Leptospirosis CPG 2010

Angelo P. Ampong, M.D. Emergency Medicine Resident EAMC

Leptospirosis
1886 Adolf Weil acute infectious disease with enlargement of spleen, jaundice, and nephritis." 1907 bacteria first observed from a post mortem renal tissue slice. 1908 Inada and Ito first identified it as the causative organism 1916 noted its presence in rats

Leptospirosis
Weil's syndrome canicola fever canefield fever nanukayami fever 7-day fever Rat Catcher's Yellows Fort Bragg fever Black jaundice Pretibial fever

Incidence
680 leptospirosis cases and 40 deaths from the disease reported every year prevalence of 10/100,000 It is seasonal with a peak incidence during the rainy months of July to October

What is leptospirosis?
infectious disease caused by genus Leptospira transmitted directly or indirectly from animals to humans - ZOONOSIS

Human-to-human transmission occurs only very rarely

Philippines: antibodies to various leptospiral serovars have been reported in:

urban domestic rats rural field rats water buffaloes cattle pigs dogs monkeys

Leptospira
corkscrew-shaped bacteria, which differ from other spirochaetes by the presence of end hooks. order Spirochaetales family Leptospiraceae genus Leptospira too thin to be visible under the ordinary microscope Dark-field microscopy

Leptospira spp
Two species were recognized: Leptospira interrogans pathogenic Leptospira biflexa saprophytic

What causes the pathological phenomena in leptospirosis? damage to the endothelial lining of small blood vessels:
interstitial nephritis and tubular, glomerular and vascular kidney lesions leading to uraemia and oliguria/anuria vascular injury to hepatic capillaries, in the absence of hepatocellular necrosis, causes jaundice inflammation of the meninges causes headache, neck stiffness, confusion, psychosis, delirium

If a patient dies from leptospirosis, what is the cause of death? Renal failure Cardiopulmonary failure widespread haemorrhage Liver failure is rare, despite the presence of jaundice

What is the outcome of leptospirosis during pregnancy? fetal death abortion Stillbirth congenital leptospirosis

How long is the incubation period? 514 days

serovar-specific antibodies are protective

a patient is immune to reinfection with the same serovar

blood invade all tissues host's immune response convoluted tubules cleared from the kidneys may persist in the eyes

Classic Leptospirosis
Septicemic (leptospiremic) phase
Lasts a week fever of sudden onset chills severe myalgia anorexia conjunctival suffusion nausea Vomiting

3- to 4-day period of relative improvement Immune Phase

leptospires cannot be cultured from blood

 Weils disease(19th century)

fever jaundice Splenomegaly

Weils disease
fever jaundice renal failure

CLINICAL RECOGNITION OF LEPTOSPIROSIS

2010 CPG
FEVER of at least 2 days AND either : residing in a flooded area or has high-risk exposure wading in floods and contaminated water contact with animal fluids swimming in flood water ingestion of contaminated water (with or without cuts or wounds) AND presenting with at least two of the following symptoms: myalgia calf tenderness conjunctival suffusion chills abdominal pain headache jaundice oliguria should be considered a suspected leptospirosis case

MILD
Any suspected case with acute febrile illness BUT with stable vital signs, anicteric sclerae with good urine output no evidence of meningismus / meningeal irritation, sepsis / septic shock, difficulty of breathing nor jaundice and can take oral medications considered MILD LEPTOSPIROSIS and can be managed on an OUT-PATIENT SETTING

MOD-SEVERE
Any suspected case with acute febrile illness unstable vital signs jaundice/icteric sclerae abdominal pain nausea vomiting and diarrhea oliguria/anuria meningismus / meningeal irritation sepsis / septic shock altered mental states or difficulty of breathing Hemoptysis

LABORATORY DIAGNOSIS OF LEPTOSPIROSIS

 it is not necessary to confirm the diagnosis before starting treatment. Early recognition and treatment is MORE important to prevent complications of the severe disease and mortality

What are the laboratory findings in patients with leptospirosis? elevated erythrocyte sedimentation rate, thrombocytopaenia leucocytosis hyperbilirubinaemia elevated serum creatinine elevated creatinine kinase elevated serum amylase

Direct Detection Method 1. Culture and isolation remains the GOLD standard BUT is time-consuming labor-intensive requires 6 to 8 weeks for the result needs darkfield microscopy and has low diagnostic yield. can identify the serovar but is insensitive. 2. Polymerase Chain Reaction (PCR) has the advantage of early confirmation diagnosis especially during the acute leptospiremic phase (first week of illness) before the appearance of.

What is the microscopic agglutination test (MAT)? determines agglutinating antibodies in the serum of a patient by mixing it in various dilutions with live or killed, formolized leptospires.

Antileptospiral antibodies present in the serum cause leptospires to stick together to form clumps

Indirect Detection Methods 1. Microagglutination Test (MAT)

a four-fold rise of the titer from acute to convalescent sera is confirmatory of the diagnosis. highly sensitive and specific time-consuming and hazardous (risk of exposure to the live antigen) Cross-reaction

2. Specific IgM Rapid Diagnostic Tests LeptoDipstick, Leptospira IgM ELISA (PanBio), MCAT and Dridot
Leptospira genus-specific IgM sensitivity : 63%-72% specificity : 93%-96% when tested in illnesses of less than 7 days. If serum samples are taken beyond 7 days, sensitivity improves to > 90%. false negative results - early stage of the illness

 Nonspecific Rapid Diagnostic Tests like LAATS (Leptospira AntigenAntibody Agglutination Test (Leptospira Serology Bio-Rad)
Leptospira antibody used as a screening test but is NOT sensitive. A positive result should be confirmed with MAT

1. Complete blood count (CBC)

leukocytosis with neutrophilia. Thrombocytopenia is common. Platelet count < 100,000/cu mm risk factor for bleeding and pulmonary hemorrhage

2. Urinalysis
proteinuria pyuria hematuria Findings may sometimes be mistaken for UTI.

3. Serum creatinine
increasing impending acute kidney injury

4. Serum creatine phosphokinase (CPK-MM)

elevated severe myalgia.

5. Liver function tests Bilirubin, ALT, AST, and alkaline phosphatase

Elevated

6. Bleeding parameters (Prothrombin time, partial thromboplastin time PTT)

may be prolonged.

SEVERE
1. Complete blood count (CBC)
leucocytosis (WBC>12,000 cells/cumm) with neutrophilia and thrombocytopenia (<100,000 cells/cu mm)

2. Serum creatinine > 3 mg/dL (or CrCl < 20 ml/min) and BUN > 23 mg/dL 3. Liver function tests - AST/ALT ratio > 4x, Bilirubin > 190 umol/L 4. Bleeding parameters - prolonged prothrombin time (PT) < 85% 5. Serum potassium > 4 mmol/L 6. Arterial blood gas (ABG)
severe metabolic acidosis(ph< 7.2, HCO3 < 10) and hypoxemia (PaO2 < 60 mmHg, SaO2 < 90%, PF ratio <250)

7. Chest radiograph demonstrating extensive alveolar infiltrates

8. Electrocardiogram showing signs of heart block, myocarditis

TREATMENT OF LEPTOSPIROSIS

MILD leptospirosis
Doxycycline amoxicillin and azithromycin

MODERATE -SEVERE leptospirosis

Penicillin G ampicillin, 3rd generation cephalosporin (cefotaxime, ceftriaxone), and parenteral azithromycin

Jarisch-Herxheimer reactions have been reported in patients with leptospirosis treated with penicillin. release of heat-stable proteins from spirochetes release of endotoxins occurs faster than the body can remove the toxins. It manifests as fever, chills, rigor, hypotension, headache, tachycardia, hyperventilation, vasodilation with flushing, myalgia and exacerbation of skin lesions. Reaction commonly occurs within two hours of drug administration, but is usually self-limiting.

inflammatory process results from activation of the cytokine cascade during the degeneration of spirochetes
tumor necrosis factor alpha interleukin-6 interleukin-8

Antibiotic therapy should be completed for 7 days, except for azithromycin

Antibiotic therapy should be started as soon as the diagnosis of leptospirosis is suspected regardless of the phase of the disease or duration of symptoms

PROPHYLAXIS FOR LEPTOSPIROSIS

PRE-EXPOSURE PROPHYLAXIS
The most effective preventive measure is avoidance of high-risk exposure
(i.e. wading in floods and contaminated water, contact with animals body fluid).

PRE-EXPOSURE PROPHYLAXIS

Pre-exposure antibiotic prophylaxis is NOT ROUTINELY RECOMMENDED

PRE-EXPOSURE PROPHYLAXIS
Doxycycline 200 mg once weekly, to begin 1 to 2 days before exposure and continued throughout the period of exposure.

PRE-EXPOSURE PROPHYLAXIS
There is NO recommended pre-exposure prophylaxis that is safe for pregnant and lactating women.

POST-EXPOSURE PROPHYLAXIS
LOW-RISK EXPOSURE

single history of wading in flood or contaminated water without wounds, cuts or open lesions of the skin.
Doxycycline 200 mg single dose within 24 to 72 hours from exposure

MODERATE-RISK EXPOSURE single history of wading in flood or contaminated water and the presence of wounds, cuts, or open lesions of the skin OR accidental ingestion of contaminated water Doxycycline 200 mg once daily for 3-5 days to be started immediately within 24 to 72 hours from exposure

POST-EXPOSURE PROPHYLAXIS
HIGH-RISK EXPOSURE continuous exposure
residing in flooded areas, rescuers and relief workers, wading in flood or contaminated water with or without wounds, cuts or open lesions of the skin. Swimming in flooded waters infested with domestic/sewer rats ingestion of contaminated water Doxycycline 200 mg once weekly until the end of exposure

POST-EXPOSURE PROPHYLAXIS

LEPTOSPIROSIS ASSOCIATED AKI

Pathophysiology

OLIGURIA
Oliguria is defined as urine output < 0.5 mL/kg/hr or <400mL/day or a self report of decreased or no urine output within the last 12 hours

DIALYSIS
Any one of the following is an indication for dialysis:

Uremic symptoms Nausea, vomiting, altered mental status, seizure, coma

Serum creatinine > 3mg /dL Serum K > 5 meq /L in an oliguric patient ARDS, pulmonary hemorrhage pH < 7.2

Fluid overload
Oliguria despite measures following the Oliguria algorithm individually or collectively they should indicate early dialysis

Presence of uremic symptoms is an absolute indication for dialysis

 non-oliguric renal failure with mild hypokalemia Oliguria with hyperkalemia poor prognosis

Algorithm for Oliguria

Oliguria - <0.5 ml/kg/hr or <400ml/day or self-report of low or no urine output in 12 hrs Mean Arterial Pressure <65 mm Hg No

Yes

Start Norepinephrine and titrate to keep MAP >65 mmHg

Monitor hourly and adjust rate of IVF to maintain euvolemia

Assess Fluid Status

Yes Hypovolemic?
Fast drip Normal Saline Solution, 20 mL/kg/hr and reassess after 15 minutes Continue hydration till euvolemic Adjust IVF rate to suit patient needs

No

Furosemide 40 mg IV bolus or Bumetamide 1 mg IV

No

Urine Output >0.5 mL/kg/hr?

Yes

Furosemide 40 mg IV bolus

Urine Output >0.5 mL/kg/hr? No

Yes Monitor hourly and adjust rate of IVF to maintain euvolemia

Double dose of furosemide hourly up to a maximum of 160 mg

Yes Urine Output >0.5 mL/kg/hr? No Acute Renal Replacement Therapy

PULMONARY COMPLICATIONS OF LEPTOSPIROSIS

Tachypnea (Respiratory Rate > 30/min) is the first sign of pulmonary involvement in most cases.

Consider lung involvement with the onset of cough, hemoptysis or dyspnea in a patient with a clinical diagnosis of leptospirosis

Pulmonary symptoms usually appear between the 4th and 6th day of disease

Most Common Complications Pulmonary hemorrhage Acute Respiratory Distress Syndrome

PULMONARY HEMORHAGE
disruption of the vascular endothelium would lead to an increase in permeability, which would in turn give rise to alveolar bleeding.
hemoptysis alveolar infiltrates (CXR)

 Bolus methyl prednisolone given within the first 12 hours of onset of respiratory involvement is life saving Methylprednisolone:1gm IV/day for 3 days followed by oral Prednisolone 1 mg/kg/day for 7 days

THANK YOU!

Renal failure