LEPTOSPIROSIS

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) 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. It 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. In 1916, Inanda and colleagues
described the organism and disease, and noted its presence in rats.

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

Scanning electron microscope 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 5 serovars of importance in the United States and Canada causing disease
in dogs (Icterohaemorrhagiae, Canicola, Pomona, Grippotyphosa, and Bratislava).
There are other (less common) infectious strains. It should however be noted that
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 voles are important primary hosts, a
wide range of other mammals including dogs, deer, rabbits, hedgehogs, cows,
sheep, raccoons, possums, skunks, and even certain marine mammals are also 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, gulleys 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. Abattoir

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 watersport enthusiasts in specific areas as
prolonged immersion in water is known to promote the entry of the bacteria. Surfers
are especially at 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. Occupations at risk include veterinarians, slaughter house workers, farmers,
sewer workers, and persons working on derelict buildings.

Symptoms

In humans, leptospiral infection causes a wide 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; because of the wide range of symptoms the infection is often wrongly
diagnosed. This leads to a lower registered number of cases than there really are.
Symptoms of leptospirosis include high fever, severe headache, chills, muscle
aches, and vomiting, and may include jaundice, red eyes, abdominal pain, diarrhea,
and/or a rash. The symptoms in humans appear after a 4–14 day incubation period.

In animals, the incubation period (time of exposure to first symptoms) 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. [4] 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), though 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). Cardiovascular problems
are also possible.

Diagnosis

Kidney tissue, using a silver staining technique, revealing the presence of

Leptospira 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) 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. 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. 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.
Preventing human infection

Preventing infection relies on a combination of techniques, and when applied

correctly it is possible to reduce the risks to almost zero even in highly-
contaminated environments.

Of course the only 100% effective way is to avoid contact with contaminated water
and animals, thus avoiding exposure to the bacterium. If you are in a high-risk area,
you should always attempt to minimise contact, as there are many hundreds of
other bacteria, viruses and parasites you may be dealing with!

Exposure to water

The vast majority of human cases are from contaminated water, and of those the
majority are occupational cases from areas of the world where agriculture and
rodents mix - rice-farming, cane-growing and so forth. Recreational exposure is
next, with cases amongst swimmers being the obvious top group. Lowest of the risk
groups is occupational exposure in the developed world - water and sewer
engineers, construction, pest control and so on.

Clearly there are problems in preventing exposure in the highest risk activities (rice-
farming and such) and in those areas the only option is to be aware of symptoms
and seek early treatment. At this time there is no universally-agreed human
vaccine, and the preventative use of antibiotics can only be considered for short
periods of very high risk due to their side effects.

Swimming is the greatest risk, and many cases are reported each year from
swimming in contaminated water in activities such as adventure racing, and simple
recreational swimming in local lakes and ponds. There is no practical way to prevent
exposure during swimming, as some water will always enter the mouth. For one-off
activities such as expeditions there is a potential argument for prophylaxis but we
would usually advise education and followup monitoring of participants rather than
widespread medication. Education is also critical for preventing children being
exposed, when playing on or near contaminated water.

Anglers using potentially contaminated sites (urban canals, small ponds etc.) and
bankside/sewer workers should wear splashproof clothing and expecially gloves.
Anglers are at higher risk as it is reasonably common to cause minor cuts with
hooks, knives and the like, and this greatly increases the ease by which the bacteria
can enter the body. Fish caught from suspect areas should of course never be
eaten. Whilst cooking does in theory kill any bacteria within a fish, very often the
level of cooking is insufficient to guarantee safety. Specific guidance is given for
protecting employees in the workplace.

Recreational exposure (swimming, waterskiing, sailing, caving, etc) is clearly done

at the person's own risk and they must weigh up their own balance of risk vs.
desire. The same preventative measures apply - minimise the risk of water entering
the body by any and all means, be aware of the symptoms and seek treatment
immediately should you feel unwell. There are no 'quick fixes' to prevent infection,
and we currently do not advise the use of antibiotics to prevent infections from
recreational exposure. Some swimmers wash their mouths with antibacterial rinse,
though this has not been proved to offer any significant benefit other than keeping
their teeth clean.

Scuba divers, who are particularly at risk of both swallowing water and contact with
broken skin, should opt for drysuits and try as much as possible to avoid swallowing
any water when purging or changing regulators. Commercial divers are required by
their employment regulations and insurance to comply with strict rules when
working in contaminated water, these include the use of hard-hat systems, wash-
down stations and regular medical testing. Specialist tasks such as police recovery
dives must also follow these protocols. It's important for divers to remember that
water can enter the mouth via the hands even without immersion, so when
preparing for a dive, washing masks, wading through shallow water or even
washing equipment after use, sensible hygiene should be followed and broken skin
covered with waterproof dressings.

Remember that this advice applies to FRESH water - the risks in saltwater
are virtually zero.

Animal exposure

One of the major concerns of people contacting us over the years is transmission
from animals. In the developed world the direct exposure to water can often be
minimised, but domestic pets can either bring in rodents or become infected
themselves, and occupational exposure to rodents and other mammals (as part of
garbage collection, pest control, construction or agriculture) is often hard to avoid.
Distinction must be made between infection and carrier-state. An infected animal
has an illness, and will either recover from it or die. A carrier has a colony of
bacteria living in their body but shows no illness. They can remain like this for their
entire lives and suffer no major adverse effects. Both are potential sources of
infection, but clearly an animal that is not a carrier will eventually be safe, one way
or another.

The dominant carriers are rats, but many other rodents and small mammals can
take the role depending on the location, such as raccoons, squirrels, field mice, etc.
- however rats are naturally incontinent and so spread far more urine than other
species. It is usually safe to assume that across the developed world, 1 in 5 wild rats
are carriers of pathogenic leptospires. Carrier-state rats emit bacteria in their urine,
and this is distributed everywhere they go - normally the bacteria die once the urine
dries out, but if it enters water the bacteria can remain viable for longer periods.
Anyone handling wild rats should be aware that their urine, damp soil, bedding and
nearby water are all potential sources of infection - and rat bites themselves can
cause infection both by leptospira and other unrelated organisms.

A dead rat (wherever it may be) remains a risk for a short while, but only in terms of
direct contact. Simple disinfection of the surface after disposal is all that is required.
Once decomposition has advanced, acidity changes in the body will kill leptospires
and of course they cannot survive on a dry skeleton. Similarly, domestic pets that
are contaminated on their coats but not infected (such as for example after
swimming) can be rinsed and dried as usual, and will be no significant risk
thereafter. Dogs and farm livestock are usually vaccinated, cats rarely contract any
infection.

A domestic or farm animal that is infected and ill will be a potential source of
infection during the first few weeks of the disease, but only in terms of bites or
contact with body fluids. Airborne and skin-to-skin transfer is almost impossible and
has never been reported in the wild. During treatment the animal should be handled
with care, and any body fluids cleaned away using disinfectant, but beyond that
there are few risks. Animals should be kept apart to minimise the risk of direct
infection, though again this is statistically rare.

Endemic exposure

Visitors and residents of countries where the bacterium is widespread (such as the
Indian subcontinent) are likely to be exposed to contaminated water as a matter of
course. In these cases it is almost impossible to prevent exposure, and the best
option is to be aware of the early symptoms and react to them. Leptospiral
contamination is akin to malaria in that it will probably always be there, and cannot
realistically be avoided in certain countries.

Visitors to these countries are at a higher risk than residents, as in the resident
population there is a statistically higher immunity, due to childhood infection or
placental antibody transfer. Having said this, there are many pathogenic serovars of
leptospira, and immunity to one does not prevent infection from the others. Nobody
is immune to the disease as a whole, and the serovars found at a selected location
can change over time as host populations change. The highest concentrations of
cases will always be in developing countries where wet farming and rodent
populations combine. Tourists visiting these areas should be aware of the risks and
limit their activities accordingly. Of course, the majority of 'tourist' activities are
perfectly safe even in areas of high risk, but the growth of 'adventure vacations'
with swimming, survival and back-country hiking all increase the dangers. As more
of the world is opened up to tourism, we must accept that the dangers of those
areas are opened up to us.

Overview of the leptospira

bacterium itself

"Leptospires are aerobic spirochetes

whose cells are flexulous, motile,
tightly coiled and have axial flagellae.
Some are pathogenic, though others
are harmless freshwater saprophytes"

• aerobic: requiring oxygen (dissolved in water) to survive.

 • spirochetes: a phylum of 6 bacterial genera, long and coily in shape (as in
the photo).
• flexulous: able to bend and wriggle.
• motile: Able to propel themselves about.
• axial flagellae: a pair of rod-like structures around which the bacteria is
'coiled', which allows the bacteria to move by turning and wriggling. There is
one from each end, both pointing towards the center.
• pathogenic: capable of causing illnesses.
• saprophytes: creatures that feed from decaying organic material.

The bacteria are in general about 0.1µm in diameter and 10-20µm in length. In
comparison, a red blood cell is about 7µm in diameter, so despite being quite long,
the very small width of leptospires makes them difficult to see under optical
microscopes unless a contrast-enhancing technique such as dark-field is used. They
are gram negative and there is no visual difference between serovars. Live
specimens move extremely quickly, and under visible light their rapid rotation can
make them appear as a chain of dots instead of a continual structure. They are
propelled by two flagella, one rooted to each end of the bacterium and inserted
within the membrane, along the axis. The result looks like the bacterium has been
wrapped around a stick, as in the photo. Virulent specimens usually have a
characteristic 'hooked' shape but straight versions are known to exist. When
damaged by chemicals or ingested by phagocytes, the bacterium can collapse into
a tiny spherical ball, where it is presumed to have no pathogenic ability. Leptonema
are generally larger (20% wider and 30% longer), and Turneria parva are smaller
(about half the size). The spiral coiling of all leptospires is right-handed (the same
as the thread on a bolt).

The ability of leptospires to move rapidy (up to 15µm per second) through water is
vital to their life cycle, as they must spread out as much as possible to maximise
the chance of infecting a new host. Their motion does not seem to help them
penetrate tissues but it does impact on their ability to enter the bloodstream.
Typically they spin rapidly on their axis, with one or both ends hooked - though
when moving 'forward' the front end is often straightened. There is of course no
ability to plan a route nor is there a defined front and back end, and they will move
either way.

Classification is based on serological analysis of the antigens of leptospires and

divides all of the bacteria into one of ten genomospecies. Each of these is divided
into serogroups, and then within each group are the serovars. There are over 200
known serovars at this time, but only a fraction of them cause the human and
animal illnesses which all fall under the term 'leptospirosis'. The majority of known
serovars are harmless organisms, or are only known to infect non-human hosts. The
pathogenic bacteria are almost entirely within the L. interrogans genomospecies,
and in that is the serogroup best known for human infection, Icterohaemorrhagiae.
Worth noting is that a genomospecies has been named after Dr Weil (L. weilii) but
this has no connection to Weil's Disease, for which the cuplrit is L. interrogans
serovar Icterohaemorrhagiae or Pomona.
Pres. Diosdado Macapagal Blvd., Metropolitan Park, Pasay
City

Submitted to:

Ms. Mapue

Submitted by:

Jely Ann M. Ramos

Group: 65