Overview
What are the signs and symptoms of malaria?
Which physical findings suggest malaria?
What should be the focus of patient history in suspected malaria?
Which blood studies should be performed in the workup of malaria?
What is the role of imaging studies in the workup of malaria?
What is the role of lab testing in the workup of malaria?
How are Plasmodium species histologically distinguished?
What is the basis for treatment selection in patients with malaria?
What are the general recommendations for pharmacologic treatment of malaria?
Which medications are used for the treatment of malaria in pregnancy?
Where is malaria most prevalent and how is malaria infection transmitted?
Which Plasmodium species cause malaria?
How are Plasmodium species that cause malaria differentiated?
How common is malaria infection caused by multiple Plasmodium species?
Who is at increased risk for malaria infection?
What is the pathogenesis of malaria?
What complications are associated with Plasmodium falciparum (P falciparum) malarial infection?
How is malaria infection transmitted?
What are possible outcomes of Plasmodium falciparum (P falciparum) malaria infection?
Which factors influence malaria immunity?
How long do Plasmodium species incubate in humans?
What is the life cycle of Plasmodia?
What are the possible sequelae from replication of Plasmodia inside red blood cells (RBCs)?
What is the role of hemozoin in the etiology of malaria?
What is the role of Plasmodia metabolism in the pathophysiology of malaria?
What is the pathogenesis of Plasmodium falciparum (P falciparum) malaria?
What is the pathophysiology of malaria caused by Plasmodium vivax (P vivax)?
What is the pathophysiology of malaria caused by Plasmodium ovale (P ovale)?
What is the disease course of malaria caused by Plasmodium malariae (P malariae)?
What is the disease course of malaria caused by Plasmodium knowlesi (P knowlesi)?
What is the incidence of malaria in the US?
What is the mortality rate for malaria?
What is the global incidence of malaria?
Which malaria comorbidity is associated with a worse prognosis?
How does the incidence of malaria vary between men and women?
Which age group is at an increased mortality risk from malaria?
What is the prognosis of malaria?
What are the possible complications of malaria caused by Plasmodium falciparum (P falciparum)?
What is the mortality rate of malaria?
What are the host protective factors against malaria?
What information about malaria should be given to individuals traveling to endemic regions?
Presentation
What should be the focus of the patient history for suspected malaria?
What is the incubation period for malaria infection and what symptoms occur?
How is the onset of malaria symptoms characterized?
What are less common symptoms of malaria?
What is the presentation of Plasmodium vivax (P vivax) malaria infection?
What is the presentation of Plasmodium malariae (P malariae) malaria infection?
What findings suggest Plasmodium knowlesi (P knowlesi) malaria?
What are the symptoms of malarial infection?
What is the presentation of severe malaria?
What are the symptoms of malaria in children?
What causes anemia in patients with malaria?
What is the treatment of renal failure in patients with severe malaria?
What are the respiratory symptoms of malaria?
DDX
Which conditions should be included in the differential diagnoses of malaria?
Workup
In travelers returning from endemic areas, which findings suggest malaria?
What should be considered in patients who do not respond to antimalarial therapy?
What lab tests are performed in the workup of malaria?
What test must be performed before treating a malaria patient with primaquine?
What is the role of blood glucose testing in the diagnosis and management of malaria?
What are the BCSH recommendations for the lab diagnosis of malaria?
What is the role of imaging studies in the workup of malaria?
What is the role of microhematocrit centrifugation in the workup of malaria?
What is the indication for fluorescent and ultraviolet testing in the workup of malaria?
What is the role of PCR assay testing in the workup of malaria?
What is the role of lumbar puncture in the workup of malaria?
What is the role of blood smears in the workup of malaria?
How are blood smears examined for malaria?
What is the difference between thick and thin blood smears in the workup of malaria?
When should alternative diagnostic methods to blood smears be used in the workup of malaria?
How effective are rapid diagnostic tests (RDT) in the workup of malaria?
What is the role of the quantitative buffy coat (QBC) technique in the diagnosis of malaria?
How should a diagnosis of malaria be reported?
What are the histologic findings for the Plasmodium species associated with malaria?
Treatment
What monitoring is needed of patients treated for malaria?
What may increase the risk of morbidity and mortality in patients with malaria?
What are approach considerations for mixed infections of malaria?
Which Plasmodium species have known resistance to antimalarial agents?
When is inpatient treatment indicated in the treatment of malaria?
What are the increased risks for pregnant women who contract malaria?
How is malaria treated during pregnancy?
What is the disease course of malaria in children?
How is malaria treated in children?
How should diet and activity be modified in patients with malaria?
What are the treatment options for severe complicated malaria?
What is the efficacy of artesunate for the treatment of malaria?
How common is drug resistance in Plasmodium falciparum (P falciparum) malaria?
What is the role of artemisinin in the treatment of malaria?
Is there a vaccine for malaria?
What are the general recommendations for the treatment of malaria?
What is the role of mefloquine hydrochloride for the treatment of malaria?
What is the role of tafenoquine (Krintafel) in preventing malaria relapse?
Which medications are used to treat malaria during pregnancy?
When is inpatient care indicated for the treatment of malaria?
How often should blood smears be obtained during the treatment of malaria?
How much DEET should be used to repel mosquitoes and prevent malaria?
What is the role of chemoprophylaxis in the prevention of malaria?
What progress is being made on the development of a malaria vaccine?
When are specialist consultations needed for the diagnosis and treatment of malaria?
What consultations are needed for the treatment of pregnant patients with malaria?
Medications
Which major drug classes are used to treat malaria?
What is the prevalence of counterfeit antimalarial drugs?
What is the role of antipyretics in the treatment of malaria?
What are the possible adverse effects of antimalarial drugs for the treatment of malaria?
What are the possible complications of high-dose quinine for the treatment of malaria?
Which medications in the drug class Antimalarials are used in the treatment of Malaria?
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Malarial merozoites in the peripheral blood. Note that several of the merozoites have penetrated the erythrocyte membrane and entered the cell.
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This micrograph illustrates the trophozoite form, or immature-ring form, of the malarial parasite within peripheral erythrocytes. Red blood cells infected with trophozoites do not produce sequestrins and, therefore, are able to pass through the spleen.
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An erythrocyte filled with merozoites, which soon will rupture the cell and attempt to infect other red blood cells. Notice the darkened central portion of the cell; this is hemozoin, or malaria pigment, which is a paracrystalline precipitate formed when heme polymerase reacts with the potentially toxic heme stored within the erythrocyte. When treated with chloroquine, the enzyme heme polymerase is inhibited, leading to the heme-induced demise of non–chloroquine-resistant merozoites.
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A mature schizont within an erythrocyte. These red blood cells (RBCs) are sequestered in the spleen when malaria proteins, called sequestrins, on the RBC surface bind to endothelial cells within that organ. Sequestrins are only on the surfaces of erythrocytes that contain the schizont form of the parasite.
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Malaria life cycle. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
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Proportion of 2021 Global Malaria Burden. Gray area accounts for the remaining estimated 4.4% of worldwide malaria burden. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
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Confirmed P falciparum or P vivax Cases Per Country 2021. The map accounts for the total of the cases per country where either species were confirmed as the primary infection. The map does not include confirmed “mixed infections.” Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
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North American Presumed and Confirmed Malaria Cases 2021. Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
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South American Presumed and Confirmed Malaria Cases 2021. Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
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African Presumed and Confirmed Malaria Cases 2021. Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
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Asian and Oceanic Presumed and Confirmed Malaria Cases 2021. Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
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South Pacific Presumed and Confirmed Malaria Cases 2021. Gray indicates that there were either no data available or there were zero endemic cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
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Global P falciparum to P vivax Case Ratios 2021. Gray indicates that there were either no data available or there were zero endemic cases. Red indicates higher proportion of P vivax cases, whereas blue indicates higher proportion of P falciparum cases. Map created using data adapted from WHO 2022 World Malaria Report [https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022].
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Thin blood smear showing the ring forms of P falciparum that look like headphones with double chromatin dots. Note how P falciparum is seen infecting erythrocytes of all ages – a trait that can be utilized by the microscopist by noting the similar size of infected erythrocytes to other surrounding uninfected erythrocytes. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
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Thick blood smear depicting the banana shaped gametocyte of P falciparum. Multiple ring-form trophozoite precursors are also visible in the background. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
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Thin blood smear of the ring forms of P vivax. Note that P vivax typically has a single chromatin dot vs the two chromatin dots in P falciparum. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
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The diagnostic form of P vivax is the amoeboid trophozoite form where the cytoplasm has finger-like projections (pseudopods) without a typical round/oval structure. These pseudopods are unique to P vivax. Numerous small pink-red dots are also seen in both P vivax and P ovale; these are known as caveola-vesicle complexes (CVCs or Schüffner’s dots) and are composed of numerous flask-like indentations on infected reticulocytes membrane skeleton associated with tube-like vesicles. CVCs are thought to play a role in nutrient uptake or release of metabolites from parasite-infected erythrocytes. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
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Thin smear of P ovale in ring stage. Note that typically there is a single chromatin dot, larger cells are infected indicative of reticulocytes, and multiple ring forms may be present intracellularly. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
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Thin smear of P ovale trophozoite. Note that this species is difficult to differentiate from P vivax as it contains CVCs (Schüffner’s dots) and infects reticulocytes; a notable unique characteristic of P ovale is the presence of fimbriae on the reticulocyte membrane, which are even more likely to be seen in gametocyte infected red blood cells. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
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Thin blood smear of “band form” trophozoite of P malariae. Note that the infected erythrocyte is smaller than surrounding cells, indicating that P malariae infects older erythrocytes. As the trophozoite matures, the cytoplasm elongates and dark pigment granules of hemozoin are visualized toward the periphery. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
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Thin blood smear of P knowlesi trophozoites. An immature ring form is seen on the right next to the mature band form trophozoite on the left. Note the small size of the infected red blood cells and how the band form is similar in appearance to P malariae. Courtesy of the Centers for Disease Control and Prevention (CDC) [https://www.cdc.gov/dpdx/malaria/index.html].
Tables
Findings |
P falciparum |
P vivax |
P ovale |
P malariae |
Only early forms present in peripheral blood |
Yes |
No |
No |
No |
Poly-infected RBCs |
Often |
Occasionally |
Rare |
Rare |
Age of infected RBCs |
RBCs of all ages |
Young RBCs |
Young RBCs |
Old RBCs |
Schüffner dots |
No |
Yes |
Yes |
No |
Other features |
Cells have thin cytoplasm, 1 or 2 chromatin dots, and applique forms. |
Late trophozoites develop pleomorphic cytoplasm. |
Infected RBCs become oval, with tufted edges. |
Bandlike trophozoites are distinctive. |
