1. LEPTOSPIROSIS
Irene Ngu

2. Epidemiology
• Distributed worldwide but mostly in the tropic
• mostly affect populations in rural settings and semi-urban
slums
• Global annual incidence of endemic human leptospirosis: 5
cases per 100 000 population
• Limited studies have suggested that the median annual
incidence:
per 100 000 population
– African Region 95.5
– Western Pacific 66.4
– Americas 12.5
– South-East Asia 4.8
– Europe 0.5
• 5 to 30% of mortality

3. Number of Leptospirosis cases
2004 - 2010
YEAR CASE DEATH
2004 263 20
2005 378 20
2006 527 22
2007 949 22
2008 1263 47
2009 1418 62
2010 1976 69
Source: Report of Morbidity & Mortality for Inpatient for the year
2004-2010 ( PER-PD206); Health Informatics Centre, MOH

6. Outbreak
• Examples of outbreak:
- athletes competing in the Eco-Challenge-Sabah 2000 in
Malaysia; 44% of those who reported feeling ill met the
case definition of leptospirosis. Significant risk factors
included kayaking and swimming in and swallowing
water from the Segama River
-Recreational area in Maran, Pahang in June 2010
- 83 people involved in a search mission after one
person went missing (drowned)
-22 suspected with leptospirosis. 8 persons
died

7. Outbreak in Sarawak 2011
• 148 cases of leptospirosis were recorded from Jan 1 to
Dec 15 (2011), a significant increase considering that
only 49 cases were recorded for the whole of 2010.
-1st outbreak happened at SMK Bandar Baru
Bintangor. 114 students were inflicted with mild flu-
like illness.
- 2nd outbreak involved 5 army recruits after they had
attended a training exercise in Lundu
Read more: http://www.theborneopost.com/2011/12/27/13-die-of-leptospirosis-in-sarawak-this-year/#ixzz1rylzqZih

8. • Epidemics are typically seen during flooding, and
changing environmental trends
• Underreported – misdiagnosed/ undiagnosed
• Age-more in 20-30 years old, rare in young
children and infant- due to low exposure.
• Children are particularly vulnerable to serious
forms of the disease.
• Sex- male > female-greater occupational
exposure to infected animals and contaminated
environment

9. Introduction
• A notifiable disease in Malaysia
• Caused by pathogenic spirochete of the genus leptospira
• L.interrogans
• L.biflexa.
• Others
• Leptospira strains have been divided into 23 sub groups
• Pathogenic or saprophytic leptospires.
• Each sub-group consists of several strains designated as
serovars.
• More than 260 serovars identified. 37 serovars in M’sia.

10. Leptospira interrogans
• A species of genus Leptospira
• Gram negative obligate aerobe spirochete
• Finely coiled, thin, motile
• Periplasmic flagellum for mobility
• 2 important pathogenic serovars from this species
are Canicola and Icterohaemorrhagiae.
• reside in alkaline water, alkaline soil- survive in
these area for months or years
• also could be found in urine

11. Mode of transmission
• Leptospira bacteria have been found in dogs, rats, livestock,
mice, rabbits, frogs, fish, snakes, and certain birds and insects.
• Transmission- direct contact with urine
- contact with soil, water, or plants that have been
contaminated by animal urine.
• Leptospira bacteria can enter the body through cuts or skin
damage areas or through mucous membranes.

15. Pathophysiology
• Gains entry via intact skin or mucosa.
• Multiplies in blood and tissue.
• Spread to any part of the body but particularly affects the
liver and kidney.
• Kidney- migrates to the interstitium, renal tubules, and
tubular lumen, causing interstitial nephritis and tubular
necrosis.
• Renal failure- Usually due to tubular damage
– hypovolemia from dehydration & altered capillary
permeability
• Liver –Centrilobular necrosis with proliferation of Kupffer
cells. Jaundice due to hepatocellular dysfunction.
• Skeletal muscle- causing edema, vacuolization of myofibrils,
and focal necrosis.

16. • Muscular microcirculation is impaired and capillary
permeability is increased, with resultant fluid leakage
and circulatory hypovolemia
• Disseminated vasculitic syndrome may result from
damage to the capillary endothelium.
• Invade aqueous humor of the eye, may persist for
many months, occ lead to chronic or recurrent
uveitis.
• The disease is most often self-limited and nonfatal.
• Systemic immune response may eliminate the organism
from the body but may also lead to a symptomatic
inflammatory reaction that can produce secondary end-
organ injury

17. Clinical Features
• incubation period -2 - 30 days (average 10 days)
• 2phases: (< 50% of cases)
• Begins with flu-like symptoms then briefly asymptomatic
until the second phase begins.
• First phase(1 week ): Septicaemic/ Leptospiremia phase
• Organism may be isolated from blood cultures,
cerebrospinal fluid (CSF), and most tissues.
• High, remittent fever(38-40oC)
• Retroorbital headache, chills and rigors
• Myalgia : paraspinal, calf, abdominal muscle
• Conjuctival suffusion
• Maculopapular/ purpuric skin rashes
• Vomitting

18. • Second stage - immune or leptospiruric stage
– Body's immunologic response to infection
– Circulating antibodies may be detected
– Organism may be isolated from urine
– It may not be recoverable from blood or CSF.
– Lasts 4-30 days
– Disease referable to specific organs is seen.
– These organs include the meninges, liver, eyes, and kidney.
• Nonspecific symptoms, i.e fever and myalgia, less severe than
in the first stage and last a few days to a few weeks.
• Aseptic meningitis is the most important clinical syndrome
observed in the immune anicteric stage.
-lasts a few days but occasionally lasts 1-2 weeks.
• Meningeal symptoms develop in 50% of patients.
• Mild delirium may also be seen.
• Weil’s disease

19. Classification
Leptospirosis
Icteric
Anicteric
leptospirosis
leptospirosis
(weil’s Syndrome)

20. Anicteric leptospirosis
•milder form of the disease.
•Almost 90% of patients have this type of illness.
• Patients have fever, myalgia but do not have jaundice.
remittent fever with chills
- Calf, abdominal & lumbosacral muscles are very
painful & severely tender.
• May have conjunctival suffusion- usually bilateral, most
marked on palpebral conjunctiva, it may be associated
with unilateral or bilateral conjunctival haemorrhage.

21. Other manifestations
•Usually intense headache, sometimes throbbing, commonly
in frontal region, often not relieved by analgesics.
•Renal- usually asymptomatic urinary abnormality i.e mild
proteinuria with few casts & cells in the urine.
•Pulmonary- cough & chest pain and in few cases by
haemoptysis.
•Hemorrhagic tendencies are also present in some patients
•All the clinical features either decrease or disappear within 2
to 3 days and then they reappear.
•DDX: malaria, dengue hemorrhagic fever, viral hepatitis etc.
•In endemic area all cases of fever with myalgia and
conjunctival suffusion should be considered as suspected
cases of leptospirosis.

22. Icteric leptospirosis
•It is the severe form of the disease.
• It is characterized by jaundice and is usually
associated with involvement of other organs.
• About 5-10% of patients have these type of
manifestations.
• profound jaundice
• renal dysfunction
• hepatic necrosis
• pulmonary dysfunction
• hemorrhagic diathesis

23. SSX
• General - rash, fever, bleeding, signs of
hypovolemia/cardiogenic shock
• Icteric - Jaundice, hepatomegaly, abdominal tenderness
• Pulmonary - Cough, hemoptysis, dyspnea, respiratory distress
• Neurologic - Cranial nerve palsies, confusion, changes in
consciousness, delirium, other signs of meningitis
• Ocular - Subconjunctival hemorrhage, uveitis, signs of
iridocyclitis or chorioretinitis
• Hematologic - Bleeding, petechiae, purpura, ecchymosis,
splenomegaly
• Cardiac - Signs of congestive heart failure, pericarditis

25. Investigations
• WBC increased - 3-26/microL; Thrombocytopenia
uncommon.
• CK elevated markly
• UFEME: proteinuria, pyuria, granular casts and occasionally
microscopic hematuria
• LFT: deranged ALT,AST in 40%, usually < 200IU/L, jaundice
in weil’s syndrome
• BUSE: Hyponatremia, hypokalemia
• CSF - neutrophilic or lymphocytic pleocytosis with minimal
to moderately elevated protein and normal glucose.
• CXR- show small nodular densities, which can progress to
confluent consolidation or a ground glass appearance
– alveolar hemorrhage, ARDS, or pulmonary edema

26. Diagnosis
• Culture from clinical specimen
– Blood- within 10 days
– CSF Within 5 - 10 days
– Urine within 10-30 days
• Serology-Rapid test, MAT(gold standard ), ELISA
– 4X rise in titres between acute and convalescent-phase
– A single titer of >1:800 is strong evidence of current or
recent infection with leptospira
– rapid tests, the microplate IgM ELISA and an IgM dot-ELISA
dipstick test
• polymerase chain reaction (PCR)

27. 1. IMR – 03-26162504 (Leptospirosis lab); 03-26162658 (Bacteriology Unit)
2. MKAK –03-61261329/1330 (Bacteriology Unit)

29. 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
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
• GI symptoms such as nausea, vomiting, abdominal pain, diarrhea

30. 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
• Positive culture for pathogenic leptospires
• Demonstration of leptospires in tissues using immunohistochemical staining
• 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.

31. Treatment
• Majority of the infection are self limiting
• Antibiotic
– Shorter duration of illness/ hospital stay, prevent
urinary shedding, rapid resolution of organ
impairment
• General supportive care
• Treatment of complication

32. Antibiotic
• Mild/ outpatient
Doxycycline 100mg BD X 1/52 (2mg/kg/day) Or
Ampicillin 500-750mg 6hourly X 1/52 Or
Amoxicillin 500mg 6hrly X 1/52
• Severe Disease:
IV penicillin G 1.5MU 6hourly X 1/52 Or
IV Ceftriaxone 1g OD X 1/52 Or
IV Cefotaxime 1g 6 hourly

33. Paediatric

34. penicillin allergy:-
• azithromycin (10 mg/kg on D1; max dose 500 mg/day,
followed by 5 mg/kg/day OD ; max dose 250 mg/day)
Or
• clarithromycin (15 mg/kg/day divided in two equal doses;
max dose 1 g/day).
Jarisch-Herxheimer reaction
• Rare complication of treatment
• release of endotoxin-like substances when large numbers
of spirocete are killed by antibiotics
• It is manifested by fever, chills, rigor, hypotension,
headache, tachycardia, hyperventilation, vasodilation with
flushing, myalgia.
• It should be treated supportively

35. Supportive care
• Patients with renal failure may require dialysis;
renal function is restored in most.
• Those with Weil syndrome may need
transfusions of whole blood, platelets, or
both.
• Supportive therapy and careful management
of renal, hepatic, hematologic, and CNS
complications are important.

36. Notification
• All probable and confirmed cases must be
notified to the nearest Health District Office
within 1 week of the date of diagnosis.
• Notification of cases can be done using Rev/ 2010
form
• All notified cases must be investigated using the
Investigation Form

38. Prevention
• Vaccination of domestic animals against leptospirosis provides
substantial protection, but is not effective in 100 percent of
animals.
• Vaccine for human not widely avaiable. Vaccines commercially
available – icterohaemorrhagiae, hardjo, pomona.
• The major control measure available for humans
– to avoid potential sources of infection such as stagnant water, water
derived from run off from animal farms
– rodent control
– protection of food from animal contamination.

39. Prophylaxis
Pre-exposure Prophylaxis
• May be considered for people at high risk of exposure to potentially
contaminated sources e.g. soldiers going into jungles, rescue team
• 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.)

40. Prophylaxis
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)

42. Reference
• Guideline for the diagnosis, management, prevention
and Control of leptospirosis in Malaysia. Disease
Control Division, Department of Public Health, MOH
Malaysia. 2011 1st edition
• www.uptodate.com
• Guidelines for prevention and control of Leptospirosis,
zoonosis division, National institute of communicable
disease, Delhi 2006
• Soo, Lau, Chew, Hu. Sarawak Handbook of Medical
Emergencies, 3rd edition, CE publication, 2011.
• http://www.who.int/topics/leptospirosis/en

45. Thank
You