Leptospirosis

 

by Jose Santiago

Disease Etiology

Leptospirosis is an infectious, zoonotic disease caused by several serotypes of the spirochete Leptospira interrogans.  Zoonotic refers to a disease that is transmitted by domestic or wild animals to humans [1].  The infection typically occurs when broken skin or mucous membranes are exposed to water or soil that has been contaminated with urine from infected animals [2].  The clinical manifestation of the disease includes fever, jaundice, skin hemorrhage, chills, muscle pain, abdominal pain and diarrhea [3] [4].

 

Disease Transmission

Leptospirosis is typically transmitted when water that has been contaminated with the urine of infected animals comes in direct contact with the mucous membranes or skin abrasions in humans [4].  Once in the body, the spirochete moves through the circulatory system and infects all of the tissues, eventually settling in the kidneys and shed in the urine for weeks after infection [10].  The transmission of the disease through person-to-person contact is not very common [4].

 

Reservoirs

Several wild and domestic animals may serve as reservoirs for to the Leptospira species; some of these include rodents, dogs, cattle, pigs and horses [4].  Given the variety of potential reservoirs involved, people who work outdoors or with animals are at a higher risk of becoming infected with the disease.  Also at higher risk of contracting the disease are people who recreate in contaminated waters [3]. 

 

Specific Microbial Characteristics

Leptospira interrogans is a spirochete (coiled, helical-shaped), gram-negative, aerobic bacteria with a thin body, hooked ends and paired axial flagella [5]. The hooks are used for attachment to the infected tissue.  The antigenic differences in the lipopolysaccharide envelopes that surround their cell walls are used to classify the different serotypes of the bacteria [5].  The optimal growth of Leptospira occurs at 28°C-30°C [5].

 

Specific Tests for Identification

Leptospirosis may be suspected by its clinical manifestation and a thorough medical history review of the patient.  Individuals who work in farms, slaughterhouses, alleys, those who swim in fresh water or victims of flooding should be highly suspicious of having contracted leptospirosis when presenting with a sudden onset of fever, headaches, muscle pain, nausea and skin rash [1] [5].  Laboratory testing is required to confirm the disease.  The laboratory tests consist of the identification of Leptospira interrogans serotypes in blood, tissue, urine and/or cerebrospinal fluid.  Among these, the testing of urine is the most reliable approach due to the presence of the bacteria in this fluid from the onset of symptoms until the third week of infection [5].  Two FDA-approved commercially available tests are an indirect hemmaglutination (MRL) and a dipstick test (PanBio) [4].  However, the most reliable test is the microscopic agglutination test performed by the CDC [5].  Silver staining and immunofluorescence can also be used to identify leptospira in tissue samples such as kidney, liver, spleen and muscles [5].

 

Signs and Symptoms

The signs and symptoms of leptospirosis are variable and can make the diagnosis challenging because of the similarities of its clinical manifestation to other diseases such as dengue and other hemorrhagic fevers [6].  Early symptoms include fever, frequent urination, skin rash that can involve the palate, muscle tenderness, stiff neck, abdominal discomfort and reddened conjunctiva [4] [5].  If the disease progresses to its severe stage the person may experience jaundice (liver damage), renal failure, myocarditis, pulmonary hemmorhagic edema, pancreatitis and vasculitis, with a mortality rate of 5-30% reported in different parts of the world [3] [4] [5] [6].

 

Historical Information

There is evidence in early medical literature of diseases and conditions that could be characterized as leptospirosis, but prior to the advent of microbiology many infectious diseases were attributed to general environmental factors, or miasmas, and not to specific microorganisms as the causative agent of the disease [9].  Leptospirosis was first described as a disease in 1886 by Adolf Weil, and the pathogen responsible (Leptospira) was independently described in the second half of the twentieth century by Inada and Ido in Japan, and Uhlenhuth and Fromme in Germany [6].  Epidemics of leptospirosis were well-documented during World War I and World War II, attributed to close trench combat, rat infestation and muddy water in the former, and to soldiers often bathing in fresh water streams during WWII [8].  A very recent theory attributes the cause of the epidemic disease that afflicted Native Americans during 1616-1619 in New England to leptospirosis [7]. 

 

Virulence Factors

The virulence factors in leptospirosis are not well understood and do not seem to be serotype-specific.  There is a wide variation in the severity of symptoms of the infected individuals that seems independent of the serotype involved [6].  For example, some individuals infected with a particular serotype of L. interrogans may display severe symptoms, while others may have mild symptoms or no symptoms at all [6].  Several factors have been suspected to contribute to the pathogenesis of the bacteria and are currently under study.  As with other pathogenic bacteria, it is believed that the method of motion and the bacterial mechanism of identification and attachment to its target cell are responsible for its infectivity and pathogenesis [10].  It is generally acknowledged that the chemotaxis system (movement in relation to specific chemical gradients) is a factor that contributes to the virulence of bacteria, and this system in L. interrogans was found to be more complex compared to other pathogenic bacteria [10].  Another potential factor that may contribute to its virulence is its unique lipopolysaccharide (LPS) structure [10].    

 

Control/Treatment

Some of the efforts for the control of leptospirosis are directed to the source of the disease while others are directed to the control of disease transmission [10].  When the animal source of the infection is detected this can be isolated (dogs, cattle), vaccinated, denied access to water sources shared with humans, sanitized or, when necessary, killed [10].  The transmission of the disease can be controlled by wearing protective clothing, covering skin lesions, avoiding the manipulation of dead animals and their bodily fluids, washing and cleaning wounds, showering after the manipulation of contaminated material, and disinfecting contaminated areas.

 

If the disease is contracted, in addition to treating the symptoms, the following antibiotics have proven successful in treating the leptospirosis:  penicillin, doxycycline, amoxycilline, erythromycin and ceftriaxone. Severe cases should be treated with high doses of intravenous penicillin and less severe cases may be treated orally with the other antibiotics [1] [10].

     

Prevention/ Vaccines

A few countries offer a human vaccine for leptospirosis, however, the vaccine is serotype-specific and the individual only gains protection to the particular strains included in the vaccine.  Also, vaccinated individuals will still shed bacteria in their urine and be able to spread the infection [10].  Domestic and farm animals may be vaccinated to prevent the spread of the disease but these will also shed the bacteria in the urine and could infect humans [3] [10].

 

In addition to vaccination, 200mg of docycycline by mouth once a week is recommended as a prophylaxis for people in high risk of exposure to the pathogen such as adventure travelers or aid workers responding to flooding or similar disaster zones [1].  The risk of contracting leptospirosis can be reduced by not swimming in potentially contaminated water and by wearing protective barriers (shoes) when walking in areas suspected of contamination (soil) [4].   

 

Local Cases/Outbreaks

Since 1995, healthcare professionals and institutions have not been required to notify the Centers for Disease Control and Prevention the number of suspected cases of leptospirosis.  Leptospirosis is currently not considered a notifiable disease in the United States [11].  Nevertheless, when there is a suspected outbreak of the disease the CDC gets involved.  The most recent outbreaks of leptospirosis reported in the United States occurred in 2005 and involved 46 individuals.  One of the outbreaks occurred in California in July, 2005 involving persons working in a drought-affected stream.  Another outbreak was reported in Florida in November, 2005 and was associated with individuals participating in an adventure race [12].

 

Global Cases/Outbreaks

Due to the similarity of leptospirosis symptoms with other diseases and the lack of accessibility worldwide to a definite diagnostic test, it is believed that the number of cases of the disease is underreported in several parts of the world [3].  As a consequence, the human cases worldwide are not very well-documented and the estimates range widely, from 0.1-1 per 100,000 in temperate climate to 10 or more in humid tropics [3].  Outbreaks of the disease are closely related to flooding, such as the outbreak in Nicaragua in the aftermath of hurricane Mitch in 1995, the outbreak in Peru and Ecuador after heavy flooding in 1998, and the outbreak in India after a cyclone in 1999.  An outbreak was also reported in the United States in 1998 [3].   

References 

 

[1] Johns Hopkins Point of Care Information Technology.  “Leptospirosis”. Last updated 08/28/2009.  http://prod.hopkinsabxguide.org/diagnosis/generalized_infx/leptospirosis.html?&contentInstanceId=255535 03/08/2010

 

[2] World Health Organization – Zoonoses and Veterinary Public Health.  “Leptospirosis”. Last updated 06/23/2009. http://www.who.int/zoonoses/diseases/leptospirosis/en   03/08/2010

 

[3] World Health Organization – Water Sanitation and Health.  “Water-related Diseases - Leptospirosis”. Last updated 2001. http://www.who.int/water_sanitation_health/diseases/leptospirosis/en  03/10/2010

 

[4] Centers for Disease Control and Prevention.  “Leptospirosis”. Last updated 10/12/2005.  http://www.cdc.gov/ncidod/dbmd/diseaseinfo/leptospirosis_g.htm 03/10/2010

 

[5] Gompf, S.; Velez, A.P.: eMedicine from WebMD. “Leptospirosis”. Last updated 08/11/2008. http://emedicine.medscape.com/article/220563-overview  03/10/2010

 

[6] World Health Organization. “Human Leptospirosis: Guidance for Diagnosis, Surveillance and Control”.  Published in 2003. http://www.who.int/csr/don/en/WHO_CDS_CSR_EPH_2002.23.pdf   03/10/2010

 

[7] Marr, J.S.; Cathey, J.T.: CDC.  “Emerging Infectious Diseases. New Hypothesis for Cause of Epidemic among Native Americans, New England, 1616–1619”. Volume 16 (2). February 2010 http://www.cdc.gov/EID/content/16/2/281.htm  03/13/2010

 

[8] Christopher, G.W., etal. Military Medicine. “History of U.S. Military Contributions to the Study of Bacterial Zoonoses”. Volume 170, p39-48. April 2005 http://web.ebscohost.com.lsproxy.austincc.edu/ehost/pdf?vid=5&hid=11&sid=636cc4db-5457-40a5-8f2b-3983d317f5ba%40sessionmgr10  03/13/2010

 

[9] Terpstra, W.J.  Indian Journal of Medical Microbiology. “Historical perspectives in Leptospirosis”. Volume 24 (4), p316-20. October 2006  http://web.ebscohost.com.lsproxy.austincc.edu/ehost/pdf?vid=6&hid=11&sid=636cc4db-5457-40a5-8f2b-3983d317f5ba%40sessionmgr10  03/13/2010

 

[10] Ren, Shuang-Xi; etal. Nature. “Unique physiological and pathogenic features of Leptospira interrogans revealed by whole-genome sequencing”. Volume 422 Issue 6934. 88-892. August 2003.  http://web.ebscohost.com.lsproxy.austincc.edu/ehost/pdf?vid=6&hid=11&sid=636cc4db-5457-40a5-8f2b-3983d317f5ba%40sessionmgr10   03/13/2010

 

[11] Centers for Disease Control and Prevention.  “Morbidity and Mortality Weekly Report”. February 9, 2009 / 56(53) 82. http://www.cdc.gov/mmwr/PDF/wk/mm5653.pdf  03/13/2010

 

[12] Centers for Disease Control and Prevention. MMWR. “Surveillance for Waterborne Disease and Outbreaks Associated with Recreational Water Use and Other Aquatic Facility-Associated Health Events --- United States, 2005-2006”. September 12, 2008 / 57(SS09);1-29 http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5709a1.htm   03/13/2010