Leptospirosis 12 Oct

8/10/2019 Leptospirosis 12 Oct.

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LEPTOSPIROSIS

Dr. SARTONO Sp PD


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Based on DNA : 17 genomospecies of pathogenic leptospires The genome sequences of 2 strains have been published Based on antigenic composition , pathogenic leptospires :

> 250 serovars ( 26 serogroups )

LEPTOSPIRES :- coiled , thin , highly motile with hooked ends & two

periplasmic flagella ( permit burrowing into tissue )- 6 20 m long & 0,1 m wide

- poorly stained , but can be seen by dark-field examinationand after silver impregnated staining

- Require special media/condition for growth ; takes weeks.


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EPIDEMIOLOGY :

Leptospirosis important zoonosis , world wide distribution ,

affecting 160 mammalian species. Reservoir :

- most important : rodents ( especially rats )- other : wild mammals / domestic & farm animals

Establish a symbiotic relationship with host & can persist inthe renal tubules for years.

Some serovars associated with particular animals e.g.- Icterohemorrhagiae & Copenhageni rats- Grippotyphosa voles- Hardjo cattle- Canicola dogs

- Pomona pigs ; but may occur in other animals.


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In most countries , leptospirosis is underestimated problem Infection occurs in the tropics ( most common ) , due to :

- climate- poor hygienic conditions favor the pathogens survivals

& distribution. Most cases in men , peak incidence :

- during summer & fall in Western countries- during rainy season in the tropics

Transmission of leptospires to humans follows :- direct contact with urine , blood , tissue from infected animal- exposure to a contaminated environment

Human to human transmission is rare Leptospires , excreted in the urine & can survive in water for

many months important vehicle for transmission


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HIGH RISK GROUPS

High risk occupational groups :

- Veterinarians- Agricultural workers- Sewage workers- Slaughterhouse employees- Workers in fishing industry

Recreational exposure & domestic-animal contact sources ofleptospirosis Recreational water activities :canoeing, windsurfing, swimming, waterskiing.

Outbreak in 1998 among athletes after triathlon in Illinois heavy rains , agricultural runoff increased contamination.

In 2000 , 80 participants contracted leptospirosis , during

multisport endurance race in Borneo, Malaysia.


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Multiplication takes place in blood & tissues Leptospires can be isolated from blood & CSF the 1st 10 -14

days. CSF exam pleocytosis , but only a minority of Px develop

symptom & signs of meningitis. All forms can damage the wall of small blood vessels

vasculitis with leakage & extravasation of cell, includinghemorrhage.

Pathogenic properties of leptospires :- adhesion to cell surfaces- cellular toxicity

Vasculitis responsible for the most important manifestations


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Mainly infect the kidney & liver, any organ may be affected. In the kidney , migrates to the interstitium , renal tubules , &

tubular lumen interstitial nephritis & tubular necrosis.Hypovolemia ( due to dehydration ) or altered capillarypermeability contribution of renal failure.

In the liver : centrilobular necrosis + proliferation of Kupffercells , but severe hepatocellular necrosis is not afeature of leptospirosis.

Pulmonary involvement : due to hemorrhage and not ofinflamation.

Skeletal muscles swelling , vacuolation of myofibrils & focalnecrosis.

Severe leptospirosis vasculitis impair microcirculation &

increase capillary permeability -> fluid leakage & hypovolemia


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CLINICAL MANIFESTATION

Many Px remain asymptomatic

Serologic evidence of past inapparent infection is frequentlyfound in persons who have been exposed but have notbecome ill.

Symptomatic cases vary from mild to serious even fatal.

> 90 % symptomatic Px have relatively mild & unicteric formof leptospirosis with or without meningitis. Severe leptospirosis with profound jaundice ( Weils

syndrome ) , develop in 5 10 % of infected individuals.

Incubation Period : 1-2 weeks , ranges from 2 20 days. Typically , acute leptospiremic phase is followed by an immuneleptospiruric phase.

The distinction between the 1 st & 2 nd phase is not always clear;

Milder cases do not always include the 2nd

phase.


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ANICTERIC LEPTOSPIROSIS Leptospirosis may present as an acute influenza-like illness,

with fever, chills, severe headache , nausea , vomiting &myalgia.

Important features : muscle pain , especially affects the calves, back & abdomen.

Less common features : sore throat and rash. Px usually has an intense headache ( frontal or retroorbital );

sometimes develops photophobia.

Mental confusion may be evident. Pulmonary involvement , manifested by cough , chest pain orhemoptysis.

The most common finding on PE : fever & conjunctivalsuffusion.


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Less common findings : muscle tenderness, lympadenopathy,

pharyngeal injection, rash, hepatomegaly & splenomegaly.

Rash : macular, maculopapular, erythemateous, urticarial,hemorrhagic.

Px -> asymptomatic within 1 week ; After interval of 1-3 days the illness recur The start of this 2nd (immune) phase coincides with the

development of antibodies ; symptoms , more variable thanthe 1st ( leptospiremic ) phase ; Usually last for a few days ,

but occasionally persist for weeks. Fever are less pronounced& myalgia less severe than in the leptospiremic phase.

Important event during the immune phase : development ofaseptic meningitis.


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Although no more than 15% of all Px have symptoms & signs

of meningitis, many Px CSF pleocytosis.

Meningeal symptoms usually disappear within a few days butmay persist for weeks ; pleocytosis disappear within 2 weeksbut occasionally persists for months.

Aseptic meningitis is more common in children. Iritis, iridocyclitis & chorioretinitis late complications , may

persistfor years. Mortality rates in anicteric leptospirosis are low although

death ( due to pulmonary hemorrhage ) occured in 2.4 %ofcases in a Chinese outbreak.


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SEVERE LEPTOSPIROSIS ( WEILS SYNDROME ) The most severe form ; characterized by :

- jaundice

- renal dysfunction- hemorrhagic diathesis- pulmonary involvement

Mortality rate : 5 15 %In Europe its frequently associated with serovar Ictero -hemorrhagiae & Copenhageni.

The onset is about the same with less severe leptospirosis ;after 4-9 days , jaundice/renal/vascular dysfunction develop.

Defervescence may be noted after the 1st week of illness , butbiphasic disease pattern (like in anicteric leptosp.), is lacking.

The jaundice is usually not associated with severe hepatic

necrosis.


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Death is rarely due to liver failure.

Hepatomegaly & tenderness (+) ; slenomegaly : 20% of cs.

Renal failure (+) in the 2nd week of illness.Hypovolemia & decreased renal perfusion ATN with oliguriaor anuria. Dialysis , is sometimes required.

Pulmonary involvement occurs frequently cough, chest pain,blood stained sputum & hemoptysis or respiratory failure.

Hemorrhagic manifestations are seen in Weils syndrome : epistaxis, petechiae, purpura & ecchymoses found commonly ;while severe GI bleeding & adrenal/subarachnoid hemorrhagedetected rarely.

Severe leptospirosis may present with rhabdomyolysis,hemolysis, myocarditis, pericarditis, CHF, cardiogenic shock,

ARDS, necrotizing pancreatitis, multiorgan failure.


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LABORATORY & RADIOLOGIC FINDINGS

The kidney invariably involved in leptospirosis urinary sediment changes ( leucocytes, erythrocytes & hyaline

or granular casts ) & mild proteinuria in anicteric leptospirosis renal failure / azotemia in severe disease. ESR , usually elevated In anicteric leptospirosis, peripheral leucocyte counts rise (

3000 26000 / L with a left shift ; in Weils syndrome ,leucocytosis is often marked. Mild thrombocytopenia occurs in 50% px & assoc. w. RF In contrast to acute viral hepatitis , leptospirosis have elevated

bilirubin, alkali phosphatase & mild increase ( 200 U/L ) ofaminotransferases. In Weils syndrome, prothrombine time may be prolonged ( can

be corrected w. Vit. K )

Creatin phosphokinase , elevated in 50% px ( DD w. Hepatitis)


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When meningeal reaction develops , pmn leucocytes

predominate initially, mononuclear cells increase later.

CSF protein elevated , but CSF glucose level , normal. In severe leptospirosis , pulmunory radiographic abnormalities,

are more common than would be expected on PE freq.lydevelop 3 9 days after the onset.

Radiographic finding : patchy alveolar pattern ( most common ) , corresponds to scattered alveolar hemorrhage ;Most often, affect the lower lobes in the periphery of the lungfields.


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DIAGNOSIS

Definite Dx of Leptospirosis , based on :

* isolation of organism from the px. or* seroconversion or* a rise in antibody titer in the microscopic agglutination test

( MAT ) ; in USA , MAT performed at CDC. In strong evident of leptospirosis infection , a single antibody

titer of 1 : 200 - 1 : 800 in the MAT is required. A four fold or greater rise in titer is detected between acute &

convalescent-phase serum specimens. Antibodies generally do not reach detectable levels until the2nd week of illness ; AB response can be affected by early Tx


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Leptospires can be isolated from blod and / or CSF during the

1st 10 days and from urine for several weeks beginning at first

week . Cultures often become positive after 2-4 weeks, with a range

of 1 week to 6 months. Urine cultures remains pos. for months or years. For isolation of leptospires from body fluids or tissues , EMJH

(Ellinghausen-Mc Cullough-Johson-Harris) medium is useful;Other medium are Fletcher or Korthof medium.

Specimens can be mailed to a reference lab. for cultureremain viable in anticoagulated blood (heparin,EDTA,citrate) ,up to 11 days.

Isolation of leptospires is important , since dark-field exam.

results in misdiagnosis.


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P f d


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Purpose of drugAdministration Regimen

Treatment

Mild leptospirosis Doxicyclin 100mg orally, bid or Ampicillin, 500-750mg orally qidor

Amoxicillin, 500mg orally qid

Moderate/severe Penicillin G, 1.5 million U IV qidleptospirosis or

Ampicillin, 1 g IV qid or Amoxicillin , 1g IV qid orCeftriazon, 1 g IV once daily orCefotaxime, 1g qid orErythromycin, 500 mg IV qid

Chemoprophylaxis Doxycyclin, 200 mg orally/week

PROGNOSIS


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PROGNOSIS- Most Px recover- Mortality rates, highest in elderly & Weils syndrome ; also

in those with pregnancy

PREVENTION- Those who may be exposed (through occupation or

recreational water activities ) should be informed about therisk.

- Avoidance of exposure to urine & tissues from infectedanimals.

- Vaccination of animals and- Rodent control

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Leptospirosis 12 Oct