The patients we are concerned about in tropical medicine are unfortunately affected by a wide range of conditions, not only those seen and studied extensively in the West, such as cancer, cardiovascular diseases and viral or bacterial infections, but also the major protozoan and metazoan conditions – the parasitic diseases. It is with this spectrum of pathophysiological changes that occurs in this last group that we are presently concerned and this communication is intended to present an overview of the subject.

Parasites can have a wide range of pathophysiological effects on the host. This review describes those associated with some parasites of major importance in man and animals. Haemoprotozoan diseases such as trypanosomiasis and malaria are primarily associated with anaemia. Such anaemias have a complex aetiology involving various mechanisms responsible for red cell destruction as well as possible defects in red cell production. In addition to these haematological effects these diseases are associated with marked disturbances in heart function and the nervous, immune and urinary systems. The other major groups of parasitic diseases are those associated with the gastrointestinal tract. The most advanced studies have been conducted on the pathophysiology of gastrointestinal nematode parasites of sheep and have revealed significant effects on feed intake, gastrointestinal function, and protein and energy metabolism. Similar studies have yet to be conducted in other hosts and parasitic diseases. There is also a need to examine in greater detail the factors which can modulate pathophysiological responses by the host to parasitic infections.

The term severe falciparum malaria implies an infection with manifestations and complications which are potentially fatal in man, the natural host for this parasite. Much that has been written on the pathophysiology of animal malarias is of doubtful relevance to the understanding of the mechanism of Plasmodium falciparum infection in man. The clinical picture of severe P. falciparum infection differs in several respects from severe animal malarias, even those of non-human primates. Cerebral dysfunction is the most common severe manifestation of falciparum malaria in man. Coma develops suddenly after a generalized convulsion or gradually towards the end of the first week of illness. There are signs of a symmetrical upper motor neurone lesion and brain-stem dysfunction, but only about 5% of survivors show persisting neurological deficit after 2 or 3 days of unconsciousness. The mortality of cerebral malaria depends on how it is defined and on the predominant age group and other factors. In patients with proved acute P. falciparum infection with unrousable coma, in whom other causes of encephalopathy have been excluded, the mortality is between 15 and 50% despite treatment with antimalarial drugs (Warrell, Looareesuwan, Warrell, Kasemsarn, Intaraprasert, Bunnag & Harinasuta, 1982).

Mucus is a sticky visco-elastic material which coats all mucosal surfaces. Florey, in 1955, noted the following three functions for gastrointestinal mucus: protection of the underlying mucosa from chemical and physical injury, lubrication of the mucosal surface to facilitate passage of luminal contents, and removal of parasites by binding and entrapment. In the 31 years since Florey's review, detailed analyses of the composition of mucus and of the biochemistry of mucin glycoproteins, as well as measurements of the physical properties of mucus from different organs and sites have yielded information at the molecular level which provide additional support for his views on its function (Allen, 1981; Forstner, Wesley & Forstner, 1982).

The inflammatory responses to lymphatic filariae and to Onchocerca volvulus are reviewed with particular attention to (1) evolutionary biology; (2) inflammatory host spectrum; (3) non-specific components; (4) immunoregulation; (5) immune evasion versus immunomodulation; (6) chronic tissue damage and scarring and (7) disease models. Basic principles of pathogenesis are emphasized, comparisons drawn with schistosome infection, and critical items of missing information are highlighted.

Recent progress in parasite immunobiology has led to the identification of several plasmodial antigens representing the target of the protective antibody response of the infected host. As a consequence, some of these antigens have been envisaged as potential malaria vaccines in man. However, in spite of these achievements, the fine mechanisms which lead to the development of a state of partial protective immunity or to the triggering of immunopathology during malaria infection are not yet fully understood. Thus, it may be appropriate to evaluate the relative importance of individual host immune responsiveness to parasite epitopes involved in the induction of immunity, or of some immunologically mediated adverse reactions such as glomerulonephritis, anaemia, thrombocytopenia, and cerebral syndrome.

During the primary immune response to an infectious agent, specific memory cells are generated which enable the immune system to respond more rapidly and efficiently to re-exposure to the same agent. Under normal circumstances, this acquired resistance leads to the effective elimination of the agent, and recovery. However, under certain circumstances these secondary infections, rather than aiding recovery, actually produce tissue damage and often contribute to the disease process. This stage has been termed hypersensitivity and such hypersensitivity reactions play an important role in the immunopathology of several diseases. Coombs & Gell (1963) have classified hypersensitivity into four types of reaction. Types I, II and III involve antibody-mediated processes whereas type IV is mediated solely by lymphocytes. Many parasitic infections have characteristics which would appear to predispose the host to the development of hypersensitivity states and consequent immunopathology. These include (1) the chronicity of the infections, (2) the release of parasite antigens in large amounts and their persistence in the circulation and host tissues, (3) the sharing of antigens between parasite and host and (4) the ability of the parasite to damage host tissues and alter their antigenicity. However, direct evidence that these mechanisms lead to the development of immunopathology in parasitic infections is limited. In this article, these four types of hypersensitivity will be briefly discussed in the context of the immunopathology following parasite infection. There then follows a more extensive consideration of type III hypersensitivity with particular emphasis on the mechanisms underlying the development of immune-complex mediated disease.

Throughout the world, infection with parasites is extremely common. Prevalence is highest in the warm countries of the tropics and subtropics, but infection occurs in all climatic zones. The figures usually quoted for the prevalence of specific parasites attain values akin to those used to describe astronomical distances. The World Health Organization (1985) estimated that some 2582 million of the earth's inhabitants live in areas where they risk contracting malaria and that many – in Africa south of the Sahara alone probably 200 million – remain chronically and persistently infected. Estimates for other parasites are similarly impressive; 600 million at risk of infection with schistosomiasis, with some 200 million actually infected; 900 million exposed to lymphatic filarial parasites, with some 90 million currently infected; for onchocerciasis, probably some 40 million cases spread throughout Africa, Central and South America and the Eastern mediterranean. Yet, impressive as these estimates may be, they are dwarfed by those for some intestinal helminths. Recent assessments suggest that 1 person in 4 of the world's population carries Ascaris lumbricoides (Schultz, 1982), while the same proportion is believed to be infected with one or other of the hookworms (Gilman, 1982).

Good wine needs no bush, and good papers need no third-party summary. The papers presented today at this symposium on the pathophysiology of parasitic disease have been splendid, and I shall not be so foolish as to attempt the impossible task of summarizing them. This stage in the meeting does, however, provide an opportunity to look forward in the light of what has been presented today, and there are some points that are of particular interest and which will bear repetition or comment in the closing minutes of this symposium.