POLICYRECOMMENDATIONSONTHEDIAGNOSIS,MANAGEMENTANDPREVENTIONOFLEPTOSPIROSIS I. OnScreeningandDiagnosis 1. Leptospirosisshouldbesuspectedamongpatientswiththefollowingclinicalmanifestations/features: a. acutefeverofatleast2days b. residinginafloodedareaORhashighriskexposure(definedaswadinginfloodsandcontaminated water,contactwithanimalfluids,swimminginfloodwateroringestionofcontaminatedwaterwith orwithoutcutsorwounds) c.

presentingwithatleasttwoofthefollowingsymptoms: myalgia calftenderness conjunctivalsuffusion chills abdominalpain headache jaundice oliguria

II.

BASIS:LeptospirosisCPG2010,p.7 OnCriteriaforHospitalAdmission 1. AnysuspectedcaseofleptospirosisassociatedwiththefollowingisBESTmanagedinaHEALTHCARE/ HOSPITALSETTING:[GradeA] a. unstablevitalsigns b. jaundice/ictericsclerae c. abdominalpain d. nausea,vomitinganddiarrhea e. oliguria/anuria f. meningismus/meningealirritation g. sepsis/septicshock h. alteredmentalstates i. difficultyofbreathing j. hemoptysis BASIS:asis,p.10

2. SuspectedcasesofleptospirosiswiththefollowingmanifestationscanbemanagedonanOUTPATIENT SETTING:[GradeA] a. stablevitalsigns b. anictericsclerae c. withgoodurineoutput d. noevidenceofmeningismus/meningealirritation e. noevidenceofsepsis/septicshock f. nodifficultyofbreathing g. nojaundice h. cantakeoralmedications BASIS:asis,p.10
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3. Leptospirosismaybeclassifiedaccordingtothefollowing: Table1.ClassificationofLeptospirosis Mild Moderate fever headache myalgia nonproductivecough maculopapularrash stablevitalsigns unstablevitalsigns

Severe

nojaundice/anictericsclerae withgoodurineoutput noevidenceofmeningismus/ meningealirritation noevidenceofsepsis/septic shock nodifficultyofbreathing difficultyofbreathing nausea,vomitinganddiarrhea conjunctivalsuffusion(redeyeswithoutexudate) Severecalfpain abdominalpain alteredmentalstates hemorrhage(mostcommonlypulmonary) myocarditis

hypotensionrefractorytofluid resuscitation jaundice/ictericsclerae oliguria/anuria renalfailure meningismus/meningeal irritation sepsis/septicshock

Clinicalfeaturesassociatedwithincreasedriskformortalityincludealteredmentalstatus,respiratory insufficiency(rales,infiltrates),hemoptysis,oligurichyperkalemicacuterenalfailure,andcardiacinvolvement (myocarditis,completeorincompleteheartblock,atrialfibrillation). BASIS:asis,p.10 OnLaboratoryTests Generally,itisnotnecessarytoconfirmthediagnosisorwaitfortheresultofthetestsbeforestarting treatment.Theclinicalassessmentandepidemiologichistoryaremoreimportant.Earlyrecognitionand treatmentisMOREimportanttopreventcomplicationsoftheseverediseaseandmortality. Ifdefinitiveorconfirmatorydiagnosisiswarrantedinsuspectedcases,thesearethelocallyavailable diagnostictestsforleptospirosis.RefertoAnnexAforthelocalguidelinesforcollectionandtransportof specimensforleptospirosis. 1. DirectDetectionMethod a. CultureandisolationGOLDstandard b. PolymeraseChainReaction(PCR)hastheadvantageofearlyconfirmationofthediagnosis especiallyduringtheacuteleptospiremicphase(firstweekofillness)beforetheappearanceof antibodies.
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III.

2.

IndirectDetectionMethods a. MicroagglutinationTest(MAT)afourfoldriseofthetiterfromacutetoconvalescentserais confirmatoryofthediagnosis.InendemicareaslikethePhilippines,asingletiterofatleast 1:1600insymptomaticpatientsisindicativeofleptospirosis. b. SpecificIgMRapidDiagnosticTestslikeLeptoDipstick,LeptospiraIgMELISA(PanBio),MCATand DridotFalsenegativeresultscanbeaproblemifthetestsareperformedduringtheearlystage oftheillness.Asecondsampleshouldbeobtainedforsuspectedcaseswithinitialnegativeor doubtfulresults. BASIS:asis,p.13 Note:PhilHealthStandardsandMonitoringDepartment(SMD)Consensus:LAATS(Leptospira AntigenAntibodyAgglutinationTest)hasnovalueintheconfirmationofleptospirosis. Thefollowingarenonspecificlaboratoryteststhatcansupportthediagnosisofleptospirosisandcan beusedtoalertthehealthpractitionertomonitorforthedevelopmentofcomplications:

3.

Table2.Nonspecificlaboratorytestsandcorrespondingfindings Laboratorytest Laboratoryfindings Completebloodcount(CBC) Mayshowperipheral leukocytosiswithneutrophilia.Thrombocytopenia withplateletcount iscommon.Plateletcountof<100,000/cummisariskfactorfor bleedingandpulmonaryhemorrhage. Severe:leucocytosis(WBC>12,000cells/cumm)withneutrophiliaand thrombocytopenia(<100,000cells/cumm) Urinalysis Showsproteinuria,pyuria,andoftenhematuria.Hyalineandgranular castsmayalsobepresentduringthefirstweekofillness.Findingsmay sometimesbemistakenforUTI. Serumcreatinine Canbeinitiallynormalandcanelevateduringthecourseoftheillness. Anincreasingserumcreatinineisindicativeofimpendingacutekidney injury. Severe:>3mg/dL(orCrCl<20ml/min)andBUN>23mg/dL Serumcreatine iselevatedinpatientswithsevere myalgia. phosphokinase(CPKMM) Liverfunctiontests Bilirubin,ALT,AST,andalkalinephosphatasemayshowslightelevation. Severe:AST/ALTratio>4x,Bilirubin>190umol/L Bleedingparameters Maybeprolonged. (Prothrombintime,partial thromboplastintimePTT) Severe:prolongedprothrombintime(PT)<85% Serumpotassium Severe:>4mmol/L Arterialbloodgas(ABG) Severe:severemetabolicacidosis(ph<7.2,HCO3<10) andhypoxemia(PaO2<60mmHg,SaO2<90%,PFratio<250) Chestradiograph Severe:demonstratingextensivealveolarinfiltrates Electrocardiogram Severe:showingsignsofheartblock,myocarditis,repolarization Abnormalities BASIS:asis,p.25
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IV.

OnTreatment Table3.DosageofAntibioticsRecommendedforLeptospirosis MildLeptospirosis Antibiotic Dosage doxycycline hydrochloride, hyclate amoxicillin azithromycin dihydrate** 100mgbidPO ModerateSevereLeptospirosis Antibiotic Dosage Firstlineagent penicillinG* 1.5MUq68h

Alternativeagents 500mgq6hor1gq8hPO ampicillinIV 1ginitially,followedby azithromycindihydrate 500mgODfor2more ceftriaxone daysPO cefotaxime

0.51.0gmq6h 500mgODfor5days 1gmq24h 1gmq6h

Step-down therapy can be instituted once patient is clinically stable and able to tolerate oral medication. Any oral antibiotic under mild leptopspirosis can be selected. * PNDF Vol. 1, 7th Ed. 2008 includes penicillin G benzathine 1.2MU vial and 2.4 MU vial; penicillin G crystalline 500,000 units vial, 1MU vial, and 5MU vial ** PNDF Vol. 1, 7th Ed. 2008 includes azithromycin 250 mg capsule,500 mg tablet,200 mg/5 mL powder for suspension, and 500 mg powder, vial as dihydrate

Antibiotictherapyshouldbestartedassoonasthediagnosisofleptospirosisissuspectedregardlessofthephase ofthediseaseordurationofsymptoms.[GradeB] BASIS:asis,p.33 V. OnProphylaxis 1. Preexposure Themosteffectivepreventivemeasureisavoidanceofhighriskexposure(i.e.wadinginfloodsand contaminatedwater,contactwithanimalsbodyfluid).Ifhighriskexposureisunavoidable,appropriate personalprotectivemeasuresincludewearingboots,goggles,overalls,andrubbergloves.[GradeA] PreexposureantibioticprophylaxisisNOTROUTINELYRECOMMENDED.However,inthoseindividuals whointendtovisithighlyendemicareasANDarelikelytogetexposed(e.g.travelers,soldiers,those engagedinwaterrelatedrecreationalandoccupationalactivities),preexposureprophylaxismaybe consideredforshorttermexposures.[GradeB]. Therecommendedregimenforpreexposureprophylaxisfornonpregnant,nonlactatingadultsis: Doxycycline(hydrochlorideandhyclate)200mgonceweekly,tobegin1to2daysbeforeexposureand continuedthroughouttheperiodofexposure.[GradeB] Currently,thereisNOrecommendedpreexposureprophylaxisthatissafeforpregnantandlactating women. BASIS:asis,p.36
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2.

Postexposure Doxycycline(hydrochlorideandhyclate)istherecommendedpostexposurechemoprophylacticagentfor leptospirosis.Thedurationofprophylaxisdependsonthedegreeofexposureandthepresenceof wounds.Individualsshouldcontinuetomonitorthemselvesforfeverandotherflulikesymptomsand shouldcontinuetowearpersonalprotectivemeasuressinceantibioticprophylaxisisnot100%effective. Thedecisiontogiveprophylaxisdependsontheriskexposureassessment. 2.1. LOWRISKEXPOSUREisdefinedasthoseindividualswithasinglehistoryofwadinginfloodor contaminatedwaterwithoutwounds,cutsoropenlesionsoftheskin. Doxycycline200mgsingledosewithin24to72hoursfromexposure[GradeB] 2.2. MODERATERISKEXPOSUREisdefinedasthoseindividualswithasinglehistoryofwadinginfloodor contaminatedwaterandthepresenceofwounds,cuts,oropenlesionsoftheskin,ORaccidental ingestionofcontaminatedwater. Doxycycline200mgoncedailyfor35daystobestartedimmediatelywithin24to72hoursfrom exposure[GradeC] 2.3. HIGHRISKEXPOSUREisdefinedasthoseindividualswithcontinuousexposure(thosehavingmore thanasingleexposureorseveraldayssuchasthoseresidinginfloodedareas,rescuersandrelief workers)ofwadinginfloodorcontaminatedwaterwithorwithoutwounds,cutsoropenlesionsof theskin.Swimminginfloodedwatersespeciallyinurbanareasinfestedwithdomestic/sewerratsand ingestionofcontaminatedwaterarealsoconsideredhighriskexposures. Doxycycline200mgonceweeklyuntiltheendofexposure[GradeB] BASIS:asis,p.38

References(Searchdate:January2012) 1. 2. TheLeptospirosisTaskForce.LeptospirosisCPG,2010 StandardsandMonitoringDepartmentConsensus.PhilippineHealthInsuranceCorporation,2012.

DISCLAIMER Theserecommendationsandrestrictionswerebasedonavailableevidenceandmaybemodifiedbasedonthe availabilityofnewevidence.Furthermore,theyshouldnotreplacegood,uptodateclinicaljudgmentbasedon thepresentcircumstancesineachcase. Allmedicinalproductsmentionedinthepolicystatementshaveaninherentriskprofileandhavetobeusedwith prudenceandcautionintheclinicalsetting.Medicinescancauseunexpectedandunwantedadversedrugeffects andreportingtheseeventstotheFoodandDrugAdministrationisrecommendedinlinewithpublicsafety.The prescribershouldreadtheproductinformationcarefullyandhelpthepatientunderstandtheserisksinrelationto thebenefitsofferedbythesemedicines.Medicinesaresafewhenusedintheproperway.

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AnnexA.Localguidelinesforcollectionandtransportofspecimensforleptospirosis
Laboratorytest Culturefor leptospira Specimentobe Collected BloodinEDTA(purple top) Citratedblood(green top) CSF Urine Besttimetocollect thespecimen Blood,CSFwithin7 daysofillness Urine2ndweekto4th weekofillness Transport Requirements Blood,CSFroom temperature Urinewithin1hr (protectfrom excessiveheator cold) RunningDays Dailyexcept Saturday Sundayand holidays Turnaround Time 6weeks Wheretosendthe specimen 1.PhilippineGeneral Hospital(PGH) MedicalResearch Laboratory(MRL) receivingcounter 2ndfloor,ERcomplex 2.ResearchInstitute forTropicalMedicine (RITM) MicrobiologyDept 9002ResearchDrive, FilinvestCorporate City,Alabang, Muntinlupa RITM MicrobiologyDept 9002ResearchDrive, FilinvestCorporate City Alabang,Muntinlupa PGHMRL receivingcounter 2ndfloor,ERcomplex TheMedicalCity PathologyLaboratory StLukesMedical Center PathologyLaboratory

PCRforLeptospira

Microscopic agglutinationtest (MATfor leptospirosis) Lepto(IgM)card kit/Dridot BioRad macroscopic agglutinationtest

BloodinEDTA(purple top) Wholebloodorserum (redtop) CSF Urine Bloodorserum preferablycollected twiceatanintervalof 10days Wholeblood,serum orPlasma Serum

Blood,CSFwithin7 days ofillness Urine2ndto4thweek >1weekofillness

Chilledorwithcold packs

Dailyexcept Saturday Sundayand holidays

2448 hours

>1weekofillness

Withiceifserum Roomtemperature ifnewlycollected blood Withice

Thursday

Thursday 3pm 4hours

Daily Cutofftime:3pm Daily

>1weekofillness

Withice

2minutes

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