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B Zelman et al. Costs of Eliminating Malaria and the Impact of the Global Fund in 34 Countries. PLoS One

High Impact Journal from Malaria Portal - 31 December 2015 - 12:00am
International financing for malaria increased more than 18-fold between 2000 and 2011; the largest source came from The Global Fund to Fight AIDS, Tuberculosis and Malaria (Global Fund). . . .
Categories: malaria news feeds

AJ Arik et al. Increased Akt signaling in the mosquito fat body increases adult survivorship. FASEB J

High Impact Journal from Malaria Portal - 31 December 2015 - 12:00am
Akt signaling regulates diverse physiologies in a wide range of organisms. . . .
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JJ Campo et al. RTS,S vaccination is associated with serologic evidence of decreased exposure to Plasmodium falciparum liver and blood stage parasites. Mol Cell Proteomics

High Impact Journal from Malaria Portal - 30 December 2015 - 12:00am
The leading malaria vaccine candidate, RTS,S, targets the sporozoite and liver stages of the Plasmodium falciparum life cycle, yet it provides partial protection against disease associated with subsequent blood-stage of infection. . . .
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C Waterman et al. Miniaturized Cultivation of Microbiota for Antimalarial Drug Discovery. Med Res Rev

High Impact Journal from Malaria Portal - 29 December 2015 - 12:00am
The ongoing search for effective antiplasmodial agents remains essential in the fight against malaria worldwide. . . .
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CV Hobbs et al. Neither the HIV Protease Inhibitor Lopinavir-Ritonavir nor the Antimicrobial Trimethoprim-Sulfamethoxazole Prevent Malaria Relapse in Plasmodium cynomolgi-Infected Non-Human Primates. PLoS One

High Impact Journal from Malaria Portal - 27 December 2015 - 12:00am
Plasmodium vivax malaria causes significant morbidity and mortality worldwide, and only one drug is in clinical use that can kill the hypnozoites that cause P. . . .
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K Schuldt et al. Endothelial protein C receptor gene variants not associated with severe malaria in ghanaian children. PLoS One

High Impact Journal from Malaria Portal - 27 December 2015 - 12:00am
Two recent reports have identified the Endothelial Protein C Receptor (EPCR) as a key molecule implicated in severe malaria pathology. . . .
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A novel locus of resistance to severe malaria in a region of ancient balancing selection

CiteULike malaria tags - 1 October 2015 - 12:32pm
Nature, Vol. advance online publication (30 September 2015), doi:10.1038/nature15390
Malaria Genomic Epidemiology Network
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Estimating malaria transmission from humans to mosquitoes in a noisy landscape

CiteULike malaria tags - 1 October 2015 - 12:20pm
Journal of The Royal Society Interface, Vol. 12, No. 111. (06 October 2015), 20150478, doi:10.1098/rsif.2015.0478
Robert Reiner, Carlos Guerra, Martin Donnelly, Teun Bousema, Chris Drakeley, David Smith
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Plasmodium Infection Is Associated with Impaired Hepatic Dimethylarginine Dimethylaminohydrolase Activity and Disruption of Nitric Oxide Synthase Inhibitor/Substrate Homeostasis

CiteULike malaria tags - 1 October 2015 - 9:38am
PLoS Pathog, Vol. 11, No. 9. (25 September 2015), e1005119, doi:10.1371/journal.ppat.1005119

Inhibition of nitric oxide (NO) signaling may contribute to pathological activation of the vascular endothelium during severe malaria infection. Dimethylarginine dimethylaminohydrolase (DDAH) regulates endothelial NO synthesis by maintaining homeostasis between asymmetric dimethylarginine (ADMA), an endogenous NO synthase (NOS) inhibitor, and arginine, the NOS substrate. We carried out a community-based case-control study of Gambian children to determine whether ADMA and arginine homeostasis is disrupted during severe or uncomplicated malaria infections. Circulating plasma levels of ADMA and arginine were determined at initial presentation and 28 days later. Plasma ADMA/arginine ratios were elevated in children with acute severe malaria compared to 28-day follow-up values and compared to children with uncomplicated malaria or healthy children (p<0.0001 for each comparison). To test the hypothesis that DDAH1 is inactivated during Plasmodium infection, we examined DDAH1 in a mouse model of severe malaria. Plasmodium berghei ANKA infection inactivated hepatic DDAH1 via a post-transcriptional mechanism as evidenced by stable mRNA transcript number, decreased DDAH1 protein concentration, decreased enzyme activity, elevated tissue ADMA, elevated ADMA/arginine ratio in plasma, and decreased whole blood nitrite concentration. Loss of hepatic DDAH1 activity and disruption of ADMA/arginine homeostasis may contribute to severe malaria pathogenesis by inhibiting NO synthesis. During a malaria infection, the vascular endothelium becomes more adhesive, permeable, and prone to trigger blood clotting. These changes help the parasite adhere to blood vessels, but endanger the host by obstructing blood flow through small vessels. Endothelial nitric oxide (NO) would normally counteract these pathological changes, but NO signalling is diminished malaria. NO synthesis is inhibited by asymmetric dimethylarginine (ADMA), a methylated derivative of arginine that is released during normal protein turnover. We found the ratio of ADMA to arginine to be elevated in Gambian children with severe malaria, a metabolic disturbance known to inhibit NO synthesis. ADMA was associated with markers of endothelial activation and impaired tissue perfusion. In parallel experiments using mice, the enzyme responsible for metabolizing ADMA, dimethylarginine dimethylaminohydrolase (DDAH), was inactivated after infection with a rodent malaria. Based on these studies, we propose that decreased metabolism of ADMA by DDAH might contribute to the elevated ADMA/arginine ratio observed during an acute episode of malaria. Strategies to preserve or increase DDAH activity might improve NO synthesis and help to prevent the vascular manifestations of severe malaria.
Jessica Chertow, Matthew Alkaitis, Glenn Nardone, Allison Ikeda, Aubrey Cunnington, Joseph Okebe, Augustine Ebonyi, Madi Njie, Simon Correa, Shamanthi Jayasooriya, Climent Casals-Pascual, Oliver Billker, David Conway, Michael Walther, Hans Ackerman
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The silent path to thousands of merozoites: the Plasmodium liver stage

CiteULike malaria tags - 30 September 2015 - 4:13pm
Nature Reviews Microbiology, Vol. 4, No. 11. (01 November 2006), pp. 849-856, doi:10.1038/nrmicro1529

Plasmodium sporozoites are deposited in the skin of their vertebrate hosts through the bite of an infected female Anopheles mosquito. Most of these parasites find a blood vessel and travel in the peripheral blood circulation until they reach the liver sinusoids. Once there, the sporozoites cross the sinusoidal wall and migrate through several hepatocytes before they infect a final hepatocyte, with the formation of a parasitophorous vacuole, in which the intrahepatic form of the parasite grows and multiplies. During this period, each sporozoite generates thousands of merozoites. As the development of Plasmodium sporozoites inside hepatocytes is an obligatory step before the onset of disease, understanding the parasite's requirements during this period is crucial for the development of any form of early intervention. This Review summarizes our current knowledge on this stage of the Plasmodium life cycle.
Miguel Prudencio, Ana Rodriguez, Maria Mota
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History of the discovery of the malaria parasites and their vectors

CiteULike malaria tags - 30 September 2015 - 4:11pm
Parasites &#38; Vectors, Vol. 3, No. 1. (01 February 2010), 5, doi:10.1186/1756-3305-3-5

Malaria is caused by infection with protozoan parasites belonging to the genus Plasmodium transmitted by female Anopheles species mosquitoes. Our understanding of the malaria parasites begins in 1880 with the discovery of the parasites in the blood of malaria patients by Alphonse Laveran. The sexual stages in the blood were discovered by William MacCallum in birds infected with a related haematozoan, Haemoproteus columbae, in 1897 and the whole of the transmission cycle in culicine mosquitoes and birds infected with Plasmodium relictum was elucidated by Ronald Ross in 1897. In 1898 the Italian malariologists, Giovanni Battista Grassi, Amico Bignami, Giuseppe Bastianelli, Angelo Celli, Camillo Golgi and Ettore Marchiafava demonstrated conclusively that human malaria was also transmitted by mosquitoes, in this case anophelines. The discovery that malaria parasites developed in the liver before entering the blood stream was made by Henry Shortt and Cyril Garnham in 1948 and the final stage in the life cycle, the presence of dormant stages in the liver, was conclusively demonstrated in 1982 by Wojciech Krotoski. This article traces the main events and stresses the importance of comparative studies in that, apart from the initial discovery of parasites in the blood, every subsequent discovery has been based on studies on non-human malaria parasites and related organisms.
Francis Cox
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Mosquito age and avian malaria infection

Malaria Journal - 30 September 2015 - 12:00pm
Background: The immune system of many insects wanes dramatically with age, leading to the general prediction that older insects should be more susceptible to infection than their younger counterparts. This prediction is however challenged by numerous studies showing that older insects are more resistant to a range of pathogens. The effect of age on susceptibility to infections is particularly relevant for mosquitoes given their role as vectors of malaria and other diseases. Despite this, the effect of mosquito age on Plasmodium susceptibility has been rarely explored, either experimentally or theoretically. Methods: Experiments were carried out using the avian malaria parasite Plasmodium relictum and its natural vector in the field, the mosquito Culex pipiens. Both innate immune responses (number and type of circulating haemocytes) and Plasmodium susceptibility (prevalence and burden) were quantified in seven- and 17-day old females. Whether immunity or Plasmodium susceptibility are modulated by the previous blood feeding history of the mosquito was also investigated. To ensure repeatability, two different experimental blocks were carried out several weeks apart. Results: Haemocyte numbers decrease drastically as the mosquitoes age. Despite this, older mosquitoes are significantly more resistant to a Plasmodium infection than their younger counterparts. Crucially, however, the age effect is entirely reversed when old mosquitoes have taken one previous non-infected blood meal. Conclusions: The results agree with previous studies showing that older insects are often more resistant to infections than younger ones. These results suggest that structural and functional alterations in mosquito physiology with age may be more important than immunity in determining the probability of a Plasmodium infection in old mosquitoes. Possible explanations for why the effect is reversed in blood-fed mosquitoes are discussed. The reversal of the age effect in blood fed mosquitoes implies that age is unlikely to have a significant impact on mosquito susceptibility in the field.
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