The prevalence of Schistosoma mansoni infections of Biomphalaria pfeifferi shows seasonal variation. Field data from Zimbabwe show annual ranges from 0 to 7%. In this paper a mathematical model of B. pfeifferi population dynamics and S. mansoni epidemiology is used as a framework for analysis of these patterns. Snail fecundity is a function of snail age and of temperature, and is apparently affected by other seasonal factors. The pre-patent period is dependent on temperature. Infection affects snail fecundity and mortality. Parameter values are derived from previous field and laboratory studies. The force-of-infection is estimated from the analysis of size-prevalence data. Using observed temperatures, model output agrees well with field data on snail abundance and prevalence of infection over a 14-month period. Seasonal variation in prevalence largely reflects variation in the pre-patent period and in snail population age structure. The possible role of seasonality in the force-of-infection is discussed. Prevalence patterns are not greatly affected by year-to-year differences in temperature. Significant seasonal variation in snail–man transmission rates is expected.

Neuroinvasive larvae of the common dog and cat roundworms, Toxocara canis and Toxocara cati, may cause severe neurological and neuropsychological disturbances in humans. Despite their pathogenic potential and high prevalence worldwide, little is known about their cell-specific influences and cerebral host–pathogen interactions in neurotoxocarosis. To address this discrepancy, a co-culture system of viable larvae with murine neuronal (CAD), oligodendrocytal (BO-1) and microglial (BV-2) cell lines has been established. Additionally, murine adult brain slices have been co-cultured with Toxocara larvae to consider complex organotypic cell–cell interplay. Cytotoxicity of larval presence was measured enzymatically and microscopically. Microscopic evaluation using trypan blue exclusion assay revealed to be less reliable and sensitive than the lactate dehydrogenase activity assay. Ultimately, even low numbers of both T. canis and T. cati larvae have impaired survival of differentiated CAD cells, which morphologically resemble primary neurons. In contrast, viability of oligodendrocytal and microglial cells as well as brain slices was not impaired by larval presence. Therefore, immune-mediated mechanisms or trauma by migrating larvae presumably induce the in vivo pathology rather than acute cytotoxic effects. Conclusively, the helminthic larvae co-culture system presented here is a valuable in vitro tool to study cell-specific effects of parasitic larvae and their products.

Syngamid strongylids of the genus Mammomonogamus undoubtedly belong among the least known nematodes with apparent zoonotic potential and the real diversity of the genus remains hard to evaluate without extensive molecular data. Eggs of Mammomonogamus sp. are frequently found in feces of African forest elephants (Loxodonta cyclotis) and western lowland gorillas (Gorilla gorilla gorilla) in Dzanga-Sangha Protected Areas. Using sedimentation-based coproscopic techniques, we found the eggs of Mammomonogamus in 19·7% elephant and 54·1% gorilla fecal samples with 8–55 and 1–24 eggs per gram of fecal sediment for elephants and gorillas, respectively. We used a combination of light microscopy, scanning electron microscopy and analysis of cytochrome c oxidase subunit I (cox1) and a partial sequence of 18S rDNA isolated from single eggs to test the hypothesis of possible Mammomonogamus conspecificity in gorillas and elephants. Whereas 18S rDNA sequences were identical in both gorillas and elephants, we distinguished seven different haplotypes within the cox1. Two haplotypes were found in both gorillas and elephants suggesting sharing of Mammomonogamus. Assignment of the parasite to M. loxodontis is proposed. Provided sequences represent the first genomic data on Mammomonogamus spp.

Eimeria mitis and E. acervulina affect different areas of the intestine. Young chicks received E. mitis with or without E. acervulina in doses ranging from 2 to 128 × 104 oocysts. Mixed infections produced significantly more severe effects on growth than single infections of either species. The ratio of villus height to total mucosal thickness was reduced throughout the intestine in birds which received the mixed infection. E. mitis and E. brunetti affect the same area of the intestine. Single infections of E. brunetti in a range of doses from 1.25 to 20 × 103 oocysts produced a similar reduction in growth. When 20 × 103 oocysts of E. mitis were inoculated simultaneously, the effect on growth was not so severe and the oocyst output of both species was reduced. E. brunetti, superimposed 1, 2 or 3 days after an E. mitis infection, produced no greater effect on growth than E. mitis alone. Similarly, infections of E. mitis, superimposed on E. brunetti had no greater effect on growth than the latter species alone. Oocyst output of E. brunetti in superimposed infections was not reduced but peak output was delayed.

Manipulative parasites with complex life cycles are known to induce behavioural and physiological changes in their intermediate hosts. Cyathocephalus truncatus is a manipulative parasite which infects Gammarus pulex as intermediate host. G. pulex males display pre-copulatory mate guarding as a response to male-male competition for access to receptive females. In this paper, we tested the influence that C. truncatus-infection might have on male G. pulex sperm number and pairing success. We considered 3 classes of G. pulex males in our experiments: (i) uninfected males found paired in the field, (ii) uninfected males found unpaired in the field, or (iii) infected males found unpaired in the field. Both infected males and uninfected unpaired males paired less with a new female than uninfected paired males did. Furthermore, infected males appear to be at a strong disadvantage when directly competing for females with a healthy rival male, and had fewer sperm in their testes. We discuss the potential effect of male and female mating strategies on such male host mating alteration.

The paper describes the development and analysis of a mathematical framework for the study of the within-host population dynamics of the interaction between macroparasites and the human immune system. Simple models of this interaction based on the proliferation of T cell clones specific to parasite antigen, and the impact of clonal expansion on parasite survival, capture the basic features of age-related changes in worm loads within human communities. The model is generalized to multiple epitopes on a single antigen, and reveals competitive exclusion amongst T cells, with a single clone becoming immunodominant in the absence of cross-reactive responses and genetic variation. The introduction of genetic heterogeneity and concomitant variability in the immunogenicity of specific epitopes induces additional complexity into the dynamical interaction. Most importantly, multiple epitope models with antigenic variation suggest that the immunodominant response may not necessarily be targeted at the epitope at which some strains show the greatest immunogenicity. High immunogenicity at a particular epitope can be masked by genetic variability even though many of the variants are more immunogenic at this epitope by comparison with the epitope to which the immunodominant immunological response is directed.

The disease known as Turning Sickness was first recorded by Mettam (1934) in this journal and later more fully described by Mettam & Carmichael (1936).

The condition has been defined as a protozoan encephalitis of cattle and one of the most striking features of the disease is the demonstration of schizonts indistinguishable from those of East Coast fever in the cerebral lesions of affected animals.

The effects of dietary urea supplementation and of a 10-week trickle infection regime, simulating chronic exposure to Haemonchus contortus, on the zymogenic population of the abomasa of Hampshire Down lambs was examined. At necropsy a variety of parameters including plasma pepsinogen concentrations, the wet weights of abomasal fundic mucosal pieces and the amounts of pepsinogen contained in them, were assessed. Tissue pepsinogen concentration was measured as the total, acid-stable proteolytic activity present in mucosal homogenates, as well as immunohistochemically. The immunohistochemical findings were quantified using computer-aided image analysis. Elevation of plasma pepsinogen concentrations in infected animals was of borderline significance (P=0·06). The fundic mucosae of infected animals were heavier (P<0·02) than those of control animals, but there was no overall change in the pepsinogen content of tissues. Immunohistochemistry revealed that infected animals had increased numbers of zymogenic cells, due to mucous cell hyperplasia and the adaptation of cells to produce both mucins and pepsinogen. The pepsinogen content of chief cells, the major source of pepsinogen in uninfected animals, was reduced in infected lambs. Image analysis confirmed that at a mid-point of the mucosa of infected animals there was increased pepsinogen-specific immunoreactivity that corresponded with areas of mucosal hyperplasia. Mucous cell hyperplasia might therefore allow the maintenance of pepsinogen secretion in infected animals even if chief cell output is reduced.

Insecticide resistance is a serious problem in the control of many vector-borne diseases, particularly in developing countries where the possibility of changing to an alternative compound may be restricted. Consequently genes giving susceptibility to insecticides in vector species can be viewed as constituting a valuable resource to be used up with discretion. The exchange of information and thought taking place in the Workshop was centred upon possible ways to conserve this resource, i.e. to slow down the evolution of resistance while maintaining adequate control, so preserving the effective life of available insecticides as long as possible. The subject was treated mainly in relation to insect vectors of disease although niost of the discussion would also be relevant to other insect pests.

A recombinant baculovirus-expressed hybrid protein containing epitopes for the C-terminal fragment of the Plasmodium falciparum precursor to the major merozoite surface antigens (PMMSA) and the tetrapeptide repeats of the circumsporozoite protein (CSP) was assessed for its immunogenicity. Murine MHC-II restriction of the antibody response to the CSP repeats was not overcome by the PMMSA component, the response to which showed no restriction. In an adjuvant trial the highest antibody titres in rabbits to both components of the hybrid were obtained using Freund's adjuvant. Lack of a boosting antibody response to the CSP repeats appeared to be linked to the conformation of the PMMSA component. Formulation of the hybrid protein into Iscoms gave antibody titres of only short duration to both components.

The population biology of the schistosome-vector snail Bulinus truncatus was studied in an irrigation area near Marrakech, Morocco, using demographic approaches, in order to estimate life-history parameters. The survey was conducted using 2 capture-mark-recapture analyses in 2 separate sites from the irrigation area, the first one in 1999 and the second one in 2000. Individuals larger than 5 mm were considered. The capture probability varied through time and space in both analyses. Apparent survival (from 0·7 to 1 per period of 2–3 days) varied with time and space (a series of sinks was considered), as well as a square function of size. These results suggest variation in population intrinsic rate of increase. They also suggest that results from more classical analyses of population demography, aiming, for example at estimating population size, should be interpreted with caution. Together with other results obtained in the same irrigation area, they also lead to some suggestions for population control.

Antibodies (Ab) recognizing G-protein coupled receptors, such as β 1 and β 2 adrenergic (anti-β 1-AR and anti-β 2-AR, respectively) and muscarinic cholinergic receptors (anti-M2-CR) may contribute to cardiac damage, however their role in chronic chagasic cardiomyopathy is still controversial. We describe that Trypanosoma cruzi-infected C3H/He mice show increased P and QRS wave duration, and PR and QTc intervals, while the most significant ECG alterations in C57BL/6 are prolonged P wave and PR interval. Echocardiogram analyses show right ventricle dilation in infected animals of both mouse lineages. Analyses of heart rate variability (HRV) in chronically infected C3H/He mice show no alteration of the evaluated parameters, while C57BL/6 infected mice display significantly lower values of HRV components, suggesting autonomic dysfunction. The time-course analysis of anti-β 1-AR, anti-β 2-AR and anti-M2-CR Ab titres in C3H/He infected mice indicate that anti-β 1-AR Ab are detected only in the chronic phase, while anti-β 2-AR and anti-M2-CR are observed in the acute phase, diminish at 60 dpi and increase again in the chronic phase. Chronically infected C57BL/6 mice presented a significant increase in only anti-M2-CR Ab titres. Furthermore, anti-β 1-AR, anti-β 2-AR and anti-M2-CR, exhibit significantly higher prevalence in chronically T. cruzi-infected C3H/He mice when compared with C57BL/6. These observations suggest that T. cruzi infection leads to host-specific cardiac electric alterations.

The induction of schistosomulicidal activity of peritoneal macrophages by concanavalin A-stimulated supernatants from long-term T-cell clones and by interferon-gamma (IFN-γ) was investigated in detail. Optimal conditions of in vitro macrophage activation by T-cell clone supernatants were established. Macrophages from 13-week S. mansoni-infected mice responded to lymphokine activation as well as resident mnacrophages from uninfecteci mice. IFN-γ was shown to play an essential role in induction of schistosomulicidal macrophage activity: recombinant IFN-γ at high concentration could induce schistosomula killing, and an anti-IFN-γ antiserum inhibited the induction ofschistosomulicidal activity by T-cell clone supernatants. Our data also indicate that macrophage activation could be obtained by IFN-γ in synergy with other lymphokines in the supernatant of long-term T-cell clones. Macrophages from mice injected with T-cell clone supernatants were primed in vivo and triggered to kill schistosomula in vitro in the presence of lipopolysaccharide (LPS). The data demonstrate that lymphokines produced by T-cell clones and, in particular, IFN-γ can participate in the activation of schistosomulicidal macrophages.

Nitric oxide (NO) produced by cytokine-activated macrophages is reported to be cytotoxic against the helminth Schistosoma mansoni, although this is a controversial issue. Previous work in our laboratory identified a fraction of S. mansoni soluble adult worm antigenic preparation (SWAP), named PIII, able to elicit significant in vitro cell proliferation and at the same time lower in vitro and in vivo granuloma formation when compared either to soluble egg antigen (SEA) or to SWAP. Here we report that, in comparison to other S. mansoni antigenic preparations (SEA and SWAP), supernatants of PBMC cultivated with PIII possess higher concentrations of interleukin-10 (IL-10) and macrophage inflammatory protein (MIP-1α), concomitantly with lower concentrations of monocyte chemoattractant protein (MCP-1) and regulated on activation, normal T expressed and secreted (RANTES). In the particular case of NO inhibition, supernatants of PBMC cultivated with PIII present decreased IL-10 levels. Altogether, these results indicate that IL-10, MIP-1α, MCP-1 and RANTES are distinctively important elements in the PIII modulating role, while NO seems to be pivotal in the regulation of granulomatous responses.

Pectoral fins from juvenile rainbow trout (Oncorhynchus mykiss) were used in a bioassay, the object of which was to quantify the effect of simulated shadow stimuli on the transmission success of the cercariae. For a period of 60 min, parasites and fins were exposed to a sequence of computer-controlled shadow stimuli, continuous light or total darkness, and subsequently the number of infections was counted. Trials were conducted with cercariae 1, 12 and 24 h old. Within the constraints of the experimental procedure, shadows were found to increase significantly the number of infections achieved by the 12-h-old parasites. As the cercariae aged, their ability to infect host tissue declined. The relevance of these results to transmission in the natural environment is discussed.

Non-pathogenic trypanosomes of the subgenus Herpetosoma are normally host specific, and laboratory models include Trypanosoma lewisi in rats and Trypanosoma musculi in mice. Two isolates of Trypanosoma grosi, originating from Apodemus agrarius and Apodemus peninsulae, grew well in Mongolian jirds, Meriones unguiculatus, after intraperitoneal inoculation of 2×105 or a minimum 500 bloodstream forms. The course of T. grosi infection in jirds resembled T. musculi infection in mice, rather than T. lewisi infection in rats. At week 2 to 3 p.i. trypanosomes disappeared from the bloodstream, and neither prednisolone treatment nor splenectomy prevented parasite elimination from the bloodstream. However, these treatments induced a marked increase in peak parasite counts. Regardless of prednisolone treatment or splenectomy, all jirds after day 21 p.i. became resistant to the reinfection. Although no trypanosomes were detected in the bloodstream of recovered jirds, dividing parasites persisted in the medullary capillaries of the kidney, like T. musculi infection in mice. We propose the T. grosi infection in jirds as an additional laboratory model for the study of non-pathogenic trypanosomes.

The macroparasites Cephenemyia trompe (Modeer) and Hypoderma (=Oedemagena) tarandi (L.) (Diptera: Oestridae), Linguatula arctica Riley, Haugerud and Nilssen (Pentastomida: Linguatulidae), Elaphostrongylus rangiferi Mitskevich (Nematoda: Protostrongylidae), and abomasal nematodes (Nematoda: Trichostrongylidae) were sampled in semidomestic reindeer calves (Rangifer tarandus (L.)) (ca. 8 months of age) in northern Norway in 1988 (n=160) and 1989 (n=191). Each parasite showed an aggregated (clumped) distribution among the hosts and fitted the negative binomial distribution. Analyses of interspecific associations in intensities showed that there was no consistent covariation among the parasites apart from a weak correlation (Kendall's tau 0·104, P=0·007) between the 2 oestrids C. trompe and H. tarandi. This lack of covariation reveals that the parasites were distributed independently of each other, and suggests that innate host resistance is not a dominant factor that has a significant simultaneous effect on all parasites. The aggregated distribution of each parasite species is hypothesized to be caused by (1) random events and heterogeneities in host behaviour that create unequal transmission (exposure) rates, or (2) by heterogeneities in parasite specific immunocompetence among host individuals. Factors in hypothesis (1) are probably the most important at low transmission rates.

Current development efforts of subunit vaccines against Toxoplasma gondii, the aetiological agent of toxoplasmosis, have been focused mainly on tachyzoite surface antigens (SAGs) such as SAG2, due to their attachment roles in the process of host-cell invasion. In the present study, we aimed to produce poly(lactide-co-glycolide) (PLG) microparticles (MPs) containing recombinant SAG2 (rSAG2) to induce improved immunity against T. gondii. The resulting PLG-encapsulated rSAG2 (PLG-rSAG2) MPs, 2·14–3·63 μm in diameter, showed 74–80% entrapment efficiency and gradually released antigenic rSAG2 protein (88·3% of the total protein load) for a long 33-day period. Peritoneal immunization with PLG-rSAG2 MPs in BALB/c mice resulted in not only sustained (10 weeks) lymphocyte proliferation and IFN-γ production but also an improved protective capacity (87%) against a lethal subcutaneous challenge of 1×104 live tachyzoites of T. gondii (RH strain). In conclusion, the sustained release of rSAG2 protein from PLG-rSAG2 MPs extends Th1 cell-mediated immunity (lymphocyte proliferation and IFN-γ production) and induces improved protection against T. gondii tachyzoite infection in mice.

An estimated quarter of the world's population possesses an infection caused by gastrointestinal nematodes, which induce a Th2 type immune response. Concomitant infection of nematodes with Mycobacterium tuberculosis, which induces a predominantly Th1 type response, is very frequent in tropical and subtropical regions. This study examined immune responses of BALB/c mice infected with Strongyloides venezuelensis and then co-infected with Mycobacterium bovis. The number of worms in the intestine, eggs in feces, cytokine production in lungs and intestine and the expression of CD80, CD86, CTLA-4 and CD28 cell markers on pulmonary cells were analysed. Our results indicate that co-infected mice had an increased parasite burden, which correlates with elevated IFN-γ and IL-10 cytokine production and decreased IL-4 and IL-13. Moreover, decreased expression of CD80 and increased expression of CTLA-4 were observed in co-infected mice. Our data point out that susceptibility to Strongyloides venezuelensis infection is increased by Mycobacterium bovis co-infection, resulting in higher parasite survival.

Trypanocide resistance remains a huge challenge in the management of animal African trypanosomiasis. Paucity of data on the prevalence of multi-drug resistant trypanosomes has greatly hindered optimal veterinary management practices. We use mathematical model predictions to highlight appropriate drug regimens that impede trypanocide resistance development in cattle. We demonstrate that using drugs in decreasing resistance order results in a negligible increase in number of cattle with resistant infection, in contrast to a more pronounced increase from trypanocide use in increasing resistance order. We demonstrate that the lowest levels of trypanocide resistance are achieved with combination therapy. We also show that increasing the number of cattle treated leads to a progressive reduction in the number of cattle with drug resistant infections for treatments of up to 80% of the cattle population for the combination treatment strategy. Our findings provide an initial evidence-based framework on some essential practices that promote optimal use of the handful of trypanocides. We anticipate that our modest forecasts will improve therapeutic outcomes by appropriately informing on the best choice, and combination of drugs that minimize treatment failure rates.