malaria: a diagnosis we can’t afford to miss!

MALARIA: A Diagnosis We MALARIA: A Diagnosis We Can’t Afford to Miss!Can’t Afford to Miss!

By Tamara F. Moise D.O.

Goals of LectureGoals of Lecture

present clinical scenarios of malariapresent clinical scenarios of malaria

review epidemiology, life cycle, review epidemiology, life cycle, pathogenesis, clinical features, pathogenesis, clinical features, diagnosis, and treatment of malariadiagnosis, and treatment of malaria

go over the relevance of this disease go over the relevance of this disease as it pertains to emergency medicineas it pertains to emergency medicine

Clinical CasesClinical Cases

Case 1Case 1: 34 year-old Asian American male, : 34 year-old Asian American male, Boston ED, 2 weeks fevers/chills, malaise, Boston ED, 2 weeks fevers/chills, malaise, n/vn/v

traveled to Ghana 11 months prior to ED traveled to Ghana 11 months prior to ED visit for 2 weeks; + prophylaxis prior to and visit for 2 weeks; + prophylaxis prior to and during his travelduring his travel

visited other ED one week prior, dx’d with visited other ED one week prior, dx’d with viral syndrome; then visited PMD viral syndrome; then visited PMD (+) (+) elevated LFT’s and thrombocytopenia elevated LFT’s and thrombocytopenia

Clinical Cases Clinical Cases

Case 2Case 2: 44 year-old Caucasian : 44 year-old Caucasian French male presented to an ICU in French male presented to an ICU in Marseilles, France with 3 day history Marseilles, France with 3 day history of feverof fever

21-day trip to Gabon, Africa21-day trip to Gabon, Africa

(-) chemoprophylaxis (-) chemoprophylaxis

Clinical Cases Clinical Cases

Case 3Case 3: 38-year-old Guyanese woman : 38-year-old Guyanese woman outpatient facility in France, 5 days outpatient facility in France, 5 days jaundicejaundice

returned from a 5-day Kenya trip; in 11 returned from a 5-day Kenya trip; in 11 days sxms starteddays sxms started

(-) chemoprophylaxis (-) chemoprophylaxis

lived in France since infancylived in France since infancy

IntroductionIntroduction Mosquito-borne protozoan infection that Mosquito-borne protozoan infection that

primarily affects RBC’sprimarily affects RBC’s

5 species of Plasmodial parasite: P. falciparum, 5 species of Plasmodial parasite: P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi P. vivax, P. ovale, P. malariae, P. knowlesi (monkey-derived malaria)(monkey-derived malaria)

P. falciparum P. falciparum deadliest deadliest

Increasing incidence due to several factors, i.e. Increasing incidence due to several factors, i.e. increasing resistance of parasites to anti-increasing resistance of parasites to anti-malarialsmalarials

EpidemiologyEpidemiology 300 to 500 million cases of malaria yearly; 700,000 300 to 500 million cases of malaria yearly; 700,000

to 2.7 million deaths to 2.7 million deaths

Deaths tend to occur in children in developing Deaths tend to occur in children in developing nationsnations

Highest risk of transmissionHighest risk of transmission rural areas, end of the rural areas, end of the rainy seasonrainy season

Regions of greatest intensity of malaria transmission Regions of greatest intensity of malaria transmission are Oceania and sub-Saharan Africa. are Oceania and sub-Saharan Africa. – For example, Kenya’s rainy season can cause its population For example, Kenya’s rainy season can cause its population

over 50-100 infectious mosquito bites per monthover 50-100 infectious mosquito bites per month

EpidemiologyEpidemiology

Epidemiology Epidemiology P. falciparum most prevalent P. falciparum most prevalent Southeast Asia, Southeast Asia,

Haiti, Dominican Republic, Oceania, Amazon Haiti, Dominican Republic, Oceania, Amazon basin of South America, tropical Africabasin of South America, tropical Africa

P. vivax P. vivax Central America, the Middle East, India Central America, the Middle East, India

U.S.U.S. CDC reported 1528 cases of malaria in CDC reported 1528 cases of malaria in 2005, 7 fatal2005, 7 fatal

Out of 775 patients in the US, 20% took malarial Out of 775 patients in the US, 20% took malarial prophylaxis as directed per CDC prophylaxis as directed per CDC

TransmissionTransmission transmitted by female Anopheles sp. transmitted by female Anopheles sp.

mosquito; dusk until dawnmosquito; dusk until dawn

other forms of transmission other forms of transmission – blood transfusion, congenitally acquired blood transfusion, congenitally acquired

disease, organ transplantation, and sharing of disease, organ transplantation, and sharing of contaminated needles contaminated needles

““Airport malaria” Airport malaria” infected mosquitoes infected mosquitoes can enter a country via airplane thereby can enter a country via airplane thereby transmitting infectiontransmitting infection

Transmission Transmission

Anopheles Mosquito

Transmission Transmission anopheles is found in all US anopheles is found in all US

excluding Hawaiiexcluding Hawaii

In non-endemic areas such as the In non-endemic areas such as the US, transmission occurs moreso via US, transmission occurs moreso via congenitally and through blood congenitally and through blood transfusion, rarely via mosquito-transfusion, rarely via mosquito-borne transmissionborne transmission

Life Cycle of MalariaLife Cycle of Malaria

Highlights of the Life CycleHighlights of the Life Cycle

Exoerythrocytic stageExoerythrocytic stage asymptomatic asymptomatic

Liver schizonts rupture after 6 to 16 daysLiver schizonts rupture after 6 to 16 days

P. vivax and P. ovale: P. vivax and P. ovale: – some parasites stay dormant in the some parasites stay dormant in the

hepatocytes and are known as hepatocytes and are known as hypnozoites; they can be reactivated and hypnozoites; they can be reactivated and cause late relapse (months to years later)cause late relapse (months to years later)

PathogenesisPathogenesis

AnemiaAnemia HypoglycemiaHypoglycemia Lactic acidosisLactic acidosis ThrombocytopeniaThrombocytopenia Microvascular dzMicrovascular dz

PathogenesisPathogenesis

anemiaanemia– the parasite alters the red cell membrane, the parasite alters the red cell membrane,

making it less deformable, resulting in making it less deformable, resulting in hemolysis and accelerated splenic hemolysis and accelerated splenic clearance, ultimately causing clearance, ultimately causing anemiaanemia

– TNF-alpha, which is released during red TNF-alpha, which is released during red cell lysis, suppresses hematopoiesis, also cell lysis, suppresses hematopoiesis, also contributing to contributing to anemiaanemia

Pathogenesis Pathogenesis hypoglycemiahypoglycemia and and lactic acidosislactic acidosis

– parasites receive their energy from anaerobic glycolysis parasites receive their energy from anaerobic glycolysis of glucose to lactic acid, which can end up inof glucose to lactic acid, which can end up in

thrombocytopenia thrombocytopenia – Increased splenic sequestration and decreased platelet Increased splenic sequestration and decreased platelet

survival survival

microvascular pathologymicrovascular pathology – falciparum forms sticky knobs on its erythrocytes’ falciparum forms sticky knobs on its erythrocytes’

surfaces. surfaces. – this causes the RBC’s to adhere to endothelial cells of this causes the RBC’s to adhere to endothelial cells of

capillaries and venules capillaries and venules sequestration of RBC’s sequestration of RBC’s microvascular pathologymicrovascular pathology / blood flow obstruction / blood flow obstruction

Pathogenesis Pathogenesis

Host GeneticsHost Genetics Several hemoglobinopathies protect Several hemoglobinopathies protect

against severe malaria, i.e. sickle cell against severe malaria, i.e. sickle cell anemia, alpha and beta thalassemiasanemia, alpha and beta thalassemias

– Sickle cell anemia patients that do not live in Sickle cell anemia patients that do not live in endemic areas may not have as much endemic areas may not have as much protection as those living in endemic areas protection as those living in endemic areas

– Evidence has shown that sickle cell genetic Evidence has shown that sickle cell genetic alterations evolved partly due to a survival alterations evolved partly due to a survival advantage against falciparum advantage against falciparum

ImmunityImmunity

Semi-immune:Semi-immune:– those who live in endemic areas develop partial those who live in endemic areas develop partial

immunity after repeated malarial infectionsimmunity after repeated malarial infections– this does not prevent them from getting re-this does not prevent them from getting re-

infectedinfected– Less severe disease courseLess severe disease course

Problem:Problem:– partial immunity wanes quickly after leaving an partial immunity wanes quickly after leaving an

endemic area endemic area

Clinical PresentationClinical Presentation

Erythrocytic stageErythrocytic stage– point at which patients become point at which patients become

symptomaticsymptomatic

Incubation periodsIncubation periods– P. falciparumP. falciparum 12-14 days 12-14 days– P. vivax and OvaleP. vivax and Ovale can be 2 months up can be 2 months up

to several yearsto several years– P. malariaeP. malariae up to 35 days, but fever can up to 35 days, but fever can

persist for years persist for years

Clinical Presentation Clinical Presentation Signs and symptoms are varied, but fever is Signs and symptoms are varied, but fever is

present in almost all non-immune individualspresent in almost all non-immune individuals

Other frequent symptoms: Other frequent symptoms: – headache - chills/sweatsheadache - chills/sweats– abd pain - n/vabd pain - n/v– fatigue - coughfatigue - cough

fevers: daily and irregular, especially in P. fevers: daily and irregular, especially in P. falciparumfalciparum

Clinical Presentation Clinical Presentation

P. falciparum is unique when P. falciparum is unique when compared to all other malarial compared to all other malarial species because it can be fatal if species because it can be fatal if untreateduntreated

– whereas in P. vivax and ovale, severe whereas in P. vivax and ovale, severe disease is uncommon; it is rare in P. disease is uncommon; it is rare in P. malariaemalariae

Clinical Presentation of Clinical Presentation of P. FalciparumP. Falciparum

High parasitemia levels; over 50% invasion of High parasitemia levels; over 50% invasion of RBC’s has been reportedRBC’s has been reported

Highest risk of severe disease is in the Highest risk of severe disease is in the following groups: following groups: – the nonimmune - children < age of 5 the nonimmune - children < age of 5 – pregnant women - asplenic ptspregnant women - asplenic pts

Higher degrees of parasitemia = higher Higher degrees of parasitemia = higher mortality (nonimmune) mortality (nonimmune)

semi-immune pts: minimal or no clinical disease w/ semi-immune pts: minimal or no clinical disease w/ high parasitemiahigh parasitemia

parasitemia level of 5% parasitemia level of 5% mortality rate inc mortality rate inc

Clinical Presentation of Clinical Presentation of P. Falciparum P. Falciparum

French retrospective study 2005, studied 42 French retrospective study 2005, studied 42 severe malaria patients b/t ’96 and ’02 , initial severe malaria patients b/t ’96 and ’02 , initial clinical profiles and eventual outcomesclinical profiles and eventual outcomes

most frequent findings: jaundice, most frequent findings: jaundice, hyperparasitemia, profound weakness; 2 patients hyperparasitemia, profound weakness; 2 patients died despite ICU intervention died despite ICU intervention

conclusion: malarial patients who initially present conclusion: malarial patients who initially present with these findings should be considered at high with these findings should be considered at high risk for deterioration and death--> should be risk for deterioration and death--> should be monitored in an ICU setting.monitored in an ICU setting.

*Badiaga et al. J Emerg Med 2005; 29:375-382

Complications of Complications of P. FalciparumP. Falciparum

Cerebral MalariaCerebral Malaria altered state of consciousness and/or seizures altered state of consciousness and/or seizures

coma or deathcoma or death

fatal without treatment; even with treatment, fatal without treatment; even with treatment, 15% of children and 20% of adults die15% of children and 20% of adults die

neurological abnormalitiesneurological abnormalities 10-12% of survivors 10-12% of survivors

Risk factors: Risk factors: – extremes of age, HIV, poor nutrition, hx of extremes of age, HIV, poor nutrition, hx of

splenectomy, pregnancy, genetic susceptibilitysplenectomy, pregnancy, genetic susceptibility

Complications of Complications of P. Falciparum P. Falciparum

Extracerebral complications:Extracerebral complications:

anemiaanemiapulmonary edema/ARDS pulmonary edema/ARDS renal failurerenal failuregastroenteritisgastroenteritis

Complications of Complications of P. Falciparum P. Falciparum

AnemiaAnemia – may require transfusionmay require transfusion– DIC may developDIC may develop

Renal FailureRenal Failure – ““Blackwater fever” : Blackwater fever” :

intravascular hemolysis intravascular hemolysis causes large amts of Hb causes large amts of Hb and malarial pigments to and malarial pigments to be present in the urinebe present in the urine

Pulmonary Pulmonary edema/ARDSedema/ARDS– Mortality rates 15%Mortality rates 15%– positive pressure positive pressure

ventilationventilation

GastroenteritisGastroenteritis – Primarily seen in Primarily seen in

childrenchildren

Clinical Presentation of other Clinical Presentation of other Plasmodial SpeciesPlasmodial Species

P. vivax / P. ovaleP. vivax / P. ovale symptoms identical for bothsymptoms identical for both parasitemia levels parasitemia levels 1-2% 1-2%

P. malariaeP. malariae low grade fevers for yearslow grade fevers for years low parasitemia levels (<1-2%)low parasitemia levels (<1-2%) mild symptoms onlymild symptoms only

P. knowlesiP. knowlesi malarial parasite of monkeys known to cause malarial parasite of monkeys known to cause

human infection (Malaysia)human infection (Malaysia) high levels of parasitemia, serious infectionshigh levels of parasitemia, serious infections

DiagnosisDiagnosis consider in any febrile patient who resided consider in any febrile patient who resided

in or traveled to a malarial region, even if in or traveled to a malarial region, even if travel was brief or in transit travel was brief or in transit

prompt testing when the diagnosis is prompt testing when the diagnosis is suspected (falciparum)suspected (falciparum)

initially missed in about 40% of US initially missed in about 40% of US civilians who die of malariacivilians who die of malaria

DiagnosisDiagnosis

Methods of dxMethods of dx: :

– light microscopylight microscopy

– fluorescent microscopy fluorescent microscopy

– antigen detection via HRP-2 and pLDH based antigen detection via HRP-2 and pLDH based serologic assays serologic assays

– PCRPCR

Diagnosis Diagnosis Light MicroscopyLight Microscopy

Giemsa-staining of thick and/or thin blood smears Giemsa-staining of thick and/or thin blood smears conventional method of diagnosing malaria conventional method of diagnosing malaria– combination is gold standard combination is gold standard

smears allow species identification smears allow species identification

can calculate the parasite density (prognosis)can calculate the parasite density (prognosis)

Dependent on microscopists’ skillsDependent on microscopists’ skills– 10% false negative10% false negative

Diagnosis Diagnosis

Stages of P. Vivax in thin blood smears

Diagnosis Diagnosis

Fluorescent MicroscopyFluorescent Microscopy

Is not as specific and sensitive as Is not as specific and sensitive as light microscopylight microscopy

cannot differentiate species and cannot differentiate species and special microscope is requiredspecial microscope is required

Diagnosis Diagnosis

Antigen Detection Test KitsAntigen Detection Test Kits A rapid simple dipstick test A rapid simple dipstick test results in 10-15 minutes results in 10-15 minutes

useful in situations where diagnostic expertise or useful in situations where diagnostic expertise or microscopic facilities are limitedmicroscopic facilities are limited

Binax NOWBinax NOW first antigen testing assay FDA approved first antigen testing assay FDA approved 20072007

Limitations: Limitations: – cannot determine degree of parasitemiacannot determine degree of parasitemia– false positives false positives – not fully reliable for accurate species diagnosisnot fully reliable for accurate species diagnosis

2 assays currently used for testing: HRP-2 and pLDH2 assays currently used for testing: HRP-2 and pLDH

Diagnosis Diagnosis

Diagnosis Diagnosis

Polymerase Chain Reaction (PCR)Polymerase Chain Reaction (PCR) Has the ability to detect parasitemia at Has the ability to detect parasitemia at

very low levelsvery low levels

Is helpful in species identification when Is helpful in species identification when microscopy is equivocalmicroscopy is equivocal

Disadvantages are high cost, labor Disadvantages are high cost, labor intensiveintensive

TreatmentTreatment supportive treatment, anti-malarial drugssupportive treatment, anti-malarial drugs

P. vivax, P. ovale, and P. malariae are P. vivax, P. ovale, and P. malariae are mostly treated on an outpt basismostly treated on an outpt basis

P. falciparum pts are generally admitted P. falciparum pts are generally admitted for observation of any complicationsfor observation of any complications– hospitalized until they are improving clinically hospitalized until they are improving clinically

and parasite count is decliningand parasite count is declining– most can be treated with oral therapymost can be treated with oral therapy severe severe

malaria requires IV therapy/ICUmalaria requires IV therapy/ICU

Treatment – Drug Treatment – Drug ResistanceResistance

ChloroquineChloroquine:: (-) resistance of P. ovale and P. malariae (-) resistance of P. ovale and P. malariae

new increasing resistance of P. vivax new increasing resistance of P. vivax still first line for P. still first line for P. vivaxvivax

Chloroquine-resistant P. falciparum Chloroquine-resistant P. falciparum worldwide except for worldwide except for Mexico, D.R., Haiti, Central American areas west of the Mexico, D.R., Haiti, Central American areas west of the Panama Canal, most of the Middle East and EgyptPanama Canal, most of the Middle East and Egypt

Chloroquine-resistance should be assumed in all pts unless Chloroquine-resistance should be assumed in all pts unless clinician is absolutely certain that the pt traveled only to clinician is absolutely certain that the pt traveled only to the areas above where resistance is not commonplace the areas above where resistance is not commonplace – Treating a pt who has a chloroquine-resistant strain with Treating a pt who has a chloroquine-resistant strain with

chloroquine puts them at increased risk of deathchloroquine puts them at increased risk of death

Treatment Treatment

Tx of other Plasmodial speciesTx of other Plasmodial species

Tx of P.FalciparumTx of P.Falciparum

Uncomplicated vs Severe Falciparum Uncomplicated vs Severe Falciparum MalariaMalaria

Tx of Falciparum Malaria in PregnancyTx of Falciparum Malaria in Pregnancy

Treatment of Other Plasmodial Treatment of Other Plasmodial SpeciesSpecies

Chloroquine: cure rates of 95% for Chloroquine: cure rates of 95% for sensitive strains of Vivax and Falciparumsensitive strains of Vivax and Falciparum– Is still very effective for Ovale and MalariaeIs still very effective for Ovale and Malariae

Primaquine is preferred treatment of P. Primaquine is preferred treatment of P. Ovale and VivaxOvale and Vivax– Must test for G6PD enzyme deficiency before Must test for G6PD enzyme deficiency before

administration to avoid severe hemolysisadministration to avoid severe hemolysis

Treatment – Uncomplicated Treatment – Uncomplicated FalciparumFalciparum

QuinineQuinine:: most commonly recommended treatment for most commonly recommended treatment for

pts with chloroquine-resistant falciparum pts with chloroquine-resistant falciparum malariamalaria

Combined w/ pyrimethamine-sulfadoxine or Combined w/ pyrimethamine-sulfadoxine or doxycyclinedoxycycline

Can also combine with Clindamycin for Can also combine with Clindamycin for pregnants pts or children < 8 yrs oldpregnants pts or children < 8 yrs old

for semi-immunefor semi-immune 3 day 3 day non-immune/SE Asia ptsnon-immune/SE Asia pts 7 day 7 day bitter taste, reversible tinnitusbitter taste, reversible tinnitus poorly poorly

toleratedtolerated

Treatment - UncomplicatedTreatment - Uncomplicated

Atovaquone-ProguanilAtovaquone-Proguanil

inhibits parasite inhibits parasite electron transportelectron transport

for prevention and for prevention and treatmenttreatment

well toleratedwell tolerated combined with combined with

ProguanilProguanil decreases decreases resistanceresistance

MefloquineMefloquine

cure rates >95% in cure rates >95% in many areasmany areas

causes vomiting causes vomiting and neurotoxicities and neurotoxicities i.e. nightmares, i.e. nightmares, seizuresseizures

not recommended not recommended for children <15 kgfor children <15 kg

Treatment - UncomplicatedTreatment - UncomplicatedArtemisininsArtemisinins

Treatment of choice for quinine-resistant P Treatment of choice for quinine-resistant P FalciparumFalciparum

Should always be combined with another Should always be combined with another agent; commonly used with lumfantrineagent; commonly used with lumfantrine

no artemisinin-containing combination no artemisinin-containing combination treatment has been proven to be superior to treatment has been proven to be superior to any otherany other

Now available in US through CDCNow available in US through CDC

Treatment - UncomplicatedTreatment - Uncomplicated

Many treatment guidelines consider Quinine Many treatment guidelines consider Quinine as first-line treatment as first-line treatment

Atovaquone-Proguanil and Artemisinin: Atovaquone-Proguanil and Artemisinin: increasingly being used due to their increasingly being used due to their decreased side effects, if availability and decreased side effects, if availability and cost are not an issuecost are not an issue

Pts on prophylaxis should be treated with a Pts on prophylaxis should be treated with a different drug if they get infecteddifferent drug if they get infected

Treatment – Severe MalariaTreatment – Severe Malaria

You have severe Falciparum malaria if:You have severe Falciparum malaria if: Altered consciousnessAltered consciousness Parasitemia of >5%Parasitemia of >5% JaundiceJaundice OliguriaOliguria Severe normocytic anemiaSevere normocytic anemia HypoglycemiaHypoglycemia Organ failure Organ failure


Malaria patients in an ICU in Cambodia


Supportive treatment is key!Supportive treatment is key! Admit these pts to ICUAdmit these pts to ICU Aggressive fever controlAggressive fever control If oliguria is not responding to fluids, If oliguria is not responding to fluids,

consider dialysisconsider dialysis Close monitoring for hypoglycemiaClose monitoring for hypoglycemia

severesevere Recommend mechanical ventilation for Recommend mechanical ventilation for

acidotic pts to prevent hypercapnia and acidotic pts to prevent hypercapnia and rise in ICPrise in ICP


Tranfuse if Hb is below 7 g/dLTranfuse if Hb is below 7 g/dL Give Vit K for abnormal bleeding Give Vit K for abnormal bleeding Use Valium for seizuresUse Valium for seizures Search for other infections and treatSearch for other infections and treat

– be aware that pts with falciparum malaria are be aware that pts with falciparum malaria are suseptible to gram-negative bacteremiasuseptible to gram-negative bacteremia

– obtain cultures and cover for gram neg, obtain cultures and cover for gram neg, especially for deteriorating ptsespecially for deteriorating pts

Treatment – Severe MalariaTreatment – Severe Malaria NJ White wrote an editorial article that looked at NJ White wrote an editorial article that looked at

previous studies of the treatment of severe malaria previous studies of the treatment of severe malaria ptspts

One of these studies which took place in Paris One of these studies which took place in Paris showed 11% mortality among 98 severe malaria pts; showed 11% mortality among 98 severe malaria pts; another study from Vietnam show a 10-40% mortality another study from Vietnam show a 10-40% mortality

White commented that the relatively low mortality in White commented that the relatively low mortality in Paris was likely due to aggressive renal treatment Paris was likely due to aggressive renal treatment with hemodialysis and mechanical ventilation, with hemodialysis and mechanical ventilation, whereas Vietnam had much less access to these whereas Vietnam had much less access to these modalitiesmodalities

White NJ. Am J Respir Crit Care Med 2003;167:673


Anti-parasitic therapyAnti-parasitic therapy

Should get IV treatment with either a Should get IV treatment with either a quinine-based or artesiminin-based quinine-based or artesiminin-based regimenregimen– Alternative is IM quinineAlternative is IM quinine


Quinine-based regimen:Quinine-based regimen:

IV quinidine gluconate IV quinidine gluconate

Watch for cardiotoxicity and Watch for cardiotoxicity and hypoglycemia!hypoglycemia!


Artemisinin-based RegimensArtemisinin-based Regimens For the most part are not available in the US, For the most part are not available in the US,

except for Artesunate which can be obtained except for Artesunate which can be obtained through CDCthrough CDC

Good for quinine-resistant falciparumGood for quinine-resistant falciparum

Many trials have shown no difference in Many trials have shown no difference in mortality between artemisinin and quinine mortality between artemisinin and quinine – However this tx is preferred if available, especially However this tx is preferred if available, especially

due to lower side effect profile due to lower side effect profile


Exchange Transfusion:Exchange Transfusion:

Recommended when parasitemia is Recommended when parasitemia is >10% or in pts with coma, renal >10% or in pts with coma, renal failure, ARDSfailure, ARDS

Rapidly removes infected RBC’s, Rapidly removes infected RBC’s, toxins, and cytokinestoxins, and cytokines


Efficacy of exchange tranfusion in Efficacy of exchange tranfusion in controversialcontroversial

Riddle et al. performed a meta-analysis Riddle et al. performed a meta-analysis comparing severe falciparum pts who comparing severe falciparum pts who received exchange transfusion vs pts who received exchange transfusion vs pts who had chemotx alonehad chemotx alone

Found that transfusion did not increase the Found that transfusion did not increase the survival ratesurvival rate– Due to study limitations, randomized control Due to study limitations, randomized control

trial is needed to determine the transfusion trial is needed to determine the transfusion efficacyefficacy

Riddle et al. Clin Infect Dis 2002;34:1192

PrognosisPrognosis

Mortality of untreated falciparum is Mortality of untreated falciparum is almost 100% and 10-40% for treatedalmost 100% and 10-40% for treated

Poor prognostic factors:Poor prognostic factors:– Age<3Age<3– SeizuresSeizures– AcidosisAcidosis– Respiratory distressRespiratory distress– papilledemapapilledema

Malaria and PregnancyMalaria and Pregnancy

Pregnant pts Pregnant pts more severe disease coursemore severe disease course

Hypoglycemia and respiratory complications are Hypoglycemia and respiratory complications are more commonmore common

drugs are safe in pregnancy:drugs are safe in pregnancy:– Chloroquine, quinidine/quinine, clindamycin, Chloroquine, quinidine/quinine, clindamycin,

azithromycin, proguanilazithromycin, proguanil

For chloroquine-resistant malaria, common tx is For chloroquine-resistant malaria, common tx is quinine + clindamycin quinine + clindamycin

Case 1Case 1

34 yr old Asian American at Boston ED, 34 yr old Asian American at Boston ED, +prophylaxis before Ghana, +prophylaxis before Ghana, +fevers/n/v+fevers/n/v

Smears + for plasmodial species with Smears + for plasmodial species with parasitemia <1%parasitemia <1%– Lab could not identify speciesLab could not identify species

Admitted and treated with chloroquine Admitted and treated with chloroquine and primaquineand primaquine

Dc’d with dx of probable P. Ovale or P. Dc’d with dx of probable P. Ovale or P. MalariaeMalariae

Case 2Case 2

44 yr old French Caucasian male who did 44 yr old French Caucasian male who did not take prophylaxis before his trip to not take prophylaxis before his trip to Gabon; had 3 days of feverGabon; had 3 days of fever

+ for P. Falciparum on smears with 5% + for P. Falciparum on smears with 5% parasitemiaparasitemia

Admitted with ARF (creatinine 7mg/dL) Admitted with ARF (creatinine 7mg/dL) and acidosis (bicarb 16 mmol/L); treated and acidosis (bicarb 16 mmol/L); treated with IV quininewith IV quinine

Died secondary to ARDS and multi-organ Died secondary to ARDS and multi-organ failure 23 days after admissionfailure 23 days after admission

Case 3Case 3

38 yr old Guyanese woman from 38 yr old Guyanese woman from France who came back from Kenya France who came back from Kenya with no prophylaxis; came with with no prophylaxis; came with jaundicejaundice

+ P. Falciparum on smears; + P. Falciparum on smears; parasitemia 30%parasitemia 30%

Admitted to ICU, went into comaAdmitted to ICU, went into coma Died on day 3 secondary to E.Coli Died on day 3 secondary to E.Coli

urosepsisurosepsis

Relevance to Emergency Relevance to Emergency MedicineMedicine

Kyriacou et al studied 20 pts diagnosed Kyriacou et al studied 20 pts diagnosed with P. Falciparum in Los Angeles in with P. Falciparum in Los Angeles in 1996; all pts had recent travel hx to 1996; all pts had recent travel hx to malarial endemic areas and fevermalarial endemic areas and fever

recent immigrants or expatriates recent immigrants or expatriates coming back from a visit to their native coming back from a visit to their native countrycountry– i.e. Africa, Central America, Indiai.e. Africa, Central America, India

Kyriacou et al. Ann Emerg Med June 1996; 27: 696-699

Relevance to Emergency Relevance to Emergency MedicineMedicine

Results:Results: MC symptoms were fever/chills/vomitingMC symptoms were fever/chills/vomiting

MC signs were tachycardia and hyperpyrexiaMC signs were tachycardia and hyperpyrexia

Malaria was considered in only 12 of the 20 ptsMalaria was considered in only 12 of the 20 pts

Only 4 pts received anti-malarials in the EDOnly 4 pts received anti-malarials in the ED

Hepatitis and gastroenteritis were the MC Hepatitis and gastroenteritis were the MC misdiagnosesmisdiagnoses

No deaths, but 2 needed transfusionNo deaths, but 2 needed transfusion


Relevance to Emergency Relevance to Emergency MedicineMedicineConclusionConclusion

imported falciparum presenting to imported falciparum presenting to ED’s is frequently misdiagnosedED’s is frequently misdiagnosed

consideration of this dz in pts with consideration of this dz in pts with travel hx to malarial regions will help travel hx to malarial regions will help our ability to diagnose falciparum our ability to diagnose falciparum malaria malaria


Take Home PointsTake Home Points diagnostic and treatment challenge for US diagnostic and treatment challenge for US

clinicians clinicians

consider malaria in all who pts who present consider malaria in all who pts who present with fever and a travel hx to endemic areas, with fever and a travel hx to endemic areas, especially natives who return back to their especially natives who return back to their country for even brief visitscountry for even brief visits

P. FalciparumP. Falciparum fatal if untreated; can kill fatal if untreated; can kill young healthy patients rapidly if not treated young healthy patients rapidly if not treated in a timely mannerin a timely manner

Questions?Questions?

ReferencesReferences1.1. Badiaga S, Brouqui P, Carpentier JP, Hovette P, Duigou, Manelli JC, Martin C, Delmont J. Badiaga S, Brouqui P, Carpentier JP, Hovette P, Duigou, Manelli JC, Martin C, Delmont J.

Severe Imported Malaria: Clinical presentation at the time of hospital admission and Severe Imported Malaria: Clinical presentation at the time of hospital admission and outcome in 42 cases diagnosed from 1996 to 2002. J Emerg Med 2005; 29:375-382outcome in 42 cases diagnosed from 1996 to 2002. J Emerg Med 2005; 29:375-382

2.2. McLachlan MJ, Weissman K, Nadel E, Brown D. Case presentations of the Harvard McLachlan MJ, Weissman K, Nadel E, Brown D. Case presentations of the Harvard emergency medicine residency. J Emerg Med 2006; 30:425-428emergency medicine residency. J Emerg Med 2006; 30:425-428

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