The Chemotherapy of Protozoal Infections of Veterinary Importance1

The use of drugs in domestic animals is dominated by considerations of cost-effectiveness and profitability. They are extensively used against coccidial infections of poultry where they are an important factor in intensive husbandry. Ionophore antibiotics, which dominate this field, may have applications in ruminants. Imidocarb is of therapeutic and prophylactic value against babesial infections and there are new prospects for control of theileriasis. Effective drugs for the control of African trypanosomiasis are limited and attention is being given to alternative uses of available compounds.     

Interferon and Interferon Inducers in Protozoal Infections

Several interferon inducers (Newcastle disease virus, statolon, and poly rI:poly rC) as well as exogenous mouse interferon protect mice from sporozoite-induced Plasmodium berghei malaria, as long as they are administered before the end of the preerythrocytic phase of development of the parasite. The protective effect of the interferon inducers was related to their interferon-inducing effect; the protective effect of the interferon preparations was related to the interferon titer of the preparations, and it exhibited other attributes of interferon such as species specificity. In contrast to sporozoite-induced infection, blood forms-induced P. berghei malaria was only weakly susceptible to the protective effect of interferon inducers. This difference may provide an approach to study the mechanism of protection. The growth in cell cultures of another intracellular protozoon, Toxoplasma gondii, is also inhibited by interferon (22). The fact that P. berghei and T. gondii (as well as another group of intracellular parasites susceptible to interferon, the Chlamydia) have their own ribosomes raises questions, concerning the role of host cell ribosomes in the host cell-parasite relationship of these intracellular parasites and in the mechanism of interferon action against them, that can be approached experimentally. The possibility of therapeutic or prophylactic application of interferon or of its inducers to certain protozoal diseases of man and of other animals is still remote, but it has to be considered for long range planning.     

Unravelling the Relationship between Animal Growth and Immune Response during Micro-Parasitic Infections

Background

Both host genetic potentials for growth and disease resistance, as well as nutrition are known to affect responses of individuals challenged with micro-parasites, but their interactive effects are difficult to predict from experimental studies alone.

Methodology/Principal Findings

Here, a mathematical model is proposed to explore the hypothesis that a host''s response to pathogen challenge largely depends on the interaction between a host''s genetic capacities for growth or disease resistance and the nutritional environment. As might be expected, the model predicts that if nutritional availability is high, hosts with higher growth capacities will also grow faster under micro-parasitic challenge, and more resistant animals will exhibit a more effective immune response. Growth capacity has little effect on immune response and resistance capacity has little effect on achieved growth. However, the influence of host genetics on phenotypic performance changes drastically if nutrient availability is scarce. In this case achieved growth and immune response depend simultaneously on both capacities for growth and disease resistance. A higher growth capacity (achieved e.g. through genetic selection) would be detrimental for the animal''s ability to cope with pathogens and greater resistance may reduce growth in the short-term.

Significance

Our model can thus explain contradicting outcomes of genetic selection observed in experimental studies and provides the necessary biological background for understanding the influence of selection and/or changes in the nutritional environment on phenotypic growth and immune response.     

Assessing Mathematical Models of Influenza Infections Using Features of the Immune Response

The role of the host immune response in determining the severity and duration of an influenza infection is still unclear. In order to identify severity factors and more accurately predict the course of an influenza infection within a human host, an understanding of the impact of host factors on the infection process is required. Despite the lack of sufficiently diverse experimental data describing the time course of the various immune response components, published mathematical models were constructed from limited human or animal data using various strategies and simplifying assumptions. To assess the validity of these models, we assemble previously published experimental data of the dynamics and role of cytotoxic T lymphocytes, antibodies, and interferon and determined qualitative key features of their effect that should be captured by mathematical models. We test these existing models by confronting them with experimental data and find that no single model agrees completely with the variety of influenza viral kinetics responses observed experimentally when various immune response components are suppressed. Our analysis highlights the strong and weak points of each mathematical model and highlights areas where additional experimental data could elucidate specific mechanisms, constrain model design, and complete our understanding of the immune response to influenza.