Experimental evaluation of the relationship between lethal or non-lethal virulence and transmission success in malaria parasite infections

BACKGROUND: Evolutionary theory suggests that the selection pressure on parasites to maximize their transmission determines their optimal host exploitation strategies and thus their virulence. Establishing the adaptive basis to parasite life history traits has important consequences for predicting parasite responses to public health interventions. In this study we examine the extent to which malaria parasites conform to the predicted adaptive trade-off between transmission and virulence, as defined by mortality. The majority of natural infections, however, result in sub-lethal virulent effects (e.g. anaemia) and are often composed of many strains. Both sub-lethal effects and pathogen population structure have been theoretically shown to have important consequences for virulence evolution. Thus, we additionally examine the relationship between anaemia and transmission in single and mixed clone infections. RESULTS: Whereas there was a trade-off between transmission success and virulence as defined by host mortality, contradictory clone-specific patterns occurred when defining virulence by anaemia. A negative relationship between anaemia and transmission success was found for one of the parasite clones, whereas there was no relationship for the other. Notably the two parasite clones also differed in a transmission phenotype (gametocyte sex ratio) that has previously been shown to respond adaptively to a changing blood environment. In addition, as predicted by evolutionary theory, mixed infections resulted in increased anaemia. The increased anaemia was, however, not correlated with any discernable parasite trait (e.g. parasite density) or with increased transmission. CONCLUSIONS: We found some evidence supporting the hypothesis that there is an adaptive basis correlating virulence (as defined by host mortality) and transmission success in malaria parasites. This confirms the validity of applying evolutionary virulence theory to biomedical research and adds support to the prediction that partially effective vaccines may select for increasingly virulent malaria parasite strains. By contrast, there was no consistent correlation between transmission and sub-lethal anaemia, a more common outcome of malaria infection. However, overall, the data are not inconsistent with the recent proposal that sub-lethal effects may impose an upper limit on virulence. Moreover, clone specific differences in transmission phenotypes linked to anaemia do suggest that there is considerable adaptive potential relating anaemia and transmission that may lead to uncertain consequences following intervention strategies

Immunoregulation of bovine macrophages by factors in the salivary glands of Rhipicephalus microplus

<p>Abstract</p> <p>Background</p> <p>Alternative strategies are required to control the southern cattle tick, <it>Rhipicephalus microplus</it>, due to evolving resistance to commercially available acaricides. This invasive ectoparasite is a vector of economically important diseases of cattle such as bovine babesiosis and anaplasmosis. An understanding of the biological intricacies underlying vector-host-pathogen interactions is required to innovate sustainable tick management strategies that can ultimately mitigate the impact of animal and zoonotic tick-borne diseases. Tick saliva contains molecules evolved to impair host innate and adaptive immune responses, which facilitates blood feeding and pathogen transmission. Antigen presenting cells are central to the development of robust T cell responses including Th1 and Th2 determination. In this study we examined changes in co-stimulatory molecule expression and cytokine response of bovine macrophages exposed to salivary gland extracts (SGE) obtained from 2-3 day fed, pathogen-free adult <it>R. microplus</it>.</p> <p>Methods</p> <p>Peripheral blood-derived macrophages were treated for 1 hr with 1, 5, or 10 μg/mL of SGE followed by 1, 6, 24 hr of 1 μg/mL of lipopolysaccharide (LPS). Real-time PCR and cytokine ELISA were used to measure changes in co-stimulatory molecule expression and cytokine response.</p> <p>Results</p> <p>Changes were observed in co-stimulatory molecule expression of bovine macrophages in response to <it>R</it>. <it>microplus </it>SGE exposure. After 6 hrs, CD86, but not CD80, was preferentially up-regulated on bovine macrophages when treated with 1 μg/ml SGE and then LPS, but not SGE alone. At 24 hrs CD80, CD86, and CD69 expression was increased with LPS, but was inhibited by the addition of SGE. SGE also inhibited LPS induced upregulation of TNFα, IFNγ and IL-12 cytokines, but did not alter IL-4 or CD40 mRNA expression.</p> <p>Conclusions</p> <p>Molecules from the salivary glands of adult <it>R. microplus </it>showed bimodal concentration-, and time-dependent effects on differential up-regulation of CD86 in bovine macrophages activated by the TLR4-ligand, LPS. Up regulation of proinflammatory cytokines and IL-12, a Th1 promoting cytokine, were inhibited in a dose-dependent manner. The co-stimulatory molecules CD80, as well as the cell activation marker, CD69, were also suppressed in macrophages exposed to SGE. Continued investigation of the immunomodulatory factors will provide the knowledge base to research and develop therapeutic or prophylactic interventions targeting <it>R. microplus</it>-cattle interactions at the blood-feeding interface.</p

World Health Organization Estimates of the Global and Regional Disease Burden of 11 Foodborne Parasitic Diseases, 2010: A Data Synthesis

We would like to acknowledge the assistance of the WHO Secretariat over the life of the FERG initiative, particularly Amy Cawthorne, Tim Corrigan, Tanja Kuchenmüller, Yuki Minato, Kurt Straif and Claudia Stein. We acknowledge the Institute for Health Metrics and Evaluation (Seattle, WA, USA) for providing data on the global burden of selected diseases.In this data synthesis, Paul Robert Torgerson and colleagues estimate the global and regional disease burden of 11 foodborne parasitic diseases.Yeshttp://www.plosmedicine.org/static/editorial#pee

Correlation between serum transferrin receptor and percentage of parasitemia in malaria. A preliminary report

The serum transferrin receptor (sTfR) concentration is an individual reflects of the extent of erythropoietic activity, and is a useful marker for monitoring erythropoiesis. Malaria is an important tropical disease with evidence of ineffective erythropoiesis. Although there have been previous reports concerning sTfR changes in malaria, these were descriptive studies of infected and non-infected case and there are no previous reports of correlation between sTfR levels and parasitemia in malaria. We performed an animal experiment to study the chronological changes in the level of serum transferrin receptor during infection with Plasmodium gallinaceum. The average level of sTfR in experimental chickens was 6.59 ± 11.29 mg/L. The average percentage of parasitemia was 3.4 ± 3.5% (range 2 to 13%). According to this study, there is significant correlation between both parameters (r = 0.921; p < 0.05)

Correlation between serum transferrin receptor and percentage of parasitemia in malaria. A preliminary report

The serum transferrin receptor (sTfR) concentration is an individual reflects of the extent of erythropoietic activity, and is a useful marker for monitoring erythropoiesis. Malaria is an important tropical disease with evidence of ineffective erythropoiesis. Although there have been previous reports concerning sTfR changes in malaria, these were descriptive studies of infected and non-infected case and there are no previous reports of correlation between sTfR levels and parasitemia in malaria. We performed an animal experiment to study the chronological changes in the level of serum transferrin receptor during infection with Plasmodium gallinaceum. The average level of sTfR in experimental chickens was 6.59 ± 11.29 mg/L. The average percentage of parasitemia was 3.4 ± 3.5% (range 2 to 13%). According to this study, there is significant correlation between both parameters (r = 0.921; p < 0.05)