Malaria, Emergency Medicine

Doctor123.org

Malaria, Emergency Medicine

Basics

Description

Pregnant patients, especially primigravida, at higher risk ‚

Oil emersion light microscopy of a thick-smear Giemsa stain: ‚

Chest radiograph " ”for pulmonary edema ‚

- Supportive therapy for complications - Chemoprophylaxis: Must be based on region of travel, check WHO database - Malarone - Daily medication - Very well tolerated - Safe in children >5 kg " “ pediatric dosing - Unsafe in pregnancy - 250/100 mg PO daily - Begin 1 " “2 days prior to entering malaria area and continue for 7 days after leaving area

Consider in patients with appropriate exposure/epidemiology and in exposed patients with fever and consistent signs and symptoms. ‚

• Protozoan infection transmitted through the Anopheles mosquito
• Incubation period 8 " “16 days
• Periodicity of the disease is due to the life cycle of the protozoan:Exoerythrocytic phase: Immature sporozoites migrate to liver, where they rapidly multiply into mature parasites (merozoites).Erythrocytic phase: Mature parasites are released into circulation and invade RBCs.Replication within RBCs followed 48 " “72 hr later by RBC lysis and release of merozoites into circulation, repeating cycleFever corresponds to RBC lysis.
• Plasmodium falciparum:Cause of most cases and almost all deathsUsually presents as an acute, overwhelming infectionAble to infect red cells of all ages:Results in greater degree of hemolysis and anemiaCauses widespread capillary obstruction:Results in end-organ hypoxia and dysfunctionMore moderate infection in people who are on or who have recently stopped prophylaxis with an agent to which the P. falciparum is resistantPost-traumatic immunosuppression may cause relapse of malaria in patients who have lived in endemic areas.
• Plasmodium vivax and Plasmodium ovale:May present with an acute febrile illnessDormant liver stages (hypnozoites) that may cause relapse 6 " “11 mo after initial infection
• Plasmodium malariae:May persist in the bloodstream at low levels up to 30 yr

• Exoerythrocytic phase: Immature sporozoites migrate to liver, where they rapidly multiply into mature parasites (merozoites).
• Erythrocytic phase: Mature parasites are released into circulation and invade RBCs.
• Replication within RBCs followed 48 " “72 hr later by RBC lysis and release of merozoites into circulation, repeating cycle
• Fever corresponds to RBC lysis.

• Cause of most cases and almost all deaths
• Usually presents as an acute, overwhelming infection
• Able to infect red cells of all ages:Results in greater degree of hemolysis and anemia
• Causes widespread capillary obstruction:Results in end-organ hypoxia and dysfunction
• More moderate infection in people who are on or who have recently stopped prophylaxis with an agent to which the P. falciparum is resistant
• Post-traumatic immunosuppression may cause relapse of malaria in patients who have lived in endemic areas.

• Results in greater degree of hemolysis and anemia

• Results in end-organ hypoxia and dysfunction

• May present with an acute febrile illness
• Dormant liver stages (hypnozoites) that may cause relapse 6 " “11 mo after initial infection

• May persist in the bloodstream at low levels up to 30 yr

Etiology

• Transmission usually occurs from the bite of infected female Anopheles mosquito.
• North American transmission possible:Anopheles mosquitoes on east and west coasts of US.Transmission may also occur through infected blood products and shared needles.

• Anopheles mosquitoes on east and west coasts of US.
• Transmission may also occur through infected blood products and shared needles.

• Sickle cell trait protective
• Cerebral malaria more common in children
• In highly endemic areas with minimal lab capability, all children presenting with febrile illness may be treated.

Diagnosis

Signs and Symptoms

• Timing:P. falciparum " ”exhibits within 8 wk of returnP. vivax " ”delayed several monthsMost symptomatic within 1 yr
• General:MalaiseChillsFever " ”usually >38 ‚ °CClassic malaria paroxysm:15 min to 1 hr of chillsFollowed by 2 " “6 hr of nondiaphoretic fever ≤39 " “42 ‚ °CProfuse diaphoresis followed by defervescencePattern every 48 hr (P. vivax and P. ovale) or every 72 hr (P. falciparum)Fever pattern may be varied; rare to have classical fever.Orthostatic hypotensionMyalgias/arthralgiasHematologyHemolysis:Blackwater fever; named from the dark color of the urine partially due to hemolysis in overwhelming P. falciparum infectionsJaundiceSplenomegaly:More common in chronic infectionsMay cause splenic rupture
• CNS " ”cerebral malaria:HeadacheFocal neurologic findingsMental status changesComaSeizures
• GI:EmesisDiarrheaAbdominal pain
• Pulmonary:Shortness of breathRalesPulmonary edema
• Severe malaria:One or more of the following:>20% mortality even with optimal managementProstration; unable to sit up by oneselfImpaired consciousnessRespiratory distress or pulmonary edemaSeizureCirculatory collapseAbnormal bleedingJaundiceHemoglobinuriaSevere anemia

• P. falciparum " ”exhibits within 8 wk of return
• P. vivax " ”delayed several months
• Most symptomatic within 1 yr

• Malaise
• Chills
• Fever " ”usually >38 ‚ °C
• Classic malaria paroxysm:15 min to 1 hr of chillsFollowed by 2 " “6 hr of nondiaphoretic fever ≤39 " “42 ‚ °CProfuse diaphoresis followed by defervescencePattern every 48 hr (P. vivax and P. ovale) or every 72 hr (P. falciparum)Fever pattern may be varied; rare to have classical fever.
• Orthostatic hypotension
• Myalgias/arthralgias
• Hematology
• Hemolysis:Blackwater fever; named from the dark color of the urine partially due to hemolysis in overwhelming P. falciparum infections
• Jaundice
• Splenomegaly:More common in chronic infectionsMay cause splenic rupture

• 15 min to 1 hr of chills
• Followed by 2 " “6 hr of nondiaphoretic fever ≤39 " “42 ‚ °C
• Profuse diaphoresis followed by defervescence
• Pattern every 48 hr (P. vivax and P. ovale) or every 72 hr (P. falciparum)
• Fever pattern may be varied; rare to have classical fever.

• Blackwater fever; named from the dark color of the urine partially due to hemolysis in overwhelming P. falciparum infections

• More common in chronic infections
• May cause splenic rupture

• Headache
• Focal neurologic findings
• Mental status changes
• Coma
• Seizures

• Emesis
• Diarrhea
• Abdominal pain

• Shortness of breath
• Rales
• Pulmonary edema

• One or more of the following:>20% mortality even with optimal managementProstration; unable to sit up by oneselfImpaired consciousnessRespiratory distress or pulmonary edemaSeizureCirculatory collapseAbnormal bleedingJaundiceHemoglobinuriaSevere anemia

• >20% mortality even with optimal management
• Prostration; unable to sit up by oneself
• Impaired consciousness
• Respiratory distress or pulmonary edema
• Seizure
• Circulatory collapse
• Abnormal bleeding
• Jaundice
• Hemoglobinuria
• Severe anemia

Essential Workup

• Demonstrates intraerythrocytic malaria parasites
• Cannot exclude diagnosis without three negative smears in 48 hr
• Only high degrees of parasitemia will be evident on a standard CBC smear.

Diagnosis Tests & Interpretation

• CBC:Anemia " ”25%Thrombocytopenia " ”70% have <150Leukocytopenia
• Electrolytes, BUN, creatinine, glucose:Renal failureHypoglycemia (rare)Lactic acidosisHyponatremia
• Urinalysis
• Liver function tests:Increased in 25%Increased bilirubin and lactate dehydrogenase are the signs of hemolysis

• Anemia " ”25%
• Thrombocytopenia " ”70% have <150
• Leukocytopenia

• Renal failure
• Hypoglycemia (rare)
• Lactic acidosis
• Hyponatremia

• Increased in 25%
• Increased bilirubin and lactate dehydrogenase are the signs of hemolysis

• Immunofluorescence assay, enzyme-linked immunosorbent assay, or DNA probes:Differentiates the type of Plasmodium present5 " “7% will have mixed infections.
• Lumbar puncture/CSF analysis:Performed to distinguish cerebral malaria from meningitisCSF lactate/protein elevated with malariaCSF pleocytosis/hypoglycemia absent with malaria

• Differentiates the type of Plasmodium present
• 5 " “7% will have mixed infections.

• Performed to distinguish cerebral malaria from meningitis
• CSF lactate/protein elevated with malaria
• CSF pleocytosis/hypoglycemia absent with malaria

Differential Diagnosis

• Meningitis
• Encephalitis
• Stroke
• Acute renal failure
• Acute hemolytic anemia
• Sepsis
• Hepatitis
• Viral diarrheal illness
• Hypoglycemic coma
• Heat stroke

Treatment

Initial Stabilization/Therapy

• ABCs
• 0.9% NS fluid bolus for hypotension
• Immediate cooling if temperature >40 ‚ °C
• Acetaminophen
• Mist/cool-air fans
• Naloxone, D50W (or Accu-Chek), and thiamine if altered mental status

Ed Treatment/Procedures

• Dependent on considering this diagnosis and identifying the type of malaria present and geographic area of acquisition
• Assume drug resistant until proven otherwise.
• To counter resistance Artemisinin combinations of antimalarials are recommended 1st line.
• Artemisinin-based combination therapy " “ choice is based on geographic region, check WHO databaseArtemether + LumefantrineArtesunate + AmodiaquineArtesunate + MefloquineArtesunate + Sulfadoxine " “Pyrimethamine
• Severe falciparum " ”IV treatment:Artesunate can be given IV or IMArtemisinin can be given rectally
• Supportive therapy for complications
• Chemoprophylaxis: Must be based on region of travel, check WHO databaseMalaroneDaily medicationVery well toleratedSafe in children >5 kg " “ pediatric dosingUnsafe in pregnancy250/100 mg PO dailyBegin 1 " “2 days prior to entering malaria area and continue for 7 days after leaving areaChloroquine:Drug of choice for travelers who want weekly medicationSafe in pregnancy300 mg PO weeklyBegin 2 wk prior to departure and continue for 4 wk after returnMefloquine:Weekly medicationSafe in pregnancy; do not use with certain psychiatric conditions250 mg PO weeklyBegin 2 wk before departure and continue for 4 wk after returnDoxycycline:Daily medicationLeast expensiveUnsafe in pregnancyUnsafe in children <8 y/oRisk with sun exposure100 mg PO dailyBegin 1 day prior to entering area and continue for 4 wk after returnPrimaquine:Daily medicationCannot use in G6PD deficiencyUnsafe in pregnancy30 mg PO every dayBegin 1 day prior to entering area and continue 1 wk after return
• Vaccine is not available, but several are in field trials.

• Artemether + Lumefantrine
• Artesunate + Amodiaquine
• Artesunate + Mefloquine
• Artesunate + Sulfadoxine " “Pyrimethamine

• Artesunate can be given IV or IM
• Artemisinin can be given rectally

• MalaroneDaily medicationVery well toleratedSafe in children >5 kg " “ pediatric dosingUnsafe in pregnancy250/100 mg PO dailyBegin 1 " “2 days prior to entering malaria area and continue for 7 days after leaving area
• Chloroquine:Drug of choice for travelers who want weekly medicationSafe in pregnancy300 mg PO weeklyBegin 2 wk prior to departure and continue for 4 wk after return
• Mefloquine:Weekly medicationSafe in pregnancy; do not use with certain psychiatric conditions250 mg PO weeklyBegin 2 wk before departure and continue for 4 wk after return
• Doxycycline:Daily medicationLeast expensiveUnsafe in pregnancyUnsafe in children <8 y/oRisk with sun exposure100 mg PO dailyBegin 1 day prior to entering area and continue for 4 wk after return
• Primaquine:Daily medicationCannot use in G6PD deficiencyUnsafe in pregnancy30 mg PO every dayBegin 1 day prior to entering area and continue 1 wk after return

• Daily medication
• Very well tolerated
• Safe in children >5 kg " “ pediatric dosing
• Unsafe in pregnancy
• 250/100 mg PO daily
• Begin 1 " “2 days prior to entering malaria area and continue for 7 days after leaving area

• Drug of choice for travelers who want weekly medication
• Safe in pregnancy
• 300 mg PO weekly
• Begin 2 wk prior to departure and continue for 4 wk after return

• Weekly medication
• Safe in pregnancy; do not use with certain psychiatric conditions
• 250 mg PO weekly
• Begin 2 wk before departure and continue for 4 wk after return

• Daily medication
• Least expensive
• Unsafe in pregnancy
• Unsafe in children <8 y/o
• Risk with sun exposure
• 100 mg PO daily
• Begin 1 day prior to entering area and continue for 4 wk after return

• Daily medication
• Cannot use in G6PD deficiency
• Unsafe in pregnancy
• 30 mg PO every day
• Begin 1 day prior to entering area and continue 1 wk after return

Medication

• Acetaminophen: 500 mg (peds: 10 " “15 mg/kg) PO q4 " “6h; do not exceed 5 doses/24 h; max. 4 g/24 h
• Artemether (20 mg) " “lumefantrine (120 mg): 6 dose regimen PO BID ƒ — 3 days
• Artesunate (50 mg) + Amodiaquine (153 mg): 3 dose regimen PO QD ƒ — 3 days
• Artesunate (50 mg) + Sulfadoxine
• Pyrimethamine (500/25): 3 dose regimen 1 tabs of Artesunate PO QD ƒ — 3 and 1 tab
• Sulfadoxine " “Pyrimethamine PO QD ƒ — 1 day
• Artesunate (50 mg) + Mefloquine (250 mg): 3 dose regimen 1 tab of Artesunate PO QD ƒ — 3 days and Mefloquine PO split over 2 " “3 days.
• Dextrose: D50W 1 amp " ”50 mL or 25 g (peds: D25W 2 " “4 mL/kg) IV
• Naloxone (Narcan): 2 mg (peds: 0.1 mg/kg) IV or IM initial dose
• Thiamine (vitamin B1): 100 mg (peds: 50 mg) IV or IM

Follow-Up

Disposition

• ICU admission for severe P. falciparum infection
• Suspected acute P. falciparum infection
• Severe dehydration
• Inability to tolerate oral solution/medication
• >3% of RBC containing parasites

• Non " “P. falciparum infection
• Able to tolerate oral medications

Pearls and Pitfalls

Additional Reading

• American Academy of Pediatrics, Committee on Infectious Diseases. Red Book. 29th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2012.
• Centers for Disease Control and Prevention. Malaria. Available at www.cdc.gov/malaria/.
• Centers for Disease Control and Prevention. Malaria hotline: 770-488-7788.
• Centers for Disease Control and Prevention. Travelers Health. Available at www.cdc.gov/travel/contentYellow Book.aspx.
• www.cdc.gov/malaria/resources/pdf/treatment.ttable.pdf
• Garner ‚ P, Gelband ‚ H, Graves ‚ P, et al. Systemic reviews in malaria: Global policies need global reviews. Infect Dis Clin North Am. 2009;23:387 " “404.
• WHO. Guidelines for the Treatment of Malaria. 2006; 266 p.

Codes

ICD9

• 084.0 Falciparum malaria [malignant tertian]
• 084.1 Vivax malaria [benign tertian]
• 084.6 Malaria, unspecified
• 084.3 Ovale malaria
• 084.4 Other malaria
• 084.5 Mixed malaria
• 084.8 Blackwater fever

ICD10

• B50.9 Plasmodium falciparum malaria, unspecified
• B51.9 Plasmodium vivax malaria without complication
• B54 Unspecified malaria
• B53.0 Plasmodium ovale malaria
• B53.8 Other malaria, not elsewhere classified

SNOMED

• 61462000 Malaria (disorder)
• 62676009 Falciparum malaria (disorder)
• 27052006 Vivax malaria (disorder)
• 19341001 Ovale malaria (disorder)
• 21070001 Mixed malaria (disorder)
• 56625005 Black water fever (disorder)