JOURNAL OF THE LOUISIANA STATE MEDICAL SOCIETY
DISCUSSION
Leptospirosis is a worldwide zoonosis of potential fatal consequence found most commonly in warm, humid climates and areas of heavy rainfall and flooding. Estimated incidence is 10 per 100,000 people per year in tropical areas, compared to 0.1 to 1 per 100,000 in temperate climates each year. 1 In the United States, it is estimated between 100 to 200 leptospirosis cases are identified annually. 2 While hundreds of mammals have been found to be potential reservoirs, the brown rat (Rattus norvegicus) is the most important source of human infection. Transmission mainly occurs via direct contact of an infected animal or via indirect contact with water or soil contaminated with urine from an infected animal. 3 Infection results in widely varied presentation, from febrile self-limited illness to severe, life-threatening and deadly disease. Weil’s disease, a severe form of icteric leptospirosis first described in 1886, is characterized by jaundice and renal failure. 4 While it has been reported that approximately 90% of infections result in febrile self-limited illness and only 10% result in Weil’s disease, the presentation seems to vary widely based on factors such as geography, infecting serovars, host factors, and others. 5,6 Currently, the reference standard diagnostic test is the Microscopic AgglutinationTest (MAT), which reacts patient’s sera with live antigen of leptospiral serovars. This test is limited by the need for live organisms and considerable expertise. A number of rapid immunoglobulin IgM ELISA tests has become more readily available, although not widely validated. 3 Recommended treatment for severe cases consists of IV penicillin or ceftriaxone, which has been shown to be non-inferior to penicillin 7 and has the benefit of once daily dosing in addition to the option of intramuscular administration. Oral antibiotic therapy consists of either doxycycline or azithromycin. 3 Despite the lack of high quality, well-designed trials showing the efficacy of antibiotic therapy, one placebo-controlled trial showed improved renal function, shortened hospital duration, and shortened febrile period with penicillin compared to placebo. 8 The paucity of data supporting antibiotic therapy likely stems from the ethical issues of trials for life-threatening illnesses caused by antibiotic- susceptible bacteria. 3 Liver damage, and subsequent elevations of liver enzymes, is caused by a combination of hepatocyte cellular death and disruption of hepatocyte intracellular junctions, which leads to leakage of bile from canaliculi into the sinusoidal blood vessels. 3 The pathophysiology of this is reflected by modest elevations in AST /ALT and a more pronounced direct hyperbilirubinemia. 9 Elevations in indirect, and thus total, bilirubin can also result from hemolysis related to sequealae of infection. 10 Lung involvement presents with hemorrhage secondary to alveolar hemorrhage and has been related to toll-like receptor (TLR) and tumor necrosis factor-alpha (TNF-α) activation and alveolar vasculitis from Leptospira lipoproteins. Cardiac involvement might occur resulting in pericarditis or myocarditis. Acute kidney injury necessitating dialysis is also linked to TLR activation
with incidence of 16-40% in which oliguria predicting worse outcomes and death. 9,11
Clinical presentation is nonspecific and may include symptoms of fevers, chills, headache, myalgia, cough, nausea, vomiting, anorexia, diarrhea, and abdominal pain among others. Conjunctival suffusion, characterized by conjunctival vessel dilation without inflammation, is a hallmark of the disease, but is usually only found in 10 – 28% of cases. 5,6 As one can imagine, any combination of these symptoms could potentially mislead physicians and lead to incorrect diagnoses, such as influenza, upper respiratory infection, acute viral syndrome, hepatitis, gastroenteritis, and meningitis. 6 Thus, a high index of clinical suspicion is warranted.
CONCLUSION
Leptospirosis is a rare but potentially fatal infectious disease that can present in a variety of nonspecific ways. A severe form of the infection is Weil’s disease, which is characterized by jaundice and progressive renal failure. In our case, the detailed history obtained on admission revealed the occupational rodent exposure, which was vital to our diagnosis. A clinician must maintain a high index of suspicion for Leptospiral disease when confronting cholestatic hepatitis, as prompt recognition and treatment are essential.
REFERENCES
1. WHO | Leptospirosis Burden Epidemiology Reference Group (LERG)." WHO. World Health Organization, 13 July 2010. Web. 07 Dec. 2016. 2. Centers for Disease Control and Prevention, author. Leptospirosis. 2015. http://www.cdc.gov/leptospirosis/health_care_workers/ 3. Haake DA, Levett PN. Leptospirosis in humans. Curr TopMicrobiol Immunol. 2015;387:65-97. doi: 10.1007/978-3-662-45059-8_5. Review. 4. Weil A. Ueber eine eigenthümliche, mit Milztumor, Icterus und Nephritis einhergehende, acute Infectionskrankheit. Dtsch Arch Klin Med . 1886; 39:209. 5. Antony SJ. Leptospirosis - An Emerging Pathogen in Travel Medicine: A Review of its Clinical Manifestations and Management. J Travel Med. 1996 Jun 1;3(2):113-118. 6. Katz AR et al. Assessment of the clinical presentation and treatment of 353 cases of laboratory-confirmed leptospirosis in Hawaii, 1974-1998. Clin Infect Dis . 2001 Dec 1;33(11):1834-41. Epub 2001 Oct 23. 7. Panaphut T1, Domrongkitchaiporn S, Vibhagool A, Thinkamrop B, SusaengratW. Ceftriaxone comparedwith sodiumpenicillin g for treatment of severe leptospirosis. Clin Infect Dis . 2003 Jun 15;36(12):1507-13. Epub 2003 Jun 6. 8. Watt G1, Padre LP, Tuazon ML, Calubaquib C, Santiago E, Ranoa CP, Laughlin LW. Placebo-controlled trial of intravenous penicillin for severe and late leptospirosis. Lancet. 1988 Feb 27;1(8583):433-5. 9. Mazhar et al, A 23-year-old Man with Leptospirosis and Acute Abdominal Pain. Hawaii J Med Public Health. 2016 Oct; 75(10): 291–294. PMCID: PMC5056631 10. Avdeeva MG, et al. The role glucose-6-phosphate dehydrogenase in pathogenesis of anemia in leptospirosis. Klin Med (Mosk). 2002; 80:42–44. [PubMed: 12138802] 11. Estavoyer JM, Racadot E, Couetdic G, Leroy J, Grosperrin L. Tumor necrosis factor in patients with leptospirosis. Rev Infect Dis . 1991;13:1245–6. [PubMed]
116 J La State Med Soc VOL 169 SEPTEMBER/OCTOBER 2017
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