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4. The effect of dosing strategies on the therapeutic efficacy of artesunate-amodiaquine for uncomplicated malaria: a meta-analysis of individual patient data.

Author

WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, Adjuik, Martin A, Allan, Richard, Anvikar, Anupkumar R, Ashley, Elizabeth A, Ba, Mamadou S, Barennes, Hubert, Barnes, Karen I, Bassat, Quique, Baudin, Elisabeth, Björkman, Anders, Bompart, François, Bonnet, Maryline, Borrmann, Steffen, Brasseur, Philippe, Bukirwa, Hasifa, Checchi, Francesco, Cot, Michel, Dahal, Prabin, D'Alessandro, Umberto, Deloron, Philippe, Desai, Meghna, Diap, Graciela, Djimde, Abdoulaye A, Dorsey, Grant, Doumbo, Ogobara K, Espié, Emmanuelle, Etard, Jean-Francois, Fanello, Caterina I, Faucher, Jean-François, Faye, Babacar, Flegg, Jennifer A, Gaye, Oumar, Gething, Peter W, González, Raquel, Grandesso, Francesco, Guerin, Philippe J, Guthmann, Jean-Paul, Hamour, Sally, Hasugian, Armedy Ronny, Hay, Simon I, Humphreys, Georgina S, Jullien, Vincent, Juma, Elizabeth, Kamya, Moses R, Karema, Corine, Kiechel, Jean R, Kremsner, Peter G, Krishna, Sanjeev, Lameyre, Valérie, Ibrahim, Laminou M, Lee, Sue J, Lell, Bertrand, Mårtensson, Andreas, Massougbodji, Achille, Menan, Hervé, Ménard, Didier, Menéndez, Clara, Meremikwu, Martin, Moreira, Clarissa, Nabasumba, Carolyn, Nambozi, Michael, Ndiaye, Jean-Louis, Nikiema, Frederic, Nsanzabana, Christian, Ntoumi, Francine, Ogutu, Bernhards R, Olliaro, Piero, Osorio, Lyda, Ouédraogo, Jean-Bosco, Penali, Louis K, Pene, Mbaye, Pinoges, Loretxu, Piola, Patrice, Price, Ric N, Roper, Cally, Rosenthal, Philip J, Rwagacondo, Claude Emile, Same-Ekobo, Albert, Schramm, Birgit, Seck, Amadou, Sharma, Bhawna, Sibley, Carol Hopkins, Sinou, Véronique, Sirima, Sodiomon B, Smith, Jeffery J, Smithuis, Frank, Somé, Fabrice A, Sow, Doudou, Staedke, Sarah G, Stepniewska, Kasia, Swarthout, Todd D, Sylla, Khadime, Talisuna, Ambrose O, Tarning, Joel, Taylor, Walter RJ, Temu, Emmanuel A, Thwing, Julie I, Tjitra, Emiliana, and Tine, Roger CK

Subjects
WorldWide Antimalarial Resistance Network (WWARN) AS-AQ Study Group, Humans, Malaria, Falciparum, Recurrence, Artemisinins, Amodiaquine, Drug Combinations, Antimalarials, Treatment Outcome, Risk Factors, Dose-Response Relationship, Drug, Middle Aged, Africa, Female, Male, Malaria, Plasmodium falciparum, Drug resistance, Artesunate, Dosing, Efficacy, Falciparum, Dose-Response Relationship, Drug, Medical and Health Sciences, General & Internal Medicine
Abstract

BackgroundArtesunate-amodiaquine (AS-AQ) is one of the most widely used artemisinin-based combination therapies (ACTs) to treat uncomplicated Plasmodium falciparum malaria in Africa. We investigated the impact of different dosing strategies on the efficacy of this combination for the treatment of falciparum malaria.MethodsIndividual patient data from AS-AQ clinical trials were pooled using the WorldWide Antimalarial Resistance Network (WWARN) standardised methodology. Risk factors for treatment failure were identified using a Cox regression model with shared frailty across study sites.ResultsForty-three studies representing 9,106 treatments from 1999-2012 were included in the analysis; 4,138 (45.4%) treatments were with a fixed dose combination with an AQ target dose of 30 mg/kg (FDC), 1,293 (14.2%) with a non-fixed dose combination with an AQ target dose of 25 mg/kg (loose NFDC-25), 2,418 (26.6%) with a non-fixed dose combination with an AQ target dose of 30 mg/kg (loose NFDC-30), and the remaining 1,257 (13.8%) with a co-blistered non-fixed dose combination with an AQ target dose of 30 mg/kg (co-blistered NFDC). The median dose of AQ administered was 32.1 mg/kg [IQR: 25.9-38.2], the highest dose being administered to patients treated with co-blistered NFDC (median = 35.3 mg/kg [IQR: 30.6-43.7]) and the lowest to those treated with loose NFDC-25 (median = 25.0 mg/kg [IQR: 22.7-25.0]). Patients treated with FDC received a median dose of 32.4 mg/kg [IQR: 27-39.0]. After adjusting for reinfections, the corrected antimalarial efficacy on day 28 after treatment was similar for co-blistered NFDC (97.9% [95% confidence interval (CI): 97.0-98.8%]) and FDC (98.1% [95% CI: 97.6%-98.5%]; P = 0.799), but significantly lower for the loose NFDC-25 (93.4% [95% CI: 91.9%-94.9%]), and loose NFDC-30 (95.0% [95% CI: 94.1%-95.9%]) (P

Published
2015

8. Clinical development of a VAR2CSA-based placental malaria vaccine PAMVAC: Quantifying vaccine antigen-specific memory B & T cell activity in Beninese primigravidae

Author

Gbédandé, Komi, Fievet, Nadine, Viwami, Firmine, Ezinmegnon, Sem, Issifou, Saadou, Chippaux, Jean-Philippe, Dossou, Yannelle, Moutairou, Kabirou, Massougbodji, Achille, Ndam, Nicaise, de Jongh, Willem Adriaan, Søgaard, T. Max M., Salanti, Ali, Nielsen, Morten A., Esen, Meral, Mordmüller, Benjamin, Deloron, Philippe, and Luty, Adrian J.F.

Published
2017
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10. Infected erythrocytes and plasma proteomics reveal a specific protein signature of severe malaria.

Author

Fraering, Jeremy, Salnot, Virginie, Gautier, Emilie-Fleur, Ezinmegnon, Sem, Argy, Nicolas, Peoc'h, Katell, Manceau, Hana, Alao, Jules, Guillonneau, François, Migot-Nabias, Florence, Bertin, Gwladys I, Kamaliddin, Claire, Aubouy, Agnes, Affolabi, Dissou, Biokou, Bibiane, Cot, Michel, Degbelo, Jean-Eudes, Deloron, Philippe, Dramane, Latifou, and Faucher, Jean-François

Abstract

Cerebral malaria (CM), the most lethal complication of Plasmodium falciparum severe malaria (SM), remains fatal for 15–25% of affected children despite the availability of treatment. P. falciparum infects and multiplies in erythrocytes, contributing to anemia, parasite sequestration, and inflammation. An unbiased proteomic assessment of infected erythrocytes and plasma samples from 24 Beninese children was performed to study the complex mechanisms underlying CM. A significant down-regulation of proteins from the ubiquitin–proteasome pathway and an up-regulation of the erythroid precursor marker transferrin receptor protein 1 (TFRC) were associated with infected erythrocytes from CM patients. At the plasma level, the samples clustered according to clinical presentation. Significantly, increased levels of the 20S proteasome components were associated with SM. Targeted quantification assays confirmed these findings on a larger cohort (n = 340). These findings suggest that parasites causing CM preferentially infect reticulocytes or erythroblasts and alter their maturation. Importantly, the host plasma proteome serves as a specific signature of SM and presents a remarkable opportunity for developing innovative diagnostic and prognostic biomarkers. Synopsis: A mass spectrometry-based proteomic screening of both plasma and infected erythrocytes from Beninese children with various clinical manifestations of malaria (Uncomplicated Malaria (UM), Severe Malarial Anemia (SMA), and Cerebral Malaria (CM)) was performed. An increase of TFRC abundance was observed in infected erythrocyte samples from CM patients when compared to UM patients, coupled with a decrease of plasmatic Transferrin levels. 20S proteasome abundance was increased in plasma from children with severe malaria (CM and SMA) compared to UM, suggesting that it could serve as potential biomarker of severe malaria. A deregulated iron metabolism pathway and an increased hemolytic anemia were described in the severe malaria groups. Six P. falciparum proteins involved in red blood cell invasion were quantified specifically in plasma samples from severe malaria cases. A mass spectrometry-based proteomic screening of both plasma and infected erythrocytes from Beninese children with various clinical manifestations of malaria (Uncomplicated malaria (UM), Severe Malarial Anemia (SMA), and Cerebral Malaria (CM)) was performed. [ABSTRACT FROM AUTHOR]

Published
2024
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18. Temporal distribution of Plasmodium falciparum recrudescence following artemisinin-based combination therapy: an individual participant data meta-analysis

Author

Dahal, Prabin, Simpson, Julie Anne, Abdulla, Salim, Achan, Jane, Adam, Ishag, Agarwal, Aarti, Allan, Richard, Anvikar, Anupkumar R., Ashley, Elizabeth A., Bassat, Quique, Borrmann, Steffen, Bousema, Teun, Bukirwa, Hasifa, Carrara, Verena, I, Corsi, Marco, D'Alessandro, Umberto, Davis, Timothy M. E., Deloron, Philippe, Desai, Meghna, Dimbu, Pedro Rafael, Djalle, Djibrine, Djimde, Abdoulaye, Dorsey, Grant, Drakeley, Chris J., Duparc, Stephan, Edstein, Michael D., Espie, Emmanuelle, Faiz, Abul, Falade, Catherine, Fanello, Caterina, Faucher, Jean-Francois, Faye, Babacar, Fortes, Filomeno de Jesus, Gadalla, Nahla B., Gaye, Oumar, Gil, J. Pedro, Gilayeneh, Julius, Greenwood, Brian, Grivoyannis, Anastasia, Hien, Tran Tinh, Hwang, Jimee, Janssens, Bart, Juma, Elizabeth, Kamugisha, Erasmus, Karema, Corine, Karunajeewa, Harin A., Kiechel, Jean R., Kironde, Fred, Kofoed, Poul-Erik, Kremsner, Peter G., Lee, Sue J., Marsh, Kevin, Mårtensson, Andreas, Mayxay, Mayfong, Menan, Herve, Mens, Petra, Mutabingwa, Theonest K., Ndiaye, Jean-Louis, Ngasala, Billy, Noedl, Harald, Nosten, Francois, Offianan, Andre Toure, Ogutu, Bernhards R., Olliaro, Piero L., Ouedraogo, Jean Bosco, Piola, Patrice, Plowe, Christopher, V, Plucinski, Mateusz M., Pratt, Oliver James, Premji, Zulfikarali, Ramharter, Michael, Rogier, Christophe, Vitare, Primum, Rombo, Lars, Rosenthal, Philip J., Sibley, Carol, Sirima, Sodiomon, Smithuis, Frank, Staedke, Sarah G., Sutanto, Inge, Talisuna, Ambrose Otau, Tarning, Joel, Taylor, Walter R. J., Temu, Emmanuel, Thriemer, Kamala, Thuy-Nhien, Nguyen, Udhayakumar, Venkatachalam, Ursing, Johan D., van Herp, Michel, van Lenthe, Marit, van Vugt, Michele, William, Yavo, Winnips, Cornelis, Zaloumis, Sophie, Zongo, Issaka, White, Nick J., Guerin, Philippe J., Stepniewska, Kasia, Price, Ric N., Arinaitwe, Emmanuel, and Group, WorldWide Antimalarial Resistance Network Methodology Study

Subjects
Infectious Medicine, Efficacy, Follow-up, Recrudescence, Artemether, Lumefantrine Drug Combination, Plasmodium falciparum, Infektionsmedicin, Distribution, Artemisinins, Malaria, Antimalarials, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, Recurrence, Child, Preschool, Humans, Parasitology, Artemether, Child
Abstract

Background The duration of trial follow-up affects the ability to detect recrudescent infections following anti-malarial treatment. The aim of this study was to explore the proportions of recrudescent parasitaemia as ascribed by genotyping captured at various follow-up time-points in treatment efficacy trials for uncomplicated Plasmodium falciparum malaria. Methods Individual patient data from 83 anti-malarial efficacy studies collated in the WorldWide Antimalarial Resistance Network (WWARN) repository with at least 28 days follow-up were available. The temporal and cumulative distributions of recrudescence were characterized using a Cox regression model with shared frailty on study-sites. Fractional polynomials were used to capture non-linear instantaneous hazard. The area under the density curve (AUC) of the constructed distribution was used to estimate the optimal follow-up period for capturing a P. falciparum malaria recrudescence. Simulation studies were conducted based on the constructed distributions to quantify the absolute overestimation in efficacy due to sub-optimal follow-up. Results Overall, 3703 recurrent infections were detected in 60 studies conducted in Africa (15,512 children aged 48 mg/kg total piperaquine (PIP) dose and 9% [95% CI 0–22%] in those treated with ≤ 48 mg/kg PIP dose. In absolute terms, the simulation study found that trials limited to 28 days follow-up following AL underestimated the risk of recrudescence by a median of 2.8 percentage points compared to day 63 estimates and those limited to 42 days following DP underestimated the risk of recrudescence by a median of 2.0 percentage points compared to day 42 estimates. The analysis was limited by few clinical trials following patients for longer than 42 days (9 out of 83 trials) and the imprecision of PCR genotyping which overcalls recrudescence in areas of higher transmission biasing the later distribution. Conclusions Restricting follow-up of clinical efficacy trials to day 28 for AL and day 42 for DP will miss a proportion of late recrudescent treatment failures but will have a modest impact in derived efficacy. The results highlight that as genotyping methods improve consideration should be given for trials with longer duration of follow-up to detect early indications of emerging drug resistance.

Published
2022

20. Protective antibodies against placental malaria and poor outcomes during pregnancy, Benin

Author

Ndam, Nicaise Tuikue, Denoeud-Ndam, Lise, Doritchamou, Justin, Viwami, Firmine, Salanti, Ali, Nielsen, Morten A., Fievet, Nadine, Massougbodji, Achille, Luty, Adrian J.F., and Deloron, Philippe

Subjects
Anemia -- Analysis -- Health aspects, Pregnancy -- Analysis -- Health aspects, Fetus -- Growth, Anemia in pregnancy -- Analysis -- Health aspects, Viral antibodies -- Analysis -- Health aspects, Infection -- Analysis -- Health aspects, Malaria -- Analysis -- Health aspects, Pregnant women -- Analysis -- Health aspects, Sulfates -- Analysis -- Health aspects, Antibodies -- Analysis -- Health aspects, Plasmodium falciparum -- Analysis -- Health aspects, Infants (Premature) -- Analysis -- Health aspects, Health
Abstract

Tissue sequestration of Plasmodium falciparum-infected erythrocytes drives malaria-related pathologic changes (1). Tissue sequestration is primarily mediated by members of the parasite variant antigen family of P falciparum erythrocyte membrane protein [...]

Published
2015
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23. Comparison of Sulfadoxine-Pyrimethamine, Unsupervised Artemether-Lumefantrine, and Unsupervised Artesunate-Amodiaquine Fixed-Dose Formulation for Uncomplicated Plasmodium falciparum Malaria in Benin: A Randomized Effectiveness Noninferiority Trial

Author

Faucher, Jean-François, Aubouy, Agnès, Adeothy, Adicat, Cottrell, Gilles, Doritchamou, Justin, Gourmel, Bernard, Houzé, Pascal, Kossou, Hortense, Amedome, Hyacinthe, Massougbodji, Achille, Cot, Michel, and Deloron, Philippe

Published
2009
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32. Artemether-lumefantrine dosing for malaria treatment in young children and pregnant women: A pharmacokinetic-pharmacodynamic meta-analysis

Author

Kloprogge, Frank, Workman, Lesley, Borrmann, Steffen, Tékété, Mamadou, Lefèvre, Gilbert, Hamed, Kamal, Piola, Patrice, Ursing, Johan, Kofoed, Poul Erik, Mårtensson, Andreas, Ngasala, Billy, Björkman, Anders, Ashton, Michael, Friberg Hietala, Sofia, Aweeka, Francesca, Parikh, Sunil, Mwai, Leah, Davis, Timothy M. E., Karunajeewa, Harin, Salman, Sam, Checchi, Francesco, Fogg, Carole, Newton, Paul N., Mayxay, Mayfong, Deloron, Philippe, Faucher, Jean François, Nosten, François, Ashley, Elizabeth A., McGready, Rose, van Vugt, Michele, Proux, Stephane, Price, Ric N., Karbwang, Juntra, Ezzet, Farkad, Bakshi, Rajesh, Stepniewska, Kasia, White, Nicholas J., Guerin, Philippe J., Barnes, Karen I., and Tarning, Joel

Subjects
Lumefantrine -- Patient outcomes, Malaria -- Development and progression -- Care and treatment, Pregnant women -- Health aspects, Artemether -- Patient outcomes, Biological sciences
Abstract

Background The fixed dose combination of artemether-lumefantrine (AL) is the most widely used treatment for uncomplicated Plasmodium falciparum malaria. Relatively lower cure rates and lumefantrine levels have been reported in young children and in pregnant women during their second and third trimester. The aim of this study was to investigate the pharmacokinetic and pharmacodynamic properties of lumefantrine and the pharmacokinetic properties of its metabolite, desbutyl-lumefantrine, in order to inform optimal dosing regimens in all patient populations. Methods and findings A search in PubMed, Embase, ClinicalTrials.gov, Google Scholar, conference proceedings, and the WorldWide Antimalarial Resistance Network (WWARN) pharmacology database identified 31 relevant clinical studies published between 1 January 1990 and 31 December 2012, with 4,546 patients in whom lumefantrine concentrations were measured. Under the auspices of WWARN, relevant individual concentration-time data, clinical covariates, and outcome data from 4,122 patients were made available and pooled for the meta-analysis. The developed lumefantrine population pharmacokinetic model was used for dose optimisation through in silico simulations. Venous plasma lumefantrine concentrations 7 days after starting standard AL treatment were 24.2% and 13.4% lower in children weighing Conclusions Our findings suggest that revised AL dosing regimens for young children and pregnant women would improve drug exposure but would require longer or more complex schedules. These dosing regimens should be evaluated in prospective clinical studies to determine whether they would improve cure rates, demonstrate adequate safety, and thereby prolong the useful therapeutic life of this valuable antimalarial treatment., Author(s): Frank Kloprogge 1,2,3, Lesley Workman 4,5, Steffen Borrmann 6,7, Mamadou Tékété 7,8, Gilbert Lefèvre 9, Kamal Hamed 10, Patrice Piola 11, Johan Ursing 12,13,14, Poul Erik Kofoed 14,15, Andreas [...]

Published
2018
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37. Plasmodium vivax malaria during pregnancy, Bolivia

Author

Brutus, Laurent, Santalla, Jose, Schneider, Dominique, Avila, Juan Carlos, and Deloron, Philippe

Subjects
Pregnancy -- Surveys, Prevalence studies (Epidemiology) -- Surveys, Infection -- Surveys, Malaria -- Surveys, Pregnant women -- Surveys, Health
Abstract

In Latin America, where malaria transmission is low and mostly unstable, Plasmodium vivax is the most prevalent malaria parasite species. Although -3 million pregnant women are exposed to malaria in [...]

Published
2013
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38. Plasmodium falciparum VAR2CSA-specific IgG subclass responses reflect protection against low birth weight and pregnancy-associated malaria

Author

Tornyigah, Bernard, d’Almeida, Tania, Escriou, Guillaume, Viwami, Firmine, Fievet, Nadine, Luty, Adrian, Massougbodji, Achille, Nielsen, Morten, Deloron, Philippe, Tuikue Ndam, Nicaise, University of Ghana, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université de Paris (UP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Copenhagen = Københavns Universitet (KU), Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 261), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), and University of Copenhagen = Københavns Universitet (UCPH)

Subjects
IgG4, Immunology, malaria, IgG3, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, VAR2CSA, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, embryonic structures, parasitic diseases, Immunology and Allergy, pregnancy, IgG subclasses, Original Research
Abstract

International audience; Sequestration of Plasmodium falciparum-infected erythrocytes expressing the VAR2CSA antigen in the placenta results in poor pregnancy outcomes, including low birth weight and maternal anemia. Antigen-specific antibody-mediated immunity is acquired during successive pregnancies. Thus, evaluating VAR2CSA-specific IgG profiles among pregnant women will increase knowledge on the immunological mechanisms associated with protection, and help in the development of VAR2CSA-based placental malaria vaccines. Using the PAMVAC candidate vaccine antigen, we assessed anti-VAR2CSA IgG subclass responses of a cohort of pregnant Beninese, and analyzed their relationships with pregnancy outcomes. Cytophilic IgG1 and IgG3 responses were the most frequent, with prevalences ranging from 28% (IgG3) up to 50% (IgG1). Elevated levels of VAR2CSA-specific total IgG and cytophilic IgG3 during pregnancy were consistently associated with higher birth weights, whilst high levels of IgG4 were associated with a reduced risk of placental infections. This suggests that protective anti-VAR2CSA IgG responses are coordinated between both cytophilic and noncytophilic antibodies.

Published
2021

39. Bonnes Pratiques Cliniques dans les pays en développement : recommandations en termes d’application

Author

Bazin, Brigitte, Chambon, Jean-François, de Rochegonde, Thierry, Deloron, Philippe, Garenne, Michel, Gersberg, Marta, Guérin, Philippe, Juillet, Yves, Lameyre, Valérie, Leblond, Annie, L’Hadj, Mohamed, Ravinetto, Rafaella, Riveau, Gilles, Schacht, Anne-Marie, Simon, François, Toneatti, Christine, Torreele, Els, Urfalino, Philippe, Bompart, François, Hirsch, François, Bertoye, Pierre-Henri, and Vray, Muriel

Published
2008
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40. Good Clinical Practice in Developing Countries: Applying Recommendations

Author

Bazin, Brigitte, Chambon, Jean-François, de Rochegonde, Thierry, Deloron, Philippe, Garenne, Michel, Gersberg, Marta, Guérin, Philippe, Juillet, Yves, Lameyre, Valérie, Leblond, Annie, L’Hadj, Mohamed, Ravinetto, Rafaella, Riveau, Gilles, Schacht, Anne-Marie, Simon, François, Toneatti, Christine, Torreele, Els, Urfalino, Philippe, Bompart, François, Hirsch, François, Bertoye, Pierre-Henri, and Vray, Muriel

Published
2008
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41. Sulfadoxine/pyrimethamine intermittent preventive treatment for malaria during pregnancy

Author

Deloron, Philippe, Bertin, Gwladys, Briand, Valerie, Massougbodji, Achille, and Cot, Michel

Subjects
Medicine, Preventive, Pregnancy, Antimalarials, Infection -- Drug therapy -- Genetic aspects, Public health, Preventive health services, Malaria -- Drug therapy -- Genetic aspects, Pregnant women -- Drug therapy, Plasmodium falciparum, Dihydrofolate reductase, Health, World Health Organization
Abstract

Malaria during pregnancy is a major cause of anemia and maternal death and one of the main causes of low birthweight (1,2). Consequently, the World Health Organization (WHO) recommends protection [...]

Published
2010
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43. Dynamics of PfEMP 1 antibody profile from birth to 12 months of age in Beninese infants

Author

Moussiliou, A., Turner, L., Cottrell, Gilles, Doritchamou, J., Gbedande, K., Fievet, Nadine, Luty, A. J. F., Massougbodji, A., Theander, T. G., Deloron, Philippe, Lavstsen, T., and Ndam, N. T.

Subjects
children, IgG, malaria, PfEMP 1, CIDR domains
Abstract

Background. Plasmodiumfalciparum-infected erythrocytes bind to specific endothelial cell receptors via members of the PfEMP1 family exported onto the erythrocyte surface. These interactions are mediated by different types of cysteine-rich interdomain region (CIDR) domains found in the N-terminal region of all PfEMP 1 . CIDR alpha 1 domains bind endothelial protein C receptor (EPCR), CIDR alpha 2-6 domains bind CD36, whereas the receptor specificity of CIDR beta/gamma/delta domains is unknown. Methods. In this study, we investigated the level of immunoglobulin (Ig)G targeting the different types of PfEMP1 CIDR during the first year of life. We used plasma collected longitudinally from children of pregnant women who had been followed closely through pregnancy. Results. Antibodies to CIDR alpha 1 domains were more frequent in cord blood compared with antibodies to CIDR alpha 2-6 domains. Higher IgG levels to EPCR-binding CIDR alpha 1 variants positively correlated with the timing of first infections. Antibodies to all PfEMP1 types declined at similar rates to the point of disappearance over the first 6 months of life. At 12 months, children had acquired antibody to all types of CIDR domains, mostly in children with documented P falciparum infections. Conclusions. These observations agree with the notion that the timing and phenotype of first P falciparum infections in life are influenced by the immune status of the mother.

Published
2020

45. Guidelines for Clinical Research in Developing Countries

Author

d’Alessandro, Umberto, Belorgey, Chantal, Bilbault, Pascal, Bompart, François, Champey, Yves, Deloron, Philippe, Demarez, Jean Paul, Dessein, Alain, Funck-Bruntano, Christian, Gersberg, Marta, Hirsch, François, Kandé, Victor, Kapere, Solomon, Lassale, Catherine, Lemerle, Jean, Pilorgé, Fabrice, Riveau, Gilles, de Rochegonde, Thierry, Simon, François, Ter-Minassian, Daniel, and Vray, Muriel

Published
2007
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46. Recommandations pour la recherche clinique dans les pays en développement

Author

d’Alessandro, Umberto, Belorgey, Chantal, Bilbault, Pascal, Bompart, François, Champey, Yves, Deloron, Philippe, Demarez, Jean Paul, Dessein, Alain, Funck-Bruntano, Christian, Gersberg, Marta, Hirsch, François, Kandé, Victor, Kapere, Solomon, Lassale, Catherine, Lemerle, Jean, Pilorgé, Fabrice, Riveau, Gilles, de Rochegonde, Thierry, Simon, François, Ter-Minassian, Daniel, and Vray, Muriel

Published
2007
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48. Comprehensive Analysis of Transcript and Protein Relative Abundance During Blood Stages of Plasmodium falciparum Infection

Author

Kamaliddin, Claire, primary, Guillochon, Emilie, additional, Salnot, Virginie, additional, Rombaut, David, additional, Huguet, Stéphanie, additional, Guillonneau, François, additional, Houzé, Sandrine, additional, Cot, Michel, additional, Deloron, Philippe, additional, Argy, Nicolas, additional, and Bertin, Gwladys I., additional

Published
2021
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50. ICAM-1 Kilifi variant is not associated with cerebral and severe malaria pathogenesis in Beninese children.

Author

Blankson, Samuel Odarkwei, Dadjé, Danielle Seri, Traikia, Nadjla, Alao, Maroufou J., Ayivi, Serge, Amoussou, Annick, Deloron, Philippe, Ndam, Nicaise Tuikue, Milet, Jacqueline, Basco, Leonardo K., Aniweh, Yaw, and Tahar, Rachida

Subjects
CEREBRAL malaria, ERYTHROCYTE membranes, ERYTHROCYTES, CELL adhesion, GENETIC polymorphisms, SICKLE cell trait
Abstract

Background: Cytoadhesion and sequestration of Plasmodium falciparum infected red blood cells (iRBC) in the microvasculature of vital organs are a major cause of malaria pathology. Several studies have provided evidence on the implication of the human host intercellular adhesion molecule-1 (ICAM-1) as a major receptor for iRBCs binding to P. falciparum erythrocyte membrane protein 1 (PfEMP1) in the development of severe and cerebral malaria. The genetic polymorphism K29M in the immunoglobulin-like domain of ICAM-1, known as ICAM-1Kilifi, has been associated with either increased or decreased risk of developing cerebral malaria. Methods: To provide more conclusive results, the genetic polymorphism of ICAM-1Kilifi was assessed by PCR and sequencing in blood samples from 215 Beninese children who presented with either mild or severe malaria including cerebral malaria. Results and conclusions: The results showed that in this cohort of Beninese children, the ICAM-1kilifi variant is present at the frequencies of 0.27, similar to the frequency observed in other African countries. This ICAM-1kilifi variant was not associated with disease severity in agreement with other findings from the Gambia, Tanzania, Malawi, Gabon, and Thailand, suggesting no evidence of a direct link between this polymorphism and the pathogenesis of severe and cerebral malaria. [ABSTRACT FROM AUTHOR]

Published
2022
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