is a form of asexual reproduction in which first, the nucleus divides several times and then the parent cell divides to form as many individual merozoites as there are nuclei. Schizogony also occurs in many other apicomplexan parasites. In P. vivax and P. ovale, not all the parasites immediately undergo schizogony but instead some remain in a quiescent state known as the hypnozoite form. These hypnozoites can remain in the liver for weeks or even years before undergoing further development. They are therefore responsible for the onset of illness/relapses long after the initial infection.
The formation of merozoites destroys their host liver cells, thereby releasing them into the blood stream. The merozoites proceed to invade red blood cells in which they transform into the trophozoite stage – these also reproduce asexually by shizogony. Because these divisions take place in red blood cells, it is referred to as erythrocytic schizogony. The ingestion of host cytoplasm by a trophozoite causes the formation of a large food vacuole. This gives the parasite the appearance of a ring of cytoplasm with the nucleus conspicuously displayed at one edge – hence, the moniker of the ‘signet ring stage’. As the trophozoite grows, its food vacuole becomes less noticeable by light microscopy, but pigment granules of hemozoin in the vacuoles become apparent. Hemozoin is an insoluble polymer of haem and is the end product of the parasite’s digestion of the host’s haemoglobin. The growth of the parasites within an infected red blood cell eventually destroys it and it ruptures. This releases the merozoites, hemozoin and other parasite waste products, and dead cell material. These merozoites then infect other red blood cells and the process of infection, replication, and destruction repeats many times. At some point in this cycle, certain merozoites transform into sexual stages referred to as macrogametocytes (female) and microgametocytes (male). These gametocytes do not develop any further and remain within their host red blood cells until a suitable female anopheline mosquito ingests them.
Shortly after ingestion by a mosquito, the male and female gametocytes swell, leave their host red blood cells, locate one another, and fuse to form a zygote. This is the only diploid stage in the whole Plasmodium life cycle. The zygote then differentiates into an ookinete. The ookinete is capable of movement and it bores through the mosquito’s gut until it comes to rest at the outer wall of the midgut epithelium where it transforms into an oocyst. Inside the oocyst further rounds of asexual multiplication take place called sporogony that result in the formation of numerous sporozoites. Once it is mature, the oocyst bursts and the sporozoites migrate through the mosquito’s haemolymph (blood) to the salivary glands. The next time the mosquito feeds, it injects the sporozoites along with its saliva. Depending upon the species of Plasmodium and mosquito, the oocyst stage lasts between 8 and 35 days, thereby making it the longest part of the life cycle. It also means that successful transmission depends heavily on the lifespan of the mosquito. This is because the mosquito must survive long enough after its initial infected blood meal for the sporozoites to form and then reach its salivary glands. Infection stimulates mosquitoes to feed more frequently, thus increasing the chances of transmission. Once infected, a mosquito remains infective for the rest of her life.
3.4.1.2 Plasmodium falciparum
This is the most dangerous species because of its capacity to cause potentially fatal cerebral malaria – also sometimes referred to as malignant tertian malaria. Its distribution has become restricted in recent years although it remains very common in tropical and sub‐tropical regions such as sub‐Saharan Africa, Southeast Asia, and parts of South America. It does not form hypnozoites, but sudden relapses (recrudescence) can occur months or even years after the last fever episode because the parasite persists in the blood at low sub‐clinical levels. The merozoites can invade and develop in both young red blood cells (reticulocytes) and mature red blood cells. Consequently, falciperan malaria is often characterised by high levels of parasitaemia.
3.4.1.3 Plasmodium vivax
The name vivax derives from the lively nature of the trophozoites in our red blood cells (vivax is the Latin adjective for vivacious). This stage often has an amoeboid appearance in blood films. Vivax malaria was once the most widespread form of the disease and common as far north as Norway and Siberia. However, as European countries developed, they largely eradicated malaria, and vivax malaria is now mostly restricted to Asia and the countries bordering the Mediterranean. However, it is still the most common Plasmodium species in most countries in which malaria remains endemic. Vivax malaria is rare in West Africa because the merozoites only penetrate red blood cells carrying the Duffy buffer blood group antigens Fy a and Fy b – and most West Africans do not express these. In addition, the merozoites cannot penetrate mature red blood cells and therefore they invade developing reticulocytes. Consequently, P. vivax cannot form the same high parasitaemias achieved by P. falciparum. Plasmodium vivax is notorious for causing latent infections in which the hypnozoite stage remains quiescent within the liver and then, after years of apparent good health, the patient suddenly develops malarial fevers. The factors determining the length of the latent period probably relate to genetic differences between the parasites causing the initial infection and/or sudden changes in the host’s immune status.
3.4.1.4 Plasmodium ovale
This species exists in many parts of the world although it is not as common as P. vivax or P. falciparum, and its natural distribution is sub‐Saharan Africa and the western Pacific. The merozoites only develop in reticulocytes and the parasitaemia tends to be low. Plasmodium ovale forms hypnozoites in the liver, and therefore, it can produce long‐lasting latent infections. Some workers consider that there are two sub‐species of P. ovale, P. ovale curtisi and P. ovale wallikeri, and these differ in their clinical manifestations.
3.4.1.5 Plasmodium malariae
This species has a worldwide distribution, but it is not common anywhere and infections are normally relatively benign. Natural infections are common in chimpanzees, but these seldom live near human dwellings, and they are probably not an important reservoir of infection. Humans and chimpanzees both experience latent P. malariae infections that persist for many years. Unlike P. vivax and P. ovale, the sudden occurrence of malarial symptoms after a period of good health is not a result of hypnozoite activation. Instead, the parasite persists within the blood for years, possibly even for life, at a very low parasitaemia and it is only when some change in the immune status of the host occurs that the numbers increase sufficient to cause fever. Unlike P. vivax and P. ovale, the merozoites of P. malariae preferentially invade older red blood cells.
3.4.1.6 Plasmodium knowlesi
This species inhabits many parts of Southeast Asia. Its normal hosts are monkeys such as the long‐tailed macaque (Macaca fascicularis). It is also capable of infecting humans and is therefore a zoonosis. Human infections are a particular problem in Sarawak and peninsular Malaysia. In blood smears, it is often mistaken for P. malariae and therefore considered ‘low risk’. Unfortunately, the consequences of misdiagnosis can be fatal. This is because P. knowlesi causes serious pathology in a similar manner to P. falciparum. Like P. vivax, the merozoites of P. knowlesi only invade red blood cells carrying the Duffy buffer blood group antigens Fy a and Fy b .
3.4.2 Genus Theileria
Several species in this genus parasitize wild and domestic animals, but the most well known is Theileria parva, which causes East Coast fever (theileriosis) in cattle in sub‐Saharan Africa. Other important species include Theileria annulata that also parasitizes cattle and Theileria hirci that infects sheep and goats – these species occur in parts of North Africa, the middle East, Europe, and Asia. Theileria parasitize red blood cells, lymphocytes, and tissue macrophages (histiocytes), and they are common causes of disease and potentially fatal infections in their mammalian hosts. Unlike the genus Babesia, the genus Theileria does not