Plasmodium vivax. Plasmodium malariae. Plasmodium falciparum. Morphological differences in the erythrocyte schizogony of the genus Plasmodium

Plasmodium vivax. Plasmodium malariae. Plasmodium falciparum. Morphological differences in the erythrocyte schizogony of the genus Plasmodium

Plasmodium, the apicomplexan that causes malaria, its life cycle between the Anopheles mosquito and a person, through the liver and again and again through red cells, how P. vivax, P. malariae and P. falciparum differ in the red cell, and malaria itself, from the fever to the severe disease, its diagnosis, treatment and prevention.

Plasmodium: the stages in the red cell
A grid of red cells as a stained thin blood film shows them, three rows and four columns. The rows, from the top: Plasmodium vivax, Plasmodium malariae, Plasmodium falciparum. The columns, from the left: the ring, the growing trophozoite, the mature schizont and the gametocyte. Top row, P. vivax: a ring with thick cytoplasm and one large chromatin dot, in a cell slightly larger than normal; then, in cells about one and a half times normal size, finely stippled with red Schüffner's dots, an irregular amoeboid trophozoite with a vacuole and fine brown pigment, a schizont of sixteen merozoites with its pigment in two clumps, and a large round gametocyte almost filling its cell. Middle row, P. malariae, in cells a little smaller than normal: a sturdy ring, a band-form trophozoite stretched across the cell with coarse dark pigment along one edge, a schizont of eight merozoites arranged in a rosette round a central mass of pigment, and a compact round gametocyte. Bottom row, P. falciparum, in normal-sized cells: two delicate small rings in one cell, one with two chromatin dots and one flattened against the cell's edge, with coarse red-purple dashes, Maurer's clefts; a compact trophozoite, also with clefts; a schizont of sixteen small merozoites round one dark mass of pigment; and a curved, banana-shaped gametocyte longer than a red cell, the cell stretched thinly round it.

Point at a name or a part to light it.

Inside the red cell, each species goes from ring to trophozoite to schizont, which bursts to release merozoites that invade new cells: erythrocytic schizogony, about every 48 hours for P. vivax and P. falciparum and 72 hours for P. malariae. A few become gametocytes instead. The species are told apart on a Giemsa-stained thin film by the size of the infected cell, the stippling in it, the shape of the stages and how many merozoites a schizont holds.

Simplified: colours: Giemsa stains the cytoplasm blue and the chromatin red; drawn in arcmed's colours instead (the protist's rose, chromatin in DNA's blue), with the stain's contrast; one typical form of each stage; a real film shows every shape in between; the P. falciparum trophozoite and schizont drawn for completeness, though they are seldom seen in the blood; male and female gametocytes not told apart; P. ovale and P. knowlesi left out, and P. malariae's Ziemann's stippling, seen only rarely.

2 sources
  1. Centers for Disease Control and Prevention. DPDx: Malaria. Last reviewed 13 December 2024.
  2. Kumar and Clark’s Clinical Medicine, 10th edition. Elsevier, 2021. Chapter 20, Infectious disease; malaria, pp. 563–567.

At a glance

  1. Plasmodium is an apicomplexan carried by female Anopheles mosquitoes. Five species infect people: P. falciparum, P. vivax, P. ovale, P. malariae and, in South-east Asia, P. knowlesi.
  2. A bite injects sporozoites, which multiply first in the liver, then again and again in red cells: about every 48 hours for most species, every 72 hours for P. malariae. The blood stages cause the disease.
  3. P. vivax and P. ovale leave dormant hypnozoites in the liver, which cause relapses; P. falciparum causes nearly all deaths, as its infected red cells stick in small vessels.
  4. The species are told apart on a Giemsa-stained blood film by the size of the infected cell, its stippling, the shape of each stage and the number of merozoites in a schizont.
  5. Treatment is artemisinin-based combination therapy, intravenous artesunate for severe malaria, and primaquine to kill hypnozoites. Prevention is nets, insecticides, prophylaxis for travellers and, for African children, vaccines.

Plasmodium and malaria

Like Toxoplasma, the malaria parasites belong to the Apicomplexa: they live inside cells and enter them with an apical complex at their front end. Their sexual cycle runs in the female Anopheles mosquito, their asexual cycles in a person.

P. falciparumP. vivaxP. ovaleP. malariae
Blood cycleabout 48 hoursabout 48 hoursabout 48 hoursabout 72 hours
Red cells it prefersanyyoung cellsyoung cellsolder cells
Hypnozoites, relapsesnoyesyesno
The diseasethe most dangerous, nearly all deathsusually milder, relapseslike P. vivaxmild, can last years; nephrotic syndrome in children

P. knowlesi is a parasite of macaque monkeys that infects people in parts of South-east Asia; its illness ranges from mild to fatal.

Malaria is found through the tropics and subtropics. In 2024 there were an estimated 282 million cases and 610,000 deaths, 95 per cent of both in the WHO's African Region, and three in four of those deaths in children under five. P. falciparum is the deadliest species and the commonest in Africa; P. vivax dominates in most countries outside sub-Saharan Africa. Travellers carry it home: more than 25,000 people from countries without malaria are infected each year.

The life cycle

Plasmodium: the life cycle
A map of the malaria parasite's life cycle. Across the top, a pale panel for the female Anopheles mosquito, drawn on the left. Along it, three stages on chips: the ookinete, formed after gametes fuse in the mosquito's gut; the oocyst on the gut wall; and the sporozoites, in the salivary glands 9 to 18 days after the meal. From the sporozoites, a bite carries them down into the patient's panel, to the liver, a panel of its own, where the link branches: to the liver schizont, which grows in a liver cell, and to the hypnozoites of P. vivax and P. ovale, dormant, with an arrow from them to the liver schizont marked relapse. From the liver schizont, merozoites go down into the blood, a panel of its own: the ring, then the trophozoite, then the schizont, whose merozoites loop back under the row to new red cells, about every 48 hours, or 72 in P. malariae. From the schizont, an arrow to the gametocytes, and from them a blood meal climbs back up to the mosquito's ookinete.

Point at a name to light its pathway.

Plasmodium needs two hosts: the female Anopheles mosquito, in which its gametes fuse, and a person, in whom it multiplies first in the liver and then again and again in red cells. The blood stages cause the disease, and the gametocytes carry it on to the next mosquito.

Simplified: a map, not anatomy: the hosts drawn as icons and the parasites drawn small, nothing to scale; each stage drawn the same for every species; the figure of the stages in the red cell tells them apart; the gametes and the zygote in the mosquito's gut not drawn apart from the ookinete; infection by blood transfusion or shared needles, without a mosquito, not drawn.

2 sources
  1. Centers for Disease Control and Prevention. DPDx: Malaria. Last reviewed 13 December 2024.
  2. Kumar and Clark’s Clinical Medicine, 10th edition. Elsevier, 2021. Chapter 20, Infectious disease; malaria, pp. 563–567.

In the mosquito. A female Anopheles that takes up gametocytes in a blood meal becomes infected. In her gut, male and female gametes fuse into a zygote, which lengthens into a motile ookinete. It crosses the gut wall and grows into an oocyst, which bursts to release sporozoites; they make their way to her salivary glands. This sporogonic cycle takes 9 to 18 days, faster in warmer weather, so the mosquito must live long enough to pass the parasite on.

In the liver. A bite injects sporozoites, which reach the liver in the blood and enter liver cells. Each grows into a liver schizont, and after some days it bursts and releases merozoites into the blood: exo-erythrocytic schizogony, which causes no symptoms. In P. vivax and P. ovale some sporozoites lie dormant instead, as hypnozoites, which can wake weeks or even years later and cause a relapse without a new bite.

In the blood. Merozoites invade red cells. Each grows from a ring into a trophozoite, which feeds on the cell's haemoglobin, and then into a schizont, which divides into new merozoites. The cell bursts and they invade new red cells: erythrocytic schizogony, about every 48 hours, or 72 in P. malariae. A few merozoites become male and female gametocytes instead, which wait in the blood for a mosquito.

Malaria can also pass without a mosquito: from mother to baby, in a blood transfusion or a transplant, and on shared needles.

In the red cell

The figure at the top of the page sets the blood stages of the three species side by side. On a thin film stained with Giemsa, the parasite's cytoplasm stains blue and its chromatin red, and as it digests haemoglobin it leaves the haem as a brown pigment, haemozoin.

P. vivaxP. malariaeP. falciparum
Infected red cellenlarged 1.5 to 2 times from the trophozoite on, with fine Schüffner's dotsnormal or smallernormal; at times Maurer's clefts
Ringthick, one large chromatin dotsturdy, one large chromatin dotdelicate, a fifth of the cell across, often two dots, several in one cell, some flat against the edge
Trophozoiteamoeboid, with a vacuole and fine yellowish-brown pigmentcompact, at times a band across the cell; coarse dark pigmentcompact; seldom seen in the blood
Mature schizont12 to 24 merozoites, almost filling the cell6 to 12 merozoites, sometimes a rosette round the pigment8 to 24 small merozoites; seldom seen in the blood
Gametocyteround to oval, filling the cellround, compact, filling the cellcrescent or sausage-shaped, longer than a red cell

The marks to know:

  • Schüffner's dots, fine red stippling over the cell, point to P. vivax (an enlarged cell) or P. ovale (a cell of about normal size, often oval).
  • The band form and the rosette schizont point to P. malariae.
  • Small, delicate rings, several in one cell, and crescent gametocytes point to P. falciparum. Its older stages are rarely seen, because the cells holding them stick in small vessels.

Malaria

How it makes people ill

The blood stages cause the disease. Each time a crop of schizonts bursts, the released parasite material sets off a surge of cytokines, and with it the fever. The anaemia has several causes: infected and uninfected red cells are destroyed, the marrow makes too few, the spleen enlarges and holds on to them, and folate runs low.

In P. falciparum, red cells holding trophozoites and schizonts stick to the lining of small vessels in the brain, kidneys, gut and other organs. They block the flow, and this sequestration underlies the severe disease.

Some people are protected. People without the Duffy antigen on their red cells, the usual type in West and Central Africa, are largely resistant to P. vivax, which uses it to enter red cells; this is why vivax malaria is rare there, though infections in Duffy-negative people do occur. And the sickle cell trait and other haemoglobin disorders protect against severe malaria, which may be why they are common where malaria is. Partial immunity builds up after many infections, and is lost after a few years without one. Children, pregnant women (in whom it can also bring an early birth or a small baby), people without a spleen and visitors from places without malaria are most at risk.

The illness

The incubation is usually 10 to 21 days, but can be longer. Malaria starts with fever, often with headache, aching, vomiting or diarrhoea, so it is easily mistaken for flu. Only after some days may the fever settle into its classic rhythm, every other day (tertian) or every third day (quartan, in P. malariae), with shaking chills, a temperature up to 41°C and drenching sweats.

  • P. vivax and P. ovale usually cause a milder illness, with slow anaemia and a tender, enlarged liver and spleen, though P. vivax can be severe. Relapses can follow for years, and, rarely, the enlarged spleen ruptures.
  • P. malariae causes a mild, chronic illness; the parasites can stay in the blood for years, and in children it can cause nephrotic syndrome.
  • Severe falciparum malaria can follow within hours, above all in children: cerebral malaria, with confusion, seizures and coma; severe anaemia; kidney failure; hypoglycaemia; acidosis; acute respiratory distress; shock and bleeding. In blackwater fever, red cells break down in the vessels and the urine turns dark. A high parasite count is itself a sign of severe disease. The cut-off varies: some textbooks use more than 1 per cent of red cells in someone without immunity, and the WHO uses more than 10 per cent in anyone. A low count does not rule severe disease out, because many infected cells are hidden in small vessels. Untreated, cerebral malaria is always fatal.

Diagnosis

  • Think of malaria in anyone with a fever who is in, or has recently left, a malarious area. Falciparum malaria seldom starts more than 3 months after leaving, but vivax malaria can first appear up to a year later.
  • Blood films stained with Giemsa are the standard: a thick film finds the parasites, a thin film shows which species and how many. At least three sets of films, 12 to 24 hours apart, are examined before malaria is ruled out.
  • Rapid antigen tests give an answer in minutes and are used alongside films, or in their place where microscopy is not available; some P. falciparum strains that lack the antigen they detect are missed. Antibody tests have no place in diagnosing acute malaria.
  • In places where malaria is common, parasites in the blood do not always mean they are the cause of the illness.

Treatment

  • Uncomplicated falciparum malaria: artemisinin-based combination therapy (ACT), such as artemether with lumefantrine, for 3 days. A course of an artemisinin is never given alone, to slow resistance: even after intravenous artesunate, an ACT finishes the treatment.
  • P. vivax, P. ovale and P. malariae: chloroquine where it still works, or an ACT. Then, for P. vivax and P. ovale, primaquine, usually for 14 days (7 days at a higher dose in some guidelines), or a single dose of tafenoquine, to kill the hypnozoites. Both can cause haemolysis in G6PD deficiency, which is tested for first, and neither is given in pregnancy.
  • Severe malaria is an emergency: intravenous artesunate, which works better than intravenous quinine, for at least 24 hours, then a full course by mouth, with intensive care as needed, watching for hypoglycaemia and fluid overload, and with blood counts every week for 4 weeks afterwards, as a late haemolysis can follow artesunate.

Resistance is spreading: to chloroquine in P. falciparum long ago and now in some P. vivax, and partial resistance to the artemisinins in South-east Asia and now in East Africa.

Prevention

  • Against the mosquito: insecticide-treated nets and indoor spraying are the two mainstays, with draining the places where mosquitoes breed.
  • For travellers: a repellent such as DEET, a net, and prophylaxis, chosen for the place and the person, continued after return, for 4 weeks with most drugs, and never 100 per cent effective.
  • In endemic areas: seasonal chemoprevention for young children during the rainy season, and, for pregnant women, who are at greater risk, preventive doses of sulfadoxine-pyrimethamine at antenatal visits from the second trimester.
  • Vaccines: two, RTS,S/AS01 and R21/Matrix-M, which act against P. falciparum, are recommended by the WHO for children where malaria is endemic, above all where transmission is moderate or high, and are being added to routine childhood immunisation across Africa.

Check yourselfAnswer, then say how sure you were: a lucky guess still counts as a weak point.

1Which species can relapse months or years after the first attack, from dormant forms in the liver?

2A thin film shows enlarged red cells stippled with fine red dots, holding amoeboid trophozoites and schizonts of about 16 merozoites. Which species is it?

3Why does a film from a patient with falciparum malaria usually show only rings and, later, gametocytes?

4Which species does a band-form trophozoite stretched across a normal-sized red cell point to?

5A traveller back from West Africa a week ago is confused, with a fever and 5 per cent of red cells parasitised. What is the first treatment?

6Which advice for a traveller to a malarious area is right?