Actively immunized mice, whole-body irradiated with 650 or 525 rad., manifested comparable levels of resistance to Schistosoma mansoni compared with unirradiated, immunized mice in spite of a marked reduction in circulating leucocytes (>90%) and platelets (>85%), and despite an abrogation of delayed-type hypersensitivity (DTH) (Type IV) response to schistosomular antigens (as determined by footpad swelling, 24 h after injection of antigen). However, limited histopathological comparison of lung sections from irradiated and unirradiated mice 7 days post-challenge showed that cellular reactions (‘foci’) around parasites were essentially similar in size and cellular composition except that in irradiated mice, eosinophils were poorly represented both in the foci and in lung tissue in general. Neither presumed immune complex-mediated (Type III, Arthus reaction) hypersensitivity (as determined by footpad swelling, 5 h after injection of antigen) nor serum anti-schistosomulum extract antibody levels (as determined by ELISA) were affected. In addition, the pattern of 125I-labelled schistosomular surface antigens immunoprecipitated with serum from irradiated and unirradiated mice was essentially similar. These results are consistent with antibody playing an important role in vaccine-induced immunity in mice but suggest that radiosensitive T cell function and radiosensitive cells, such as platelets and polymorphonuclear cells, including eosinophils, may not be essential.

Many clinically useful antibacterial drugs have intracellular target sites. Therefore, in order to reach their targets, these compounds must be able to cross bacterial outer and cytoplasmic membranes. Considerable information is available on the mechanisms by which antibiotics cross bacterial membranes and, in many cases, it is now possible to define the molecular basis of their uptake. Passage of drugs across the outer membrane of Gram-negative bacteria can occur by diffusion through porin channels (e.g. β-lactams and tetracyclines), by facilitated diffusion using specific carriers (e.g. albomycin), or by self-promoted uptake (e.g. aminoglycosides and polymyxins). Transfer of antibiotics across the bacterial cytoplasmic membrane is usually mediated by active, carrier-mediated, transport systems normally operating to transport essential solutes into the cell. For example, the antibiotic streptozotocin bears sufficient structural resemblance to N-acetyl-D-glucosamine to be transported by the phosphoenolpyruvate : phosphotransferase system, and D-cycloserine is recognized by the D-alanine, proton motive force dependent transport system. However, in some cases (e.g. tetracycline) although carrier-mediated transport is implied by the observation that drug uptake is energy dependent, the nature of the membrane carrier(s) responsible is unknown. Knowledge acquired from studies on bacterial peptide transport has been successfully used to deliver (or smuggle) amino acid mimetics disguised as peptides into the bacterial cell. These amino acid mimetics, although often poorly transported in their own right, are frequently potent inhibitors of bacterial peptidoglycan or lipopolysaccharide synthesis once they have gained access to the interior of the cell.

The cercaria of Trichobilharzia ocellata finds and identifies its duck host with a seriesof different behavioural phases. Dispersal and selection of the water surface as microhabitat is achieved by an intermittent swimming behaviour, which is governed by the interplay of passive dropping with forward and backward swimming movements and includes a positive phototactic and a geonegative orientation. Then the cercariae tend to cling to the water surface in an energy-saving resting position. A movement towards the duck feet as the site of entry occurs when shadows evoke forward swimming movements, which are directed away from the source of light, i.e. normally downwards. Forward swimming movements are also stimulated by touch, but only in free-swimming cercariae and not when these are in the resting position. Attachments occur only when a substrate is touched during forward swimming movements. Attachments are stimulated by warm substrates (1 °C temperature difference triggers a nearly maximal response) and by chemical components of duck-foot skin, and the readiness to attach is increased when the forward swimming movement is started by shadow stimuli.

L-amino acid esters such as leucine methyl ester (Leu-OMe) destroy Leishmania mexicana amazonensis amastigotes by a mechanism which may involve hydrolysis of the compounds by parasite enzymes. Moreover, several esters (e.g. Ile-OMe) prevent the killing of parasites by Leu-OMe, perhaps by inhibition of the hydrolytic enzymes. We show here that certain amino acid amides are also leishmanicidal. Killing of Leishmania within macrophages was assessed microscopically, and that of isolated amastigotes was measured by reduction of the tetrazolium MTT. Amino acid amides were generally less active than the methyl esters and several were more toxic to the macrophages, as determined by inspection of Giemsa-stained preparations. Ranks of activity of the amides on isolated amastigotes were Trp > Leu > Phe > Met > Tyr. The amides of Ala, Gly, Val, Ile, His and D-Leu were inactive. This pattern of activity is similar to that of amino acid methyl esters. Ile-NH2 and a few other amides protected intracellular as well as isolated parasites from killing by Leu-OMe. Conversely, Ile-OMe reduced the toxicity of Leu-NH2 for isolated amastigotes. None of the esters or amides assayed prevented the destruction of Leishmania by Trp-NH2. The results are compatible with the view that amino acid esters and amides may be recognized by the same or similar parasite enzymes.

Female DBA/2 mice were found to be highly resistant to Leishmania mexicana and rarely developed lesions even when inoculated subcutaneously with high numbers (5 × 106) of amastigotes. Male DBA/2 mice, on the other hand, were much more susceptible to this parasite and often developed non-healing lesions even when inoculated subcutaneously with comparatively few (5 × 104) amastigotes. Conversely, although both male and female DBA/2 mice developed ulcerating lesions when inoculated subcutaneously with L. major amastigotes, lesions invariably healed in males but did not heal in females. Male DBA/2 mice recovered from L. major infection subsequently were found to be resistant to subcutaneous challenge with L. mexicana. Conversely female DBA/2 mice that had failed to develop lesions when infected with L. mexicana developed lesions which healed following subcutaneous challenge with L. major. Thus there is bilateral cross-immunity between L. mexicana and L. major in DBA/2 mice which overrides differences in sex-determined susceptibility to both organisms.

Naive CBA mice and mice vaccinated 4 weeks previously with gamma-irradiated cercariae were challenged percutaneoualy with normal cercariae and the skin site of challenge removed at various times to provide samples for histological examination. Neutrophil abscesses surrounding schistosomula as well as cast cercarial tails were identified at the skin surface in both naive/challenged and vaccinated/challenged mice. The dermis in both groups of animals became infiltrated with mononuclear cells and granulocytes. Neutrophils were the predominant granulocyte in naive/challenged skin but eosinophils replaced neutrophils by 48 h post-challenge in skin from vaccinated mice. Schistosomula with adherent mononuclear cells and granulocytes were identified preferentially in the dermis of vaccinated mice; such larvae frequently exhibited subtegumental vacuolation. A further major characteristic of vaccinated/challenged skin was the formation, from 18 h, of extensive subdermal inflammatory foci, consisting of up to 50% mononuclear cells and 50% eosinophils. These foci invariably surrounded one or more larval parasites which were seen by both optical and scanning electron microscopy to have a morphology typical of lung stage rather than skin stage schistosomula. Dead, infiltrated parasites were also recognized within the subdermal foci. Our data support the view that vaccine immunity in this mouse model is mediated primarily in the skin and indicate that challenge attrition involves immobilization and killing of larval parasites by effector cells within subdermal inflammatory foci.

Trichobilharzia ocellata cercariae attach readily to the foot skin of their duck host, but poorly to preen-gland contents. The attachment to duck foot disappears when the skin surface lipids are extracted, and can be restored by reapplication of the lipids to the skin. Hydrophilic skin extracts are without any effect. Thin-layer chromatographic fractionation of duck-foot skin surface lipids reveals cholesterol and ceramides as attachment stimuli. A stimulation of cercarial attachment by these hydrophobic host signals is supported by the host identification pattern of the cercariae, which secures a close contact with encountered substrates.

This essay deals in turn with the six main mechanisms that are believed to be involved in the passage of small molecules across the cell membrane of yeasts and fungi. Such solutes include amino acids, carbohydrates, purines and pyrimidines and other nutrients, among which are the ions K+, , or . The subject has been reviewed extensively (see, for example, Eddy, 1982; Cooper, 1982; Serrano, 1984; Harold, 1986). Transport systems relate to chemotherapy in two ways. First, they may themselves be potential targets for drug action. Second, they may deliver a drug to its intracellular target, the drug being an illicit passenger in a transport system with a different primary role. Most of our knowledge about yeast and fungal transport is currently based on studies with relatively few species selected because they are known to be amenable to genetic and biochemical analysis. The organisms include representative strains of Neurospora crassa or of Saccharomyces cerevisiae and selected species of Rhodotorula and Schizosaccharomyces. Fungal organisms pathogenic to man, such as Candida albicans, those causing either systemic fungal infections (see Kerridge, 1986; Shepherd, Poulter & Sullivan, 1985), or the numerous fungal diseases of plants have been little used as models of nutrient transport, despite their clinical or economic importance. Whether all these ecologically diverse organisms, which in evolutionary terms are only distantly related, employ only the transport mechanisms so far discovered in Saccharomyces cerevisiae is an open question.

Merocyanin 540 (Mc540) is a fluorescent compound which is thought to bind to membranes in which there are substantial amounts of lipid in the lipid-crystalline phase. It is shown here to be of value in detecting the transformation by both mechanical and skin-penetration methods of the cercaria to the schistosomulum. The cercaria does not appear to bind Mc540, but the schistosomulum, binds Mc540 initially, in its anterior region, and at later times over the entire surface. The suggestion that transformation involves changes in the surface membrane lipid phase from gel to liquid-crystalline phase is supported by fluorescence recovery after photobleaching results with 5-N-(octadecanoyl)-amino fluorescein, a lipophilic dye which appears to be immobile in the cercaria, but fully mobile in the 40 min schistosomulum.

Examples of the apparently stochastic nature of freshwater fish helminth communities illustrating the erratic and unpredictable occurrence and distribution of many species are provided for six species of fish from several localities throughout Britain. By focussing on parasite colonization strategies two categories of helminths are recognized: autogenic species which mature in fish and allogenic species which mature in vertebrates other than fish and have a greater colonization potential and ability. Three groups of fish are distinguished: salmonids, in which helminth communities are generally dominated by autogenic species which are also responsible for most of the similarity within and between localities; cyprinids, in which they are dominated by allogenic species which are also responsible for most of the similarity within and between localities; and anguillids, whose helminth communities exhibit intermediate features with neither category consistently dominating nor providing a clear pattern of similarity. Recognition and appreciation of the different colonization strategies of autogenic and allogenic helminths in respect of host vagility and ability to cross land or sea barriers and break down habitat isolation, and their period of residence in a locality, whether transient or permanent, provides an understanding of, and explanation for, the observed patchy spatial distribution of many helminths. Comparison with other parts of the world indicates that colonization is a major determinant of helminth community structure.

The asexual stages of Plasmodium living within the erythrocyte result in growth-related changes in the permeability properties of the red cell for substances such as glucose, amino acids, purine nucleosides, sodium, potassium, calcium, zinc, iron and several antimalarial drugs such as chloroquine, amodiaquine and mefloquine. In most cases such changes do not appear to be due to a modification in the affinity or specificity of red cell transporters; indeed, for most substances the membrane-associated transporters are either unaffected or are partially inactivated. In malaria-infected erythrocytes, where a striking increase in influx has been observed, it has been attributed to the insertion of parasite-encoded transporters into the red cell membrane or the formation of aqueous leaks and/or pores. Leak formation, in the vast majority of cases, does not appear to be dependent on the insertion of plasmodial proteins into the red cell membrane. However, since the data presently available are less than satisfactory for discriminating amongst the various possible transport mechanisms future studies will require painstaking efforts and carefully controlled conditions to discriminate amongst the various transport systems which are operational in the malaria-infected red cell and the parasite.

Experimental work has established that a sexual process can occur in African trypanosomes (Jenni, Marti, Schweizer, Betschart, Le Page, Wells, Tait, Paindavoine, Pays & Steinert, 1986; Paindavoine, Zampetti-Bosseler, Pays, Schweizer, Guyaux, Jenni & Steinert, 1986; Tait, personal communication). However, the role of the process in natural populations of trypanosomes is poorly understood. This paper considers what information can be gained from analyses of isoenzyme polymorphism. A cladistic approach is used to help determine whether trypanosome diversity could have been produced by mutation alone. When applied to three East African populations of Trypanosoma brucei it provides evidence that some diversity has arisen through a sexual process; this explains the variation observed within a locality and can account for the evolution of differences between localities. However, the extent to which genetic exchange currently operates is less clear. Analysis of genotype frequencies indicates that agreements with Hardy-Weinberg expectations can be obtained even if genetic exchange exerted no influence over genotype frequencies. Moreover, analysis of joint locus frequencies reveals disequilibrium between loci and that trypanosome populations may be lacking several genotype combinations. Thus, genetic exchange may not occur sufficiently frequently, or in such a way as to break up associations between loci. The relevance of these observations to the evolution of strain differences within T. brucei is discussed.

An antigen in homogenates of adult Schistosoma mansoni worms grown in mice, and immunoprecipitated by polyspecific rabbit antiserum, has been identified as contrapsin, a mouse serine protease inhibitor (serpin). In the serum of some mice infected with S. mansoni contrapsin was found with altered immunoelectrophoretic characteristics when compared with contrapsin from uninfected mice.

Praziquantel (500 mg/kg) administered orally to BALB/c mice with secondary equine E. granulosus daily for 21, 30 or 30 + 30 days without the drug resulted in the majority of cysts, using bench criteria of turgidity and eosin exclusion, being assessed as ‘alive’. Ultrastructural examination of 54 of these ‘alive’ cysts did not support this conclusion. They all showed increased vesiculation of the germinal layer leading, in many, to the loss of its integrity. Increased mitochondrial numbers occurred frequently. The longer drug treatments appeared to have greater effects on the germinal layer of ‘alive’ cysts and there was no detectable re-establishment of structural organization within 30 days after drug withdrawal. Subjectively, there was no substantial difference between cysts from 4-month and 9-month infections or between affected peritoneal and hepatic cysts. Tissue from collapsed cysts was necrotic. Peak serum levels of praziquantel (6430–6136 μg/l) occurred 5–10 min after drug administration (500 mg/kg) and dropped rapidly to less than 10 μg/l at 3 h. In an in vitro study at praziquantel concentrations of 1000 and 5000 μg/l over a 10-day period, most cysts were judged ‘alive’ by bench criteria but showed ultrastructurally a time- and concentration-dependent loss of integrity identical to that seen in vivo. Turgidity and eosin exclusion therefore underestimate the effect of praziquantel and the results indicate that in vitro experiments can fulfil a legitimate preliminary role in a hydatid chemotherapy programme.

Trichinous mice were killed and their carcasses maintained at room temperature or subzero temperatures for varying lengths of time. Some worm parameters were measured after direct isolation from carcasses while others were measured following passage through a second round of hosts. Glycogen and trehalose levels in infective 1st-stage larvae (L1) isolated directly from carcasses maintained at room temperature were significantly less than controls (day 0) after day 4 post-kill (p.k.). By day 21 p.k. among L1 isolated directly from mouse carcasses those observed coiled or moving had decreased by around 20% compared to day 0 p.k. The percentage of L1 isolated from carcasses on several days p.k., used to infect mice and recovered as pre-adult worms declined significantly after they had remained in carcasses for 14 days. Only 2·6% of muscle larvae isolated from carcasses on day 21 p.k. and used to infect mice were recoverable as pre-adults. Pre-adult worms raised in mice infected with larvae from day 7 carcasses had about 50% less glycogen than worms raised in mice infected with larvae isolated from fresh carcasses (day 0 p.k.). The fecundity in vitro of adult worms isolated from mice on day 7 following infection with infective L1 larvae maintained in carcasses held at room temperature for 0–16 days declined only when adult worms developed from larvae recovered from carcasses at 3 days following host death. Following 24 h at temperatures below freezing, infectivity of L1 larvae isolated from frozen carcasses was reduced by 97%. Carbohydrate levels remained high in larvae from carcasses frozen for up to 4 days.

During their life-cycle many parasites experience a wide range of environments including free living and those provided by a variety of intermediate and final hosts. The nutritional requirements of parasites are met by physiological processes adapted to exploit the physico-chemical characteristics provided by different hosts. In helminth parasites these adaptations are frequently expressed on the tegumentary surface. As an example of adaptations within the Trematoda, the control of monosaccharide transport in Proterometra sp. is described. Environmental sodium, although not directly involved in the uptake process, nevertheless regulates the expression of transport capabilities. In the Cestoda, the uptake of monosaccharides and amino acids is described for Hymenolepis diminuta. The metacestode of this tapeworm inhabits the blood system of an arthropod, and the adult the gut of a mammal. There are quantitative and qualitative differences in the amino acids and monosaccharides in these two environments and these are reflected in the transport mechanisms exhibited by the two forms of the life-cycle. In Echinococcus granulosus the transfer of amino acids, sugars and macromolecules across the membranes of hydatid cysts and protoscoleces is described. The major difference between these two stages in the life-cycle relates to the ability of hydatid cysts to absorb macromolecules, whereas protoscoleces are impermeable to these compounds. The potential for future work is emphasized.

Two groups of H-2 congenic strains of mice were compared for their susceptibility to a primary infection with the nematode Trichuris muris. Mice of the BALB genetic background were markedly more resistant than mice of the BIO genetic background, as reflected by the rate of expulsion of T. muris from the large intestine. Within each of the two groups of H-2 congenic strains mice possessing the H-2k haplotype (BALB/k, B10.BR) were more susceptible to infection than mice expressing other haplotypes; B10 background strains expressing H-2b (B10) or H-2q (B10.G) alleles were the most resistant of the four congenic strains studied. Differential resistance was observed within three of the four BIO congenic strains and this is discussed in terms of rate of development of the protective immune response in relation to worm development. The results support the conclusion that both H-2-linked and non-H-2 genes play important roles in controlling the immune response which expels worms from the gut.

Several major groups of parasitic helminths (Monogenea, Digenea and Nematoda) possess two surfaces that are potentially absorptive in nature. These are an external surface, a tegument in the platyhelminths and cuticle in the nematodes, and the intestine. This paper discusses the relative contributions of these absorptive surfaces in the nutrition of these parasitic helminths. There are many factors that determine the availability of, and a parasite's ability to absorb nutrients via either of these surfaces, and this review discusses individually some of the more important morphological, physiological and environmental factors affecting the potential nutritional roles of these surfaces. It is clear from such a summary of previous studies that the intestines and teguments (cuticles) of helminth parasites can each serve an important nutritional role. However, insufficient data make it impossible at this time to determine the relative nutritional roles of these surfaces in any single parasitic helminth.

In a combined field and laboratory study, the eggs and 3rd-stage infective larvae of the human hookworm Necator americanus were recovered from the creek waters of the Niger Delta, Nigeria. They were tested for viability and infectivity. Eggs recovered from fresh water creeks showed a viability or hatching index of between 17·5 and 23·7%. Eggs recovered from brackish water showed a viability index of 18·8–21·4% in ‘normal’ cultures, and a maximum index of 6·3% when cultured in brackish water. The differences in the viability indices of these eggs were not significant (P > 0·05). Infective 3rd-stage larvae were recovered from both fresh creek water (205–258 L3/litre of water), and brackish water (45 L3/litre of water). Larvae hatched from brackish water eggs that were cultured in the brackish water were 20% infective by 3 days, but lost all infective potential by 7 days posthatching. Larvae from fresh water eggs, cultured in fresh water and ‘normal’ laboratory cultures reached 50% infectivity in 3–5 days, losing potential infectivity in 11–15 days posthatching. The infectivity patterns of larvae recovered directly from fresh and brackish waters did not differ significantly (P > 0·05) from the infectivity patterns of larvae recovered from laboratory cultures of eggs from all the experimental sources. Although larvae recovered directly from fresh and brackish waters survived in these respective media under laboratory conditions, there was a significant difference (P < 0·05) in their survival patterns. The survival and infectivity rates of field larvae were considerably reduced over time relative to control larvae. These results indicate that both contaminated fresh and brackish water creeks and their banks may form additional hookworm infection foci in areas where various water contact activities are carried out by the human host population.

The plerocercoid of Callitetrarhynchus gracilis was found in the body cavity of 14 species of fishes from Bermuda. The scolex, having completed its development, continues to grow within the blastocyst. The two mobile bothridia possess lateral grooves containing backwardly directed spines. Rapid evagination of the proboscides is effected by two layers of contra-rotating spiral muscles in the walls of the proboscis bulbs. The proboscis retractor is protected from constriction, during contraction of the bulbs, by a rigid ring at the junction of bulb and sheath. Nine series of extrinsic muscles anchor the proboscis sheaths to the body wall and a ladder-like series of dorsal, ventral and lateral muscles anchors the bulbs to one another. The bulbar nerves arise from the lateral nerve cords and are joined by a series of central ring commissures along the length of the bulbs. Uniciliate sensilla occur on the scolex and glandular cells in the peduncle.