Malaria is a potentially life-threatening parasitic disease caused by infection with Plasmodium protozoa transmitted by an infective female Anopheles mosquito. Plasmodium falciparum infection carries a poor prognosis with a high mortality if untreated, but it has an excellent prognosis if diagnosed early and treated appropriately.


Signs and symptoms of malaria

Patients with malaria typically become symptomatic a few weeks after infection, though the symptomatology and incubation period may vary, depending on host factors and the causative species. Clinical symptoms include the following:
Headache (noted in virtually all patients with malaria)
  • Cough
  • Fatigue
  • Malaise
  • Shaking chills
  • Arthralgia
  • Myalgia
  • Paroxysm of fever, shaking chills, and sweats (every 48 or 72 hours, depending on species)

Less common symptoms include the following:

  • Anorexia and lethargy
  • Nausea and vomiting
  • Diarrhea
  • Jaundice
  • Most patients with malaria have no specific physical findings, but splenomegaly may be present. Severe malaria manifests as the following:
  • Cerebral malaria (sometimes with coma)
  • Severe anemia
  • Respiratory abnormalities: Include metabolic acidosis, associated respiratory distress, and pulmonary edema; signs of malarial hyperpneic syndrome include alar flaring, chest retraction, use of accessory muscles for respiration, and abnormally deep breathing
  • Renal failure (typically reversible)

Diagnosis of malaria

The patient history should include inquiries into the following:
  • Recent or remote travel to an endemic area
  • Immune status, age, and pregnancy status
  • Allergies or other medical conditions
  • Medications currently being taken
The following blood studies should be ordered:
  • Blood culture
  • Hemoglobin concentration
  • Platelet count
  • Liver function
  • Renal function
  • Electrolyte concentrations (especially sodium)
  • Monitoring of parameters suggestive of hemolysis (haptoglobin, lactic dehydrogenase [LDH], reticulocyte count)
  • In select cases, rapid HIV testing
  • White blood cell count: Fewer than 5% of malaria patients have leukocytosis; thus, if leukocytosis is present, the differential diagnosis should be broadened
  • If the patient is to be treated with primaquine, glucose-6-phosphate dehydrogenase (G6PD) level
  • If the patient has cerebral malaria, glucose level to rule out hypoglycemia

The following imaging studies may be considered:

Chest radiography, if respiratory symptoms are present
Computed tomography of the head, if central nervous system symptoms are present

Specific tests for malaria infection should be carried out, as follows:
  • Microhematocrit centrifugation (sensitive but incapable of speciation)
  • Fluorescent dyes/ultraviolet indicator tests (may not yield speciation information)
  • Thin (qualitative) or thick (quantitative) blood smears (standard): Note that 1 negative smear does not exclude malaria as a diagnosis; several more smears should be examined over a 36-hour period
  • Alternatives to blood smear testing (used if blood smear expertise is insufficient): Include rapid diagnostic tests, polymerase chain reaction assay, nucleic acid sequence-based amplification, and quantitative buffy coat
  • Histologically, the various Plasmodium species causing malaria may be distinguished by the following:
  • Presence of early forms in peripheral blood
  • Multiply infected red blood cells
  • Age of infected RBCs
  • Schüffner dots


Treatment is influenced by the species causing the infection, including the following:
  • Plasmodium falciparum
  • P vivax
  • P ovale
  • P malariae
  • P knowlesi
In the United States, patients with P falciparum infection are often treated on an inpatient basis to allow observation for complications. Patients with non– P falciparum malaria who are well can usually be treated on an outpatient basis.

General recommendations for pharmacologic treatment of malaria are as follows:

P falciparum malaria: Quinine-based therapy is with quinine (or quinidine) sulfate plus doxycycline or clindamycin or pyrimethamine-sulfadoxine; alternative therapies are artemether-lumefantrine, atovaquone-proguanil, or mefloquine

P falciparum malaria with known chloroquine susceptibility (only a few areas in Central America and the Middle East): Chloroquine

P vivax, P ovale malaria: Chloroquine plus primaquine

P malariae malaria: Chloroquine

P knowlesi malaria: Same recommendations as for P falciparum malaria

Pregnant women (especially primigravidas) are up to 10 times more likely to contract malaria than nongravid women and have a greater tendency to develop severe malaria. Medications that can be used for the treatment of malaria in pregnancy include the following:
  • Chloroquine
  • Quinine
  • Atovaquone-proguanil
  • Clindamycin
  • Mefloquine
  • Sulfadoxine-pyrimethamine (avoid in first trimester)
  • Artemether-lumefantrine
  • Artesunate and other antimalarials