Peter G. Kremsner

Intermittent Preventive Treatment against Malaria in Infants in Gabon-A Randomized, Double-Blind, Placebo-Controlled Trial

BACKGROUNDnIntermittent preventive treatment aims to maximize the protective effects of malaria chemoprophylaxis while minimizing the deleterious effects.nnnMETHODSnIn Gabon, 1189 infants received either sulfadoxine-pyrimethamine (SP; 250 and 12.5 mg, respectively) or placebo at 3, 9, and 15 months of age. Children were actively followed-up until 18 months of age.nnnRESULTSnIn the intention-to-treat population at 18 months of follow-up, 84 children (17%) in the SP group had > or =1 episode of anemia, versus 108 (21%) in the placebo group (protective efficacy, 22% [95% confidence interval {CI}, -1% to 40%]; P=.06). In the intervention group, there were 66 episodes during 485 person-years at risk, compared with 79 episodes during 497 years in the placebo group (protective efficacy, 17% [95% CI, -24% to 45%; P=.36). The effects were similar at 12 months of follow-up. The study drug was safe and well tolerated.nnnCONCLUSIONSnThe intervention was efficacious, producing a reduction in risk for anemia but a smaller effect against malaria. It is a valuable additional tool to control malaria in a highly vulnerable age group. Remaining important questions are currently being addressed in further studies.nnnTRIAL REGISTRATIONnClinicalTrials.gov identifier: NCT00167843.

A Duffy Binding—Like Domain Is Involved in the NKp30-Mediated Recognition of Plasmodium falciparum—Parasitized Erythrocytes by Natural Killer Cells

The recent demonstration that purified natural killer (NK) cells lyse Plasmodium falciparum-parasitized red blood cells (Pf-pRBCs) suggests that innate immunity is important in malaria. NK cell killing--presumably an early host response to infection--requires intimate contact between NK natural cytotoxicity receptors (NCRs) and ligands expressed on the surface of Pf-pRBCs. We investigated whether the Duffy binding-like (DBL)-1 alpha domain of P. falciparum erythrocyte membrane protein-1 (PfEMP-1) expressed on parasitized erythrocytes rendered Pf-pRBCs susceptible to NK cell lysis. We showed that with NKp30-immunoglobulin and NKp46-immunoglobulin fusion proteins and DBL-1alpha peptides NCRs are involved in the NK cell-Pf-pRBC interaction. This interaction was direct, specific, and functional, leading to perforin production and granzyme B release. The prior treatment of NK cells with DBL-1 alpha peptides abolished both this interaction and killing activity, suggesting that DBL-1 alpha -NCRs interaction is the key recognition mechanism leading to parasite killing by NK cells.

Randomized Controlled Trial of Fosmidomycin-Clindamycin versus Sulfadoxine-Pyrimethamine in the Treatment of Plasmodium falciparum Malaria

ABSTRACT Fosmidomycin-clindamycin therapy given every 12 h for 3 days was compared with a standard single oral dose of sulfadoxine-pyrimethamine. The two treatments showed comparably good tolerabilities and had an identical high degree of efficacy of 94% in a randomized trial carried out with 105 Gabonese children aged 3 to 14 years with uncomplicated malaria. These antimalarials merit further clinical exploration.

History and perspectives of medical research at the Albert Schweitzer Hospital in Lambaréné, Gabon

ZusammenfassungAlbert Schweitzer gründete 1913 in Lambaréné, Gabun, eines der ersten tropischen Spitäler, das vorrangig der Gesundheitsversorgung der einheimischen Bevölkerung gewidmet war. 1981 wurde am Albert Schweitzer Spital eine medizinische Forschungseinrichtung gegründet (www.lambarene.org). Diese Einrichtung entwickelte sich in den letzten 15 Jahren zu einer der weltweit führenden Forschungsstätten im Bereich der klinischen tropenmedizinischen Forschung, besonders im Bereich der Malaria. Durch den Bau eines eigens für molekularbiologische und immunologische Forschung bestimmten Gebäudes wird nun auch die Grundlagenforschung am Albert Schweitzer Spital möglich. Kürzlich wurde auch ein in Afrika einzigartiger postgradueller Lehrgang in Klinischer Forschung etabliert.SummaryIn 1913 Albert Schweitzer founded one of the first modern hospitals in Africa dedicated to the health of the local population. The Albert Schweitzer Hospital is located in Lambaréné, a small town in Gabon. In 1981 a research department – the Medical Research Unit – was established with the aim to perform research in the field of infectious diseases (www.lambarene.org). The main focus lies on clinical research on malaria and other parasitic diseases. Studies on the molecular biology and immunology of parasitic diseases are fostered since the inauguration of a novel building dedicated for basic science. A training program in clinical research in tropical diseases for African scientists has been set up recently.

Artesunate – amodiaquine combination therapy for falciparum malaria in young Gabonese children

BackgroundArtesunate-amodiaquine combination for the treatment of childhood malaria is one of the artemisinin combination therapies (ACTs) recommended by National authorities in many African countries today. Effectiveness data on this combination in young children is scarce.MethodsThe effectiveness of three daily doses of artesunate plus amodiaquine combination given unsupervised (n = 32), compared with the efficacy when given under full supervision (n = 29) to children with falciparum malaria were assessed in an unrandomized study.Results61 patients analysed revealed a PCR-corrected day-28 cure rate of 86 % (25 of 29 patients; CI 69 – 95 %) in the supervised group and 63 % (20 of 32 patients; CI 45 – 77 %) in the unsupervised group. The difference in outcome between both groups was statistically significant (p = 0.04). No severe adverse events were reported.ConclusionThe effectiveness of this short course regimen in young children with falciparum malaria could be augmented by increased adherence and improved formulation.

Comparison of PCR-based detection of Plasmodium falciparum infections based on single and multicopy genes

PCR-based assays are the most sensitive and specific methods to detect malaria parasites.This study compared the diagnostic accuracy of three PCR-based assays that do not only differ in their sequence target, but also in the number of copies of their target region, for the detection of Plasmodium falciparum in 401 individuals living in a malaria-endemic area in Nigeria. Compared to a composite reference generated from results of all the 3 PCR assays, the stevor gene amplification had a sensitivity of 100% (Kappa = 1; 95% CI = 1.000–1.000), 83% (Kappa = 0.718; 95% CI = 0.648–0.788) by SSUrRNA gene PCR and 71% (Kappa = 0.552; 95% CI = 0.478–0.627) by the msa-2 gene amplification.Results from this study indicate that the stevor gene amplification is the most sensitive technique for the detection of P. falciparum. This assay may be an important reference standard, especially when a confirmatory technique with high sensitivity and specificity is needed for ruling out P. falciparum infection.

New method to quantify erythrophagocytosis by autologous monocytes

Anemia is the net result of decreased red blood cell (RBC) production and increased removal of RBCs. Replication and maturation of erythroid precursors and RBC lysis can be measured by standardized in vitro methods and surrogate markers, respectively. In contrast, erythrophagocytosis by autologous phagocytes is more difficult to quantify.

The fight against malaria -- this month in Vienna.

Malaria, tuberculosis and AIDS are the three most devastating infectious diseases. Every year there are about 500 million new cases of malaria and two million people die. Plasmodium falciparum is the most common and life threatening malarial parasite infecting humans. Whereas there has been no more autochthonous malaria in Europe for about 50 years, travellers are importing malaria to Europe from endemic countries, mostly from tropical Africa [1]. Plasmodium falciparum malaria is most prevalent in Africa and the majority of deaths due to malaria occur in young African children [2]. Another group at risk of malaria are pregnant women. Therefore control measures against malaria are most often focussed on children and pregnant women. Efficient control of malaria in a region must be an integrated approach consisting of a diversity of interventions, such as education of people, vector control, vector avoidance, prompt and efficient malaria treatment of cases and prophylactic antimalarial measures. After the classical antimalarials had lost their efficiency to treat malaria adaequately, new antimalarial compounds and new antimalarial combinations had to be developed to avert a malaria disaster [3–5]. Antimalarial combinations, mainly using artemisinins together with old drugs or modified old drugs, have recently been developed or are under development [6–8]. However, combinations of new drugs with a novel mechanism of action would be preferable, especially in the light of alarming news about the spread of drug-resistant parasites and a decrease of artemisinine sensitivity of parasites [9, 10]. Properly tested and developed drugs against malaria in The fight against malaria – this month in Vienna