Author:
Roger M.Barkin
JordanMoskoff
Description
- Protozoan infection transmitted through the Anopheles mosquito
- Incubation period 8-16 d
- 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 the U.S.
- Transmission may also occur through infected blood products and shared needles
Pediatric Considerations |
- 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
|
Pregnancy Prophylaxis |
| Pregnant patients, especially primigravida, at higher risk |
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-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, shock
- Hypoglycemia
- Renal impairment
- Abnormal bleeding
- Jaundice
- Hemoglobinuria
- Acidosis
- Severe anemia
- Recurrent, recrudescent and reinfection may occur
Essential Workup
Oil emersion light microscopy of a thick-smear Giemsa stain:
- Demonstrates intraerythrocytic malaria parasites
- Cannot exclude diagnosis without 3 negative smears in 48 hr
- Only high degrees of parasitemia will be evident on a stand ard CBC smear
Diagnostic 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
- Detection of parasites on Giemsa-stained thick and thin blood smear in expert hand s. Operator dependent. If negative initially, may need to repeat over next 72 hr
- Lumbar puncture/CSF analysis:
- Performed to distinguish cerebral malaria from meningitis
- CSF lactate/protein elevated with malaria
- CSF pleocytosis/hypoglycemia absent with malaria
- Rapid diagnostic tests. Qualitative results. Antigen-based tests may distinguish species
- Molecular tests are used to research epidemiology. CDC offers PCR
Differential Diagnosis
- Meningitis
- Encephalitis
- Stroke
- Acute renal failure
- Acute hemolytic anemia
- Sepsis
- Hepatitis
- Viral diarrheal illness
- Hypoglycemic coma
- Heat stroke
Initial Stabilization/Therapy
ED Treatment/Procedures
- Dependent on considering this diagnosis and identifying the type of malaria present, sensitivity, 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 and severity of illness. Check WHO/CDC database
- Quinine
- 542-mg base PO t.i.d for 3-7 d in adults
- Quinidine IV (available from Eli Lilly 800-821-0538). May be considered if Artesunate not available
- Associated with prolonged QT interval
- For severe cases
- Atovaquone (250 mg) - Proquanil (100 mg) (Malarone). 4 tablets as single-daily dose for 3 consecutive days; pediatric tablet available as 4th of adult strength
- Nonsevere chloroquine-sensitive infection may be treated with chloroquine 600-mg base immediately followed by 300-mg base at 6, 24, and 48 hr in adults
- Severe falciparum - IV treatment:
- Artesunate can be given IV or IM
- Artesunate IV available at CDC 770-488-7788
- Supportive therapy for complications
- Chemoprophylaxis: Must be based on region of travel, check WHO/CDC database
- Mosquito avoidance measures should be observed with all travel to areas with malaria
- In areas where malaria occurs only sporadically and the risk is low, mosquito avoidance should be used and chemoprophylaxis may not be necessary
- Malarone
- Daily medication
- Very well tolerated
- Safe in children >5 kg - pediatric dosing
- Unsafe in pregnancy
- 250/100 mg PO daily
- Begin 1-2 d prior to entering malaria area and continue for 7 d after leaving area
- Atovaquone (250 mg) and Proguanil (100 mg)
- Chloroquine:
- Drug of choice for travelers who want weekly medication if traveling to area without chloroquine resistance
- Safe in pregnancy
- 300-mg chloroquine base (500-mg chloroquine salt) 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 yo
- Risk with sun exposure
- 100 mg PO daily
- Begin 1 d 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 d prior to entering area and continue 1 wk after return
- Vaccine is not available, but several are in field trials
- New drugs and insecticides are being investigated
- Combination artemisinin regimens used with insecticide treated bed netting has significantly reduced incidence
Medication
- Acetaminophen: 500 mg (peds: 10-15 mg/kg) PO q4-6h; do not exceed 5 doses/24 hr; max. 4 g/24 hr
- Artemether (40 mg) - lumefantrine (240 mg): 3-day schedule with a total of 6 doses PO. 2 tablets b.i.d for adults. Pediatric preparation available
- Atovaquone (250 mg) - Proguanil (100 mg): 4 adult tablets per day for 3 d for adults
- Artesunate (100 mg) - Amodiaquine (270 mg): 1-dose regimen PO QD × 3 d for adults
- Artesunate (100 mg) - Mefloquine (220 mg): 3-dose regimen; 2 tab PO QD × 3 d for adults
- 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
- Other drug regimens may be considered in consultation with the CDC reflecting sensitivity and severity of disease
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
- Young children and immunocompromised patients
Discharge Criteria
- Non-P. falciparum infection
- Stable and able to tolerate oral medications
- Close follow-up required
Issues for Referral
Infectious disease consultation should be obtained when malaria is considered. Consultation with local experts or the CDC should be utilized when the diagnosis is confirmed because of the complexity of treatment drug regimens for different species and must reflect the severity of disease.