Publications (9)28 Total impact
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Dataset: IV-AS-regimen-severe malaria-JID2012
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Article: Patterns of biomedical science production in a sub-Saharan research center.
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ABSTRACT: Research activities in sub-Saharan Africa may be limited to delegated tasks due to the strong control from Western collaborators, which could lead to scientific production of little value in terms of its impact on social and economic innovation in less developed areas. However, the current contexts of international biomedical research including the development of public-private partnerships and research institutions in Africa suggest that scientific activities are growing in sub-Saharan Africa. This study aims to describe the patterns of clinical research activities at a sub-Saharan biomedical research center. In-depth interviews were conducted with a core group of researchers at the Medical Research Unit of the Albert Schweitzer Hospital from June 2009 to February 2010 in Lambaréné, Gabon. Scientific activities running at the MRU as well as the implementation of ethical and regulatory standards were covered by the interview sessions. The framework of clinical research includes transnational studies and research initiated locally. In transnational collaborations, a sub-Saharan research institution may be limited to producing confirmatory and late-stage data with little impact on economic and social innovation. However, ethical and regulatory guidelines are being implemented taking into consideration the local contexts. Similarly, the scientific content of studies designed by researchers at the MRU, if local needs are taken into account, may potentially contribute to a scientific production with long-term value on social and economic innovation in sub-Saharan Africa. Further research questions and methods in social sciences should comprehensively address the construction of scientific content with the social, economic and cultural contexts surrounding research activities.BMC Medical Ethics 03/2012; 13:3. · 1.74 Impact Factor -
Article: A simplified intravenous artesunate regimen for severe malaria.
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ABSTRACT: We compared a conventional empirically derived regimen with a simplified regimen for parenteral artesunate in severe malaria. This was a randomized, double-blind, placebo-controlled comparison to assess the noninferiority of a simplified 3-dose regimen (given at 0, 24, and 48 hours) compared with the conventional 5-dose regimen of intravenous artesunate (given at 0, 12, 24, 48, and 72 hours) in African children with Plasmodium falciparum malaria with a prespecified delta of 0.2. The total dose of artesunate in each group was 12 mg/kg. The primary end point was the proportion of children clearing ≥ 99% of their admission parasitemia at 24 hours. Safety data, secondary efficacy end points, and pharmacokinetics were also analyzed. In 171 children (per protocol), 78% of the recipients (95% confidence interval [CI], 69%-87%) in the 3-dose group achieved ≥ 99% parasite clearance 24 hours after the start of treatment, compared with 85% (95% CI, 77%-93%) of those receiving the conventional regimen (treatment difference, -7.2%; 95% CI, -18.9% to 4.4%). Dihydroartemisinin was cleared slightly more slowly in those children receiving the higher 3-dose regimen (7.4 vs 8.8 L/h for a 13-kg child; P 5 .008). Pharmacodynamic analysis suggests that 3 doses of artesunate were not inferior to 5 doses for the treatment of severe malaria in children. NCT00522132.The Journal of Infectious Diseases 12/2011; 205(2):312-9. · 6.41 Impact Factor -
Article: Phenotypic characterization of mononuclear blood cells from pregnant Gabonese and their newborns.
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ABSTRACT: As many studies have analysed the immunological phenotype of either neonatal cord or maternal blood during pregnancy, but few have compared paired maternal and neonatal samples, we designed and conducted such a study in a Central African setting. We used flow cytometric analyses with blood samples from pairs of Gabonese mothers and their newborns to determine the cellular composition of mononuclear cells as well as the activation status of T and B lymphocytes and antigen-presenting cells. The results indicate higher activation levels of neonatal cells involved in the first-line defence against pathogens such as natural killer cells, while the neonatal T- and B-cell compartment as well as the neonatal monocyte subpopulations shows a less mature phenotype. Our findings likely reflect a specific neonatal defence mechanism that compensates for otherwise poorly developed immune responses at birth, especially important in an area with a high burden of infectious agents such as Gabon. The data contribute to the establishment of reference values for the mother-neonate relationship in African regions that have similar environmental characteristics.Tropical Medicine & International Health 06/2011; 16(9):1061-9. · 2.80 Impact Factor -
Article: Pentoxifylline as an adjunct therapy in children with cerebral malaria.
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ABSTRACT: Pentoxifylline (PTX) affects many processes that may contribute to the pathogenesis of severe malaria and it has been shown to reduce the duration of coma in children with cerebral malaria. This pilot study was performed to assess pharmacokinetics, safety and efficacy of PTX in African children with cerebral malaria. Ten children admitted to the high dependency unit of the Kilifi District Hospital in Kenya with cerebral malaria (Blantyre coma score of 2 or less) received quinine plus a continuous infusion of 10 mg/kg/24 hours PTX for 72 hours. Five children were recruited as controls and received normal saline instead of PTX. Plasma samples were taken for PTX and tumour necrosis factor (TNF) levels. Blantyre Coma Score, parasitemia, hematology and vital signs were assessed 4 hourly. One child (20%) in the control group died, compared to four children (40%) in the PTX group. This difference was not significant (p = 0.60). Laboratory parameters and clinical data were comparable between groups. TNF levels were lower in children receiving PTX. The small sample size does not permit definitive conclusions, but the mortality rate was unexpectedly high in the PTX group.Malaria Journal 01/2010; 9:368. · 3.19 Impact Factor -
Article: Pregnancy-associated malaria affects toll-like receptor ligand-induced cytokine responses in cord blood.
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ABSTRACT: Pregnancy-associated malaria is known to modify fetal immunity. Most previous studies have been cross-sectional in nature and have focused on the priming of acquired immune responses in utero. In this context, the influence of the timing and/or duration of placental infection with Plasmodium falciparum are unknown, and changes to innate immune responses have not been studied extensively. Pregnant women in Gabon, where P. falciparum infection is endemic, were followed up through monthly clinical and parasitological examinations from the second trimester to delivery. Cells of neonates born to mothers who had acquired P. falciparum infection <or=1 month before delivery had significantly altered interferon-gamma and tumor necrosis factor-alpha responses after stimulation with the Toll-like receptor (TLR) ligands lipopolysaccharide and polyinosine-polycytidylic acid, compared with cells of neonates born either to mothers free of P. falciparum infection or to mothers who were successfully treated for malaria during pregnancy. An independent association between parity and neonatal TLR responsiveness was also discerned in our study. P. falciparum infection history during pregnancy appears to have a pronounced effect on neonatal innate immune responses. The observed effects may have profound implications for the outcome of newly encountered infections in early life.The Journal of Infectious Diseases 10/2008; 198(6):928-36. · 6.41 Impact Factor -
Article: Comparison of immunological status of African and European cord blood mononuclear cells.
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ABSTRACT: The cellular aspects of the immunologic development of the fetus during pregnancy have been studied mainly in populations living in economically well developed countries, and there is no data concerning variation of the neonatal cellular immune system in geographically distinct areas with different environments. Here, we report a comparative immunologic marker analysis of the circulating mononuclear cell subsets in unstimulated cord blood of newborns from Gabon and Austria, assessing the activation and maturation status of T and B lymphocytes as well as antigen-presenting cells. Cells and markers hypothesized to be modulated by frequent exposure to microorganisms and parasites such as regulatory T cells and the expression of toll-like receptor 2 on antigen-presenting cells were also studied. We found marked differences in terms of expression of immunologic markers between the two populations, pointing to a comparatively enhanced maturation status of the neonatal immune system in general in the African setting. The observations suggest that environmental factors, including differential exposure to pathogens as well as nutritional differences, may have substantial impact on the development of the fetal immune system.Pediatric Research 08/2008; 64(6):631-6. · 2.70 Impact Factor -
Article: Antibodies to rifin: a component of naturally acquired responses to Plasmodium falciparum variant surface antigens on infected erythrocytes.
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ABSTRACT: We used a pool of recombinant rifin proteins to pre-adsorb antibodies to rifin in the plasma of semi-immune African (Gabonese) adults and showed that this results in a reduction in the level of IgG antibody reactivity to variant surface antigens (VSA) measured in a standardized flow cytometric assay with a panel of heterologous parasite isolates. The same methods demonstrated a similar but less-marked contribution of antibodies to the duffy binding-like 1alpha (DBL-1alpha ) domain to the overall anti-VSA response. Thus, we conclude that both antibodies to rifin and, to a lesser extent, antibodies directed to conserved regions of the Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) DBL-1alpha domain contribute to the overall antibody response to VSA. We also assessed the associations between these different antibody responses in a cohort of Gabonese children. We found marked differences related to the childrens' history of presentation with either mild or severe malaria, but no consistent pattern that would indicate a specific role or influence of antibody responses to rifin.The American journal of tropical medicine and hygiene 09/2004; 71(2):179-86. · 2.59 Impact Factor -
Article: Temporal variations in immune responses to conserved regions of Plasmodium falciparum merozoite surface proteins related to the severity of a prior malaria episode in Gabonese children.
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ABSTRACT: We measured cellular and humoral responses to conserved regions of Plasmodium falciparum merozoite surface proteins 1 and 2 (MSP-1 and MSP-2) at different times during and after acute infection in matched groups of Gabonese children who presented with either mild or severe malaria. We used an MSP-1(19) recombinant protein and peptides corresponding to conserved epitopes in MSP-1 and MSP-2 N- and C-terminal regions. The prevalences of peptide-induced cell-mediated responses were maximal in both groups when they were healthy, but were consistently higher in the mild malaria group, whereas peptide-specific antibody responses were consistently highest in the severe malaria group. Recombinant MSP-1(19) protein-specific antibody levels in the 2 groups were similar both prior to and 1 month post-treatment but declined later when the children were healthy and parasite-free, to a significantly lower level in those admitted with severe malaria, reflecting the profile of the predominant MSP-1(19)-specific immunoglobulin G1 isotype. This finding implies a defect in the ability of children with a history of severe malaria to maintain an antibody response putatively associated with immunity to P. falciparum malaria.Transactions of the Royal Society of Tropical Medicine and Hygiene 97(4):455-61. · 2.16 Impact Factor
Top Journals
Institutions
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2008–2011
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Eberhard-Karls-Universität Tübingen
- Department of Tropical Medicine
Tübingen, Baden-Wuerttemberg, Germany
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