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Author(s): Ngozi A. Erondu [sup.1] [sup.2] , Ifeyinwa Aniebo [sup.1] [sup.3] [sup.4] , Catherine Kyobutungi [sup.5] , Janet Midega [sup.1] [sup.6] , Emelda Okiro [sup.7] , Fredros Okumu [sup.1] [sup.8] [...]

The multiprotein complex PTEX enables malaria-causing parasites to survive inside red blood cells. Studies reveal how PTEX assembles, and identify a function for one of the complex's proteins, EXP2.Structural analysis reveals how the PTEX complex assembles., Author(s): Tania F. de Koning-WardAuthor Affiliations:Spotlight on proteins that aid malaria PTEX consists of five proteins[sup.3] : HSP101, PTEX150, EXP2, PTEX88 and TRX2. Multiple HSP101, PTEX150 and EXP2 molecules assemble [...]

During their intraerythrocytic development, malaria parasites export hundreds of proteins to remodel their host cell. Nutrient acquisition, cytoadherence and antigenic variation are among the key virulence functions effected by this erythrocyte takeover. Proteins destined for export are synthesized in the endoplasmic reticulum (ER) and cleaved at a conserved (PEXEL) motif, which allows translocation into the host cell via an ATP-driven translocon called the PTEX complex. We report that plasmepsin V, an ER aspartic protease with distant homology to the mammalian processing enzyme BACE, recognizes the PEXEL motif and cleaves it at the correct site. This enzyme is essential for parasite viability and ER residence is essential for its function. We propose that plasmepsin V is the PEXEL protease and is an attractive enzyme for antimalarial drug development., The human malaria parasite Plasmodium falciparum exports an estimated 200-300 proteins into the host erythrocyte (1,2). In doing so, the parasite remodels the cytoskeleton and plasma membrane to create cytoadherence [...]

For many pathogens the availability of genome sequence, permitting genome-dependent methods of research, can partially substitute for powerful forward genetic methods (genome-independent) that have advanced model organism research for decades. [...]

Plasmodium knowlesi is an intracellular malaria parasite whose natural vertebrate host is Macaca fascicularis (the 'kra' monkey); however, it is now increasingly recognized as a significant cause of human malaria, [...]

Malaria continues to devastate sub-Saharan Africa owing to the emergence of drug resistance to established antimalarials and to the lack of an efficacious vaccine. Plasmodium species have a unique streamlined purine pathway in which the dual specificity enzyme purine nucleoside phosphorylase (PNP) functions in both purine recycling and purine salvager (1-4). To evaluate the importance of PNP in an in vivo model of malaria, we disrupted PyPNP, the gene encoding PNP in the lethal Plasmodium yoelii YM strain. P. yoelii parasites lacking PNP were attenuated and cleared in mice. Although able to form gametocytes, PNP-deficient parasites did not form oocysts in mosquito midguts and were not transmitted from mosquitoes to mice. Mice given PNP-deficient parasites were immune to subsequent challenge to a lethal inoculum of P. yoelii YM and to challenge from P. yoelii 17XNL, another strain. These in vivo studies with PNP-deficient parasites support purine salvage as a target for antimalarials. They also suggest a strategy for the development of attenuated nontransmissible metabolic mutants as blood-stage malaria vaccine strains., Malaria is caused by a protozoan parasite of the genus Plasmodium and is the most deadly vector-borne disease in the world. The World Health Organization estimates that there are 300--500 [...]

In 1987 Rip Ballou taped an ice-cream carton to his arm. The young US Army doctor was doing his bit for science; inside the carton five hungry mosquitoes set about [...]

The success of immunization with irradiated sporozoites is unparalleled among the current vaccination approaches against malaria, but its mechanistic underpinnings have yet to be fully elucidated. Using a model mimicking natural infection by Plasmodium yoelii, we delineated early events governing the development of protective CD8[sup.+] T-cell responses to the circumsporozoite protein. We demonstrate that dendritic cells in cutaneous lymph nodes prime the first cohort of CD8[sup.+] T cells after an infectious mosquito bite. Ablation of these lymphoid sites greatly impairs subsequent development of protective immunity. Activated CD8[sup.+] T cells then travel to systemic sites, including the liver, in a sphingosine-1-phosphate (S1P)-dependent fashion. These effector cells, however, no longer require bone marrow-derived antigen-presenting cells for protection; instead, they recognize antigen on parenchymal cells--presumably parasitized hepatocytes. Therefore, we report an unexpected dichotomy in the tissue restriction of host responses during the development and execution of protective immunity to Plasmodium., Author(s): Sumana Chakravarty [1]; Ian A Cockburn [1]; Salih Kuk [1]; Michael G Overstreet [1]; John B Sacci [2]; Fidel Zavala (corresponding author) [1] After an animal has been immunized [...]

Plasmodium falciparum, the malaria parasite, is a successful human pathogen, and specific immunity to malaria is attributed to the occurrence of cytotoxic lymphocytes or antibodies. It is shown that intact malaria-infected erythrocytes bind to dendritic cells and inhibit their maturation, reducing their ability to stimulate T cells.

Efforts to improve the health of a community will not succeed if the community does not want them to.Efforts to improve the health of a community will not succeed if the community does not want them to., Author(s): Lucas LaursenAuthor Affiliations:How building trust has proved central to overcoming malaria Researchers at the Macha Research Trust have made strides in tackling malaria in southern Zambia. [see PDF for [...]

Research has identified xanthurenic acid as being a gametocyte-activating factor in malaria disease transmission. Gametogenesis can be induced in vitro with low concentrations of xanthurenic acid at pH concentrations of between 7.4 and 8.0 to 8.2. Further drugs research will be based on these findings in a bid to stop malaria transmission.

African studies show that severe malaria is linked with the ability of erythrocytes infected with Plasmodium falciparum parasite to bind uninfected erythrocytes into rosettes. A study shows that the parasite ligand for P.falciparum clone rosetting is PfEMP1 and that complement-receptor 1 is important to the formation of rosettes. The new adhesive function for PfEMP1 is described, indicating that the CR1 polymorphisms in Africans influencing erythrocyte and PfEMP1 interaction, could protect against malaria.

A large case-control study of Gambian children reveals that homozygotes for the TNF2 allele, a variation in the TNF-alpha gene promoter region, are associated with death or chronic neurological sequelae due to cerebral malaria. The disease association characteristic of the TNF2 allele is independent of HLA class I and class II variation, and indicates that modulatory cytokine gene polymorphisms influence the consequence of chronic infection. However, a biological advantage in homozygotes counters the manifestation of elevated risk of cerebral malaria.

There are trillions of cells in the human body and around 200 distinct cell types, some of which can be hijacked as safe houses by deadly pathogens. Malaria parasites, which [...]

BRENDAN S. CRABB & JAMES G. BEESON Unravel natural immunity Burnet Institute, Melbourne, Australia Parasite development goes through several distinct stages in both the human host and mosquito (see 'One [...]

We previously showed that Plasmodium falciparum has the type II fatty acid synthesis (FAS) pathway and outlined the uniqueness of this pathway in terminating at C14 acyl chain. That the [...]

Author(s): Michael F Good [1]; Denise L Doolan [1] The causative agent of malaria, the Plasmodium sp. parasite, was shown to be transmitted by mosquitoes over 100 years ago. Since [...]

Author(s): Peter R. Preiser [1] Malaria, one of the most widespread infectious diseases, is caused by the protozoan parasite Plasmodium. Nearly half of the population of the world is at [...]

Bowman and colleagues have revealed the entire sequence of the Plasmodium falciparum chromosome 3, giving 7% of the total P. falciparum genome. The genome is complex but there is a certain organization where clusters of genes encoding proteins produced at similar stages in the life cycle appear to be grouped in certain chromosomes. The genome sequence should be used to identify new drug targets, to help in developing vaccines and to understand the pathogenesis of malaria.

Microorganisms have developed many strategies to suppress or subvert the immune system, and successful ones can fine-tune immune responses. The malaria parasite Plasmodium falciparum, lives in red blood cells and is transmitted by mosquitoes. Urban and colleagues have discovered a new way in which P. falciparum checks the immune system, by preventing maturation of dendritic cells. This impedes functional activity of dendritic cells, and it is suggested that the antigen PfEMP1 is responsible for binding to dendritic cells.

Research on pregnant women and their susceptibility to malaria has been carried out in Kenya and on the Thai-Burmese border. Women pregnant for the first time are more likely to suffer attacks of malaria, and this is linked to lack of anti-adhesion antibodies. Such antibodies provide protection for pregnant women against malaria. There is a strong case for the development of an anti-adhesion vaccine to protect women against maternal malaria in tropical countries.

Spence, P.J. et al. Nature 498, 228-231 (2013) The authors show that transmission of the malaria parasite Plasmodium chabaudi chabaudi through its mosquito vector modifies the asexual blood-stage parasite, thus [...]

A newly published comprehensive analysis of global spending on antimalaria efforts found that annual funding nearly tripled from 2006 to 2010, growing from just under $1 billion to more than [...]

Malaria researchers are disputing a high-profile paper that suggests the disease may kill twice as many people worldwide as previously estimated. The research (C. J. L. Murray et al. Lancet [...]

The periodicity of the life cycle of malaria parasites during host infection suggests that these organisms are regulated by circadian rhythms. Aidan O'Donnell at the University of Edinburgh, UK, and [...]

Jun 24 A close study of blood samples taken from 190 yellow baboons (Papio cynocephalus) revealed a genetic variation associated with the emergence of malaria resistance in wild baboons (Nature, [...]

Innate immune defenses in the mosquito gut, triggered by normal microflora, may influence whether plasmodium parasites can develop successfully inside their vector hosts, report Yuemei Dong and colleagues in PLoS [...]

Jan 16 Researchers identified two key proteins, named TRAP and saglin, that allow the malaria-causing Plasmodium parasite to invade mosquito salivary glands, an essential step in the spread of malaria [...]

The malaria parasite seems to take an hour or more to wiggle to its first target, the liver, after being injected into a person by a mosquito. Anthony Siau et [...]

An international meeting in Scheveningen, the Netherlands, rejected moves by the US to set up a common fund for malaria research, saying that it was premature and unworkable. It was concluded that the Multilateral Initiative on Malaria can only progress in fighting malaria by a long term effort made by the various agencies working together.

There is an increasing consensus that malaria deserves special attention as it kills over 1 million people each year, and one third of all people live in areas where they risk catching it. The parasite is also becoming increasingly resistance to drugs, while research and development of new drugs has been virtually abandoned. However the Multilateral Initiative in Malaria (MIM) has been set up by research and development agencies and industry to help reverse withdrawal from the field.

The Wellcome Trust's Unit for Policy Research in Science and Medicine reported that funding for malaria research has dwindled considerably, despite the continued health risks posed by the disease. The trust attributed the significant decline in malaria research funding to reduced US military spending.

A genomic research institute, which will conduct research on the genome of the malaria causing bacterium Plasmodium falciparum, will be established in Tunisia. Dr. Daniel Cohen, Director of the Centre des Etudes du Polymorphisme Humain in Paris, France, is responsible for the establishment of the institute, which will need nearly $5 billion. The institute's research programs will involve the determination of cloned DNA expression tags and complete sequencing of the bacterial genome.