LEPTOSPIROSIS

Background
• Leptospirosis is a bacterial disease
that affects humans and animals (a
zoonotic disease). It is caused by
bacteria of the genus Leptospira.
• The leptospiral serovars are
naturally carried in the renal tubules
of rodents, wild and domestic
animals.
• The clinical manifestations of the
disease vary from mild, nonspecific
illness through to severe illness
resulting in acute renal failure,
hepatic failure and pulmonary
haemorrhage.
Scientific Beginning
• 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
 • 1. Direct contact with urine or tissue of
infected animal
- Through skin abrasions, intact mucus
membrane
Modes of • 2. Indirect contact
Transmission - Broken skin with infected soil, water or
vegetation
- Ingestion of contaminated food & water
• 3. Droplet infection
- Inhalation of droplets of infected urine
 Pathophysiology
Leptospira enter the body via contact of the organism with abrasions
or mucous membranes; often as a result of contact with Leptospira
contaminated urine or soil.
There is an incubation period of 2–20 days.
This is followed by a biphasic disease, with an acute spiraemic phase
of approximately 7 days followed by an immunogenic phase
characterised by the production of IgM and later IgG antibodies.
The systemic illness is a consequence of Leptospira invading target
organs such as the kidneys, lungs and liver, resulting in a systemic
vasculitic reaction with endothelial damage
Clinical features and
complications
• Typical symptoms reported in the acute
spiraemic phase include: fever,
headaches, myalgias, rigors, arthalgia,
nausea, vomiting and jaundice. Less
common signs include hepato-
splenomegaly and lymphadenopathy.
• The most serious sequelae occurs during
the immune phase of the disease,
including acute renal failure, hepatic
failure, aseptic meningitis and severe
pulmonary hemorrhage syndrome.
 • Conjunctival suffusion (red
conjunctiva) together with
jaundice is a specific feature of
leptospirosis.
• Dry cough is observed in
Pathognomonic of leptospirosis 20–57% of people with
leptospirosis.
• Thus, this clinical feature can
mislead a doctor to diagnose
the disease as a respiratory
illness. Additionally,
gastrointestinal symptoms such
as nausea, vomiting, abdominal
pain, and diarrhoea frequently
• Leptospira spreads rapidly to all organs through
the bloodstream. They mainly affect the liver.
They invade spaces between hepatocytes,
causing apoptosis. The damaged hepatocytes
and hepatocyte intercellular junctions cause
leakage of bile into the bloodstream, causing
elevated levels of bilirubin, resulting in
jaundice.
• The classic form of severe leptospirosis, known
as Weil's disease, is characterised by liver
damage (causing jaundice), kidney failure, and
bleeding, which happens in 5–10% of those
infected. Lung and brain damage can also occur.
CASE
CLASSIFICATION
• 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.
Clinical case
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, diarrhea
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 10th 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 two (2) different
rapid diagnostic tests.
Laboratory Diagnosis
• The MAT is considered the "gold standard" or cornerstone of
serodiagnosis because of its unsurpassed diagnostic
(serovar/serogroup) specificity in comparison with other currently
available tests.
• Simple serological screening method can be done using the rapid test
kit for Leptospira.
• The ELISA/other rapid tests detect IgM antibodies. The presence of
IgM antibodies may indicate current or recent leptospirosis. A
patient’s serum may be positive 5 to 10 days after onset of symptoms
but not usually before this.
If the initial sample was taken at an early stage in the infection, the
ELISA test may be positive but MAT negative. Therefore a follow-up
sample is required.

The diagnosis is also confirmed by isolation of Leptospires from blood

(first 7 days) or CSF (days 4-10) during the acute illness, from urine
(days ≥ 7) and from tissue samples, by using special media.

For postmortem diagnosis, in addition to serology and culture,

leptospires can be demonstrated in tissues using PCR or
immunohistochemical staining, notably by direct immunofluorescence.
 • For the purpose of notification, all probable
and confirmed cases must be notified to the
NOTIFICATION nearest Health District Office within 1 week
of the date of diagnosis.
TREATMENT
Early treatment with antibiotics is essential.
Adults
• 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), tetracycline,
ampicillin or amoxicillin.
• Third generation cephalosporins, such as ceftriaxone and cefotaxime, and
quinolone antibiotics may also be effective. Jarisch-Herxheimer reactions may
occur after the start of antimicrobial therapy.
• Monitoring and supportive care as appropriate, e.g. dialysis, mechanical
ventilation
Pediatrics
Preferred Alternative Comments

Penicillin:
Penicillin G100000U/ kg/ >8yrs: use in moderate to severe disease
Dose Doxycycline caution in impaired renal function
IV 6hourly x 4mg/kg/dose oral Jarisch-Herxheimer reaction has
7days 12hourly x 7days been
• <8yrs:
Ampicillin
described in patients with
leptospirosis
75-100mg/kg/dose oral Doxycycline:
6hourly x 7days used for only mild disease
or can cause permanent discoloration
• Amoxicillin of teeth
50mg/kg/dose oral 6- Ampicillin/Amoxycillin:
8hourly x 7days 2nd line agent or for pts < 8yrs
Jarisch- • A Jarisch-Herxheimer reaction may occur
following antimicrobial therapy for leptospirosis;

Herxheimer • this is an acute inflammatory response to

clearance of spirochetes from the circulation and
is characterized clinically by fever, rigors, and
reaction hypotension.
• In one series including 262 patients with
leptospirosis, a Jarisch-Herxheimer reaction
occurred in 21 percent of cases; risk factors
included infection with the L.
interrogans serogroup Australis strain and <3
days between symptom onset and antibiotic
therapy
PROPHYLAXIS

The cost effectiveness

and risk versus
benefits of antibiotic
prophylaxis for
leptospirosis remains
unclear. If prophylaxis is
considered, the possible
options include
 • 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:

Pre-exposure Doxycycline 200mg stat dose then weekly throughout

the stay OR
Prophylaxis 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.)
Empirical treatment for Post-Exposure
• 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)
Case Study
10 years old, Malay girl
Underlying Bronchial Asthma
p/w: rapid breathing for 1 day
taken MDI Salbutamol 2 puff X1 but not relieve

- Fever for 6 days

- Cough and runny nose for 2 days
- Reduce oral intake since day 1 of illness
- Diarrhea for 3 days
3 times a day, Bristol 6, no blood
- Lethargic
- History of travelling mass gathering at Malacca
Otherwise,
no vomiting
no history of visiting to jungle, not from dengue hot spot area
On examination:
l Alert, lethargic looking, sunken eyes, conjunctivitis, toungue coated, dry lips
l good pulse volume, warm peripheries, CRT<2sec
l No rashes noted
l Lung: Equal air entry, bilateral crepts, no rhonchi
l CVS: DRNM
l Per Abdomen: soft no guarding, tender over suprapubic region
l No lymph nodes palpable
l BP 91-99/50-62 HR 123-129 T 38.2 SPO2 98-99% under RA

was given bolus 20cc/kg over 30 minutes at triage in view of lethargic

Blood investigations
FBC: Hb 14.7n TWC 3.2 Plt 115
Repeated FBC post bolus: Hb 13.1 TWC 2.3 Plt 72
RP: Urea 6.7 Creat 99 Na 134 K 3.79
LFT: AST 96.8 ALT 17.2 ALP 277 Alb 43.1
CK 551 LDH 853
Dengue serology: Negative
ECG: sinus tachycardic, bedside ECHO no vegetation no pericardial effusion
CXR: Bilateral opacity
Was admitted to ward for
1. Bronchopneumomia complicated with septicemia shock with AKI and
myocarditis, cover for viral
2. Underlying mild persistent bronchial asthma
Admitted with NPO2
Given T PCM 500mg QID and IV Augmentin 1.1g TDS

In ward, hemodynamically unsupported, but had persistent fever.

Leptospirosis serology IgM positive thus diagnosis was revised to
Leptospirosis and antibiotic was escalated to IV Ceftriazone (50mg/kg).
Blood investigations
PBF (6/2/23):
1. Features suggesstive of underlying infection / inflammation
2. Thrombocytopenia secondary to peripheral platelet consumption /
destruction

Lepto MAT (7/2/23): Equivocal

Blood C+S (7/3/23): 5 Days NOG
Mycoplasma (9/3/23): Negative
RSV: Negative
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