Transcript LEPTOSPIROSIS

Leptospirosis-synonyms
► Mud
fever
► Japanese seven day fever
► Leptospiral Jaundice
► Spirochete Jaundice
► Autumn fever
► Elippani (mal)
Introduction
Leptospirosis is a most widespread zoonotic
disease in the world caused by the
pathogenic bacteria called leptospires.
► Generally it is transmitted by the infected
urine of rodents.
► Case fatality may vary from 0.3 – 8 %.
► Severe form of leptospirosis is called Weil’s
Syndrome
► Also included as water borne disease
►
Distribution
Worldwide disease.
► Most common in tropical & subtropical
areas with high rainfall.
► In India with frequent outbreaks in
Maharashtra ,Gujarat, Karnataka, Kerala &
Andaman islands especially during the
monsoon.
►
Leptospirosis:
(A re-emerging disease)
Endemic in South East Asia Region
► 12 out of 18 areas with the highest incidence are located
in SEAR (Pappas, 2008)
► Major outbreaks reported more notably in India, Indonesia,
Sri Lanka and Thailand.
► Outbreaks in SEAR as well as in South and North America
Leptospirosis as a re-emerging infectious disease
►
Incidence
No: of cases worldwide is not known precisely.
► 0.1 – 1 /100,000 per year in temperate climates.
► 10 – 100 /100,000 per year in humid tropics.
► During outbreaks & in high exposure risk groups
it may reach >100 per 100,000.
►
History of Leptospirosis
► Adolf
Weil described leptospirosis as a
disease entity in 1886.
Leptospirosis in India
► 1931
– An outbreak in Andaman islands.
► 1960 – Serological evidence
► 1983 – An outbreak in cattles
► Now endemic in all parts of India.
► All cases of fever with jaundice are now
screened for leptospirosis as a
mandatory laboratory test.
Leptospirosis in Kerala
► Reported
in Kerala from 1997 onwards .
► Increasing trend of incidence is clearly
seen.
► Case fatality rate in 2005 -10.62%
2006 -13.78%
up to June 2007 -10.53%
► Majority of cases occurred in late
Monsoon.
Epidemiological
determinants
Causative agent - Leptospira
► Corkscrew
-shaped delicate flexible
spirochetes.
► About 6 – 20 micrometer long & 0.1
micrometer thick.
► Posses a large number of closely wound
spirals & characteristic end hooks.
► Actively motile.
Causative agent - Leptospira
Leptospira
Too thin to visible under ordinary
microscope.
► dark field micros copy is using.
► Order-Spirochaetals.
► Family- Leptospiraceae.
► Genus- Leptospira
►
Bacteriology
1.Taxonomy and Classification
A. Serological classification (prior to 1989)
– Divided into two speies
• L. interrogans, comprising all pathogenic strains
• L. biflexa, containing the saprophytic strains
– Divided into numerous serovars
• defined by agglutination after cross-absorption
with homologous antigen
• Serovars that are antigenically related have
traditionally been grouped into serogroups
LEPTOSPIRA
L.INTERRGANS
L.BIFLEX
ICTERROHAEMORRHAGIAE-SERO.GP
Icterrohaemorrhagiae,copenhageni,smithi etc
Serovar
OVER 200 SEROVARS HAVE BEEN IDENTIFIED &
ASSEMBLED IN 23 SEROGROUPs.
A new serovar Barathy strain Kolenchery belonging to the Austarlis
group has been identified from Kerala.
Epidemiology
► Animals
can be divided into
 maintenance hosts
 accidental (incidental) hosts.
► The
most important maintenance hosts are
small mammals
Reservoir of infection
► Rodents –(Rattus rattus ,Rattus norvegicus,
Mus musculus )
► Dogs
► Wild
animals
► Domesticated animals
► Caged game animals
Epidemiology
► Different
animals may be reservoirs of
distinct serovars,
 rats are generally maintenance hosts for
serovars lcterohaemorrhagiae and Ballum
 dairy cattle may harbor serovars hardjo,
pomona
 pigs may harbor pomona,tarassovi,
Epidemiology
► Human
infections may be acquired through
 occupational exposures
 recreational exposures
 avocational exposures
►•
Direct or Indirect contact with infected
animals
Resistance- leptospira
► Very
susceptible to heat
► 10 mnts at 50 degree centigrade
► 10 seconds in 60 degree centi:
► Sensitive to acid
► Readily destroyed by chlorine
Epidemiology
► Under
laboratory conditions, leptospires in water
at room temperature remain viable for several
months at pH 7.2 to 8.0, but in river water
survival is shorter and is prolonged at lower
temperatures
► The
presence of domestic sewage decreases the
survival time to a matter of hours, but in an
oxidation ditch filled with cattle slurry, viable
leptospires were detected for several weeks
Epidemiology
► When
soil was contaminated with urine
from infected rats or voles, leptospires
survived for approximately 2 weeks
► in
rain-water-flooded soil it survived for at
least 3 weeks
Epidemiology
► Portal
of entry
– usually
• abrasions or cuts in the skin or via the
conjunctiva
• infection may take place via intact skin after
prolonged immersion in water
Environmental factors
► Endemic
in many countries.
► Has a seasonal distribution.
► Associated with
Poor housing
Limited water supply
Rodent intensity.
Leptospirosis as Epidemic
► Associated
with
1. Changes in human behavior
2. Contamination of water by animal /
sewage
3. Changes in animal reservoir density
4. Follow natural disasters like cyclones &
floods
Source of infection
► Leptospires
are excreted in the urine
of infected animals ,rodents etc.
Host factor
Age –most affected age group is 20-40 yrs
Children acquire infection from domestic dogs
► Sex - males are more prone to get infection
► Occupation – agricultural & live stock farmers
► Immunity – Asolid serovar specific immunity
follows an infection
►
Risk groups
► Agricultural
& Live stock farmers
► Workers in rice fields & sugar cane fields
► Underground sewers
► Meat & animal handlers
► Swimmers
Leptospirosis: an emerging zoonose
amplified by seasonal flooding
Occupational vulnerability: about
75% of leptospirosis cases are farmers
Vectors of leptospirosis:
Rice field rodents (Bandicota
sp. And Rattus sp.)
Leptospira
interrogans,
transported by water
in the environment
Recreational vulnerability affecting
a wider range of rural populations
Mode of transmission
1. Direct contact with urine or tissue of infected
animal
a.through skin abrasions
b.intact mucus mem:
2. Indirect contacta.broken skin with infected soil,water or
vegetation
b.through ingestion of food & water
contaminated with leptospira
3. Droplet infection- inhalation of droplets of
infected urine
Leptospires in the body
TISSUES
BLOOD
ORGANS
LEPTOSPIRA
URINE
CONVOLUTED
TUBULES
OF
KIDNEY
f. Pathology
► Leptospirosis
is characterized by the development
of vasculitis, endothelial damage, and inflammatory infiltrates composed of moncytic cells, plasma
cells, histiocytes, and neutrophils.
► On
gross examination, petechial hemorrhages are
common and may be extensive, and organs are
often discolored due to the degree of icterus
► The
histopathology is most marked in the liver,
kidneys, heart, and lungs, but other organs may
also be affected according to the severity of the
individual infection.
Pathogenesis of severe
disease
Leptospira
Damage to small
blood vessels
Massive migration of fluid from
Intravesicular to interstitial compartment
Renal dysfunction,vascular injury
To internal organs
vasculitis
Direct cytotoxic injury
Immunological injury
Spectrum of illness
Clinical patterns-as per WHO
1. Mild –influenza like illness
2. Weil’s syndrome characterised by
jaundice,renal failure,haemorrhage,
&myocarditis with arrhythimias
3. Meningitis/ Meningo encephalitis
4. Pulmonary haemorrhage with respiratory
failure
Incubation period
► Usually
10 days
Range- 4-20 days
Clinical Features Of Leptospirosis
► The
spectrum of symptoms is extremely
broad; the classical syndrome of Weil’s disease
represents only the most severe presentation
► The
clinical presentation of leptospirosis is
biphasic
 acute or septicemic phase-1w
 immune phase-antibody production and
excretion of leptospires in the urine
Clinical Features Of Leptospirosis
► Most
of the complications of leptospirosis
are associated with localization of
leptospires within the tissues during the
immune phase and thus occur during the
second week of the illness.
a. Anicteric Leptospirosis
► The
great majority of infections caused by leptospires are either subclinical or of very mild severity,
and patients will probably not seek medical
attention.
► A smaller proportion of infections, but the
overwhelming majority of the recognized cases,
present with a febrile illness of sudden onset.
► Aseptic meningitis may be found in < 25% of all
leptospirosis cases, 62% of children < 14 years old
Leptospirosis: (Symptoms)
Leptospirosis - Challenge
Anicteric Leptospirosis:
The patients present with :
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Fever - Patients have remittent fever with chills. It may be
moderate to severe.
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Myalgia - It is a very characteristic fi nding in leptospirosis. Calf, abdominal & lumbosacral muscles are very painful
& severely tender. This symptom is very useful in differentiating leptospirosis from other diseases causing fever.
There is associated increase in serum Creatinine Phosphokinase (C.P.K.) which helps in differentiating leptospirosis
from other illnesses.
Anicteric Leptospirosis:
The patients present with :
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Conjunctival Suffusion - There is reddish colouration of
conjunctiva. Very useful sign in leptospirosis. Usually
bilateral, most marked on palpebral conjunctiva, it may be
associated with unilateral or bilateral conjunctival
haemorrhage.
• Headache - Usually intense, sometimes throbbing,
commonly in frontal region. It is often not relieved by
analgesics.
Anicteric Leptospirosis:
The patients present with :
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Renal manifestations - Some form of renal involvement
is invariable in leptospirosis. It usually occurs as asymptomatic urinary abnormality in the form of mild proteinuria
with few casts & cells in the urine. Severe renal involvement in the form of acute renal failure, (which occurs in
icteric leptospirosis) is rare.
►
Pulmonary manifestations - Manifested in most cases
through cough & chest pain and in few cases by haemoptysis. Severe involvement leading to respiratory failure
does not occur in anicteric leptospirosis.
Anicteric Leptospirosis:
The patients present with :
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Hemorrhage - Hemorrhagic tendencies are also present
in some cases.
Note: All the clinical features either decrease or disappear within two
to three days and then they reappear.
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Differential diagnosis - The patients of anicteric
leptospirosis are likely to be misdiagnosed as malaria,
dengue hemorrhagic fever, viral hepatitis etc.
Note: In endemic area all cases of fever with myalgia and conjunctival suffusion should be considered as suspected cases of
leptospirosis.
Icteric Leptospirosis:
This is the more severe form of leptospirosis. As the name
suggests all patients have jaundice. Patients present with:
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Fever
Same as in anicteric leptospirosis
but may be more severe.
Myalgia
Headache
Conjuctival suffusion
Oliguria/Anuria and/or proteinuria
Nausea, vomiting
Abdominal pain
Icteric Leptospirosis:
( Weil’s syndrome )
► In
addition, they have features of organ involvement. An individual patient may have features of one or more organ involvement. The
more severe form of disease with severe liver
and kidney involvement is known as Weil’s
syndrome.
Icteric Leptospirosis: (Renal)
Renal involvement is almost invariably present in leptospirosis. In severe cases patients have acute renal failure and
present with:
 Decreased urine output (oliguria or even anuria)
 Oedema may be present on face and feet.
 Features of uremia like breathlessness, convulsion, delirium
and altered level of consciousness may be present in very
severe cases.
The renal dysfunction worsens during the fi rst week to the
end of 2nd week, after which it starts improving and
complete recovery occurs by the end of the 4th week.
There is usually no residual renal dysfunction.
Icteric Leptospirosis: (Hepatic)
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Jaundice is the most important clinical feature. It may be mild to
severe. It starts after 4 to 7 days of illness. Hepatic encephalopathy or death due to hepatic failure is rare. Hepatomegaly &
tenderness in right hypochondrium are usually detected.
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Laboratory investigations show raised level of serum bilirubin
(direct) and alkaline phosphatase. SGOT & SGPT are either normal or mildly elevated. This helps to differentiate leptospirosis
from viral hepatitis where SGPT is markedly elevated and also
from alcoholic hepatitis where SGOT is markedly elevated. High
level of Creatinine Phosphokinase (CPK) is suggestive of Leptospirosis. It is normal in viral hepatitis and alcoholic hepatitis helps
in differential diagnosis.
Hepatic changes in leptospirosis
In severe cases even where hepatic dysfunction and jaundice are present
hepatocellular necrosis is unusual but large amounts of bilirubin can be seen in
the hepatocytes. After specific chemotherapy, the liver function usually returns
to normal.
Icteric Leptospirosis:
(Pulmonary involvement)
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High mortality due to pulmonary involvement is becoming
a feature in Leptospirosis.
There are wide variations in pulmonary presentation. It is
the commonest cause of death due to leptospirosis.
Symptoms: In mild cases patient will show only cough,
chest pain and blood tinged sputum. In severe cases
patients have cough, haemoptysis, rapidly increasing
breathlessness which may lead to respiratory failure and
death.
Icteric Leptospirosis:
(Pulmonary involvement)
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On examination, these patients have increased respiratory
rate with basal creptations, which rapidly spread upwards
to middle and upper lobes.
X-ray shows basal and mid zone opacity in severe cases. It
may be normal in mild cases.
The under lying pathology is intra-alveolar haemorrhage.
More than ninety percent (90%) of deaths due to
leptospirosis occur due to pulmonary alveolar
haemorrhage.
Icteric Leptospirosis:
(Cardiovascular system involvement)
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Patients can have any one or more of the following
features:
Haemorrhage
They occur because of
1) Thrombocytopenia,
2) Disseminated Intra-vascular Coagulation (DIC),
3) Secondary to liver involvement leading to coagulation
factor defi ciency.
Patients may have spontaneous superfi cial bleeding i.e.
petechial, purpura, epistaxis or GIT bleeding. In severe
cases ecchymosis or intra-cranialhaemorrhage can occur.
Icteric Leptospirosis:
(Cardiovascular system involvement)
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Hypotension Shock: Patient will have hypotension, cold
clammy extremities, tachycardia, thready pulse. JVP is either
normal or decreased. Echocardiography reveals normal systolic
function of left ventricle hence hypotension is due to either
dehydration or peripheral vasodilatation.
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Arrhythmias: Patient presents with palpitation and syncope &
irregular pulse. Common arrhythmias seen are supraventricular
tachyarrythmias and various degrees of A.V. blocks. Ventricular
tachyarrhythmias are infrequent. ST Segment depression and
T wave inversion may be present in some patients.
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All patients with severe , multiple organ involvement should be
referred to tertiary care centres.
b. Ocular Involvement
► Conjunctival
suffusion in the presence of scleral
icterus is said to be pathognomonic of Weil’s
disease
► Anterior
Uveitis may present weeks, months, or
occasionally years after the acute stage.
► Chronic
visual disturbance, persisting 20 years or
more after the acute illness, has been reported
c. Ocular Involvement
Subconjunctival haemorrhages in leptospirosis
Icteric Leptospirosis:
c. Icteric leptospirosis
► Icteric
leptospirosis is a much more severe disease
in which the clinical course is often very rapidly
progressive.
► Severe
cases often present late in the course of
the disease, and this contributes to the high
mortality rate, which ranges between 5 and 15%.
► Between
5 and 10% of all patients with leptospirosis have the icteric form of the disease
Diagnosis
►Suspected
clinically by
Deep jaundice
Sub- conjunctival haemorrhage
Muscle tenderness
Decreased urine output
Possible exposure to rat’s urine
Diagnosis by lab methods
► Presence
of proteinuria, RBC ,cell casts.
► Polymorphonuclear leucocytosis & high ESR.
► Thrombocytopenia in peripheral smear.
► Elevated serum creatinine.
► Positive Weil’s antibody test.
d. Other Complications
► Acute
infection in pregnancy has been
reported to cause abortion and fetal death,
but not invariably so.
►a
neonate developed jaundice
e. Chronic or Latent Infection
► This
patient exhibited a negligible antibody
response to the infecting strain, suggesting
the presence of an immune defect.
 Retinal pathology
 Meningitis
Ocular Involvement
Uveitis in leptospirosis
During the recovery phase of leptospirosis, iridocyclitis or uveitis (as seen here)
may be associated with the immunological response, often several weeks or
months following the initial infection. This photograph of the fundus was taken 3
months after the patient developed acute systemic leptospirosis.
Laboratory diagnosis
► Dark
field microscopy (MAT)
► Culture from blood (IgM ELISA)
► PCR
► Blood-First week.
► Urine-Second up to sixth week (intermittently).
► ELISA- Genus specific.
► MAT – Serovar / serogroup specific.
► RAPID Test – Lepto- Tek –Dri –Dot.
Differential diagnosis
Influenza;
► Dengue and dengue haemorrhagic fever;
► Yellow fever and other viral haemorrhagic
fevers;
► Malaria
► Pyelo nephritis
► Aseptic meningitis
► Viral hepatitis
► Typhoid & other enteric fevers
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Complications
► Renal
failure
► Acute hepatic failure
► Acute cardio vascular failure
► Haemorrhage
► Meningitis
► pneumonia
Prognosis
► Mortality
of severe leptospirosis is high .
range varies =3.5 to 40 %
Cause of death
► Renal
failure
► Cardio pulmonary failure
► Widespread haemorrhage
► Liver failure rare
Recovery from Leptospirosis
► Most
patient recover completely.
► Some patients may take months/years.
► Late sequlae may occur.
General measures
Complete bed rest
► Light easily digestible diet
► Plenty of oral fluids
► Anti-pyretic medication as needed
► Patients with complication shall be admitted
► Sodium, pottassium & phosphorus may be
restrictd
► Nephrotoxic drugs should be avoided
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Treatment
Penicillin is the drug of choice when given
early -7 days.
► If penicillin allergic tetracycline
/erythromycin.
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Hepatic involvement
► Jaundice-
mild to severe
starts 4-7 days following illness
acute liver failure is rare
elevation of serum bilirubin with raised alkaline
phosphatase, CPK is very much elevated.
Treatment- mainly symptomatic & supportive.
Hephatic encephalopathy- proteins restricted.
Coagulation failure is corrected with Vit-K.
RENAL INVOLVEMENT
► Invariably
seen in all cases.
► Urine is abnormal with cells
► Creatinine levels elevate later
► Renal failure may be oliguria or anuria.
► Treatment-severe patients require dialysis
support.
Pulmonary complications
► Cough
& hemoptysis ,may progress rapidly
to breathlessness & res: failure
► >9% mortality is due to alveolar
hemorrhage
► Treatment- continuous oxygen therapy &
ventilatory support
Cardiovascular
complications
► Hypotension&
shock due to intravascular fluid
leak
► Myocarditis with serious arrhythimias & cardiac
failure.
► Hemorrhage- fatal GI hemorrrhage, hemetemsis,
alveolar hemorrhage & epistaxis
► Treatment- fluid replacement ,vasopressors
,arrhythimias should be treated in the ICU setting
Immunization
► Immunity
to leptospirosis is largely humoral
and is relatively serovar specific. Thus, immunization protects against disease caused by
the homologous serovar or antigenically similar
serovars only.
A case history
►A
25 year old man is brought to the Out
Patient Department with history of fever of
3 days duration with following symptoms &
signs.
High grade fever of continuous nature.
Generalized aches & severe myalgia.
Yellowish discoloration of eyes & urine.
Non-specific head ache.
Natural maintenance hosts
& serovars
► Rats
–
icterohaemorrhagiae,copenhageni
& smithi, etc
► Dogs – canicola etc
► Cattle – pomona ,hardjo ,etc
Epidemiology
► Leptospirosis
is presumed to be the most
widespread zoonosis in the world
► Either direct or indirect contact with the
urine of an infected animal
► The incidence is significantly higher in
warm climate countries than in temperate
regions
Epidemiology
► Many
animals are seronegative carriers. After
infection, leptospires localize in the kidneys and
are excreted intermittently in the urine
► Many
of these outbreaks have followed extended periods of hot, dry weather, when pathogenic leptospires presumably have multiplied in
freshwater ponds or rivers. Cases of leptospirosis also follow extensive flooding
Epidemiology
► Other
 excretion of leptospires in human urine months
after recovery
 sexual intercourse during convalescence
 Water-borne transmission has been
documented
Treatment
► Treatment
of leptospirosis differs depending on
the severity and duration of symptoms at the
time of presentation.
► Patients
with mild, flu-like symptoms require
only symptomatic treatment but should
cautioned to seek further medical help if they
develop jaundice
Laboratory diagnosis
(Blood culture)
► Ideal
time:
 Within 10 days of the onset of the disease.
 Sample should be collected before antibiotics are
started.
► Media:
 EMJH, Fletcher’s and Stuart’s (commercially available or
obtain from the designated regional/ district laboratory)
Laboratory diagnosis
(Blood culture)
Procedure:
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Swab the area with the spirit.
Draw the blood using sterile syringe and needle by vein puncture.
Take 2 tubes containing 5 ml EMJH medium and inoculate two drops
of blood in the fi rst tube and four drops in the second tube.
Incubate at 300C for 4-6 weeks.
Examine the culture using dark fi eld illumination initially on 1st, 3rd
and 5th days followed by at 7-10 days interval upto 6 weeks.
Selective culture media containing 5FU 50-1000 μg/ml or a
combination of nalidiocic acid 50 μg/ml; vancomycin 10 μg/ml and
polymixin B sulphate 5 units/ml or a combination of actidione 100
μg/ml, bacitracin 40 μg/ml, 5-FU 250 mg/ml, neomycin sulphate 2
μg/ml, polymixin B sulphate 0.2 μg/ml and refampicin 10 μg/ml can
be used to avoid the contamination.
Management of severe cases
► Should
be treated in higher centre with facilities
for organ support.
► Organ dysfunction may be treated on standard
lines.
► There is nothing specific treatment to
leptospirosis.
► Hypovolemia should be corrected with normal
saline.
► Adequate calories (1000Kcal+100Kcal/year of
age) may be given.
Interventions at the level of
human host
► Raising
awareness about the disease.
► Antibiotic prophylaxis- Doxycycline give some
degree of protection.It can reduce the severity of
disease.
► Immunization in available countries.Vaccine give
protection only against the specific serovar.
► Health education.
Leptospirosis - Challenges
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Mimics other diseases; clinical diagnosis is essentially
one of exclusion
Severe form around 20% with organ failure requiring
secondary and tertiary care
Definitive diagnosis through laboratory; not widely
available
Is yet to be considered a priority disease in most SEA
countries
Generalized underreporting of cases
Prevention and control remains difficult to implement
Socio-cultural, economic, environmental
and ecological perspectives
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Common in occupations with frequent exposure to contaminated
environment and carrier animals
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Same group reported to have poor knowledge of the disease,
probably related to level of education (Wiwanitkit, 2006)
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Low socio-economic status independently contribute to the risk
of infection (Reis, et al, 2008)
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Anthropogenic environmental changes (e.g., land use change)
documented prior to outbreaks in Peru, Hawaii (Wilcox & Gubler,
2005) and could have played a role in Sri Lanka outbreaks
►
Understanding human behaviour, practices and worldview may
prove useful in the success of programmes
Late complications
► Chronic
fatigue
► Neuro-psychiatric sym : - Headache ,paresis
,paralysis ,mood swings & depression.
► Uveitis & Iridocyclitis
Management
SYMPTOMS
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Leptospirosis in humans may show a wide variety of
symptoms and signs including:
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fever;
severe headache;
myalgias;
conjunctival suffusion;
jaundice;
general malaise;
stiff neck;
chills;
abdominal pain;
joint pain;
anorexia;
nausea;
vomiting;
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– diarrhoea;
– oliguria/anuria;
– haemorrhages;
– skin rash;
– photophobia;
– cough;
– cardiac arrhythmia;
– hypotension;
– mental confusion;
– psychosis;
– delirium.
Clinical variety
1.Mild / Anicteric
Presents with fever , myalgia
conjunctival suffusion & head ache.
2. Severe (Weil’s syndrome ) / Icteric
Present with jaundice & renal failure
along with all features of mild cases
Multiple organ involvement manifest as
different complications.
Three epidemiological patterns of
leptospirosis were defined by Faine
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The first occurs in temperate climates where few
serovars are involved and human infection almost
invariably occurs by direct contact with infected
animals though farming of cattle and pigs
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The second occurs in tropical wet areas, within which
there are many more serovars infecting humans and
animals and larger numbers of reservoir species,
including rodents, farm animals, and dogs
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The third pattern comprises rodent-borne infection in
the urban environment. (slum)
Leptospirosis – Epidemiology