1.02.2010
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Announcements / Press Releases
African Leaders Malaria Alliance (ALMA) Convenes during African Union Summit [ALMA] — (English)
ALMA will host its first working session at the African Union in Addis Ababa, Ethiopia on February 1, 2010. Convened by President Jakaya Kikwete of Tanzania, African Heads of State and Government will work through challenges and highlight progress to date in the effort to protect all people at-risk from the disease. Both events kick-off the countdown to United Nations Secretary-General Ban Ki-moon’s call for universal coverage of malaria interventions by December 31, 2010...
Monitoring and Evaluation Reference Group (MERG) Meeting [MERG] — (English)
The RBM Monitoring and Evaluation Reference Group held its 14th meeting to review progress made over the last 6 months and plan for the preparation and release of a series of reports on recent achievements and outstanding challenges in malaria control. Mexico and Brazil shared their experience with fighting malaria in the Americas...
Procurement and Supply Chain Management Working Group (PSMWG) Meeting [PSM] — (English)
Representatives from more than 40 partner organisations and endemic countries gathered in January 2010 for the 5th PSM Working Group meeting of the Roll Back Malaria Partnership (RBM). Discussions focused on challenges and next steps in scaling up malaria commodities to reach the 2010 targets and achieving the RBM Partnership 2010-2011 Work Plan targets. Representatives of other RBM Working Groups also joined the meeting to ensure better coordination among the Partnership's different mechanisms...
Zinduka! Malaria Haikubaliki Launch Concert [Malaria Haikubaliki: Tushirikiane Kuitokomeza] — (English)
February 13th, Leaders Club, Dar es Salaam, Tanzania...
RBM HARMONIZATION WORKING GROUP 7th MEETING SUMMARY [HWG] — (English)
With 428 days to go until the 31 December 2010 target for Universal Coverage, one of the key priorities for the HWG is to support countries to achieve that goal. In addition to being a forum for information sharing across the Working Group, additional objectives will focus on: operationalizing and learning from the results of the Round 8 Signature Support Assessment; agreement on coordination mechanisms to provide support to countries to implement their 2010 roadmaps; and agreeing on our workplan and priorities for the coming year. While this is our 7th meeting, we are still learning and therefore in order to ensure the HWG approach appropriately meets country priorities, a special session with program managers from Ghana, Kenya, and Nigeria has also been included in this agenda to jointly determine the HWG’s 2010-2011 priorities and ensure these are appropriately tailored to helping countries meet their malaria control objectives...
2010 Annual Letter from Bill Gates: Introduction [B&M Gates Foundation] — (English)
Two years ago, Melinda and I challenged the health field to set a goal of eventually eradicating malaria. Because it is such a widespread disease, the foundation has backed a number of different types of innovations...
Business Engagement on Malaria in Africa [GBC] — (English)
The majority of new malaria cases and deaths occur in sub-Saharan Africa. Stakeholders from private, public and governmental sectors are coordinating their efforts to address the disease-as evidenced by increased global advocacy and funding for malaria control interventions. The Roll Back Malaria Partnership, a collection of key stakeholders, has defined ambitious goals towards malaria control and elimination...
Exchange of Notes for Grant Aid for the Republic of Congo (The Project for Infectious Diseases Prevention for Children in the Republic of Congo) through the United Nations Children's Fund (UNICEF) [Government of Japan] — (English)
In the Republic of Congo, malaria is the leading cause of mortality among children under five years of age, infants, and expectant and nursing mothers. This grant aid will provide through UNICEF the funds required for the distribution of medications including antimalarial medicines, medications for the correction of anemia, in order to combat malaria, and medicine to counteract diarrhea to regional health facilities across the country...
Uganda Red Cross in aggressive move to fight malaria in Eastern Uganda [Uganda Red Cross] — (English)
Uganda Red Cross Society (URCS) has conducted 155, 739 house to house visits in three districts of Mbale, Kaberamaido and Manafwa encouraging communities to keep their mosquito nets hanged up in a move aimed at combating the deadly malaria...
DRIVE AGAINST MALARIA Update [DAM]
We kennen Julia Samuel nog als presentatrice van Veronica. In 1998 reed zij voor het televieprogramma De Heilige Koe met David Robertson in een Land Rover door Afrika...
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Articles requiring subscription
GSK makes structures of potential antimalarials freely available [BMJ 2010;340:c465] — (English)
GlaxoSmithKline has announced that it will make the chemical structures of 13 500 compounds with potential antimalarial activity freely available on scientific websites to encourage research into new drugs for malaria...
Assessment of the Impact of Climate Shifts on Malaria Transmission in the Sahel [EcoHealth, 10.1007/s10393-010-0274-5] — (English)
We seek to evaluate the impact of hypothetical climate change scenarios on malaria transmission in the Sahel by using a novel mechanistic, high spatial- and temporal-resolution coupled hydrology and agent-based entomology model...
Artemisinin and its derivatives: a novel class of anti-malarial and anti-cancer agents [Chem. Soc. Rev., 2010, 39, 435 - 454, DOI: 10.1039/b816679j] — (English)
In this tutorial review, an effort towards presentation of a comprehensive account of the recent developments on various kinds of artemisinin derivatives including artemisinin dimers, trimers and tetramers has been made and their efficacy towards malaria parasites and different cancer cells lines was compared with that of artemisinins, and various other anti-malarial and anti-cancer drugs. It is expected that this review will provide first-hand information on artemisinin chemistry to organic/medicinal chemists, and pharmacologists working on anticancer and anti-malarial drug development...
The coming-out of malaria gametocytes [Journal of Biomedicine and BiotechnologyVolume 2010 (2010), Article ID 976827, 11 pagesdoi:10.1155/2010/976827] — (English)
This review summarizes recent findings on the role of gametocytes during transmission to the mosquito and particularly focuses on the molecular mechanisms underlying gametocyte activation and emergence from the host erythrocyte during gametogenesis...
Murine Cerebral Malaria Is Associated with a Vasospasm-Like Microcirculatory Dysfunction, and Survival upon Rescue Treatment Is Markedly Increased by Nimodipine [American Journal of Pathology, doi:10.2353/ajpath.2010.090691 ] — (English)
Brain hemodynamics in cerebral malaria (CM) is poorly understood, with apparently conflicting data showing microcirculatory hypoperfusion and normal or even increased blood flow in large arteries. Using intravital microscopy to assess the pial microvasculature through a closed cranial window in the murine model of CM by Plasmodium berghei ANKA, we show that murine CM is associated with marked decreases (mean: 60%) of pial arteriolar blood flow attributable to vasoconstriction and decreased blood velocity...
Full-length recombinant Plasmodium falciparum VAR2CSA binds specifically to CSPG and induces potent parasite adhesion blocking antibodies [Journal of Molecular Biology, doi:10.1016/j.jmb.2010.01.040] — (English)
This is the first study to describe the successful production and functionality of a full-length PfEMP1. The specificity of the binding and anti-adhesion potency of induced IgG, together with high-yield production, encourages the use of full-length PfEMP1 in vaccine development strategies...
Exploring metabolomic approaches to analyse phospholipid biosynthetic pathways in Plasmodium [Parasitology, doi:10.1017/S0031182009991934 ] — (English)
The field of metabolomics is just in its infancy in P. falciparum, hence in this review, we concentrate on the available methodologies and their potential applications for deciphering important biochemical processes of the parasite, such as the astonishingly diverse phospholipid biosynthesis pathways. Elucidating the regulation of the biosynthesis of these crucial metabolites could help design of future anti-malarial drugs...
Integration of control of neglected tropical diseases into health-care systems: challenges and opportunities [The Lancet, Volume 375, Issue 9709, 9 January 2010-15 January 2010, Pages 160-165] — (English)
Although progress has been made in the fight against neglected tropical diseases, current financial resources and global political commitments are insufficient to reach the World Health Assembly's ambitious goals. Increased efforts are needed to expand global coverage. These efforts will involve national and international harmonisation and coordination of the activities of partnerships devoted to control or elimination of these diseases. Rational planning and integration into regular health systems is essential to scale up these interventions to achieve complete eradication of these diseases. Programmes with similar delivery strategies and interventions—such as those for onchocerciasis, lymphatic filariasis, and soil-transmitted helminthiasis—could be managed on the same platform and together. Furthermore, better-resourced programmes—such as those for malaria, HIV/AIDS, and tuberculosis—could work closely with those for neglected tropical diseases to their mutual benefit and the benefit of the entire health system..
Intermittent preventive therapy for malaria in pregnancy: is sulfadoxine-pyrimethamine the right drug? [Clinical Pharmacology & Therapeutics (2010) 87 2, 160–162. doi:10.1038/clpt.2009.284] — (English)
Pregnant women are at particularly high risk for morbidity and mortality from malaria, and pregnancy can markedly affect drug pharmacokinetics, yet the pharmacokinetics of antimalarial drugs in pregnancy has been little studied. An important malaria-control measure in Africa is intermittent preventive therapy (IPT) with sulfadoxine–pyrimethamine (SP) during pregnancy. We discuss IPT with SP in light of several concerns and highlight recent findings from a pharmacokinetic study of SP in this population...
In a Randomized Controlled Trial of Iron Fortification, Anthelmintic Treatment and Intermittent Preventive Treatment of Malaria for Anemia Control in Ivorian Children, only Anthelmintic Treatment Shows Modest Benefit [J. Nutr. (January 28, 2010). doi:10.3945/jn.109.114256] — (English)
In this study, we aimed to assess the effect of iron fortification, intermittent preventive treatment (IPT) of malaria, and anthelmintic treatment on hemoglobin concentration and anemia prevalence among school children...
HO-1 polymorphism as a genetic determinant behind the malaria resistance afforded by haemolytic disorders [Medical Hypotheses, doi:10.1016/j.mehy.2009.12.010] — (English)
Here, we suggest that allelic variants of HO-1, which display significant differences in terms of protein expression, have been selected in endemic malaria areas since the HO-1 enzyme can enhance the protection against malaria conferred by haemolytic diseases This protection apply mainly in what concerns protection against severe malaria forms. Therefore, HO-1 genotyping would be fundamental to determine resistance of a given individual to lethal forms of malaria as well as to common clinical complications typical to haemolytic diseases and would be helpful in the establishment of public health politics...
Countdown to 2015: comparing progress towards the achievement of the health Millennium Development Goals in Ethiopia and other sub-Saharan African countries [Transactions of the Royal Society of Tropical Medicine and Hygiene, doi:10.1016/j.trstmh.2009.12.009] — (English)
Regarding MDG6, good progress was observed in controlling HIV/AIDS and malaria, whereas MDG indicators related to tuberculosis are still below international standards. Therefore, performance was not uniform across programmes. In general, interventions that can be routinely scheduled, such as immunisation, had much higher coverage than those that rely on functional health systems and clinical services proximate to households with 24 h availability, such as skilled care at birth. These mixed results highlight that, although MDGs focus on specific diseases and conditions, targets cannot be achieved without strengthening health systems. It is for this reason that the strategic health plan in Ethiopia is focusing on high-impact and cost-effective health interventions and on health systems strengthening...
Epidemiology and control of frontier malaria in Brazil: lessons from community-based studies in rural Amazonia [Transactions of the Royal Society of Tropical Medicine and Hygiene, doi:10.1016/j.trstmh.2009.12.010] — (English)
We describe the epidemiology of malaria in a frontier agricultural settlement in Brazilian Amazonia. We analysed the incidence of slide-confirmed symptomatic infections diagnosed between 2001 and 2006 in a cohort of 531 individuals (2281.53 person-years of follow-up) and parasite prevalence data derived from four cross-sectional surveys...
A Simple Score to Predict the Outcome of Severe Malaria in Adults [Clinical Infectious Diseases 2010;50:000–000 ] — (English)
Patients with a CAM score <2 at hospital admission may be safely treated in a general ward, provided that renal function can be monitored...
Involvement of CD8(+) T cells in protective immunity against murine blood-stage infection with Plasmodium yoelii 17XL strain [European Journal of Immunology, Volume 9999 Issue 999A,] — (English)
In developing malaria vaccines, the most crucial step is to elucidate the mechanisms involved in protective immunity against the parasites. We found that CD8+ T cells contribute to protective immunity against infection with blood-stage parasites of Plasmodium yoelii ...
Plasmodium falciparum genome-wide scans for positive selection, recombination hot spots and resistance to antimalarial drugs [Nature Genetics, Published online: 31 January 2010 | doi:10.1038/ng.528] — (English)
Antimalarial drugs impose strong selective pressure on Plasmodium falciparum parasites and leave signatures of selection in the parasite genome1, 2; screening for genes under selection may suggest potential drug or immune targets3. Genome-wide association studies (GWAS) of parasite traits have been hampered by the lack of high-throughput genotyping methods, inadequate knowledge of parasite population history and time-consuming adaptations of parasites to in vitro culture. Here we report the first Plasmodium GWAS, which included 189 culture-adapted P. falciparum parasites genotyped using a custom-built Affymetrix molecular inversion probe 3K malaria panel array with a coverage of ~1 SNP per 7 kb. Population structure, variation in recombination rate and loci under recent positive selection were detected. Parasite half-maximum inhibitory concentrations for seven antimalarial drugs were obtained and used in GWAS to identify genes associated with drug responses. This study provides valuable tools and insight into the P. falciparum genome...
A cell-based high-throughput screen validates the plasmodial surface anion channel as an antimalarial target [Molecular Pharmacology Fast Forward. Published on January 25, 2010 as doi:10.1124/mol.109.062711] — (English)
The plasmodial surface anion channel (PSAC) is an unusual small conductance ion channel induced on erythrocytes infected with plasmodia, including parasites responsible for human malaria. Although broadly available inhibitors produce microscopic clearance of parasite cultures at high concentrations and suggest PSAC is an antimalarial target, they have low affinity for the channel and may interfere with other parasite activities. To address these concerns, we developed a miniaturized assay for PSAC activity and carried out a high-throughput inhibitor screen. Approximately 70,000 compounds from synthetic and natural product libraries were screened, revealing inhibitors from multiple structural classes including two novel and potent heterocyclic scaffolds. Single channel patch-clamp studies indicated that these compounds act directly on PSAC, further implicating a proposed role in transport of diverse solutes. A statistically significant correlation between channel inhibition and in vitro parasite killing by a family of compounds provided chemical validation of PSAC as a drug target. These new inhibitors should be important research tools and may be starting points for much-needed antimalarial drugs...
Both hemolytic anemia and malaria parasite-specific factors increase susceptibility to non-typhoidal Salmonella infection in mice [Infect. Immun. doi:10.1128/IAI.00887-09] — (English)
Severe pediatric malaria is an important risk factor for developing disseminated infections with non-typhoidal Salmonella serotypes (NTS). While recent animal studies on this subject are lacking, early work suggests that an increased risk for developing systemic NTS infection during malaria is caused by hemolytic anemia, which leads to reduced macrophage microbicidal activity. Here we established a model for oral S. enterica serotype Typhimurium (S. Typhimurium) challenge in mice infected with Plasmodium yoelii nigeriensis. Initial characterization of this model showed that 5 days after co-inoculation, P. y. nigeriensis infection increased recovery of S. Typhimurium from liver and spleen by approximately 1000-fold. The increased bacterial burden could only be partially recapitulated by antibody-mediated hemolysis, which increased recovery of S. Typhimurium from liver and spleen by tenfold. These data suggested that both hemolysis and P. y. nigeriensis specific factors contributed to increased susceptibility to S. Typhimurium. The mechanism by which hemolysis impaired resistance to S. Typhimurium was further investigated. In vitro, S. Typhimurium was recovered in two-fold higher numbers 24 hours after infection of hemophagocytic macrophages compared to mock-treated macrophages, making it unlikely that reduced macrophage microbicidal activity was solely responsible for hemolysis-induced immunosuppression during malaria. Infection with P. y. nigeriensis, but not antibody-mediated hemolysis, reduced serum levels of IL-12p70 in response to S. Typhimurium challenge. Collectively, studies establishing a mouse model for this co-infection suggest that multiple distinct malaria-induced immune defects contribute to increased susceptibility to S. Typhimurium...
Loss to Self-Heal Malaria upon Taurine Transporter Deletion [Infect. Immun. doi:10.1128/IAI.01159-09] — (English)
Our data indicate that taut-controlled taurine homeostasis is essential for resistance to P. chabaudi malaria. Taurine deficiency, however, due to taut deletion impairs eryptosis of P. chabaudi parasitized erythrocytes and expedites increases in systemic levels of TNF, IL-1, and ammonia presumably contributing to multi-organ failure in P. chabaudi-infected taut-/- mice...
Antimalarial and antitrypanosomal activity of a series of amide and sulfonamide derivatives of a 2,5-diaminobenzophenone [Bioorganic & Medicinal Chemistry, doi:10.1016/j.bmc.2009.09.043 ] — (English)
Here, we describe a series of readily obtainable benzophenone derivatives with antimalarial and antitrypanosomal activity. The most active compounds display submicromolar activity against Plasmodium falciparum. Micromolar activity is obtained against Trypanosoma brucei. Main problem of the compounds is low selectivity. However, there are indications that separation of antimalarial and cytotoxic activity might by possible. In addition, some compounds inhibit human ABC transporter with nanomolar activity...
Vaccination with recombinant Plasmodium vivax MSP-10 formulated in different adjuvants induces strong immunogenicity but no protection [Vaccine, doi:10.1016/j.vaccine.2009.09.046 ] — (English)
Although largely considered benign, Plasmodium vivax causes disease in nearly 75 million people each year and the available strategies are not sufficient to reduce the burden of disease, therefore pointing to vaccine development as a cost-effective control measure. In this study, the P. vivax merozoite surface protein 10 (MSP-10) was expressed as a recombinant protein in Escherichia coli and purified by affinity chromatography. High antigenicity was observed since sera from P. vivax-infected patients strongly recognized rPvMSP10. The immunogenicity of rPvMSP10 was tested in Aotus monkeys, comparing responses induced by formulations with Freund's adjuvant, Montanide ISA720 or aluminum hydroxide. All formulations produced high antibody titers recognizing the native protein in late schizonts. Despite inducing strong antibody production, none of the formulations protected immunized Aotus monkeys upon experimental challenge...
Search for new pharmacophores for antimalarial activity. Part III: synthesis and bioevaluation of new 6-thioureido-4-anilinoquinazolines [European Journal of Medicinal Chemistry, Volume 44, Issue 11, November 2009, Pages 4404-4412 doi:10.1016/j.ejmech.2009.06.001 ] — (English)
Syntheses and in vitro antimalarial evaluation of 42 new thioureidoquinazolines have been carried out. Several analogs showed promising antimalarial effect in the in vitro investigation against chloroquine-sensitive 3D7 strain of Plasmodium falciparum whereas one of the compounds shows 50% curative effect in the mouse model at an oral dose of 100 mg/kg × 4 days against multidrug resistant Plasmodium yoelii nigeriensis...