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COMMENTARY
Year : 2012  |  Volume : 2  |  Issue : 1  |  Page : 38-39

Leptospirosis: A case of "overdiagnosis" and "underdiagnosis"


1 Department of Nephrology, Pusphagiri Institute of Medical Sciences, Thiruvalla, Kerala, India
2 Department of Nephrology, Medical College, Kozhikkode, Kerala, India

Date of Web Publication3-Dec-2012

Correspondence Address:
Ramachandran Kasi Visweswaran
Department of Nephrology, Pusphagiri Institute of Medical Sciences, Thiruvalla, Kerala
India
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Source of Support: None, Conflict of Interest: None


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How to cite this article:
Visweswaran RK, Sreelatha M. Leptospirosis: A case of "overdiagnosis" and "underdiagnosis". J Acad Med Sci 2012;2:38-9

How to cite this URL:
Visweswaran RK, Sreelatha M. Leptospirosis: A case of "overdiagnosis" and "underdiagnosis". J Acad Med Sci [serial online] 2012 [cited 2019 Dec 14];2:38-9. Available from: http://www.e-jams.org/text.asp?2012/2/1/38/104014

Leptospirosis is now recognized as an emerging global public heath problem. It is a common zoonosis and occurs in most countries in tropical and temperate zones irrespective of the label of a "developed" or "developing" attached to the name of a country. In the developing world, it occurs as an occupational hazard, whereas in the developed world, it may be a recreational hazard. The common factor in both situations is contact with water contaminated with infected urine of rodents or other animals carrying the organism. The first clinical form of Leptospirosis was described by Adolf Weil in 1886 as "Acute infectious disease with enlargement of spleen, Jaundice and nephritis." It was labelled as "Weil's syndrome" only later. The organism was observed first in 1907 from post-mortem renal tissue slice and in 1914, Inada and Ito saw the organism in the liver of Guinea pig injected with the serum of a patient suffering from "Weil's syndrome" and described it as the causative organism. [1] The name Weil's disease was later changed to "Leptospirosis." The fact that it is known by many names in different parts of the world (Canicola fever, Canefeild fever, ManuKayami fever, Pretibial fever, Seven day fever, Swineherd 's fever, Swamp fever, Mud fever, Fort Bragg fever, etc.) speaks for the wide prevalence of the disease.

The crude estimated incidence according to the WHO is between 1 to 10 per million in temperate climates, around 100 per million in tropical climates, and over 1000 per million during epidemics. [2],[3] Warm climate, water logging, or moist soil contaminated with infected rat's urine are favourable conditions and hence usually outbreaks occur in post-monsoon months. The rat carries the organisms in the proximal tubule where they multiply and get excreted through the urine at the rate of millions of organisms/mL while not suffering from the disease. Leptospira survive better in stagnant water with slightly alkaline pH, low salinity, and not directly exposed to sunlight. These ideal conditions prevail on the banks of backwaters of Kerala. One of the earliest epidemics in recent past was recorded in Kottayam during the 1980s and presented at the sixth Asian Pacific Congress of Nephrology in 1986. [4] Thereafter, numerous epidemics and mini epidemics have been reported from many geographical regions across India.

Leptospira (Lepto = thin/fine, Spira = coil) are thin, coiled, motile, slow growing, aerobic organisms belonging to spirochete family. The length varies from 6 to 20 μm. The organism has an outer envelope (OE), periplasmic space, cell wall, cell contents, and flagella. The glucolipopotein (GLP) is a heat stable toxin and can inhibit sodium-potassium ATPase. It also mediates release of IL8, IL1, IL 6, and TNFalpha. The presence or the absence of some GLPs determines whether the organism is saprophytic (L. Bireflexa) or pathogenic (L. Interrogans). The interrogans strain can be identified by noting hooked end like a "question mark" at the tip of the organism. The L. Interrogans complex is divided into 26 sero-groups and 250 different serovars have been identified.

Humans get infected due to entry of the organisms through cuts or abrasions in skin or through intact mucous membrane. Certain occupations are more predisposed to getting the infection-farmers, slaughter house workers, veterinary workers, military personnel. Recreational activities like fresh water swimming, kayaking, and canoeing or even house hold exposure to urine of infected rodents, pets, or walking in water-logged areas contaminated with infected rodent urine.

The organisms multiply in the blood during the leptospiremic phase which lasts for 7-10 days. The organism localizes in the liver, kidneys, and CSF and is excreted through urine. The urinary excretion will be maximal during the early stages but the recovery or demonstration in urine by dark field illumination or culture is usually difficult. If the urine samples are collected after the patient receives systemic alkalis, the yield from culture for leptospira from urine may be higher.

Symptoms develop by 10 days (2-26 day) of exposure to organism. The initial leptospiremic phase may be asymptomatic or associated with "flu-like" symptoms. The organisms are not pyogenic and so acute inflammatory response does not occur. The next phase called the immune phase is associated with systemic and organ specific manifestations like meningitis, hepatitis, renal involvement, hemorrhagic manifestations, pulmonary involvement, fluid and electrolyte disturbances, muscle involvement with rhabdomyolysis, hypotension, and shock. The leptospiral polysaccharides mediate platelet aggregation followed by bleeding, stimulate immune system causing macrophage and B-cell activation and complement-mediated damage. [5]

Renal involvement is mainly due to interstitial nephritis and tubular necrosis. AKI due to leptospirosis is usually nonoliguric with high fractional execretion of K+, leading to hypokalemia. Hypokalemia is also seen in the diuretic phase of ATN. Hyperkalemia may be a problem in those with extensive muscle injury with oliguria and dialysis-dependant AKI.

Leptospirosis is a clinical diagnosis. The modifications to the Faine's criteria proposed by Shivakumar et al. can be used in the clinical setting considering the fact that the milder forms of anicteric Leptospirosis may contribute to nearly 90% of the cases. [6] The IgM antileptospira antibody appears by 3 to 7 days of exposure. Rising titers are more important than a single value. A single antibody titers more than 1:200 to 1:800 may be diagnostic or a four-fold rise in antibody titers is required for diagnosis. The titer can remain elevated for months or ever years. Many subjects could have had asymptomatic past infection with raised antibody titers. The definitive serological investigation is microscopic agglutination test (MAT), the "Gold standard" serologic test. MAT is the reference method and the sero-group-specific assay. Diagnosis of Leptospira by MAT often requires paired serum samples, one acute and one convalescent serum samples, which delay the diagnosis. MAT is necessary for research purposes only and is available only in reference laboratories. IgM-ELISA is more sensitive than MAT. The indirect hemagglutination assay (IHA) has sensitivity of 92% and specificity of 95%. The test is positive in 3 to 5 days of infection. Leptospira antigen detection by RIA detects 10 4 to 10 5 leptospiras/ml and the ELISA detects 10 5 copies /ml. Antigen is detected in blood during the first 10 days of infection. Clean urine should be collected and inoculated into appropriate culture medium within 2 h after voiding. Culture media used are polysorbate-Albumin media and EMJH / Fletcher/Korthof media. Culture takes several weeks and hence its utility is limited in clinical practice. PCR can rapidly conform the diagnosis in the early face of the disease, but does not identify the infecting serovar.

Although leptospirosis is a self-limiting disease, since the causative organism is highly susceptible to antibiotics and mortality is high in those with multiorgan involvement, it is advisable to treat with a course of intravenous crystalline penicillin. The role of antibiotics after 5 th day of onset of illness is controversial. Most clinicians prefer to "err on the wrong side" and administer a course antibiotics empirically even if the patient presents late. Laboratory confirmation is not mandatory for starting treatment if the clinical features are suggestive of Leptospirosis. Aggressive supportive care with strict attention to fluid and electrolyte balance is essential. Most patients require intravascular fluid replacement with crystalloids, as there is excessive third space loss into inflamed muscle compartment. Renal replacement therapy is indicated in acute kidney injury with peritoneal dialysis, hemodialysis, or continuous renal replacement therapies.

Prophylactic treatment with doxycline/amoxicillin decreases the risk of developing the disease. Killed whole-cell leptospiral vaccines for humans are available in some countries. Vaccination using the outer envelope GLPs have also been developed. [7] However, these vaccines do not induce long-term protection against infection and do not provide cross-protective immunity against heterogeneous Leptospira serovars.

In the paper "Clinical profile and outcome of leptospirosis at tertiary care centre in Western Maharashtra" by Patil et al. published in this issue, the authors have reported 23 cases of leptospirosis and added another region in India where leptospirosis is prevalent. In areas where there is an awareness of leptospirosis among the medical personnel, it tends to be over diagnosed, whereas in some areas where it is not known to be prevalent, it is not diagnosed at all. More awareness is required for diagnosis of this condition but too much importance to the blood test should be avoided. Leptospirosis is a clinical diagnosis and sending Leptospira antibody as a routine investigation in all cases of suspected typhoid, pyogenic infection with fever, or PUO is not warranted because in these situations, there would be no reason to suspect Leptospirosis.

 
  References Top

1.Inada R, Ito G, Hoki R, Kaneko R, Ito H. The etiology, mode of infections and specific therapy of Weil's disease. J Exp Med 1916;23:377-402.  Back to cited text no. 1
    
2.Pavli A, Maltezou HC. Travel acquired leptospirosis. J Travel Med 2008;15:447-53.  Back to cited text no. 2
[PUBMED]    
3.WHO: Zoonosis and vetenerary public health, Leptospirosis Burden Epidemiology Reference Group (LERG). World Health Organization: Leptospriosis Epidemic Research Group; 1978.   Back to cited text no. 3
    
4.Visweswaran K, Varghese PK, Raveendran M. Pattern and prognosis of acute renal failure in Weil's syndrome. Proceedings of 3 rd Asian Pacific Congress of Nephrology; 1986. p. 59.  Back to cited text no. 4
    
5.Kasi Visweswaran R. An overview of leptospirosis: Renal and Hepatic syndrome. In: Textbook of Nephrology for the Asian-Pacific physicians. Mandal AK, editor. Second ed. New Delhi: Jaypee Brothers Medical Publishers (P) Ltd; 2004. p. 133-40.  Back to cited text no. 5
    
6.Shivakumar S, Shareek PS. Diagnosis of leptospirosis utilizing modified Faine's criteria. J Assoc Physicians India 2004;52:678-9.  Back to cited text no. 6
[PUBMED]    
7.Koizumi N, Watanabe H. Leptospirosis vaccines: Past, present and future (Symposium). J Postgrad Med 2005;51:210-4.  Back to cited text no. 7
[PUBMED]  Medknow Journal  




 

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