Malaria is a potentially life‑threatening tropical disease caused by Plasmodium parasites, which are transmitted through the bite of an infected female Anopheles mosquito. The clinical presentation and prognosis of the disease depend on the Plasmodium species. Malaria has an incubation period of 7–30 days and may present with relatively unspecific symptoms like fever, nausea, and vomiting. Therefore, it is often misdiagnosed. Clinically suspected cases are confirmed by direct parasite detection in a blood smear. Patients are treated with antimalarial drugs (e.g., chloroquine, quinine), some of which may also be used as prophylaxis during trips to endemic regions. However, the most important preventive measure is adequate protection against the Anopheles mosquito (e.g., mosquito nets, repellents, protective clothing, etc.). Malaria is a notifiable disease and should be suspected in all patients with fever and a history of travel to an endemic region.
- Most cases of malaria occur in tropical Africa (West and Central Africa).
- Transmission also occurs in other tropical and subtropical regions such as Asia (e.g., India, Thailand, Indonesia), and Latin America (e.g., Brazil, Colombia)
Epidemiological data refers to the US, unless otherwise specified.
Pathogen: Plasmodia 
- Eukaryotic parasites (belonging to the Sporozoa group)
- For different species, see table below
- Vector: the female Anopheles mosquito
- Host: humans
Partial resistance against malaria 
- Carriers of sickle‑cell mutation
- Individuals with either certain Duffy antigens are resistant to P. vivax and P. knowlesi  or no
- Other hemoglobinopathies (e.g., thalassemia, HbC)
- Infection with malaria subsequently leads to the development of specific Plasmodium antibodies that result in partial immunity for a limited amount of time (less than a year)
|Different species of plasmodium ||Disease||Fever spikes|
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Life cycle of Plasmodium (simplified) 
Asexual development in humans
- Transmission of Plasmodium sporozoites via Anopheles mosquito bite → sporozoites travel through the bloodstream to the liver of the host
- Liver: sporozoites enter hepatocytes → sporozoites multiply asexually → schizonts are formed containing thousands of merozoites → release of merozoites into the bloodstream
Circulatory system (two possible outcomes)
- Merozoites enter erythrocytes → maturation to trophozoites → red cell schizonts are formed containing thousands of merozoites → release of merozoites into the bloodstream (which causes fever and other manifestations of malaria) → penetration of erythrocytes recurs
- Merozoites enter erythrocytes → differentiation into gametocytes (male or female)
Sexual development in female Anopheles mosquito
- A mosquito bites an infected human and ingests gametocytes → gametocytes mature within the mosquito intestines → sporozoites are formed and these migrate to the salivary glands → transmission of sporozoites to humans via mosquito bite
- See “ ” in “Diagnostics” below.
- 7–30 days 
Infection → asymptomatic parasitemia → uncomplicated illness → severe malaria → death
- Asymptomatic parasitemia: Especially in endemic regions, cases of asymptomatic plasmodia carriers are reported. 
- Tertian and quartan malaria are associated with less severe symptoms; , the involvement of fewer organs (rarely CNS or gastrointestinal symptoms), and a markedly lower risk of severe malaria.
- Following the successful treatment of tertian malaria, dormant P. ovale or P. vivax forms (hypnozoites) may persist within the liver and cause reinfection (relapse) after months or even years.
General symptoms 
- Flu‑like symptoms, headache
- High fever
Organ-specific symptoms 
- Liver: hepatosplenomegaly, discrete jaundice
Severe malaria 
- Description: potentially fatal manifestation or complication of malaria
- Etiology: most commonly a result of falciparum malaria
- Pathophysiology: infected erythrocytes occlude capillaries, which can lead to severe organ dysfunction
- Kidneys: flank pain, oliguria, hemoglobinuria, acute kidney injury
- Cerebral: hallucinations, confusion, impaired consciousness, seizures, or even coma
- Cardiopulmonary: heart failure, pulmonary edema, ARDS, shock
- Hematologic: severe anemia, coagulation disorders
- Metabolic: hypoglycemia, metabolic acidosis
- Hyperparasitemia: > 5% of RBC are infected with plasmodia
- History: recent or distant travel to regions where malaria is endemic
- Description: confirms suspected cases by visualizing parasites within RBCs
Best initial test: thick blood smear
- High sensitivity
- Detects the presence of parasites
- Confirmatory testing: thin blood smear
Evaluation of negative test results 
- If parasite densities are very low, malaria may be initially undetectable.
- If an initial test result is negative, blood smears should be repeated three times every 12–24 hours
- If all three sets are negative, malaria can be ruled out.
|Developmental stages of Plasmodium in RBCs |
|All Plasmodium spp.||Plasmodium falciparum|
|Immature trophozoite|| || |
|Mature trophozoite|| || |
|Immature schizont|| || |
|Mature schizont|| |
If symptoms persist despite negative microscopy and rapid testing, blood smears should be repeated 3 times every 12-24 hours.
Other tests 
- Rapid diagnostic tests (RDTs)
- Serological tests
General considerations 
- When choosing antimalarial drugs, age, side effects, cost, geographic region, and dosing schedule should all be taken into consideration.
- The increasing resistance to chloroquine due to the development of efflux membrane pumps (especially in P. falciparum) should also be considered.
Tertian and quartan malaria
|Overview of treatment for tertian and quartan malaria|
|P. vivax, P. ovale||Chloroquine-sensitive|
|P. malariae, P. knowlesi|
|Overview of treatment for falciparum malaria|
|Severity of disease||Region||Treatment|
|Uncomplicated falciparum malaria|| |
|Severe falciparum malaria|| || |
Side effects of antimalarial medication 
|Drug||Most important side effects|
Mosquito bite prevention 
- Exercise particular caution during peak biting periods 
- Mosquito nets
- Protective clothing (covering most of the skin, light colors)
- Mosquito repellent, such as DEET (N,N-diethyl-meta-toluamide)
- Reduce breeding sites (e.g., eliminate pools of water, optimize plant watering)
- Insecticide spraying
Malaria prophylaxis 
- Should be initiated before traveling to regions with a high risk of malaria; , e.g., tropical Africa, Asia, and Latin America
- Drug of choice is based on the region travelled
- Areas with P. falciparum
- Areas without P. falciparum; (some areas of Central/South America, Mexico, China, South Korea): primaquine
- Agents that are safe during pregnancy: chloroquine, mefloquine
Prophylactic medication cannot prevent infection but instead suppresses the course of the disease and its symptoms by killing the parasite within the host before it can cause severe disease. There is no prophylactic medication that provides protection against all species of the Plasmodium genus.
Standby emergency treatment 
Obligation to report
- Report all laboratory‑confirmed cases of malaria to the local or state health department.