17.12.2007
The Intolerable Burden of Malaria: A New Look at the Numbers [The American Journal of Tropical Medicine and Hygiene, January 2001, Volume 64, 1 Supplement] — (English)
The ears of the hippopotamus: manifestations, determinants, and estimates of the malaria burden; The malaria burden and Africa; The malaria burden and the need for research and capacity strengthening in Africa; The intolerable burden of malaria: a new look at the numbers; The public health impact of chloroquine resistance in Africa; All-cause mortality among young children in western Kenya. VI: the Asembo Bay Cohort Project; The burden of malaria in pregnancy in malaria-endemic areas; The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa; The cost-effectiveness of antenatal malaria prevention in sub-Saharan Africa; Gaps in the childhood malaria burden in Africa: cerebral malaria, neurological sequelae, anemia, respiratory distress, hypoglycemia, and complications of pregnancy; Impact of Plasmodium falciparum malaria on performance and learning: review of the evidence; Toward a framework and indicators for monitoring Roll Back Malaria; The economic burden of malaria; The neglected burden of Plasmodium vivax malaria...
Haemoglobin and haematocrit: the threefold conversion is also non valid for assessing anaemia in Plasmodium vivax malaria-endemic settings [Malaria Journal 2007, 6:166 (17 December 2007)] — (English)
The study shows that the standard threefold conversion from haematocrit to haemoglobin underestimates the prevalence of anaemia and low levels of haemoglobin in children and adults with vivax malaria...
Complement activation in Ghanaian children with severe Plasmodium falciparum malaria [Malaria Journal 2007, 6:165 (17 December 2007)] — (English)
This study shows that complement activation contributes to anaemia and respiratory distress in acute childhood malaria, possibly through induction of erythrophagocytosis and haemolysis...
Sequence analysis of Plasmodium falciparum cytochrome b in multiple geographic sites [Malaria Journal 2007, 6:164 (17 December 2007)] — (English)
A study of sequence variation of Plasmodium falciparum cytochrome b from various locations on three continents discussing possible relevance to clinical failure...
Ghana: U.S. Joins Country's Anti-Malaria Crusade [Accra Mail (Accra)] — (English)
The United States (U.S.) Ambassador to Ghana, Madam Pamela E. Bridgewater has launched a National Malaria Control Programme called the President's Malaria Initiative (PMI) at Agona Abodum in the Central Region...
If malaria can be transmitted through a mosquito's bite, why not HIV? [Scienceline] — (English)
In a typical meal, a mosquito eats just a thousandth to a hundredth of a milliliter out of the average person’s 5.5 liters of blood. That’s like drinking a two-liter soda bottle of water out of an Olympic-sized pool. From its tiny snack, the mosquito has hardly a chance of ingesting HIV. While the amount of the virus in blood varies from a few dozen to several hundred thousand viruses per milliliter, usually the levels are low. Blood left on the sloppy mosquito’s mouth is highly unlikely to have any HIV in it. If the mosquito bit someone with 1,000 viruses per milliliter, for example, there would be a 1 in 10 million chance of injecting just one virus body into another victim...
16.12.2007
WHO recommended insecticide products treatment of mosquito nets for malaria vector control [WHOPES] — (English)
Updated December 2007...
WHO recommended long-lasting insecticidal mosquito nets [WHOPES] — (English)
Updated December 2007...
MIM News and Opportunities [MIM] — (English)
December issue...
15.12.2007
New target for anti-malaria drugs [BBC -
United Kingdom] — (English)
Targeting a key protein may help overcome the malaria parasite's increasing resistance to conventional drugs, UK researchers say...
Ausbruch kommt oft erst später
[Allgemeine Zeitung - Germany] — (Deutsch)
Eine Malaria kann auch vergleichsweise lange nach dem Urlaub ausbrechen. Die meisten Attacken treten innerhalb von drei Monaten nach der Rückkehr auf, teilt der Berufsverband Deutscher Internisten mit...
Malaria noch Wochen nach dem Urlaub möglich [Die Welt - Germany] — (Deutsch)
Eine Malaria kann auch vergleichsweise lange nach dem Urlaub ausbrechen, warnen Internisten. Außerdem im Travel Ticker: Zwei neue Lufthansa-Ziele in China, die Christusstatue in Rio de Janeiro bekommt ein Lifting, zwei neue Ryanair-Ziele in Polen und außerdem: Weitere Kreuzfahrtanbieter führen Treibstoffzuschlag ein...
14.12.2007
Eradicating Malaria [editorial] [Calibre MacroWorld - United States ] — (English)
At a "Health Summit" organised by the 19 Governors of Northern States in Kaduna recently it was emphasised that strategies should be developed to reduce the scourge of malaria. Organised in conjunction with the United Nations Children's Education Fund, UNICEF, the summit discussed on the possibility of reducing the level of infant mortality of children under five years of age from malaria...
Mal 47 Malaria Vaccine Trial - So Far So Good [Silo Breaker - United States ] — (English)
Fifteen months after the first trial of the phase 2 (Mal 47) of the RTS'S malaria vaccine was administered to children in the Kintampo North and South Districts, ADM can confirm that most of these children are looking healthy and strong. Lawrence Gyabaa, Assistant Research Officer, KHRC who has done a study on the Mal 47 told ADM that the primary objective of his study was to investigate how community members perceived malaria prevention through the use of vaccines...
Erderwärmung fördert Verbreitung von Tropenkrankheiten [net-tribune - Germany] — (Deutsch)
Eine Rückkehr der Malaria hält der Infektiologe dagegen für unwahrscheinlich. Bis 1955 habe es zwar an Nord- und Ostsee und am Niederrhein immer wieder Fälle gegeben. Die Malaria sei in Europa aber durch die Verbesserung der Wohnverhältnisse und die Trockenlegung von Feuchtgebieten besiegt worden. Auch große Cholera-Epidemien träten nur in Ländern ohne sichere Trinkwasserversorgung auf...
Ghana: Country Gets $51 Million for Malaria Control [Public Agenda (Accra)] — (English)
In Ghana, malaria accounts for more than 44 percent of visits to health facilities. UNICEF estimates that 20 thousand Ghanaian children under the age of five die each year of malaria...
No malaria for 34 years - Adeboye [Nigerian Tribune - Ibadan,Nigeria] — (English)
THE General Overseer of the Redeemed Christian Church of God (RCCG), Pastor Enoch Adeboye, has highlighted the power of God when he claimed that he had not had malaria since he became born again in 1973...
Malaria cases on rise in Morang [Gorkhapatra - Kathmandu,Nepal] — (English)
District Public Health Office in Morang informed that cases of malaria have been increased in the North-east part of the district for some time...
13.12.2007
Triple identity for malaria [Nature] — (English)
A major puzzle in understanding malaria is the wide range of clinical conditions seen in infected children — from mild flu-like symptoms to coma and death. A large-scale transcriptional analysis of malaria parasites isolated from human patients has uncovered a possible clue to this variation: Plasmodium falciparum exists in its human host in three different physiological states. These can be described as active growth, a response to starvation, and an environmental stress response. This finding has important implications both for treatment with current drugs and for future drug and vaccine development...
Malaria Parasites May Be Allies Against Drug Resistance [Scientific American - United States] — (English)
At least a million people die of malaria every year. And one problem with treating the disease may be…treating the disease. The current dosages of drugs used to fight malaria may sometimes make the problem worse—by allowing the malaria-causing parasites to become drug resistant faster. That’s what evolutionary biologists said recently in the Proceedings of the National Academy of Sciences...
Competitive release and facilitation of drug-resistant parasites after therapeutic chemotherapy in a rodent malaria model [PNAS - United States] — (English)
Malaria infections frequently consist of mixtures of drug-resistant and drug-sensitive parasites. If crowding occurs, where clonal population densities are suppressed by the presence of coinfecting clones, removal of susceptible clones by drug treatment could allow resistant clones to expand into the newly vacated niche space within a host. Theoretical models show that, if such competitive release occurs, it can be a potent contributor to the strength of selection, greatly accelerating the rate at which resistance spreads in a population. A variety of correlational field data suggest that competitive release could occur in human malaria populations, but direct evidence cannot be ethically obtained from human infections. Here we show competitive release after pyrimethamine curative chemotherapy of acute infections of the rodent malaria Plasmodium chabaudi in laboratory mice. The expansion of resistant parasite numbers after treatment resulted in enhanced transmission-stage densities. After the elimination or near-elimination of sensitive parasites, the number of resistant parasites increased beyond that achieved when a competitor had never been present. Thus, a substantial competitive release occurred, markedly elevating the fitness advantages of drug resistance above those arising from survival alone. This finding may explain the rapid spread of drug resistance and the subsequently brief useful lifespans of some antimalarial drugs. In a second experiment, where subcurative chemotherapy was administered, the resistant clone was only partly released from competitive suppression and experienced a restriction in the size of its expansion after treatment. This finding raises the prospect of harnessing in-host ecology to slow the spread of drug resistance...
General Assembly urges stepped up effort to meet 'World Fit for Children' pledges, as high-level review of 2002 special session concludes at Headquarters [ReliefWeb - United Kingdom] — (English)
Eritrea was also combating HIV and AIDS, as well as other diseases such as malaria and tuberculosis. It had exceeded the Roll Back Malaria goal, and was now ranking as one of the top five countries in Africa in fighting that disease...
Studies from A. Kaiser et al add new findings in the area of malaria [Calibre Macroworld - United States] — (English)
According to recent research from Germany, "The increasing resistance of the malaria parasites enforces alternative directions in finding new drug targets (see also Malaria). Present findings from the malaria parasite Plasmodium vivax, causing tertiary malaria, suggest eukaryotic initiation factor 5A (eIF-5A) to be a promising target for the treatment of malaria."...
Ghana: Clinical Trials of Malaria Vaccine To Ascertain Safety, Efficacy Begin [Therapeutics Daily - United States] — (English)
Clinical trials aimed at ascertaining the safety of a malaria vaccine when given alongside polio and tuberculosis vaccines, have begun here...
Rwanda: Eradicate Malaria With Growth, Not Nets [The New Times (Kigali)] — (English)
This month, the World Health Organization (WHO) will give four brands of Long-Lasting Insecticide-Treated mosquito net its seal of approval, increasing the total to seven. This is good news. The market for these anti-malarial bed-nets is mainly foreign aid agencies which only buy WHO-approved nets, so more authorised products will increase competition, drive prices down a bit and should, in theory, make them more available to those in need. But aid donors' single-minded determination to give everyone nets is just not going to eradicate malaria...
Ghana: Single Dose Malaria Therapy Under Trial at KHRC [Accra Mail (Accra)] — (English)
Kintampo Health Research Centre (KHRC) is undertaking a study aimed to obtain a safe, effective and affordable Artemisinin-based Combination Therapy (ACT) for the treatment of uncomplicated Plasmodium falciparum malaria, especially in Africa...
Institut Pasteur develops a candidate vaccine against malaria [Afriqu'Echos Magazine - Ecublens-Lausanne,Switzerland] — (English)
Malaria beware ! Following on from the GSK laboratory news last month, it’s now the turn of the Institut Pasteur to announce the development of a candidate vaccine which, conceptually speaking, has largely proved its interest. Its code name is MSP3. If the trials currently under way prove conclusive, this will be excellent news for the 2 thousand million people under threat from this disease across the world...
Malaria is a bane on national economy - Health Minister [Joy Online - Accra,Ghana] — (English)
Major Courage Quashigah (rtd), Health Minister on Monday considered malaria as a serious threat to the peoples’ health and the economy, stressing the need for urgent actions to prevent the disease from eroding the National Health Insurance Fund...
Turning plants into pills in Kenya [SciDev.Net - United Kingdom] — (English)
Traditional healers are joining forces with plant chemists in Kenya to develop antimalarials isolated from plants, reports Tatum Anderson...
BinaxNOW Malaria FDA cleared - Unique rapid diagnostic testing from Inverness Medical [Labhoo - United Kingdom ] — (English)
Inverness Medical offers BinaxNOW Malaria for the rapid diagnosis of malaria infection - the only rapid test for malaria cleared by the FDA. BinaxNOW Malaria detects Plasmodium falciparum, P. vivax, P. malariae and P. ovale antigens in whole blood in as little as 15 minutes and is ideal for field or laboratory use with its easy-to-use test card format. Consequently, this can ensure the most appropriate treatment is administered before protracted laboratory tests are complete, helping to prevent the occurrence of unnecessary complications...
12.12.2007
A Randomized Open-Label Trial of Artesunate- Sulfadoxine-Pyrimethamine with or without Primaquine for Elimination of Sub-Microscopic P. falciparum Parasitaemia and Gametocyte Carriage in Eastern Sudan [PLOS One] — (English)
Addition of primaquine to artemisinin combination treatment did not improve elimination of parasitaemia and prevention of gametocyte carriage in carriers with low-density parasitaemia in the dry season...
High Resolution Population Maps for Low Income Nations: Combining Land Cover and Census in East Africa [PLOS One] — (English)
We find that this semi-automated population distribution mapping at unprecedented spatial resolution produces more accurate results than existing products and can be undertaken for as little as $0.01 per km2. The resulting population maps are a product of the Malaria Atlas Project (MAP: http://www.map.ox.ac.uk) and are freely available...
WNBA Star Ruth Riley Joins the UN Foundation and Nothing But Nets in Distributing 133,000 Nets [ OurSports Center - United States ] — (English)
The Women's National Basketball Association and Nothing But Nets- a global, grassroots campaign to prevent malaria-announced today that San Antonio Silver Stars Center Ruth Riley will travel to Mali, Africa as part of a United Nations Foundation and Nothing But Nets delegation to observe the distribution of over two million long-lasting insecticide-treated bed nets to children and their families. Nothing But Nets campaign supporters funded 133,000 of the bed nets being distributed December 13-19, 2007 as part of the largest integrated health campaign in Mali, where malaria is a leading cause of death for children under five. By the end of the integrated health campaign, all children under five will be protected by an insecticide-treated net...
Nothing But Nets Delivers 133,000 Anti-Malaria Nets to Children and Families in Mali as Part of National, Integrated Health Campaign [PR Web - United States ] — (English)
As part of an integrated, national health campaign in Mali targeting more than 2.8 million children under the age of five, Nothing But Nets — a global, grassroots campaign to prevent malaria — announced today it is delivering 133,000 long-lasting insecticide-treated nets to children and families to prevent the transmission of malaria. Malaria is a leading cause of death for children under five in the country...
American star athletes deliver anti-malaria nets in Mali [ Christian Today - United Kingdom ] — (English)
American sports stars are lending a hand in delivering 133,000 insecticide-treated nets to children and families in Mali beginning Thursday...
Study reveals malaria threat [AntiguaSun - St' John's,Antigua and Barbuda] — (English)
In a first of its kind study of mosquitoes in Antigua, the Center for Tropical Diseases and International Travels has discovered the potential for the spread of malaria through the existence of the anopheles mosquito in Antigua...
South Africa: Questions Over State Drive Against Malaria [Business Day (Johannesburg)] — (English)
Researchers have identified serious discrepancies in the number of malaria deaths recorded by the health department and those captured by Statistics SA, suggesting health care workers are failing to notify authorities when patients die from the disease...
Nigeria: One-Day Anti-Malarial Drug Launched in Kano [Leadership (Abuja)] — (English)
Nigerian German Chemicals Plc, on Thursday in Kano launched its new product, ARCO, a new range of Naphatholine anti-malarial drug into the Northern market, as part of the company's effort to keep malaria under check in the country...
11.12.2007
UN Special Rapporteur on Right to Health Calls on All Actors to Fulfil their Human Rights Duties in the Fight against Malaria [Malaria Consortium] — (English)
On Human Rights Day, the UN Special Rapporteur on the Right to Health, Professor Hunt, called for urgent monitoring and accountability and better coordination from all parties - developing and developed states, the international community, and the private and public actors, including pharmaceutical companies - to ensure the "Right to the highest attainable health" for all, and to fight malaria, a preventable and treatable disease that kills more than 1 million people every year...
Making a malaria vaccine à la Louis Pasteur [IHT - United States] — (English)
Sanaria Inc. (meaning "healthy air," a play on the Italian "mal'aria" or "bad air") is making a vaccine the old-fashioned way, more or less as Louis Pasteur did...
Experimental Malaria Vaccine Shows Promise in Africa [PBS - USA] — (English)
Malaria kills one African child about every 30 seconds. Now, a vaccine developed by GlaxoSmithKline and the Bill and Melinda Gates Foundation shows promise in reducing the rate of severe malaria by as much as 50 percent. Susan Dentzer reports from Tanzania...
Health Ministry: Socatra Island is free from malaria [Yemen News Agency - Yemen] — (English)
National Program of Fighting Malaria of the health ministry announced that Socatra Island is free from malaria,26sep.net reported on Tuesday...
UN Reports Fewer Children Dying From Preventable Causes [Voice of America - USA] — (English)
A new report finds that last year the number of children dying before their fifth birthday fell below 10 million for the first time since the United Nations has been keeping records. But, the U.N. Children's Fund, which has just launched its latest Progress For Children Study, reports much more needs to be done to improve the health and well being of children around the world. Data collected from more than 50 countries is used to monitor progress towards international goals and targets, including the Millennium Development Goals. Lisa Schlein reports for VOA from Geneva...
Sanaria takes new approach for malaria vaccine [FierceBiotech - United States] — (English)
The New York Times profiles Sanaria, a Maryland vaccines company that is taking a cue from Louis Pasteur in developing a new way to combat malaria. Instead of relying on fragments of the parasite's protein to trigger an immune response--the common approach for vaccine development--Sanaria takes the whole parasite and weakens it with gamma rays so it can't multiply, an advance on Pasteur's method of weakening rabies bacilli by air drying them...
South Africa: Malaria Drugs at State Clinics From Next Year [Business Day (Johannesburg)] — (English)
The health department will start providing malaria-prevention drugs at state clinics next year, a move likely to be of particular benefit to low- income migrant workers who travel to high-risk areas of SA and southern Africa...
Articles requiring subscription
The Exoneme Helps Malaria Parasites to Break out of Blood Cells [Cell, Volume 131, Issue 6, 14 December 2007, Pages 1036-1038] — (English)
Malaria parasites must invade the erythrocytes of its host, to be able to grow and multiply. Having depleted the host cell of its nutrients, the parasites break out to invade new erythrocytes. In this issue of Cell, Yeoh et al. (2007) discover a new organelle, the exoneme, that contains a protease SUB1, which helps the parasite to escape from old erythrocytes and invade new ones...
Subcellular Discharge of a Serine Protease Mediates Release of Invasive Malaria Parasites from Host Erythrocytes [Cell, Volume 131, Issue 6, 14 December 2007, Pages 1072-1083] — (English)
The most virulent form of malaria is caused by waves of replication of blood stages of the protozoan pathogen Plasmodium falciparum. The parasite divides within an intraerythrocytic parasitophorous vacuole until rupture of the vacuole and host-cell membranes releases merozoites that invade fresh erythrocytes to repeat the cycle. Despite the importance of merozoite egress for disease progression, none of the molecular factors involved are known. We report that, just prior to egress, an essential serine protease called PfSUB1 is discharged from previously unrecognized parasite organelles (termed exonemes) into the parasitophorous vacuole space. There, PfSUB1 mediates the proteolytic maturation of at least two essential members of another enzyme family called SERA. Pharmacological blockade of PfSUB1 inhibits egress and ablates the invasive capacity of released merozoites. Our findings reveal the presence in the malarial parasitophorous vacuole of a regulated, PfSUB1-mediated proteolytic processing event required for release of viable parasites from the host erythrocyte...
Malaria: Differential parasite drive [Nature 450, 955-956 (13 December 2007) | doi:10.1038/450955a; Published online 12 December 2007] — (English)
Our knowledge of the inner workings of malaria parasites comes largely from lab-based studies. But parasites growing in humans may have greater metabolic flexibility than those growing in Petri dishes...
Distinct physiological states of Plasmodium falciparum in malaria-infected patients [Letter
Nature 450, 1091-1095 (13 December 2007) | doi:10.1038/nature06311; Received 17 May 2007] — (English)
Infection with the malaria parasite Plasmodium falciparum leads to widely different clinical conditions in children, ranging from mild flu-like symptoms to coma and death. Despite the immense medical implications, the genetic and molecular basis of this diversity remains largely unknown. Studies of in vitro gene expression have found few transcriptional differences between different parasite strains. Here we present a large study of in vivo expression profiles of parasites derived directly from blood samples from infected patients. The in vivo expression profiles define three distinct transcriptional states. The biological basis of these states can be interpreted by comparison with an extensive compendium of expression data in the yeast Saccharomyces cerevisiae. The three states in vivo closely resemble, first, active growth based on glycolytic metabolism, second, a starvation response accompanied by metabolism of alternative carbon sources, and third, an environmental stress response. The glycolytic state is highly similar to the known profile of the ring stage in vitro, but the other states have not been observed in vitro. The results reveal a previously unknown physiological diversity in the in vivo biology of the malaria parasite, in particular evidence for a functional mitochondrion in the asexual-stage parasite, and indicate in vivo and in vitro studies to determine how this variation may affect disease manifestations and treatment...
Évaluation de l'application du protocole national de traitement du paludisme simple dans les formations sanitaires de la ville de Kigali, Rwanda [Médecine et Maladies Infectieuses, In Press, Corrected Proof, Available online 11 December 2007] — (Français)
Les auteurs recommandent une formation du personnel soignant des FOSA sur le protocole national. Les données suggèrent également la nécessité d’accompagner la modification du protocole national d’une évaluation, réalisée avec la participation des prestataires de soins, de l’efficacité et des effets indésirables éventuels de la nouvelle stratégie...
Perceptions and home management practices of malaria in some rural communities in Abeokuta, Nigeria [Travel Medicine and Infectious Disease, In Press, Corrected Proof, Available online 11 December 2007] — (English)
Summary
A survey was carried out in five rural communities that enjoy agricultural extension services from the University of Agriculture Abeokuta. Questionnaires and focus group discussions (FGDs) were used to assess perceptions and home management practices of malaria infection. The inhabitants considered malaria (which they refer to as “Iba Otutu”) has the least dangerous of other types of common fever such as yellow fever and typhoid fever. A vast majority of the respondents (73%) attributed malaria infection to doing of strenuous jobs in the hot sun, while only 11.7% attributed it to mosquito bites. Hunger, eating or drinking of contaminated food or water were other sources of malaria infection mentioned by the respondent. During the FGDs, another source of infection of malaria identified was excessive exposure to heat of fire used in frying cassava (garri), therefore those frying garri and those spreading cassava flakes in the sun were identified as most vulnerable to malaria infection. During the FGD, high level of malaria infection in children was attributed to children playful activities in the sun. It is believed that malaria infection will occur even without mosquito bites but with exposure to these other factors especially the intense heat of the sun. Respondents showed good knowledge of malaria symptoms even in infants and children. However, in the event of malaria infection consumption of herbal preparations is the first line of treatment. Drug hawkers that sell modern drugs in the communities were mainly consulted for malaria treatment. The antimalarial drugs bought were often wrongly used and none of the respondents were aware of the current trend in malaria management with modern drugs. Hospital visitation is usually after many days of persistent illness without improvement despite all forms of self medication. The main measure used against malaria vectors was insecticide coils (74.6%). None of the respondents used insecticide treated net (ITN). Distance, cost and poor quality of hospital treatment were reasons for refusal to seek proper medical care. Health education and improved health care services are recommended for these farmers in order for them to be able to translate extension services provided into maximum agricultural yields
...
Expression and enzymatic characterizationof the soluble recombinant plasmepsin Ifrom [Protein Engineering, Design and Selection.2007; 0: gzm066v1-9] — (English)
The plasmepsins are involved in the degradation of host cell hemoglobin during malaria infection. Plasmepsin I (PM I) initiates the degradative process, and has been suggested as an attractive target for the treatment of malaria. The production of active recombinant PM I, however, has been challenging. We report for the first time, the expression and partial characterization of soluble recombinant PM I from Plasmodium falciparum in which a truncated form of PM I (Lys77P-Leu329) (P indicates a propart residues) was fused to thioredoxin in the pET32b(+) vector, Trx-tPM I and expressed in Escherichia coli Rosetta-gami B (DE3)pLysS. The soluble fusion protein was purified from cell culture using a combination of Ni(2+) affinity and gel filtration chromatography and was capable of autocatalytic activation at pH 4.0-5.5, which occurred at Leu116P-Ser117P, seven residues upstream of the native cleavage site (Gly123P-Asn1). The mature tPM I (mtPM I) was capable of hydrolyzing both human hemoglobin with a pH optimum of pH 2.8-4.0 and the synthetic fluorogenic peptide EDANS-CO-CH(2)-CH(2)-CO-ALERMFLSFP-Dap(DABCYL)-OH with a dual pH optima of pH 2.5-3.0 and pH 4.5-5.5. Using the synthetic substrate, mtPM I exhibited kinetic parameters comparable to native PM I....
Role of TLRs/MyD88 in host resistance and pathogenesis during protozoan infection: lessons from malaria [Semin Immunopathol. 2007 Dec 11] — (English)
Toll-like receptors (TLRs) are important to initiate the innate immune response to a wide variety of pathogens. The protective role of TLRs during infection with protozoan parasites has been established. In this regard, malaria represents an exception where activation of TLRs seems to be deleterious to the host. In this article, we review the recent findings indicating the contrasting role of Myeloid Differentiation Primary-Response gene 88 (MyD88) and TLRs during malaria and infection with other protozoa. These findings suggest that MyD88 may represent an Achilles’ heel during Plasmodium infection...
Humoral responses to P. falciparum blood stage antigens (MSP3, MSP1-19, GLURP and AMA1) and their association with the incidence of clinical malaria in children living in a seasonal malaria transmission area of Burkina Faso (West Africa) [Infect Immun. 2007 Dec 10] — (English)
There is longstanding evidence that immunoglobulins IgG have a role in protection against clinical malaria, and human antibodies of the cytophilic subclasses are thought to be particularly critical in this respect. In this cohort study, 286 Burkinabe children aged 6 months to 15 years were kept under malaria surveillance in order to assess the protective role of antibody responses against four antigens which are currently being evaluated as vaccine candidates (AMA1, MSP1-19, MSP3, and GLURP). Total IgG, IgM, and IgG subclass responses were measured just before the malaria transmission season. The incidence of malaria was 2.4 episodes per child year at risk. After adjusting for the confounding effects of age, the level of total IgG to GLURP was strongly associated with reduced malaria incidence (rate ratio associated with a doubling of total IgG IRR=0.79, 95%CI:0.66-0.94, P =0.009.); there was a borderline statistical significance association between the level of total IgG to MSP3 and malaria incidence, and no evidence of an association for total IgG to AMA1 and to MSP1-19. Of the IgG subclass responses studied only IgG3 and IgG4 against GLURP and IgG1 against AMA1 were associated with reduced risk of clinical malaria. There was no evidence of an interaction between responses to AMA1 and baseline parasitaemia in their effects on malaria incidence. Currently included in malaria vaccine formulations for clinical trials in human, these blood stage antigens (AMA1 and GLURP) offer good prospects for malaria vaccine development...
Bilirubin inhibits Plasmodium falciparum growth through the generation of reactive oxygen species [Free Radical Biology and Medicine] — (English)
Free heme is very toxic because it generates highly reactive hydroxyl radicals (OH) to cause oxidative damage. Detoxification of free heme by the heme oxygenase (HO) system is a very common phenomenon by which free heme is catabolized to form bilirubin as an end product. Interestingly, the malaria parasite, Plasmodium falciparum, lacks an HO system, but it forms hemozoin, mainly to detoxify free heme. Here, we report that bilirubin significantly induces oxidative stress in the parasite as evident from the increased formation of lipid peroxide, decrease in glutathione content, and increased formation of H2O2 and OH. Bilirubin can effectively inhibit hemozoin formation also. Furthermore, results indicate that bilirubin inhibits parasite growth and induces caspase-like protease activity, up-regulates the expression of apoptosis-related protein (Gene ID PFI0450c), and reduces the mitochondrial membrane potential. OH scavengers such as mannitol, as well as the spin trap α-phenyl-n-tert-butylnitrone, effectively protect the parasite from bilirubin-induced oxidative stress and growth inhibition. These findings suggest that bilirubin, through the development of oxidative stress, induces P. falciparum cell death and that the malaria parasite lacks an HO system probably to protect itself from bilirubin-induced cell death as a second line of defense...
Localization of Candidate Regions Maintaining a Common Polymorphic Inversion (2La) in Anopheles gambiae [PLoS Genet. 2007 Dec 7] — (English)
Chromosomal inversion polymorphisms are thought to play a role in adaptive divergence, but the genes conferring adaptive benefits remain elusive. Here we study 2La, a common polymorphic inversion in the African malaria vector Anopheles gambiae. The frequency of 2La varies clinally and seasonally in a pattern suggesting response to selection for aridity tolerance. By hybridizing genomic DNA from individual mosquitoes to oligonucleotide microarrays, we obtained a complete map of differentiation across the A. gambiae genome. Comparing mosquitoes homozygous for the 2La gene arrangement or its alternative (2L+a), divergence was highest at loci within the rearranged region. In the 22 Mb included within alternative arrangements, two 1.5 Mb regions near but not adjacent to the breakpoints were identified as being significantly diverged, a conclusion validated by targeted sequencing. The persistent association of both regions with the 2La arrangement is highly unlikely given known recombination rates across the inversion in 2La heterozygotes, thus implicating selection on genes underlying these regions as factors responsible for the maintenance of 2La. Polymorphism and divergence data are consistent with a model in which the inversion is maintained by migration-selection balance between multiple alleles inside these regions, but further experiments will be needed to fully distinguish between the epistasis (coadaptation) and local adaptation models for the maintenance of 2La...
Bionomics of malaria vectors and relationship with malaria transmission and epidemiology in three physiographic zones in the Senegal River Basin [Acta Tropica] — (English)
Following the implementation of two dams in the Senegal River, entomological and parasitological studies were conducted in three different ecological zones in the Senegal River Basin (the low valley of Senegal River, the Guiers Lake area and the low valley of Ferlo) every 3 month in June 2004, September 2004, December 2004 and March 2005. The objective of this work was to study the influence of environmental heterogeneities on vector bionomics and malaria epidemiology. Mosquitoes were collected when landing on human volunteers and by pyrethrum spray catches. In the parasitological survey, blood samples were taken from a cohort of schoolchildren under 9 years during each entomology survey. Seven anopheline species were collected: Anopheles arabiensis, Anopheles gambiae M form, Anopheles funestus, Anopheles pharoensis, Anopheles coustani, Anopheles wellcomei and Anopheles rufipes. A. arabiensis, A. funestus and A. pharoensis were predominant in the low valley of the Senegal River, A. funestus in the Guiers Lake area and A. arabiensis in the low valley of Ferlo. Mosquito populations' dynamics varied temporally depending on the rainy season for each zone. The anthropophilic rates varied between 6 and 76% for A. gambiae s.l. and 23 and 80% for A. funestus. Only 4/396 A. pharoensis and 1/3076 A. funestus tested carried Plasmodium falciparum CS antigen. These results suggest the implication of A. pharoensis in malaria transmission. The related entomological inoculation rates were estimated to 10.44 in Mbilor and 3 infected bites in Gankette Balla and were due, respectively, to A. pharoensis and A. funestus. Overall, 1636 thick blood smears were tested from blood samples taken from schoolchildren with, respectively, a parasite and gametocyte average prevalence of 9 and 0.9%. The parasite prevalence was uniformly low in Mbilor and Gankette Balla whereas; it increased in September (16%) and then remained stable in December and March (22%) in Mboula where malaria transmission was not perceptible. However, significant differences were observed over time for parasite prevalence in Mbilor and Mboula villages whereas; it was only in Gankette Balla village where gametocyte prevalence was significantly different over time. Our study demonstrates the influence of ecological changes resulted from dams implementation in the Senegal River on the composition of vectorial system, malaria transmission and epidemiology. Such changes should be thoroughly surveyed in order to prevent any possible malaria outbreak in the Senegal River Basin...
Filling the gap of intracellular dephosphorylation in the Plasmodium falciparum vitamin B1 biosynthesis [Molecular and Biochemical Parasitology] — (English)
Thiamine pyrophosphate (TPP), the active form of vitamin B1, is an essential cofactor for several enzymes. Humans depend exclusively on the uptake of vitamin B1, whereas bacteria, plants, fungi and the malaria parasite Plasmodium falciparum are able to synthesise thiamine monophosphate (TMP) de novo. TMP has to be dephosphorylated prior to pyrophosphorylation in order to obtain TPP. In P. falciparum the phosphatase capable to catalyse this reaction has been identified by analysis of the substrate specificity. The recombinant enzyme accepts beside vitamin B1 also nucleotides, phosphorylated sugars and the B6 vitamer pyridoxal 5′-phosphate. Vitamin B1 biosynthesis is known to occur in the cytosol. The cytosolic localisation of this phosphatase was verified by transfection of a GFP chimera construct. Stage specific Northern blot analysis of the phosphatase clearly identified an expression profile throughout the entire erythrocytic life cycle of P. falciparum and thereby emphasises the importance of dephosphorylation reactions within the malaria parasite...
Blood coagulation in falciparum malaria-a review [Parasitology Research] — (English)
Falciparum malaria infection influences blood coagulation by various interacting pathobiological mechanisms, the most important being the overwhelming response of the host to sepsis resulting in a cytokine storm. In addition, the parasite infects the red cells leading to changes in the red cell phospholipid composition which supports blood coagulation. Red cells infected with Plasmodium falciparum also adhere to deeper tissue capillary endothelium leading to profound damage to endothelial cells leading to further activation. This results in widespread consumption of platelets and activation of blood coagulation which at times culminates in a clinically and pathologically detectable disseminated intravascular coagulation (DIC). Monocyte–macrophage system also gets activated in this infection compounding the hypercoagulable state. Heavy parasitaemia leading to occlusion of hepatic microcirculation leads to abnormalities in synthesis and secretion of coagulation factors and their inhibitors. Drugs used in the treatment for falciparum malaria can cause thrombocytopaenia, bone marrow suppression and haemolytic anaemia, all of which can interfere indirectly with blood coagulation. Microparticle formation from platelets, red cells and macrophages also causes widespread activation of blood coagulation, and this recently observed mechanism is the focus of intense research in many other inflammatory and neoplastic conditions where there is activation of blood coagulation system. Thus, in severe falciparum malaria, there is activation of blood coagulation system along with thrombocytopaenia, even before widespread DIC and coagulation failure occur...
Central pontine myelinolysis in a case of cerebral malaria [BJR] — (English)
Central pontine myelinolysis (CPM) is a clinical condition characterized by myelin destruction in the rostral part of the pons. It is commonly found in association with alcoholism, rapidly corrected hyponatraemia and electrolyte abnormalities. We describe here an unusual case of CPM occurring in a patient with cerebral malaria...
Sensitive Detection of Malaria Infection by Third Harmonic Generation Imaging [ Biophys J. 2007 Dec 7] — (English)
Malaria remains a major health concern worldwide, with 350 to 500 million cases reported annually in endemic countries. In this study, we report a novel and highly sensitive optical based detection of malaria infected blood cells by third harmonic generation (THG) imaging of hemozoin pigment that is naturally deposited by the parasite during its lifecycle. The THG signal from the hemozoin was greater than we have observed in any cell type with signal to background ratios that reach 1000:1. This method allows a rapid and robust detection of early stage infections of blood cells. The immense nonlinear response of the intrinsic parasitic by-product pigments suggests that automated optical detection by THG could be used for sensitive and rapid screening of parasite infection in blood samples...
Reactive oxygen species modulate Anopheles gambiae immunity against bacteria and plasmodium [J. Biol. Chem.] — (English)
The involvement of reactive oxygen species (ROS) in mosquito immunity against bacteria and Plasmodium was investigated in the malaria vector Anopheles gambiae. Strains of An. gambiae with higher systemic levels of ROS survive better a bacterial challenge, while reduction of ROS by dietary administration of antioxidants significantly decreases survival, indicating that ROS are required to mount effective antibacterial responses. Expression of several ROS detoxification enzymes increases in the midgut and fat body following a blood meal. Furthermore, expression of several of these enzymes increases to even higher levels when mosquitoes are fed a P. berghei-infected meal, indicating that the oxidative stress following a blood meal is exacerbated by Plasmodium infection. Paradoxically, a complete lack of induction of catalase mRNA and lower catalase activity were observed in P. berghei-infected midguts. This suppression of midgut catalase expression is a specific response to ookinete midgut invasion and is expected to lead to higher local levels of hydrogen peroxide. Further reduction of catalase expression by dsRNA-mediated gene silencing promoted parasite clearance by a lytic mechanism and reduced infection significantly. High mosquito mortality is often observed after P. berghei infection. Death appears to result in part from excess production of ROS, as mortality can be decreased by oral administration of uric acid, a strong antioxidant. We conclude that ROS modulate An. gambiae immunity, and that the mosquito response to P. berghei involves a local reduction of detoxification of hydrogen peroxide in the midgut that contributes to limit Plasmodium infection through a lytic mechanism...
The in vitro anti-plasmodial and in vivo anti-malarial efficacy of combinations of some medicinal plants used traditionally for treatment of malaria by the Meru community in Kenya [Journal of Ethnopharmacology ] — (English)
The use of herbal drugs as combinations has existed for centuries in several cultural systems. However, the safety and efficacy of such combinations have not been validated. In this study, the toxicity, anti-plasmodial and antimalarial efficacy of several herbal drug combinations were investigated. Lannea schweinfurthii, Turraea robusta and Sclerocarya birrea, used by traditional health practitioners in Meru community, were tested for in vitro anti-plasmodial and in vivo anti-malarial activity singly against Plasmodium falciparum and Plasmodium berghei, respectively. Methanolic extract of Turraea robusta was the most active against Plasmodium falciparum D6 strain. Aqueous extracts of Lannea schweinfurthii had the highest anti-plamodial activity followed by Turraea robusta and Sclerocarya birrea. D6 was more sensitive to the plant extracts than W2 strain. Lannea schweinfurthii extracts had the highest anti-malarial activity in mice followed by Turraea robusta and Sclerocarya birrea with the methanol extracts being more active than aqueous ones. Combinations of aqueous extracts of the three plants and two others (Boscia salicifolia and Rhus natalensis) previously shown to exhibit anti-plasmodial and anti-malarial activity singly were tested in mice. Marked synergy and additive interactions were observed when combinations of the drugs were assayed in vitro. Different combinations of Turraea robusta and Lannea schweinfurthii exhibited good in vitro synergistic interactions. Combinations of Boscia salicifolia and Sclerocarya birrea; Rhus natalensis and Turraea robusta; Rhus natalensis and Boscia salicifolia; Turraea robusta and Sclerocarya birrea; and Lannea schweinfurthii and Boscia salicifolia exhibited high malaria parasite suppression (chemo-suppression >90%) in vivo when tested in mice. The findings are a preliminary demonstration of the usefulness of combining several plants in herbal drugs, as a normal practice of traditional health practitioners...
Variation in use of erythrocyte invasion pathways by Plasmodium falciparum mediates evasion of human inhibitory antibodies [The Journal of Clinical Investigation] — (English)
Antibodies that inhibit Plasmodium falciparum invasion of erythrocytes are believed to be an important component of immunity against malaria. During blood-stage infection, P. falciparum can use different pathways for erythrocyte invasion by varying the expression and/or utilization of members of 2 invasion ligand families: the erythrocyte-binding antigens (EBAs) and reticulocyte-binding homologs (PfRhs). Invasion pathways can be broadly classified into 2 groups based on the use of sialic acid (SA) on the erythrocyte surface by parasite ligands. We found that inhibitory antibodies are acquired by malaria-exposed Kenyan children and adults against ligands of SA-dependent and SA-independent invasion pathways, and the ability of antibodies to inhibit erythrocyte invasion depended on the pathway used by P. falciparum isolates. Differential inhibition of P. falciparum lines that varied in their use of specific EBA and PfRh proteins pointed to these ligand families as major targets of inhibitory antibodies. Antibodies against recombinant EBA and PfRh proteins were acquired in an age-associated manner, and inhibitory antibodies against EBA175 appeared prominent among some individuals. These findings suggest that variation in invasion phenotype might have evolved as a mechanism that facilitates immune evasion by P. falciparum and that a broad inhibitory response against multiple ligands may be required for effective immunity...
Evaluation of Senegalese plants used in malaria treatment: Focus on Chrozophora senegalensis [Journal of Ethnopharmacology ] — (English)
An ethnobotanical study was conducted in the Dakar area of Senegal to investigate the species used in the treatment of malaria. Seven plants are principally used: Cissampelos mucronata, Maytenus senegalensis, Terminalia macroptera, Bidens engleri, Ceratotheca sesamoides, Chrozophora senegalensis and Mitracarpus scaber. From a bibliographic study, it had been shown that the Cissampelos mucronata, Maytenus senegalensis and Terminalia macroptera have already been studied by several authors, and so only Bidens engleri, Ceratotheca sesamoides, Chrozophora senegalensis and Mitracarpus scaber were evaluated in the present study. For each plant, extracts were prepared with different solvents and tested in vitro on two chloroquine-resistant Plasmodium falciparum strains. Crude extracts from the leaves and the stems of Chrozophora senegalensis showed the best in vitro results. The IC50 value of an aqueous extract of Chrozophora senegalensis was 1.6 μg/ml without cytotoxicity. The in vivo antiplasmodial activity of Chrozophora extracts was determined by both the oral and the intraperitoneal ways. The stages of Plasmodium cycle targeted by Chrozophora were then studied in vitro. These results could justify the traditional use of this plant in malaria treatment...
Regulation of carbohydrate metabolism and flight performance by a hypertrehalosaemic hormone in the mosquito Anopheles gambiae [Journal of Insect Physiology ] — (English)
The role of adipokinetic hormones (AKHs) in the regulation of carbohydrate and lipid metabolism and flight performance was evaluated for females of the African malaria mosquito, Anopheles gambiae. Injection of various dosages of synthetic Anoga-AKH-I increased carbohydrate levels in the haemolymph and reduced glycogen reserves in sugar-fed females but did not affect lipid levels. Anoga-AKH-I enhanced the flight performance of both intact and decapitated sugar-fed females, during a 4 h flight period. Anoga-AKH-II had no effect on carbohydrate or lipid levels or flight performance, thus its function remains unknown. Targeted RNA-interference lowered Anoga-AKH receptor expression in sugar-fed females, consequently injections of Anoga-AKH-I failed to mobilize glycogen reserves. Taken together, these results show that a primary role for the neurohormone, Anoga-AKH-I, is to elevate trehalose levels in the haemolymph of female mosquitoes...
Vaccination with a Plasmodium chabaudi adami multivalent DNA vaccine cross-protects A/J mice against challenge with P. c. adami DK and virulent Plasmodium chabaudi chabaudi AS parasites [International Journal for Parasitology] — (English)
A current goal of malaria vaccine research is the development of vaccines that will cross-protect against multiple strains of malaria. In the present study, the breadth of cross-reactivity induced by a 30K multivalent DNA vaccine has been evaluated in susceptible A/J mice (H-2a) against infection with the Plasmodium chabaudi adami DK strain and a virulent parasite subspecies, Plasmodium chabaudi chabaudi AS. Immunized A/J mice were significantly protected against infection with both P. c. adami DK (31–40% reduction in cumulative parasitemia) and P. c. chabaudi AS parasites, where a 30–39% reduction in cumulative parasitemia as well as enhanced survival was observed. The 30K vaccine-induced specific IFN-γ production by splenocytes in response to native antigens from both P. c. chabaudi AS and P. c. adami DK. Specific antibodies reacting with surface antigens expressed on P. c. adami DS and P. c. chabaudi AS infected red blood cells, and with opsonizing properties, were detected. These results suggest that multivalent vaccines encoding conserved antigens can feasibly induce immune cross-reactivity that span Plasmodium strains and subspecies and can protect hosts of distinct major histocompatibility complex haplotypes...
Gene expression analysis reveals early changes in several molecular pathways in cerebral malaria-susceptible mice versus cerebral malaria-resistant mice [BMC Genomics 2007, 8:452] — (English)
Our microarray analysis highlighted marked changes in several molecular pathways in CM-S compared to CM-R mice, particularly at early stages of infection. This study revealed some promising areas for exploration that may both provide new insight into the knowledge of CM pathogenesis and the development of novel therapeutic strategies...
Plasmodium malariae infection in spite of previous anti-malarial medication [Parasitology Research] — (English)
Plasmodium malariae is regarded as usually being susceptible to all anti-malarials whether applied for prophylaxis or treatment. We report on three cases of P. malariae infection which occurred 12–14 weeks after anti-malarial chemoprophylaxis or treatment with mefloquine or atovaquone/proguanil. The most likely explanation for the failure of mefloquine and atovaquone/proguanil to prevent quartan malaria occurring some months later is the insufficient effect on the particularly long-lasting pre-erythrocytic development stages of P. malariae...
Protection against malaria a real possibility [J Clin Invest. 2007 December 3] — (English)
The results of an early-stage clinical trial have brought closer the prospect of a vaccine to help protect infants and children from becoming infected with a parasite that causes the most deadly form of malaria, a disease that, according to the WHO, kills more than one million people every year...
Prepared in cooperation with WHO ANGOLA INFO.
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