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leptospirosis

Zoonosis. Etiology: 1) infection with spirochetes of the genus Leptospira 2) direct contact with urine, blood or tissue from an infected animal or exposure to a contaminated water Epidemiology: 1) occurs most commonly in tropics 2) 40-120 cases reported in US annually 3) occupational groups at risk: veterinarians, agricultural workers, sewage workers, slaughterhouse employees, workers in the fishing industry 4) recreational water & domestic animal contact use increase risk 5) outbreaks occur with heavy rains & flooding Pathology: 1) organisms may enter host through abrasions in the skin or through intact mucous membranes 2) multiplication in blood & in tissues 3) vasculitis most important manifestation of disease 4) kidney: interstitial nephritis & tubular necrosis 5) liver: centrilobular necrosis with proliferation of Kupffer cells 6) pulmonary involvement may result in pneumonia, hemoptysis, or ARDS [7] 7) skeletal muscle: vacuolization of myofibrils & focal necrosis 8) antibodies eliminate organism from host except in eye, proximal renal tubules & brain where organism may persist for weeks or months 9) Leptospires in aqueous humor may result in recurrent uveitis - conjunctival suffusion [5] 10) Leptospires in CSF appear not to cause damage to brain 11) antibodies may also produce symptomatic inflammatory response 12) Weil syndrome (severe, icteric leptospirosis) - hepatic necrosis, nephropathy, pulmonary disease [5] Clinical manifestations: 1) may be asymptomatic 2) symptoms vary from mild to serious, even fatal 3) 90% of patients have mild disease 4) incubation period 2-26 days, generally 1-2 weeks 5) may present as an acute flu-like syndrome a) fever/chills b) severe headache (aseptic meningitis) c) nausea/vomiting d) myalgia (especially calves, back, abdomen) e) cough, dyspnea [4] f) nonbloody diarrhea [4] 6) sore throat & rash (maculopapular) less common - generalized rash is rare [5] 7) conjunctivitis; scleral hemorrhage in some cases 8) most patients become asymptomatic within 1 week 9) illness may recur after an interval of 1-3 days a) referred to as immune phase b) coincides with development of antibodies c) aseptic meningitis may develop during immune phase 1] symptoms generally disappear after a few days 2] symptoms may persist for years 10) Weil syndrome (severe, icteric leptospirosis)- jaundice Laboratory: 1) urinalysis: proteinuria, leukocytes, erythrocytes, hyaline or granular casts 2) urine culture (after 1 week) 3) erythrocyte sedimentation rate (ESR) generally elevated 4) complete blood count (CBC): a) leukocytosis with a left shift b) mild thrombocytopenia (associated with renal failure) 5) blood culture (1st 4-10 days) 6) liver function tests (LFTs) a) elevated serum bilirubin b) elevated alkaline phosphatase c) mild increases (to 200 U/L) of serum transaminases 7) prothrombin time may be prolonged in Weil's syndrome (may be corrected with vitamin K) 8) serum lipase markedly elevated (case report) [4] 9) serum creatine kinase increased (50%) 10) cerebrospinal fluid (CSF): a) neutrophils predominate initially b) increases in lymphocytes occur later c) protein may be increased d) glucose normal e) Leptospira culture (1st 4-10 days) 11) Leptospira serology a) microscopic agglutination test (MAT) & ELISA (CDC) [7] b) antibody titer > 1:100 is diagnostic 12) Leptospira antigen 13) Leptospira DNA 14) Leptospira culture 15) isolation of organisms a) from blood or CSF during 1st 4-10 days of illness b) from urine after 1 to several weeks c) culture media 1] Ellinghausen-McCullough-Johnson-Harris (EMJH) 2] Fletcher 3] Korthoff d) Leptospira remain viable in uncoagulated blood for up to 11 days e) isolation is the only means of identifying serotype (called serovar) 16) Leptospira identified in specimen - darkfield examination frequently results in misdiagnosis 17) see ARUP consult [2] Radiology: - chest X-ray a) abnormalities develop after 3-9 days b) most commonly patch alveolar pattern that corresponds to patchy alveolar hemorrhage c) abnormalities most often affects lower lobes & periphery of lung fields Differential diagnosis: 1) malaria 2) enteric fever 3) viral hepatitis 4) dengue 5) Hantavirus infection 6) Rocky Mountain spotted fever Complications: 1) Jarisch-Herxheimer reaction 2) renal failure requiring dialysis 3) Weil's syndrome 4) iritis, iridocyclitis & chorioretinitis are late complications that may persist for years 5) severe pulmonary hemorrhagic syndrome infrequent, but high mortality [7] 6) death (most patients recover) a) mortality highest among elderly b) high fetal mortality when associated with pregnancy Management: 1) general - treatment should be begun as soon as possible - treatment begun after 4 days is still effective 2) pharmaceutical agents a) mild disease - doxycycline 100 mg PO BID for 7 days - ampicillin 500-750 mg PO QID for 7 days - amoxicillin 500 mg PO QID for 7 days b) moderate to severe disease - penicillin G 1.5 million units IV QID for 7 days - ampicillin 1 g IV QID for 7 days - erythromycin 1 g IV QID for 7 days c) prophylaxis: doxycycline 200 mg PO once a week

Related

Leptospira

Specific

Weil's syndrome

General

spirochete infection

References

  1. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 92, 1036-38
  2. ARUP Consult: Leptospira Species The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/content/leptospira-species
  3. Gompf SG, Bronze MS Medscape: Leptospirosis http://emedicine.medscape.com/article/220563-overview
  4. Mixter S, Manesh RS, Keller SC et al Spiraling Out of Control Engl J Med 2017; 376:2183-2188. June 1, 2017 PMID: 28564558 http://www.nejm.org/doi/full/10.1056/NEJMcps1610072
  5. Medical Knowledge Self Assessment Program (MKSAP) 17, 18. American College of Physicians, Philadelphia 2015, 2018
  6. Londeree WA. Leptospirosis: the microscopic danger in paradise. Hawaii J Med Public Health. 2014 Nov;73(11 Suppl 2):21-3. Review. PMID: 25478298 Free PMC Article
  7. Jilg N, Lau ES, Baker MA et al A Treacherous Course N Engl J Med 2021; 384:860-865. March 4 PMID: 33657298 https://www.nejm.org/doi/full/10.1056/NEJMcps2020668