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, and Pretibial fever[1]:290) is a bacterial zoonotic disease caused by spirochaetes of
the genus Leptospira 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.

Causes
Leptospirosis is caused by a spirochaete bacterium called Leptospira spp. that has at least
5 serovars 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
contract the disease.

Symptoms
Leptospiral infection in humans causes a range of symptoms, and some infected persons
may have no symptoms at all. Leptospirosis is a biphasic 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.

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.

Diagnosis
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) and PCR. 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 includes dengue 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.

Prevention
Doxycycline may be used to prevent infection in adventure travelers to high risk areas.

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). Corticosteroids
administration 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.

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.

History
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.