Leptospirosis

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Epidemiology: m.c. in tropics and sub- tropics ! m.c. in men ! peaks during summer and fall and during rainy season in ! tropics high risk occupations: veterinarians, agri. workers, sewage ! workers, slaughterhouse employees and in fishing industry risk factors: direct or indirect contact with animals, exposure ! to water and soil contaminated with in the Phils: endemic during the rainy months of June- Aug. ! Transmission 1. direct contact with urine, blood or tissue from an infected animal or exposure to environmental conditions. 2. Human- human (controversial)  is an impt. vehicle for transmission. ! are due to exposure to flood waters contaminated by ! urine from infected animals

Entry (through cuts, abraded skin or mucous memb.)

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Coiled, thin, highly motile organism Have hooked ends and 2 periplasmic flagella " motility Stain poorly but can be seen microscopically by dark- filed exams and after silver impregnation Takes weeks- months for cultures to become positive

Leptospiremic phase Organisms proliferate and disseminate hematogenously Initial incubation where leptospires can be isolated from bloodstream (2- 28 days)

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Organisms survives and evade the complement killing by binding "a strong inhibitor of complement system Lepstospires resist ingestion and killing by neutrophils, monocytes and macrophages

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IMMUNE PHASE Appearance of antibodies but disappearance of leptospires in the blood Bacteria persist in various organs including

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Acute tubular damage and interstitial nephritis "interstitial edema and acute tubular necrosis deregulation of the expression of several transporters along the nephron, including the proximal sodium-hydrogen exchanger 3 (NHE3), aquaporins 1 and 2 (AQP1 and AQP2), Na+-K+ ATPase, and the Na-K-2Cl cotransporter NKCC2, "

: Bleeding and multi- organ failure- clinical hallmarks of the disease (when the dse is severe) Mild presentations occur as a $ : 1- 2 weeks but can range 1- 30 days $ It is : $ a. - fever of 3- 10 days and organism can be cultured from blood b. - antibodies appear in the blood, but leptospires disappear, therefore culture of organism is taken from the urine sample. nd Milder cases- do not include the 2  phase ! Severe cases- are usually monophasic ! Acute febrile illness for at least 2 days + either residing in a flooded area or high risk exposure + presenting at least 2 of the ff: o myalgia, calf tenderness, conjunctival suffusion, chills, abd’nal pain, h/a, jaundice or oliguria "  SHOULD BE  (grade A)

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flu-like illness of sudden onset, with fever, chills, headache, nausea, vomiting, abdominal pain, conjunctival suffusion (redness without exudate), and myalgia Muscle pain is intense and especially affects the .

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: depends on the production of circulating antibodies to serovarspecific LPS. Activation of TLR- 2 and TLR- 4 are also demonstrated

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: focal necrosis, foci of inflammation, and plugging of bile canaliculi. No widespread hepatocellular necrosis Petechiae hge.

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The headache is intense, localized to the (resembling that occurring in dengue), and sometimes accompanied by photophobia Aseptic meningitis (more common with children) : fever, conjunctival suffusion, pharyngeal injection, muscle tenderness, lymphadenopathy, rash, meningismus, hepatomegaly, and splenomegaly. natural course of mild leptospirosis usually involves spontaneous resolution within

rapidly progressive and is associated with a case– fatality rate ranging from 1 to 50%. # Higher mortality rates are associated with an age >40, altered mental status, acute renal failure, respiratory insufficiency, hypotension, and arrhythmias # classic presentation, often referred to as , encompasses the triad of hemorrhage,  jaundice, and acute kidney injury or (fever, jaundice and renal failure in the handouts)

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 standard Time consuming and labor intensive  result needs dark- field microscopy

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can identify serovar but

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Adv: early confirmation of the dse esp. during the acute phase of the illness before the appearance of antibodies

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4- fold increase in titer from acute to convalescent is

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adv: highly sensitive and specific disadv: timeconsuming and hazardous to perform, cross reactions may occur in the Phils, single titer of at least 1:1600 in symptomatic px is

Pre- exposure   200mg once weekly, to being 1-2 days before exposure and continued throughout the period of exposure. Post- exposure   200mg, duration depends on the degree of exposure and the presence of wounds. a. Low-risk exposure:   200mg single dose within 24-72 hours from exposure. [Grade B] b. Moderate-risk exposure:   200mg once daily for 3-5 days to be started immediately within 24-72 hours from exposure. [Grade C] c. High-risk exposure:  200mg once weekly until the end of exposure. [Grade B]

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Serologic tests for In early stage of the dse, prone to false negative results

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Detects antibody through an agglutination reaction Used as screening test but NOT sensitive

CBC- leukocytosis with neutrophilia, thrombocytopenia U/A- proteinuria, pyuria and often hematuria, hyaline and granular casts Serum Creatinine- can be normal but can increase along the process CPK- MM- elevated in pxs w/ severe myalgia Liver fxn tests- slight increase bilirubin, ALT, AST and alkaline phosphatase Bleeding parameters- prolonged PT and PTT

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: Most pxs recover Post- leptospirosis sxs: depression- like nature Leptospirosis during pregnancy is associated with high fetal mortality rates.

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 is the drug of choice. Alternative drugs: Amoxicillin and Azithromycin dihydrate.

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 remains the drug of choice. Alternative drugs: Ampicillin, 3rd generation cephalosporin (Cefotaxime, Ceftriaxone), and parenteral Azithromycin dihydrate. Antibiotic therapy should be , except for  which could be given for 3 days. Indications for dialysis Uremic symptoms – nausea, vomiting, altered mental status, ! seizure, coma Serum creatinine > 3mg/dL ! Serum Potassium > 5meq/L in an oliguric patient ! ARDS, pulmonary hemorrhage ! pH < 7.2 ! Fluid overload ! Oliguria despite measures following the algorithm ! #

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