A song for the unsung: The relevance of Plasmodium vinckei as a laboratory rodent malaria system

Rodent malaria parasites (RMPs) allow the study of malaria parasite biology across its entire life cycle through a vertebrate host and a mosquito vector under laboratory conditions. Among the four RMPs originally collected from wild thicket rats in sub-Saharan Central Africa and adapted to laboratory mice, Plasmodium vinckei has the largest geographical range and includes the largest number of sub-species, demonstrating its deep genetic diversity. Despite affording the same advantages as other RMP species and additionally displaying a large degree of phenotypic and genotypic diversity, P. vinckei has seen limited use in the laboratory. Here, we review the contribution of P. vinckei to our understanding of malaria and highlight the areas where it could offer an advantage over other RMP species in future studies

New drug-target associations disclosed in the present study.

<p>(NA: not available; codes in brackets represent the target Identity Code of DrugBank. Toxicity data is cited from DrugBank; FAS: Fatty Acid Synthesis; LD50: drug dose that results in death of 50% of the animals).</p

Flowchart summarizing the work pipeline and corresponding results.

<p>(*denotes the targets that were discarded on the basis of having chemical affinity to dietary supplements/nutraceuticals).</p

Distribution of the expected apicoplast targets according to their predicted metabolic function in the apicoplast.

<p>Distribution of the expected apicoplast targets according to their predicted metabolic function in the apicoplast.</p

Examples of drug-target associations previously determined, that were correctly identified in the present study.

<p>(codes in brackets represent the target Identity Code of DrugBank. In the cases of Fosmidomycin, Triclosan and Geldanamycin, there are no homologous targets represented because they were identified using STITCH3.1 which uses an algorithm where homologous targets are not displayed).</p

Morphological change of the <i>Plasmodium yoelii</i> merozoite after released from red blood cell (RBC).

<p>The major axis (A), minor axis (B), longitudinal cross section area (C), and circularity (D) were measured every 10 sec from RBC rupture to pre-invasion for invasive merozoites (n = 9–12). The average and the error representing one standard deviation were plotted in the line charts. Circularity was calculated using the following formula: Circularity = 4πArea/Perimeter². A value of 1 indicates a perfect circle and the value of 0 indicates an increasingly elongated polygon. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050780#pone.0050780.s001" target="_blank">Table S1</a> for detail values. (E) Time-lapse sequence of merozoite release of <i>P. yoelii</i> 17XL was recorded every 0.1 sec. Arrowhead indicates same invasive merozoite in the sequence and the arrow indicates an attachment of an immature flat elongated oval merozoite. A mature spherical invasive merozoite attached to the RBC and deformed RBC (Pre-invasion) at 180 sec. The bar represents 5 µm.</p

Kinetic difference in red blood cell (RBC) invasion between <i>Plasmodium</i> species.

<p>The median time for each step are shown as a box plot with whiskers from minimum to maximum. The interquartile range shows as box with the median marked as a horizontal line, minimum and maximum from lower and upper quartile represent error bar. <i>P</i> values were determined using the Mann-Whitney U test. See <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0050780#pone.0050780.s001" target="_blank">Table S1</a> for detail values.</p

Time-lapse imaging for the rupture of schizont-infected red blood cells.

<p>Images were captured every 0.1 sec with transmitted light for <i>Plasmodium yoelii</i> 17XL (A), <i>P. yoelii</i> 17X1.1 (B), and <i>Plasmodium falciparum</i> 3D7 line (C). The bars represent 5 µm.</p

<i>Schistosoma mansoni</i> infection suppresses the growth of <i>Plasmodium yoelii</i> parasites in the liver and reduces gametocyte infectivity to mosquitoes

<div><p>Malaria and schistosomiasis are major parasitic diseases causing morbidity and mortality in the tropics. Epidemiological surveys have revealed coinfection rates of up to 30% among children in Sub-Saharan Africa. To investigate the impact of coinfection of these two parasites on disease epidemiology and pathology, we carried out coinfection studies using <i>Plasmodium yoelii</i> and <i>Schistosoma mansoni</i> in mice. Malaria parasite growth in the liver following sporozoite inoculation is significantly inhibited in mice infected with <i>S</i>. <i>mansoni</i>, so that when low numbers of sporozoites are inoculated, there is a large reduction in the percentage of mice that go on to develop blood stage malaria. Furthermore, gametocyte infectivity is much reduced in mice with <i>S</i>. <i>mansoni</i> infections. These results have profound implications for understanding the interactions between <i>Plasmodium</i> and <i>Schistosoma</i> species, and have implications for the control of malaria in schistosome endemic areas.</p></div

Congenital malaria in China from 1963 to 2010.

<p>Abbreviations of affected provinces: AH: Anhui; CQ: Chongqin; GS: Gansu; GX: Guangxi; GD: Guangdong; HB: Hubei; HLJ: Heilongjiang; HN1: Hunan; HN2: Hainan; HN3: Henan; JS: Jiangsu; JX: Jiangxi; SC: Sichuan; SD: Shandong; XZ: Xizang; YN: Yunnan; ZJ: Zhejiang.</p