.org]
Hematuria
  • During the first 6 days of this undiagnosed illness azotemia increased, a pericardial friction rub occurred, and hematuria was present.[ncbi.nlm.nih.gov]
  • The patients with thrombocytopenia had higher frequencies of dehydration (53% vs. 35.3%, p 0.001), epistaxis (5.7% vs. 0.8%, p 0.033), hematemesis (13% vs. 4.6%, p 0.006), myalgia (91.5% vs. 84.5%, p 0.038), hematuria (54.8% vs. 37.6%, p 0.011), metabolic[ncbi.nlm.nih.gov]
  • […] findings for leptospirosis and Weil's disease are leukocytosis, thrombocytopenia, elevated blood urea nitrogen (BUN), creatinine, and liver transaminases (alanine and aspartate aminotransferases, or ALT and AST), hyperbilirubinemia, proteinuria, pyuria, hematuria[symptoma.com]
  • Urinalysis may reveal proteinuria, pyuria, and occasional microscopic hematuria[ 2 ]. Creatine kinase and serum amylase may also be elevated.[doi.org]
Headache
  • Technical Information for Leptospirosis Clinical Features Symptoms of leptospirosis include fever, headache, chills, muscle aches, vomiting/diarrhea, cough, conjunctival suffusion, jaundice, and sometimes a rash.[web.archive.org]
  • Mnemonic for leptospirosis "LEPTOSPIRO " Lymphadenopathy Encephalitis (And meningitis) Pain in abdomen Transmitted through animal urine Occipital headache Suffusion (conjunctival) Pericorneal reddening, Photophobia Iridocyclitis Retro orbital pain, Rash[medicowesome.com]
  • Symptoms of leptospirosis (Weils disease) are a flu like illness with persistent and severe headache leading to vomiting and should be reported to your doctor immediately. Make sure you tell the Dr that you might have been in contact with rat urine.[ukmalt.com]
  • Leptospirosis typically presents as a nonspecific, acute febrile illness characterized by fever, myalgia, and headache and may be confused with other entities such as influenza and dengue fever.[ncbi.nlm.nih.gov]
Confusion
  • This interest has prompted confusion and anxiety among recreational water user groups such as canoeists who had not previously seen themselves as being particularly at risk.[ncbi.nlm.nih.gov]
  • A confusing array of laboratory tests is described for the detection of this spirochete and antibodies. The conventional tests include direct microscopy, culture and the most widely used reference standard method -the microscopic agglutination test.[ncbi.nlm.nih.gov]
  • Leptospirosis typically presents as a nonspecific, acute febrile illness characterized by fever, myalgia, and headache and may be confused with other entities such as influenza and dengue fever.[ncbi.nlm.nih.gov]
  • Sometimes the fever may fluctuate and other symptoms such as a rash, jaundice, confusion, depression, kidney failure, liver failure and meningitis may occur. The incubation period is usually 10 days but can range from 4 to 19 days.[hellandback.ie]
  • It is vital that the doctor be told of any waterborne activity you have been involved in as the symptoms are easily confused with those of flu and if you have an otherwise ‘clean occupation’ the possibility of Weil’s Disease may be overlooked in the early[rya.org.uk]

Workup

Because of the possibly life-threatening outcome of Weil's disease, the diagnosis must be made as early as possible. Signs and symptoms of Weil's disease and the initial stages of leptospirosis are not specific for the disease, making a detailed patient history pivotal in identifying recent exposure to contaminated waters, either through the occupational setting (veterinarians, farm and rice workers, hunters, shelter workers, etc.) or during recreational activities (swimming, fishing, caving, rowing) [2]. Furthermore, a thorough physical examination can reveal the potential site where the bacteria may have gained entry into the circulation, but also assess the extent of symptoms and organ involvement, after which a meticulous laboratory workup is necessary. A complete blood count (CBC) renal and kidney function tests, urinalysis and in the setting of meningitis-like symptoms, a lumbar puncture are vital [4]. Typical findings for leptospirosis and Weil's disease are leukocytosis, thrombocytopenia, elevated blood urea nitrogen (BUN), creatinine, and liver transaminases (alanine and aspartate aminotransferases, or ALT and AST), hyperbilirubinemia, proteinuria, pyuria, hematuria, and pleocytosis in the cerebrospinal fluid (CSF), respectively [4] [6] [7]. Moreover, serum inflammatory markers, such as erythrocyte sedimentation rate (ESR), will also be raised [4] [6]. A definite diagnosis, however, is made after confirming Leptospira in urine, blood, or CSF obtained from the patient. In the initial stages of the infection (first 10 days), microscopic detection of bacteria from any of the mentioned samples is widely recommended, primarily because results are provided within the hour, whereas cultivation, equally effective in the first several days, takes at least a few weeks to yield conclusive results [2] [3] [4]. However, low specificity/sensitivity rates require additional testing in most cases [3]. Thus, confirmation of immunoglobulin (Ig) M-specific antibodies through microscopic agglutination test (MAT) or enzyme-linked immunoassay (ELISA) and use of molecular methods - polymerase chain reaction (PCR), are advocated in the later stages of the disease [3] [4] [5] [6].

Pyuria
  • Typical findings for leptospirosis and Weil's disease are leukocytosis, thrombocytopenia, elevated blood urea nitrogen (BUN), creatinine, and liver transaminases (alanine and aspartate aminotransferases, or ALT and AST), hyperbilirubinemia, proteinuria, pyuria[symptoma.com]
  • Urinalysis may reveal proteinuria, pyuria, and occasional microscopic hematuria[ 2 ]. Creatine kinase and serum amylase may also be elevated.[doi.org]

Treatment

  • Role of various antibiotics in treatment of leptospirosis is uncertain, and can be attributed to nonavailability of adequate clinical trials. Role of penicillin in the treatment of leptospirosis can be debated.[ncbi.nlm.nih.gov]
  • Outcomes of treatment for all randomized patients. Overall outcomes of treatment (i.e., death and clinical treatment failure, duration of fever, and duration of organ dysfunction after treatment) were similar among the 3 treatment groups.[doi.org]
  • The distributions of prior antimicrobial treatment were similar in the two treatment groups (data not shown here).[doi.org]
  • […] that treatment prevents progression to severe disease.[doi.org]
  • Treatment with antibiotics and supportive care can manage a high percentage of cases successfully. Newer vaccines developed in response to the change in frequency of certain serovars may decrease the incidence of clinical disease.[ncbi.nlm.nih.gov]

Prognosis

  • The prognosis of all these patients, including that of Weil's disease was excellent. Early recognition and initiation of antibiotic therapy were found to be important.[ncbi.nlm.nih.gov]
  • Prognosis The vast majority of leptospiral infections are self-limiting. However, Weil's disease has a mortality rate of 5-10%.[patient.info]
  • This multisystem illness has a rapidly progressive and often fulminant course characterized by jaundice, hemorrhage, and acute renal failure. 9,13,21,31,34 Thrombocytopenia occurs in up to 50% of cases and is associated with poorer prognosis.[dx.doi.org]

Etiology

  • Etiologic Agent Leptospires are long, thin, motile spirochetes. They may be free-living or associated with animal hosts and survive well in fresh water, soil, and mud in tropical areas.[web.archive.org]
  • Inada and his co-workers 2 in a remarkable series of reports delineated the clinical and pathological picture, described the etiological agent and named it Spirochaeta icterohaemorrhagica.[annals.org]
  • J Exp Med 26:341–353 PubMedCentral PubMed CrossRef Google Scholar Inada R, Ido Y, Hoki R, Kaneko R, Ito H (1916) The etiology, mode of infection, and specific therapy of Weil’s disease (Spirochaetosis Icterohaemorrhagica).[doi.org]
  • Of note, rash as a clinical manifestation of leptospirosis is very rare, and in fact is suggestive of other etiologies in a patient with febrile illness[ 13 ].[doi.org]

Epidemiology

  • The epidemiology of leptospirosis has been modified by changes in animal husbandry, climate, and human behavior. Resurgent interest in leptospirosis has resulted from large outbreaks that have received significant publicity.[ncbi.nlm.nih.gov]
  • Abstract The epidemiological distribution and clinical features of 12 cases of Weil's disease from Turkey, are reviewed. The disease is most common in male farmers from rural areas. Myalgia and jaundice were recorded in all patients.[ncbi.nlm.nih.gov]
  • This review examines the epidemiology of leptospirosis in the UK, over the period 2006-10, the clinical features, diagnostic techniques and treatment.[ncbi.nlm.nih.gov]
  • The aim of this article is to provide clinicians with a concise review of the epidemiology, pathophysiology, clinical features, diagnosis, management and prevention of leptospirosis.[ncbi.nlm.nih.gov]
  • In this Review, we discuss the recent advances in our understanding of the epidemiology, taxonomy, genomics and the molecular basis of virulence in leptospires, and how these properties contribute to the mechanism of pathogenesis of leptospirosis.[ncbi.nlm.nih.gov]
Sex distribution
Age distribution

Pathophysiology

  • The aim of this article is to provide clinicians with a concise review of the epidemiology, pathophysiology, clinical features, diagnosis, management and prevention of leptospirosis.[ncbi.nlm.nih.gov]

Prevention

  • Prevention of leptospirosis revolves around the 'cover-wash-clean up' strategy.[ncbi.nlm.nih.gov]
  • Surveillance The attached excerpt provides WHO recommended standards and strategies for the surveillance, prevention and control of Leptospirosis.[who.int]
  • Gaps in understanding and of adherence to preventive advice were identified. Accordingly, it was concluded that health education for canoeists could be improved.[ncbi.nlm.nih.gov]
  • In addition to their involvement in the prevention, diagnosis, and treatment of leptospirosis in animals, veterinarians serve an important role in public health by providing guidance and information on risk factors and prevention and control measures.[ncbi.nlm.nih.gov]
  • Treatment of leptospirosis involves supportive care and antibiotics, and prevention includes environmental steps and annual vaccination of dogs at risk.[ncbi.nlm.nih.gov]

References

Article

  1. Niloofa R, Fernando N, de Silva NL, et al. Diagnosis of Leptospirosis: Comparison between Microscopic Agglutination Test, IgM-ELISA and IgM Rapid Immunochromatography Test. Dellagostin OA, ed. PLoS ONE. 2015;10(6):e0129236.
  2. Haake DA, Levett PN. Leptospirosis in Humans. Curr Top Microbiol Immunol. 2015;387:65-97.
  3. Musso D, La Scola B. Laboratory diagnosis of leptospirosis: a challenge. J Microbiol Immunol Infect. 2013;46(4):245-252.
  4. Budihal SV, Perwez K. Leptospirosis Diagnosis: Competancy of Various Laboratory Tests. J Clin Diagn Res. 2014;8(1):199-202.
  5. Kokudo T, Nakamura I, Nakamura-Uchiyama F, Komiya N, Ohnishi K. Weil's disease in a patient living in Tokyo. Intern Med. 2009;48(18):1707-1710.
  6. Mandell GL, Bennett JE, Dolin R. Mandel, Douglas and Bennett's Principles and Practice of Infectious Diseases. 8th ed. Philadelphia, Pennsylvania: Churchill Livingstone; 2015.
  7. Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology. Seventh edition. Philadelphia: Elsevier/Saunders; 2013.

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Last updated: 2018-06-22 12:22