Leptospirosis

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Leptospirosis

Classification and external resources

Leptospirose magnified 200 times with dark-field microscope

ICD-10 A27.

OMIM 607948

DiseasesDB 7403

MedlinePlus 001376

eMedicine med/1283 emerg/856ped/1298

MeSH C01.252.400.511

Leptospirosis (also known as Weil's disease, Weil's syndrome, canicola fever, canefield
fever, nanukayami fever, 7-day fever, Rat Catcher's Yellows, Fort Bragg fever, andPretibial fever[1]:290) is
a bacterial zoonotic disease caused by spirochaetes of the genusLeptospira that affects humans and a wide
range of animals, including mammals, birds, amphibians, and reptiles. The disease was first described by Adolf
Weil in 1886 when he reported an "acute infectious disease with enlargement of
spleen, jaundice and nephritis".Leptospira was first observed in 1907 from a post mortem renal tissue slice.[2] In
1908, Inada and Ito first identified it as the causative organism [3] and in 1916 noted its presence in rats.[4]
Though being recognised among the world's most common zoonoses, leptospirosis is a relatively rare
bacterial infection in humans. The infection is commonly transmitted to humans by allowing water that has been
contaminated by animal urine to come in contact with unhealed breaks in the skin, eyes or with the mucous
membranes. Outside of tropical areas, leptospirosis cases have a relatively distinct seasonality with most of
them occurring August–September/February–March.

[ edit]Causes

Scanning electron micrograph of a number of Leptospira sp. bacteria atop a 0.1 µm polycarbonate filter

Leptospirosis is caused by a spirochaete bacterium called Leptospira spp. that has at least 5serovars of
importance in the United States and Canada causing disease in dogs (Icterohaemorrhagiae, Canicola,
Pomona, Grippotyphosa, and Bratislava)[5]. There are other (less common) infectious strains. Genetically
different leptospira organisms may be identical serologically and vice versa. Hence, an argument exists on the
basis of strain identification. The traditional serologic system is seemingly more useful from a diagnostic and
epidemiologic standpoint at the moment (which may change with further development and spread of
technologies like PCR).

Leptospirosis is transmitted by the urine of an infected animal and is contagious as long as it is still moist.
Although rats, mice and moles are important primary hosts, a wide range of other mammals including dogs,
deer, rabbits, hedgehogs, cows, sheep, raccoons, possums, skunks, and certain marine mammals are able to
carry and transmit the disease as secondary hosts. Dogs may lick the urine of an infected animal off the grass
or soil, or drink from an infected puddle. There have been reports of "house dogs" contracting leptospirosis
apparently from licking the urine of infected mice that entered the house. The type of habitats most likely to
carry infective bacteria are muddy riverbanks, ditches, gullies, and muddy livestock rearing areas where there
is regular passage of either wild or farm mammals. There is a direct correlation between the amount of rainfall
and the incidence of leptospirosis, making it seasonal in temperate climates and year-round in tropical climates.

Leptospirosis is also transmitted by the semen of infected animals.[6] Slaughterhouse workers can contract the
disease through contact with infected blood or body fluids.
Humans become infected through contact with water, food, or soil containing urine from these infected animals.
This may happen by swallowing contaminated food or water, or through skin contact. The disease is not known
to be spread from person to person and cases of bacterial dissemination in convalescence are extremely rare
in humans. Leptospirosis is common among water-sport enthusiasts in specific areas as prolonged immersion
in water is known to promote the entry of the bacteria. Surfers and whitewater paddlers [7] are at especially high
risk in areas that have been shown to contain the bacteria, and can contract the disease by
swallowing contaminated water, splashing contaminated water into their eyes or nose, or exposing open
wounds to infected water.[8] Occupations at risk include veterinarians, slaughterhouse workers, farmers, sewer
workers, and people working on derelict buildings, rowers are also sometimes known to contact the disease.[5]

[ edit]Symptoms
Leptospiral infection in humans causes a range of symptoms, and some infected persons may have no
symptoms at all. Leptospirosis is abiphasic disease that begins with flu-like symptoms (fever, chills, myalgias,
intense headache). The first phase resolves, and the patient is briefly asymptomatic until the second phase
begins. This is characterized by meningitis, liver damage (causing jaundice), and renal failure. The infection is
often wrongly diagnosed due to the wide range of symptoms. This leads to a lower registered number of cases
than actually exist. Symptoms of leptospirosis include high fever, severe headache, chills, muscle aches,
and vomiting, and may include jaundice, red eyes, abdominal pain, diarrhea, and rash. The symptoms in
humans appear after a 4–14 day incubation period.

The incubation period (time of exposure to first symptoms) in animals is anywhere from 2 to 20 days. In dogs
the liver and kidney are most commonly damaged by leptospirosis. Vasculitis can occur, causing edema and
potentially disseminated intravascular coagulation (DIC).Myocarditis, pericarditis, meningitis, and uveitis are
also possible sequelae.[5] One should strongly suspect leptospirosis and include it as part of a differential
diagnosis if the sclerae of the dog's eyes appear jaundiced (even slightly yellow). The absence of jaundice
does not eliminate the possibility of leptospirosis, and its presence could indicate hepatitis or other liver
pathology rather than leptospirosis. Vomiting, fever, failure to eat, reduced urine output, unusually dark or
brown urine, and lethargy are also indications of the disease.

[ edit]Complications
Complications include meningitis, extreme fatigue, hearing loss, respiratory distress, azotemia, and renal
interstitial tubular necrosis, which results in renal failure and often liver failure (the severe form of this disease is
known as Weil's disease, though it is sometimes named Weil Syndrome).[9] Cardiovascular problems are also
possible.

[ edit]Diagnosis
Kidney tissue, using a silver stainingtechnique, revealing the presence ofLeptospira bacteria

On infection the microorganism can be found in blood for the first 7 to 10 days (invoking serologically
identifiable reactions) and then moving to the kidneys. After 7 to 10 days the microorganism can be found in
fresh urine. Hence, early diagnostic efforts include testing a serum or blood sample serologically with a panel of
different strains. It is also possible to culture the microorganism from blood, serum, fresh urine and possibly
fresh kidney biopsy. Kidney function tests (Blood Urea Nitrogen and creatinine) as well as blood tests for liver
functions are performed. The latter reveal a moderate elevation of transaminases. Brief elevations of aspartate
aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) levels are
relatively mild. These levels may be normal, even in children with jaundice. Diagnosis of leptospirosis is
confirmed with tests such as Enzyme-Linked Immunosorbent Assay (ELISA) andPCR. Serological testing, the
MAT (microscopic agglutination test), is considered the gold standard in diagnosing leptospirosis. As a large
panel of different leptospira need to be subcultured frequently, which is both laborious and expensive, it is
underused, mainly in developing countries.

Differential diagnosis list for leptospirosis is very large due to diverse symptomatics. For forms with middle to
high severity, the list includesdengue fever and other hemorrhagic fevers, hepatitis of various etiologies,
viral meningitis, malaria and typhoid fever. Light forms should be distinguished from influenza and other related
viral diseases. Specific tests are a must for proper diagnosis of leptospirosis. Under circumstances of limited
access (e.g., developing countries) to specific diagnostic means, close attention must be paid to anamnesis of
the patient. Factors like certain dwelling areas, seasonality, contact with stagnant contaminated water (Bathing
swimming, working on flooded meadows, etc.) and/or rodents in the medical history support the leptospirosis
hypothesis and serve as indications for specific tests (if available).

Leptospira can be cultured in Ellinghausen-McCullough-Johnson-Harris medium, which is incubated at 28 to

30 °C.[10] The median time to positivity is three weeks with a maximum of 3 months. This makes culture
techniques useless for diagnostic purposes, but is commonly used in research.

[ edit]Prevention
Doxycycline may be used to prevent infection in adventure travelers to high risk areas.[11]

[ edit]Treatment
Leptospirosis treatment is a relatively complicated process comprising two main components: suppressing the
causative agent and fighting possible complications. Aetiotropic drugs are antibiotics, such
as cefotaxime, doxycycline, penicillin, ampicillin, and amoxicillin (doxycycline can also be used as
a prophylaxis). There are no human vaccines; animal vaccines are only for a few strains, and are only effective
for a few months. Human therapeutic dosage of drugs is as follows: doxycycline 100 mg orally every 12 hours
for 1 week or penicillin 1–1.5 MU every 4 hours for 1 week. Doxycycline 200–250 mg once a week is
administered as a prophylaxis.[citation needed] In dogs, penicillin is most commonly used to end the leptospiremic
phase (infection of the blood), and doxycycline is used to eliminate the carrier state.

Supportive therapy measures (esp. in severe cases) include detoxification and normalization of the hydro-
electrolytic balance. Glucose and salt solution infusions may be administered; dialysis is used in serious cases.
Elevations of serum potassium are common and if the potassium level gets too high special measures must be
taken. Serum phosphorus levels may likewise increase to unacceptable levels due to renal failure. Treatment
for hyperphosphatemia consists of treating the underlying disease, dialysis where appropriate, or oral
administration of calcium carbonate, but not without first checking the serum calcium levels (these two levels
are related). Corticosteroidsadministration in gradually reduced doses (e.g., prednisolone starting from 30–
60 mg) during 7–10 days is recommended by some specialists in cases of severe haemorrhagic effects. Organ
specific care and treatment are essential in cases of renal, liver or heart involvement.

[ edit]Epidemiology
Annual rates of infection vary from 0.02 per 100,000 in temperate climates to 10 to 100 per 100,000 in tropical
climates.[11]
[ edit]History

The Indian lifestyle exposed them to the leptospiral life cycle.

Leptospirosis was postulated as the cause of an epidemic among native Americans along the coast of present-
day Massachusetts that occurred immediately before the arrival of the Pilgrims in 1620 and wiped out most of
the native population.[12] Earlier proposals included plague, yellow
fever, smallpox, influenza,chickenpox, typhus, typhoid fever, trichinellosis, meningitis, and syndemic infection
of hepatitis B virus with the delta agent.[13][14][15][16] None are as consistent with all the evidence as leptospirosis.
While the disease may have been brought to the New World by Europeans, its spread was also influenced by
the high-risk quotidian activities of the Native Americans. The leptospirosis hypothesis is supported by the
occurrence of modern outbreaks identified as severe leptospirosis, some accompanied by high mortality rates
(the Andaman Islands in the late 1980s, the Philippines in 2009, Ireland in 2010).[17][18][19]

The cause of this epidemic has been a mystery, while other outbreaks in the same time frame are fairly well
established. The epidemic is considered a pivotal event in American history since the failure of the Plymouth
Bay colony might have meant the failure of British colonization in North American [20] A noted historian has said
that the epidemic was the most important event in American history between the discovery of America by
Columbus and the signing of the Declaration of Independence.[citation needed]

Before Weil's characterization in 1886, the disease known as infectious jaundice was very likely the same as
Weil's disease, or severe icteric leptospirosis. During the Egyptian campaign, Napoleon's army suffered from
what was probably infectious jaundice.[21] Infectious jaundice occurred among troops during the American Civil
War.[22] It was also reported among troops at Gallipoli and other battles of World War I, where the sodden
conditions of trench warfare favored infection. Terms used in early 20th century descriptions of leptospirosis
include the pseudo-dengue of Java, seven-day fever, autumn fever, Akiyama disease and marsh or swamp
fever. L icterohaemorrhagieae was identified as the causative agent in Pre-World War II outbreaks in Japan,
which were characterized by jaundice and a high mortality rate.

[ edit]References
1. ^ James, William D.; Berger, Timothy G.; et al. (2006). Andrews' Diseases of
the Skin: clinical Dermatology. Saunders Elsevier. ISBN 0-7216-2921-0.

2. ^ Stimson AM (1907). "Note on an organism found in yellow-fever

tissue." Public Health Reports 22:541.

3. ^ Inada R, Ito Y. A report of the discovery of the causal organism (a new

species of spirocheta) of Weil's disease. Tokyo Ijishinshi. 1908;1915:351-60.

4. ^ Inanda R, Ido Y, Hoke R, Kaneko R, Ito H. The Etiology, Mode of Infection

and Specific Therapy of Weil's Disease. J Exper Med 23;377:1916.

5. ^ a b c Langston CE, Heuter KJ (July 2003). "Leptospirosis. A re-emerging

zoonotic disease". The Veterinary clinics of North America. Small animal

practice 33 (4): 791–807. doi:10.1016/S0195-5616(03)00026-

3. PMID 12910744.

6. ^ Kiktenko VS; Balashov, NG; Rodina, VN (1976). "Leptospirosis infection

through insemination of animals". J Hyg Epidemiol Microbiol Immunol. 21 (2):

207–213. PMID 987112.

7. ^ Kayaking as a risk factor for leptospirosis. Shaw RD, Mo Med. 1992;
89(6):354-7 (ISSN: 0026-6620)

8. ^ Seven Surfing Sicknesses, .

9. ^ Weil syndrome definition - Medical Dictionary definitions of popular medical

terms easily defined on MedTerms

10. ^ Rule PL, Alexander AD (1986). "Gellan gum as a substitute for agar in
leptospiral media". J Clin Microbiol 23 (3): 500–504.PMID 3754265.

11. ^ a b Pavli A, Maltezou HC (2008). "Travel-acquired leptospirosis". J Travel

Med 15 (6): 447–53. doi:10.1111/j.1708-8305.2008.00257.x.PMID 19090801.

12. ^ Marr JS, Cathey JT. New hypothesis for cause of an epidemic among
Native Americans, New England, 1616–1619. Emerg Infect Dis [serial on the

Internet]. 2010 February, DOI: 10.3201/edi1602.090276 CDC.gov

13. ^ Webster N. A brief history of epidemic and pestilential diseases. Hartford

(CT): Hudson and Goodwin; 1799

14. ^ Williams H. The epidemic of the Indians of New England, 1616-1620, with
remarks on Native American infections. John Hopkins Hospital Bulletin.

190920:340-9.

15. ^ Bratton TL. The identity of the New England Indian epidemic of 1616-19.
Bull Hist Med. 1988;62:351-83.

16. ^ Speiss A, Speiss BD. New England pandemic of 1616-1622. cause and
archeological implication. Man in the Northeast. 1987;34:71-83.

17. ^ Vijayachari P, Sugunan AP, Sharma S, Roy S, Natarajaseenivasan K,

Sehgal SC. Leptospirosis in the Andaman Islands, India. Trans R Soc Trop

Med Hyg. 2008;102:117-22. DOI: 10.1016/j.trstmh.2007.08.012

18. ^ ProMED-mail. Leptospirosis - Philippines (02): background. ProMED-mail

2009; 18 Oct: 20091018.3579. Promedmail.org, Accessed 16 January 2010.

19. ^ ProMED-mail. Leptospirosis, fatal - Ireland (02): background. ProMED-mail

2010; 06 Jan: 20100106.0055. Promedmail.org Accessed 16 January 2010.

20. ^ 1616: The Counterfactual

21. ^ Strong RP. Stitt's Diagnosis, Prevention and Treatment of Tropical

Diseases. Seventh Edition. Blakiston: York PA; 1944.
 22. ^ Neill M. The problem of acute infectious jaundice in the United States.
Public Health Rep. 1918;33:717-26.

[ edit]External links
 The Leptospirosis Information Center

 U.S. Disease Control and Prevention Center page on Leptospirosis

 Leptonet.net - the Leptospirosis information portal

 International Leptospirosis Society page

 A Symposium on Leptospirosis: Collection of peer-reviewed articles from The

Journal of Postgraduate Medicine

 Leptoinfo.com - A website for Dog Owners and Veterinary Professionals

dedicated to sharing information on Leptospirosis in Canada

[ edit]Further reading
 Bharti, A. R., et al. (2003), "Leptospirosis: a zoonotic disease of global
importance", Lancet Infect. Dis. 3:12 757-71
[hide]
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Infectious diseases · Bacterial diseases: non-proteobacterial G- (primarily A00-A79, 001-041,080-109)

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