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

  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]

  This was also known as tibial fever. Autumn fever (Akiyami fever from the Japanese) Due to the periodicity in temperate climates. [dx.doi.org]

  Yellow fever Relapsing fever Scrub typhus Dengue fever Legionnaires' disease Toxic shock syndrome Investigations The initial diagnosis of leptospirosis is based on clinical features. [patient.info]

  Wikipedia: Leptospirosis Weil's syndrome canicola fever canefield fever nanukayami fever 7-day fever Rat Catcher's Yellows Fort Bragg fever black jaundice ... caused by infection with bacteria of the genus Leptospira and affects humans as well as other [memidex.com]

• Chills

  \ 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]

  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 Symptoms may include fever, headaches, chills, severe muscle pain in the calves and thighs, vomiting, diarrhoea and bloodshot eyes. [hellandback.ie]

  Nature of the disease Leptospiral infections take many different clinical forms, usually with sudden onset of fever, headache, myalgia, chills, conjunctival suffusion and skin rash. [who.int]

• Rigor

  R50.9 ICD-10-CM Diagnosis Code R50.9 Fever, unspecified 2016 2017 2018 2019 Billable/Specific Code Applicable To Fever NOS Fever of unknown origin [FUO] Fever with chills Fever with rigors Hyperpyrexia NOS Persistent fever Pyrexia NOS icterohemorrhagic [icd10data.com]

  Although few rigorous studies have considered the environmental phase of infectious Leptospira bacteria, relevant observations about their presence and survival have been compiled since the beginning of the 20th century ( 30 ) and suggest that environmental [doi.org]

  […] the commencement of antibiotic therapy can sometimes be associated with the development of a Jarisch–Herxheimer reaction. 75 This can start within 1–2 h of the treatment with bacteriocidal antibiotics and consists of a spectrum of fever, tachycardia, rigors [dx.doi.org]

  It is characterized by sudden onset of the following: Fever (38-40 C) Rigors Headache, retro-orbital pain, photophobia Muscle pain localized to the calf and lumbar areas Conjunctival suffusion Dry cough Nausea and vomiting, diarrhea More severe disease [emedicine.com]

• 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]

  Here is what Asus has to say about this new low in the hunt for the ROG Phone 2 Android 10 update: When I said “around the corner” for the first time (which was about 1 month ago), this is what I believed and truly hoped but since then we’ve had to postpone [piunikaweb.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]

  Hunt, PT, DPT PHYSICAL THERAPIST Education: Ithaca College, Bachelor of Science in Clinical Science and Master of Science in Physical Therapy; Simmons College, Doctor of Physical Therapy Licenses: Physical Therapy Special Training/Certification: Mat Pilates [spauldingrehab.org]

• Fatigue

  References: [1] [2] [3] Sleep and Fatigue: Director’s Briefing Fatigue is common amongst the population, but particularly among those working abnormal hours, and can arise from excessive working time or poorly designed shift patterns. [shponline.co.uk]

  "The extreme and continued muscle and joint pain and the fact he is still extremely fatigued and feverish show all the classic signs of Weil's. He is undergoing tests but at least he's in good hands." [independent.ie]

  After an incubation period that can vary from three days to three weeks, most patients suffer severe headaches, red eyes, muscle pains, fatigue, nausea and a temperature of 39C or above. [theguardian.com]

  Sensitivity to light, chills, muscle pain, fatigue and vomiting are also common features of the infection. Due to the likeness, Leptospirosis could be easily dismissed as something less threatening. [devshp.ubmemea.webfactional.com]

  CRITICAL PLANE METHOD FOR MULTIAXIAL FATIGUE LIFE ASSESSMENT OF COMPONENTS UNDER COMBINED BENDING-TORSION LOADING International Journal of Fracture Fatigue and Wear. 3, 90-96 JIAWA LU, W. SUN, A.A. BECKER and ABDULLAH AZIZ SAAD, 2015. [nottingham.ac.uk]

• Cough

  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]

  Ask for an urgent appointment if you have: yellow skin and eyes ( jaundice ) swollen ankles, feet or hands chest pain shortness of breath coughing up blood You might have a serious infection that needs to be treated quickly. [nhs.uk]

  Many infections are mild with fever, headache, myalgia, anorexia, nausea and vomiting, dry cough and lethargy. Affected patients may not seek medical attention. [patient.info]

  Other symptoms may include: conjunctivitis, vomiting, diarrhea, stomach pain, jaundice, cough, and rarely a skin rash. [cdc.gov]

• 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]

• Vomiting

  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]

  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 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]

  After an incubation period that can vary from three days to three weeks, most patients suffer severe headaches, red eyes, muscle pains, fatigue, nausea and a temperature of 39C or above. [theguardian.com]

  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]

  Signs & Symptoms Symptoms of Weil syndrome usually start abruptly, with headache, disturbances in consciousness, pain in muscles and abdomen, a stiff neck, lack of appetite (anorexia), chills, nausea, vomiting, and fever. [rarediseases.org]

• 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]

  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]

  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]

  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]

  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]

• Jaundice

  Severe leptospirosis characterised by profound jaundice is referred to as Weil's disease. [ncbi.nlm.nih.gov]

  Jaundice in experimental leptospirosis in guinea pigs. Can J Comp Med 1977;41:182-7. [Figure 1] [jdrntruhs.org]

  (L. interrogans, especially serotype icterohaemorrhagiae) Note: If left untreated, Weil's disease may cause life-threatening damage to the brain, kidneys, lungs, liver, or heart. — called also leptospiral jaundice, Weil's syndrome [merriam-webster.com]

• Hepatomegaly

  Weil syndrome is characterized by dysfunction of the kidneys and liver, abnormal enlargement of the liver (hepatomegaly), persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice), and/or alterations in consciousness. [rarediseases.org]

  Hepatomegaly. Kidney dysfunction (leptospiral nephropathy) is usual, sometimes with life-threatening acute kidney injury with signs of uraemia and disturbance of consciousness. [patient.info]

  Only 10% of patients with mild leptospirosis progress to the severe form (Weil's disease).[3] Severe leptospirosis (Weil disease, icterohemorrhagic leptospirosis) Clinical features are due to systemic spread and multiorgan involvement Hepatitis; hepatomegaly [amboss.com]

• 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]

  After an incubation period that can vary from three days to three weeks, most patients suffer severe headaches, red eyes, muscle pains, fatigue, nausea and a temperature of 39C or above. [theguardian.com]

  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]

• 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]

  Hemorrhage can occur as petechiae, purpura, conjunctival hemorrhage and gastrointestinal hemorrhage. MOF is associated with a very high mortality. [jdrntruhs.org]

• 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]

  Small purplish-red spots (petechiae) may appear, caused by hemorrhages in the skin. Enlarged lymph nodes, and continued fever may occur for several days. [rarediseases.org]

• Myalgia

  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]

• 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]

  Prostration, coughing, expectoration of blood-stained sputum (hemoptysis), and nosebleed (epistaxis) may also occur. Yellowing of the skin (jaundice), bleeding in muscles, gastrointestinal tract, and visceral organs may be widespread. [rarediseases.org]

• Oliguria

  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. [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]

  Clinical trials included for meta-analysis were compared on the basis of mortality, fever days, numbers of patients presenting with oliguria, and number of patients undergoing need-based dialysis. [ncbi.nlm.nih.gov]

  The considerable tubulo-interstitial involvement explains hypokalaemia such as constant and relevant characteristic of leptospirosis-AKI at the time of diagnosis, regardless of hypercatabolism, rhabdomyolysis, acidosis or oliguria. [elsevier.es]

• 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]

  […] 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]

  Kidney abnormalities may include the appearance of protein (proteinuria), pus (pyuria), or blood in the urine (hematuria), and an excess of urea in the blood (azotemia). The kidney is often enlarged, and its capsule is tense. [rarediseases.org]

• Kidney Failure

  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]

  There is significant and rapid organ damage: liver and kidney failure can occur within 10 days, leading to jaundice (these are the only cases that can properly be called Weil's disease). [theguardian.com]

  Symptoms can range from none at all to a mild flu-like illness, or a more severe illness called Weil's disease, with jaundice and kidney failure. In most cases, with antibiotic treatment, the person will make a complete recovery. [bbc.com]

• Renal Insufficiency

  We report the first case to our knowledge of leptospirosis in a liver transplant recipient who developed jaundice and renal insufficiency. [doi.org]

  In icteric leptospirosis (Weil's syndrome), persistent high fever and jaundice are usually associated with hepatic dysfunction, renal insufficiency, hemorrhage and multi-organ failure (MOF). [jdrntruhs.org]

  Tetracyclines are used but they have disadvantages and are contraindicated for people with renal insufficiency, for children and for pregnant women. Doxycycline is recommended for treatment and short-term chemoprophylaxis. [scielo.br]

• Headache

  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]

  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]

  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 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]

• 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]

  […] cases have been reported in which the etiologic agent was shown to be L. icterohaemorrhagiae.4 In these thirteen cases the clinical course did not differ materially from the usual course.5 In five cases the diagnosis was not made until autopsy.6 Some confusion [jamanetwork.com]

  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]

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]

  Kidney abnormalities may include the appearance of protein (proteinuria), pus (pyuria), or blood in the urine (hematuria), and an excess of urea in the blood (azotemia). The kidney is often enlarged, and its capsule is tense. [rarediseases.org]

  Urinalysis may reveal proteinuria, pyuria, and occasional microscopic hematuria[ 2 ]. Creatine kinase and serum amylase may also be elevated. [doi.org]

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.