Leptospirosis is a worldwide public health problem. In humid tropical and subtropical areas, where most developing countries are found, it is a greater problem than in those with a temperate climate. The magnitude of the problem in tropical and subtropical regions can be largely attributed to climatic and environmental conditions but also to the great likelihood of contact with a Leptospira-contaminated environment caused by, for example, local agricultural practices and poor housing and waste disposal, all of which give rise to many sources of infection. In countries with temperate climates, in addition to locally acquired leptospirosis, the disease may also be acquired by travellers abroad, and particularly by those visiting the tropics. Leptospirosis is a potentially serious but treatable disease. Its symptoms may mimic those of a number of other unrelated infections such as influenza, meningitis, hepatitis, dengue or viral haemorrhagic fevers. Some of these infections, in particular dengue, may give rise to large epidemics, and cases of leptospirosis that occur during such epidemics may be overlooked. For this reason, it is important to distinguish leptospirosis from dengue and viral haemorrhagic fevers, etc. in patients acquiring infections in countries where these diseases are endemic. At present, this is still difficult, but new developments may reduce the technical problems in the near future. It is necessary, therefore, to increase awareness and knowledge of leptospirosis as a public health threat.

1. LEPTOSPIROSIS
NURUL HIDAYU | NASHRIQ AIMAN | AUDI ADIBAH

2. INTRODUCTION
• Leptospirosis is an infectious
disease caused by pathogenic
bacteria called leptospires, that are
transmitted directly or indirectly
from animals to humans. It is
therefore a zoonosis. Human-to-
human transmission occurs only
very rarely.
• It often peaks seasonally,
sometimes in outbreaks, and is
often linked to climate changes, to
poor urban slum communities, to
occupation or to recreational
activities.
• The clinical course in humans ranges
from mild to lethal with a broad
spectrum of symptoms and clinical
signs.

3. Leptospirosis occurs worldwide but is most common in
tropical and subtropical areas with high rainfall. The disease is
found mainly wherever humans come into contact with the
urine of infected animals or a urine-polluted environment.
DISTRIBUTION
INCIDENCE
 The number of human cases worldwide is not known precisely.
 Estimated annual incidence (WHO)
—0.1 to 1 per 100 000 per year in temperate climates
—10 or more per 100 000 per year in the humid tropics
 Estimated case-fatality rates in different parts of the world have been
reported to range from <5% to 30%
 Seasonal – peak in summer, during rainy/monsoon season

4. Why is there a lack of
recognition of leptospirosis?
 Clinical manifestation wide and varied
 May mimic many other diseases, e.g.
dengue fever and other viral
haemorrhagic diseases
 Diagnostic capabilities are not readily
available (especially in countries
where the disease is highly endemic)
 poor surveillance and reporting of
cases

5. Exposure depends on chance contacts between human and
infected animals or a contaminated environment through
occupational and/or recreational activities. Some groups are
at higher risk to contract the disease such as:
 Workers in the agricultural sectors
 Sewerage workers
 Livestock handlers
 Pet shops workers
 Military personnel
 Search and rescue workers in high risk environment
 Disaster relief workers (e.g. during floods)
 People involved with outdoor/recreational activities such
as water recreational activities, jungle trekking, etc.
 Travelers who are not previously exposed to the bacteria
in their environment especially those travellers and/or
participants in jungle adventure trips or outdoor sport
activities
 People with chronic disease and open skin wounds.
HIGH RISK GROUPS

6. MICROBIOLOGY
Causal agent:
 Leptospira Interrogans is pathogenic to human.
 Pathogenic leptospires belong to the genus
Leptospira (long corkscrew-shaped bacteria, too
thin to be visible under the ordinary
microscope); dark-field microscopy is required.
Main modes of transmission:
 Infection is acquired from contact through
skin, mucosa/ conjunctiva with water or soil
contaminated with the urine of rodents,
carrier or diseased animals in the
environment.
 Ingestion of contaminated water may also
cause infection. There is no documentation of
human to human transmission.
 The incubation usually lasts about 10 days (2
to 30 days).
Most common host: rodent,
especially the common rat
(Rattus norvegicus)

8. • Infection  leptospires appear in the blood 
invade all tissues and organs particularly affecting
the liver and kidney  cleared from the body by
the host's immune response
• May also settle in the convoluted tubules of the
kidneys  shed in the urine for a few weeks to
several months or longer
• Subsequently cleared from the kidneys and other
organs (may persist in the eyes for much longer)
• Produces endotoxin  attach onto the endothelial
cells  capillary vasculitis (endothelial necrosis and
lymphocytic infiltration)
PATHOPHYSIOLOGY

9. • Vasculitis and leakage  petechiae,
intraparenchymal bleeding and bleeding along
serosa and mucosa
• Lost of fluids into the third space  hypovolaemic
shock and vascular collapse
• Humans react to an infection by producing specific
anti-Leptospira antibodies
• Seroconversion – as early as 5–7 days after the
onset of disease – sometimes only after 10 days or
longer – IgM appear somewhat earlier than IgG and
generally remain detectable for months or even
years but at low titre.
PATHOPHYSIOLOGY

10. CLASSIFICATION

11. LEPTOSPIREMIC PHASES

12. Figure 1: Leptospiremic phases in conjunction with the laboratory methods of
diagnosis.
Note: Biphasic nature of leptospirosis and relevant investigations at different stages
of disease. Specimens 1 and 2 for serology are acute-phase specimens, 3 is a
convalescent-phase sample which may facilitate detection of a delayed immune
response, and 4 and 5 are follow-up samples which can provide epidemiological
information, such as the presumptive infecting serogroup

13. • The incubation period is usually 10 days, with a
range of 2 to 30 days.
• The clinical manifestations are highly variable.
Typically, the disease presents in four broad clinical
categories:
(i) a mild, influenza-like illness (ILI);
(ii) Weil's syndrome characterized by jaundice, renal
failure, haemorrhage and myocarditis with arrhythmias;
(iii) meningitis / meningoencephalitis;
(iv) pulmonary haemorrhage with respiratory failure.
CLINICAL MANIFESTATIONS

15. • Clinical diagnosis is difficult because of the varied and
non-specific presentation.
• Confusion with other diseases, e.g. dengue and other
haemorrhagic fevers, malaria, typhoid, melioidosis,
influenza, etc. is particularly common in the tropics.
Presentations may also overlap as the infection
progresses.
CLINICAL MANIFESTATIONS
If a patient dies from leptospirosis, what is the cause
of death?
Important causes of death include renal failure,
cardiopulmonary failure, and widespread haemorrhage.
Liver failure is rare, despite the presence of jaundice.

16. Multiorgan involvement
 Ocular
—Suffusion – dilation of the conjunctival vasculature,
subconjuctival haemorrhage, uveitis
—Icterus scleral with conjunctival suffusion-pathognomic of
Weil’s disease
 GI
– Jaundice not associated with hepatocellular necrosis.
Bilirubin, ALT, AST will normalise
 Renal
– Acute tubular necrosis (direct leptospire injury)
– Interstitial nephritis (relate to Ag-Ab complexes)
CLINICAL MANIFESTATIONS

17.  Cardiac – Myocarditis, 1st degree heart block, coronary
arteritis
 Pulmonary
– Spectrum ranging from cough, dyspnoea, haemoptysis
to ARDS
– Pulmonary haemorrhage may cause death
– Radiology reveals diffuse small opacities which may
disseminate or coalesce
– a sign of intra-alveolar and interstitial haemorrhage
CLINICAL MANIFESTATIONS

19. If patients survive, do they fully
recover from leptospirosis?
 Most patients recover completely from leptospirosis. In some patients, however,
recovery may take months or even years. Late sequelae may occur.
 Late sequelae include chronic fatigue and other neuropsychiatric symptoms such
as headache, paresis, paralysis, mood swings and depression. In some cases,
uveitis and iridocyclitis may be a late presentation of leptospirosis.
 Ocular symptoms are probably attributable to the persistence of leptospires in the
eyes, where they are sheltered from the patient's immune response.
 Apart from eye involvement, the pathogenesis of alleged late or persistent
symptoms is unknown. The existence of persistent or chronic infections has not
been confirmed and "scars" caused during the acute disease have not been
demonstrated.
What are the late sequelae in
leptospirosis?

20. HOW TO DIAGNOSE ?

21. CASE CLASSIFICATION
CLINICAL CASE
A case that is compatible with the following clinical description:
 Acute febrile illness with history of exposure to water and/or environment
possibly contaminated with infected animal urine with ANY of the following
symptoms: Headache
 Myalgia particularly associated with the calf muscles and lumbar region
 Arthralgia
 Conjunctival suffusion
 Meningeal irritation
 Anuria or oliguria and/or proteinuria
 Jaundice
 Hemorrhages (from the intestines and lungs)
 Cardiac arrhythmia or failure
 Skin rash
 Gastrointestinal symptoms such as nausea, vomiting, abdominal pain, diarrhoea
Leptospirosis is difficult to distinguish from a number of other diseases on clinical
grounds alone. History of possible exposure is paramount to aid clinical diagnosis.

22. CASE CLASSIFICATION
PROBABLE CASE
A clinical case AND positive ELISA/other Rapid tests.
CONFIRMED CASE
A confirmed case of leptospirosis is a suspected OR probable case with any one of
the following laboratory tests:
 Microscopic Agglutination Test (MAT),
For single serum specimen - titre ≥1:400
For paired sera - four fold or greater rise in titre
 Positive PCR (samples should be taken within 10 days of disease onset)
 Positive culture for pathogenic leptospires (blood samples should be taken
within 7 days of onset and urine sample after the 10 th day)
 Demonstration of leptospires in tissues using immunohistochemical staining
(e.g. in post mortem cases)
 In places where the laboratory capacity is not well established, a case can be
considered as confirmed if the result is positive by 2 different rapid diagnostic
tests.
 Cases that require confirmation are:
i. Hospitalized cases
ii. All suspected leptospirosis death cases

25. TREATMENT

26.  Severe cases are usually treated with high
doses of IV C-penicillin (2 M units 6 hourly for
5-7 days).
 Less severe cases treated orally with
antibiotics such as doxycycline (2 mg/kg up to
100 mg 12-hourly for 5-7 days), ampicillin or
amoxicillin.
 Third generation cephalosporin, such as
ceftriaxone and cefotaxime, and quinolone
antibiotics may also be effective.
 Monitoring and supportive care as
appropriate, e.g. dialysis, mechanical
ventilation.

27. Pre-exposure Prophylaxis Empirical treatment for Post-Exposure
 May be considered for people at high risk
of exposure to potentially contaminated
sources e.g. soldiers going into jungles,
rescue team, persons involved in activities
in possible high risk areas e.g. adventurous
sports.
 Dose:
Doxycycline 200mg stat dose then
weekly throughout the stay
OR
Azithromycin 500mg stat dose then
weekly throughout the stay (For
pregnant women and those who are
allergic to Doxycycline)
However the benefit of pre-exposure
prophylaxis remains controversial where
possible benefits need to be balanced with
potential side effects (e.g. doxycycline induced
photosensitivity, nausea, etc.)
 In an outbreak, there may be a role for
post exposure prophylaxis for those
exposed to a common source as the
index case.
 Dose:
Doxycycline 200mg stat dose then
followed by 100mg BD for 5 – 7 days for
those symptomatic with the first onset
of fever.
OR
Azithromycin 1gm on Day-1, followed by
Azithromycin 500mg daily for 2 days
(For pregnant women and those who
are allergic to Doxycycline)
PROPHYLAXIS

28. REFERENCE
 GUIDELINES FOR THE DIAGNOSIS, MANAGEMENT,
PREVENTION AND CONTROL OF LEPTOSPIROSIS IN
MALAYSIA BY WHO & ILS & KKM
 DAVIDSON’S PRINCIPLE & PRACTICE OF MEDICINE
22ND EDITION