Basics
Description
- 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 cycle
- Fever corresponds to RBC lysis.
- Plasmodium falciparum:
- 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.
- Plasmodium vivax and Plasmodium ovale:
- May present with an acute febrile illness
- Dormant 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
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.
- 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.
Pregnant patients, especially primigravida, at higher risk ‚
Diagnosis
Signs and Symptoms
- Timing:
- P. falciparum " ”exhibits within 8 wk of return
- P. vivax " ”delayed several months
- Most symptomatic within 1 yr
- General:
- Malaise
- Chills
- Fever " ”usually >38 ‚ °C
- Classic malaria paroxysm:
- 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.
- 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 infections
- May cause splenic rupture
- CNS " ”cerebral malaria:
- Headache
- Focal neurologic findings
- Mental status changes
- Coma
- Seizures
- GI:
- Emesis
- Diarrhea
- Abdominal pain
- Pulmonary:
- Shortness of breath
- Rales
- Pulmonary edema
- Severe malaria:
- One or more of the following:
- >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
Oil emersion light microscopy of a thick-smear Giemsa stain: ‚
- 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
Lab
- CBC:
- Anemia " ”25%
- Thrombocytopenia " ”70% have <150
- Leukocytopenia
- Electrolytes, BUN, creatinine, glucose:
- Renal failure
- Hypoglycemia (rare)
- Lactic acidosis
- Hyponatremia
- Urinalysis
- Liver function tests:
- Increased in 25%
- Increased bilirubin and lactate dehydrogenase are the signs of hemolysis
Imaging
Chest radiograph " ”for pulmonary edema ‚
Diagnostic Procedures/Surgery
- Immunofluorescence assay, enzyme-linked immunosorbent assay, or DNA probes:
- Differentiates the type of Plasmodium present
- 5 " “7% will have mixed infections.
- Lumbar puncture/CSF analysis:
- 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 database
- Artemether + Lumefantrine
- Artesunate + Amodiaquine
- Artesunate + Mefloquine
- Artesunate + Sulfadoxine " “Pyrimethamine
- Severe falciparum " ”IV treatment:
- Artesunate can be given IV or IM
- Artemisinin can be given rectally
- 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
- Chloroquine:
- 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
- Mefloquine:
- 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
- Doxycycline:
- 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
- Primaquine:
- 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
- Vaccine is not available, but several are in field trials.
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
Admission Criteria
- 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
Discharge Criteria
- Non " “P. falciparum infection
- Able to tolerate oral medications
Pearls and Pitfalls
Consider in patients with appropriate exposure/epidemiology and in exposed patients with fever and consistent signs and symptoms. ‚
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)