More about malaria
The lifecycle of plasmodia – from vector to victim
Human malarial plasmodia have a highly complex life cycle linking a host (man) with a vector (mosquitoes of the genus Anopheles). The parasite’s sexual reproduction phase takes place in the mosquito vector, whilst asexual reproduction phases occur in the human host.
1. A female Anopheles mosquito that has already sucked up infected blood from one human passes on a malarial infection by biting another victim.
2. The mosquito’s saliva contains sporozoites (thread-like forms of the parasite), which pass into the victim’s blood.
3. In the human host, the sporozoites rapidly (within 20 minutes) penetrate parenchymal cells of the liver. Herethey transform into large tissue schizonts that reproduce asexually to generate large numbers of merozoites.11
4. After 5-20 days, the merozoites rupture the liver cells and start an erythrocytic cycle.
5. & 6. During the erythrocytic cycle, the merozoitesinvade red blood cells in the peripheral blood stream, where they feed on haemoglobin and multiply further. This results in a huge, periodic amplification of parasite populations. In 2-day cycles, they rupture the erythrocytes, releasing the merozoites, which promptly invade and destroy more erythrocytes. The release of merozoites produces the characteristic bouts of fever in the patient11, 27
7. After this asexual propagation, some merozoites develop into gametocytes, (sexual forms),which are ingested by the next mosquito sucking blood.
8. In the mosquito gut, male and female gametes emerge from the gametocytes and fuse into zygotes, which migrate into the gut wall. There, they produce oocysts, each of which generates around 1000 sporozoites.
After about two weeks, sporozoites migrate into the mosquito’s salivary gland.28, 29 They develop over 9 days or so, becoming highly infective. They are then injected into a human when the mosquito next feeds — thus closing the cycle.
After invading hepatocytes, some merozoites of P. vivax and P. ovale (but not of P. falciparum or P. malariae) transform into hypnozoites that remain dormant for some time. Re-activation leads to relapses, which can occur weeks, months, or years after the initial infection.27
See also What is recrudescence?
Immunity against plasmodia
Frequent or chronic exposure to infection with malaria parasites over prolonged periods produces varying degrees of immunity - from partial to full. However, human defence mechanisms are not fully effective against these parasites, and total immunity is not possible, even for a short period of time, or even in people in hyperendemic areas.9
Non-immune malaria patients may have as many as 1600 parasites per 1000 erythrocytes. However, partially or fully immune people still have as many as one P. falciparum per 106 to 1025 erythrocytes.9 This explains why clinical break-through attacks can occur without re-infection, in seemingly immune people whose normal defence mechanisms are compromised.
Gametocyte carriers
Apart from break-through attacks, immune people generally do not develop symptoms, despite being infected with malarial plasmodia. However, such people still develop gametocytes. Therefore, in areas of high endemicity, immune adults represent a large reservoir of infection, which threatens the non-immune population. Infants below age 5 are particularly susceptible as they have not yet developed sufficient immunity.11 Parasite carriers can actually trigger small epidemics of malaria in communities of non-immune people.
Theoretically, eradication of gametocytes would significantly help to break the vicious circle of infection. Existing antimalarials such as chloroquine, quinine, and related quinoline-ring antimalarials are unable to kill mature gametocytes.27
Coartem® /Riamet® / is gametocidal, and may therefore play an important role in gametocyte eradication programs.
Life cycle of the parasite and the clinical course of malaria
The characteristic cyclical fevers of malaria can be linked to the stages of the very specialised life cycle of the parasite.
A. Prodromal or cold stage
Headache, lethargy, nausea and vomiting, diarrhoea and muscular aches and pains.
B. Hot stage
Fever, aching, shivering.
C. Sweating stage
Copious sweating, temperature fall, sleep.
Disease caused by the four types of malaria is similar, although falciparum malaria differs from the others in some important respects. In particular, the differences involve the way in which the parasites multiply in the blood. P. falciparum can invade erythrocytes at any stage of maturity, but P. ovale and P. vivax only invade relatively young red cells, while P. malariae attacks older cells. In addition, with falciparum malaria, infected blood cells stick to small blood vessel walls, causing microvascular blockage in vital organs. This does not occur with the other types of malaria.
All of the common symptoms of malaria are associated with the invasion of the erythrocytes and the subsequent destruction of these cells. The characteristic fever occurs when the infected red cells burst and release merozoites, haemoglobin and protozoal toxins into the bloodstream.
Attacks by the merozoite stage of the malaria parasite on erythrocytes are responsible for the characteristic symptoms of malaria.
The early symptoms of infection are non-specific, consisting of headache, lethargy, nausea and vomiting, diarrhoea and muscular aches and pains.
These symptoms appear when, at first, small numbers of erythrocytes are destroyed. As the parasites multiply, however, huge numbers are released simultaneously, producing the characteristic bouts of fever.
The characteristic fever or paroxysm may peak at 40°C.
Each attack lasts for up to 12 hours, except for falciparum malaria where attacks may last for as long as 36 hours. During an attack the initial symptoms are enhanced, and fever can reach very high levels (up to 40°C or higher). The time to the next fever or paroxysm depends upon the time it takes for the next generation of schizonts to mature and release their swarm of merozoites.
