The immune response to leishmaniasis is complex, and the result of infection depends on both the genetic composition of the Leishmania species and the immunity of the host. Clinical and experimental evidence suggest that the activation of B cells leads to exacerbation of visceral leishmaniasis. However, the role of B-1 cells (a subtype of B lymphocytes) in the pathogenesis of experimental visceral leishmaniasis has not yet been elucidated. In this study, we investigated the importance of B-1 cells in experimental infection with Leishmania. (L.) chagasi. Our results showed that BALB/XID mice (X-linked immunodeficient mice which are genetically deficient in B-1 cells) infected with L. (L.) chagasi for 45 days had a significant reduction in parasite load in the spleen when compared with control mice. Cytokine analysis showed that the BALB/XID mice had lower amounts of IL-10 in their sera compared with control group. In addition, the transfer of B-1 cells from wild type mice into IL-10KO animals led to an increase in susceptibility to L. (L.) chagasi infection in the IL-10KO mice, suggesting that the IL-10 produced by these cells is important in experimental infection. Our results suggest that B-1 cells may play an important role in susceptibility to L. (L.) chagasi.

As the currently only available molluscicide, niclosamide has been widely used for snail control for over 2 decades in China. There is therefore a concern about the emergence of niclosamide-resistant snail populations following repeated, extensive use of the chemical. The purpose of this study was to investigate the likelihood of niclosamide resistance in Oncomelania hupensis in China. Active adult O. hupensis snails derived from 20 counties of 10 schistosomiasis-endemic provinces of China, of 10 snails in each drug concentration, were immersed in solutions of 1, 0·5, 0·25, 0·125, 0·063, 0·032, 0·016 and 0·008 mg L−1 of a 50% wettable powder of niclosamide ethanolamine salt (WPN) for 24 and 48 h at 25 °C, and the median lethal concentration (LC50) was estimated. Then, the 24- and 48-h WPN LC50 values were compared with those determined in the same sampling sites in 2002. The results indicated that the 24- and 48-h WPN LC50 values for O. hupensis were not significantly different from those determined in 2002 (P = 0·202 and 0·796, respectively). It is concluded that the current sensitivity of O. hupensis to niclosamide has not changed after more than 2 decades of repeated, extensive application in the main endemic foci of China, and there is no evidence of resistance to niclosamide detected in O. hupensis.

Single percutaneous immunizations of Fischer rats with 1000 ultra-violet attenuated Schistosoma japonicum cercariae induced 52–88% resistance to challenge 4 weeks later. Increasing this to 3 immunizations induced 90% resistance to challenge, and this level of protection remained undiminished for up to 40 weeks after vaccination. Rats vaccinated with gamma-irradiated S. mansoni cercariae were resistant to challenge with S. mansoni but not S. japonicum. Similarly rats vaccinated with u.v.-attenuated S. japonicum cercariae were not resistant to heterologous challenge. Thus irradiated vaccines are species-specific in both permissive and non-permissive hosts.

The frequency distribution of parasites in hosts commonly follows a negative binomial or similar distribution. Under certain conditions the magnitude of parasite-associated host mortality can be estimated by comparing the tail of the observed distribution to that of the distribution predicted from the first few points of the data. For the technique to work the following assumptions need to be met: mortality in lightly infected fish must be rare; infection and consequent mortality occur only in fish younger than those sampled; and the frequency distribution of the parasite at the time of infection should conform to a known probability distribution. The method was applied to frequency distributions of blastocysts of Callitetra rhynchus gracilis in 898 Saurida tumbil (Bloch) and 5013 S. undosquamis (Richardson). Parasite-associated mortality in S. tumbil was calculated to be at least 11 % in males and 2% in females. For S. undosquamis, estimated mortality was about 5% in males and 3% in females. The numbers of parasites estimated to produce a 0·5 probability of death, the parasitological equivalent of an LD50 were 3·4 and 5·7 for S. tumbil males and females, and 18 and 3 for S. undosquamis males and females respectively.

The generative mechanism(s) of aggregation and predisposition to Ascaris lumbricoides and A. suum infections in their host population are currently unknown and difficult to elucidate in humans and pigs for ethical/logistical reasons. A recently developed, optimized murine model based on 2 inbred strains, putatively susceptible (C57BL/6j) and resistant (CBA/Ca) to infection, was exploited to elucidate further the basis of the contrasting parasite burdens, most evident at the pulmonary stage. We explored the kinetics of early infection, focusing on the composite lobes of the liver and lung, over the first 8 days in an effort to achieve a more detailed understanding of the larval dispersal over time and the point at which worm burdens diverge. Larval recoveries showed a heterogenous distribution among the lobes of the lungs, being higher in the right lung of both strains, and in the susceptible strain larvae accumulating preferentially in 2 (caudal and middle) of the 4 lobes. Total larval burdens in these 2 lobes were largely responsible for the higher worm burdens in the susceptible strain. While total lung larval recoveries significantly differed between mouse strains, a difference in liver larval burdens was not observed. However, an earlier intense inflammatory response coupled with more rapid tissue repair in the hepatic lobes was observed in CBA/Ca mice, in contrast to C57BL/6j mice, and it is possible that these processes are responsible for restricting onward pulmonary larval migration in the resistant genotype.

Previous studies have shown that host immunity regulates the fecundity of nematodes. The present study was aimed at clarifying the reversible nature of fecundity in response to changes of immunological status and to determine which effector cells are responsible for compromising fecundity in Heligmosomoides polygyrus. Enhanced fecundity was observed in immunocompromised SCID and nu/nu mice compared to those in the corresponding wild-type mice, with significantly fewer numbers of intrauterine eggs produced in the wild-type than in the immunodeficient mice. When 14-day-old adult worms from BALB/c mice were transplanted into naïve BALB/c mice, their fecundity increased significantly as early as 24 h post-transplantation, but not when they were transferred into immune mice, suggesting the plastic and reversible nature of fecundity in response to changes in host immunological status. In mast cell-deficient W/Wv mice, nematode fecundity was significantly higher than in mast cell-reconstituted W/Wv or +/+ mice. The serum levels of the mast-cell protease mMCP1 were markedly increased in the wild-type as well as the mast cell-reconstituted W/Wv, but not in the W/Wv, SCID, or nu/nu mice during infection. These findings raise the interesting possibility that certain activities of mast cells, either directly or indirectly, regulate parasite fecundity during infection.

An in vitro investigation has been made of the relative roles of the gut and tegument in the absorption of the neutral amino acids L-alanine and L-leucine by a marine fish-gill parasite, Diclidophora merlangi. The use of ligatures to preclude oral ingestion of trace-labelled medium has proved inadequate, invariably damaging the tegument, as revealed by stereoscan electron microscopy, and resulting in artifactual levels of absorption. Three alternative procedures have given consistently reliable data on the route of entry of low molecular weight substrates. (1) Ultrastructural examination of worms previously incubated in electron-dense cationic tracers has shown that, in vitro, there is no oral intake of sea water. (2) The suspending of worms in trace-labelled medium with the mouth out of the medium and comparing amino acid uptake with that of worms totally immersed in medium has revealed no statistically significant difference in the absorption levels. (3) Application of section (freeze-dried) auto-radiography to detect diffusible isotope has demonstrated directly transtegumental absorption of a neutral amino acid. It is concluded from these experiments that Diclidophora has a tegumental transport system for absorbing certain neutral amino acids, and whilst, clearly, the worm is sanguinivorous and digests blood in a well-developed gut, it may also be capable of supplementing this diet with low molecular weight organic nutrient absorbed directly from sea water via the tegument.

Mice infected heavily with Schistosoma mansoni cercariae were treated 6 days later with Praziquantel and the parasites studied 1 h post-treatment. Immunofluorescence experiments showed that parasite surface antigens became available for labelling in larvae harvested from Praziquantel-treated mice, but not from untreated mice. Red blood cell antigens acquired from the host were localized on all lung worms studied. The distribution of each set of antigens, as revealed by fluorescence-labelling was, however, quite different. The lungs of heavily infected, drug-treated mice, exhibited severe haemorrhages which occurred in a dose-dependent manner. Fewer haemorrhages were found when heavily infected mice were treated simultaneously with Praziquantel and Aprotinin, a proteinase inhibitor. These results indicate that Praziquantel treatment in vivo induces the exposure of parasite antigens on lung-stage worms and may cause the release of parasite-derived enzymes which induce haemorrhages in the lung tissue of the host.

Observations have been made on the distribution of faecal deposits on a number of small fields of varying size stocked with varying numbers of sheep. These studies were undertaken to examine certain hypotheses proposed in the construction of mathematical models for the distribution of strongyloid nematode infective larvae in pastures grazed by sheep.

The negative binomial distribution was found to provide a reasonable empirical description of the distribution of faeces, although there was evidence of departure from the negative binomial on the largest field.

Although, tentatively, the distributions were additive with respect to the number of sheep, there was evidence of departure from additivity in respect of field area and time. The implications of these findings for the model are discussed.

Significant positive correlations were found between successive time intervals in the number of faecal deposits present in individual subplots of the majority of fields. It is suggested that these arise from the tendency of sheep to use the same portion of a field for resting and rumination when heavy concentrations of faeces are deposited. The effects of this and other possible patterns of grazing and faecal deposition are discussed in relation to the intake of strongyloid infective larvae.

The average number of discrete deposits of faeces on pasture produced per sheep per day was greater in flocks producing faeces in pellet form than in flocks producing soft faecal masses. However, within faeces types, there was evidence that the expected number of deposits produced per sheep per day could reasonably be assumed constant.

The greater part of this work was carried out while one of us (A.D.D.) was the holder of a C.S.I.R.O. Overseas Research Studentship. For his advice and constructive criticism I am much indebted to Dr H. D. Crofton, under whose supervision this study was undertaken. My thanks go also to Professor J. E. Harris, C.B.E., F.R.S., for the provision of facilities in the Department of Zoology, and to Professor T. K. Ewer and Mr M. R. McCrea for their willing co-operation in the provision and handling of pastures and sheep at the School of Veterinary Science, Langford.

Mr David Culpin and Mrs Jean Williams, of the Division of Mathematical Statistics, were responsible for programming and organizing the calculations on the CDC 3200 Computer, and were consistently helpful in proposing and criticizing tests and procedures.

Although purely vertically transmitted parasites are predicted to cause low pathogenicity in their hosts, the effects of such parasites on host fitness under stressful environmental conditions have not previously been assessed. Here, we investigate the effects of Nosema granulosis, a vertically transmitted, microsporidian parasite of the brackish water amphipod Gammarus duebeni, on host growth and survival under conditions of host–host competition and limited food. The parasite had no effect on host survival, but caused a reduction in juvenile growth. Stressful environmental conditions also led to a reduction in G. duebeni growth. However, we found no evidence to support the prediction that parasitized hosts would suffer a greater reduction in fitness than uninfected hosts under adverse environmental conditions. We interpret our results in the context of selection for successful vertical parasite transmission.

125I-Schistosoma mansoni schistosomulum surface antigens were immunoprecipitated with human antibodies from individual Egyptian patients diagnosed as being either acutely or chronically infected with S. mansoni. Both sets of patients were found to have IgG antibodies in their sera capable of immunoprecipitating the major Mr > 200, 38 and 32K antigens. However, the immunoprecipitation of the Mr 200K antigen was found to constitute a significantly greater proportion of the total precipitate achieved with acute sera than with chronic sera. The Mr 38 and 32K antigens were more variably precipitated by the acute sera than the chronic sera but the proportion of the total precipitation that these two antigens constituted was not found to be significantly different between the two sets of sera. Immunoprecipitation with pooled antibodies absorbed with egg and adult worm homogenates which had been treated to remove either carbohydrate or polypeptide epitopes demonstrated that the Mr > 200K antigen was the principal target of egg-cross-reactive anti-carbohydrate antibody amongst the antigens detected. The Mr 38 and 32K antigens were found to be precipitated by antibodies to protease-sensitive and periodate-insensitive polypeptide epitopes. These results are consistent with egg-cross-reactive anti-carbohydrate IgG antibody making a greater contribution to schistosomulum surface recognition in acute infection than in chronic infection. Indeed the presence of a higher level of egg-cross-reactive and anti-carbohydrate antibody directed against schistosomulum surface epitopes in an acute serum pool than in a chronic serum pool was confirmed by measurement of antibody binding to whole schistosomula.

The results of ultrastructural studies and histochemical tests on the capsule of Trichinella spiralis are given. The capsule wall is shown to consist of two layers, an outer region of tightly compacted fibrils and an inner region of fibrils dispersed through matrix cytoplasm. Histochemical tests show the capsule wall to consist mainly of collagen and cystine. The appearance of the matrix, which is packed with mitochondria, rough endoplasmic reticulum, smooth reticulum and Golgi complexes, together with the histochemical reaction to the five enzymes tested, strongly suggests that the matrix is a region of high metabolic activity. Although there are several very large nuclei in the matrix there is no evidence of cell walls; consequently the matrix is a syncytium.

I wish to thank the A.R.C. for financial support while this work was carried out. I should also like to thank Dr D. L. Lee for his advice on many occasions and the late Professor Boyd of the Anatomy Department, University of Cambridge, for the use of the electron microscope in that Department.

Theileria annulata infects and reversibly transforms bovine leucocytes. The parasite-transformed cells are immortalized, metastatic and express a number of metalloproteinases including matrix metalloproteinase 9 which they secrete. All the metalloproteinases observed on substrate gels are inhibited by tissue inhibitor of metalloproteinase 1 and 4 synthetic inhibitors BB94, GM6001, BRL29808AI and Ro31–4724. We have adapted an in vitro assay for metastatic behaviour that measures the ability of parasitized cells to cross reconstituted basement membrane, Matrigel™. Using this we demonstrated that macroschizont-infected cells are invasive in vitro and that their invasive properties can be almost eliminated by the same specific inhibitors of metalloproteinases as used in the substrate gels. This demonstrates that the metastatic behaviour of the infected cells is due in part to metalloproteinase activity and strongly suggests a role for the metalloproteinases we observed on gels. This is further supported by the fact that an attenuated vaccine line which shows much reduced metalloproteinase activity also exhibits a marked reduction in metastatic behaviour. We suggest that these metalloproteinases are virulence factors mediating some pathological features of the disease and their loss in the vaccine line could provide an explanation for attenuation.

The aim of this study was to assess the effect of two doses of 40 mg/kg praziquantel with 2 weeks interval versus a standard single dose of 40 mg/kg on cure rates, egg reduction, intensity of infection, and micro-haematuria in Schistosoma haematobium infections. A randomised controlled intervention study was carried out among school-aged children in two different endemic settings with follow-up at 3, 6 and 18 months following drug administration. Differences in cure rates between the two treatment regimens were not significant. However, in high transmission areas, the double treatment regimen was more effective in egg reduction than single treatment regimen and the difference in egg reduction between the two treatments was significant at 3 months (P<0·005), 6 months (P<0·0001) and 18 months (P<0·003) after treatment. There was a significant difference in the effect of the two treatments on prevalence of micro-haematuria at 18-month follow-up in both Koulikoro (P<0·001) and Selingue (P<0·003). The study shows that although no significant difference could be observed in the overall cure-rates between the two treatment regimens, the effect of double treatment was a significant reduction in infection intensity as well as micro-haematuria which may have a great impact in reducing subtle morbidity.

The biological parameters which generate seasonal fluctuations in the size of populations of Caryophyllaeus laticeps are examined in detail. A mathematical model is formulated to describe the dynamics of the adult parasite within the fish host Abramis brama, and the predictions of the model are compared with observed population data.

The seasonality of parasite population size is shown to be caused by the combined effects of a temperature dependent mortality rate and fluctuations in host feeding activity, which controls the immigration rate of larval parasites. The observed overdispersed distribution of adult parasite numbers within the host population is shown to be generated by variability in feeding habits between individual members of the fish population.

The theoretical population model is used as a framework for the investigation of, among other factors, the comparative influences of the immigration and death rates on the dynamics of the adult parasite, the future behaviour of the system under altered environmental conditions and the importance of chance effects in the dynamics of individual parasite populations within a single host.

The stability of the dynamics of the complete life-cycle of C. laticeps is discussed in relation to the inherent biological complexity of host/helminth parasite interactions.

Six different histochemical techniques were employed to study the sites of deposition of glycogen, other carbohydrates, and carbohydrate complexes in uninfected Crassostrea virginica and those parasitized by the larvae of the trematode Bucephalus sp. The carbohydrate and carbohydrate complexes occurring in the parasites were also studied.

In uninfected oysters, glycogen is stored in the digestive diverticula, in Leydig cells located between the diverticula in the digestive gland, in the matrices of the palps, mantle, and gills, in walls of blood vessels, and in ova. There is a marked reduction of stored glycogen at these sites in infected oysters. In addition, the glycogen-storing diverticular cells and the interdiverticular Leydig cells are ruptured and/or lysed and the enclosed glycogen is expelled to the exterior.

Glycogen is found in the sporocysts; however, very little if any is present in cells comprising young germ balls. It is only after the elongate germ balls commence differentiating into cercariae that glycogen appears in their bodies.

In uninfected oysters, glucose deposits are present in the same Leydig cells in which stored glycogen is found. Glucose is believed to be the hexose from which the stored glycogen is synthesized. In infected oysters, the reduction of glucose in Leydig cells is almost complete.

There are histochemically demonstrable amounts of glucose in the blood vessels and sinuses of infected oysters while such is not the case in uninfected ones. This phenomenon is explained by the destruction of the sites of glycogen synthesis and storage in infected oysters, thus bringing about hyperglycaemia resulting from the accumulation of glucose taken in from the exterior.

The presence of glucose deposits adhering to the gill surfaces of infected oysters may represent the direct absorption of glucose from the environment and contribute to the hyperglycaemic conditions.

The absorption of glucose by sporocysts is suggested by the finding of this hexose adhering to the exterior and in the wall of certain sporocysts.

Gamma metachromatic globules are present in the digestive diverticula of uninfected oysters. Their number is increased in infected oysters. In addition, the connective tissue layers abutting the base of the epithelial lining of the stomach and intestine and the fibres at the base of the surface epithelium of the gills of uninfected and infected oysters are metachromatic. Metachromasia at these sites is believed to be due to acid mucopolysaccharides.

Acid mucopolysaccharides are present in certain cells intermingled among the ciliated epithelial lining of the gastric and intestinal walls and in secretory cells along the surface of the mantle, gills and palps. The histochemical reactions at these sites remain unaltered in infected oysters.

Only older sporocysts include acid mucopolysaccharides in the walls.

In older germ balls, acid mucopolysaccharides are present in the small somatic cells situated on the surface, beneath the enveloping membrane. These are believed to be cuticle-secreting cells.

In developing cercariae, acid mucopolysaccharides are found in the cuticle and certain parenchymal cells.

There is an increase in the number of ‘brown cells’ in infected oysters. The smallest and largest do not include acid mucopolysaccharides but those that measure between 0·006 and 0·012 mm are partially or totally positive for acid mucopolysaccharide. Slight metachromasia and sphingomyelins also are associated with certain ‘brown cells’ found in the digestive glands of infected oysters.

Large ‘brown cells’ in the intertubular spaces in the digestive glands of both uninfected and infected oysters have been observed to undergo division.

Interleukin (IL)-13-associated signal pathway plays an important role in schistosomiasis hepatic fibrosis. In this study we tried to investigate the effects of corilagin to ameliorate schistosomiasis hepatic fibrosis through regulating IL-13-associated signal pathway in vitro and in vivo. Cellular model was set up with hepatic stellate cells-T6 cells stimulated by rIL-13 and male Balb/c mice were infected with Schistosoma japonicum cercariaeas as animal model. Liver histological changes were observed with haematoxylin and eosin staining. Masson staining was employed to observe the change of egg granulomas. Expression of Col (collagen) and Col III were examined with Immunohistochemistry. Western bolt was employed to detect the JAK-1 and IL13Rα1 proteins. The mRNA expression of Col I, Col III, IL-13, JAK-1 and IL13Rα1 were tested by quantitative polymerase chain reaction. As a result, less inflammatory changes were found in all corilagin groups compared with model group and praziquantel group. The mRNA levels of Col I, Col III, IL-13, JAK-1 and IL13Rα1 were significantly decreased after corilagin intervention (P < 0·01). JAK-1 and IL-13Rα1 protein levels were also greatly decreased in the corilagin groups (P < 0·01). In conclusion, corilagin could ameliorate schistosomiasis hepatic fibrosis by down-regulating the expression of IL-13 and signal molecules in IL-13 pathway.

Trajectories of life-history traits such as growth and reproduction generally level off with age and increasing size. However, colonial animals may exhibit indefinite, exponential growth via modular iteration thus providing a long-lived host source for parasite exploitation. In addition, modular iteration entails a lack of germ line sequestration. Castration of such hosts by parasites may therefore be impermanent or precluded, unlike the general case for unitary animal hosts. Despite these intriguing correlates of coloniality, patterns of colonial host exploitation have not been well studied. We examined these patterns by characterizing the responses of a myxozoan endoparasite, Tetracapsuloides bryosalmonae, and its colonial bryozoan host, Fredericella sultana, to 3 different resource levels. We show that (1) the development of infectious stages nearly always castrates colonies regardless of host condition, (2) castration reduces partial mortality and (3) development of transmission stages is resource-mediated. Unlike familiar castrator-host systems, this system appears to be characterized by periodic rather than permanent castration. Periodic castration may be permitted by 2 key life history traits: developmental cycling of the parasite between quiescent (covert infections) and virulent infectious stages (overt infections) and the absence of germ line sequestration which allows host reproduction in between bouts of castration.

Binding of promastigotes to the sand fly midgut epithelium is regarded as an essential part of the Leishmania life cycle in the vector. Among Leishmania surface molecules putatively involved in attachment to the sand fly midgut, two GPI-anchored molecules are the most prominent: lipophosphoglycan (LPG) and promastigote surface protease gp63. In this work, we examined midgut attachment of Leishmania lines mutated in GPI-anchored molecules and compared results from 2 different techniques: in vivo development in sand flies and in vitro competitive binding assays using fluorescently labelled parasites. In combination with previous studies, our data provide additional support for (1) an LPG-independent parasite-binding mechanism of Leishmania major within the midgut of the permissive vector Phlebotomus perniciosus, and provide strong support for (2) the crucial role of L. major LPG in specific vector Phlebotomus papatasi, and (3) a role for Leishmania amazonensis gp63 in Lutzomyia longipalpis midgut binding. Moreover, our results suggest a critical role for GPI-anchored proteins and gp63 in Leishmania mexicana attachment to L. longipalpis midguts, as the wild type (WT) line accounted for over 99% of bound parasites.

Virulence is part of the proximate base to the understanding of host–parasite interactions, and therefore it is crucial to interpret parasite-induced damage as an outcome of co-evolution between parasite and host. We experimentally investigated the impact of 2 congeneric ticks with contrasting transmission modes and host specificity, on the health of songbird nestlings (Parus major). The nidicolous Ixodes arboricola lives in tree holes where it obtains blood from adult birds and their nestlings, hence is prone to vertical transmission. All developmental stages of the field-dwelling Ixodes ricinus feed on different host taxa, hence are prone to horizontal transmission. Within each nest we infested 3 nestlings with varying loads of I. ricinus and 3 with Ixodes arboricola. Ixodes arboricola had no negative effects on nestling health (haematocrit, inflammation, body size, body condition). Body size was positively associated with the number of feeding I. arboricola adults. In contrast, I. ricinus infestations by nymphs and adult ticks led to haematocrit reductions. Furthermore, I. arboricola was a more prudent feeder, with longer feeding durations for smaller bloodmeals. Although the negative effects on nestling health were limited, our results are in line with current theories, stating that virulence increases with horizontal transmission, reduced dependence on individual hosts and reduced relatedness among co-exploiting ticks.