Senior Management Opportunities at the Global Fund (deadline for applications - February 29)
Director of Strategy, Policy and Performance
Director of Partnerships, Communications and Resource Mobilization
Director of Country Programs
Director of Finance and Procurement
Director of Corporate Services
MACEPA positions:
Monitoring & Evaluation Officer, MACEPA (3176)
Production Manager, MACEPA (3157)
Communications Associate, MACEPA (3189)
Program Manager, MACEPA (3107)
Senior Technical Advisor, MACEPA (3188)
Senior Monitoring & Evaluation Officer, MACEPA (3170)
Program Officer, Advocacy, Policy and Communications (3108)
Program Coordinator, MACEPA (3190)
Please apply on line
PSI Sudan: is requesting the services of a consultant to draft a procurement and supply chain management plan and M&E plan for the Global Fund Round Seven Malaria grant in advance of an LFA assessment in Southern Sudan in April, 2008.
For details please contact Marcie Cook
18.02.2008
Bush highlights malaria campaign [BBC - UK] — (English)
Mr Bush handed out bed nets on his visit to Arusha President George W Bush has said the US will help provide 5.2 million mosquito nets as part of a broader campaign to tackle malaria in sub-Saharan Africa...
President Bush Tours Meru District Hospital, Discusses Malaria [The White House - US] — (English)
THE PRESIDENT: Habari zenu. We have just toured the hospital here, which is on the forefront of Tanzania's fight against malaria. I want thank you, Doc, for leading the tour, and for your compassion. I appreciate the Commissioner welcoming us to the district. I also want to thank Minister Mwakyusa for joining us here in Arusha. I'm grateful to members of the Diplomatic Corps who have joined us...
Bush Touts Anti-Malaria Efforts On Tanzania Stop of African Tour [WSJ - US] — (English)
President Bush handed out hugs and bed nets to battle malaria in Tanzania's rural north Monday, saying the U.S. is part of an international effort to provide enough mosquito netting to protect every child under five in the east African nation...
Tanzanie : Bush annonce une vaste campagne de lutte contre le paludisme [Journal L'Alsace - France] — (Français)
Le président américain George W. Bush a annoncé aujourd'hui à Arusha (Tanzanie) un vaste programme de distribution gratuite de moustiquaires en Tanzanie pour renforcer la lutte contre le paludisme...
Bush unveils anti-malaria plan [Sunday Times - South Africa] — (English)
US President George W. Bush unveiled today a new plan to distribute special bed-nets to defend every Tanzanian child aged one to five from the mosquitoes that spread deadly malaria...
Household cost of malaria overdiagnosis in rural Mozambique [Malaria Journal 2008, 7:33 (18 February 2008)] — (English)
The retrospective study examines the incidence of repeat health consultations in correctly and incorrectly diagnosed malaria patients in a real-life situation: it shows that overdiagnosis of malaria results in a greater number of visits and associated cost for adult patients, and that the poorest individuals pay significantly more proportionally for their healthcar...
Welche Seuchen Deutschland bedrohen [Berliner Morgenpost - Germany] — (Deutsch)
Bill Gates will die Malaria auf der Erde ausrotten. Wie realistisch ist diese Vision?... Stefan Kaufmann: Das ist wirklich eine sehr mutige Ankündigung, denn die Malaria ist nicht leicht zu besiegen. Aber ausgeschlossen ist es nicht. Die Ausrottung von HIV ist gewiss viel schwieriger...
Tropenreisen: Malaria-Schutz nicht vergessen! [gesundheit.de - Germany] — (Deutsch)
Wer eine Fernreise in tropische Länder plant, sollte unbedingt an einen ausreichenden Schutz vor der Infektionskrankheit Malaria denken. "2006 wurden 566 nach Deutschland importierte Fälle gemeldet, 5 Reiserückkehrer sind daran gestorben", warnt Prof. Thomas Löscher vom Berufsverband Deutscher Internisten (BDI)...
17.02.2008
Tanzania's 'Magic Power' net is malaria's new foe [AFP via Goodle News] — (English)
US President George W. Bush will discover one of Africa's most powerful weapons in the fight against malaria: a mosquito net treated with an insecticide that stays potent for five years... "Insecticide-treated bed nets are one of the key tools to prevent malaria and it is important that everybody living in malaria endemic regions has access to one," said Awa Marie Coll-Seck, the executive director of the Roll Back Malaria Partnership...
Kidney drug could save children from malaria brain damage [Guardian Unlimited - UK] — (English)
Researchers have discovered that a drug, widely used in the West by kidney-failure patients, could protect millions of children from the brain damage inflicted by severe malaria. The breakthrough is the work of scientists based at laboratories run by Britain's Medical Research Council in Gambia. They found that children whose blood contains high levels of the hormone erythropoietin (Epo) recover from cerebral malaria, the deadliest form of the disease, better than those who have less...
Trial and error - the war on malaria [Guardian Unlimited - UK] — (English)
It is the world's deadliest disease, killing more than 900,000 a year in Africa alone. But can Bill Gates's dollars create a vaccine that would save a continent's children?...
Two million infested with malaria in Burundi annually [Afrik.com - Paris,France] — (English)
Malaria affects between two million and 2.5 million people per year in Burundi, which makes it the first cause of mortality in the country, Burundi Public Health Minister, Dr Emmanuel Gikoro, declared Sunday...
Alerta de "Malaria" en la República Dominicana [Diaro] — (Español)
Las autoridades de Salud Pública de Canadá Public Health Agency of Canada (PHAC) , están alertando a sus ciudadanos desde la semana pasada, de que si planean viajar de vacaciones a la República Dominicana, deben tomar medicamentos para evitar la infección...
16.02.2008
Gates Foundation's Influence Criticized [NYT - US] — (English)
The chief of malaria for the World Health Organization has complained that the growing dominance of malaria research by the Bill and Melinda Gates Foundation risks stifling a diversity of views among scientists and wiping out the world health agency’s policy-making function...
Unpopular at home, Bush basks in African praise [Reuters South Africa - Johannesburg,South Africa] — (English)
In a reference to Bush's domestic problems, Kikwete added: "Different people may have different views about you and your administration and your legacy. "But we in Tanzania, if we are to speak for ourselves and for Africa, we know for sure that you, Mr. President, and your administration have been good friends of our country and have been good friends of Africa."...
Text of Bush on Africa -Part II [The Associated Press] — (English)
Malaria is another devastating killer. In some African countries, malaria takes as many lives as HIV/AIDS. And the vast majority of those taken by malaria are children under the age of five. Every one of these deaths is unnecessary, because the disease is entirely preventable and treatable. So in 2005, America launched a five-year, $1.2 billion initiative to provide the insecticide-treated beds, indoor spraying, cutting-edge drugs that are necessary to defeat this disease. It's not a complicated strategy. It doesn't take a lot of medical research. We know how to solve the problem. That's why I put the admiral there. He knows how to solve problems. He can get us from point A to point B in a straight line. Well, nearly straight line...
Africa: Working With Partners, President Has Impacted Disease and Conflict, Administration Official Says [allAfrica.com] — (English)
Shortly before she departed Washington with the entourage, Assistant Secretary of State for African Affairs Jendayi Frazer told AllAfrica's Katy Gabel in a wide-ranging interview that the purpose of Bush's trip is "to look at his major initiatives," including efforts to fight HIV/Aids and malaria. "As the president always says, there's no reason for a child to die because it's been bitten by a mosquito," Frazer said...
15.02.2008
WHO welcomes UN Secretary-General's new envoy for malaria [WHO] — (English)
WHO Director-General Dr Margaret Chan welcomes Ray Chambers in his new global role in malaria control. United Nations Secretary-General Ban Ki-moon today announced the appointment of Mr Chambers as his Special Envoy for Malaria...
US businessman Chambers to head UN malaria drive [Reuters South Africa - Johannesburg,South Africa] — (English)
The United Nations appointed U.S. businessman and philanthropist Ray Chambers on Thursday as special envoy for malaria to lead an ambitious bid to slash deaths from the disease in the next few years...
UN names US philanthropist as special envoy for malaria [AFP] — (English)
UN chief Ban Ki-moon on Thursday appointed US philanthropist Ray Chambers as his special envoy for malaria in a bid to give the disease a higher international profile...
A new look inside the brain at cerebral malaria [Science Centric - Sofia,Sofia Town,Bulgaria] — (English)
In the study, a protein (known as a single-chain antibody) that specifically binds a region of the GPIIb/IIIa receptor that is expressed only on activated platelets was attached to microparticles of iron oxide. Using this contrast reagent, it was possible to detect by magnetic resonance imaging (MRI) activated platelets in the brain of mice 6 days after they were infected with Plasmodium berghei. At this time point after infection, clinical symptoms of the disease had not appeared and activated platelets in the brain could not be detected by conventional MRI. These data led the authors to suggest that targeted contrast reagents similar to the one described in their study might prove useful for diagnostic, mechanistic, and therapeutic analyses...
Parasite Biology Clarified With New Model [Science Daily (press release) - USA] — (English)
Apicomplexa may be unfamiliar to most people. But the parasites it describes are all too familiar--causing malaria, toxoplasmosis and several other diseases. These scourges are complex and difficult to study, but a new model system may change that...
Travellers to DR not being warned of malaria risk [CTV.ca - Canada] — (English)
Public health authorities are once again reminding Canadian travellers thinking of a tropical getaway to the Dominican Republic that they need to take anti-malarial medication...
Costs and effects of the Tanzanian national voucher scheme for insecticide-treated nets [Malaria Journal 2008, 7:32 (15 February 2008)] — (English)
The debate continues to rage regarding the relative roles of different models of ITN delivery and, in most studies, the relative cost effectiveness of each is difficult to compare in the absence of reliable data. This paper presents the first study to explore a scaled up voucher model...
Angola: Health Ministry to Present Inquiry On Malaria Indicators [Angola Press Agency (Luanda)] — (English)
A workshop on the presentation of the results of an "Inquiry on Malaria Indicators in Angola" will be held on 18-19 February, in Luanda, by the Health Ministry (Minsa)...
14.02.2008
Genetically altered mosquitoes help fight malaria [Johns Hopkins News-Letter - Baltimore,MD,USA] — (English)
Improved knowledge of the workings of the Anopheles immune system hints at the possibility of creating genetically modified Plasmodium-resistant mosquitoes to stop the spread of malaria. It appears that a protein called GNBP is necessary for mosquitoes that harbor the Plasmodium parasite...
Santé: Un programme contre le paludisme au Bénin [ Arfriqueenligne - France ] — (English)
Le président béninois, Yayi Boni, a procédé jeudi à Cotonou au lancement d'un programme de lutte contre le paludisme initié par le président américain, George Bush, pour 15 pays africains...
13.02.2008
Malaria warning as UK becomes warmer [Telegraph.co.uk - United Kingdom] — (English)
The UK is to be hit by regular malaria outbreaks, fatal heatwaves and contaminated drinking water within five years because of global warming, the Government has warned the N...
Global warmth may bring malaria back to the UK [Times Online - UK] — (English)
Global warmth may bring malaria back to the UKPaul Simons: Weather Eye
According to a Department of Health report issued this week, the South of England may experience outbreaks of malaria during the next 50 to 100 years because of warmer weather...
Global and regional child mortality and burden of disease attributable to zinc deficiency [European Journal of Clinical Nutrition advance online publication 13 February 2008; doi: 10.1038/ejcn.2008.9] — (English)
Zinc deficiency contributes to substantial morbidity and mortality, especially from diarrhea. Zinc supplementation provided as an adjunct treatment for diarrhea may be the best way to target children most at risk of deficiency...
Pregnancy Outcome and Placenta Pathology in Plasmodium berghei ANKA Infected Mice Reproduce the Pathogenesis of Severe Malaria in Pregnant Women [PLOS One] — (English)
Pregnancy-associated malaria (PAM) is expressed in a range of clinical complications that include increased disease severity in pregnant women, decreased fetal viability, intra-uterine growth retardation, low birth weight and infant mortality. The physiopathology of malaria in pregnancy is difficult to scrutinize and attempts were made in the past to use animal models for pregnancy malaria studies. Here, we describe a comprehensive mouse experimental model that recapitulates many of the pathological and clinical features typical of human severe malaria in pregnancy. We used P. berghei ANKA-GFP infection during pregnancy to evoke a prominent inflammatory response in the placenta that entails CD11b mononuclear infiltration, up-regulation of MIP-1 alpha chemokine and is associated with marked reduction of placental vascular spaces. Placenta pathology was associated with decreased fetal viability, intra-uterine growth retardation, gross post-natal growth impairment and increased disease severity in pregnant females. Moreover, we provide evidence that CSA and HA, known to mediate P. falciparum adhesion to human placenta, are also involved in mouse placental malaria infection. We propose that reduction of maternal blood flow in the placenta is a key pathogenic factor in murine pregnancy malaria and we hypothesize that exacerbated innate inflammatory responses to Plasmodium infected red blood cells trigger severe placenta pathology. This experimental model provides an opportunity to identify cell and molecular components of severe PAM pathogenesis and to investigate the inflammatory response that leads to the observed fetal and placental blood circulation abnormalities...
Sulfadoxine-pyrimethamine-based combinations for malaria: a randomised blinded trial to compare efficacy, safety and selection of resistance in Malawi [PLOS One] — (English)
The combination AQ+SP was highly efficacious, despite the low efficacy of SP alone; however, we found evidence that AQ may exert selective pressure for resistance associated mutations many weeks after treatment. This study confirms the return of CQ sensitivity in Malawi and importantly, shows no evidence of the re-emergence of pfcrt 76T after treatment with CQ or AQ. Given the safety record of AQ when used as a prophylaxis, our observations of marked falls in neutrophil counts in the AQ+SP group requires further scrutiny...
Annotation of the Malaria Parasite's Genome Using Comparative Expression Profiling [PLOS One] — (English)
A fundamental problem in systems biology and whole genome sequence analysis is how to infer functions for the many uncharacterized proteins that are identified, whether they are conserved across organisms of different phyla or are phylum-specific. This problem is especially acute in pathogens, such as malaria parasites, where genetic and biochemical investigations are likely to be more difficult. Here we perform comparative expression analysis on Plasmodium parasite life cycle data derived from P. falciparum blood, sporozoite, zygote and ookinete stages, and P. yoelii mosquito oocyst and salivary gland sporozoites, blood and liver stages and show that type II fatty acid biosynthesis genes are upregulated in liver and insect stages relative to asexual blood stages. We also show that some universally uncharacterized genes with orthologs in Plasmodium species, Saccharomyces cerevisiae and humans show coordinated transcription patterns in large collections of human and yeast expression data and that the function of the uncharacterized genes can sometimes be predicted based on the expression patterns across these diverse organisms. We also use a comprehensive and unbiased literature mining method to predict which uncharacterized parasite-specific genes are likely to have roles in processes such as gliding motility, host-cell interactions, sporozoite stage, or rhoptry function. These analyses, together with protein-protein interaction data, provide probabilistic models that predict the function of 926 uncharacterized malaria genes and also suggest that malaria parasites may provide a simple model system for the study of some human processes. These data also provide a foundation for further studies of transcriptional regulation in malaria parasites...
Phase 1 Study of a Combination AMA1 Blood Stage Malaria Vaccine in Malian Children [PLOS One] — (English)
AMA-C1 vaccine is well tolerated and immunogenic in children in this endemic area although the antibody response was short lived...
East Africa: Region to Get Cheaper Mosquito Nets [The Monitor (Kampala) via allAfrica.com] — (English)
HIGH quality mosquito bed nets, long unaffordable to millions of poor people in Uganda and the East African region could now become affordable following the commissioning of a factory in Arusha last week...
12.02.2008
Researchers hunt down fake drug [Nature News] — (English)
Unprecedented pursuit of drug counterfeiters nabs distributors of fake malaria drugs...
A Collaborative Epidemiological Investigation into the Criminal Fake Artesunate Trade in South East Asia [PLOS Medicine] — (English)
An international multi-disciplinary group obtained evidence that some of the counterfeit artesunate was manufactured in China, and this prompted a criminal investigation. International cross-disciplinary collaborations may be appropriate in the investigation of other serious counterfeit medicine public health problems elsewhere, but strengthening of international collaborations and forensic and drug regulatory authority capacity will be required...
Scientists and police lift lid on fake malaria drugs [Reuters UK - UK] — (English)
Scientists and police have exposed a major Asian trade in life-threatening fake malaria drugs, resulting in the seizure of hundreds of thousands of tablets and the arrest of a dealer in southern China...
Fake Malaria Drugs Made In China: Tracking Down The Threat To Global Health [Science Daily (press release) - USA] — (English)
A unique collaboration between scientists, public health workers and police has led to the arrest by the Chinese authorities of alleged traders of fake anti-malarial drugs in southern China and the seizure of a large quantity of drugs. The work, involving teams from across the globe, has highlighted both the growing threat posed by fake pharmaceuticals and the complexities of tracking down those responsible for the trad...
CSI: Malaria – medics help bust fake drugs ring [New Scientist (subscription) - UK] — (English)
Call it CSI: Malaria. This is a real-life tale with a plot to rival any TV crime drama – a crack medical team has hooked up with Interpol and the Chinese security services to disrupt the deadly trade in counterfeit drugs. Now two Chinese nationals face trial charged with distributing fake versions of the anti-malarial drug artesunate...
Scientists trace fake anti-malaria pills to dealer in southern China [Independent - London,England,UK] — (English)
Scientists and police have struck back against the global menace of counterfeit drugs in a unique collaboration that has led to the seizure of hundreds of thousands of fake anti-malaria tablets and the arrest of a key dealer in southern China...
Science Detectives and the Giant Malaria Drug Bust [io9 - San Francisco,CA,USA] — (English)
It's one of the coolest science detective stories in recent memory. The ingredients of this tale include 240,000 blisterpacks of fake malaria drugs, a tiny amount of flower pollen, and forensic palynology. A gang selling fake malaria drugs all across Asia had made millions (killing lots of people in the process), and covered their tracks quite efficiently. But there was one thing they hadn't bargained for. The air around their pill-fabrication plant had left an indelible mark on their products...
A Success Story for Malaria Control [Voice of America - USA] — (English)
A W.H.O. study in four African countries shows how medicine and treated bed nets can mean a big drop in child deaths...
The Fight Against Malaria (By Aisha El-Awady) [Journal of Turkish Weekly - Ankara,Turkey] — (English)
With 40 percent of the world's population living in malaria-endemic regions, malaria is by far the most important tropical parasitic disease affecting humankind and killing more people than any other communicable disease, with the exception of tuberculosis...
Sulphadoxine/pyrimethamine versus amodiaquine for treating uncomplicated childhood malaria in Gabon: a randomized trial to guide national policy [Malaria Journal 2008, 7:31 (12 February 2008)] — (English)
The level of resistance to amodiaquinbe, observed in the present study, may compromise efficacy and duration of use of the AQ/AS combination. Gabonese policy-makers need to plan country-wide and close surveillance of AQ/AS efficacy to determine whether, and for how long, these new recommendations for the treatment of uncomplicated malaria remain valid...
Mangalore: City in control of Malaria [Mangalorean.com - Mangalore,India] — (English)
Mangalore as a city that is enlightened and medically equipped to handle the scrouge of Malaria is now feeling confident of controlling the deadly infection...
Helminth Infection and Eosinophilia and the Risk of Plasmodium falciparum Malaria in 1- to 6-Year-Old Children in a Malaria Endemic Area [PLoS Negl Trop Dis. 2008 Feb 6] — (English)
Malaria infection and other parasitic infections are widespread in developing countries. There is evidence from some studies that intestinal worm infections may increase the risk of developing febrile malaria. However, the evidence is mixed, and some studies have found no effect or even protective effects. A vaccine trial was recently conducted to assess the efficacy of a candidate malaria vaccine. Episodes of malaria were monitored. The vaccine was not protective, but data was also recorded on the prevalence of worm infections. The rates of febrile malaria did not seem to vary according to worm infection in this study. However, because of the relatively low prevalence of worm infection, the study did not have high power. Given the conflicting findings in the literature, and the potential for the effect of worm infection to vary geographically, it is important that larger, definitive studies are conducted, since even quite small effects might be important for global public health...
Congo-Kinshasa: 100 millions de dollars pour lutter contre le VIH et le paludisme [Le Phare (Kinshasa) via allAfrica.com] — (Français)
Il y a d'abord le montant additionnel de 69.984.033 dollars d'un accord de subvention signé par le Programme des Nations Unies pour le Développement avec le Fonds mondial de lutte contre le sida, la tuberculose et le paludisme. Cadre de cet accord : le financement du Fonds mondial accordé à la RDC depuis janvier 2005...
Liberia: Bush Malaria Initiative Donates Drugs [The Inquirer (Monrovia) via allAfrica.com] — (English)
The country office of USAID/Liberia on behalf of President W. Bush Malaria Initiative Program for Africa, yesterday presented to the Ministry of Health and Social Welfare over nearly half a million doses of artemisinin- based combination therapy (ACT) drugrs to the Ministry of Health for the treatment of malaria in the country...
Articles requiring subscription
Rapid Diagnostic Tests for Malaria at Sites of Varying Transmission Intensity in Uganda [The Journal of Infectious Diseases 2008;197:510–518 ] — (English)
Based on the high PPV and NPV, HRP2-based RDTs are likely to be the best diagnostic choice for areas with medium-to-high malaria transmission rates in Africa...
Antibodies to Pre‐erythrocytic Plasmodium falciparum Antigens and Risk of Clinical Malaria in Kenyan Children [The Journal of Infectious Diseases 2008;197:519–526 ] — (English)
Kenyan children with high levels of IgG antibodies to the pre-erythrocytic antigens CSP, LSA-1, and TRAP have a lower risk of developing clinical malaria than children without high levels of these antibodies. The decreased risk of clinical malaria may be mediated in part by prevention of high-density parasitemia...
Potent Antimalarial and Transmission‐Blocking Activities of Centanamycin, a Novel DNA‐Binding Agent [The Journal of Infectious Diseases 2008;197:527–534 ] — (English)
Most treatments for malaria target the blood stage of infection in the human host, although few can also block transmission of the parasite to the mosquito. We show here that the compound centanamycin is very effective against blood-stage malarial infections in vitro and in vivo and has profound effects on sexual differentiation of the parasites in mosquitoes. After drug treatment, parasite development is arrested within the midguts of mosquitoes, failing to produce the infective forms that migrate to the salivary glands. The mechanism of parasite death is associated with modification of Plasmodium genomic DNA. We detected DNA damage in parasites isolated from mice 24 h after treatment with centanamycin, and, importantly, we also detected this DNA damage in parasites within mosquitoes that had fed on these mice 10 days earlier. This demonstrates that damage to parasite DNA during blood-stage infection persists from the vertebrate to the mosquito host and provides a novel biochemical strategy to block malaria transmission...
Insect repellents: Historical perspectives and new developments [Journal of the American Academy of Dermatology, doi:10.1016/j.jaad.2007.10.005] — (English)
Arthropod bites remain a major cause of patient morbidity. These bites can cause local or systemic effects that may be infectious or inflammatory in nature. Arthropods, notably insects and arachnids, are vectors of potentially serious ailments including malaria, West Nile virus, dengue, and Lyme disease. Measures to curtail the impact of insect bites are important in the worldwide public health effort to safely protect patients and prevent the spread of disease. The history of insect repellent (IR) lends insight into some of the current scientific strategies behind newer products. Active ingredients of currently available IRs include N,N-diethyl-3-methylbenzamide (DEET), botanicals, citronella, and, the newest agent, picaridin. Currently, the Environmental Protection Agency's registered IR ingredients approved for application to the skin include DEET, picaridin, MGK-326, MGK-264, IR3535, oil of citronella, and oil of lemon eucalyptus. DEET has reigned as the most efficacious and broadly used IR for the last 6 decades, with a strong safety record and excellent protection against ticks, mosquitoes, and other arthropods. Newer agents, like picaridin and natural products such as oil of lemon eucalyptus are becoming increasingly popular because of their low toxicity, comparable efficacy, and customer approval. Various characteristics and individual product advantages may lead physicians to recommend one agent over another...
Polymerase chain reaction-based identification of Plasmodium (Huffia) elongatum, with remarks on species identity of haemosporidian lineages deposited in GenBank [Parasitology Research] — (English)
Numerous lineages of avian malaria parasites of the genus Plasmodium have been deposited in GenBank. However, only 11 morphospecies of Plasmodium have been linked to these lineages. Such linking is important because it provides opportunities to combine the existing knowledge of traditional parasitology with novel genetic information of these parasites obtained by molecular techniques. This study linked one mitochondrial cytochrome b (cyt b) gene lineage with morphospecies Plasmodium (Huffia) elongatum, a cosmopolitan avian malaria parasite which causes lethal disease in some birds. One species of Plasmodium (mitochondrial cyt b gene lineage P-GRW6) was isolated from naturally infected adult great reed warblers (Acrocephalus arundinaceus) and inoculated to one naive juvenile individual of the same host species. Heavy parasitaemia developed in the subinoculated bird, which enabled identification of the morphospecies and deposition of its voucher specimens. The parasite of this lineage belongs to P. elongatum. Illustrations of blood stages of this parasite are given. Other lineages closely related to P. elongatum were identified. The validity of the subgenus Huffia is supported by phylogenetic analysis. Mitochondrial cyt b gene lineages, with GenBank accession nos. AF069611 and AY733088, belong to Plasmodium cathemerium and P. elongatum, respectively; these lineages have been formerly attributed to P. elongatum and P. relictum, respectively. Some other incorrect species identifications of avian haematozoa in GenBank have been identified. We propose a strategy to minimise the number of such mistakes in GenBank in the future...
Malaria Treatment with Atovaquone-Proguanil in Malaria-immune Adults; Implications for Malaria Intervention Trials and for Pre-Exposure Prophylaxis of Malaria [Antimicrob. Agents Chemother. doi:10.1128/AAC.01367-07] — (English)
Eighty adults in holoendemic Kenya received presumptive treatment with atovaquone/proguanil and were followed closely. The time to first Plasmodium falciparum parasitemia was 32 days. This prolonged prophylaxis period has implications for study design when used in malaria intervention trials and cautiously suggests clinical investigation for potential pre-exposure prophylaxis of malaria...
Simvastatin treatment shows no effect on the incidence of cerebral malaria or parasitemia during experimental malaria [Antimicrob. Agents Chemother. doi:10.1128/AAC.01428-07] — (English)
Statins, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, reduce in vitro growth of Plasmodium falciparum...
The Wheat Germ Cell-Free Based Production of Malaria Proteins for Discovery of Novel Vaccine Candidates [Infect. Immun. doi:10.1128/IAI.01539-07] — (English)
One of the major bottlenecks in malaria research has been the difficulty in recombinant protein expression. Here, we report the application of the wheat germ cell-free system for the successful production of malaria proteins. For proof-of-principle, the Pfs25, PfCSP and PfAMA1 proteins were chosen. These genes contain very high A/T sequences and are also difficult to express as recombinant proteins. In our wheat germ cell-free system, both native and codon optimized version of the Pfs25 genes produced equal amount of proteins. PfCSP and PfAMA1genes without any codon optimization were also expressed. The products were soluble, with yields between 50-200 µg/ml of the translation mixture, indicating that the cell-free system can be used to produce malaria proteins without any prior optimization of their biased codon usage. Biochemical and immunocytochemical analyses of antibodies raised in mice against each protein revealed that every antibody retained its high specificity to the parasite protein in question. The development of parasites in mosquitoes fed patient blood carrying P. falciparum gametocytes and supplemented with our mouse anti-Pfs25 sera was strongly inhibited, indicating that both Pfs25-3D7/WG and Pfs25-TBV/WG retained their immunogenicity. Lastly, we carried out a parallel expression assay of proteins of blood stage P. falciparum. The PCR products of 124 P. falciparum genes chosen from the available database were used directly in a small-scale format of transcription and translation reactions. Autoradiogram testing revealed the production of 93 proteins. Application of this new cell-free based protocol for the discovery of malaria vaccine candidates will be discussed...
Single-dose immunogenicity and protective efficacy of simian adenoviral vectors against Plasmodium berghei [European Journal of Immunology] — (English)
Simian adenoviral vectors (SAd) offer an attractive alternative to standard human adenovirus serotype 5 (AdH5) subunit vaccination, due to pre-existing immunity affecting vaccine performance. We have used a mouse model of liver-stage malaria to test the efficiency of three chimpanzee-origin adenoviral vectors, AdC6, AdC7 and AdC9 containing ME.TRAP as an insert. AdC7 and AdC9 elicited strong immunogenicity (20% of CD8+ T cells in spleen), equivalent to or outperforming AdH5 and inducing sterile protection in 92% (C9), 83% (H5 and C7) and 67% (C6) of the mice, providing the first evidence of single-dose protection to Plasmodium berghei. Protection was afforded by the SAd despite high levels of pre-existing immunity to AdH5. Phenotypic analysis showed that all adenoviral vectors (Ad) elicited CD8+ T cell responses with an effector memory T cell (TEM) phenotype. By contrast, vaccination with poxviral vectors did not confer protection to P. berghei and induced a predominantly CD8+ central memory T cell (TCM) response. Multifunctional CD8+ T cell responses (co-expressing IFN-, TNF- and IL-2) were also induced by the Ad in higher percentages than the poxviral vectors. Our data suggest that TEM cells are important as a first line of defense against fast-replicating pathogens such as murine Plasmodium and demonstrate the potential of replication-defective SAd as future malaria vaccines for humans...
Antimalarial drugs and malignancy: no evidence of a protective effect in rheumatoid arthritis [Annals of the Rheumatic Diseases 2008;67:277-278; doi:10.1136/ard.2007.07570] — (English)
Antimalarial agents, particularly hydroxychloroquine, are frequently used drugs in rheumatology, particularly in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A growing awareness of increased malignancies in these autoimmune rheumatic conditions has raised suspicions that drugs may alter cancer risk in such patients. In vitro, antimalarial agents have been invoked as potentially increasing or decreasing neoplastic processes in breast cancer cells. It has also been suggested that these drugs may decrease the in vitro activity of lymphocytic leukaemia cells. However, there exists no definitive literature to show any explicit effect of antimalarial agents on cancer risk in clinical populations...
Four distinct pathways of hemoglobin uptake in the malaria parasite Plasmodium falciparum [Proc Natl Acad Sci U S A. 2008 Feb 8] — (English)
During the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, which we term the "Big Gulp," appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment-the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (>0.004 fl) vesicles that are marked by the early endosomal regulatory protein Rab5a. A third process, also arising from cytostomes, creates long thin tubes previously termed cytostomal tubes in an actin-dependent manner. The fourth pathway, which we term phagotrophy, is similar to the Big Gulp in that it more closely resembles phagocytosis, except that phagotrophy does not require actin polymerization. Each of these four processes has aspects that are unique to Plasmodium, thus opening avenues to antimalarial therapy...
High levels of erythropoietin are associated with protection against neurological sequelae in African children with cerebral malaria [Proc Natl Acad Sci U S A. 2008 Feb 8] — (English)
Cerebral malaria (CM) in children is associated with a high mortality and long-term neurocognitive sequelae. Both erythropoietin (Epo) and vascular endothelial growth factor (VEGF) have been shown to be neuroprotective. We hypothesized that high plasma and cerebrospinal fluid (CSF) levels of these cytokines would prevent neurological sequelae in children with CM. We measured Epo, VEGF, and tumor necrosis factor in paired samples of plasma and CSF of Kenyan children admitted with CM. Logistic regression models were used to identify risk and protective factors associated with the development of neurological sequelae. Children with CM (n = 124) were categorized into three groups: 76 without sequelae, 32 with sequelae, and 16 who died. Conditional logistic regression analysis matching the 32 patients with CM and neurological sequelae to 64 patients with CM without sequelae stratified for hemoglobin level estimated that plasma Epo (>200 units/liter) was associated with >80% reduction in the risk of developing neurological sequelae [adjusted odds ratio (OR) 0.18; 95% C.I. 0.05-0.93; P = 0.041]. Admission with profound coma (adjusted OR 5.47; 95% C.I. 1.45-20.67; P = 0.012) and convulsions after admission (adjusted OR 16.35; 95% C.I. 2.94-90.79; P = 0.001) were also independently associated with neurological sequelae. High levels of Epo were associated with reduced risk of neurological sequelae in children with CM. The age-dependent Epo response to anemia and the age-dependent protective effect may influence the clinical epidemiology of CM. These data support further study of Epo as an adjuvant therapy in CM...
Antimalarial dosing regimens and drug resistance [Trends Parasitol. 2008 Feb 7] — (English)
The contribution of underdosing to antimalarial treatment failure has been underappreciated. Most recommended dosage regimens are based on studies in non-pregnant adult patients. Young children and pregnant women, who bear the heaviest malaria burden, have the highest treatment failure rates. This has been attributed previously to lower immunity, although blood concentrations of many antimalarial drugs are significantly lower in pregnant women and young children than in non-pregnant adults. Nevertheless, there have been no studies of higher dosages. Sub-therapeutic concentrations will certainly contribute to poorer responses to treatment and will fuel the emergence and spread of antimalarial drug resistance. There is an urgent need for studies to optimise antimalarial dosage regimens in infants, young children and pregnant women, both to improve cure rates and to prolong the useful therapeutic lives of antimalarial drugs...
Disruption of Rosetting in Plasmodium falciparum Malaria with Chemically Modified Heparin and Low Molecular Weight Derivatives Possessing Reduced Anticoagulant and Other Serine Protease Inhibition Activities [J Med Chem. 2008 Feb 9] — (English)
Severe malaria has been, in part, associated with the ability of parasite infected red blood cells to aggregate together with uninfected erythrocytes to form rosettes via the parasite protein PfEMP-1. In this study, inhibitors of rosetting by the Plasmodium falciparum strain R-29, based on chemically modified heparin polysaccharides (IC 50 = 1.97 x 10 (-2) and 3.05 x 10 (-3) mg.mL (-1)) and their depolymerized, low molecular weight derivatives were identified with reduced anticoagulant and protease (renin, pepsin, and cathepsin-D) activities. Low molecular weight derivatives of the two most effective inhibitors were shown to have distinct minimum size and strain-specific structural requirements for rosette disruption. These also formed distinct complexes in solution when bound to platelet-factor IV...
The relationship between terrorist activities and cases of malaria in the eastern and south-eastern regions of Turkey, 1984–1998 [Transactions of the Royal Society of Tropical Medicine and Hygiene, Volume 102, Issue 3, March 2008, Pages 255-258] — (English)
The objective of this study was to determine whether cases of malaria are related to terrorist activities that have occurred in the eastern and south-eastern regions of Turkey. Some of the determinants related to malaria have been investigated using a national dataset for 11 provinces located in these regions of Turkey. In these regions, both terrorist activity and cases of malaria were common from 1984 to 1998. A multiple regression technique was used to identify the variables that are significantly associated with cases of malaria. Annual incidence of malaria was chosen as the dependent variable along with three independent (explanatory) variables: annual number of terrorist incidences, people per healthcare technician and number of thick blood films per 100 000 people. Based on this analysis, it is determined that the annual number of terrorist incidences has been associated with the annual number of malaria cases in these regions of Turkey since the beginning of terrorist activity in 1984...
Implications of imaging malaria sporozoites [Trends in Parasitology, In Press, Corrected Proof, Available online 14 February 2008 ] — (English)
The sporozoites of Plasmodium parasites undergo several transmigrations before their establishment in the hepatocytes of a vertebrate host. Techniques that illustrate parasite intra-vital migration and their interaction with host cells will advance the understanding of parasite biology. In a recent publication, Amino et al. provided a detailed protocol for in vivo imaging of Plasmodium berghei sporozoites in the dermis. The report has important implications in the dissection of malaria parasite biology...
Insect repellents: Historical perspectives and new developments [Journal of the American Academy of Dermatology, In Press, Corrected Proof, Available online 13 February 2008 ] — (English)
Arthropod bites remain a major cause of patient morbidity. These bites can cause local or systemic effects that may be infectious or inflammatory in nature. Arthropods, notably insects and arachnids, are vectors of potentially serious ailments including malaria, West Nile virus, dengue, and Lyme disease. Measures to curtail the impact of insect bites are important in the worldwide public health effort to safely protect patients and prevent the spread of disease. The history of insect repellent (IR) lends insight into some of the current scientific strategies behind newer products. Active ingredients of currently available IRs include N,N-diethyl-3-methylbenzamide (DEET), botanicals, citronella, and, the newest agent, picaridin. Currently, the Environmental Protection Agency's registered IR ingredients approved for application to the skin include DEET, picaridin, MGK-326, MGK-264, IR3535, oil of citronella, and oil of lemon eucalyptus. DEET has reigned as the most efficacious and broadly used IR for the last 6 decades, with a strong safety record and excellent protection against ticks, mosquitoes, and other arthropods. Newer agents, like picaridin and natural products such as oil of lemon eucalyptus are becoming increasingly popular because of their low toxicity, comparable efficacy, and customer approval. Various characteristics and individual product advantages may lead physicians to recommend one agent over another...
Structures of P. falciparum Protein Kinase 7 Identify an Activation Motif and Leads for Inhibitor Design [Structure, Volume 16, Issue 2, 12 February 2008, Pages 228-238] — (English)
Malaria is a major threat to world health. The identification of parasite targets for drug development is a priority and parasitic protein kinases suggest themselves as suitable targets as many display profound structural and functional divergences from their host counterparts. In this paper, we describe the structure of the orphan protein kinase, Plasmodium falciparum protein kinase 7 (PFPK7). Several Plasmodium protein kinases contain extensive insertions, and the structure of PFPK7 reveals how these may be accommodated as excursions from the canonical eukaryotic protein kinase fold. The constitutively active conformation of PFPK7 is stabilized by a structural motif in which the role of the conserved phosphorylated residue that assists in structuring the activation loop of many protein kinases is played by an arginine residue. We identify two series of PFPK7 ATP-competitive inhibitors and suggest further developments for the design of selective and potent PFPK7 lead compounds as potential antimalarials...
Prepared in cooperation with WHO ANGOLA INFO.
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