- Clinical science
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 7–42 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 a 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.
- Eukaryotic parasites belonging to the Sporozoa group
- For different species, see the table below.
- Vector: : the female Anopheles mosquito
- Host: humans
- Partial resistance against malaria
|Different species of plasmodium||Disease||Fever spikes|
| ||Every 48 hours|
| ||Every 72 hours|
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 of female) → a mosquito bites an infected human and ingests gametocytes
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
Immature trophozoite: thick, dark purple ring‑shaped inclusions (similar to signet ring cell carcinoma)
- With Plasmodium falciparum: fine rings
Mature trophozoite: ameboid rings
- With Plasmodium falciparum: finer rings in comparison to immature trophozoites
Immature schizont: irregular round, ameboid, almost filling the entire erythrocyte
- With Plasmodium falciparum: hardly detectable in the blood
Mature schizont: conglomerate of 6–24 merozoites (round with central darkening), which develops from an immature schizont
- With Plasmodium falciparum: hardly detectable in the blood
Incubation: 7–42 days
- Relapse in P. ovale or P. vivax infection
- Following the successful treatment of tertian malaria, some Plasmodium forms (hypnozoites) may persist within the liver and cause reinfection after lying dormant for months or even years.
- Asymptomatic parasitemia: Especially in endemic regions, cases of asymptomatic plasmodia carriers are reported.
- Recurrence in P. malariae infection: Following the treatment of quartan malaria, parasitemia can recur after several days or weeks, even if no parasites are detectable.
- Course: 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.
- Flu‑like symptoms
- High fever
- Weakness, paleness, dizziness
- Increased bleeding risk → in severe cases, disseminated intravascular coagulation may occur.
- Gastrointestinal: diarrhea, abdominal pain, nausea, and vomiting
- Liver: hepatosplenomegaly, discrete jaundice
- Severe malaria: can lead to severe organ dysfunction
- History: recent or distant travel to regions where malaria is endemic
Blood smear: 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
- Lower sensitivity than thick blood smear, but higher specificity
- Parasites are visible within red blood cells since the morphology of erythrocytes is preserved.
- Allows determination of Plasmodium species
- Evaluation of parasite concentration
- Evaluation of parasite and erythrocyte morphology
Rapid diagnostic tests (RDTs)
- Determination of specific malaria antigens, e.g., HRP2, pLDH, and aldolase
- Benefits: quick determination of malaria infection in areas lacking high‑quality malaria microscopy
- All RDT results should always be confirmed via microscopy (if available).
- High sensitivity
- Expensive and unavailable in regions with limited resources
- Not appropriate for acute diagnosis of malaria because antibodies are undetectable for 1–2 weeks
- Positive serological results indicate past contact with Plasmodium
If symptoms persist despite negative microscopy and rapid testing, diagnostics should be repeated every eight hours for several days!
When choosing antimalarial drugs, age, side effects, cost, geographic region, and dosing schedule should all be taken into consideration.
|P. vivax (chloroquine‑resistant)|
- Treatment of choice: or
|Severity of disease||Region||Treatment|
|Uncomplicated falciparum malaria||Chloroquine‑sensitive|
|Severe falciparum malaria||All regions|
Side effects of antimalarial medication
|Drug||Most important side effects|
- 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
- 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 area
- 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, atovaquone, proguanil, mefloquine
Prophylactic medication cannot prevent infection but suppresses the clinical course and symptoms by killing the parasite before it can cause a severe infection. There is no prophylactic medication that provides protection against all potential parasites.
Obligation to report
Report all laboratory‑confirmed cases of malaria to the local or state health department.