Section 1 The adversaries – microbes
5 The protozoa
Protozoa are single-celled animals, ranging in size from 2 to 100 nm. Many species are free-living, but others are important parasites of humans. Some free-living species can infect humans opportunistically. Protozoa continue to multiply in their host until controlled by its immune response or by treatment and thus may cause particularly severe disease in immunocompromised individuals. Protozoal infections are most prevalent in tropical and subtropical regions, but also occur in temperate regions. Protozoa may cause disease directly (e.g. the rupture of red cells in malaria), but more often the pathology is caused by the host’s response. Of all parasites, malaria presents the biggest and most severe global problem and kills > 1.5 million people each year, mostly young children.
Protozoa can infect all the major tissues and organs of the body
Protozoa infect body tissues and organs as:
• intracellular parasites in a wide variety of cells (red cells, macrophages, epithelial cells, brain, muscle)
• extracellular parasites in the blood, intestine or genitourinary system.
The locations of the species of greatest importance are shown in Figure 5.1. Intracellular species obtain nutrients from the host cell by direct uptake or by ingestion of cytoplasm. Extracellular species feed by direct nutrient uptake or by ingestion of host cells. Reproduction of protozoa in humans is usually asexual, by binary or multiple division of growing stages (trophozoites). Sexual reproduction is normally absent or occurs in the insect vector phase of the life cycle, where present. Cryptosporidium is exceptional in undergoing both asexual and sexual reproduction in humans. Asexual reproduction gives the potential for a rapid increase in number, particularly where host defence mechanisms are impaired. For this reason some protozoa are most pathogenic in the very young (e.g. Toxoplasma in the fetus and in neonates). The AIDS epidemic has focused attention on a number of protozoa which give rise to opportunistic infections in immunocompromised individuals. These include Cryptosporidium, Isospora and members of the Microsporidia. New parasites continue to emerge, e.g. Cyclospora cayetanensis, a food-borne and water-borne cause of diarrhea, which became recognized in the early 1990s.
Figure 5.1 The occurrence of protozoan parasites in the body. *Can also occur in other sites. CNS, central nervous system.
Protozoa have evolved many sophisticated strategies to avoid host responses
Extracellular species evade immune recognition of their plasma membrane. The interface between host and extracellular protozoa is the parasite’s plasma membrane, and examples of strategies to avoid immune recognition of this surface include the following:
• Trypanosomes undergo repeated antigenic variation of surface antigens.
• Malaria parasites show polymorphisms in dominant surface antigens.
• Amoebae can consume complement at the cell surface.
Intracellular species evade host defence mechanisms. Although intracellular stages are removed from direct contact with antibody, complement and phagocytes, their antigens may be expressed at the surface of the host cell, which can then be a target for cytotoxic effectors. Survival within cells, particularly within macrophages (Leishmania, Toxoplasma), involves a variety of devices to evade or inactivate the harmful effects of intracellular enzymes or reactive oxygen and nitrogen metabolites.
Protozoa use a variety of routes to infect humans
Many extracellular protozoa are transmitted by ingestion of food or water contaminated with transmission stages such as cysts, but Trichomonas vaginalis is transmitted through sexual activity, and the trypanosomes by insect vectors. The most important intracellular species – Plasmodiumand Leishmania – are also insect transmitted, but others (Toxoplasma) can be acquired by ingestion or from the mother in utero (Table 5.1).
Table 5.1 Summary of the location, transmission and diseases caused by protozoan parasites
• Protozoa are single-celled animals, occurring both as free-living organisms and as parasites. Both can cause disease in humans.
• The single most important protozoal disease is malaria, which causes some 1.5 million deaths each year.
• Protozoa live both outside and within cells, and have complex ways of avoiding the responses of their hosts.
• Most infections are acquired through ingestion of contaminated water or food, or via insect vectors. A few are transmitted from mother to fetus.
Malaria provides a good example of human–protozoan conflict. After a period in the liver, the malaria parasite spends all of its time inside the red cell. It grows, divides and releases new parasites by rupturing the red cell. At this stage, the parasite wins the conflict by hiding away inside a cell, a non-nucleated cell that cannot respond defensively. How can the host protect itself immunologically? It has a number of difficult choices. It can try to destroy the parasite inside the cell by producing toxic mediators or it can try to destroy the parasite and the cell together by targeting antibodies against antigens from the parasite that appear on the red cell surface, though the parasite presents a moving target as P. falciparum is adept at antigenic variation. Both of these are risky strategies. Toxic mediators can affect the host as well as the parasites, particularly if, as infalciparum malaria, the parasite-infected cells are lodged inside capillaries in vital organs. Destroying red cells can contribute to anaemia, and the by-products of destruction can also be toxic. A significant part of the pathology associated with malaria is therefore a cost of the host defending itself – game set and match to the parasite, although a dead host is of no further use to the parasite. Though treatment with antimalarials can be highly effective, if they are given late, the patient may still succumb as a result of complications despite clearance of parasites from the blood. Furthermore, the malaria parasite is adept at developing drug resistance, another example of the moving target.