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Plasmodium falciparum is a single-celled parasitic protozoan of the phylum Apicomplexa (order Haemosporida, family Plasmodiidae) and the main cause of severe malaria in humans. It is transmitted between people by the bite of infected female Anopheles mosquitoes, chiefly members of the Anopheles gambiae complex and Anopheles funestus in Sub-Saharan Africa, and increasingly by the invasive urban species Anopheles stephensi. It is the most dangerous of the species of Plasmodium that infect humans, the others being P. vivax, P. ovale, P. malariae, and the monkey parasite P. knowlesi.

Plasmodium falciparum causes the great majority of malaria deaths, estimated at about 600,000 a year, of which roughly 94% occur in Sub-Saharan Africa, mostly in children under five and in pregnant women. It has also been one of the strongest selective forces acting on the human genome. Unlike P. vivax and P. malariae, which prefer young or old red blood cells, P. falciparum invades cells of all ages and can therefore reach very high densities in the blood. It also exports adhesive proteins, principally PfEMP1, that cause infected red cells to stick to the lining of small blood vessels in the brain, placenta, lungs, and kidneys.

Because the parasite's sexual stages develop inside a mosquito whose body temperature follows that of the air, the time it needs to become infectious, its survival, and the geographic limits of transmission all depend on temperature, water availability, and climate change.

Cross-Species Zoonotic Transfer from Western Gorillas (Laverania)

Plasmodium falciparum belongs to the subgenus Laverania, named after Alphonse Laveran, who first observed malaria parasites in human blood in 1880. For many years it was thought that the parasite had evolved alongside the human lineage from a common ancestor shared with the chimpanzee parasite P. reichenowi, over several million years.

This view was overturned in 2010 by studies of parasite DNA in the faeces of wild African apes, carried out by Beatrice Hahn, Paul Sharp, Franck Prugnolle, and colleagues. The subgenus contains at least seven host-specific species: P. reichenowi, P. gaboni, and P. billcollinsi in chimpanzees, and P. praefalciparum, P. adleri, and P. blacklocki in western gorillas. All known human P. falciparum strains form a single group nested within the diversity of P. praefalciparum, a parasite of western lowland gorillas.

Molecular clock estimates suggest that P. falciparum entered humans through a single transfer from a gorilla, probably in central or western Africa, at some point in the last tens of thousands of years, although estimates vary widely. The resulting population passed through a severe genetic bottleneck and then expanded rapidly, apparently in step with the spread of agriculture in Africa and the rise of mosquito populations adapted to feeding on humans.

Two changes appear to underlie the switch from gorillas to humans:

• Loss of a sialic acid. Apes carry an enzyme, encoded by the CMAH gene, that converts the sialic acid Neu5Ac into Neu5Gc on the red cell surface. About two to three million years ago the human lineage lost this gene, so human red cells carry only Neu5Ac. P. falciparum uses an invasion protein, EBA-175, that binds Neu5Ac on human glycophorin A.
• A change in PfRH5. To enter a red cell, the parasite depends on reticulocyte-binding protein homologue 5 (PfRH5), which binds the human receptor basigin (CD147). Related ape parasites cannot bind human basigin. The region of the genome containing the rh5 gene has an unusual evolutionary history: it appears to have been transferred between Laverania lineages rather than inherited in the normal way, and subsequent changes in the protein allowed it to bind the human receptor. The details remain under investigation.

Extreme AT-Rich Chromosomal Core and Subtelomeric Var Repertoires

The genome of the reference strain 3D7, published in 2002, consists of about 23 million base pairs on 14 chromosomes and encodes roughly 5,300 protein-coding genes.

It has one of the most adenine- and thymine-rich genomes known among eukaryotes. Overall the genome is about 81% A+T. In protein-coding regions this falls to about 75%, which biases codon usage and produces proteins rich in repeated runs of asparagine and lysine. In introns and the regions between genes, A+T content exceeds 90%. The bias arises from a high rate of spontaneous conversion of cytosine to uracil and from slippage of the replication machinery across long runs of A and T, which also produces frequent insertions and deletions.

Each chromosome has two distinct regions:

• The core. The central portion, about 85% of each chromosome, has the same gene order as in related Plasmodium species, is packaged in an open form of chromatin, and contains the genes needed for normal cell function.
• The subtelomeres. Near the chromosome ends lie repetitive sequences followed by large families of variable genes: about 60 var genes encoding PfEMP1, roughly 150 to 200 rif genes, and 30 to 40 stevor genes. These regions cluster together at the edge of the nucleus, are packaged in a closed, silenced form of chromatin marked by the modification H3K9me3 and the protein PfHP1, and recombine frequently with one another, continually generating new variants.

The Mitochondrial and Apicoplast Non-Photosynthetic Organellar Genomes

The parasite has two organelles with their own genomes, both inherited from the female parent.

• The mitochondrial genome is about 6 kb and is the smallest known in any eukaryote. Arranged as repeating units joined end to end, it encodes just three proteins of the electron transport chain — cytochrome c oxidase subunits I and III and cytochrome b — together with fragmented ribosomal RNAs; everything else is imported from the cytoplasm. In blood stages the mitochondrion lacks a complete citric acid cycle. Its essential role is to re-oxidize ubiquinol so that the enzyme dihydroorotate dehydrogenase can function. That enzyme is required for making pyrimidines, which the parasite cannot obtain any other way.
• The apicoplast is a 35 kb circular genome in a non-photosynthetic plastid surrounded by four membranes. The organelle derives from a red alga that an ancestral cell engulfed, which in turn had acquired its plastid from a cyanobacterium. The apicoplast genome encodes about 30 proteins, mostly components of a bacterial-type ribosome, while some 500 further proteins are imported from the cytoplasm. The organelle carries out several bacterial-type pathways, including fatty acid synthesis, iron–sulfur cluster assembly, part of heme synthesis, and the MEP pathway for making isoprenoid precursors. Work by Ellen Yeh and Joseph DeRisi showed that in blood stages only the last of these is essential: parasites deprived of the apicoplast survive if supplied with the isoprenoid precursor isopentenyl pyrophosphate. This explains the "delayed death" caused by antibiotics such as doxycycline, clindamycin, and azithromycin, which block apicoplast function. Treated parasites complete one cycle normally but fail in the second, because their daughter cells inherit a defective organelle.

Pre-Erythrocytic Sporozoite Invasion and Merosome Egress

Plasmodium falciparum alternates between humans, where it multiplies asexually and produces sexual forms, and female Anopheles mosquitoes, where fertilization and further multiplication occur. It passes through more than ten distinct cell types. Invasion of host cells depends on three kinds of secretory organelle at the parasite's front end — micronemes, rhoptries, and dense granules — and on an actin–myosin motor that drives gliding movement.

Infection begins when a mosquito probes the skin and injects sporozoites into the dermis, typically a few tens of them, along with its saliva.

1. Movement through the skin. Sporozoites glide through tissue at a few micrometres per second. To cross cell barriers they secrete pore-forming proteins that let them pass through cells without being trapped inside them.
2. Entry into liver cells. Reaching the bloodstream, sporozoites arrive in the liver within an hour. Their surface is coated with circumsporozoite protein (CSP), which contains a central repeat of the four amino acids Asn-Ala-Asn-Pro (NANP). CSP binds heparan sulfate on the surface of hepatocytes. Contact triggers cleavage of the protein, exposing an adhesive region and allowing invasion, which also requires the host proteins CD81 and SR-BI.
3. Multiplication and release. Unlike P. vivax and P. ovale, which can leave dormant forms (hypnozoites) in the liver that cause relapses months or years later, P. falciparum forms none. Each sporozoite that invades a liver cell divides repeatedly over about a week, producing on the order of tens of thousands of merozoites without causing symptoms. These are released into the bloodstream enclosed in packets of host membrane called merosomes, which protect them from immune cells until they break up in the lung capillaries.

All the symptoms and all the deaths caused by malaria arise from the repeating cycle of invasion and multiplication in red blood cells, which takes about 48 hours.

Multi-Step Erythrocyte Invasion: EBA-175, PfRH5–Basigin, and the Moving Junction

Merozoites survive only a few minutes outside a cell and must invade within about a minute. Invasion proceeds in four steps:

1. Attachment. Merozoite surface proteins, principally MSP-1, bind weakly to the red cell surface.
2. Reorientation and commitment. Proteins of the erythrocyte-binding-like family (EBA-175, which binds glycophorin A, and others) and the reticulocyte-binding homologue family help the merozoite turn so that its front end faces the cell. A complex containing PfRH5 then binds basigin. This step is essential in all strains and triggers a flow of calcium into the red cell.
3. Forming the junction. The parasite injects its own receptor proteins (RON2, RON4, and RON5) into the red cell membrane. The parasite protein AMA1 binds RON2, forming a ring-shaped junction between the two cells.
4. Entry. The parasite's motor draws this ring from front to back, pulling the merozoite into the cell while surface proteins are shed behind it. The membrane closes behind the parasite to form a parasitophorous vacuole.

Inside the red cell, which has no nucleus and little machinery of its own, the parasite passes through three stages:

1. Ring stage (roughly the first 20 hours): a thin, cup-shaped cell that looks like a signet ring on a stained blood film, with a low rate of metabolism.
2. Trophozoite stage (about 20 to 36 hours): the main growth phase. The parasite takes in most of the red cell's contents and digests them in an acidic compartment, the food vacuole. A series of proteases breaks down hemoglobin into amino acids. Because adult human hemoglobin contains no isoleucine, the parasite must take this amino acid from the blood plasma through channels it creates in the red cell membrane.

Digesting hemoglobin releases large amounts of heme, which is toxic: it damages membranes and generates reactive oxygen species. The parasite cannot break down the porphyrin ring, so instead it converts heme into an insoluble crystalline form called hemozoin, in which the iron atom of one molecule binds a side chain of the next.

1. Schizont stage (about 36 to 48 hours) and rupture: the parasite divides into 16 to 32 merozoites arranged around the residual hemozoin. At the end of the cycle, a signalling cascade involving protein kinase G and the protease PfSUB1 breaks first the vacuole membrane and then the red cell, releasing merozoites together with hemozoin and other inflammatory material into the blood.

The PTEX Translocon, Maurer's Clefts, and PfAP2-G Sexual Commitment

Because a mature red cell has no machinery for making or moving proteins, the parasite exports 400 or more of its own proteins into the cell. Most carry a short signal sequence near one end, known as the PEXEL motif, which is cut by an enzyme in the parasite before export. The proteins are then threaded through a channel in the vacuole membrane called PTEX, made up of the proteins HSP101, PTEX150, and EXP2.

Once in the red cell, exported proteins build flattened membrane structures called Maurer's clefts, which sort and deliver parasite proteins to the cell surface. There they form thousands of small bumps, or knobs, which display PfEMP1 and stiffen the red cell membrane considerably.

Asexual parasites are digested if a mosquito takes them up, so transmission depends on a small proportion of parasites, typically a few per cent per cycle, switching to sexual development and becoming gametocytes.

The switch is controlled by the transcription factor PfAP2-G. During asexual growth its gene is kept silent in closed chromatin. The protein GDV1 can remove this silencing, and once PfAP2-G is produced it activates its own gene, locking in the change, so that all the merozoites from a single schizont become either male or female gametocytes.

What triggers the switch is not fully resolved. Work by Matthias Marti and colleagues indicated that parasites take up the host lipid lysophosphatidylcholine from serum, and that when this is scarce, as in the bone marrow or at high parasite densities, the parasite must make membrane lipids by a route that consumes the cell's supply of methyl groups. The resulting shortage is thought to reduce the chromatin modifications that keep the gene silent. Drug treatment and other stresses also increase sexual commitment.

Gametocytes of P. falciparum take 10 to 12 days to mature through five stages, longer than in other human malaria parasites. The species name comes from the Latin falx, a sickle, referring to their crescent shape.

• Immature stages. Developing gametocytes are stiff and would be destroyed in the spleen, so they leave the circulation and mature in the bone marrow, where an internal skeleton of microtubules draws the cell out into a crescent.
• Mature gametocytes. After about ten days, this skeleton is dismantled and the cell becomes flexible again. Mature male and female gametocytes, with females outnumbering males several times over, re-enter the bloodstream and circulate until a mosquito takes them up.

Synchronous Schizont Rupture, Rosetting, and Endothelial Cytoadherence

Three features make P. falciparum far more dangerous than the other human malaria parasites:

1. Unrestricted invasion and rapid growth. Because it invades red cells of any age and produces 16 to 32 merozoites every 48 hours, the number of parasites can rise roughly tenfold every two days, reaching more than 5% and occasionally over 20% of all red cells.
2. Sequestration. From roughly 16 hours after invasion, mature parasites disappear from the circulating blood because infected cells stick to the walls of small vessels in the brain, placenta, and other organs. Infected cells also bind uninfected red cells, forming clusters known as rosettes, and bind platelets. Sequestration keeps the stiffened, knobby cells out of the spleen, where they would otherwise be destroyed.
3. Inflammation. When schizonts rupture, hemozoin coated with parasite DNA and membrane anchors activates immune receptors on monocytes and other cells, producing surges of inflammatory signalling molecules including tumor necrosis factor and interleukin 1 beta. These cause the characteristic cycle of chills, high fever, and sweating that recurs every 48 hours, and they increase the stickiness of blood vessel walls.

Clonal Antigenic Variation of var Genes and EPCR/VAR2CSA Receptor Tropism

Sequestration depends on Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), a large protein displayed on the knobs of infected red cells. Each parasite carries about 60 different var genes encoding versions of this protein, built from two kinds of module: Duffy-binding-like domains and cysteine-rich interdomain regions.

To avoid antibodies while remaining able to adhere, the parasite expresses only one var gene at a time, keeping the rest silenced in closed chromatin. Occasionally a parasite switches to a different gene. Estimates of the switching rate vary, from well below 1% to a few per cent per generation. Switching produces successive waves of parasites with different surface proteins, and because different versions bind different host receptors, it also changes which organs are affected:

PfEMP1 variants, their receptors, and associated disease

Severe malaria also takes other forms. Severe anaemia results not only from the destruction of infected cells but from the removal of many uninfected ones, perhaps eight to ten for each infected cell, together with suppression of red cell production in the bone marrow. Other presentations include metabolic acidosis with raised blood lactate, low blood sugar, acute respiratory distress, and acute kidney injury, including the haemoglobin-staining of urine known as blackwater fever.

In 1949, J. B. S. Haldane proposed what became known as the malaria hypothesis: that inherited blood disorders are common in malarious regions because carrying one copy of the responsible gene protects against malaria, offsetting the harm caused in those who inherit two copies. This is a form of balancing selection, and malaria has provided some of its clearest examples.

Human genetic variants associated with protection against P. falciparum

The Duffy-negative blood type, which is almost universal in West and Central Africa, gives near-complete protection against P. vivax, because that parasite depends on a single receptor. P. falciparum has several alternative routes of invasion and is unaffected.

Three related measures are used:

1. The entomological inoculation rate is the number of infectious mosquito bites a person receives per year, calculated as the biting rate multiplied by the proportion of mosquitoes carrying sporozoites. Across Africa it ranges from below 0.1 at the dry or highland margins to several hundred in areas of year-round transmission.
2. The parasite rate is the proportion of children aged 2 to 10 with parasites in their blood. It is used to classify areas as having low (under 10%), moderate (10 to 50%), high (50 to 75%), or very high (above 75%) transmission.
3. The reproduction number R₀ is the number of new infections arising from one infected person. For P. falciparum in areas of intense transmission it is extremely high, with estimates in the hundreds or above. Two features account for this: an untreated infection can persist for months, continually producing gametocytes, because antigenic variation allows it to evade antibodies; and the main African mosquitoes feed almost exclusively on humans. Transmission is also concentrated on a minority of people who receive most of the bites, which raises R₀ further.

People living in malarious areas never become completely immune to infection. Because each parasite carries about 60 var genes and local parasite populations contain many versions of these and other surface proteins, immunity is built up gradually over years of repeated infection. It develops in a particular order:

• Protection against severe disease comes first, usually within the first few years of life in areas of intense transmission. The variants that cause cerebral malaria are relatively few and structurally similar, so antibodies against them are acquired early. As a result, the risk of death is concentrated between about six months of age, when antibodies from the mother have waned, and five years.
• Protection against high parasite densities comes later, over 5 to 15 years, as antibodies accumulate against a wide range of surface and invasion proteins. Infections then tend to be asymptomatic and of low density.
• Immunity requires continued exposure. Antibody levels fall within months to a couple of years if exposure stops, partly because the parasite interferes with the development of lasting antibody-producing cells. This explains a long-recognized pattern: where transmission is low or episodic, immunity is never established and severe malaria occurs at all ages, whereas where transmission is intense, adults carry parasites without symptoms and deaths are concentrated in young children.

Inside the human body the parasite is held at about 37 °C. In the mosquito, by contrast, all stages are exposed to the temperature of the surrounding air.

In the classical model of Detinova and Moshkovsky, the time required to complete development in the mosquito, the extrinsic incubation period n, depends on temperature as:

with 16 °C taken as the temperature below which development stops. The equivalent threshold for P. vivax is lower, about 14.5 °C, which is why that species historically reached colder regions.

Development is also limited at high temperatures, failing above roughly 33 to 35 °C, so modern models use a curve that rises from a lower limit, peaks, and falls to an upper limit, rather than increasing without bound.

What matters epidemiologically is not the incubation period alone but the proportion of infected mosquitoes that survive it, which is e^−_μn_, where μ is the daily death rate. This makes transmission extremely sensitive to temperature. Taking a daily survival of 0.88, corresponding to an average lifespan of about eight days:

• At 18 °C, development takes about 55 days, and only about 0.08% of infected mosquitoes survive long enough to transmit. Transmission is effectively impossible.
• At 20 °C, development takes about 28 days, and roughly 3% survive.
• At 25 °C, development takes 11 to 12 days while mosquito survival remains good. Transmission is close to its maximum.
• At 30 °C, development takes 8 to 9 days, but mosquito survival begins to fall.
• Above 33 to 35 °C, both parasite development and mosquito survival fail.

Work by Krijn Paaijmans, Matthew Thomas, and colleagues showed that using average temperatures alone gives misleading results, because mosquitoes and parasites experience daily swings often exceeding 10 °C.

Because the relationship between temperature and development is curved rather than straight, the average of the rates over a fluctuating day differs from the rate at the average temperature, a consequence of Jensen's inequality:

• In cool highlands, where mean temperatures may be below the threshold for development, afternoon warmth lifts conditions above it for several hours each day, allowing development to proceed in steps. Transmission is therefore possible at lower mean temperatures than a constant-temperature model would predict.
• In hot lowlands, where mean temperatures are already near the optimum, afternoon peaks exceed the upper limit for both parasite and mosquito, so fluctuation reduces transmission below what the mean temperature implies.

Several changes in the distribution of P. falciparum are expected or already under way:

• Spread to higher elevations. Because temperature falls by about 6.5 °C per kilometre of altitude, each degree of warming moves the threshold for transmission some 150 m upslope. In the densely populated highlands of East Africa, this brings valleys into the range where transmission becomes possible, exposing populations with little acquired immunity.
• Invasion of cities by Anopheles stephensi. Urban growth in Africa historically reduced malaria, because the main rural mosquitoes need clean sunlit pools. Since its detection in Djibouti in 2012, where it was associated with a large resurgence of malaria, the Asian species An. stephensi has spread to several African countries. It breeds in water tanks, cisterns, and wells rather than rain pools, so transmission is less tied to the rainy season, and it tolerates higher temperatures than the African species.
• Floods and cyclones. Because warmer air holds more moisture, heavy rainfall events are intensifying. Floods following tropical cyclones in southeastern Africa, and the Pakistan floods of 2022, left large areas of standing water while destroying housing and interrupting control programmes, and were followed by sharp increases in malaria.

Mechanisms of Drug Action and Transporter/Kelch13 Resistance

Because a single patient may carry enormous numbers of parasites, and because the parasite recombines sexually in the mosquito, P. falciparum has evolved resistance to every class of antimalarial drug in turn.

Antimalarial drugs and resistance mechanisms

Selection of pfhrp2/pfhrp3 Diagnostic Escape Mutants

Where microscopy is unavailable, infection is usually confirmed with rapid diagnostic tests, most of which detect a parasite protein called histidine-rich protein 2 (PfHRP2) and cross-react with a related protein, PfHRP3.

Neither protein is essential to the parasite, and both genes lie in unstable regions near the ends of chromosomes. Because only patients who test positive receive treatment, parasites that have lost these genes have an advantage. Strains lacking both genes were first reported in the Peruvian Amazon in 2010 and have since become common in parts of the Horn of Africa, in some surveys accounting for a substantial proportion of infections. They give negative test results even when the patient is seriously ill. Loss of pfhrp2 alone does not always cause a negative result, because the related protein can compensate. Affected countries are switching to tests that also detect a second, essential parasite protein.

To protect artemisinin-based combination therapies, which remain the standard treatment, several approaches are used:

• Seasonal malaria chemoprevention. Monthly courses of sulfadoxine–pyrimethamine with amodiaquine are given to young children through the rainy season across the Sahel, reaching tens of millions of children each year and reducing malaria episodes by around 75%.
• Triple combinations and new drugs. Adding a second long-acting partner drug to an artemisinin derivative can slow resistance, particularly when the two partners select for opposing changes in the parasite. New drugs with different targets are in development, including cipargamin, which blocks a sodium pump in the parasite membrane, ganaplacide, and inhibitors of the pyrimidine pathway.
• Single-dose primaquine. Standard treatment kills immature gametocytes but not mature ones. A single low dose of primaquine clears these within days, preventing onward transmission. The World Health Organization considers this dose safe without prior testing for G6PD deficiency.

Vaccine development has long been hampered by the parasite's complex life cycle and variable surface proteins. Three approaches are now in use or under development.

1. Vaccines against sporozoites. RTS,S/AS01 and R21/Matrix-M both target the circumsporozoite protein, fusing part of it to the hepatitis B surface antigen so that the proteins assemble into particles. These stimulate antibodies that can immobilize sporozoites before they reach the liver.

• RTS,S/AS01, recommended by the World Health Organization in 2021, combines the fusion protein with four parts of unfused hepatitis B antigen. Efficacy against clinical malaria is around 50% in the first year, falling to roughly 36% over four years. Higher protection has been achieved by giving it seasonally alongside chemoprevention, but that reflects the combination rather than the vaccine alone.
• R21/Matrix-M, developed at the University of Oxford and recommended in 2023, contains only the fusion protein, with no excess hepatitis B antigen. This increases the density of the malaria epitopes on the particle surface. In trials it achieved about 75% efficacy over a year at seasonal sites and somewhat less where transmission is year-round, and it requires far less material per dose.

1. Long-acting antibodies. The antibodies CIS43LS and L9LS were isolated from volunteers immunized with weakened sporozoites. They bind parts of the circumsporozoite protein that the parasite cannot easily alter. Both have been modified to extend their lifetime in the blood to several months, and single doses have given high levels of protection across a transmission season in early trials.
2. Vaccines against blood stages and transmission. Because protection against sporozoites fails if even one reaches the liver, vaccines against the blood stage are also being developed, principally targeting PfRH5, which varies little because it is exposed only briefly during invasion. Transmission-blocking vaccines instead target proteins on the sexual stages, so that antibodies taken up by a feeding mosquito prevent the parasite developing inside it.

Why is Plasmodium falciparum much deadlier than other human malaria parasites?

Unlike *P. vivax* (which only infects young reticulocytes comprising ~1% of red cells), *P. falciparum* uses its essential PfRH5–basigin invasion complex to infect red blood cells of all ages, enabling parasitemia to exceed 5% to 20% of circulating erythrocytes. Furthermore, it exports PfEMP1 adhesins to surface knobs that glue infected red cells to brain and placental capillary walls (sequestration), avoiding splenic clearance while triggering lethal cerebral edema and metabolic acidosis.

How does sickle cell trait (HbAS) protect carriers from severe P. falciparum malaria?

Heterozygous carriers of the β-globin Glu6Val (HbS) mutation enjoy ~90% protection against severe and cerebral malaria without suffering sickle cell disease. Parasitized HbAS red cells prematurely sickle under the low oxygen tension of deep capillaries and are cleared by splenic macrophages, while intracellular HbS polymer instability disrupts actin remodeling and Maurer's cleft trafficking, blunting surface display of adhesive PfEMP1 knobs.

How do pfkelch13 mutations cause partial resistance to artemisinin?

Artemisinin is a prodrug whose endoperoxide bridge must be cleaved by ferrous iron (Fe²⁺)-heme released during hemoglobin digestion to generate parasite-killing free radicals. Mutations in the propeller domain of PfKelch13 (such as C580Y and R561H) reduce the endocytic uptake of host hemoglobin in young ring-stage parasites, lowering the pool of free heme available to activate artemisinin and allowing rings to survive the drug's short (~1–2 hour) plasma half-life.

• Malaria
• Antimalarial medication
• Malaria vaccine
• Artemisinin-based combination therapy
• Apicomplexan life cycle