Malaria

Conference

11/4/2015

Presenter: Edouard Coupet, MD

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THE CASE

CC: “Joint pain”

HPI:

• 23 yo F sent to ED by PMD for “joint pain”
• Reports polyarthralgias x 1 day
• Denies CP or SOB
• Subjective fevers
• Visited Nigeria 4 weeks prior
• Did not take malaria ppx

PMH/PSH: HbSS

Medications: Denies

Allergies: NKMA

Physical Exam

Vitals: T 97.1, HR 102, BP 143/73, RR 16, O2 97% on RA

General: NAD

Skin: Jaundiced

HEENT: Scleral icterus

CVS: Tachycardic, regular rhythm, no murmurs

Pulm: CTAB

Extremities: No erythema, no visible e/o trauma, FROM

Studies: 

CBC: Hgb 4.1, Hct 11.3, WBC 20.4, Plt 98, Retic 11.2

Chem: Na 137, K 3.3, CO2 19, Gluc 127, AG 22

LFTs: T. bili 40.1, D. bili 22.8, AST 226, ALT 91, Alk P 247

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MALARIA

Background:

• Most common cause of hemolytic anemia worldwide
• Most significant disease acquired from travel to tropics
• P. falciparum most deadly parasite; most common form in Africa, Haiti, New Guinea
• P. vivax more common in Central America, Indian subcontinent
• Incubation period = 8-25 days (generally)
• Mortality = 10-50% if untreated
• Clinical signs of infection occur during the erythrocytic phase
  • Cyclical symptoms = erythrocytes lyse due to intracellular replication → merozoites released → new erythrocytes infected
• Parasitized cells lose flexibility → obstruct microcirculation → tissue anoxia of lungs/kidneys/brain
• Parasite may not be visualized on smear due to sequestration

How do I make the diagnosis?

• Symptoms
  • Periodic fevers
  • Malaise
  • HA
  • CP
  • Cough
  • Abd pain
  • Arthralgia
  • Diarrhea
• Paroxysms may not be present in patient’s who received chemoprophylaxis
• Splenomegaly, abdominal tenderness
• Anemia, jaundice
• Coma, altered mental status
• Blood smear
  • First smear positive in >90% of cases
  • If initial negative, must be repeated BID x 2-3 days for proper exclusion of malaria
  • Determines degree of parasitemia and type (i.e. P. falciparum)
• Additional lab findings
  • Normocytic anemia
  • Thrombocytopenia
  • ↑ ESR
  • ↑ LDH
  • LFT abnormalities
  • ↑ Cr
  • Hyponatremia
  • Hypoglycemia
  • False positive VDRL

What makes malaria deadly?

• Hemolysis can lead to severe anemia
• Sequestration → splenomegaly → splenic rupture
• Immune mediated glomerulonephritis
• Cerebral edema (mortality rate >20%)
  • LP: ↑ opening pressure, ↑ protein, mild pleocytosis
• Noncardiogenic pulmonary edema
• Renal failure (ATN)
• Hypoglycemia
• Adherence of infected cells to endothelium → tissue hypoxia

What is “uncomplicated” P. falciparum and how is it managed in the ED?

• Uncomplicated:
  • No e/o organ dysfunction
  • Parasitemia <5%
  • Able to tolerate PO
• Hospitalize:
  • Severe clinical manifestations in non-immune host for P. falciparum or P. knowlesi 
• Report to state health department
• For non-pregnant patients (3 day course)
  • Artemether + lumefantrine
  • Artesunate + amodiaquine
  • Artesunate + mefloquine
  • Dihydroartemisinin + piperaquine
  • Artesunate + sulfadoxine–pyrimethamine (SP)
• For pregnant (1st trimester)
  • Quinine + clindamycin x 7 days
• Additional considerations
  • Avoid artesunate + SP in HIV/AIDS patients taking co-trimoxazole
  • Avoid artesunate + amodiaquine in HIV/AIDS patients taking efavirenz or zidovudine

And if it’s severe?

• Severe P. falciparum malaria:
  • GCS < 11
  • Generalized weakness
  • >2 convulsions within 24 hours
  • Acidosis
  • Shock
  • Pulmonary edema
  • Cr > 3 mg/dL or BUN >20
  • T. bili >50 + parasite count >100,000
  • Significant hemorrhage
  • Hgb <7 g/dL, Hct <20%
  • Glucose <40 mg/dL
  • Hyperparasitemia >10%
• Do not delay treatment in the unstable patient if strong suspicion for malaria as initial smear may be falsely negative
• Treatment (IV for ≥24 hours then 3 days PO course)
  • Artesunate (IV)
    • Clears malaria faster than quinine
    • Distributed only through CDC
  • Quinidine (IV) also appropriate choice; more available in US

What do I do for the associated complications?

• AMS
  • Due to cerebral sequestration of infected erythrocytes
  • Requires LP to rule out meningitis as cause
  • Seizures commonly reported in children and to be treated with benzodiazepines
  • Steroids of no benefit
• Anemia
  • Transfuse at Hgb <4 g/dL or <6 g/dL if AMS, acidosis, shock, or parasitemia >20%
  • There is no evidence to support exchange transfusions as an adjunct and is not recommended by CDC or WHO
• Respiratory distress
  • Patient may develop noncardiogenic pulmonary edema (similar to ARDS)
  • Supplemental O2 to be administered
  • May require mechanical ventilation

REFERENCES

Bremen, Joel. “Clinical manifestations of malaria.” Up To Date. http://www.uptodate.com, 5 Nov. 2015. Web. 30 Nov. 2015. http://www.uptodate.com/contents/clinical-manifestations-of-malaria

Kyriacou DN, Spira AM, Talan DA, Mabey DC. Emergency department presentation and misdiagnosis of imported falciparum malaria. Ann Emerg Med. 1996;27(6):696-9.

Taylor, Terrie. “Treatment of severe falciparum malaria.” Up To Date. http://www.uptodate.com, 29 Oct. 2015. Web. 30 Nov. 2015. http://www.uptodate.com/contents/treatment-of-severe-falciparum-malaria

Tintinalli, Judith E., and J. Stephan. Stapczynski. Tintinalli’s Emergency Medicine: A Comprehensive Study Guide. 7th ed. New York: McGraw-Hill, 2011.

World Health Organization. Guidelines for the treatment of malaria, 3rd ed, WHO, Geneva 2015. http://www.who.int/malaria/publications/atoz/9789241549127/en/