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SinghiS
ChaudharyD
VargheseGM GUIDELINES
BhallaA
KarthiN Year:2014|Volume:18|Issue:2|Page:6269
KalantriS Tropicalfevers:Managementguidelines
PeterJV
MishraR
BhagchandaniR SunitSinghi1,DhruvaChaudhary2,GeorgeMVarghese3,AshishBhalla4,NKarthi5,SKalantri6,JVPeter7,
MunjalM RajeshMishra8,RajeshBhagchandani9,MMunjal10,TDChugh11,NarendraRungta12
ChughTD 1DepartmentofPediatricsandInchargePICUandEmergencyServices,PGIMER,Chandigarh,India
RungtaN 2DepartmentofPulmonologyandCriticalCarePGIMS,Haryana,India
3Infectiousdisease,ChristianMedicalCollege,Vellore,TamilNadu,India
SearchinGoogleScholar
4DepartmentofInternalMedicine,PGIMER,Chandigarh,India
for
5DepartmentofPediatrics,PGIMER,Chandigarh,India
SinghiS 6DepartmentofInternalMedicine,JLNMedicalCollegeWardha,Wardha,Maharashtra,India
ChaudharyD 7CriticalCareMedicine,ChristianMedicalCollege,Vellore,TamilNadu,India
VargheseGM
8ConsultantPhysicianandIntensivist,Ahmedabad,Gujarat,India
BhallaA
KarthiN 9ConsultantIntensivist,ApexHospital,Bhopal,MadhyaPradesh,India
KalantriS 10ConsultantIntensivist,JeevanrekhaCriticalCareandTraumaHospital,Jaipur,Rajasthan,India
PeterJV 11ProfessorEmeritusPathology,PGIMS,Rohtak,Haryana,India
MishraR 12CriticalCareMedicine,JeevanrekhaCriticalCareandTraumaHospital,Jaipur,Rajasthan,India
BhagchandaniR
MunjalM
ChughTD
RungtaN DateofWebPublication 30Jan2014

Relatedarticles CorrespondenceAddress:
NarendraRungta
Tropicalfever CriticalCareMedicine,JeevanrekhaCriticalCareandTraumaHospital,Jaipur,Rajasthan
Dengue India
Malaria
Typhoid
Leptospirosis SourceofSupport:None,ConflictofInterest:None
Scrubtyphus
Sepsis
Influenza Check 3
Guidelines
DOI:10.4103/09725229.126074
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EmailAlert* Abstract
AddtoMyList*
*Registrationrequired(free) Tropicalfeversweredefinedasinfectionsthatareprevalentin,orareuniquetotropicalandsubtropicalregions.
Someoftheseoccurthroughouttheyearandsomeespeciallyinrainyandpostrainyseason.Concernedabout
INTHISArticle highprevalenceandmorbidityandmortalitycausedbytheseinfections,andoverlappingclinicalpresentations,
Abstract difficultiesinarrivingatspecificdiagnosesandneedforearlyempirictreatment,IndianSocietyofCriticalCare
Introduction Medicine(ISCCM)constitutedanexpertcommitteetodevelopaconsensusstatementandguidelinesfor
managementofthesediseasesintheemergencyandcriticalcare.Thecommitteedecidedtofocusonmost
Methods commoninfectionsonthebasisofavailableepidemiologicdatafromIndiaandoverallexperienceofthegroup.
ResultsandReco...
Appendix1 Theseincludeddenguehemorrhagicfever,rickettsialinfections/scrubtyphus,malaria(usuallyfalciparum),
http://www.ijccm.org/article.asp?issn=09725229year=2014volume=18issue=2spage=62epage=69aulast=Singhi 1/9
2/19/2017 Tropicalfevers:ManagementguidelinesSinghiS,ChaudharyD,VargheseGM,BhallaA,KarthiN,KalantriS,PeterJV,MishraR,BhagchandaniR,

References typhoid,andleptospirabacterialsepsisandcommonviralinfectionslikeinfluenza.Thecommitteerecommendsa
ArticleTables 'syndromicapproach'todiagnosisandtreatmentofcriticaltropicalinfectionsandhasidentifiedfivemajorclinical
syndromes:undifferentiatedfever,feverwithrash/thrombocytopenia,feverwithacuterespiratorydistress
syndrome(ARDS),feverwithencephalopathyandfeverwithmultiorgandysfunctionsyndrome.Evidencebased
ArticleAccessStatistics algorithmsarepresentedtoguidecriticalcarespecialiststochoosereliablerapiddiagnosticmodalitiesandearly
Viewed 8139 empirictherapybasedonclinicalsyndromes.
Printed 206
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SinghiS,ChaudharyD,VargheseGM,BhallaA,KarthiN,KalantriS,PeterJV,MishraR,BhagchandaniR,
MunjalM,ChughTD,RungtaN.Tropicalfevers:Managementguidelines.IndianJCritCareMed201418:62
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MunjalM,ChughTD,RungtaN.Tropicalfevers:Managementguidelines.IndianJCritCareMed[serial
online]2014[cited2017Feb19]18:629.Availablefrom:http://www.ijccm.org/text.asp?2014/18/2/62/126074
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Introduction
HospitalManagement
EveryyeardifferentpartsofIndiaarehitbyseasonalfeversinthepostmonsoonperiod.Thesefeversinclude
Dengue,Malaria,ScrubTyphus,Leptospirosis,Typhoidfeverandsomeotherfeversleadingtoveryhigh
morbidityandmortality.Alargenumberofthesepatientsrequireintensivecareunit(ICU)carelikemechanical
ventilation,renalreplacementstherapy,vasopressorsupport,bloodandbloodcomponenttherapyduetosingleor
multiorganfailure.Theclinicalpictureofthesediseasesissooverlappingthatitisalmostimpossibletoachieve
differentialdiagnosisofthesediseasesinemergencyandICUsettingswhenthetimeavailableforinterventionis
limited.IndianSocietyofCriticalCareMedicine(ISCCM)wasseizedofthematterforseveralyears.Giventhis
background,ISCCMdecidedtodevelopaconsensusstatementandguidelinesformanagementofthesediseasesin
ICU.

Methods

Anexpertcommitteeconsistingofscientists,teachersandresearchersfromIndiawasconstitutedtodiscussthis
topic,tracktheliterature,sharetheexperienceandbrainstormtodevelopguidelines.Thecommitteeincluded
Clickonimagefordetails. expertsfromCriticalcare,EmergencyMedicine,Infectiousdiseases,InternalMedicine,Pediatrics,Microbiology
[Appendix1].

ThegroupofexpertsafterexchangingnotesonEmailsestablishedaliteraturebank,whichwassharedbyallthe
members.EachonesharedhisinputsonEmailwithall.Thus,athoroughreviewofliteraturewasdoneusing
availableresourcesincludingPubMed.Thescopeofreviewcoveredboth,adultsandchildren,presentinginICU.
Thisresultedinbackgroundresource.Theneachexpertwasallottedaspecifictopicfordiscussionfromthe
reviewedliteratureandpreparingaPowerPointpresentationonthesame.Allexpertsgottogetherfor2daysfora
facetofacemeetingandhadextensivebrainstorming,discussionbasedonliteratureandPowerPointpresentations
preparedbyeachexpert.Inferencesweredrawnbasedontheavailableevidenceandexpertopinion.Theneach
expertwasfurtherrequestedtocompilerecommendationsonthetopicallottedtohimbasedonthediscussions.
Therecommendationswereagainsharedanddiscussedonemeetings.Finallyafterfull1year'ssearch,work,
brainstormingandcoordination,aconsensusstatementhasbeenarrivedwhichisstronglyevidencebased.

Thelevelsofevidenceusedinthisguidelinearegivenin[Table1].Itistobenotedthatthehierarchyofevidence
relatetothestrengthofliteratureandnottoclinicalimportance.

Table1:Hierarchyofevidence

Clickheretoview

Tropicaldiseasesweredefinedasdiseasesthatareprevalentin,oruniquetotropicalandsubtropicalregions.The
diseasesarelessprevalentintemperateclimates,dueinparttotheoccurrenceofacoldseason,whichcontrolsthe
insectpopulationbyforcinghibernation.[1]Mostoftendiseaseistransmittedbyaninsect"bite",whichcauses
transmissionoftheinfectiousagent.TheIndiansubcontinentbyitsverylocationrepresentsoneofthelargest
tropicalandsubtropicalregionswithmanyoftheseinfectionsbeingprevalent.Someoftheseoccurthroughoutthe
yearandsomearegreatlyinfluencedbytheseasons(especiallyrainyseason)andgeography.[2]Onthebasisof
limitedepidemiologicdatafromthenorth(Rohtak)andSouth(Vellore)andoverallexperienceofthegroup,itwas
decidedtofocusonsevenmostcommoninfections,withreferencetootherinfectionswhereverappropriate.[3],[4],
[5]Thesearedengue,rickettsialinfectionsespeciallyscrubtyphus,malaria(usuallyduetoPlasmodium

falciparum),typhoidandleptospirosisbacterialsepsisandcommonviralinfectionslikeinfluenza.Itwas
recognizedthatoccasionallythepatientsmayhaveconcomitantinfectionsandcanpresentwithatypical
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manifestations.[6],[7],[8]

Thegroupacceptedthatmanagementofsickpatientswithtropicalinfectionsmustbeginassoonasthepatient
reportstotheemergencydepartment/ICUinahospital.Theseinfectionsmustbesuspectedinallfebrilepatientsas
delayintheinstitutionofspecifictherapymayleadtoincreasedmorbidityandmortality.Sincethesymptomsof
manyinfectionsmayoverlapwithoneanotherandwithseverebacterialsepsis,itmaybeverydifficulttoidentify
theseinfectionsatthetimeofpresentation.Yet,mostofthetime,empirictherapyneedstobeinitiatedatthe
outset.Therecanbenouniformguidelineforempirictherapybuttrendsoftropicalinfectionsshouldguidethe
treatingphysician.Inasickpatient,theideaistohitwideandhitearlywiththeintentiontodeescalateoncethe
definitivediagnosisisestablished.[9]

ResultsandRecommendations

Thegroupagreedthata"syndromicapproach"totropicalinfectionscanguidetheintensivistsregardingthe
commonestetiologies,investigativemodalitiesandhelpthemtochooseearlyempirictherapy.Foreaseof
diagnosistheseinfectionsweredividedintofivemajorsyndromes:undifferentiatedfever,feverwith
rash/thrombocytopenia,feverwithacuterespiratorydistresssyndrome(ARDS),feverwithencephalopathyand
feverwithmultiorgandysfunctionsyndrome.[10]Commoninfectionsthatarelikelytocausethesesyndromesare
asfollows[Table2]:

Table2:SyndromebasedTreatmentguidelinesforcriticaltropicalinfections

Clickheretoview

Undifferentiatedfever

Malaria(P.falciparum),scrubtyphus,leptospirosis,typhoid,dengueandothercommonviralillness.

Feverwithrash/thrombocytopenia

Dengue,rickettsialinfections,meningococcalinfection,malaria(usuallyfalciparum),leptospirosis,measles,
rubellaandotherviralexantem.

FeverwithARDS

Scrubtyphus,falciparummalaria,influenzaincludingH1N1,leptospirosis,hantavirusinfection,meliodosis,
severecommunityacquiredpneumoniasduetoLegionellaspp.andStreptococcuspneumoniaeanddiffuse
alveolarhemorrhageduetocollagenvasculardiseases.

Febrileencephalopathy

Encephalitis(Herpessimplexvirusencephalitis,JapaneseBandotherviralencephalitis),meningitis(S.
pneumoniae,Neisseriameningitidis,Haemophilusinfluenzae,enteroviruses),scrubtyphus,cerebralmalariaand
typhoidencephalopathy.

Feverwithmultiorgandysfunction

Bacterialsepsis,falciparummalaria,leptospirosis,scrubtyphus,dengue,hepatitisAorEwithfulminanthepatic
failureandhepatorenalsyndrome,Hantavirusinfection,hemophagocytosisandmacrophageactivation
syndrome.

AnalgorithmicapproachforthediagnosisandmanagementofcriticaltropicalinfectionsisgiveninFlowChart
1[Additionalfile1]and2[Additionalfile2].

Followingarethesyndromebasedmanagementprinciplesforcriticaltropicalinfections.

Specificinfections

Salientfeaturesofcommontropicalinfectionsaregivenbelow.

Scrubtyphus

Causativeorganism:Orientiatsutsugamushi
Vector:chiggers(larvaofTrombiculidmite).

OutbreaksarereportedfromalloverIndiastartingfromthesubHimalayanbelttomoreeasternandsouthern
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Indianregions.[11],[12],[13]

Pathophysiology:Theorganisminfectsvascularendotheliumwithsubsequentvascularinjuryinorganslikethe
skin,liver,kidneys,meningesandbrainresultinginmultiorganmanifestations.

ClinicalFeatures:Incubationperiod:13weeks:

Fever,headacheandmyalgia,breathingdifficulty,delirium,vomiting,cough,jaundice
Eschar.

Complications:OverwhelmingpneumoniawithARDSlikepresentation,hepatitis,asepticmeningitis,
myocarditisanddisseminatedintravascularcoagulation(DIC).

LabDiagnosis(Serology):[14]

WeilFelix:poorsensitivityandspecificity
Indirectfluorescentantibody:"Goldstandard"(LevelIIA)
Enzymelinkedimmunosorbentassay(ELISA)forimmunoglobulinG(IgG)andIgMantibodies:sensitivity
andspecificity>90%.

Treatment:[15],[16]

Firstline:Doxycycline100mgBDfor7days(LevelIA)
AzithromycinorRifampicinorchloramphenicolasalternativesinchildrenandpregnantwomen.(Level
IIB).

Leptospirosis

Causativeorganism:Leptospirainterrogans
Sourceofinfection:Directcontactofskinormucosawithwatercontaminatedwithurineorbodyfluidofan
infectedanimal.

Peakincidenceduringtherainyseason.Rampantinsouthern,westernandeasternIndia.Increasingincidencein
"nonendemic"northernIndia.[17],[18]

Pathophysiology:Leptospiresmultiplyinthesmallbloodvesselendothelium,resultingindamageandvasculitis
andclinicalmanifestations.

Clinicalfeatures:Incubationperiod:usually514daysbutcanbe72htoamonthormore.

Biphasicclinicalpresentation:

Anictericleptospirosis

Abruptonsetoffever,chills,headache,myalgia,abdominalpain,conjunctivalsuffusion,transientskinrash.
Ictericleptospirosis(Weil'sdisease)occursin515%Jaundice,proteinuria,hematuria,oliguriaand/or
anuria,pulmonaryhemorrhages,ARDS,myocarditis.

Diagnosis:[19],[20]

Raisedcreatinephosphokinaselevels,Culture(blood,cerebrospinalfluid(CSF),urine)
Positiveserology
Microscopicagglutinationtest(Sensitivity3063%,specificity>97%)
IgMELISA(Sensitivity5289%,specificity>94%).

Treatment:[21],[22]

Firstline:PenicillinG1.5MU6hourlyfor7days(LevelIA)
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Firstline:PenicillinG1.5MU6hourlyfor7days(LevelIA)

Alternative:Thirdgenerationcephalosporins.OralDoxycyclineinuncomplicatedinfections.

Plasmaexchange,corticosteroidsandintravenous(i.v.)Iginselectedpatients(LevelIII)inwhomconventional
therapydoesnotelicitaresponse.

Dengue

Causativeorganism:Denguevirus(Flavivirus)serotypes14.

Vector:Aedesmosquitoes:

DengueisendemicthroughoutIndiawitharecentresurgenceofepidemicsoverthepasttwodecades.[23]

Pathogenesis:

Crossreactive(butnonneutralizing)antidengueantibodiesfrompreviousinfectionenhancenewly
infectingstrainwithviraluptakeofmonocytesandmacrophages
Amplifiedcascadeofcytokinesandcomplementactivation
Endothelialdysfunction,plateletdestructionandconsumptionofcoagulationfactors,Plasmaleakageand
hemorrhagicmanifestations.

Clinicalfeatures:Incubationperiod410days:[24]

Denguefever

Headache,retroorbitalpain,myalgia,arthralgia,rash

DengueHemorrhagicfever

Thrombocytopenia(<100,000),skin,mucosalandgastrointestinalbleeds,thirdspacing,riseinhematocrit

Dengueshocksyndrome

Weakpulse,coldclammyextremities,pulsepressure<20mmHg,hypotension
Expandeddenguesyndrome

Encephalitis,myocarditis,hepatitis,renalfailure,ARDS,hemophagocytosis.

Diagnosis:

Nonstructuralprotein1antigendetection(Rapidcardtest)Sensitivity7693%,Specificity>98%.[25]
IgM,IgGserology(IgGtiter>1:1280is90%sensitiveand98%specific).

Treatment:[26]

Isotonicfluidinfusionjustsufficienttomaintaineffectivecirculationduringtheperiodofplasmaleakage
guidedbyserialhematocritdeterminations.(LevelIA)
Bloodtransfusionisdoneonlywithovertbleeding/rapidfallinhematocrit.

Malaria

Causativeorganism:Plasmodiumprotozoa(P.falciparum,Plasmodiumvivax,Plasmodiummalariae[Odisha]).

Vector:Anophelesmosquito.

PlasmodiumspeciesareunevenlydistributedacrossIndia.Orissa,Chhattisgarh,WestBengal,Jharkhandand
Karnatakacontributethemosttotheendemicity.[27]

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Pathophysiology:

Mechanicalmicrocirculatoryobstructioncausedbycytoadherencetothevascularendotheliumof
parasitizedRBCandsequestration
Intravascularhemolysis.

Clinicalfeatures:

Paroxysmoffever,shakingchillsandsweatsoccurevery48or72h,dependingonspecies.Hepatosplenomegaly
maybepresent.

Manifestationsofseveremalaria:[28]

Cerebralmalaria(sometimeswithcoma)
Severeanemia
Hypoglycemia
Metabolicacidosis
Acuterenalfailure(serumcreatinine>3mg/dl)
ARDS
Shock("algidmalaria")
DIC
Hemoglobinuria
10.Hyperparasitemia(>5%).

Diagnosis:

Microscopy:ThicksmearsparasitedetectionThinsmearsspeciesidentification
Quantitativebuffycoattest
Rapiddiagnostictests(RDTs)histidinerichprotein,lactatedehydrogenaseantigenbasedimmune
chromatography(LevelIA)
Sensitivityandspecificity>95%

MalariaruledoutiftwonegativeRDTs.[29]

Treatment:[28]

Drugofchoice:Artesunate(LevelIA)
Dose:2.4mg/kgi.v.bolusatadmission,12hand24hfollowedbyonceadayfor7days+Doxycycline
100mgp.o.12hourly.

Alternative:Quinine20mg/kgloadingdose,followedby10mg/kgi.v.infusion8hourly+Doxycycline100mg
p.o.12hourly.

Clindamycinisrecommendedinplaceofdoxycyclineinpregnantwomenandchildren.(LevelIA)Exchange
transfusionisatreatmentoptionforparasitemia>10%.(itisnotrecommendedwithArtesunate,LevelIIA).

Entericfever

Causativeorganism:Salmonellatyphi,serovarparatyphiA,BorC
Transmission:focallycontaminatedfoodandwater
Mostprevalentinurbanareas,withhighincidenceinchildren15yearsofageandyounger.[30]

Pathophysiology:Bacteriaspreadthroughoutthereticuloendothelialsystemandinareasofgreatestmacrophage
concentrationsuchasthePeyer'spatches.

Clinicalfeatures:Incubationperiod114days.

Manifestations:

1stweekfever,headache,relativebradycardia
2ndweekAbdominalpain,diarrhea,constipation,hepatoslenomegaly,encephalopathy
3rdweekIntestinalbleeding,perforation,MODS.
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3rdweekIntestinalbleeding,perforation,MODS.

Diagnosis:[31]

Typhidot(RDT)Sensitivity9597%,Specificity>89%,LevelIII
Widaltestnonspecific
BloodcultureGoldstandard,positivein4080%ofpatients
Bonemarrowculturessensitivity8095%mayremainpositiveevenafter5daysofpretreatment.

Treatment:[32]

Firstline:Ceftriaxonei.v.5075mg/kg/dayfor1014days(LevelIA)tocoverMDRS.typhi.
AzithromycinandCiprofloxacinarealternatives

Considerdexamethasone3mg/kgfollowedby1mg/kg6hourlyfor48hinselectedcaseswithencephalopathy,
hypotensionorDIC(LevelIB).

Japaneseencephalitis

Causativeorganism:Japaneseencephalitisvirus,

Vector:Culextritaeniorhynchus.

PrevalentinSouthern,centralandNorthEasternIndianstatessuchasUttarPradesh,Haryana,Bihar,Maharastra,
AndhraPradeshandTamilNadu.[33]

Pathophysiology:Virusreachesthecentralnervoussystemthroughleukocytesandaffectsvariouspartsofthe
braintocausevascularcongestion,microglialproliferation,formationofgliomesenchymalnodules,focalor
confluentareasofcysticnecrosisandcerebraledema.

Clinicalfeatures:Incubationperiodaverages68days,witharangeof415days.

Prodromalperiodfever,headache,vomitingandmyalgia.

Neurologicalfeatures[34]rangefrommildconfusiontoagitationtoovertcoma.Parkinsonlikeextrapyramidal
signsarecommon,includingmasklikefacies,tremor,rigidityandchoreoathetoidmovements.

Diagnosis:

IgMcaptureELISASerum:sensitivity8593%,Specificity9698%,CSF:Sensitivity6580%,Specificity89
100%.

Treatment:

SupportiveAirwaymanagement,seizurecontrolandmanagementofraisedintracranialpressure.

Appendix1

ISCCMtropicalfeverExpertCommittee

Chairperson:DrNarendraRungta,Chief,CriticalCareMedicine,JeevanrekhaCriticalCareandTrauma
Hospital,Jaipur.

Members

1.Dr.TDChugh,ProfessorEmeritusPathology,PGIMS,Rohtak.
2.ProfessorSunitSinghi,Head,DepartmentofPediatricsandInchargePICUandEmergencyServices,
PGIMER,Chandigarh.
3.ProfessorSPKalantri,DeptofInternalMedicine,JLNMedicalCollegeWardha.
4.Professor,DhruvaChaudhary,Head,PulmonologyandCriticalCarePGIMS,Rohtak.
5.ProfessorGeorgeVerghese,Head,Infectiousdisease,ChristianMedicalCollege,Vellore.
6.ProfessorJVPeter,Head,CriticalCareMedicine,ChristianMedicalCollege,Vellore.
7.Dr.AshishBhalla,AssociateProfessor,PGIMER,Chandigarh.
8.DrRajeshMishra,ConsultantPhysicianandIntensivist,Ahmedabad.
9.DrRajeshBhagchandani,IntensivistApexHospital,Bhopal.

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Tables

[Table1],[Table2]

Thisarticlehasbeencitedby
1 ApproachtoClinicalSyndromeofJaundiceandEncephalopathyinTropics
AnilC.Anand,HitendraK.Garg
JournalofClinicalandExperimentalHepatology.2014
[Pubmed]|[DOI]

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