A thorough study of parasitic helminth antigens is a pre-requisite for control programmes based on accurate immunochemical diagnosis, protection by vaccination and perhaps immune modulation to diminish pathological sequelae. Studies should be directed at the identification of those stage- or age-specific surface, secreted and somatic antigens which are involved in the host-parasite interactions responsible for immunity and/or pathology. Current methods of diagnosis of parasitic infections often fail to detect low-level patent infections, which incurs the risk of having a reservoir capable of perpetuating infections. There is, then, an urgent requirement for accurate immunochemical diagnosis, to be used in association with, and for the evaluation of, drug treatment and vector elimination, in parasite control programmes. Given the high sensitivity of current immunoassay technology, the only bar to establishing the necessary immunological tests is the choice of suitably specific antigen/antibody systems. Assays designed to detect parasite products or antigens are a major priority, as they indicate current infection, whereas those which detect antibody only indicate exposure to infection, which may or may not be current. Surface and secreted antigens are the most likely targets for protective immune responses and thus form a logical focus for vaccine design. The cestodes, which present such strong evidence for immunity following natural infection, are likely to yield effective vaccines by modern procedures. Certain antigens must, however, stimulate the humoral and/or cellular responses which are responsible for the undesirable immunopathological consequences of many helminthic diseases. The nematodes and trematodes furnish some extreme examples of such pathology. The ultimate objective in identifying these particular antigens is to utilize them in the appropriate down-regulation of the immune response responsible for such pathology. As an illustration, we have presented an interesting correlation between one particular clinical condition of onchocerciasis (Sowda) and the serological response, defined both in terms of the parasite antigens and an immunoglobulin class-restricted antibody response. Finally, the complexity of these parasite systems and the host response to the parasite should not be underestimated. Modern analytical techniques allow their detailed analysis in terms of the humoral antibody responses and afford the possibility of the future development of control and disease management procedures tailored to each individual host-parasite system. However, novel systems are required to complete the analysis of the cellular components of the immune response to parasite antigens, and functional studies are needed to determine the role that these parasite antigens play in the complex interaction between parasite and host.

Parasitic infections in man and domestic animals exhibit two striking characteristics (a) their prevalence is high, but infections are unequally distributed among individuals within populations and (b) immunity is often slow to develop and appears, at best, only partially effective. Recent immunological and epidemiological studies suggest that effective immunity can develop, but that high prevalence within populations reflects the operation, not only of socio-economic and climatic factors, or husbandry practices, but also of powerful environmentally induced constraints upon the development of resistance. Immunogenetic studies suggest the operation of additional constraints which reflect individual genetic characteristics, and which influence the ability to develop and express effective immunity. A full understanding of all constraints is necessary before levels of population and individual resistance to infection can be increased; the need for such understanding has become more pressing with the prospect that anti-parasite vaccines may become available. Two aspects of environmentally induced constraints are considered, those arising from nutritional inadequacies and those resulting from exposure to infection in early life. Both are discussed primarily in terms of helminth parasites. Genetically determined constraints are discussed with reference to MHC-restricted recognition of malarial peptide vaccines and in terms of Class II molecule-directed control of T-cell function in Leishmania infections. Genetic influences are also considered from the standpoint of inflammatory cell function, in immunity against intestinal nematodes and in vaccine-induced immunity against Schistosoma. Finally, parasite-induced constraints, particularly those which down-regulate protective responses are discussed briefly.

Survival of the trypanosome (Trypanosoma brucei) population in the mammalian body depends upon paced stimulation of the host's humoral immune response by different antigenic variants and serial sacrifice of the dominant variant (homotype) so that minority variants (heterotypes) can continue the infection and each become a homotype in its turn. New variants are generated by a spontaneous switch in gene expression so that the trypanosome puts on a surface coat of a glycoprotein differing in antigenic specificity from its predecessor. Homotypes appear in a characteristic order for a given trypanosome clone but what determines this order and the pacing of homotype generation so that the trypanosome does not quickly exhaust its repertoire of variable antigens, is not clear. The tendency of some genes to be expressed more frequently than others may reflect the location within the genome and mode of expression of the genes concerned and may influence homotype succession. Differences in the doubling time of different variants or in the rate at which trypanosomes belonging to a particular variant differentiate into non-dividing (vector infective) stumpy forms have also been invoked to explain how a heterotype's growth characteristics may determine when it becomes a homotype. Recent estimations of the frequency of variable antigen switching in trypanosome populations after transmission through the tsetse fly vector, however, suggest a much higher figure (0·97–2·2 × 10−3 switches per cell per generation) than that obtained for syringe-passed infections (10−5–10−7 switches per cell per generation) and it seems probable that most of the variable antigen genes are expressed as minority variable antigen types very early in the infection. Instability of expression is a feature of trypanosome clones derived from infective tsetse salivary gland (metacyclic) trypanosomes and it is suggested that high switching rates in tsetse-transmitted infections may delay the growth of certain variants to homotype status until later in the infection.

Genetic exchange is now known to occur during the life-cycle of many parasitic protozoa, including malaria parasites, coccidia and trypanosomes. The process is studied by making deliberate crosses between cloned organisms differing in clearly defined markers. In malaria parasites, crosses have been made between parasites differing in characters such as isoenzymes, antigens and other proteins, drug sensitivity, and chromosome and other DNA polymorphisms. Crosses are made by transmitting a mixture of gametes of each clone through mosquitoes to allow cross-fertilization to take place, and examining the resulting progeny by cloning for organisms exhibiting non-parental combinations of characters. The inheritance of many characters, such as antigen and protein variants, is in accordance with Mendelian expectations for a haploid organism. Recombination occurs at a higher than expected frequency. Studies on chromosomes have show that crossing-over events commonly occur following meiosis of hybrid zygotes. Repetitive DNA and subtelomeric regions of chromosomes appear to be particularly susceptible to such recombination events. In trypanosomes, crosses between clones of Trypanosoma brucei have shown that hybrids are formed during tsetse fly transmission. The organism appears to be mainly diploid, but some characters including certain chromosomes seem to be inherited in a non-Mendelian manner.

The paper examines non-linear dynamical phenomena in host—parasite interactions by reference to a series of different problems ranging from the impact on transmission of control measures based on vaccination and chemotherapy, to the effects of immunological responses targeted at different stages in a parasite's life-cycle. Throughout, simple mathematical models are employed to aid in interpretation. Analyses reveal that the influence of a defined control measure on the prevalence or intensity of infection, whether vaccination or drug treatment, is non-linearly related to the magnitude of control effort (as defined by the proportion of individuals vaccinated or treated with a drug). Consideration of the relative merits of gametocyte and sporozoite vaccines against malarial parasites suggests that very high levels of cohort immunization will be required to block transmission in endemic areas, with the former type of vaccine being more effective in reducing transmission for a defined level of coverage and the latter being better with respect to a reduction in morbidity. The inclusion of genetic elements in analyses of the transmission of helminth parasites reveals complex non-linear patterns of change in the abundance of different parasite genotypes under selection pressures imposed by either the host immunological defences or the application of chemotherapeutic agents. When resistance genes are present in parasite populations, the degree to which abundance can be suppressed by chemotherapy depends critically on the frequency and intensity of application, with intermediate values of the former being optimal. A more detailed consideration of the impact of immunological defences on parasite population growth within an individual host, by reference to the erythrocytic cycle of malaria, suggests that the effectiveness of a given immunological response is inversely related to the life-expectancy of the target stage in the parasite's developmental cycle.

During the last decade there has been a great increase in the number of countries that have endorsed the primary health care (PHC) policy at national level, set up national guidelines for it and launched its large-scale implementation. In addition, there have been many important developments with regard to appropriate, cost-effective technologies, training concepts and approaches to securing community participation. These achievements have produced numerous encouraging results. However, although the control of parasitic infections integrated into PHC systems has often been initially successful, these achievements could often not be sustained. Using case studies, mainly concerning schistosomiasis, as examples, control technologies and their applicability within PHC are discussed at three levels; the identification of public health priorities, the community-based implementation of control and the process of evaluation and monitoring. There is a great potential for the integration of a substantial part of control activities, particularly morbidity control, into PHC, provided that the aims and sequences of control activities are well matched with the felt needs of the communities concerned. This implies that the biomedical researcher, the epidemiologist and the health planner need to consider the indigenous health perspectives of the affected community. For example, recent progress in the laboratory in the development of vaccines against parasites needs to be complemented by field studies that continuously validate, standardize and assess the applicability of the proposed measures. This kind of interplay will form the basis for participatory approaches in health planning and make it possible for control activities to be integrated into existing PHC structures and to respond to the needs of the communities concerned.

Throughout evolution, enzymes and their metabolites have been highly conserved. Parasites are no exception to this and differ most markedly by the absence of metabolic pathways that are present in the mammalian host. In general, parasites are metabolically lazy and rely on the metabolism of the host both for a supply of prefabricated components such as purines, fatty acids, sterols and amino acids and for the removal of end-products. Nonetheless, parasites are metabolically highly sophisticated in that (1) they retain the genetic capacity to induce many pathways, when needed, and (2) they have developed complex mechanisms for their survival in the host. Certain unique features of the metabolism of trypanosomes, leishmania, malaria and anaerobic protozoa will be discussed. This will include (1) glycolysis and electron transport with reference to the unique organelles: the glycosome and the hydrogenosome, (2) purine salvage, pyrimidine biosynthesis and folic acid metabolism and (3) polyamine and thiol metabolism with special reference to the role of the unique metabolite of trypanosomes and leishmanias, trypanothione.

The complex life-cycles of parasitic animals are a product of exploiting the process of development to generate organisms with different biological potentials within a species. Successive stages of the parasite adapt to functions such as host invasion and transmission, and to the colonization of a variety of niches, often involving different hosts, tissues or cells. Understanding the molecular basis of adaptive biology among parasities is a major challenge that lies at the heart of research in contemporary parasitology. Differences in scale at the levels of genomic complexity and cell biology exist between most parasitic protozoa and helminths, rendering a cautionary note to making generalized observations. The two principal approaches used to gain insights into adaptive specializations are to start with a biological activity and identify the molecule, or select molecules with particular properties and deduce function. Both have their part to play, with their inherent advantages and limitations, and both are illustrated with examples of studies on adaptive biology among parasitic nematodes.

The DNA of a parasite is the ultimate blueprint of that parasite, the one characteristic which normally remains unchanged during every stage of the life-cycle. All the DNA sequence in the egg of a species of parasite are also in the larvae and adults of the same species. The same DNA is present in the parasite whether it is in a free-living stage, in an invertebrate vector or in a vertebrate host such as man. The molecular basis for DNA diagnosis is to allow labelled single-stranded species or strain-specific DNA sequences, selected from well-characterized reference species, to find and hybridize with homologous DNA from, or in, the unknown isolates of parasites. DNA probes are now available for most vector borne parasitic diseases. Parasitological identification problems are mostly concerned with distinguishing closely related strains or subspecies, for example detecting Taenia solium eggs as opposed to T. saginata eggs, or finding which of the 15 man-infecting subspecies of Leishmania is present in a single cutaneous lesion, the commonest clinical sign of the disease, or in a sandfly. For efficient hybridization by the present methods there has to be enough of a particular sequence present in a parasite's genome to make a feasible target. Therefore, DNA probes for parasites have been selected from repetitive, reiterated or multicopy DNA with intrinsic extensive sequence variation. DNA, which is free of coding restraint, can evolve rapidly to give differences between species, so that introns, ribosome gene spacers, variant genes, pseudo-genes and non-conserved DNA have all been used for DNA diagnosis. The major problems of sequence selection have been greatly aided by the use of recombinant DNA methods, which have the added advantage of economical production of DNA probes. The unique characteristics of kinetoplast mini-circle DNA in Leishmania has allowed the selection of a complex species, subspecies, strain and even isolate-specific DNA probes. These have been used successfully for Southern filter endonuclease fragment DNA identification, for dot-blot recognition of less than 200 parasites and non-radioactive detection of DNA sequence homology by ‘in situ’ hybridization and light microscopy in a single Leishmania cell. The adaptation of the forensic human genetic fingerprinting technique has allowed identification of L. braziliensis DNA in human biopsy material, even the presence of a vast excess of human DNA. Fingerprinting with ribosomal spacer-derived recombinant DNA probes has been used to discriminate Echinococcus species. The identification of Taenia species has been accomplished using probes from a genomic library of size-selected DNA fragments, and synthetic oligonucleotides are available for Onchocerca subspecies detection. The new technologies combining repeated genomic sequence probes with pulse field separation of the chromosomes of parasites, has opened up new avenues of research. Double probes for the simultaneous identification of the insect vector and the carried parasite have recently been reported. Lastly, the polymerase chain reaction technique has given us the opportunity of amplifying even single copy genes in one parasite to give sufficient DNA for positive identification. DNA diagnosis in parasitology is now on a par with the DNA diagnosis of viruses and human genetic disorders. The last ten years have seen many exciting developments in DNA diagnosis; the next years should see DNA diagnosis routinely used in epidemiological and clinical situations in countries where parasitic diseases are a major public health problem.

Work reported at this meeting has described the exploitation of variation in parasite phenotype in disciplines ranging from molecular taxonomy and drug development, through the understanding of host-parasite interaction, to the evolution of parasite populations and determining the potential efficacy of vaccine programmes.