The regulation of immunological responses to parasitic infections and the development of tolerance.

It is well established that specific unresponsiveness to immunization can be induced by prolonged exposure to antigenic proteins. More generally, many parasitic infections, such as the helminth worms and the Leishmania parasites, appear to be able to persist in some of their human hosts over long periods of time, via what appears to be an ability to induce defective or inappropriate T-cell responses (= tolerance). Recent research has suggested that cytokines, produced by specific subsets of CD4+ T-cells (characterized by cytokine secretory profiles and growth properties), have an important, and often complex, role in promoting or inhibiting host protective immunity to parasitic infections. By examination of the population dynamics of the stimulation and regulation of cellular responses to infection, via the use of simple mathematical models, we show that nonlinear interactions between CD4+ T-cell subsets and their secreted cytokines can result in either host protection or immunological unresponsiveness, depending on the magnitude and duration of exposure to parasitic infection. Analyses also identify a possible mechanism to explain the stimulation of two separate peaks of enhanced T-cell-mediated responses over a wide range of levels of antigenic exposure.     

Effect of desiccation on tolerance of salmonella enterica to multiple stresses

Reducing the available water in food is a long-established method for controlling bacterial growth in the food industry. Nevertheless, food-borne outbreaks of salmonellosis due to consumption of dry foods have been continuously reported. Previous studies showed that dried Salmonella cells acquire high tolerance to heat and ethanol. In order to examine if dehydration also induces tolerance to other stressors, dried Salmonella enterica serotype Typhimurium cells were exposed to multiple stresses, and their viability was assessed. Indeed, desiccated S. Typhimurium acquired higher tolerance to multiple stressors than nondesiccated cells. The dried cells were significantly more resistant to most stressors, including ethanol (10 to 30%, 5 min), sodium hypochlorite (10 to 100 ppm, 10 min), didecyl dimethyl ammonium chloride (0.05 to 0.25%, 5 min), hydrogen peroxide (0.5 to 2.0%, 30 min), NaCl (0.1 to 1 M, 2 h), bile salts (1 to 10%, 2 h), dry heat (100°C, 1 h), and UV irradiation (125 μW/cm(2), 25 min). In contrast, exposure of Salmonella to acetic and citric acids reduced the survival of the dried cells (1.5 log) compared to that of nondesiccated cells (0.5 log). Three other S. enterica serotypes, S. Enteritidis, S. Newport, and S. Infantis, had similar stress responses as S. Typhimurium, while S. Hadar was much more susceptible and gained tolerance to only a few stressors. Our findings indicate that dehydration induces cross-tolerance to multiple stresses in S. enterica, demonstrating the limitations of current chemical and physical treatments utilized by the food industry to inactivate food-borne pathogens.     

The serodiagnosis of parasitic infections

Recently, the term of clinical immunoparasitology has been coined to indicate the application of immunological methods to the laboratory diagnosis of parasitic infections. In particular, serological diagnosis (indirect diagnosis) is useful especially in the cases of toxocarosis, trichinellosis, echinococcosis, cysticercosis, toxoplasmosis, amoebic abscess, some filariasis, visceral leishmaniasis, schistosomiasis. When possible, for infections caused by protozoa or helminths, the "gold standard" is represented by direct diagnosis performed by microscopic and/or macroscopic observation of the parasite. In any case, immunological results must be interpreted in consideration of the clinical picture of the patient and confirmed possibly by finding the parasite or its genome, even using molecular methods. Furthermore, since the presence of specific antibodies can reveal an acquired infection, but not necessarily a disease, it is particularly helpful, in addition to a qualitative evaluation, a quantitative one, by determining the serum antibody titre. After recovery, the antibody levels decrease, however, they may persist for long periods, for this reason they do not help in evaluating the treatment outcome. Interpretation of serological results may be difficult when the patients originate from areas where the suspected infection is endemic, in that case, a serum positivity could reflect an old exposition to the parasite, therefore it is not related to the present clinical status. Furthermore, serology may frequently result falsely negative in not immunocompetent subjects (organ transplanted, HIV positive individuals, premature babies, diabetics). Clinicians can interpret correctly the serological results only if the Parasitology laboratory inform them about the significant diagnostic values, the sensitivity and the specificity of the test in use. At present time, many diagnostic kits for immunoparasitology are commercially available, and industries are developing newer and newer ones (which are not always validated). In relation to this aspect, it should be helpful, for each of parasitic infection, to establish reference centers, not only to control the quality of commercial kits, but also as a reference point to those laboratories which use "in house" kits. To this regard, the recent establishment of a European Centre for Control of Infectious Diseases will help. The antigen characteristics (crude, E/S, recombinant, synthetic) for assays searching for antibodies (IHA, IFA, EIA, WB) of different classes, the controls to choose for these assays, the specimen requirements will be discussed. The recent findings on the serological diagnosis of intestinal protozoa infections, malaria, leishmaniasis, echinococcosis, cysticercosis, trichinellosis, toxocariasis, schistosomiasis, strongyloidiasis will be presented.     

Water contamination reduces the tolerance of coral larvae to thermal stress

Coral reefs are highly susceptible to climate change, with elevated sea surface temperatures (SST) posing one of the main threats to coral survival. Successful recruitment of new colonies is important for the recovery of degraded reefs following mortality events. Coral larvae require relatively uncontaminated substratum on which to metamorphose into sessile polyps, and the increasing pollution of coastal waters therefore constitutes an additional threat to reef resilience. Here we develop and analyse a model of larval metamorphosis success for two common coral species to quantify the interactive effects of water pollution (copper contamination) and SST. We identify thresholds of temperature and pollution that prevent larval metamorphosis, and evaluate synergistic interactions between these stressors. Our analyses show that halving the concentration of Cu can protect corals from the negative effects of a 2-3°C increase in SST. These results demonstrate that effective mitigation of local impacts can reduce negative effects of global stressors.     

Controllable infections and the self-regulation of parasitic systems

The control of the epidemic process is based on the knowledge of the mechanisms of self-regulation, developed in the process of evolution, in the relationship of the host and parasite populations under the changing conditions of the social and natural environment. The problem of the global and regional liquidation of infections controllable by means of immunoprophylactic measures is considered.     

Relatedness affects competitive performance of a parasitic plant (Cuscuta europaea) in multiple infections

Theoretical models predict that parasite relatedness affects the outcome of competition between parasites, and the evolution of parasite virulence. We examined whether parasite relatedness affects competition between parasitic plants (Cuscuta europaea) that share common host plants (Urtica dioica). We infected hosts with two parasitic plants that were either half-siblings or nonrelated. Relative size asymmetry between the competing parasites was significantly higher in the nonrelated infections compared to infections with siblings. This higher asymmetry was caused by the fact that the performance of some parasite genotypes decreased and that of others increased when grown in multiple infections with nonrelated parasites. This result agrees with the predictions of theories on the evolution of parasite virulence: to enhance parasite transmission, selection may favour reduced competition with genetically related parasites in hosts infected by several genotypes. However, in contrast to the most common predictions, nonrelated infections were not more virulent than the sibling infections.     

Desiccation‐tolerance in bdelloid rotifers facilitates spatiotemporal escape from multiple species of parasitic fungi

Asexuality has major theoretical advantages over sexual reproduction. Nevertheless, obligately asexual metazoan lineages seldom endure over evolutionary time. The Red Queen hypothesis posits that their limited capacity to generate genetic novelty leads to extermination by rapidly evolving parasites and pathogens. At first glance, rotifers of the class Bdelloidea appear to contradict this view: they have reproduced asexually for over 30 Myr without being overwhelmed by parasites. However, there are special ecological conditions under which Red Queen models can accommodate this unusual outcome. If hosts disperse rapidly within a structured metapopulation during a parasite‐free life stage, then in principle they can become spatiotemporally decoupled from coevolving antagonists, and persist without sex. Intriguingly, bdelloid rotifers form dormant propagules when desiccated, which disperse easily by wind. In previous experiments, 7 days of desiccation and wind dispersal removed a fungal parasite from populations of one bdelloid species, allowing them to disperse independently. Here, I extend this finding to two additional bdelloid species and five more fungal parasites, and demonstrate its robustness under various desiccation regimes, and in the presence of multiple parasites. Results support the hypothesis that the unusual physiology of anciently asexual bdelloid rotifers helps them escape fungal parasites in space and time. © 2011 The Linnean Society of London, Biological Journal of the Linnean Society, 2011, 104 , 564–574.     

Human ecology and parasitic infections. 1. The effect of occupation on the prevalence of parasitic infections in Calabar, Nigeria.

One thousand six hundred people belonging to three different occupational groups were randomly selected. Blood, urine and stool specimens were collected from them and processed for the detection of any parasitic infections. The results show 28.5% infection rate with one or more species of intestinal parasites; 50.7% in the school children, 17.3% among the farmers, and 12% among the soldiers. Results of blood examination showed 5.3%, 8.0% and 2.0% infection rates for P. falciparum in the school pupils, farmers and soldiers respectively, while 31.3% of the three groups were infected with the microfilaria of Dipetalonema perstans, and Loa loa. These were found in 60.7% of the farmers and none at all in the other two groups. Urine examination yielded no positive cases of urinary schistosomiasis and only one case of Trichomonas vaginalis. These results reflect the endemicity of the respective parasites, the degree of their sanitary awareness and their exposure frequencies to the pathogens as a result of their daily activities.     

Multi-immunodot for rapid differential diagnosis of eosinophilic meningitis due to parasitic infections

A multi-dot enzyme-linked immunosorbent assay (ELISA) was developed for the rapid and simple differential diagnosis of eosinophilic meningitis due to helminth infections. Ultrafiltered, purified antigens of Parastrongylus (=Angiostrongylus) cantonensis, Gnathostoma spinigerum and Taenia solium metacestodes, the most common parasites that invade the central nervous system and cause eosinophilic pleocytosis, were dotted onto a single nitrocellulose membrane strip. Antigen-coated strips, when blocked with 5% skimmed milk and dried, were stable for at least 6 months at 4 degrees C. With peroxidase conjugated anti-human immunoglobulins and 4-chloro-1-naphthol as a substrate, antibodies in the corresponding patients' sera were clearly detected on the membrane strip as well-defined blue dots. Although cross-reactions between P. cantonensis and G. spinigerum antigens were observed with the use of partially purified antigens, the darkest dot correlated well with the infecting parasites in all cases. This fast, easy and economical multiple dot-blot ELISA method is useful for the differential diagnosis of eosinophilic meningitis caused by parasitic helminths, as semi-purified antigens can be easily obtained by ultrafiltration and used. Further improvements using highly specific parasite antigens may make this multi-immunodot test more suitable for wide-scale use in field studies and diagnostic laboratories.     

Effect of p-chlorophenylalanine on the acquisition of tolerance to barbital

The effect of p-chlorophenylalanine (p-CPA) pretreatment on barbital tolerance in the rat as measured by motor impairment on the moving belt test was examined in two separate studies. The first used a 2 X 2 design with doses of p-CPA (125 mg/kg) or water, and sodium barbital (300 mg/kg) or water. The treatments continued for 28 days with tests every 7 days. The p-CPA dose used was previously shown to produce and maintain greater than 95% depletion of brain serotonin (5-HT). Tolerance developed to the test doses, and even greater tolerance to the chronic treatment doses. In both cases the p-CPA slowed the development of tolerance without altering the acute response to the challenge dose of barbital. The second study involved only a p-CPA-barbital group and a water-barbital group. In this case treatment lasted for up to 8 days, with separate subgroups being tested only once each at 2-day intervals, in order to prevent the tests from affecting the rate of tolerance development. This experiment confirmed that p-CPA slowed the development of barbital tolerance. The present findings provide additional support for the possibility that 5-HT may be involved in the development of tolerance to sedatives (e.g., alcohol, pentobarbital).