14.01.2008
Polymorphisms of TNF-enhancer and gene for FcgammaRIIa correlate with the severity of falciparum malaria in the ethnically diverse Indian population [Malaria Journal 2008, 7:13 (14 January 2008)] — (English)
Association of specific TNF and FCGR2A SNPs with cytokine levels and disease severity/resistance was indicated in patients from areas with differential disease endemicity. The data emphasizes the need for addressing the contribution of human genetic factors in malaria in the context of disease epidemiology and population genetic substructure within India...
Blood Collection Steps Risk Contagion [Korea Times - South Korea] — (English)
The government's decision to make it easier to donate blood in malaria-risk areas underlines the country's acute blood shortage but also raises concern over possible negative side-effects. Some experts say the proposed emergency measures run the risk of producing a contaminated supply...
13.01.2008
Uganda: Free Nets Changing Lives of Women in Amuria [New Vision (Kampala)] — (English)
Malaria is estimated to kill one child in Africa every 30 seconds. In Uganda, the disease is the leading killer of pregnant women and children under five, accounting for 320 deaths daily. But there is new evidence that sleeping under treated mosquito nets regularly can save many lives. It is for this reason that Malaria Consortium has intervened to distribute free LLINs to vulnerable groups through antenatal care services in the five northern districts of Uganda...
Uganda: Spraying of DDT Begins Next Month [New Vision (Kampala) via AllAfrica.com] — (English)
THE Ministry of Health will next month begin the spraying of DDT in people's residences to combat malaria...
MIM News and Opportunities [MIM] — (English)
More news, opportunities, events, jobs and archives at the MIM Website...
Malaria: still a huge killer [The Australian Financial Review via TradingMarkets.com] — (English)
It is estimated that of the 500 million people in developing countries who catch malaria, up to 2.5 million die. Over 90 per cent of the fatalities represent children under the age of five and most are located in Africa. In 1998 the World Health Organization declared the mosquito "public health enemy number one". GlaxoSmithKline has been a partner in the development of a vaccine that reduced infection rates 65 per cent in three months and 35 per cent over six months. The Bill & Melinda Gates Foundation has committed $US258.3 million ($A291 million) to malaria R&D...
12.01.2008
Congo-Kinshasa: Un candidat-vaccin contre le paludisme à l'Institut Pasteur [Le Potentiel (Kinshasa) via allAfrica.com] — (Français)
Sus au paludisme ! L'Institut Pasteur de Paris annonce la mise au point d'un candidat-vaccin «qui a largement prouvé, conceptuellement, son intérêt ». Son nom de code : MSP3...
High schooler raises money to fight malaria [Arkansas Catholic - Little Rock,AR,USA] — (English)
This fall Garrett Quinn started his senior year at Catholic High School in Little Rock. But at the same time he launched a campaign to help prevent malaria-related deaths in Africa...
Horton students aim to "Save 1,000 Lives" [novanewsnow.com] — (English)
It's heartbreaking to hear, but the majority of children born in Africa will never make it to their fifth birthday. This startling fact has resonated with a group of students at Horton High School in Greenwich, who have initiated a fundraising campaign to purchase mosquito netting to help protect youth in Africa from contracting malaria...
11.01.2008
Africa: An Admiral Wages War on Malaria [allAfrica.com] — (English)
Admiral R. Timothy Ziemer — the first-ever U.S. Malaria Coordinator – says the goal has been achieved in 15 targeted African nations. AllAfrica's Charles Cobb Jr. spoke with him...
Estimation of heterogeneity in malaria transmission by stochastic modelling of apparent deviations from mass action kinetics [Malaria Journal 2008, 7:12 (11 January 2008)] — (English)
A new look at a critical issue in malaria epidemiology: the paper takes data on the probability of infection of different cohorts of children and statistically models them as a function of the entomological inoculation rate measured by human biting collections...
Distribution of Anopheles in Vietnam, with particular attention to malaria vectors of the Anopheles minimus complex [Malaria Journal 2008, 7:11 (11 January 2008)] — (English)
Large entomological surveys based on cattle collections and molecular identifications carried out in 23 sites throughout northern, central and south-eastern regions of Vietnam...
Differential evolution of anti-VAR2CSA IgG3 in primigravidae and multigravidae pregnant women infected by Plasmodium falciparum [Malaria Journal 2008, 7:10 (11 January 2008)] — (English)
Primigravidae without an infected placenta have higher levels of IgG3 antibodies against the VAR2CSA epitope suggesting that the antibodies against this epitope are protective in promigravidae...
How antimalarial drug resistance affects post treatment prophylaxis [Malaria Journal 2008, 7:9 (11 January 2008)] — (English)
Slowly-eliminated antimalarial drugs suppress malaria reinfections for a period of time, an effect called post-treatment prophylaxis, which represents an important component of treatment responses. Antimalarial drug resistance shortens the period of post-treatment prophylaxis...
U. Utah research shows protein increases malaria deaths in mice [Micromedex - United Kingdom] — (English)
. Utah research shows protein increases malaria deaths in mice 2008 Daily Utah Chronicle Via UWIRE SALT LAKE CITY -- A new study shows that genetically-engineered mice lacking a certain protein have a greater chance of surviving malaria. Guy Zimmerman, a U professor in internal medicine...
Bono parle de l’Afrique avec Sarkozy [Libération - France] — (Français)
Les deux hommes s’étaient croisés rapidement au sommet du G8 à Heiligendamm (Allemagne), en juin, mais n’avaient jamais eu de tête-à-tête. Le chanteur engagé et le président show-biz ont discuté hier après-midi de l’Afrique. Bono, qui dirige l’ONG DATA, en a profité pour rappeler à Sarkozy les engagements de la France sur l’aide au développement. Une manière élégante de souligner qu’ils étaient loin d’être tenus, voire en recul. Selon DATA, la France, qui s’est fixé pour objectif d’atteindre 0,7 % du PIB en aide au développement d’ici à 2012, n’a dépensé que 0,31 % en 2006. «Le Président a admis qu’il serait très très difficile de tenir cette promesse [faite par Jacques Chirac en 2002, ndlr]», a reconnu le chanteur. Sarkozy a toutefois promis de rétablir 20 millions d’euros, supprimés récemment, d’aide au Fond global de lutte contre le sida et le paludisme...
Immer mehr Regen: Malariagefahr im südlichen Afrika steigt! [Abenteuer Reisen - Germany] — (Deutsch)
Die Weltgesundheitsorganisation (WHO) warnt davor, dass im südlichen Afrika in dieser Saison das Malaria-Übertragungsrisiko steigen könnte...
Botswana: Warning - Avoid Malaria [Mmegi via AllAfrica.com] — (English)
If only people heeded the health messages, more lives could be saved against the preventable disease of malaria...
10.01.2008
Why do chimps eat dirt? [Nature - United Kingdom] — (English)
Chimpanzees in Uganda have been spotted eating dirt along with fistfuls of leaves. This might help to increase the plants' anti-malarial properties, say researchers...
Malariaprophylaxe aus der Natur [Wissenschaft - Germany] — (Deutsch)
Schimpansen fressen Erde zum Schutz vor dem Wechselfieber...
Zimbabwe: 200 000 to Receive Mosquito Nets []The Herald (Harare) — (English)
Pregnant women and children under five years in seven areas where malaria is endemic will receive about 200 000 long-lasting treated mosquito nets acquired through a US$1,9 million grant from the Japanese government...
Gabon: Le personnel de la santé militaire renforce ses capacités dans la lutte contre le paludisme à Libreville [Gabonews (Libreville) via allAfrica.com] — (Français)
A la demande des autorités sanitaires militaires gabonaises, supervisé par le Programme national de lutte contre le paludisme, les personnels de santé militaires vont pendant dix jours apprendre des méthodes plus efficaces de lutte et de prévention contre le paludisme au Gabon, a constaté GABONEWS...
Botswana: Malaria Pandemic Threatens Northwest [Mmegi/The Reporter (Gaborone) via AllAfrica.com] — (English)
There were at least six malaria deaths and 16, 495 malaria cases in Botswana in 2007. According to Ministry of Health, this is compared to the 2006, where there were 42 deaths and 19, 938 malaria cases...
9.01.2008
Climate Change Fueling Malaria in Kenya, Experts Say [National Geographic - Washington,DC,USA] — (English)
Malaria has long been endemic to Kenya's humid coast and swampy lowland regions, but it has only rarely reached Njoki's village on the slopes of Mount Kenya...
A Parasite Shows Its Plantlike Side [Science Magazine - USA] — (English)
The single-celled creatures known as protozoans are primitive, exotic, and sometimes just plain weird, resembling animals, plants, or a combination of both. Researchers now report that one animal-like, parasitic protozoan relies on a biochemical pathway that is strikingly plantlike. The discovery could open up a new method of attacking protozoans that cause diseases such as malaria...
Malaria risk and access to prevention and treatment in the paddies of the Kilombero Valley, Tanzania [ReliefWeb (press release) - Geneva,Switzerland] — (English)
Living in the shamba does not appear to result in a higher fever-risk. Mosquito nets usage and treatment of fever in health facilities reflect awareness of malaria. Inability to obtain drugs in the fields may contribute to less irrational use of drugs but may pose an additional burden on poor farming households. A comprehensive approach is needed to improve access to treatment while at the same time assuring rational use of medicines and protecting fragile livelihoods...
Microbially Derived Artemisinin Highlighted in American Journal of Tropical Medicine... [Reuters - USA] — (English)
The Institute for OneWorld Health (iOWH), the US-based non-profit pharmaceutical company that develops drugs for people with infectious diseases in the developing world, today announced that an article describing groundbreaking research in semisynthetic artemisinin has been published in the American Journal of Tropical Medicine and
Hygiene's (AJTMH) special malaria burden supplement Defining and Defeating the Intolerable Burden of Malaria III: Progress and Perspectives...
Malaria risk and access to prevention and treatment in the paddies of the Kilombero Valley, Tanzania
[Malaria Journal 2008, 7:8 (9 January 2008)] — (English)
Living in the shamba does not appear to result in a higher fever-risk. Mosquito nets usage and treatment of fever in health facilities reflect awareness of malaria. Inability to obtain drugs in the fields may contribute to less irrational use of drugs but may pose an additional burden on poor farming households. A comprehensive approach is needed to improve access to treatment while at the same time assuring rational use of medicines and protecting fragile livelihoods...
Feasibility and acceptability of artemisinin-based combination therapy for the home management of malaria in four African sites [Malaria Journal 2008, 7:6 (8 January 2008)] — (English)
ACTs can be successfully integrated into the HMM strategy...
Improving equity in malaria treatment: Relationship of socio-economic status with health-seeking as well as with perceptions of ease of using the services of different providers for the treatment of malaria in Nigeria [Malaria Journal 2008, 7:5 (8 January 2008)] — (English)
Inequities exist in how different SES groups perceive the levels of ease of accessibility and utilization of different providers for malaria treatment. The differentials in perceptions of ease of access and use as well as health seeking for different malaria treatment providers among SES groups could be decreased by reducing barriers such as the cost of treatment by making health services accessible, available and at reduced cost for all groups...
Sénégal: De nouvelles subventions pour la lutte contre le paludisme [Agence de Presse Sénégalaise (Dakar) via allAfrica.com] — (Français)
Le Malaria consortium, une organisation internationale non gouvernementale basée à Londres, a annoncé trois nouvelles subventions pour des projets de plaidoyer contre le paludisme dans 12 pays africains, a-t-on appris de source sûre...
Malaria is under control, says health department [Sowetan - Soweto,South Africa] — (English)
The Limpopo department of health and social development has downplayed fears of a malaria outbreak in the province. This follows reports that more cases of malaria have been recorded in the province than in the previous years. The province has recorded 500 cases of malaria in the past two months...
Malaria outbreak in Hanjin shipyard under control -- DOH [Inquirer.net - Philippines] — (English)
The malaria outbreak that affected at least 321 workers and residents in and around a Korean shipbuilding facility in Subic, Zambales, last year is now under control, the chief of the Department of Health in Central Luzon said on Wednesday...
8.01.2008
Sinobiomed Subsidiary Receives US $1.24 Million Funding to Accelerate Clinical Trial & Development of Malaria Vaccine [CNNMoney.com - USA] — (English)
Sinobiomed Inc. is pleased to announce that that its 82% owned subsidiary, Shanghai Wanxing Bio-pharmaceuticals Co., Ltd., has been granted government funding of RMB 9 million (US $1.24 million) to continue the clinical trial of its recombinant malaria vaccine and advance its development with partner Second Military Medical University. The funding is the largest the Chinese government has ever granted to a biopharmaceutical company...
Innovation et philanthropie dopent le marché des vaccins [Le Monde - France] — (Français)
D'autres produits nouveaux sont attendus au cours des années à venir : des vaccins contre la dengue (1 milliard de dollars, soit 680 millions d'euros, de chiffre d'affaires attendu), le paludisme, les nouvelles formes de tuberculose, la méningite B... La recherche actuelle est aussi beaucoup dopée par les fonds débloqués tant en Europe qu'aux Etats-Unis pour réduire les risques d'une éventuelle pandémie aviaire...
Functional deficit of T regulatory cells in Fulani, an ethnic group with low susceptibility to Plasmodium falciparum malaria [PNAS, 3 January 2008] — (English)
Previous interethnic comparative studies on the susceptibility to malaria performed in West Africa showed that Fulani are more resistant to Plasmodium falciparum malaria than are sympatric ethnic groups. This lower susceptibility is not associated to classic malaria-resistance genes, and the analysis of the immune response to P. falciparum sporozoite and blood stage antigens, as well as non-malaria antigens, revealed higher immune reactivity in Fulani. In the present study we compared the expression profile of a panel of genes involved in immune response in peripheral blood mononuclear cells (PBMC) from Fulani and sympatric Mossi from Burkina Faso. An increased expression of T helper 1 (TH1)-related genes (IL-18, IFN, and TBX21) and TH2-related genes (IL-4 and GATA3) and a reduced expression of genes distinctive of T regulatory activity (CTLA4 and FOXP3) were observed in Fulani. Microarray analysis on RNA from CD4+CD25+ (T regulatory) cells, performed with a panel of cDNA probes specific for 96 genes involved in immune modulation, indicated obvious differences between the two ethnic groups with 23% of genes, including TGFβ, TGFβRs, CTLA4, and FOXP3, less expressed in Fulani compared with Mossi and European donors not exposed to malaria. As further indications of a low T regulatory cell activity, Fulani showed lower serum levels of TGFβ and higher concentrations of the proinflammatory chemokines CXCL10 and CCL22 compared with Mossi; moreover, the proliferative response of Fulani to malaria antigens was not affected by the depletion of CD25+ regulatory cells whereas that of Mossi was significantly increased. The results suggest that the higher resistance to malaria of the Fulani could derive from a functional deficit of T regulatory cells...
A combined transcriptome and proteome survey of malaria parasite liver stages [PNAS] — (English)
For 50 years since their discovery, the malaria parasite liver stages (LS) have been difficult to analyze, impeding their utilization as a critical target for antiinfection vaccines and drugs. We have undertaken a comprehensive transcriptome analysis in combination with a proteomic survey of LS. Green fluorescent protein-tagged Plasmodium yoelii (PyGFP) was used to efficiently isolate LS-infected hepatocytes from the rodent host. Genome-wide LS gene expression was profiled and compared with other parasite life cycle stages. The analysis revealed 2,000 genes active during LS development, and proteomic analysis identified 816 proteins. A subset of proteins appeared to be expressed in LS only. The data revealed exported parasite proteins and LS metabolic pathways including expression of FASII pathway enzymes. The FASII inhibitor hexachlorophene and the antibiotics, tetracycline and rifampicin, that target the apicoplast inhibited LS development, identifying FASII and other pathways localized in the apicoplast as potential drug targets to prevent malaria infection...
Upstream Biosciences and ProvLab collaborate on malaria treatment [Trading Markets (press release) - Los Angeles,CA,USA] — (English)
Upstream Biosciences has entered into collaboration with the Provincial Laboratory for Public Health in Alberta, Canada to begin in vitro testing of Upstream's novel compounds for the potential treatment of malaria...
Articles requiring subscription
A new Inequity-in-Health Index based on Millenium Development Goals: methodology and validation [J Clin Epidemiol. 2008 Feb;61(2):142-50] — (English)
Six variables were used for constructing the IHI was constructed with six variables: underweight children, child mortality, death from malaria in children aged 0–4, death from malaria at all ages, births attended by skilled health personnel, and immunization against measles. The IHI had high internal consistency (Cronbach's alpha = 0.8504), was reliable (Spearman > 0.9, P = 0.0000), and had 0.3033π around the world (range: 0π–0.5984π). IHI had high correlation with the human development and poverty indexes, health gap indicator, life expectancy at birth, probability of dying before 40 years of age, and Gini coefficients (Spearman > 0.7, P = 0.0000). IHI discriminated countries by income, region, indebtedness, and corruption level (Kruskal Wallis, P < 0.01). IHI had sensitivity to change (P = 0.0000)...
Progress in malaria control in endemic areas [Travel Medicine and Infectious Disease, In Press, Corrected Proof, Available online 10 January 2008] — (English)
The international community is now making a serious effort to bring malaria under control. Funds for malaria control have become available on a scale not seen since the days of the eradication campaign 50 years ago. These new resources are being used largely to support a supply of artemisinin combination therapy to replace ineffective chloroquine and sulphadoxixne pyrimethamine for first line treatment of malaria and for the provision of long-lasting, insecticide treated bednets. There are early indications from several countries in Africa that this renewed effort at malaria control is beginning to have an effect but additional tools will probably be needed, including a highly effective vaccine, if the ultimate goal of malaria eradication is to be achieved...
Improved T cell responses to Plasmodium falciparum circumsporozoite protein in mice and monkeys induced by a novel formulation of RTS,S vaccine antigen [Vaccine, In Press, Uncorrected Proof, Available online 7 January 2008] — (English)
Protection against Plasmodium falciparum sporozoite infection can be achieved by vaccination with the recombinant circumsporozoite protein-based vaccine RTS,S formulated with the AS02A adjuvant system. Since this protection is only partial and wanes over time, we have developed a new RTS,S-based vaccine adjuvanted with AS01B. RTS,S/AS01B-induced high specific antibody titers and increased the frequency of mouse CD4+ and CD8+ T cells expressing IFNγ, and of monkey CD4+ T cells expressing IL-2 and/or IFNγ and/or TNFα upon stimulation with vaccine antigens. Our data provides clear evidence that combining RTS,S antigen with a potent adjuvant induces strong humoral and cellular responses in vivo...
Treatment and prevention of malaria in pregnancy and newborn [J Perinat Med. 2008;36(1):15-29] — (English)
Pregnant women are at increased risk for malaria infection. Although important advances have been made in the last years, the mechanisms that explain the increased susceptibility are not yet fully understood. Malaria infection in pregnancy is associated with maternal and fetal morbidity and mortality. The severity of the disease depends on the level of pre-pregnancy acquired immunity against malaria, and the consequences of infection are more severe in non-immune women. In highly endemic areas, the frequency and severity of the infection is higher in primigravida and decreases with increasing parity. In non-immune women, the risk is similar across the parity and malaria may be an important direct cause of maternal mortality. Malaria infection during pregnancy has important negative effects on infant's health, causing intrauterine growth retardation and prematurity or directly through congenital infection. In this paper, we review the pathology, diagnosis, and current recommendations for treatment and prevention of malaria in the pregnant woman and her infant...
Inhibition of glutathione- S -transferase from Plasmodium yoelii by protoporphyrin IX, cibacron blue and menadione: implications and therapeutic benefits [Parasitol Res. 2008 Jan 5] — (English)
The rapidly developing resistance to drugs used for prophylaxis and treatment of malaria makes the identification of novel drug targets necessary. Glutathione-S-transferase (GST, E.C. 2.5.1.18), an important enzyme of the glutathione (GSH) cycle, is considered to be an essential detoxification enzyme in malarial parasites. Selective inhibition of this enzyme from malarial parasites by various classes of inhibitors may be viewed as a potential chemotherapeutic strategy to combat malaria. Purified GST from Plasmodium yoelii was inhibited by compounds like protoporphyrin IX, cibacron blue, as well as by the GSH depletor menadione. Cytosolic GST was inhibited to varying degrees by each compound. A characteristic inhibitor constant (K i) was obtained for each inhibitor. The possible consequences of selective inhibition of parasitic GST to that of the host are discussed in relation to the chemotherapy of malaria...
Overt bleeding in malarial patients: experience and review [Blood Coagulation & Fibrinolysis. 19(1):1-4, January 2008] — (English)
At present, malaria - one of the most important parasitic infections - is increasing globally. Bleeding is an important clinical manifestation of malaria. The current review presents the author's experience of overt bleeding presentations of 50 Thai patients with malaria infection who visited a rural hospital in Chiangmai, Thailand. In addition, the literature on malarial bleeding is reviewed. In conclusion, overt bleeding is not uncommon in malaria. General practitioners in the endemic areas should be aware of malarial infection in any patient presenting with unexplained fever and bleeding...
Population pharmacokinetics of piperaquine after two different treatment regimens of dihydroartemisinin-piperaquine in patients with Plasmodium falciparum malaria in Thailand [Antimicrob Agents Chemother. 2008 Jan 7] — (English)
The population pharmacokinetics of piperaquine in adults and children with uncomplicated Plasmodium falciparum malaria treated with two different dosage regimens of dihydroartemisinin-piperaquine were characterized. Piperaquine pharmacokinetics in 98 Burmese and Karen patients aged 3-55 years were described by a two-compartment disposition model with first-order absorption and inter-individual random variability on all parameters, and were similar with the three and four dose regimens. Children had a lower body-weight normalized oral clearance than adults, resulting in longer terminal elimination half-lives and higher total exposure of piperaquine (AUCday 0-63). But children had lower plasma concentrations in the therapeutically relevant post-treatment prophylactic period (AUCday 3-20) because of smaller body-weight normalized central volumes of distribution and shorter distribution half-lifes. Our data lend further support of a simplified once daily treatment regimen to improve treatment adherence and efficacy, and indicate that weight adjusted piperaquine doses in children may need to be higher than in adults...
Biochemical and genetic analysis of the phosphoethanolamine methyltransferase of the human malaria parasite plasmodium falciparum [J. Biol. Chem, 10.1074/jbc.M709869200] — (English)
The PfPMT enzyme of P. falciparum, the agent of severe human malaria, is a member of a large family of known and predicted phosphoethanolamine methyl-transferases (PMTs) recently identified in plants, worms, insects and protozoa. Functional studies in P. falciparum revealed that PfPMT plays a critical role in the synthesis of phosphatidylcholine via a plant-like pathway involving serine decarboxylation and phosphoethanolamine methylation. Despite their important biological functions, PMT structures have not yet been solved and nothing is known about which amino acids in these enzymes are critical for catalysis and binding to s-adenosyl-methionine (SAM) and phosphoethanolamine substrates. Here we have performed a mutational analysis of PfPMT focused on 24 residues within and outside the predicted catalytic motif. The ability of PfPMT to complement the choline auxotrophy of a yeast mutant defective in phospholipid methylation enabled us to characterize the activity of the PfPMT mutants. Mutations in residues Asp61, Gly83 and Asp128 dramatically altered PfPMT activity, and its complementation of the yeast mutant. Our analyses identify the importance of these residues in PfPMT activity and set the stage for advanced structural understanding of this class of enzymes...
Bionomics, taxonomy, and distribution of the major malaria vector taxa of Anopheles subgenus Cellia in Southeast Asia: An updated review [Infect Genet Evol. 2007 Nov 29] — (English)
There is high diversity of Anopheles mosquitoes in Southeast Asia and the main vectors of malaria belong to complexes or groups of species that are difficult or impossible to distinguish due to overlapping morphological characteristics. Recent advances in molecular systematics have provided simple and reliable methods for unambiguous species identification. This review summarizes the latest information on the seven taxonomic groups that include principal malaria vectors in Southeast Asia, i.e. the Minimus, Fluviatilis, Culicifacies, Dirus, Leucosphyrus, and Sundaicus Complexes, and the Maculatus Group. Main issues still to be resolved are highlighted. The growing knowledge on malaria vectors in Southeast Asia has implications for vector control programs, the success of which is highly dependant on precise information about the biology and behavior of the vector species. Acquisition of this information, and consequently the application of appropriate, sustainable control measures, depends on our ability to accurately identify the specific vectors...
Glucose-6-phosphate dehydrogenase deficiency [Lancet. 2008 Jan 5;371(9606):64-74] — (English)
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common human enzyme defect, being present in more than 400 million people worldwide. The global distribution of this disorder is remarkably similar to that of malaria, lending support to the so-called malaria protection hypothesis. G6PD deficiency is an X-linked, hereditary genetic defect due to mutations in the G6PD gene, which cause functional variants with many biochemical and clinical phenotypes. About 140 mutations have been described: most are single base changes, leading to aminoacid substitutions. The most frequent clinical manifestations of G6PD deficiency are neonatal jaundice, and acute haemolytic anaemia, which is usually triggered by an exogenous agent. Some G6PD variants cause chronic haemolysis, leading to congenital non-spherocytic haemolytic anaemia. The most effective management of G6PD deficiency is to prevent haemolysis by avoiding oxidative stress. Screening programmes for the disorder are undertaken, depending on the prevalence of G6PD deficiency in a particular community...
Characterization of a conserved rhoptry-associated leucine zipper-like protein in the malaria parasite Plasmodium falciparum [Infect Immun. 2008 Jan 3] — (English)
One of the key processes in the pathobiology of the malaria parasite is the invasion and subsequent modification of the human erythrocyte. In this complex process an unknown number of parasite proteins are involved, some of which are leading vaccine candidates. The majority of the proteins that play a pivotal role in invasion are either stored in the apical secretory organelles, or located on the surface of the merozoite, the invasive stage of the parasite. Using transcriptional and structural features of these known proteins we performed a genome wide search that identified 49 hypothetical proteins with a high probability of being located on the surface of the merozoite or in the secretory organelles. Of these candidates we characterized a novel leucine-zipper like protein in Plasmodium falciparum that is conserved in Plasmodium spp. This protein is expressed in late blood stages and localizes to the rhoptries of the parasite. We demonstrate that this Plasmodium spp. specific protein has a high degree of conservation within field isolates, that it is refractory to gene knock-out attempts and thus might play an important role in invasion...
Chemical attenuation of Plasmodium berghei sporozoites induces sterile immunity in mice [Infect Immun. 2008 Jan 3] — (English)
Radiation or genetic attenuation of Plasmodium sporozoites are two approaches for whole organism vaccines that are protective against malaria. We evaluated chemical attenuation of sporozoites as an alternative vaccine strategy. Sporozoites were treated with the DNA sequence-specific alkylating agent centanamycin, a compound that significantly affects blood stage parasitemia and transmission of murine malaria and also inhibits P. falciparum growth in vitro. Here, we show that treatment of P. berghei sporozoites with centanamycin impaired parasite function both in vitro and in vivo. Infectivity of hepatocytes by sporozoites in vitro was significantly reduced and treated parasites showed arrested liver stage development. Inoculation of mice with sporozoites that were treated in vitro with centanamycin failed to produce blood stage infections. Furthermore, BALB/c and C57/BL6 mice vaccinated with treated sporozoites were protected against subsequent challenge with wild type sporozoites. Our findings demonstrate that chemically attenuated sporozoites (CAS) could be a viable alternative for the production of an effective liver stage vaccine for malaria...
What is the most effective and safe malaria prophylaxis during pregnancy? [J Fam Pract. 2008 Jan] — (English)
Chloroquine and mefloquine have superior safety profiles in pregnancy, though all antimalarials are effective for prophylaxis. Antimalarials will decrease the severity of maternal malaria infection and malaria-associated anemia, while decreasing the incidence of low birth weight and perinatal death in women having their first or second baby (strength of recommendation [SOR]: A, based on systematic review of consistent, good-quality patient-oriented evidence). You can determine malaria risk and sensitivity of Plasmodium species by country at wwwn.cdc.gov/travel/destinationList.aspx. Urge women to delay travel until after pregnancy if possible (SOR: C, based on patient-oriented expert opinion)...
Spatial Variation of Malaria Incidence in Young Children from a Geographically Homogeneous Area with High Endemicity [The Journal of Infectious Diseases 2008;197:85–93] — (English)
The exact location of households in villages is an independent and important factor for the variation of malaria incidence in children from high‐transmission areas. This fact should be considered in the planning of intervention trials and in spatial targeting of malaria interventions at a local level...
Platelet‐Induced Clumping of Plasmodium falciparum–Infected Erythrocytes from Malawian Patients with Cerebral Malaria—Possible Modulation In Vivo by Thrombocytopenia [The Journal of Infectious Diseases 2008;197:72–78] — (English)
Platelets may play a role in the pathogenesis of human cerebral malaria (CM), and they have been shown to induce clumping of Plasmodium falciparum–parasitized red blood cells (PRBCs) in vitro. Both thrombocytopenia and platelet-induced PRBC clumping are associated with severe malaria and, especially, with CM. In the present study, we investigated the occurrence of the clumping phenomenon in patients with CM by isolating and coincubating their plasma and PRBCs ex vivo. Malawian children with CM all had low platelet counts, with the degree of thrombocytopenia directly proportional to the density of parasitemia. Plasma samples obtained from these patients subsequently induced weak PRBC clumping. When the assays were repeated, with the plasma platelet concentrations adjusted to within the physiological range considered to be normal, massive clumping occurred. The results of this study suggest that thrombocytopenia may, through reduction of platelet-mediated clumping of PRBCs, provide a protective mechanism for the host during CM...
Direct In Vivo Assessment of Microcirculatory Dysfunction in Severe Falciparum Malaria [The Journal of Infectious Diseases 2008;197:79–84 ] — (English)
Erythrocyte velocities were measured directly in 43 adult patients with severe falciparum malaria, of whom 20 died. Microcirculatory blood flow was markedly disturbed, with heterogeneous obstruction that was proportional to severity of disease. Blocked capillaries were found in 29 patients (67%) and were associated with concurrent hyperdynamic blood flow (erythrocyte velocity, >750 mm/s) in adjacent vessels in 27 patients (93%). The proportion of blocked capillaries correlated with the base deficit in plasma and with the concentration of lactate. Abnormalities disappeared when the patients recovered. In healthy individuals and in patients with uncomplicated malaria or sepsis, no stagnant erythrocytes were detected, and, in patients with sepsis, hyperdynamic blood flow was prominent...
Spiro- and dispiro-1,2-dioxolanes: contribution of iron(II)-mediated one-electron vs two-electron reduction to the activity of antimalarial peroxides [ J Med Chem. 2007 Nov 15;50(23):5840-7.] — (English)
Fourteen spiro- and dispiro-1,2-dioxolanes were synthesized by peroxycarbenium ion annulations with alkenes in yields ranging from 30% to 94%. Peroxycarbenium ion precursors included triethylsilyldiperoxyketals and -acetals derived from geminal dihydroperoxides and from a new method employing triethylsilylperoxyketals and -acetals derived from ozonolysis of alkenes. The 1,2-dioxolanes were either inactive or orders of magnitude less potent than the corresponding 1,2,4-trioxolanes or artemisinin against P. falciparum in vitro and P. berghei in vivo. In reactions with iron(II), the predominant reaction course for 1,2-dioxolane 3a was two-electron reduction. In contrast, the corresponding 1,2,4-trioxolane 1 and the 1,2,4-trioxane artemisinin undergo primarily one-electron iron(II)-mediated reductions. The key structural element in the latter peroxides appears to be an oxygen atom attached to one or both of the peroxide-bearing carbon atoms that permits rapid -scission reactions (or H shifts) to form primary or secondary carbon-centered radicals rather than further reduction of the initially formed Fe(III) complexed oxy radicals...
Childhood Asymptomatic Malaria and Nutritional Status among Port Harcourt Children [East African Journal of Public Health, Vol 4 No 2, October 2007] — (English)
From this study the authors concluded that the presence of under-nutrition places children (especially below 5 years of age) at higher risk of malaria related morbidity. Children in malaria endemic areas need adequate nutrition to withstand the negative impact of malaria...
Malaria control among children under five in sub-Saharan Africa: the role of empowerment and parents’ participation besides the clinical strategies [Rural and Remote Health 7 (online), November 2007: 840 10 pp. 190] — (English)
The problem of malaria control in children under 5 years now exceeds a simple biomedical vision of health. Under-five malaria control should also involve parents and nonmedical community sectors. The concern of this study was to establish whether there are interventions relating to under-five malaria control that impact on the target communities...
Prepared in cooperation with WHO ANGOLA INFO.
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