Leptospirosis

Suresh Kumar
Infectious Diseases unit
Hospital Sungai Buloh

Suresh, HSB
 "Bathe and you will become
clean. So he went down and
immersed himself seven times in
the Jordan, as Elisha had told
him to do. And his flesh became
clean once more like the flesh of
a small child."
II Kings 5:14

Suresh, HSB
 AN OUTBREAK OF
LEPTOSPIROSIS AMONG ISRAELI
TROOPS NEAR THE JORDAN
RIVER

Am. J. Trop. Med. Hyg., 74(1), 2006, pp.

127-131
E. HADAD, A. PIROGOVSKY, C. BARTAL, J. GILAD*, A. BARNEA, S.
YITZHAKI, I. GROTTO, R. D. BALICER, AND E. SCHWARTZ

Suresh, HSB
Suresh, HSB
 Leptospirosis outbreaks in Malaysia
 Outbreak of Acute Febrile Illness Among Atheletes
Participating in Eco-Challenge-Sabah 2000---
Borneo, Malaysia, 2000
 Segama River was the primary source of infection
 68 (44%) met clinical case definition of leptospirosis
CDC, MMWR Weekly Jan 19, 2001/50(02);21-24
• Outbreak associated with swimming (46 cases),
Beaufort, Sabah,
Koay et al, MJM, 2004
• Outbreaks amongst military personnel, Perak 2005
& 2006, 2008
• Outbreaks amongst PKN trainees, Melaka, 2006,
2007
• Outbreak following flood in Johor

Dr FAIRUZ AMRAN, Institute for Medical Research

Leptospires
• Tightly coiled
spirochetes
• Requires
special media
to grow
• Very slow
grower

Suresh, HSB
 Classification
• Serological classification
• 2 species
• L. interrogans – all pathogenic
strains
• L. biflexia – saphyrophytic
strains from the environment
• L. interrogans has more than
200 serovars
• Serovars that are
antigenically related are
grouped into serogroups

CMR, Apr 2001. p296-326

Suresh, HSB
 Risk factors for Infection
• Occupational
• Direct contact – livestock farmers, veterinarians
• Indirect contact – sewer workers, soldiers, miners,
rice field workers, Palm plantations
• Activities of daily care
• Walking bare foot in damp conditions
• Gardening with bare hands
• Dogs, rats
• Recreational
• Water sports

Suresh, HSB
Leptospirosis – Disease of Leisure

Suresh, HSB
 Transmission

Maintenance host
(Kidneys)

Urine

Forest Pastures Rice fields Houses Waters Rivers

Susceptible Hosts
 MAINTENANCE HOSTS

PIGS RATS DOGS CATTLE

(pomona) (34 serovars) (canicola) (hardjo)

ENVIRONMENT
 Serological Prevalence in
Domestic animals
Cattle 558/1378 40.5 %
Buffaloes 133/429 31.0 %
Pigs 139/869 16.0 %
Goats 29/657 4.4 %
Sheep 3/44 6.8 %

Overall 862/3377 25.5 %

Bahaman, A.R. , Ibrahim, A.L. and Adam, H. (1987): Serological prevalence of leptospiral
infection in domestic animals in West Malaysia. Epidemiology and Infection 99: 379-392
 Leptospirosis in Malaysia, 2007: Serovar types by MAT

Ballum
Grippotyph
Tarrasovi
Icterohemo
Pomona
Celledoni
Canicola
Hardjo
Autumnalis
Hebdomad
Australis
Pyrogenes
Cynopteri
Javanica
Djasiman
Bataviae
Sejroe
0 20 40 60 80 100 120

Dr FAIRUZ AMRAN, Institute for Medical Research

 Clinical Presentation
• Typically, the disease presents in four
broad clinical categories:
1. mild, influenza-like illness;
2. Weil's syndrome characterized by jaundice, renal
failure, haemorrhage and myocarditis with
arrhythmias;
3. meningitis/meningoencephalitis;
4. pulmonary haemorrhage with respiratory failure
Leptospirosis-Associated Pulmonary Haemorrhage
Syndrome (LPHS).

Suresh, HSB
 Clinical Presentation
• Acute sudden-onset headache
• Fever of over 39°C
• Bilateral conjunctival suffusion ('pink-
eye'),
• Myalgia (particularly associated with the
calf muscles and lumbar region)
• Clinical signs of meningism
(photophobia, neck stiffness, etc.)

Suresh, HSB
Clinical findings for 353 confirmed cases of
leptospirosis,
Hawaii, 1974–1998.

• Fever - 99%
• Myalgia - 91%
• Headache - 89%
• Backache – 51%
• Jaundice – 39%
• Conjunctival suffusion – 28%
• Nuchal rigidity – 27%
CID 2001; 33:1834–41
Suresh, HSB
• The diagnosis is more difficult when
patients present with symptoms of
cough, dyspnoea, nausea, vomiting,
abdominal pain, diarrhoea, arthralgias
and a skin rash

Suresh, HSB
Clinical findings for 353 confirmed cases of
leptospirosis,
Hawaii, 1974–1998.

• Chills – 87%
• Anorexia – 82%
• Nausea – 77%
• Vomiting – 73%
• Arthralgia – 59%
• Diarrhea – 53%
• Abdominal pain – 51%
CID 2001; 33:1834–41
Suresh, HSB
• 19 year old malay male was admitted on
17.05.05 in Malacca general hospital
• 1 week history of fever and sore throat.
• Cough initially whitish, became blood stained 3
days later
• He developed dyspnoeic and had pleuritic chest
pain one day prior to admission.
• On admission to GH Malacca, he was fever,
39oC with no jaundice.
• Required ventilation on the same day of
admission for pulmonary hemorrhage

Suresh, HSB
• Chest x-ray showed, diffuse alveolar
shadows relatively sparing the apices.
• Hb 10g/dl, TWC 8.5x109/L, Platelet count
128x109/l,
• Creatinine 113mmol/l, ALT 32U/L,
• APTT ration 0.99, INR 1.03.

Suresh, HSB
• Dengue IgM, SARS antibody test,
Mycoplasma and HIV serology were
negative.
• Avian Flu PCR, was negative.
• However his Leptosirosis serology was
positive, 1:840.
• He had a history of going to Air Terjun
Lata Kijang in Perak, a week prior to
admission.

Suresh, HSB
 Pulmonary hemorrhage
• Several reports of leptospirosis presenting
as pulmonary hemorrhage from Taiwan,
UK, USA, India, Brazil and tropical areas
of Australia
• In Peru, 7 patients with histories of only
urban exposure to leptospirosis had
severe pulmonary manifestations
• Clin Infect Dis, 2005. 40(3): p. 343-51.
• In Seychelles (Indian Ocean), 19% of the
patients had pulmonary hemorrhage
• Am J Trop Med Hyg, 1998. 59(6): p. 933-40.

Suresh, HSB
 Frequent cause of
undifferentiated febrile illness

Suresh, HSB
Pau da Lima,Brazil- Cohort Study
of Leptospirosis
 3-5% of slum residents are infected each year.
 Severe disease-to-infection ratio is 1:152

• Re-infection is a frequent phenomenon in slum

communities.
 Secondary infection rate of 15% per year
• 26 / Bangladeshi/ Male
• No known medical illness
• c/o Fever x 5 days
• Arthralgia, myalgia and retro-orbital pain
• Poor oral intake
• Vomiting for 2 days
• Diarrhoea (4-5x / day) for 2 days
• Abdominal pain for 2 days

Suresh, HSB
• No headache, giddiness.
• No SOB, No abdominal distention
• No hx of recent travel, no hx of water
sports

• Been in Malaysia for the past 6 months

• Lives in Shah Alam
• History of recent fogging around place of
stay

Suresh, HSB
 On examination
• Alert, conscious, GCS 15/15
• Dehydrated
• Pink, no jaundice
• Conjunctiva injected
• CVS- s1s2, DRNM
• Lungs clear, A/E equal
• P/A – epigastric tenderness. No ascites.
• No lymphadenopathy

Suresh, HSB
• BP: 110/70 mmHg
• PR: 80/min, regular, good volume
• CRT < 2 seconds
• SpO2 100 % under Room Air

Suresh, HSB
 Results
• FBC at presentation (HTAR):
HCT: 44%, Plt: 166, WBC: 3.5

• Repeat FBC at ED HSB:

HCT: 42%, Plt: 145, WBC : 3.2,

Impression : Dengue Fever with dehydration

Suresh, HSB
 Management
• Admitted
• Run 2 pints NS over 2 Hours,
Then, another 2 pints NS over 4 Hours
• FBC repeated after the 4 pints
• Maintained 5 pints NS over 24 hours
• IV maxalon 10 mg stat and tds

Suresh, HSB
 Progress (Day 2)
• Day 6 of illness
• Not tolerating well orally
• Still having epigastric discomfort
• Nauseated
• VS stable, not tachycardic
• T still spiking , 38.3 OC
• Maintained on 6 pints IV drip

Suresh, HSB
 Progress (Day 3)
• Day 7 of illness
• Still c/o abdominal pain
• No bleeding tendencies
• VS stable, Not tachycardic
• T still spiking at about 380 C
• BFMP and Leptospira serology sent
• FBC : PLT 111, Hct: 38.8
• IV drip cut down to 4 pints NS over 24
hours
Suresh, HSB
 Progress (Day 3)
• Day 8 of fever
• Still unable to tolerate orally
• Persistent abdominal pain
• Diarrhoea 6x/day
• BP stable, PR: 64
• Continued IV drip 4pints NS
• HCt: 41.8, Plt : 133, Hb: 15.6
• Started Doxycycline 100mg bd
• Temperature started to settle after starting
doxycycline
Suresh, HSB
 Progress (Day 4)
• Day 9 of illness, Day 2 Doxycycline
• Felt better
• No more abdominal pain, no more
vomiting
• Able to tolerate well orally
• Hydration good
• VS stable. Afebrile.
• FBC: Hb: 15.6, PLt: 140, HCT: 42.1
• Discharged well on 2/1/07

Suresh, HSB
 Date Day Of Illness HB HCT Platelet
29/12/06 6 14.2 42 145
14.6 39.6 121
30/12/06 7 14.8 42.9 134
15.3 41.6 129
31/12/06 8 14.1 38 112
14.7 38.5 111
1/1/07 9 16.6 45.5 94
15.6 41.8 133
14.8 40.1 139
2/1/07 10 15.6 42.1 140

Suresh, HSB
• BFMP : Negative
• Stool Ova and Cysts : Negative
• Dengue IgM / IgG: Detected
• Serum amylase : 100
• RP : Normal
• PT/ APTT : Normal
• ALT : 46 (slightly raised)
• ALP, Bilirubin : Normal
• Anti Leptospiral IgM : POSITIVE at 1:320

Suresh, HSB
Suresh, HSB
Started Doxy
Investigations

Suresh, HSB
• Raised ESR
• Neutrophilia (>70%)
• Left shift
• Dengue – atypical lymphocytes
• Thrombocytopenia,
• Albuminuria is seen in every case to some extent, with
casts.
• Serum creatinine, Blood urea - often elevated.
• non-oliguric hypokalemic form of acute renal insufficiency
• For cases with hepatic pathology, serum bilirubin is often
dramatically elevated but aminotransferases are not.

Suresh, HSB
• Microscopic agglutination test
(MAT)
• Labour intensive and requires
expertise
• Positive 10-12 days after onset of
symptoms
• Antibody response delayed by
early antibiotic therapy
• Positive threshold for reaction
• Controversial
• Some consider a titre of 1:100
positive, whilst others accept 1:200,
1:400 or 1:800

Suresh, HSB
 Serological diagnosis
• ELISA – IgM
• More sensitive
• Positive 6-8 days after onset of symptoms
• Positive about 48 hours faster
• Ig M negative - faster
• Useful to differentiate between current and
previous leptospirosis

Suresh, HSB
 Problems with serology
• Anti-whole (total) Leptospira antibodies
may persist for years after exposure
• 2 or even 3 samples taken at 7 – 10
days intervals are most useful to
conclusively diagnose.

Suresh, HSB
 Point of care testing
• Dip-S-Ticks assay
• Sensitivity of
approximately
• 27% at 3 days following
onset of fever
• 84% for specimens
collected within 7--9 days
• nearly 100% by 10--12
days.

MMWR Morb Mortal Wkly Rep. 2001 Jan 19;50(2):21-4.

Suresh, HSB
 PCR

• PCR can rapidly confirm the diagnosis

in the early phase of the disease,
• before antibody titres are at detectable
levels.

Suresh, HSB
Treatment

Suresh, HSB
 Treatment

• Mild flu like symptoms – symptomatic

treatment
• Mild cases – Doxycycline
• Moderate to severe cases – Penicillin
• Other drugs found to be effective
• Ceftriaxone
• Cefotaxime

Suresh, HSB
• ‘Patients treated with antibiotics before
7 days after symptom onset
experienced a significant shortening in
their duration of illness’ – CID 2001;
33:1834–41

Suresh, HSB
• Case fatality
• Weil’s disease - 10%
• Severe Pulmonary hemorrhage – 50%
• Poor prognostic factors
• Old age
• Renal failure
• Respiratory insufficiency
• Poor GCS

Suresh, HSB
Leptospirosis-Associated Pulmonary
Haemorrhage Syndrome (LPHS)
 Pulse corticosteroid therapy
(Shenoy, Postgrad Med, 2003)
• Methylprednisolone 1gm IV daily for 3 days followed by
oral prednisolone 1 mg/kg for 7 days
• Compared to retrospective cohorts
• Mortality was 18% (3/17) in patients who received MP,
as compared with 62% (8/13 patients) in those who did
not (p<0.02)
• Corticosteroids affected outcome only if given within
the first 12 hours after the onset of pulmonary
manifestations
• DDAVP - 0.3 µg/kg in 30 ml of saline as
a 30 min infusion
• Repeated 2-3 times at 12- 24 hour
interval if necessary
Prophylaxis ?

Suresh, HSB
 Cochrane Database Syst Rev. 2000;
(4):CD001305

• Symptomatic, verified leptospirosis:

• 0.6% (3/509) versus 4.9% (25/ 513);
• Number needed-to-treat 24 (95% confidence
interval 17 to 43).
• Adverse effects: 3% (13/469) versus 0.2%
(1/471);
• Number needed-to-harm 39 (95% confidence
interval 25 to 100)

Suresh, HSB
 Prophylaxis in an endemic
area.
• Leptospirosis occurs as seasonal
outbreaks, lasting for about 3 weeks
during October-November in North
Andaman
• No difference in the infection rates
• Statistically significant difference was
observed in the clinical disease attack
rates (3.11 vs. 6.82%)

Suresh, HSB
 Post exposure prophylaxis
• Sao Paulo, Brazil
• Oral doxycycline (200 mg, single dose)
after high exposure to potentially
contaminated water
• Protective but not statistically significant

Rev Inst Med Trop Sao Paulo. 1998 Jan-Feb;40(1):59-61

Suresh, HSB
 Prophylaxis
• Possible options
• Weekly Doxycycline 200mg
• Half-life of Doxycycline is 18 hours
• Stat dose after exposure
• Self-initiated treatment with 7 day course of
doxycyline with onset of fever
• Cost effectiveness and risk versus
benefits still unclear

Suresh, HSB
Thank you

Suresh, HSB