hosted by

Christophe ROGIER

Pr. Christophe ROGIER, MD, PhD 
Professeur agrégé du Val de Grâce


Institut Pasteur de Madagascar
B.P. 1274
101 Antananarivo

Tel.: +261 202241272
Fax.: +261 202241534
Cell.:+261 320541200 / +33 660056846
Email: &

Journal articles

C Sokhna, M O Ndiath, C Rogier (2013)  The changes in mosquito vector behaviour and the emerging resistance to insecticides will challenge the decline of malaria.   Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases Jun  
Abstract: The preventive measures against malaria recommended by the WHO include anti-vector procedures such as indoor residual spraying, the use of long-lasting insecticide-treated bed-nets, and the destruction of larval breeding sites. The presence of insecticide-treated materials inside the mosquito habitat has consequences for the vector's population, reducing density, survival, contact with humans, and feeding frequency. However, the effectiveness of these tools is being challenged by the emergence of insecticide resistance. The evolution of resistance to insecticides in Anopheles threatens to thwart the goal of decreasing malaria transmission, in an arms race between malaria control programmes and the vector populations. Multiple mechanisms of resistance to insecticides have been observed in Anopheles populations, including target site mutation (knockdown resistance), increased metabolic detoxification, and remarkable behavioural adaptation. These disturbing observations all show the capacity of Anopheles to adapt to and circumvent strategies aimed at reducing malaria transmission. Thus, by using nets to protect ourselves, are we providing Anopheles with the entire arsenal needed to hit much harder?
Aurélie Pascual, Bécaye Fall, Nathalie Wurtz, Mansour Fall, Cheikhou Camara, Aminata Nakoulima, Eric Baret, Bakary Diatta, Khadidiatou Ba Fall, Pape Saliou Mbaye, Yaya Diémé, Raymond Bercion, Hervé Bogreau, Sébastien Briolant, Christophe Rogier, Boubacar Wade, Bruno Pradines (2013)  In vitro susceptibility to quinine and microsatellite variations of the Plasmodium falciparum Na+/H+ exchanger transporter (Pfnhe-1) gene in 393 isolates from Dakar, Senegal.   Malaria journal 12: 06  
Abstract: Although the World Health Organization recommends replacing quinine (QN) by artesunate due to its increased efficacy and the higher tolerance to the drug in both adults and children, QN remains a first-line treatment for severe malaria, especially in Africa. Investigations of microsatellite Pfnhe-1âms4760 polymorphisms in culture-adapted isolates from around the world have revealed that an increase in the number of DNNND amino acid motifs was associated with decreased QN susceptibility, whereas an increase in the number of DDNHNDNHNND motifs was associated with increased QN susceptibility.
Gaëtan Texier, Vanessa Machault, Meili Barragti, Jean-Paul Boutin, Christophe Rogier (2013)  Environmental determinant of malaria cases among travellers.   Malaria journal 12: 03  
Abstract: Approximately 125 million travellers visit malaria-endemic countries annually and about 10,000 cases of malaria are reported after returning home. Due to the fact that malaria is insect vector transmitted, the environment is a key determinant of the spread of infection. Geo-climatic factors (such as temperature, moisture, water quality) determine the presence of Anopheles breeding sites, vector densities, adult mosquito survival rate, longevity and vector capacity. Several studies have shown the association between environmental factors and malaria incidence in autochthonous population. The association between the incidence of clinical malaria cases among non-immune travellers and environmental factors is yet to be evaluated. The objective of the present study was to identify, at a country scale (Ivory Coast), the environmental factors that are associated with clinical malaria among non-immune travellers, opening the way for a remote sensing-based counselling for malaria risk prevention among travellers.
Serge-Brice Assi, Marie-Claire Henry, Christophe Rogier, Joël Dossou-Yovo, Martine Audibert, Jacky Mathonnat, Thomas Teuscher, Pierre Carnevale (2013)  Inland valley rice production systems and malaria infection and disease in the forest region of western Cote d'Ivoire.   Malaria journal 12: 1. Jul  
Abstract: This study aimed to determine the epidemiological impact of rice cultivation in inland valleys on malaria in the forest region of western Cote d'Ivoire. The importance of malaria was compared in terms of prevalence and parasite density of infections and also in terms of clinical malaria incidence between three agro-ecosystems: (i) uncultivated inland valleys, (R0), (ii) inland valleys with one annual rice cultivation in the rainy season, (R1) and (iii) developed inland valleys with two annual rice cultivation cycles, (R2).
Bouh Abdi Khaireh, Ashenafi Assefa, Hawa Hassan Guessod, Leonardo K Basco, Mohamed Abdi Khaireh, Aurélie Pascual, Sébastien Briolant, Samatar Mohamed Bouh, Ismaïl Hassan Farah, Habib Moussa Ali, Abdoul-Ilah Ahmed Abdi, Mouna Osman Aden, Zamzam Abdillahi, Souleiman Nour Ayeh, Houssein Youssouf Darar, Jean-Louis Koeck, Christophe Rogier, Bruno Pradines, Hervé Bogreau (2013)  Population genetics analysis during the elimination process of Plasmodium falciparum in Djibouti.   Malaria journal 12: 06  
Abstract: Case management of imported malaria within the context of malaria pre-elimination is increasingly considered to be relevant because of the risk of resurgence. The assessment of malaria importation would provide key data i) to select countries with propitious conditions for pre-elimination phase and ii) to predict its feasibility. Recently, a sero-prevalence study in Djibouti indicated low malaria prevalence, which is propitious for the implementation of pre-elimination, but data on the extent of malaria importation remain unknown.
Albin Fontaine, Thierry Fusaï, Sébastien Briolant, Sylvain Buffet, Claude Villard, Emilie Baudelet, Mathieu Pophillat, Samuel Granjeaud, Christophe Rogier, Lionel Almeras (2012)  Anopheles salivary gland proteomes from major malaria vectors.   BMC genomics 13: 11  
Abstract: Antibody responses against Anopheles salivary proteins can indicate individual exposure to bites of malaria vectors. The extent to which these salivary proteins are species-specific is not entirely resolved. Thus, a better knowledge of the diversity among salivary protein repertoires from various malaria vector species is necessary to select relevant genus-, subgenus- and/or species-specific salivary antigens. Such antigens could be used for quantitative (mosquito density) and qualitative (mosquito species) immunological evaluation of malaria vectors/host contact. In this study, salivary gland protein repertoires (sialomes) from several Anopheles species were compared using in silico analysis and proteomics. The antigenic diversity of salivary gland proteins among different Anopheles species was also examined.
Zakia M I Ali, Mahfoud Bakli, Albin Fontaine, Nawal Bakkali, Vinh Vu Hai, Stephane Audebert, Yvan Boublik, Frederic Pagès, Franck Remoué, Christophe Rogier, Christophe Fraisier, Lionel Almeras (2012)  Assessment of Anopheles salivary antigens as individual exposure biomarkers to species-specific malaria vector bites.   Malaria journal 11: 12  
Abstract: Malaria transmission occurs during the blood feeding of infected anopheline mosquitoes concomitant with a saliva injection into the vertebrate host. In sub-Saharan Africa, most malaria transmission is due to Anopheles funestus s.s and to Anopheles gambiae s.l. (mainly Anopheles gambiae s.s. and Anopheles arabiensis). Several studies have demonstrated that the immune response against salivary antigens could be used to evaluate individual exposure to mosquito bites. The aim of this study was to assess the use of secreted salivary proteins as specific biomarkers of exposure to An. gambiae and/or An. funestus bites.
Clémentine Roucher, Christophe Rogier, Fambaye Dieye-Ba, Cheikh Sokhna, Adama Tall, Jean-François Trape (2012)  Changing malaria epidemiology and diagnostic criteria for Plasmodium falciparum clinical malaria.   PloS one 7: 9. 09  
Abstract: In tropical Africa, where malaria is highly endemic, low grade infections are asymptomatic and the diagnosis of clinical malaria is usually based on parasite density. Here we investigate how changes in malaria control and endemicity modify diagnostic criteria of Plasmodium falciparum attacks.
Vanessa Machault, Cécile Vignolles, Frédéric Pagès, Libasse Gadiaga, Yves M Tourre, Abdoulaye Gaye, Cheikh Sokhna, Jean-François Trape, Jean-Pierre Lacaux, Christophe Rogier (2012)  Risk mapping of Anopheles gambiae s.l. densities using remotely-sensed environmental and meteorological data in an urban area: Dakar, Senegal.   PloS one 7: 11. 11  
Abstract: High malaria transmission heterogeneity in an urban environment is basically due to the complex distribution of Anopheles larval habitats, sources of vectors. Understanding 1) the meteorological and ecological factors associated with differential larvae spatio-temporal distribution and 2) the vectors dynamic, both may lead to improving malaria control measures with remote sensing and high resolution data as key components. In this study a robust operational methodology for entomological malaria predictive risk maps in urban settings is developed.
Sébastien Briolant, Hervé Bogreau, Marine Gil, Housem Bouchiba, Eric Baret, Rémy Amalvict, Christophe Rogier, Bruno Pradines (2012)  The F423Y mutation in the pfmdr2 gene and mutations N51I, C59R, and S108N in the pfdhfr gene are independently associated with pyrimethamine resistance in Plasmodium falciparum isolates.   Antimicrobial agents and chemotherapy 56: 5. 2750-2752 May  
Abstract: Screening for in vitro susceptibility to pyrimethamine and sequencing of the pfmdr2 and pfdhfr genes were performed in 140 Plasmodium falciparum isolates. The risk of in vitro resistance to pyrimethamine was analyzed with a logistic regression model. The mutation F423Y in pfmdr2 (odds ratio [OR] = 2.12 [confidence interval {CI}, 1.02 to 4.59]; P = 0.0489) and the mutation N51I, C59R, or S108N in pfdhfr (OR = 42.34 [CI, 5.52 to 324.61]; P = 0.0003) were independently associated with in vitro resistance to pyrimethamine.
Jean-Baptiste Souraud, Sébastien Briolant, Jérome Dormoi, Joel Mosnier, Hélène Savini, Eric Baret, Rémy Amalvict, Raoulin Soulard, Christophe Rogier, Bruno Pradines (2012)  Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model.   Malaria journal 11: 01  
Abstract: One of the major complications of Plasmodium falciparum infection is cerebral malaria (CM), which causes one million deaths worldwide each year, results in long-term neurological sequelae and the treatment for which is only partially effective. Statins are recognized to have an immunomodulatory action, attenuate sepsis and have a neuroprotective effect. Atorvastatin (AVA) has shown in vitro anti-malarial activity and has improved the activity of mefloquine (MQ) and quinine.
Erhan Yalcindag, Eric Elguero, Céline Arnathau, Patrick Durand, Jean Akiana, Timothy J Anderson, Agnes Aubouy, François Balloux, Patrick Besnard, Hervé Bogreau, Pierre Carnevale, Umberto D'Alessandro, Didier Fontenille, Dionicia Gamboa, Thibaut Jombart, Jacques Le Mire, Eric Leroy, Amanda Maestre, Mayfong Mayxay, Didier Ménard, Lise Musset, Paul N Newton, Dieudonné Nkoghé, Oscar Noya, Benjamin Ollomo, Christophe Rogier, Vincent Veron, Albina Wide, Sedigheh Zakeri, Bernard Carme, Eric Legrand, Christine Chevillon, Francisco J Ayala, François Renaud, Franck Prugnolle (2012)  Multiple independent introductions of Plasmodium falciparum in South America.   Proceedings of the National Academy of Sciences of the United States of America 109: 2. 511-516 Jan  
Abstract: The origin of Plasmodium falciparum in South America is controversial. Some studies suggest a recent introduction during the European colonizations and the transatlantic slave trade. Other evidence--archeological and genetic--suggests a much older origin. We collected and analyzed P. falciparum isolates from different regions of the world, encompassing the distribution range of the parasite, including populations from sub-Saharan Africa, the Middle East, Southeast Asia, and South America. Analyses of microsatellite and SNP polymorphisms show that the populations of P. falciparum in South America are subdivided in two main genetic clusters (northern and southern). Phylogenetic analyses, as well as Approximate Bayesian Computation methods suggest independent introductions of the two clusters from African sources. Our estimates of divergence time between the South American populations and their likely sources favor a likely introduction from Africa during the transatlantic slave trade.
Aurélie Pascual, Philippe Parola, Françoise Benoit-Vical, Fabrice Simon, Denis Malvy, Stéphane Picot, Pascal Delaunay, Didier Basset, Danièle Maubon, Bernard Faugère, Guillaume Ménard, Nathalie Bourgeois, Claude Oeuvray, Eric Didillon, Christophe Rogier, Bruno Pradines (2012)  Ex vivo activity of the ACT new components pyronaridine and piperaquine in comparison with conventional ACT drugs against isolates of Plasmodium falciparum.   Malaria journal 11: 02  
Abstract: The aim of the present work was to assess i) ex vivo activity of pyronaridine (PND) and piperaquine (PPQ), as new components of artemisinin-based combination therapy (ACT), to define susceptibility baseline, ii) their activities compared to other partner drugs, namely monodesethylamodiaquine (MDAQ), lumefantrine (LMF), mefloquine (MQ), artesunate (AS) and dihydroartemisinin (DHA) against 181 Plasmodium falciparum isolates from African countries, India and Thailand, and iii) in vitro cross-resistance with other quinoline drugs, chloroquine (CQ) or quinine (QN).
Alassane Dicko, Moussa Konare, Djibril Traore, Jean Testa, Roger Salamon, Ogobara Doumbo, Christophe Rogier (2012)  The implementation of malaria intermittent preventive trialtreatment with sulphadoxine-pyrimethamine in infants reduced all-cause mortality in the district of Kolokani, Mali: results from a cluster randomized control.   Malaria journal 11: 03  
Abstract: Malaria intermittent preventive treatment of malaria in infant with sulphadoxine-pyrimethamine (IPTi-SP) reduced the incidence of malaria and anaemia by 30% and 20% respectively. The strategy is now a recommended policy for malaria control. However, there was no published study on the impact of the strategy on mortality. The present study assessed the impact of the implementation of IPTi-SP in health services in Mali on all-cause mortality.
Nathalie Wurtz, Bécaye Fall, Aurélie Pascual, Silmane Diawara, Kowry Sow, Eric Baret, Bakary Diatta, Khadidiatou B Fall, Pape S Mbaye, Fatou Fall, Yaya Diémé, Christophe Rogier, Raymond Bercion, Sébastien Briolant, Boubacar Wade, Bruno Pradines (2012)  Prevalence of molecular markers of Plasmodium falciparum drug resistance in Dakar, Senegal.   Malaria journal 11: 06  
Abstract: As a result of the widespread resistance to chloroquine and sulphadoxine-pyrimethamine, artemisinin-based combination therapy (ACT) (including artemether-lumefantrine and artesunate-amodiaquine) has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Intermittent preventive treatments with anti-malarial drugs based on sulphadoxine-pyrimethamine are also given to children or pregnant women once per month during the transmission season. Since 2006, there have been very few reports on the susceptibility of Plasmodium falciparum to anti-malarial drugs. To estimate the prevalence of resistance to several anti-malarial drugs since the introduction of the widespread use of ACT, the presence of molecular markers associated with resistance to chloroquine and sulphadoxine-pyrimethamine was assessed in local isolates at the military hospital of Dakar.
Vincent Corbel, Martin Akogbeto, Georgia B Damien, Armel Djenontin, Fabrice Chandre, Christophe Rogier, Nicolas Moiroux, Joseph Chabi, Bio Banganna, Gil G Padonou, Marie-Claire Henry (2012)  Combination of malaria vector control interventions in pyrethroid resistance area in Benin: a cluster randomised controlled trial.   The Lancet infectious diseases 12: 8. 617-626 Aug  
Abstract: Malaria control efforts and elimination in Africa are being challenged by the development of resistance of parasites to antimalarial drugs and vectors to insecticides. We investigated whether the combination of long-lasting insecticidal mosquito nets (LLINs) with indoor residual spraying (IRS) or carbamate-treated plastic sheeting (CTPS) conferred enhanced protection against malaria and better management of pyrethroid-resistance in vectors than did LLINs alone.
Papa M Drame, Vanessa Machault, Abdoulaye Diallo, Sylvie Cornélie, Anne Poinsignon, Richard Lalou, Mbacké Sembène, Stéphanie Dos Santos, Christophe Rogier, Frédéric Pagès, Jean-Yves Le Hesran, Franck Remoué (2012)  IgG responses to the gSG6-P1 salivary peptide for evaluating human exposure to Anopheles bites in urban areas of Dakar region, Sénégal.   Malaria journal 11: 03  
Abstract: Urban malaria can be a serious public health problem in Africa. Human-landing catches of mosquitoes, a standard entomological method to assess human exposure to malaria vector bites, can lack sensitivity in areas where exposure is low. A simple and highly sensitive tool could be a complementary indicator for evaluating malaria exposure in such epidemiological contexts. The human antibody response to the specific Anopheles gSG6-P1 salivary peptide have been described as an adequate tool biomarker for a reliable assessment of human exposure level to Anopheles bites. The aim of this study was to use this biomarker to evaluate the human exposure to Anopheles mosquito bites in urban settings of Dakar (Senegal), one of the largest cities in West Africa, where Anopheles biting rates and malaria transmission are supposed to be low.
Souleymane Doucoure, François Mouchet, Amandine Cournil, Gilbert Le Goff, Sylvie Cornelie, Yelin Roca, Mabel Guerra Giraldez, Zaira Barja Simon, Roxanna Loayza, Dorothée Misse, Jorge Vargas Flores, Annie Walter, Christophe Rogier, Jean Pierre Herve, Franck Remoue (2012)  Human antibody response to Aedes aegypti saliva in an urban population in Bolivia: a new biomarker of exposure to Dengue vector bites.   The American journal of tropical medicine and hygiene 87: 3. 504-510 Sep  
Abstract: Aedes mosquitoes are important vectors of re-emerging diseases in developing countries, and increasing exposure to Aedes in the developed world is currently a source of concern. Given the limitations of current entomologic methods, there is a need for a new effective way for evaluating Aedes exposure. Our objective was to evaluate specific antibody responses to Aedes aegypti saliva as a biomarker for vector exposure in a dengue-endemic urban area. IgG responses to saliva were strong in young children and steadily waned with age. Specific IgG levels were significantly higher in persons living in sites with higher Ae. aegypti density, as measured by using entomologic parameters. Logistic regression showed a significant correlation between IgG to saliva and exposure level, independently of either age or sex. These results suggest that antibody responses to saliva could be used to monitor human exposure to Aedes bites.
Bouh Abdi Khaireh, Sébastien Briolant, Aurélie Pascual, Madjid Mokrane, Vanessa Machault, Christelle Travaillé, Mohamed Abdi Khaireh, Ismail Hassan Farah, Habib Moussa Ali, Abdul-Ilah Ahmed Abdi, Souleiman Nour Ayeh, Houssein Youssouf Darar, Lénaïck Ollivier, Mohamed Killeh Waiss, Hervé Bogreau, Christophe Rogier, Bruno Pradines (2012)  Plasmodium vivax and Plasmodium falciparum infections in the Republic of Djibouti: evaluation of their prevalence and potential determinants.   Malaria journal 11: 11  
Abstract: Formerly known as a hypoendemic malaria country, the Republic of Djibouti declared the goal of pre-eliminating malaria in 2006. The aim of the present study was to evaluate the prevalence of Plasmodium falciparum, Plasmodium vivax and mixed infections in the Djiboutian population by using serological tools and to identify potential determinants of the disease and hotspots of malaria transmission within the country.
E Sagui, N Resseguier, V Machault, L Ollivier, E Orlandi-Pradines, G Texier, F Pages, R Michel, B Pradines, S Briolant, A Buguet, C Tourette-Turgis, C Rogier (2011)  Determinants of compliance with anti-vectorial protective measures among non-immune travellers during missions to tropical Africa   Malar J 10:  
Abstract: BACKGROUND: The effectiveness of anti-vectorial malaria protective measures in travellers and expatriates is hampered by incorrect compliance. The objective of the present study was to identify the determinants of compliance with anti-vectorial protective measures (AVPMs) in this population that is particularly at risk because of their lack of immunity. METHODS: Compliance with wearing long clothing, sleeping under insecticide-impregnated bed nets (IIBNs) and using insect repellent was estimated and analysed by questionnaires administered to 2,205 French military travellers from 20 groups before and after short-term missions (approximately four months) in six tropical African countries (Senegal, Ivory Coast, Chad, Central African Republic, Gabon and Djibouti). For each AVPM, the association of "correct compliance" with individual and collective variables was investigated using random-effect mixed logistic regression models to take into account the clustered design of the study. RESULTS: The correct compliance rates were 48.6%, 50.6% and 18.5% for wearing long clothing, sleeping under bed nets and using repellents, respectively. Depending on the AVPM, correct compliance was significantly associated with the following factors: country, older than 24 years of age, management responsibilities, the perception of a personal malaria risk greater than that of other travellers, the occurrence of life events, early bedtime (i.e., before midnight), the type of stay (field operation compared to training), the absence of medical history of malaria, the absence of previous travel in malaria-endemic areas and the absence of tobacco consumption.There was no competition between compliance with the different AVPMs or between compliance with any AVPM and malaria chemoprophylaxis. CONCLUSION: Interventions aimed at improving compliance with AVPMs should target young people without management responsibilities who are scheduled for non-operational activities in countries with high risk of clinical malaria. Weak associations between compliance and history of clinical malaria or variables that pertain to threat perception suggest that cognition-based interventions referencing a "bad experience" with clinical malaria could have only a slight impact on the improvement of compliance. Further studies should focus on the cognitive and behavioural predictors of compliance with AVPMs.
Notes: Sagui, Emmanuel xD;Resseguier, Noemie xD;Machault, Vanessa xD;Ollivier, Lenaick xD;Orlandi-Pradines, Eve xD;Texier, Gaetan xD;Pages, Frederic xD;Michel, Remy xD;Pradines, Bruno xD;Briolant, Sebastien xD;Buguet, Alain xD;Tourette-Turgis, Catherine xD;Rogier, Christophe xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2011 Aug 10;10:232.
A Pascual, M Henry, S Briolant, S Charras, E Baret, R Amalvict, E Huyghues des Etages, M Feraud, C Rogier, B Pradines (2011)  In vitro activity of Proveblue (methylene blue) on Plasmodium falciparum strains resistant to standard antimalarial drugs   Antimicrob Agents Chemother 55: 5. 2472-4  
Abstract: The geometric mean 50% inhibitory concentration (IC50) for Proveblue, a methylene blue complying with the European Pharmacopoeia, was more active on 23 P. falciparum strains than chloroquine, quinine, mefloquine, monodesethylamodiaquine, and lumefantrine. We did not find significant associations between the Proveblue IC50 and polymorphisms in the pfcrt, pfmdr1, pfmdr2, pfmrp, and pfnhe-1 genes or the copy numbers of the pfmdr1 and pfmdr2 genes, all of which are involved in antimalarial resistance.
Notes: Pascual, Aurelie xD;Henry, Maud xD;Briolant, Sebastien xD;Charras, Serge xD;Baret, Eric xD;Amalvict, Remy xD;Huyghues des Etages, Emilie xD;Feraud, Michel xD;Rogier, Christophe xD;Pradines, Bruno xD;United States xD;Antimicrobial agents and chemotherapy xD;Antimicrob Agents Chemother. 2011 May;55(5):2472-4. Epub 2011 Feb 22.
A Pascual, L K Basco, E Baret, R Amalvict, D Travers, C Rogier, B Pradines (2011)  Use of the atmospheric generators for capnophilic bacteria Genbag-CO2 for the evaluation of in vitro Plasmodium falciparum susceptibility to standard anti-malarial drugs   Malar J 10:  
Abstract: BACKGROUND: The aim of this study was to evaluate the cultivation system in which the proper atmospheric conditions for growing Plasmodium falciparum parasites were maintained in a sealed bag. The Genbag(R) system associated with the atmospheric generators for capnophilic bacteria Genbag CO2(R) was used for in vitro susceptibility test of nine standard anti-malarial drugs and compared to standard incubator conditions. METHODS: The susceptibility of 36 pre-identified parasite strains from a wide panel of countries was assessed for nine standard anti-malarial drugs (chloroquine, quinine, mefloquine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone and pyrimethamine) by the standard 42-hour 3H-hypoxanthine uptake inhibition method using the Genbag CO2(R) system and compared to controlled incubator conditions (5% CO2 and 10% O2). RESULTS: The counts per minute values in the control wells in incubator atmospheric conditions (5% CO2 and 10% O2) were significantly higher than those of Genbag(R) conditions (2738 cpm vs 2282 cpm, p < 0.0001). The geometric mean IC50 estimated under the incubator atmospheric conditions was significantly lower for atovaquone (1.2 vs 2.1 nM, p = 0.0011) and higher for the quinolines: chloroquine (127 vs 94 nM, p < 0.0001), quinine (580 vs 439 nM, p < 0.0001), monodesethylamodiaquine (41.4 vs 31.8 nM, p < 0.0001), mefloquine (57.5 vs 49.7 nM, p = 0.0011) and lumefantrine (23.8 vs 21.2 nM, p = 0.0044). There was no significant difference of IC50 between the 2 conditions for dihydroartemisinin, doxycycline and pyrimethamine.To reduce this difference in term of anti-malarial susceptibility, a specific cut-off was estimated for each drug under Genbag(R) conditions by regression. The cut-off was estimated at 77 nM for chloroquine (vs 100 nM in 10% O2), 611 nM for quinine (vs 800 nM), 30 nM for mefloquine (vs 30 nM), 61 nM for monodesethylamodiaquine (vs 80 nM) and 1729 nM for pyrimethamine (vs 2000 nM). CONCLUSIONS: The atmospheric generators for capnophilic bacteria Genbag CO2(R) is an appropriate technology that can be transferred to the field for epidemiological surveys of drug-resistant malaria. The present data suggest the importance of the gas mixture on in vitro microtest results for anti-malarial drugs and the importance of determining the microtest conditions before comparing and analysing the data from different laboratories and concluding on malaria resistance.
Notes: Pascual, Aurelie xD;Basco, Leonardo K xD;Baret, Eric xD;Amalvict, Remy xD;Travers, Dominique xD;Rogier, Christophe xD;Pradines, Bruno xD;Comparative Study xD;Evaluation Studies xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2011 Jan 14;10:8.
V Machault, C Vignolles, F Borchi, P Vounatsou, F Pages, S Briolant, J P Lacaux, C Rogier (2011)  The use of remotely sensed environmental data in the study of malaria   Geospat Health 5: 2. 151-68  
Abstract: Mapping and anticipating risk is a major issue in the fight against malaria, a disease causing an estimated one million deaths each year. Approximately half the world's population is at risk and it is of prime importance to evaluate the burden of malaria at the spatial as well as the temporal level. The role of the environment with regard to the determinants of transmission and burden of the disease are described followed by a discussion of special issues such as urban malaria, human population mapping and the detection of changes at the temporal scale. Risk maps at appropriate scales can provide valuable information for targeted control and the present review discusses the essentials of principles, methods, advantages and limitations of remote sensing along with a presentation of ecological, meteorological and climatologic data which rule the distribution of malaria. The panel of commonly used analytic methods is examined and the methodological limitations are highlighted. A review of the literature details the increasing interest in the use of remotely sensed data in the study of malaria, by mapping or modeling several malariometric indices such as prevalence, morbidity and mortality, which are discussed with reference to vector breeding, vector density and entomological inoculation rate, estimates of which constitute the foundation for understanding endemicity and epidemics.
Notes: Machault, Vanessa xD;Vignolles, Cecile xD;Borchi, Francois xD;Vounatsou, Penelope xD;Pages, Frederic xD;Briolant, Sebastien xD;Lacaux, Jean-Pierre xD;Rogier, Christophe xD;Research Support, Non-U.S. Gov't xD;Review xD;Italy xD;Geospatial health xD;Geospat Health. 2011 May;5(2):151-68.
J B Sarr, E Orlandi-Pradines, S Fortin, C Sow, S Cornelie, F Rogerie, S Guindo, L Konate, T Fusai, G Riveau, C Rogier, F Remoue (2011)  Assessment of exposure to Plasmodium falciparum transmission in a low endemicity area by using multiplex fluorescent microsphere-based serological assays   Parasit Vectors 4:  
Abstract: BACKGROUND: The evaluation of malaria transmission intensity is a crucial indicator for estimating the burden of malarial disease. In this respect, entomological and parasitological methods present limitations, especially in low transmission areas. The present study used a sensitive multiplex assay to assess the exposure to Plasmodium falciparum infection in children living in an area of low endemicity. In three Senegalese villages, specific antibody (IgG) responses to 13 pre-erythrocytic P. falciparum peptides derived from Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, Csp and Pf11.1 proteins were simultaneously evaluated before (June), at the peak (September) and after (December) the period of malaria transmission, in children aged from 1 to 8 years. RESULTS: Compared to other antigens, a high percentage of seropositivity and specific antibody levels were detected with Glurp, Salsa1, Lsa3NR2, and Lsa1J antigens. The seropositivity increased with age for all tested antigens. Specific IgG levels to Glurp, Salsa1, Lsa3NR2, and Lsa1J were significantly higher in P. falciparum infected children compared to non-infected and this increase is significantly correlated with parasite density. CONCLUSION: The multiplex assay represents a useful technology for a serological assessment of rapid variations in malaria transmission intensity, especially in a context of low parasite rates. The use of such combined serological markers (i.e. Glurp, Lsa1, Lsa3, and Salsa) could offer the opportunity to examine these variations over time, and to evaluate the efficacy of integrated malaria control strategies.
Notes: Sarr, Jean Biram xD;Orlandi-Pradines, Eve xD;Fortin, Sonia xD;Sow, Cheikh xD;Cornelie, Sylvie xD;Rogerie, Francois xD;Guindo, Soihibou xD;Konate, Lassana xD;Fusai, Thierry xD;Riveau, Gilles xD;Rogier, Christophe xD;Remoue, Franck xD;Evaluation Studies xD;Research Support, Non-U.S. Gov't xD;England xD;Parasites & vectors xD;Parasit Vectors. 2011 Nov 7;4:212.
J F Trape, A Tall, N Diagne, O Ndiath, A B Ly, J Faye, F Dieye-Ba, C Roucher, C Bouganali, A Badiane, F D Sarr, C Mazenot, A Toure-Balde, D Raoult, P Druilhe, O Mercereau-Puijalon, C Rogier, C Sokhna (2011)  Malaria morbidity and pyrethroid resistance after the introduction of insecticide-treated bednets and artemisinin-based combination therapies : a longitudinal study   Lancet Infect Dis 11: 12. 925-32  
Abstract: BACKGROUND: Substantial reductions in malaria have been reported in several African countries after distribution of insecticide-treated bednets and the use of artemisinin-based combination therapies (ACTs). Our aim was to assess the effect of these policies on malaria morbidity, mosquito populations, and asymptomatic infections in a west African rural population. METHODS: We did a longitudinal study of inhabitants of Dielmo village, Senegal, between January, 2007, and December, 2010. We monitored the inhabitants for fever during this period and we treated malaria attacks with artesunate plus amodiaquine. In July, 2008, we offered longlasting insecticide (deltamethrin)-treated nets (LLINs) to all villagers. We did monthly night collections of mosquitoes during the whole study period, and we assessed asymptomatic carriage from cross-sectional surveys. Our statistical analyses were by negative binomial regression, logistic regression, and binomial or Fisher exact test. FINDINGS: There were 464 clinical malaria attacks attributable to Plasmodium falciparum during 17,858 person-months of follow-up. The incidence density of malaria attacks averaged 5.45 (95% CI 4.90-6.05) per 100 person-months between January, 2007, and July, 2008, before the distribution of LLINs. Incidence density decreased to 0.41 (0.29-0.55) between August, 2008, and August, 2010, but increased back to 4.57 (3.54-5.82) between September and December, 2010--ie, 27-30 months after the distribution of LLINs. The rebound of malaria attacks were highest in adults and children aged 10 years or older: 45 (63%) of 71 malaria attacks recorded in 2010 compared with 126 (33%) of 384 in 2007 and 2008 (p<0.0001). 37% of Anopheles gambiae mosquitoes were resistant to deltamethrin in 2010, and the prevalence of the Leu1014Phe kdr resistance mutation increased from 8% in 2007 to 48% in 2010 (p=0.0009). INTERPRETATION: Increasing pyrethroid resistance of A gambiae and increasing susceptibility of older children and adults, probably due to decreasing immunity, caused the rebound and age shift of malaria morbidity. Strategies to address the problem of insecticide resistance and to mitigate its effects must be urgently defined and implemented. FUNDING: Institut de Recherche pour le Developpement and the Pasteur Institute of Dakar.
Notes: Trape, Jean-Francois xD;Tall, Adama xD;Diagne, Nafissatou xD;Ndiath, Ousmane xD;Ly, Alioune B xD;Faye, Joseph xD;Dieye-Ba, Fambaye xD;Roucher, Clementine xD;Bouganali, Charles xD;Badiane, Abdoulaye xD;Sarr, Fatoumata Diene xD;Mazenot, Catherine xD;Toure-Balde, Aissatou xD;Raoult, Didier xD;Druilhe, Pierre xD;Mercereau-Puijalon, Odile xD;Rogier, Christophe xD;Sokhna, Cheikh xD;Research Support, Non-U.S. Gov't xD;United States xD;The Lancet infectious diseases xD;Lancet Infect Dis. 2011 Dec;11(12):925-32. Epub 2011 Aug 17.
S Briolant, S Pelleau, H Bogreau, P Hovette, A Zettor, J Castello, E Baret, R Amalvict, C Rogier, B Pradines (2011)  In vitro susceptibility to quinine and microsatellite variations of the Plasmodium falciparum Na+/H+ exchanger (Pfnhe-1) gene : the absence of association in clinical isolates from the Republic of Congo   Malar J 10: 1.  
Abstract: BACKGROUND: Quinine is still recommended as an effective therapy for severe cases of Plasmodium falciparum malaria, but the parasite has developed resistance to the drug in some cases. Investigations into the genetic basis for quinine resistance (QNR) suggest that QNR is complex and involves several genes, with either an additive or a pairwise effect. The results obtained when assessing one of these genes, the plasmodial Na+/H+ exchanger, Pfnhe-1, were found to depend upon the geographic origin of the parasite strain. Most of the associations identified have been made in Asian strains; in contrast, in African strains, the influence of Pfnhe on QNR is not apparent. However, a recent study carried out in Kenya did show a significant association between a Pfnhe polymorphism and QNR. As genetic differences may exist across the African continent, more field data are needed to determine if this association exists in other African regions. In the present study, association between Pfnhe and QNR is investigated in a series of isolates from central Africa. METHODS: The sequence analysis of the polymorphisms at the Pfnhe-1 ms4760 microsatellite and the evaluation of in vitro quinine susceptibility (by isotopic assay) were conducted in 74 P. falciparum isolates from the Republic of Congo. RESULTS: Polymorphisms in the number of DNNND or NHNDNHNNDDD repeats in the Pfnhe-1 ms4760 microsatellite were not associated with quinine susceptibility. CONCLUSIONS: The polymorphism in the microsatellite ms4760 in Pfnhe-1 that cannot be used to monitor quinine response in the regions of the Republic of Congo, where the isolates came from. This finding suggests that there exists a genetic background associated with geographic area for the association that will prevent the use of Pfnhe as a molecular marker for QNR. The contribution of Pfnhe to the in vitro response to quinine remains to be assessed in other regions, including in countries with different levels of drug pressure.
Notes: Briolant, Sebastien xD;Pelleau, Stephane xD;Bogreau, Herve xD;Hovette, Philippe xD;Zettor, Agnes xD;Castello, Jacky xD;Baret, Eric xD;Amalvict, Remy xD;Rogier, Christophe xD;Pradines, Bruno xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2011 Feb 11;10(1):37.
N Wurtz, K Mint Lekweiry, H Bogreau, B Pradines, C Rogier, A Ould Mohamed Salem Boukhary, J E Hafid, M S Ould Ahmedou Salem, J F Trape, L K Basco, S Briolant (2011)  Vivax malaria in Mauritania includes infection of a Duffy-negative individual   Malar J 10:  
Abstract: BACKGROUND: Duffy blood group polymorphisms are important in areas where Plasmodium vivax is present because this surface antigen is thought to act as a key receptor for this parasite. In the present study, Duffy blood group genotyping was performed in febrile uninfected and P. vivax-infected patients living in the city of Nouakchott, Mauritania. METHODS: Plasmodium vivax was identified by real-time PCR. The Duffy blood group genotypes were determined by standard PCR followed by sequencing of the promoter region and exon 2 of the Duffy gene in 277 febrile individuals. Fisher's exact test was performed in order to assess the significance of variables. RESULTS: In the Moorish population, a high frequency of the FYBES/FYBES genotype was observed in uninfected individuals (27.8%), whereas no P. vivax-infected patient had this genotype. This was followed by a high level of FYA/FYB, FYB/FYB, FYB/FYBES and FYA/FYBES genotype frequencies, both in the P. vivax-infected and uninfected patients. In other ethnic groups (Poular, Soninke, Wolof), only the FYBES/FYBES genotype was found in uninfected patients, whereas the FYA/FYBES genotype was observed in two P. vivax-infected patients. In addition, one patient belonging to the Wolof ethnic group presented the FYBES/FYBES genotype and was infected by P. vivax. CONCLUSIONS: This study presents the Duffy blood group polymorphisms in Nouakchott City and demonstrates that in Mauritania, P. vivax is able to infect Duffy-negative patients. Further studies are necessary to identify the process that enables this Duffy-independent P. vivax invasion of human red blood cells.
Notes: Wurtz, Nathalie xD;Mint Lekweiry, Khadijetou xD;Bogreau, Herve xD;Pradines, Bruno xD;Rogier, Christophe xD;Ould Mohamed Salem Boukhary, Ali xD;Hafid, Jamal Eddine xD;Ould Ahmedou Salem, Mohamed Salem xD;Trape, Jean-Francois xD;Basco, Leonardo K xD;Briolant, Sebastien xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2011 Nov 3;10:336. doi: 10.1186/1475-2875-10-336.
M O Vareil, O Tandonnet, A Chemoul, H Bogreau, M Saint-Leger, M Micheau, P Millet, J L Koeck, A Boyer, C Rogier, D Malvy (2011)  Unusual transmission of Plasmodium falciparum, Bordeaux, France, 2009   Emerg Infect Dis 17: 2. 248-50  
Abstract: Plasmodium falciparum malaria is usually transmitted by mosquitoes. We report 2 cases in France transmitted by other modes: occupational blood exposure and blood transfusion. Even where malaria is not endemic, it should be considered as a cause of unexplained acute fever.
Notes: Vareil, Marc Olivier xD;Tandonnet, Olivier xD;Chemoul, Audrey xD;Bogreau, Herve xD;Saint-Leger, Melanie xD;Micheau, Maguy xD;Millet, Pascal xD;Koeck, Jean Louis xD;Boyer, Alexandre xD;Rogier, Christophe xD;Malvy, Denis xD;Case Reports xD;United States xD;Emerging infectious diseases xD;Emerg Infect Dis. 2011 Feb;17(2):248-50.
K M Lekweiry, L K Basco, M S Salem, J E Hafid, A Marin-Jauffre, A O Weddih, S Briolant, H Bogreau, B Pradines, C Rogier, J F Trape, A O Boukhary (2011)  Malaria prevalence and morbidity among children reporting at health facilities in Nouakchott, Mauritania   Trans R Soc Trop Med Hyg 105: 12. 727-33  
Abstract: Although malaria has become a serious public health problem in Mauritania since the late 1990s, few documented data on its epidemiology exist. The objective of this study was to assess the morbidity of clinical malaria among children in Nouakchott. Three hundred and one febrile children, consulting at three health facilities of Nouakchott, were screened for malaria in 2009 (n=216) and 2010 (n=85). Plasmodium species identification and parasite density were determined by microscopic examination of Giemsa-stained thin and thick films and confirmed by rapid diagnostic test and nested PCR. Of 301 febrile children, 105 (34.9%) were malaria-positive by nested PCR and 87 (28.9%) by microscopy. Plasmodium vivax represented 97.1% (102/105) and P. falciparum accounted for 2.9% (3/105) of positive cases. All positive children under five years old were infected with P. vivax. The highest numbers of malaria positives were found during or shortly after the rainy season and the lowest during the dry season. Fifty-four of 105 (51.4%) malaria cases, all with P. vivax, had never travelled outside Nouakchott. Individuals belonging to the Moors ethnic group represented 97.0% of P. vivax cases. Results of the present study indicate that malaria is endemic in Nouakchott and that P. vivax is the principal causative agent. Regular surveillance is required to monitor malaria prevalence and incidence, and further measures are needed to counter the possible spread of malaria in the country.
Notes: Lekweiry, Khadijetou Mint xD;Basco, Leonardo K xD;Salem, Mohamed Salem O Ahmedou xD;Hafid, Jamal Eddine xD;Marin-Jauffre, Adeline xD;Weddih, Abdallahi O xD;Briolant, Sebastien xD;Bogreau, Herve xD;Pradines, Bruno xD;Rogier, Christophe xD;Trape, Jean-Francois xD;Boukhary, Ali O Mohamed Salem O xD;Research Support, Non-U.S. Gov't xD;England xD;Transactions of the Royal Society of Tropical Medicine and Hygiene xD;Trans R Soc Trop Med Hyg. 2011 Dec;105(12):727-33. doi: 10.1016/j.trstmh.2011.09.004. Epub 2011 Oct 21.
V Robert, J F Trape, C Rogier (2011)  Malaria parasites : elimination is not eradication   Clin Microbiol Infect 17: 11. 1597-9  
Notes: Robert, V xD;Trape, J-F xD;Rogier, C xD;Editorial xD;France xD;Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases xD;Clin Microbiol Infect. 2011 Nov;17(11):1597-9. doi: 10.1111/j.1469-0691.2011.03657.x. Epub 2011 Sep 22.
A Fontaine, S Bourdon, M Belghazi, M Pophillat, P Fourquet, S Granjeaud, M Torrentino-Madamet, C Rogier, T Fusai, L Almeras (2011)  Plasmodium falciparum infection-induced changes in erythrocyte membrane proteins   Parasitol Res  
Abstract: Over the past decade, advances in proteomic and mass spectrometry techniques and the sequencing of the Plasmodium falciparum genome have led to an increasing number of studies regarding the parasite proteome. However, these studies have focused principally on parasite protein expression, neglecting parasite-induced variations in the host proteome. Here, we investigated P. falciparum-induced modifications of the infected red blood cell (iRBC) membrane proteome, taking into account both host and parasite proteome alterations. Furthermore, we also determined if some protein changes were associated with genotypically distinct P. falciparum strains. Comparison of host membrane proteomes between iRBCs and uninfected red blood cells using fluorescence-based proteomic approaches, such as 2D difference gel electrophoresis revealed that more than 100 protein spots were highly up-represented (fold change increase greater than five) following P. falciparum infection for both strains (i.e. RP8 and Institut Pasteur Pregnancy Associated Malaria). The majority of spots identified by mass spectrometry corresponded to Homo sapiens proteins. However, infection-induced changes in host proteins did not appear to affect molecules located at the outer surface of the plasma membrane. The under-representation of parasite proteins could not be attributed to deficient parasite protein expression. Thus, this study describes for the first time that considerable host protein modifications were detected following P. falciparum infection at the erythrocyte membrane level. Further analysis of infection-induced host protein modifications will improve our knowledge of malaria pathogenesis.
Notes: Journal article xD;Parasitology research xD;Parasitol Res. 2011 Jul 9.
B Fall, S Diawara, K Sow, E Baret, B Diatta, K B Fall, P S Mbaye, F Fall, Y Dieme, C Rogier, B Wade, R Bercion, B Pradines (2011)  Ex vivo susceptibility of Plasmodium falciparum isolates from Dakar, Senegal, to seven standard anti-malarial drugs   Malar J 10:  
Abstract: BACKGROUND: As a result of widespread chloroquine and sulphadoxine-pyrimethamine resistance, artemisinin-based combination therapy (ACT) (which includes artemether-lumefantrine and artesunate-amodiaquine) has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Since then, there have been very few reports on the ex vivo susceptibility of Plasmodium falciparum to anti-malarial drugs. To examine whether parasite susceptibility has been affected by the widespread use of ACT, the ex vivo susceptibility of local isolates was assessed at the military hospital of Dakar. METHODS: The ex vivo susceptibility of 93 P. falciparum isolates from Dakar was successfully determined using the Plasmodium lactate dehydrogenase (pLDH) ELISA for the following drugs: chloroquine (CQ), quinine (QN), mefloquine (MQ), monodesethylamodiaquine (MDAQ), lumefantrine (LMF), dihydroartemisinin (DHA) and doxycycline (DOX). RESULTS: After transformation of the isolate IC50 in ratio of IC50 according to the susceptibility of the 3D7 reference strain (isolate IC50/3D7 IC50), the prevalence of the in vitro resistant isolates with reduced susceptibility was 50% for MQ, 22% for CQ, 12% for DOX, 6% for both QN and MDAQ and 1% for the drugs LMF and DHA. The highest significant positive correlations were shown between responses to CQ and MDAQ (r = 0.569; P < 0.0001), LMF and QN (r = 0.511; P < 0.0001), LMF and DHA (r = 0.428; P = 0.0001), LMF and MQ (r = 0.413; P = 0.0002), QN and DHA (r = 0.402; P = 0.0003) and QN and MQ (r = 0.421; P = 0.0001). CONCLUSIONS: The introduction of ACT in 2002 has not induced a decrease in P. falciparum susceptibility to the drugs DHA, MDAQ and LMF, which are common ACT components. However, the prevalence of P. falciparum isolates with reduced susceptibility has increased for both MQ and DOX. Taken together, these data suggest that intensive surveillance of the P. falciparum in vitro susceptibility to anti-malarial drugs in Senegal is required.
Notes: Fall, Becaye xD;Diawara, Silmane xD;Sow, Kowry xD;Baret, Eric xD;Diatta, Bakary xD;Fall, Khadidiatou B xD;Mbaye, Pape S xD;Fall, Fatou xD;Dieme, Yaya xD;Rogier, Christophe xD;Wade, Boubacar xD;Bercion, Raymond xD;Pradines, Bruno xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2011 Oct 20;10:310.
F Dubar, T J Egan, B Pradines, D Kuter, K K Ncokazi, D Forge, J F Paul, C Pierrot, H Kalamou, J Khalife, E Buisine, C Rogier, H Vezin, I Forfar, C Slomianny, X Trivelli, S Kapishnikov, L Leiserowitz, D Dive, C Biot (2011)  The antimalarial ferroquine : role of the metal and intramolecular hydrogen bond in activity and resistance   ACS Chem Biol 6: 3. 275-87  
Abstract: Inhibition of hemozoin biocrystallization is considered the main mechanism of action of 4-aminoquinoline antimalarials including chloroquine (CQ) but cannot fully explain the activity of ferroquine (FQ) which has been related to redox properties and intramolecular hydrogen bonding. Analogues of FQ, methylferroquine (Me-FQ), ruthenoquine (RQ), and methylruthenoquine (Me-RQ), were prepared. Combination of physicochemical and molecular modeling methods showed that FQ and RQ favor intramolecular hydrogen bonding between the 4-aminoquinoline NH group and the terminal amino group in the absence of water, suggesting that this structure may enhance its passage through the membrane. This was further supported by the use of Me-FQ and Me-RQ where the intramolecular hydrogen bond cannot be formed. Docking studies suggest that FQ can interact specifically with the {0,0,1} and {1,0,0} faces of hemozoin, blocking crystal growth. With respect to the structure-activity relationship, the antimalarial activity on 15 different P. falciparum strains showed that the activity of FQ and RQ were correlated with each other but not with CQ, confirming lack of cross resistance. Conversely, Me-FQ and Me-RQ showed significant cross-resistance with CQ. Mutations or copy number of pfcrt, pfmrp, pfmdr1, pfmdr2, or pfnhe-1 did not exhibit significant correlations with the IC(50) of FQ or RQ. We next showed that FQ and Me-FQ were able to generate hydroxyl radicals, whereas RQ and me-RQ did not. Ultrastructural studies revealed that FQ and Me-FQ but not RQ or Me-RQ break down the parasite digestive vacuole membrane, which could be related to the ability of the former to generate hydroxyl radicals.
Notes: Dubar, Faustine xD;Egan, Timothy J xD;Pradines, Bruno xD;Kuter, David xD;Ncokazi, Kanyile K xD;Forge, Delphine xD;Paul, Jean-Francois xD;Pierrot, Christine xD;Kalamou, Hadidjatou xD;Khalife, Jamal xD;Buisine, Eric xD;Rogier, Christophe xD;Vezin, Herve xD;Forfar, Isabelle xD;Slomianny, Christian xD;Trivelli, Xavier xD;Kapishnikov, Sergey xD;Leiserowitz, Leslie xD;Dive, Daniel xD;Biot, Christophe xD;Research Support, Non-U.S. Gov't xD;United States xD;ACS chemical biology xD;ACS Chem Biol. 2011 Mar 18;6(3):275-87. Epub 2011 Jan 7.
A Fontaine, I Diouf, N Bakkali, D Misse, F Pages, T Fusai, C Rogier, L Almeras (2011)  Implication of haematophagous arthropod salivary proteins in host-vector interactions   Parasit Vectors 4:  
Abstract: The saliva of haematophagous arthropods contains an array of anti-haemostatic, anti-inflammatory and immunomodulatory molecules that contribute to the success of the blood meal. The saliva of haematophagous arthropods is also involved in the transmission and the establishment of pathogens in the host and in allergic responses. This survey provides a comprehensive overview of the pharmacological activity and immunogenic properties of the main salivary proteins characterised in various haematophagous arthropod species. The potential biological and epidemiological applications of these immunogenic salivary molecules will be discussed with an emphasis on their use as biomarkers of exposure to haematophagous arthropod bites or vaccine candidates that are liable to improve host protection against vector-borne diseases.
Notes: Fontaine, Albin xD;Diouf, Ibrahima xD;Bakkali, Nawal xD;Misse, Dorothee xD;Pages, Frederic xD;Fusai, Thierry xD;Rogier, Christophe xD;Almeras, Lionel xD;Research Support, Non-U.S. Gov't xD;Review xD;England xD;Parasites & vectors xD;Parasit Vectors. 2011 Sep 28;4:187.
A Dicko, S O Toure, M Traore, I Sagara, O B Toure, M S Sissoko, A T Diallo, C Rogier, R Salomon, A de Sousa, O K Doumbo (2011)  Increase in EPI vaccines coverage after implementation of intermittent preventive treatment of malaria in infant with Sulfadoxine -pyrimethamine in the district of Kolokani, Mali : results from a cluster randomized control trial   BMC Public Health 11:  
Abstract: BACKGROUND: Even though the efficacy of Intermittent Preventive Treatment in infants (IPTi) with Sulfadoxine-Pyrimethamine (SP) against clinical disease and the absence of its interaction with routine vaccines of the Expanded Immunization Programme (EPI) have been established, there are still some concerns regarding the addition of IPTi, which may increase the work burden and disrupt the routine EPI services especially in Africa where the target immunization coverage remains to be met. However IPTi may also increase the adherence of the community to EPI services and improve EPI coverage, once the benefice of strategy is perceived. METHODS: To assess the impact of IPTi implementation on the coverage of EPI vaccines, 22 health areas of the district of Kolokani were randomized at a 1:1 ratio to either receive IPTi-SP or to serve as a control. The EPI vaccines coverage was assessed using cross-sectional surveys at baseline in November 2006 and after one year of IPTi pilot-implementation in December 2007. RESULTS: At baseline, the proportion of children of 9-23 months who were completely vaccinated (defined as children who received BGG, 3 doses of DTP/Polio, measles and yellow fever vaccines) was 36.7% (95% CI 25.3% -48.0%). After one year of implementation of IPTi-SP using routine health services, the proportion of children completely vaccinated rose to 53.8% in the non intervention zone and 69.5% in the IPTi intervention zone (P <0.001).The proportion of children in the target age groups who received IPTi with each of the 3 vaccinations DTP2, DTP3 and Measles, were 89.2% (95% CI 85.9%-92.0%), 91.0% (95% CI 87.6% -93.7%) and 77.4% (95% CI 70.7%-83.2%) respectively. The corresponding figures in non intervention zone were 2.3% (95% CI 0.9% -4.7%), 2.6% (95% CI 1.0% -5.6%) and 1.7% (95% CI 0.4% - 4.9%). CONCLUSION: This study shows that high coverage of the IPTi can be obtained when the strategy is implemented using routine health services and implementation results in a significant increase in coverage of EPI vaccines in the district of Kolokani, Mali.
Notes: Dicko, Alassane xD;Toure, Sidy O xD;Traore, Mariam xD;Sagara, Issaka xD;Toure, Ousmane B xD;Sissoko, Mahamadou S xD;Diallo, Alpha T xD;Rogier, Christophe xD;Salomon, Roger xD;de Sousa, Alexandra xD;Doumbo, Ogobara K xD;Randomized Controlled Trial xD;Research Support, Non-U.S. Gov't xD;England xD;BMC public health xD;BMC Public Health. 2011 Jul 18;11:573. doi: 10.1186/1471-2458-11-573.
A Fontaine, A Pascual, I Diouf, N Bakkali, S Bourdon, T Fusai, C Rogier, L Almeras (2011)  Mosquito salivary gland protein preservation in the field for immunological and biochemical analysis   Parasit Vectors 4:  
Abstract: Mosquito salivary proteins are involved in several biological processes that facilitate their blood feeding and have also been reported to elicit an IgG response in vertebrates. A growing number of studies have focused on this immunological response for its potential use as a biological marker of exposure to arthropod bites. As mosquito saliva collection is extremely laborious and inefficient, most research groups prefer to work on mosquito salivary glands (SGs). Thus, SG protein integrity is a critical factor in obtaining meaningful data from immunological and biochemical analysis. Current methodologies rely on an immediate freezing of SGs after their collection. However, the maintenance of samples in a frozen environment can be hard to achieve in field conditions. In this study, SG proteins from two mosquito species (Aedes aegypti and Anopheles gambiae s.s.) stored in different media for 5 days at either +4 degrees C or room temperature (RT) were evaluated at the quantitative (i.e., ELISA) and qualitative (i.e., SDS-PAGE and immunoblotting) levels. Our results indicated that PBS medium supplemented with an anti-protease cocktail seems to be the best buffer to preserve SG antigens for 5 days at +4 degrees C for ELISA analysis. Conversely, cell-lysis buffer (Urea-Thiourea-CHAPS-Tris) was best at preventing protein degradation both at +4 degrees C and RT for further qualitative analysis. These convenient storage methods provide an alternative to freezing and are expected to be applicable to other biological samples collected in the field.
Notes: Fontaine, A xD;Pascual, A xD;Diouf, I xD;Bakkali, N xD;Bourdon, S xD;Fusai, T xD;Rogier, C xD;Almeras, L xD;Evaluation Studies xD;Research Support, Non-U.S. Gov't xD;England xD;Parasites & vectors xD;Parasit Vectors. 2011 Mar 8;4:33.
A Fontaine, A Pascual, E Orlandi-Pradines, I Diouf, F Remoue, F Pages, T Fusai, C Rogier, L Almeras (2011)  Relationship between exposure to vector bites and antibody responses to mosquito salivary gland extracts   PLoS One 6: 12.  
Abstract: Mosquito-borne diseases are major health problems worldwide. Serological responses to mosquito saliva proteins may be useful in estimating individual exposure to bites from mosquitoes transmitting these diseases. However, the relationships between the levels of these IgG responses and mosquito density as well as IgG response specificity at the genus and/or species level need to be clarified prior to develop new immunological markers to assess human/vector contact. To this end, a kinetic study of antibody levels against several mosquito salivary gland extracts from southeastern French individuals living in three areas with distinct ecological environments and, by implication, distinct Aedes caspius mosquito densities were compared using ELISA. A positive association was observed between the average levels of IgG responses against Ae. caspius salivary gland extracts and spatial Ae. caspius densities. Additionally, the average level of IgG responses increased significantly during the peak exposure to Ae. caspius at each site and returned to baseline four months later, suggesting short-lived IgG responses. The species-specificity of IgG antibody responses was determined by testing antibody responses to salivary gland extracts from Cx. pipiens, a mosquito that is present at these three sites at different density levels, and from two other Aedes species not present in the study area (Ae. aegypti and Ae. albopictus). The IgG responses observed against these mosquito salivary gland extracts contrasted with those observed against Ae. caspius salivary gland extracts, supporting the existence of species-specific serological responses. By considering different populations and densities of mosquitoes linked to environmental factors, this study shows, for the first time, that specific IgG antibody responses against Ae. caspius salivary gland extracts may be related to the seasonal and geographical variations in Ae. caspius density. Characterisation of such immunological-markers may allow the evaluation of the effectiveness of vector-control strategies or estimation of the risk of vector-borne disease transmission.
Notes: Fontaine, Albin xD;Pascual, Aurelie xD;Orlandi-Pradines, Eve xD;Diouf, Ibrahima xD;Remoue, Franck xD;Pages, Frederic xD;Fusai, Thierry xD;Rogier, Christophe xD;Almeras, Lionel xD;Research Support, Non-U.S. Gov't xD;United States xD;PloS one xD;PLoS One. 2011;6(12):e29107. Epub 2011 Dec 14.
L Gadiaga, V Machault, F Pages, A Gaye, F Jarjaval, L Godefroy, B Cisse, J P Lacaux, C Sokhna, J F Trape, C Rogier (2011)  Conditions of malaria transmission in Dakar from 2007 to 2010   Malar J 10:  
Abstract: BACKGROUND: Previous studies in Dakar have highlighted the spatial and temporal heterogeneity of Anopheles gambiae s.l. biting rates. In order to improve the knowledge of the determinants of malaria transmission in this city, the present study reports the results of an extensive entomological survey that was conducted in 45 areas in Dakar from 2007 to 2010. METHODS: Water collections were monitored for the presence of anopheline larvae. Adult mosquitoes were sampled by human landing collection. Plasmodium falciparum circumsporozoite (CSP) protein indexes were measured by ELISA (enzyme-linked immunosorbent assay), and the entomological inoculation rates were calculated. RESULTS: The presence of anopheline larvae were recorded in 1,015 out of 2,683 observations made from 325 water collections. A water pH of equal to or above 8.0, a water temperature that was equal to or above 30 degrees C, the absence of larvivorous fishes, the wet season, the presence of surface vegetation, the persistence of water and location in a slightly urbanised area were significantly associated with the presence of anopheline larvae and/or with a higher density of anopheline larvae. Most of the larval habitats were observed in public areas, i.e., freely accessible. A total of 496,310 adult mosquitoes were caught during 3096 person-nights, and 44967 of these specimens were identified as An.gambiae s.l. The mean An. gambiae s.l. human-biting rate ranged from 0.1 to 248.9 bites per person per night during the rainy season. Anopheles arabiensis (93.14%), Anopheles melas (6.83%) and An. gambiae s.s. M form (0.03%) were the three members of the An. gambiae complex. Fifty-two An. arabiensis and two An. melas specimens were CSP-positive, and the annual CSP index was 0.64% in 2007, 0.09% in 2008-2009 and 0.12% in 2009-2010. In the studied areas, the average EIR ranged from 0 to 17.6 infected bites per person during the entire transmission season. CONCLUSION: The spatial and temporal heterogeneity of An. gambiae s.l. larval density, adult human-biting rate (HBR) and malaria transmission in Dakar has been confirmed, and the environmental factors associated with this heterogeneity have been identified. These results pave the way for the creation of malaria risk maps and for a focused anti-vectorial control strategy.
Notes: Gadiaga, Libasse xD;Machault, Vanessa xD;Pages, Frederic xD;Gaye, Abdoulaye xD;Jarjaval, Fanny xD;Godefroy, Lydie xD;Cisse, Birane xD;Lacaux, Jean-Pierre xD;Sokhna, Cheikh xD;Trape, Jean-Francois xD;Rogier, Christophe xD;England xD;Malaria journal xD;Malar J. 2011 Oct 21;10:312.
S Briolant, M Henry, C Oeuvray, R Amalvict, E Baret, E Didillon, C Rogier, B Pradines (2010)  Absence of association between piperaquine in vitro responses and polymorphisms in the pfcrt, pfmdr1, pfmrp, and pfnhe genes in Plasmodium falciparum   Antimicrob Agents Chemother 54: 9. 3537-44  
Abstract: We have analyzed the profiles of 23 of Plasmodium falciparum strains for their in vitro chemosusceptibilities to piperaquine (PPQ), dihydroartemisinin (DHA), chloroquine, monodesethylamodiaquine, quinine, mefloquine, lumefantrine, atovaquone, pyrimethamine, and doxycycline (DOX) in association with polymorphisms in genes involved in quinoline resistance (Plasmodium falciparum crt [pfcrt], pfmdr1, pfmrp, and pfnhe). The 50% inhibitory concentrations (IC(50)s) for PPQ ranged from 29 to 98 nM (geometric mean = 57.8 nM, 95% confidence interval [CI] = 51 to 65) and from 0.4 to 5.8 nM for DHA (geometric mean = 1.8 nM, 95% CI = 1.4 to 2.3). We found a significant positive correlation between the responses to PPQ and DHA (r(2) = 0.17; P = 0.0495) and between the responses to PPQ and DOX (r(2) = 0.41; P = 0.001). We did not find a significant association between the PPQ IC(50) (0.0525 < P < 0.9247) or the DHA IC(50) (0.0138 < P < 0.9018) and polymorphisms in the pfcrt, pfmdr1, pfmrp, and pfnhe-1 genes. There was an absence of cross-resistance with quinolines, and the IC(50)s for PPQ and DHA were found to be unrelated to mutations in the pfcrt, pfmdr1, pfmrp, and pfnhe-1 transport protein genes, which are involved in quinoline antimalarial drug resistance. These results confirm the interest in and the efficacy of the combination of PPQ and DHA for areas in which parasites are resistant to chloroquine or other quinolines.
Notes: Briolant, Sebastien xD;Henry, Maud xD;Oeuvray, Claude xD;Amalvict, Remy xD;Baret, Eric xD;Didillon, Eric xD;Rogier, Christophe xD;Pradines, Bruno xD;Research Support, Non-U.S. Gov't xD;United States xD;Antimicrobial agents and chemotherapy xD;Antimicrob Agents Chemother. 2010 Sep;54(9):3537-44. Epub 2010 Jun 14.
N Resseguier, V Machault, L Ollivier, E Orlandi-Pradines, G Texier, B Pradines, J Gaudart, A Buguet, C Tourette-Turgis, C Rogier (2010)  Determinants of compliance with malaria chemoprophylaxis among French soldiers during missions in inter-tropical Africa   Malar J 9:  
Abstract: BACKGROUND: The effectiveness of malaria chemoprophylaxis is limited by the lack of compliance whose determinants are not well known. METHODS: The compliance with malaria chemoprophylaxis has been estimated and analysed by validated questionnaires administered before and after the short-term missions (about four months) in five tropical African countries of 2,093 French soldiers from 19 military companies involved in a prospective cohort study. "Correct compliance" was defined as "no missed doses" of daily drug intake during the entire mission and was analysed using multiple mixed-effect logistic regression model. RESULTS: The averaged prevalence rate of correct compliance was 46.2%, ranging from 9.6%to 76.6% according to the companies. Incorrect compliance was significantly associated with eveningness (p = 0.028), a medical history of clinical malaria (p < 0.001) and a perceived mosquito attractiveness inferior or superior to the others (p < 0.007). Correct compliance was significantly associated with the systematic use of protective measures against mosquito bites (p < 0.001), the type of military operations (combat vs. training activities, p < 0.001) and other individual factors (p < 0.05). CONCLUSIONS: The identification of circumstances and profiles of persons at higher risk of lack of compliance would pave the way to specifically targeted strategies aimed to improve compliance with malaria chemoprophylaxis and, therefore, its effectiveness.
Notes: Resseguier, Noemie xD;Machault, Vanessa xD;Ollivier, Lenaick xD;Orlandi-Pradines, Eve xD;Texier, Gaetan xD;Pradines, Bruno xD;Gaudart, Jean xD;Buguet, Alain xD;Tourette-Turgis, Catherine xD;Rogier, Christophe xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2010 Feb 3;9:41.
N Steenkeste, W O Rogers, L Okell, I Jeanne, S Incardona, L Duval, S Chy, S Hewitt, M Chou, D Socheat, F X Babin, F Ariey, C Rogier (2010)  Sub-microscopic malaria cases and mixed malaria infection in a remote area of high malaria endemicity in Rattanakiri province, Cambodia : implication for malaria elimination   Malar J 9:  
Abstract: BACKGROUND: Malaria microscopy and rapid diagnostic tests are insensitive for very low-density parasitaemia. This insensitivity may lead to missed asymptomatic sub-microscopic parasitaemia, a potential reservoir for infection. Similarly, mixed infections and interactions between Plasmodium species may be missed. The objectives were first to develop a rapid and sensitive PCR-based diagnostic method to detect low parasitaemia and mixed infections, and then to investigate the epidemiological importance of sub-microscopic and mixed infections in Rattanakiri Province, Cambodia. METHODS: A new malaria diagnostic method, using restriction fragment length polymorphism analysis of the cytochrome b genes of the four human Plasmodium species and denaturing high performance liquid chromatography, has been developed. The results of this RFLP-dHPLC method have been compared to 1) traditional nested PCR amplification of the 18S rRNA gene, 2) sequencing of the amplified fragments of the cytochrome b gene and 3) microscopy. Blood spots on filter paper and Giemsa-stained blood thick smears collected in 2001 from 1,356 inhabitants of eight villages of Rattanakiri Province have been analysed by the RFLP-dHPLC method and microscopy to assess the prevalence of sub-microscopic and mixed infections. RESULTS: The sensitivity and specificity of the new RFLP-dHPLC was similar to that of the other molecular methods. The RFLP-dHPLC method was more sensitive and specific than microscopy, particularly for detecting low-level parasitaemia and mixed infections. In Rattanakiri Province, the prevalences of Plasmodium falciparum and Plasmodium vivax were approximately two-fold and three-fold higher, respectively, by RFLP-dHPLC (59% and 15%, respectively) than by microscopy (28% and 5%, respectively). In addition, Plasmodium ovale and Plasmodium malariae were never detected by microscopy, while they were detected by RFLP-dHPLC, in 11.2% and 1.3% of the blood samples, respectively. Moreover, the proportion of mixed infections detected by RFLP-dHPLC was higher (23%) than with microscopy (8%). CONCLUSIONS: The rapid and sensitive molecular diagnosis method developed here could be considered for mass screening and ACT treatment of inhabitants of low-endemicity areas of Southeast Asia.
Notes: Steenkeste, Nicolas xD;Rogers, William O xD;Okell, Lucy xD;Jeanne, Isabelle xD;Incardona, Sandra xD;Duval, Linda xD;Chy, Sophy xD;Hewitt, Sean xD;Chou, Monidarin xD;Socheat, Duong xD;Babin, Francois-Xavier xD;Ariey, Frederic xD;Rogier, Christophe xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2010 Apr 22;9:108.
H Savini, J B Souraud, S Briolant, E Baret, R Amalvict, C Rogier, B Pradines (2010)  Atorvastatin as a potential antimalarial drug : in vitro synergy in combinational therapy with dihydroartemisinin   Antimicrob Agents Chemother 54: 2. 966-7  
Notes: Savini, Helene xD;Souraud, Jean Baptiste xD;Briolant, Sebastien xD;Baret, Eric xD;Amalvict, Remy xD;Rogier, Christophe xD;Pradines, Bruno xD;Letter xD;Research Support, Non-U.S. Gov't xD;United States xD;Antimicrobial agents and chemotherapy xD;Antimicrob Agents Chemother. 2010 Feb;54(2):966-7. Epub 2009 Nov 30.
S Briolant, N Wurtz, A Zettor, C Rogier, B Pradines (2010)  Susceptibility of Plasmodium falciparum isolates to doxycycline is associated with pftetQ sequence polymorphisms and pftetQ and pfmdt copy numbers   J Infect Dis 201: 1. 153-9  
Abstract: BACKGROUND: Doxycycline is used in combination with quinine for malaria treatment or alone for malaria chemoprophylaxis. However, the occurrence of malaria after doxycycline chemoprophylaxis has been reported. Identification of genetic determinants that contribute to the susceptibility of Plasmodium falciparum to doxycycline will be important for the detection and surveillance of doxycycline resistance. METHODS: Sequence analysis of 11 genes (pftufA, pfEF-TS, pfmdt, pftetQ, pfrps3, pfrps7, pfrps8, pfrps9, pfrps11, pfrps14, and pfrps17) and evaluation of pfmdt and pftetQ copy numbers by quantitative real-time polymerase chain reaction were conducted in 90 African P. falciparum isolates that were obtained from 14 countries and that belonged to phenotypic groups differing in their doxycycline median inhibitory concentrations. RESULTS: We found that pfmdt copy number of >1 (adjusted odds ratio [OR], 7.09 [95% confidence interval {CI}, 1.58-31.82]; P=.011), pftetQ copy number of >1 (adjusted OR, 5.23 [95% CI, 1.06-25.77]; P=.042), and KYNNNN amino acid motif repeats of <3 (adjusted OR, 3.00 [95% CI, 1.02-8.86]; P=.046) were independently associated with decreased susceptibility to doxycycline. CONCLUSIONS: Our findings suggest that pfmdt and pftetQ copy numbers and pftetQ sequence polymorphisms are potential molecular markers of decreased in vitro susceptibility to doxycycline in African P. falciparum isolates.
Notes: Briolant, Sebastien xD;Wurtz, Nathalie xD;Zettor, Agnes xD;Rogier, Christophe xD;Pradines, Bruno xD;Research Support, Non-U.S. Gov't xD;United States xD;The Journal of infectious diseases xD;J Infect Dis. 2010 Jan 1;201(1):153-9.
A Dicko, I Sagara, A A Djimde, S O Toure, M Traore, S Dama, A I Diallo, A Barry, M Dicko, O M Coulibaly, C Rogier, A de Sousa, O K Doumbo (2010)  Molecular markers of resistance to sulphadoxine-pyrimethamine one year after implementation of intermittent preventive treatment of malaria in infants in Mali   Malar J 9:  
Abstract: BACKGROUND: Intermittent preventive treatment in infants (IPTi) with sulphadoxine-pyrimethamine (SP) given during routine vaccinations is efficacious in preventing malaria disease and shows no interaction with the vaccines. However, there is a fear that IPTi may result in a rapid increase of parasite resistance to SP. METHODS: To evaluate the impact of IPTi on SP-resistance point mutations, the 22 health sub-districts in the district of Kolokani, Mali, were randomized in a 1:1 ratio and starting in December 2006, IPTi with SP was implemented in 11 health sub-districts (intervention zone), while the other 11 health sub-districts served as the control (non-intervention zone). Blood smears and blood dots on filter paper were obtained from children aged 0-5 years, randomly selected in each of heath sub-districts during two cross-sectional surveys. The first survey was conducted in May 2007 before the start of the transmission season to collect baseline prevalence of the molecular markers of resistance to SP and the second in December 2007 after the end of the transmission season and one year after implementation of IPTi. A total of 427 and 923 randomly selected blood samples from the first and second surveys respectively were analysed by PCR for dhfr and dhps mutations. RESULTS: Each of the three dhfr mutations at codons 51, 59 and 108 was present in 35% and 57% of the samples during the two surveys with no significant differences between the two zones. Dhps mutations at codons 437 and 540 were present respectively in about 20% and 1% of the children during the two surveys in both zones at similar proportion. The prevalence of quadruple mutants (triple dhfr-mutants + dhps-437G) associated with in-vivo resistance to SP in Mali after one year implementation of IPTi was also similar between the two zones (11.6% versus 11.2%, p = 0.90) and to those obtained at baseline survey (10.3% versus 8.1%). CONCLUSION: This study shows no increase in the frequency of molecular markers of SP resistance in areas where IPTi with SP was implemented for one year.
Notes: Dicko, Alassane xD;Sagara, Issaka xD;Djimde, Abdoulaye A xD;Toure, Sidy O xD;Traore, Mariam xD;Dama, Souleymane xD;Diallo, Abdoulbaki I xD;Barry, Amadou xD;Dicko, Mohamed xD;Coulibaly, Oumar M xD;Rogier, Christophe xD;de Sousa, Alexandra xD;Doumbo, Ogobara K xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2010 Jan 10;9:9.
N Wurtz, S Briolant, M Gil, V Parquet, M Henry, E Baret, R Amalvict, L Almeras, C Rogier, B Pradines (2010)  Synergy of mefloquine activity with atorvastatin, but not chloroquine and monodesethylamodiaquine, and association with the pfmdr1 gene   J Antimicrob Chemother 65: 7. 1387-94  
Abstract: OBJECTIVES: The aim of the study was to assess the in vitro potentiating effects of atorvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in combination with mefloquine, chloroquine or monodesethylamodiaquine against Plasmodium falciparum and to evaluate whether the effects of atorvastatin could be associated with mutations or gene copy number in multidrug resistance (MDR)-like protein genes. METHODS: The susceptibilities of 21 parasite strains to combinations of atorvastatin with mefloquine, chloroquine or monodesethylamodiaquine were assessed using the in vitro isotopic microtest. Genotypes and gene copy number were assessed for pfmdr1, pfmdr2 and pfmrp genes. RESULTS: Atorvastatin demonstrated synergistic effects in combination with mefloquine. The mefloquine IC(50) (50% inhibitory concentration) was reduced by 7%, 24% and 37% in the presence of atorvastatin at concentrations of 0.1, 0.5 and 1.0 microM, respectively. The synergistic effect of atorvastatin on the response to mefloquine was significantly associated with pfmdr1 copy number. The concentration of atorvastatin that could reduce the IC(50) of mefloquine by 50% was 2.4 +/- 1.3 microM for the 12 strains that contained one copy of pfmdr1 and 5.8 +/- 2.1 microM for the 9 strains that contained two copies or more. The synergistic effect of atorvastatin in combination with mefloquine was found to be significantly unrelated to mutations in pfmdr1, pfmdr2 or pfmrp genes. CONCLUSIONS: The synergy of the effect of mefloquine at concentrations relevant to its achievable plasma concentrations in patients taking 80 mg of atorvastatin daily suggests that atorvastatin will be a good candidate in combination with mefloquine for malaria treatment.
Notes: Wurtz, Nathalie xD;Briolant, Sebastien xD;Gil, Marine xD;Parquet, Veronique xD;Henry, Maud xD;Baret, Eric xD;Amalvict, Remy xD;Almeras, Lionel xD;Rogier, Christophe xD;Pradines, Bruno xD;Research Support, Non-U.S. Gov't xD;England xD;The Journal of antimicrobial chemotherapy xD;J Antimicrob Chemother. 2010 Jul;65(7):1387-94. Epub 2010 May 25.
S Briolant, L Almeras, M Belghazi, E Boucomont-Chapeaublanc, N Wurtz, A Fontaine, S Granjeaud, T Fusai, C Rogier, B Pradines (2010)  Plasmodium falciparum proteome changes in response to doxycycline treatment   Malar J 9:  
Abstract: BACKGROUND: The emergence of Plasmodium falciparum resistance to most anti-malarial compounds has highlighted the urgency to develop new drugs and to clarify the mechanisms of anti-malarial drugs currently used. Among them, doxycycline is used alone for malaria chemoprophylaxis or in combination with quinine or artemisinin derivatives for malaria treatment. The molecular mechanisms of doxycycline action in P. falciparum have not yet been clearly defined, particularly at the protein level. METHODS: A proteomic approach was used to analyse protein expression changes in the schizont stage of the malarial parasite P. falciparum following doxycycline treatment. A comparison of protein expression between treated and untreated protein samples was performed using two complementary proteomic approaches: two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and isobaric tagging reagents for relative and absolute quantification (iTRAQ). RESULTS: After doxycycline treatment, 32 and 40 P. falciparum proteins were found to have significantly deregulated expression levels by 2D-DIGE and iTRAQ methods, respectively. Although some of these proteins have been already described as being deregulated by other drug treatments, numerous changes in protein levels seem to be specific to doxycycline treatment, which could perturb apicoplast metabolism. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to confirm this hypothesis. CONCLUSIONS: In this study, a specific response to doxycycline treatment was distinguished and seems to involve mitochondrion and apicoplast organelles. These data provide a starting point for the elucidation of drug targets and the discovery of mechanisms of resistance to anti-malarial compounds.
Notes: Briolant, Sebastien xD;Almeras, Lionel xD;Belghazi, Maya xD;Boucomont-Chapeaublanc, Elodie xD;Wurtz, Nathalie xD;Fontaine, Albin xD;Granjeaud, Samuel xD;Fusai, Thierry xD;Rogier, Christophe xD;Pradines, Bruno xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2010 May 25;9:141.
A Fontaine, M Pophillat, S Bourdon, C Villard, M Belghazi, P Fourquet, C Durand, D Lefranc, C Rogier, T Fusai, L Almeras (2010)  Specific antibody responses against membrane proteins of erythrocytes infected by Plasmodium falciparum of individuals briefly exposed to malaria   Malar J 9:  
Abstract: BACKGROUND: Plasmodium falciparum infections could lead to severe malaria, principally in non-immune individuals as children and travellers from countries exempted of malaria. Severe malaria is often associated with the sequestration of P. falciparum-infected erythrocytes in deep micro-vascular beds via interactions between host endothelial receptors and parasite ligands expressed on the surface of the infected erythrocyte. Although, serological responses from individuals living in endemic areas against proteins expressed at surface of the infected erythrocyte have been largely studied, seldom data are available about the specific targets of antibody response from travellers. METHODS: In order to characterize antigens recognized by traveller sera, a comparison of IgG immune response against membrane protein extracts from uninfected and P. falciparum-infected red blood cells (iRBC), using immunoblots, was performed between non exposed individuals (n = 31) and briefly exposed individuals (BEI) (n = 38) to malaria transmission. RESULTS: Immune profile analysis indicated that eight protein bands from iRBC were significantly detected more frequently in the BEI group. Some of these antigenic proteins were identified by an original immuno-proteomic approach. CONCLUSION: Collectively, these data may be useful to characterize the singular serological immune response against a primary malaria infection in individuals briefly exposed to transmission.
Notes: Fontaine, Albin xD;Pophillat, Matthieu xD;Bourdon, Stephanie xD;Villard, Claude xD;Belghazi, Maya xD;Fourquet, Patrick xD;Durand, Claude xD;Lefranc, Didier xD;Rogier, Christophe xD;Fusai, Thierry xD;Almeras, Lionel xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2010 Oct 11;9:276.
C Czeher, R Labbo, G Vieville, I Arzika, H Bogreau, C Rogier, L Diancourt, S Brisse, F Ariey, J B Duchemin (2010)  Population genetic structure of Anopheles gambiae and Anopheles arabiensis in Niger   J Med Entomol 47: 3. 355-66  
Abstract: The increasing usage of long-lasting insecticide-treated nets allows protection of millions of people from malaria infection. Monitoring studies should be planned during any wide-scale malaria control program integrating insecticide-treated materials, to evaluate their effects and effectiveness on epidemiologically relevant parameters. Such operational control interventions may be challenged by insecticide resistance spread within vector populations, as a result of wide insecticide pressure. A nationwide distribution of long-lasting insecticidal nets was implemented throughout Niger in 2005. We studied the population genetic structure of major malaria vectors across Nigerien Sahel, and investigated potential effects of this large malaria control intervention. Wild-caught Anopheles gambiae sensu lato females from seven villages and two wet seasons were genotyped at 12 microsatellite loci. The genetic diversity within both species appeared homogenous between villages and years. The estimated genetic differentiation among samples was very low within both species, indicating high gene flow across the area. An absence of differentiation was also found between 2005 and 2006 wet seasons, for all samples but one, showing that the net distribution did not impact significantly the genetic diversity and structure of vector populations in a single year. We provide valuable results participating to document effects of large malaria control programs, to maximize the efficiency of available tools in future interventions.
Notes: Czeher, Cyrille xD;Labbo, Rabiou xD;Vieville, Gaelle xD;Arzika, Ibrahim xD;Bogreau, Herve xD;Rogier, Christophe xD;Diancourt, Laure xD;Brisse, Sylvain xD;Ariey, Frederic xD;Duchemin, Jean-Bernard xD;Research Support, Non-U.S. Gov't xD;United States xD;Journal of medical entomology xD;J Med Entomol. 2010 May;47(3):355-66.
A B Ly, A Tall, R Perry, L Baril, A Badiane, J Faye, C Rogier, A Toure, C Sokhna, J F Trape, R Michel (2010)  Use of HRP-2-based rapid diagnostic test for Plasmodium falciparum malaria : assessing accuracy and cost-effectiveness in the villages of Dielmo and Ndiop, Senegal   Malar J 9:  
Abstract: BACKGROUND: In 2006, the Senegalese National Malaria Control Programme (NMCP) has recommended artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria and, in 2007, mandated testing for all suspected cases of malaria with a Plasmodium falciparum HRP-2-based rapid diagnostic test for malaria (RDT(Paracheck). Given the higher cost of ACT compared to earlier anti-malarials, the objectives of the present study were i) to study the accuracy of Paracheck compared to the thick blood smear (TBS) in two areas with different levels of malaria endemicity and ii) analyse the cost-effectiveness of the strategy of the parasitological confirmation of clinically suspected malaria cases management recommended by the NMCP. METHODS: A cross-sectional study was undertaken in the villages of Dielmo and Ndiop (Senegal) nested in a cohort study of about 800 inhabitants. For all the individuals consulting between October 2008 and January 2009 with a clinical diagnosis of malaria, a questionnaire was filled and finger-prick blood samples were taken both for microscopic examination and RDT. The estimated costs and cost-effectiveness analysis were made considering five scenarios, the recommendations of the NMCP being the reference scenario. In addition, a sensitivity analysis was performed assuming that all the RDT-positive patients and 50% of RDT-negative patients were treated with ACT. RESULTS: A total of 189 consultations for clinically suspected malaria occurred during the study period. The sensitivity, specificity, positive and negative predictive values were respectively 100%, 98.3%, 80.0% and 100%. The estimated cost of the reference scenario was close to 700 euros per 1000 episodes of illness, approximately twice as expensive as most of the other scenarios. Nevertheless, it appeared to us cost-effective while ensuring the diagnosis and the treatment of 100% of malaria attacks and an adequate management of 98.4% of episodes of illness. The present study also demonstrated that full compliance of health care providers with RDT results was required in order to avoid severe incremental costs. CONCLUSIONS: A rational use of ACT requires laboratory testing of all patients presenting with presumed malaria. Use of RDTs inevitably has incremental costs, but the strategy associating RDT use for all clinically suspected malaria and prescribing ACT only to patients tested positive is cost-effective in areas where microscopy is unavailable.
Notes: Ly, Alioune Badara xD;Tall, Adama xD;Perry, Robert xD;Baril, Laurence xD;Badiane, Abdoulaye xD;Faye, Joseph xD;Rogier, Christophe xD;Toure, Aissatou xD;Sokhna, Cheikh xD;Trape, Jean-Francois xD;Michel, Remy xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2010 Jun 4;9:153.
L Almeras, A Fontaine, M Belghazi, S Bourdon, E Boucomont-Chapeaublanc, E Orlandi-Pradines, M Baragatti, N Corre-Catelin, P Reiter, B Pradines, T Fusai, C Rogier (2010)  Salivary gland protein repertoire from Aedes aegypti mosquitoes   Vector Borne Zoonotic Dis 10: 4. 391-402  
Abstract: Diseases caused by arthropod-borne viruses are a significant threat to the health of human and animal populations throughout the world. Better knowledge of the molecules synthesized in the salivary gland and saliva of hematophagous arthropods could be of use for improving the control of pathogen transmission. Recently, a sialome analysis of three Aedes aegypti mosquito colonies (PAEA, Rockefeller, and Formosus) carried out in our laboratory allowed us to identify 44 saliva proteins. Of these secreted proteins, none was exclusively expressed in one colony, suggesting that expression of salivary proteins is highly conserved across populations. In another study, we reported that some of these salivary proteins could be used as the genus-specific markers for travelers' exposure to mosquito vectors. Here, comparison of salivary gland protein profiles between these same three Ae. aegypti colonies was performed using the one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) difference gel electrophoresis method. As observed at the saliva level, no significant differences were detected between these three colonies. The salivary gland protein repertoire from the Ae. aegypti mosquito was analyzed using a proteomic approach. One hundred and twenty proteins were identified in these salivary glands representing the largest description of the Ae. aegypti salivary gland protein catalog. We succeeded in identifying 15 secreted proteins, some of which have already been reported as being involved in blood feeding. A comparison of the proteins identified between the salivary glands and the sialome is discussed.
Notes: Almeras, Lionel xD;Fontaine, Albin xD;Belghazi, Maya xD;Bourdon, Stephanie xD;Boucomont-Chapeaublanc, Elodie xD;Orlandi-Pradines, Eve xD;Baragatti, Meli xD;Corre-Catelin, Nicole xD;Reiter, Paul xD;Pradines, Bruno xD;Fusai, Thierry xD;Rogier, Christophe xD;Research Support, Non-U.S. Gov't xD;United States xD;Vector borne and zoonotic diseases (Larchmont, N.Y.) xD;Vector Borne Zoonotic Dis. 2010 May;10(4):391-402.
E Marion, S Eyangoh, E Yeramian, J Doannio, J Landier, J Aubry, A Fontanet, C Rogier, V Cassisa, J Cottin, A Marot, M Eveillard, Y Kamdem, P Legras, C Deshayes, J P Saint-Andre, L Marsollier (2010)  Seasonal and regional dynamics of M. ulcerans transmission in environmental context : deciphering the role of water bugs as hosts and vectors   PLoS Negl Trop Dis 4: 7.  
Abstract: BACKGROUND: Buruli ulcer, the third mycobacterial disease after tuberculosis and leprosy, is caused by the environmental mycobacterium M. ulcerans. Various modes of transmission have been suspected for this disease, with no general consensus acceptance for any of them up to now. Since laboratory models demonstrated the ability of water bugs to transmit M. ulcerans, a particular attention is focused on the transmission of the bacilli by water bugs as hosts and vectors. However, it is only through detailed knowledge of the biodiversity and ecology of water bugs that the importance of this mode of transmission can be fully assessed. It is the objective of the work here to decipher the role of water bugs in M. ulcerans ecology and transmission, based on large-scale field studies. METHODOLOGY/PRINCIPAL FINDINGS: The distribution of M. ulcerans-hosting water bugs was monitored on previously unprecedented time and space scales: a total of 7,407 water bugs, belonging to large number of different families, were collected over one year, in Buruli ulcer endemic and non endemic areas in central Cameroon. This study demonstrated the presence of M. ulcerans in insect saliva. In addition, the field results provided a full picture of the ecology of transmission in terms of biodiversity and detailed specification of seasonal and regional dynamics, with large temporal heterogeneity in the insect tissue colonization rate and detection of M. ulcerans only in water bug tissues collected in Buruli ulcer endemic areas. CONCLUSION/SIGNIFICANCE: The large-scale detection of bacilli in saliva of biting water bugs gives enhanced weight to their role in M. ulcerans transmission. On practical grounds, beyond the ecological interest, the results concerning seasonal and regional dynamics can provide an efficient tool in the hands of sanitary authorities to monitor environmental risks associated with Buruli ulcer.
Notes: Marion, Estelle xD;Eyangoh, Sara xD;Yeramian, Edouard xD;Doannio, Julien xD;Landier, Jordi xD;Aubry, Jacques xD;Fontanet, Arnaud xD;Rogier, Christophe xD;Cassisa, Viviane xD;Cottin, Jane xD;Marot, Agnes xD;Eveillard, Matthieu xD;Kamdem, Yannick xD;Legras, Pierre xD;Deshayes, Caroline xD;Saint-Andre, Jean-Paul xD;Marsollier, Laurent xD;Research Support, Non-U.S. Gov't xD;United States xD;PLoS neglected tropical diseases xD;PLoS Negl Trop Dis. 2010 Jul 6;4(7):e731.
V Machault, C Vignolles, F Pages, L Gadiaga, A Gaye, C Sokhna, J F Trape, J P Lacaux, C Rogier (2010)  Spatial heterogeneity and temporal evolution of malaria transmission risk in Dakar, Senegal, according to remotely sensed environmental data   Malar J 9: 1.  
Abstract: ABSTRACT: BACKGROUND: The United Nations forecasts that by 2050, more than 60% of the African population will live in cities. Thus, urban malaria is considered an important emerging health problem in that continent. Remote sensing (RS) and geographic information systems (GIS) are useful tools for addressing the challenge of assessing, understanding and spatially focusing malaria control activities. The objectives of the present study were to use high spatial resolution SPOT (Satellite Pour l'Observation de la Terre) satellite images to identify some urban environmental factors in Dakar associated with Anopheles arabiensis densities, to assess the persistence of these associations and to describe spatial changes in at-risk environments using a decadal time scale. METHODS: Two SPOT images from the 1996 and 2007 rainy seasons in Dakar were processed to extract environmental factors, using supervised classification of land use and land cover, and a calculation of NDVI (Normalized Difference Vegetation Index) and distance to vegetation. Linear regressions were fitted to identify the ecological factors associated with An. arabiensis aggressiveness measured in 1994-97 in the South and centre districts of Dakar. Risk maps for populated areas were computed and compared for 1996 and 2007 using the results of the statistical models. RESULTS: Almost 60% of the variability in anopheline aggressiveness measured in 1994-97 was explained with only one variable: the built-up area in a 300-m radius buffer around the catching points. This association remained stable between 1996 and 2007. Risk maps were drawn by inverting the statistical association. The total increase of the built-up areas in Dakar was about 30% between 1996 and 2007. In proportion to the total population of the city, the population at high risk for malaria fell from 32% to 20%, whereas the low-risk population rose from 29 to 41%. CONCLUSIONS: Environmental data retrieved from high spatial resolution SPOT satellite images were associated with An. arabiensis densities in Dakar urban setting, which allowed to generate malaria transmission risk maps. The evolution of the risk was quantified, and the results indicated there are benefits of urbanization in Dakar, since the proportion of the low risk population increased while urbanization progressed.
Notes: Journal article xD;Malaria journal xD;Malar J. 2010 Sep 3;9(1):252.
E Ambrosino, C Dumoulin, E Orlandi-Pradines, F Remoue, A Toure-Balde, A Tall, J B Sarr, A Poinsignon, C Sokhna, K Puget, J F Trape, A Pascual, P Druilhe, T Fusai, C Rogier (2010)  A multiplex assay for the simultaneous detection of antibodies against 15 Plasmodium falciparum and Anopheles gambiae saliva antigens   Malar J 9:  
Abstract: ABSTRACT: BACKGROUND: Assessment exposure and immunity to malaria is an important step in the fight against the disease. Increased malaria infection in non-immune travellers under anti-malarial chemoprophylaxis, as well as the implementation of malaria elimination programmes in endemic countries, raises new issues that pertain to these processes. Notably, monitoring malaria immunity has become more difficult in individuals showing low antibody (Ab) responses or taking medications against the Plasmodium falciparum blood stages. Commonly available techniques in malaria seroepidemiology have limited sensitivity, both against pre-erythrocytic, as against blood stages of the parasite. Thus, the aim of this study was to develop a sensitive tool to assess the exposure to malaria or to bites from the vector Anopheles gambiae, despite anti-malarial prophylactic treatment. METHODS: Ab responses to 13 pre-erythrocytic P. falciparum-specific peptides derived from the proteins Lsa1, Lsa3, Glurp, Salsa, Trap, Starp, CSP and Pf11.1, and to 2 peptides specific for the Anopheles gambiae saliva protein gSG6 were tested. In this study, 253 individuals from three Senegalese areas with different transmission intensities and 124 European travellers exposed to malaria during a short period of time were included. RESULTS: The multiplex assay was optimized for most but not all of the antigens. It was rapid, reproducible and required a small volume of serum. Proportions of Ab-positive individuals, Ab levels and the mean number of antigens (Ags) recognized by each individual increased significantly with increases in the level of malaria exposure. CONCLUSION: The multiplex assay developed here provides a useful tool to evaluate immune responses to multiple Ags in large populations, even when only small amounts of serum are available, or Ab titres are low, as in case of travellers. Finally, the relationship of Ab responses with malaria endemicity levels provides a way to monitor exposure in differentially exposed autochthonous individuals from various endemicity areas, as well as in travellers who are not immune, thus indirectly assessing the parasite transmission and malaria risk in the new eradication era.
Notes: Ambrosino, Elena xD;Dumoulin, Chloe xD;Orlandi-Pradines, Eve xD;Remoue, Franck xD;Toure-Balde, Aissatou xD;Tall, Adama xD;Sarr, Jean Biram xD;Poinsignon, Anne xD;Sokhna, Cheikh xD;Puget, Karine xD;Trape, Jean-Francois xD;Pascual, Aurelie xD;Druilhe, Pierre xD;Fusai, Thierry xD;Rogier, Christophe xD;England xD;Malaria journal xD;Malar J. 2010 Nov 8;9:317.
Y R Lawaly, A Sakuntabhai, L Marrama, L Konate, W Phimpraphi, C Sokhna, A Tall, F D Sarr, C Peerapittayamongkol, C Louicharoen, B S Schneider, A Levescot, A Talman, I Casademont, D Menard, J F Trape, C Rogier, J Kaewkunwal, T Sura, I Nuchprayoon, F Ariey, L Baril, P Singhasivanon, O Mercereau-Puijalon, R Paul (2010)  Heritability of the human infectious reservoir of malaria parasites   PLoS One 5: 6.  
Abstract: BACKGROUND: Studies on human genetic factors associated with malaria have hitherto concentrated on their role in susceptibility to and protection from disease. In contrast, virtually no attention has been paid to the role of human genetics in eliciting the production of parasite transmission stages, the gametocytes, and thus enhancing the spread of disease. METHODS AND FINDINGS: We analysed four longitudinal family-based cohort studies from Senegal and Thailand followed for 2-8 years and evaluated the relative impact of the human genetic and non-genetic factors on gametocyte production in infections of Plasmodium falciparum or P. vivax. Prevalence and density of gametocyte carriage were evaluated in asymptomatic and symptomatic infections by examination of Giemsa-stained blood smears and/or RT-PCR (for falciparum in one site). A significant human genetic contribution was found to be associated with gametocyte prevalence in asymptomatic P. falciparum infections. By contrast, there was no heritability associated with the production of gametocytes for P. falciparum or P. vivax symptomatic infections. Sickle cell mutation, HbS, was associated with increased gametocyte prevalence but its contribution was small. CONCLUSIONS: The existence of a significant human genetic contribution to gametocyte prevalence in asymptomatic infections suggests that candidate gene and genome wide association approaches may be usefully applied to explore the underlying human genetics. Prospective epidemiological studies will provide an opportunity to generate novel and perhaps more epidemiologically pertinent gametocyte data with which similar analyses can be performed and the role of human genetics in parasite transmission ascertained.
Notes: Lawaly, Yaye Ramatoulaye xD;Sakuntabhai, Anavaj xD;Marrama, Laurence xD;Konate, Lassana xD;Phimpraphi, Waraphon xD;Sokhna, Cheikh xD;Tall, Adama xD;Sarr, Fatoumata Diene xD;Peerapittayamongkol, Chayanon xD;Louicharoen, Chalisa xD;Schneider, Bradley S xD;Levescot, Anais xD;Talman, Arthur xD;Casademont, Isabelle xD;Menard, Didier xD;Trape, Jean-Francois xD;Rogier, Christophe xD;Kaewkunwal, Jaranit xD;Sura, Thanyachai xD;Nuchprayoon, Issarang xD;Ariey, Frederic xD;Baril, Laurence xD;Singhasivanon, Pratap xD;Mercereau-Puijalon, Odile xD;Paul, Rick xD;Research Support, Non-U.S. Gov't xD;United States xD;PloS one xD;PLoS One. 2010 Jun 29;5(6):e11358.
J R Mourou, T Coffinet, F Jarjaval, B Pradines, R Amalvict, C Rogier, M Kombila, F Pages (2010)  Malaria transmission and insecticide resistance of Anopheles gambiae in Libreville and Port-Gentil, Gabon   Malar J 9:  
Abstract: ABSTRACT: BACKGROUND: Urban malaria is a major health priority for civilian and militaries populations. A preliminary entomologic study has been conducted in 2006-2007, in the French military camps of the two mains towns of Gabon: Libreville and Port-Gentil. The aim was to assess the malaria transmission risk for troops. METHODS: Mosquitoes sampled by human landing collection were identified morphologically and by molecular methods. The Plasmodium falciparum circumsporozoite (CSP) indexes were measured by ELISA, and the entomological inoculation rates (EIR) were calculated for both areas. Molecular assessments of pyrethroid knock down (kdr) resistance and of insensitive acetylcholinesterase resistance were conducted. RESULTS: In Libreville, Anopheles gambiae s.s. S form was the only specie of the An. gambiae complex present and was responsible of 9.4 bites per person per night. The circumsporozoite index was 0.15% and the entomological inoculation rate estimated to be 1.23 infective bites during the four months period. In Port-Gentil, Anopheles melas (75.5% of catches) and An. gambiae s.s. S form (24.5%) were responsible of 58.7 bites per person per night. The CSP indexes were of 1.67% for An. gambiae s.s and 0.28% for An. melas and the EIRs were respectively of 1.8 infective bites per week and of 0.8 infective bites per week. Both kdr-w and kdr-e mutations in An. gambiae S form were found in Libreville and in Port-Gentil. Insensitive acetylcholinesterase has been detected for the first time in Gabon in Libreville. CONCLUSION: Malaria transmission exists in both town, but with high difference in the level of risk. The co-occurrence of molecular resistances to the main families of insecticide has implications for the effectiveness of the current vector control programmes that are based on pyrethroid-impregnated bed nets.
Notes: Mourou, Jean-Romain xD;Coffinet, Thierry xD;Jarjaval, Fanny xD;Pradines, Bruno xD;Amalvict, Remi xD;Rogier, Christophe xD;Kombila, Maryvonne xD;Pages, Frederic xD;England xD;Malaria journal xD;Malar J. 2010 Nov 11;9:321.
V Parquet, M Henry, N Wurtz, J Dormoi, S Briolant, M Gil, E Baret, R Amalvict, C Rogier, B Pradines (2010)  Atorvastatin as a potential anti-malarial drug : in vitro synergy in combinational therapy with quinine against Plasmodium falciparum   Malar J 9:  
Abstract: BACKGROUND: Quinine (QN) remains the first line anti-malarial drug for the treatment of complicated malaria in Europe and Africa. The emergence of QN resistance has been documented. QN resistance is not yet a significant problem, but there is an urgent need to discover partners for use in combination with QN. The aim of the study was to assess the in vitro potentiating effects of atorvastatin (AVA), a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, in combination with QN against Plasmodium falciparum and to evaluate whether the effects of AVA could be associated with gene copy number or mutations in genes involved in QN resistance, such as pfcrt, pfmdr1, pfmrp and pfnhe. METHODS: The susceptibilities to combination of AVA with QN were assessed against 21 parasite strains using the in vitro isotopic microtest. Genotypes and gene copy number were assessed for pfcrt, pfmdr1, pfmdr2, pfmrp genes. In addition, the number of DNNND, DDNHNDNHNN repeats in pfnhe-1 ms4760 and the ms4760 profile were determined for each strains of P. falciparum. RESULTS: AVA demonstrated synergistic effects in combination with QN against 21 P. falciparum strains. The QN IC50 was reduced by 5% (0% to 15%; 95%CI: 1%-8%), 10% (3% to 23%; 95%CI: 7%-14%) and 22% (14% to 40%; 95%CI: 19%-25%) in presence of AVA at concentrations of 0.1, 0.5 and 1.0 microM, respectively. These reductions were all significant (p < 0.009). The reduction in the QN IC50 in presence of AVA was not significantly correlated with the QN IC50 (r = 0.22, P = 0.3288) or the AVA IC50 (r = 0.03, P = 0.8946). The synergistic effect of AVA in combination with QN was not significantly associated with polymorphisms in the pfcrt, pfmdr1, pfmrp, and pfnhe-1 genes that could be involved in QN resistance. The synergistic effect of AVA on QN responses was not significantly associated with pfmdr1 copy number (P = 0.0428). CONCLUSION: The synergistic effect of AVA in combination with QN was found to be unrelated to mutations occurring in transport protein genes involved in QN drug resistance. The different mechanisms of drug uptake and/or mode of action for AVA compared to the other anti-malarial drugs, as well as the AVA-mediated synergy of the anti-malarial effect of QN, suggests that AVA will be a good candidate for combinatorial malaria treatment. All of these observations support calls for both an in vivo evaluation with pharmacokinetic component and clinical trials of AVA as an anti-malarial therapy.
Notes: Parquet, Veronique xD;Henry, Maud xD;Wurtz, Nathalie xD;Dormoi, Jerome xD;Briolant, Sebastien xD;Gil, Marine xD;Baret, Eric xD;Amalvict, Remy xD;Rogier, Christophe xD;Pradines, Bruno xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2010 May 25;9:139.
B Pradines, T Pistone, K Ezzedine, S Briolant, L Bertaux, M C Receveur, D Parzy, P Millet, C Rogier, D Malvy (2010)  Quinine-resistant malaria in traveler returning from Senegal, 2007   Emerg Infect Dis 16: 3. 546-8  
Abstract: We describe clinical and parasitologic features of in vivo and in vitro Plasmodium falciparum resistance to quinine in a nonimmune traveler who returned to France from Senegal in 2007 with severe imported malaria. Clinical quinine failure was associated with a 50% inhibitory concentration of 829 nmol/L. Increased vigilance is required during treatment follow-up.
Notes: Pradines, Bruno xD;Pistone, Thierry xD;Ezzedine, Khaled xD;Briolant, Sebastien xD;Bertaux, Lionel xD;Receveur, Marie Catherine xD;Parzy, Daniel xD;Millet, Pascal xD;Rogier, Christophe xD;Malvy, Denis xD;Case Reports xD;United States xD;Emerging infectious diseases xD;Emerg Infect Dis. 2010 Mar;16(3):546-8.
B Pradines, S Briolant, M Henry, C Oeuvray, E Baret, R Amalvict, E Didillon, C Rogier (2010)  Absence of association between pyronaridine in vitro responses and polymorphisms in genes involved in quinoline resistance in Plasmodium falciparum   Malar J 9: 1.  
Abstract: ABSTRACT: BACKGROUND: The aim of the present work was to assess the in vitro cross-resistance of pyronaridine with other quinoline drugs, artesunate and several other commonly used anti-malarials and to evaluate whether decreased susceptibility to pyronaridine could be associated with genetic polymorphisms in genes involved in reduced quinoline susceptibility, such as pfcrt, pfmdr1, pfmrp and pfnhe. METHODS: The in vitro chemosusceptibility profiles of 23 strains of Plasmodium falciparum were analysed by the standard 42-hour 3H-hypoxanthine uptake inhibition method for pyronaridine, artesunate, chloroquine, monodesethylamodiaquine, quinine, mefloquine, lumefantrine, atovaquone, pyrimethamine and doxycycline. Genotypes were assessed for pfcrt, pfmdr1, pfnhe-1 and pfmrp genes. RESULTS: The IC50 values for pyronaridine ranged from 15 to 49 nM (geometric mean = 23.1 nM). A significant positive correlation was found between responses to pyronaridine and responses to artesunate (r2 = 0.20; P = 0.0317) but too low to suggest cross-resistance. No significant correlation was found between pyronaridine IC50 and responses to other anti-malarials. Significant associations were not found between pyronaridine IC50 and polymorphisms in pfcrt, pfmdr1, pfmrp or pfnhe-1. CONCLUSION: There was an absence of cross-resistance between pyronaridine and quinolines, and the IC50 values for pyronaridine were found to be unrelated to mutations in the transport protein genes pfcrt, pfmdr1, pfmrp or pfnhe-1, known to be involved in quinoline resistance. These results confirm the interest and the efficacy of the use of a combination of pyronaridine and artesunate in areas in which parasites are resistant to quinolines.
Notes: Journal article xD;Malaria journal xD;Malar J. 2010 Nov 25;9(1):339.
C Pennetier, J Chabi, T Martin, F Chandre, C Rogier, J M Hougard, F Pages (2010)  New protective battle-dress impregnated against mosquito vector bites   Parasit Vectors 3:  
Abstract: ABSTRACT: BACKGROUND: Mixing repellent and organophosphate (OP) insecticides to better control pyrethroid resistant mosquito vectors is a promising strategy developed for bed net impregnation. Here, we investigated the opportunity to adapt this strategy to personal protection in the form of impregnated clothes. METHODS: We compared standard permethrin impregnated uniforms with uniforms manually impregnated with the repellent KBR3023 alone and in combination with an organophosphate, Pirimiphos-Methyl (PM). Tests were carried out with Aedes aegypti, the dengue fever vector, at dusk in experimental huts. RESULTS: Results showed that the personal protection provided by repellent KBR3023-impregnated uniforms is equal to permethrin treated uniforms and that KBR3023/PM-impregnated uniforms are more protective. CONCLUSION: The use of repellents alone or combined with OP on clothes could be promising for personal protection of military troops and travellers if residual activity of the repellents is extended and safety is verified.
Notes: Pennetier, Cedric xD;Chabi, Joseph xD;Martin, Thibaud xD;Chandre, Fabrice xD;Rogier, Christophe xD;Hougard, Jean-Marc xD;Pages, Frederic xD;England xD;Parasites & vectors xD;Parasit Vectors. 2010 Sep 1;3:81.
S Rebaudet, H Bogreau, R Silai, J F Lepere, L Bertaux, B Pradines, J Delmont, P Gautret, P Parola, C Rogier (2010)  Genetic structure of Plasmodium falciparum and elimination of malaria, Comoros archipelago   Emerg Infect Dis 16: 11. 1686-94  
Abstract: The efficacy of malaria control and elimination on islands may depend on the intensity of new parasite inflow. On the Comoros archipelago, where falciparum malaria remains a major public health problem because of spread of drug resistance and insufficient malaria control, recent interventions for malaria elimination were planned on Moheli, 1 of 4 islands in the Comoros archipelago. To assess the relevance of such a local strategy, we performed a population genetics analysis by using multilocus microsatellite and resistance genotyping of Plasmodium falciparum sampled from each island of the archipelago. We found a contrasted population genetic structure explained by geographic isolation, human migration, malaria transmission, and drug selective pressure. Our findings suggest that malaria elimination interventions should be implemented simultaneously on the entire archipelago rather than restricted to 1 island and demonstrate the necessity for specific chemoresistance surveillance on each of the 4 Comorian islands.
Notes: Rebaudet, Stanislas xD;Bogreau, Herve xD;Silai, Rahamatou xD;Lepere, Jean Francois xD;Bertaux, Lionel xD;Pradines, Bruno xD;Delmont, Jean xD;Gautret, Philippe xD;Parola, Philippe xD;Rogier, Christophe xD;Research Support, Non-U.S. Gov't xD;United States xD;Emerging infectious diseases xD;Emerg Infect Dis. 2010 Nov;16(11):1686-94.
N Kheliouen, F Viwami, F Lalya, N Tuikue-Ndam, E C Moukoko, C Rogier, P Deloron, A Aubouy (2010)  Plasmodium falciparum parasites causing cerebral malaria share variant surface antigens, but are they specific?   Malar J 9:  
Abstract: BACKGROUND: Variant surface antigens (VSA) expressed on the surface of Plasmodium falciparum-infected red blood cells constitute a key for parasite sequestration and immune evasion. In distinct malaria pathologies, such as placental malaria, specific antibody response against VSA provides protection. This study investigated the antibody response specifically directed against VSA expressed by parasites isolated from individuals presenting a given type of clinical presentation. METHODS: Plasma and isolates were obtained from four groups of Beninese subjects: healthy adults, patients presenting uncomplicated malaria (UM), cerebral malaria (CM), or pregnancy-associated malaria (PAM). The reactivity of plasma samples from each clinical group was measured by flow cytometry against parasites isolated from individuals from each clinical group. RESULTS: Antibody responses against VSAUM were predominant in CM, UM and HA plasmas. When analysed according to age in all plasma groups, anti-VSACM and -VSAUM antibody levels were similar until six years of age. In older groups (6-18 and >19 years of age), VSAUM antibody levels were higher than VSACM antibody levels (P = .01, P = .0008, respectively). Mean MFI values, measured in all plasmas groups except the PAM plasmas, remained low for anti-VSAPAM antibodies and did not vary with age. One month after infection the level of anti-VSA antibodies able to recognize heterologous VSACM variants was increased in CM patients. In UM patients, antibody levels directed against heterologous VSAUM were similar, both during the infection and one month later. CONCLUSIONS: In conclusion, this study suggests the existence of serologically distinct VSACM and VSAUM. CM isolates were shown to share common epitopes. Specific antibody response to VSAUM was predominant, suggesting a relative low diversity of VSAUM in the study area.
Notes: Kheliouen, Nabila xD;Viwami, Firmine xD;Lalya, Francis xD;Tuikue-Ndam, Nicaise xD;Moukoko, Else C Eboumbou xD;Rogier, Christophe xD;Deloron, Philippe xD;Aubouy, Agnes xD;Research Support, Non-U.S. Gov't xD;England xD;Malaria journal xD;Malar J. 2010 Jul 27;9:220.
Véronique Parquet, Sébastien Briolant, Marylin Torrentino-Madamet, Maud Henry, Lionel Almeras, Rémy Amalvict, Eric Baret, Thierry Fusaï, Christophe Rogier, Bruno Pradines (2009)  Atorvastatin is a promising partner for antimalarial drugs in treatment of Plasmodium falciparum malaria.   Antimicrob Agents Chemother 53: 6. 2248-2252 Jun  
Abstract: Atorvastatin (AVA) is a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. AVA exposure resulted in the reduced in vitro growth of 22 Plasmodium falciparum strains, with the 50% inhibitory concentrations (IC(50)s) ranging from 2.5 microM to 10.8 microM. A significant positive correlation was found between the strains' responses to AVA and mefloquine (r = 0.553; P = 0.008). We found no correlation between the responses to AVA and to chloroquine, quinine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone, or doxycycline. These data could suggest that the mechanism of AVA uptake and/or the mode of action of AVA is different from those for other antimalarial drugs. The IC(50)s for AVA were unrelated to the occurrence of mutations in the transport protein genes involved in quinoline antimalarial drug resistance, such as the P. falciparum crt, mdr1, mrp, and nhe-1 genes. Therefore, AVA can be ruled out as a substrate for the transport proteins (CRT, Pgh1, and MRP) and is not subject to the pH modification induced by the P. falciparum NHE-1 protein. The absence of in vitro cross-resistance between AVA and chloroquine, quinine, mefloquine, monodesethylamodiaquine, lumefantrine, dihydroartemisinin, atovaquone, and doxycycline argues that these antimalarial drugs could potentially be paired with AVA as a treatment for malaria. In conclusion, the present observations suggest that AVA is a good candidate for further studies on the use of statins in association with drugs known to have activities against the malaria parasite.
Boris Pastorino, Elodie Boucomont-Chapeaublanc, Christophe N Peyrefitte, Maya Belghazi, Thierry Fusaï, Christophe Rogier, Hugues J Tolou, Lionel Almeras (2009)  Identification of cellular proteome modifications in response to West Nile virus infection.   Mol Cell Proteomics 8: 7. 1623-1637 Jul  
Abstract: Flaviviruses are positive-stranded RNA viruses that are a public health problem because of their widespread distribution and their ability to cause a variety of diseases in humans. West Nile virus is a mosquito-borne member of this genus and is the etiologic agent of West Nile encephalitis. Clinical manifestations of West Nile virus infection are diverse, and their pathogenic mechanisms depend on complex virus-cell interactions. In the present work, we used proteomics technology to analyze early Vero cell response to West Nile infection. The differential proteomes were resolved 24 h postinfection using two-dimensional DIGE followed by mass spectrometry identification. Quantitative analysis (at least 2-fold quantitative alteration, p < 0.05) revealed 127 differentially expressed proteins with 68 up-regulated proteins and 59 down-regulated proteins of which 93 were successfully identified. The implication for mammalian cellular responses to this neurotropic flavivirus infection was analyzed and made possible more comprehensive characterization of the virus-host interactions involved in pathogenesis. The present study thus provides large scale protein-related information that should be useful for understanding how the host metabolism is modified by West Nile infection and for identifying new potential targets for antiviral therapy.
Lucie Guetzoyan, Xiao-Min Yu, Florence Ramiandrasoa, Stéphanie Pethe, Christophe Rogier, Bruno Pradines, Thierry Cresteil, Martine Perrée-Fauvet, Jean-Pierre Mahy (2009)  Antimalarial acridines: synthesis, in vitro activity against P. falciparum and interaction with hematin.   Bioorg Med Chem 17: 23. 8032-8039 Dec  
Abstract: A series of acridine derivatives were synthesised and their in vitro antimalarial activity was evaluated against one chloroquine-susceptible strain (3D7) and three chloroquine-resistant strains (W2, Bre1 and FCR3) of Plasmodium falciparum. Structure-activity relationship showed that two positives charges as well as 6-chloro and 2-methoxy substituents on the acridine ring were required to exert a good antimalarial activity. The best compounds possessing these features inhibited the growth of the chloroquine-susceptible strain with an IC(50)0.07 microM, close to that of chloroquine itself, and that of the three chloroquine-resistant strains better than chloroquine with IC(50)0.3 microM. These acridine derivatives inhibited the formation of beta-hematin, suggesting that, like CQ, they act on the haem crystallization process. Finally, in vitro cytotoxicity was also evaluated upon human KB cells, which showed that one of them 9-(6-ammonioethylamino)-6-chloro-2-methoxyacridinium dichloride 1 displayed a promising antimalarial activity in vitro with a quite good selectivity index versus mammalian cell on the CQ-susceptible strain and promising selectivity on other strains.
Nitchakarn Noranate, Franck Prugnolle, Hélène Jouin, Adama Tall, Laurence Marrama, Cheikh Sokhna, Marie-Thérèse Ekala, Micheline Guillotte, Emmanuel Bischoff, Christiane Bouchier, Jintana Patarapotikul, Jun Ohashi, Jean-François Trape, Christophe Rogier, Odile Mercereau-Puijalon (2009)  Population diversity and antibody selective pressure to Plasmodium falciparum MSP1 block2 locus in an African malaria-endemic setting.   BMC Microbiol 9: 10  
Abstract: BACKGROUND: Genetic evidence for diversifying selection identified the Merozoite Surface Protein1 block2 (PfMSP1 block2) as a putative target of protective immunity against Plasmodium falciparum. The locus displays three family types and one recombinant type, each with multiple allelic forms differing by single nucleotide polymorphism as well as sequence, copy number and arrangement variation of three amino acid repeats. The family-specific antibody responses observed in endemic settings support immune selection operating at the family level. However, the factors contributing to the large intra-family allelic diversity remain unclear. To address this question, population allelic polymorphism and sequence variant-specific antibody responses were studied in a single Senegalese rural community where malaria transmission is intense and perennial. RESULTS: Family distribution showed no significant temporal fluctuation over the 10 y period surveyed. Sequencing of 358 PCR fragments identified 126 distinct alleles, including numerous novel alleles in each family and multiple novel alleles of recombinant types. The parasite population consisted in a large number of low frequency alleles, alongside one high-frequency and three intermediate frequency alleles. Population diversity tests supported positive selection at the family level, but showed no significant departure from neutrality when considering intra-family allelic sequence diversity and all families combined. Seroprevalence, analysed using biotinylated peptides displaying numerous sequence variants, was moderate and increased with age. Reactivity profiles were individual-specific, mapped to the family-specific flanking regions and to repeat sequences shared by numerous allelic forms within a family type. Seroreactivity to K1-, Mad20- and R033 families correlated with the relative family genotype distribution within the village. Antibody specificity remained unchanged with cumulated exposure to an increasingly large number of alleles. CONCLUSION: The Pfmsp1 block2 locus presents a very large population sequence diversity. The lack of stable acquisition of novel antibody specificities despite exposure to novel allelic forms is reminiscent of clonal imprinting. The locus appears under antibody-mediated diversifying selection in a variable environment that maintains a balance between the various family types without selecting for sequence variant allelic forms. There is no evidence of positive selection for intra-family sequence diversity, consistent with the observed characteristics of the antibody response.
Lionel Almeras, Albin Fontaine, Maya Belghazi, Stéphanie Bourdon, Elodie Boucomont-Chapeaublanc, Eve Orlandi-Pradines, Meli Baragatti, Nicole Corre-Catelin, Paul Reiter, Bruno Pradines, Thierry Fusai, Christophe Rogier (2009)  Salivary Gland Protein Repertoire from Aedes aegypti Mosquitoes.   Vector Borne Zoonotic Dis Oct  
Abstract: Abstract Diseases caused by arthropod-borne viruses are a significant threat to the health of human and animal populations throughout the world. Better knowledge of the molecules synthesized in the salivary gland and saliva of hematophagous arthropods could be of use for improving the control of pathogen transmission. Recently, a sialome analysis of three Aedes aegypti mosquito colonies (PAEA, Rockefeller, and Formosus) carried out in our laboratory allowed us to identify 44 saliva proteins. Of these secreted proteins, none was exclusively expressed in one colony, suggesting that expression of salivary proteins is highly conserved across populations. In another study, we reported that some of these salivary proteins could be used as the genus-specific markers for travelers' exposure to mosquito vectors. Here, comparison of salivary gland protein profiles between these same three Ae. aegypti colonies was performed using the one-dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) difference gel electrophoresis method. As observed at the saliva level, no significant differences were detected between these three colonies. The salivary gland protein repertoire from the Ae. aegypti mosquito was analyzed using a proteomic approach. One hundred and twenty proteins were identified in these salivary glands representing the largest description of the Ae. aegypti salivary gland protein catalog. We succeeded in identifying 15 secreted proteins, some of which have already been reported as being involved in blood feeding. A comparison of the proteins identified between the salivary glands and the sialome is discussed.
Nicolas Steenkeste, Sandra Incardona, Sophy Chy, Linda Duval, Marie-Thérèse Ekala, Pharath Lim, Sean Hewitt, Tho Sochantha, Doung Socheat, Christophe Rogier, Odile Mercereau-Puijalon, Thierry Fandeur, Frédéric Ariey (2009)  Towards high-throughput molecular detection of Plasmodium: new approaches and molecular markers.   Malar J 8: 04  
Abstract: BACKGROUND: Several strategies are currently deployed in many countries in the tropics to strengthen malaria control toward malaria elimination. To measure the impact of any intervention, there is a need to detect malaria properly. Mostly, decisions still rely on microscopy diagnosis. But sensitive diagnosis tools enabling to deal with a large number of samples are needed. The molecular detection approach offers a much higher sensitivity, and the flexibility to be automated and upgraded. METHODS: Two new molecular methods were developed: dot18S, a Plasmodium-specific nested PCR based on the 18S rRNA gene followed by dot-blot detection of species by using species-specific probes and CYTB, a Plasmodium-specific nested PCR based on cytochrome b gene followed by species detection using SNP analysis. The results were compared to those obtained with microscopic examination and the "standard" 18S rRNA gene based nested PCR using species specific primers. 337 samples were diagnosed. RESULTS: Compared to the microscopy the three molecular methods were more sensitive, greatly increasing the estimated prevalence of Plasmodium infection, including P. malariae and P. ovale. A high rate of mixed infections was uncovered with about one third of the villagers infected with more than one malaria parasite species. Dot18S and CYTB sensitivity outranged the "standard" nested PCR method, CYTB being the most sensitive. As a consequence, compared to the "standard" nested PCR method for the detection of Plasmodium spp., the sensitivity of dot18S and CYTB was respectively 95.3% and 97.3%. Consistent detection of Plasmodium spp. by the three molecular methods was obtained for 83% of tested isolates. Contradictory results were mostly related to detection of Plasmodium malariae and Plasmodium ovale in mixed infections, due to an "all-or-none" detection effect at low-level parasitaemia. CONCLUSION: A large reservoir of asymptomatic infections was uncovered using the molecular methods. Dot18S and CYTB, the new methods reported herein are highly sensitive, allow parasite DNA extraction as well as genus- and species-specific diagnosis of several hundreds of samples, and are amenable to high-throughput scaling up for larger sample sizes. Such methods provide novel information on malaria prevalence and epidemiology and are suited for active malaria detection. The usefulness of such sensitive malaria diagnosis tools, especially in low endemic areas where eradication plans are now on-going, is discussed in this paper.
C Rogier, M - C Henry, J - F Trape (2009)  Epidemiologic evaluation of malaria in endemic areas   Med Trop (Mars) 69: 2. 123-142 Apr  
Abstract: For decades malarial control has been implemented to control the impact of the disease on the health of populations living in endemic zones. The use of artemisinine combination therapy, intermittent preventive treatment for children and pregnant women, vector-control methods such as long-lasting insecticide-impregnated mosquito nets and indoor remanent insecticide spraying has proven to be effective. These practices have lead to such an extensive reduction of the malaria burden in some endemic areas that the objective of eradication that was unimaginable a few years ago is now back to the forefront. Regardless of the method chosen, careful evaluation and surveillance of its effectiveness in man is necessary. Achieving epidemiologic impact is the main goal of malaria control methods. The main measures for evaluation involve parasitological and clinical aspects of human malaria. The purpose of this article is to review methods used for epidemiologic evaluation of malaria burden.
C Rogier, M C Henry, M Rowland, P Carnevale, F Chandre, V Corbel, C Curtis, J M Hougard (2009)  Guidelines for phase III evaluation of vector control methods against malaria   Med Trop (Mars) 69: 2. 173-184 Apr  
Abstract: Most new vector control methods against malaria involve the use of pesticides. Prior to release of these products for general use, their efficacy, persistence, and cross-resistance must be tested on mosquito colonies raised in the laboratory (phase I) then on wild mosquitoes in the field (small-scale), individual dwellings, or experimental huts (phase II). The goal of phase III studies is to evaluate the efficacy and effectiveness of the vector-control product or method against malaria in a population at regular risk for transmission. The main objective of phase III tests is to measure the epidemiologic impact, e.g. on the incidence or prevalence of malaria in humans. This article presents guidelines for carrying out phase III tests of vector-control methods against malaria (e.g. home insecticide spraying or insecticide-impregnated bednet use). It was written by participants in a workgroup formed to define recommendations for the WHOPES (WHO Pesticide Evaluation Scheme).
Vanessa Machault, Libasse Gadiaga, Cécile Vignolles, Fanny Jarjaval, Samia Bouzid, Cheikh Sokhna, Jean-Pierre Lacaux, Jean-François Trape, Christophe Rogier, Frédéric Pagès (2009)  Highly focused anopheline breeding sites and malaria transmission in Dakar.   Malar J 8: 06  
Abstract: BACKGROUND: Urbanization has a great impact on the composition of the vector system and malaria transmission dynamics. In Dakar, some malaria cases are autochthonous but parasite rates and incidences of clinical malaria attacks have been recorded at low levels. Ecological heterogeneity of malaria transmission was investigated in Dakar, in order to characterize the Anopheles breeding sites in the city and to study the dynamics of larval density and adult aggressiveness in ten characteristically different urban areas. METHODS: Ten study areas were sampled in Dakar and Pikine. Mosquitoes were collected by human landing collection during four nights in each area (120 person-nights). The Plasmodium falciparum circumsporozoite (CSP) index was measured by ELISA and the entomological inoculation rates (EIR) were calculated. Open water collections in the study areas were monitored weekly for physico-chemical characterization and the presence of anopheline larvae. Adult mosquitoes and hatched larvae were identified morphologically and by molecular methods. RESULTS: In September-October 2007, 19,451 adult mosquitoes were caught among which, 1,101 were Anopheles gambiae s.l. The Human Biting Rate ranged from 0.1 bites per person per night in Yoff Village to 43.7 in Almadies. Seven out of 1,101 An. gambiae s.l. were found to be positive for P. falciparum (CSP index = 0.64%). EIR ranged from 0 infected bites per person per year in Yoff Village to 16.8 in Almadies. The An. gambiae complex population was composed of Anopheles arabiensis (94.8%) and Anopheles melas (5.2%). None of the An. melas were infected with P. falciparum. Of the 54 water collection sites monitored, 33 (61.1%) served as anopheline breeding sites on at least one observation. No An. melas was identified among the larval samples. Some physico-chemical characteristics of water bodies were associated with the presence/absence of anopheline larvae and with larval density. A very close parallel between larval and adult densities was found in six of the ten study areas. CONCLUSION: The results provide evidence of malaria transmission in downtown Dakar and its surrounding suburbs. Spatial heterogeneity of human biting rates was very marked and malaria transmission was highly focal. In Dakar, mean figures for transmission would not provide a comprehensive picture of the entomological situation; risk evaluation should therefore be undertaken on a small scale.
V Machault, F Pages, C Rogier (2009)  Contribution of remote sensing to malaria control   Med Trop (Mars) 69: 2. 151-159 Apr  
Abstract: Despite national and international efforts, malaria remains a major public health problem and the fight to control the disease is confronted by numerous hurdles. Study of space and time dynamics of malaria is necessary as a basis for making appropriate decision and prioritizing intervention including in areas where field data are rare and sanitary information systems are inadequate. Evaluation of malarial risk should also help anticipate the risk of epidemics as a basis for early warning systems. Since 1960-70 civilian satellites launched for earth observation have been providing information for the measuring or evaluating geo-climatic and anthropogenic factors related to malaria transmission and burden. Remotely sensed data gathered for several civilian or military studies have allowed setup of entomological, parasitological, and epidemiological risk models and maps for rural and urban areas. Mapping of human populations at risk has also benefited from remotely sensing. The results of the published studies show that remote sensing is a suitable tool for optimizing planning, efficacy and efficiency of malaria control.
T Coffinet, C Rogier, F Pages (2009)  Evaluation of the anopheline mosquito aggressivity and of malaria transmission risk: methods used in French Army   Med Trop (Mars) 69: 2. 109-122 Apr  
Abstract: Identification of the anopheline mosquito species involved in local transmission as well as knowledge of its biology and behavior is necessary for malaria vector control. To allow such study, two methods are usually used to capture adult mosquitoes, i.e., night catches on human volunteers and light-trap collections with human bait. The purpose of this article is to describe these two methods including their advantages and disadvantages as well as a method of surveying breeding sites as implemented by French Army personnel.
Nicolas Steenkeste, Marie-Agnès Dillies, Nimol Khim, Odile Sismeiro, Sophy Chy, Pharath Lim, Andreas Crameri, Christiane Bouchier, Odile Mercereau-Puijalon, Hans-Peter Beck, Mallika Imwong, Arjen M Dondorp, Duong Socheat, Christophe Rogier, Jean-Yves Coppée, Frédéric Ariey (2009)  FlexiChip package: an universal microarray with a dedicated analysis software for high-thoughput SNPs detection linked to anti-malarial drug resistance.   Malar J 8: 10  
Abstract: BACKGROUND: A number of molecular tools have been developed to monitor the emergence and spread of anti-malarial drug resistance to Plasmodium falciparum. One of the major obstacles to the wider implementation of these tools is the absence of practical methods enabling high throughput analysis. Here a new Zip-code array is described, called FlexiChip, linked to a dedicated software program, which largely overcomes this problem. METHODS: Previously published microarray probes detecting single-nucleotide polymorphisms (SNP) associated with parasite resistance to anti-malarial drugs (ResMalChip) were adapted for a universal microarray FlexiChip format. To evaluate the overall sensitivity of the FlexiChip package (microarray + software), the results of FlexiChip were compared to ResMalChip microarray, using the same extension probes and with the same PCR products. In both cases, sequence results were used as gold standard to calculate sensitivity and specificity. FlexiChip results obtained with a set of field isolates were then compared to those assessed in an independent reference laboratory. RESULTS: The FlexiChip package gave results identical to the ResMalChip results in 92.7% of samples (kappa coefficient 0.8491, with a standard error 0.021) and had a sensitivity of 95.88% and a specificity of 97.68% compared to the sequencing as the reference method. Moreover the method performed well compared to the results obtained in the reference laboratories, with 99.7% of identical results (kappa coefficient 0.9923, S.E. 0.0523). CONCLUSION: Microarrays could be employed to monitor P. falciparum drug resistance markers with greater cost effectiveness and the possibility for high throughput analysis. The FlexiChip package is a promising tool for use in poor resource settings of malaria endemic countries.
C Rogier, M C Henry, C Luxemburger (2009)  Methods for the phase IV evaluation of malaria vector control interventions: a case-control study of the effectiveness of long lasting impregnated bed nets after their deployment in Benin   Med Trop (Mars) 69: 2. 195-202 Apr  
Abstract: Vector-control measures are a component of integrated malaria control strategies. After evaluation in phase III pilot studies, these measures are currently being deployed in many endemic malaria zones. Their effectiveness must be evaluated under actual conditions of use but it is not ethically acceptable to use unexposed individuals for control groups. In a attempt to overcome this problem, a case-control study was undertaken to evaluate the effectiveness of long-lasting insecticide treated mosquito nets (LLITN) against clinical malaria attacks due to Plasmodium falciparum in an endemic area of southern Benin. During a 4-month period (July to October 2008), 35 clinically documented cases of uncomplicated malaria (fever + parasite density > 3000/microL) were diagnosed in children less than 5 years old from 6 villages in the Tori Bossito medical district. The parents of these children were interviewed at the same time as the parents of 181 children randomly selected from the same 6 villages. A total of 115 of the randomly selected children who had not been feverish during study period were used as controls. The proportion of children having consistently slept under LLITN throughout the study period was 46% in the case group and 78% in the control group (OR=0.32, 95%CI: 0.15-0.71). These data show that the LLITN provided a significant level of protection, i.e., 68% (IC95%: 29%-85%). This case-control study shows that vector control measures can be effectively evaluated after deployment in population. The limitations of this methodology are discussed.
L Almeras, E Orlandi-Pradines, A Fontaine, C Villard, E Boucomont, L Denis de Senneville, M Baragatti, A Pascual, B Pradines, N Corre-Catelin, F Pages, P Reiter, C Rogier, T Fusai (2009)  Sialome individuality between Aedes aegypti colonies.   Vector Borne Zoonotic Dis 9: 5. 531-541 Oct  
Abstract: Aedes aegypti is responsible for the transmission of arboviruses. The Yellow Fever, Dengue and Chikungunya viruses are transmitted to the vertebrate host by injection of infected saliva during the blood meal of its vectors. Saliva contains different components with various biochemical activities; anti-hemostatic, angiogenic, inflammatory, and immunomodulatory. This work compares the sialomes of three Ae. aegypti colonies (Rockefeller, PAEA, and Formosus), where the repertoire of salivary proteins from these colonies was analyzed by a proteomic approach. This study indicated that major proteins were detectable in the three colonies. However, differences in the abundance of some saliva proteins have been observed between the three Ae. aegypti colonies.
Meili Baragatti, Florence Fournet, Marie-Claire Henry, Serge Assi, Herman Ouedraogo, Christophe Rogier, Gérard Salem (2009)  Social and environmental malaria risk factors in urban areas of Ouagadougou, Burkina Faso.   Malar J 8: 01  
Abstract: BACKGROUND: Despite low endemicity, malaria remains a major health problem in urban areas where a high proportion of fevers are presumptively treated using anti-malarial drugs. Low acquired malaria immunity, behaviour of city-dwellers, access to health care and preventive interventions, and heterogenic suitability of urban ecosystems for malaria transmission contribute to the complexity of the malaria epidemiology in urban areas. METHODS: The study was designed to identify the determinants of malaria transmission estimated by the prevalence of anti-circumsporozoite (CSP) antibodies, the prevalence and density of Plasmodium falciparum infection, and the prevalence of malarial disease in areas of Ouagadougou, Burkina-Faso. Thick blood smears, dried blood spots and clinical status have been collected from 3,354 randomly chosen children aged 6 months to 12 years using two cross-sectional surveys (during the dry and rainy seasons) in eight areas from four ecological strata defined according to building density and land tenure (regular versus irregular). Demographic characteristics, socio-economic information, and sanitary and environmental data concerning the children or their households were simultaneously collected. Dependent variables were analysed using mixed multivariable models with random effects, taking into account the clustering of participants within compounds and areas. RESULTS: Overall prevalences of CSP-antibodies and P. falciparum infections were 7.7% and 16.6% during the dry season, and 12.4% and 26.1% during the rainy season, respectively, with significant differences according to ecological strata. Malaria risk was significantly higher among children who i) lived in households with lower economic or education levels, iii) near the hydrographic network, iv) in sparsely built-up areas, v) in irregularly built areas, vi) who did not use a bed net, vii) were sampled during the rainy season or ii) had traveled outside of Ouagadougou. CONCLUSION: Malaria control should be focused in areas which are irregularly or sparsely built-up or near the hydrographic network. Furthermore, urban children would benefit from preventive interventions (e.g. anti-vectorial devices or chemoprophylaxis) aimed at reducing malaria risk during and after travel in rural areas.
Sébastien Briolant, Meili Baragatti, Philippe Parola, Fabrice Simon, Adama Tall, Cheikh Sokhna, Philippe Hovette, Modeste Mabika Mamfoumbi, Jean-Louis Koeck, Jean Delmont, André Spiegel, Jacky Castello, Jean Pierre Gardair, Jean Francois Trape, Maryvonne Kombila, Philippe Minodier, Thierry Fusai, Christophe Rogier, Bruno Pradines (2009)  Multinormal in vitro distribution model suitable for the distribution of Plasmodium falciparum chemosusceptibility to doxycycline.   Antimicrob Agents Chemother 53: 2. 688-695 Feb  
Abstract: The distribution and range of 50% inhibitory concentrations (IC(50)s) of doxycycline were determined for 747 isolates obtained between 1997 and 2006 from patients living in Senegal, Republic of the Congo, and Gabon and patients hospitalized in France for imported malaria. The statistical analysis was designed to answer the specific question of whether Plasmodium falciparum has different phenotypes of susceptibility to doxycycline. A triple normal distribution was fitted to the data using a Bayesian mixture modeling approach. The IC(50) geometric mean ranged from 6.2 microM to 11.1 microM according to the geographical origin, with a mean of 9.3 microM for all 747 parasites. The values for all 747 isolates were classified into three components: component A, with an IC(50) mean of 4.9 microM (+/-2.1 microM [standard deviation]); component B, with an IC(50) mean of 7.7 microM (+/-1.2 microM); and component C, with an IC(50) mean of 17.9 microM (+/-1.4 microM). According to the origin of the P. falciparum isolates, the triple normal distribution was found in each subgroup. However, the proportion of isolates predicted to belong to component B was most important in isolates from Gabon and Congo and in isolates imported from Africa (from 46 to 56%). In Senegal, 55% of the P. falciparum isolates were predicted to be classified as component C. The cutoff of reduced susceptibility to doxycycline in vitro was estimated to be 35 microM.
Pembe Issamou Mayengue, Adrian J F Luty, Christophe Rogier, Meili Baragatti, Peter G Kremsner, Francine Ntoumi (2009)  The multiplicity of Plasmodium falciparum infections is associated with acquired immunity to asexual blood stage antigens.   Microbes Infect 11: 1. 108-114 Jan  
Abstract: We evaluated the relationship between immune response markers and the multiplicity of Plasmodium falciparum infections in order to assess the validity of the latter as an indicator of the acquisition of anti-malarial immunity. Parasite populations present during malaria episodes of 64 Gabonese children who presented with at least 4 such attacks during active follow-up over a 7-year period were characterized using MSP-1 and MSP-2 PCR-based methods. Plasma samples taken at healthy and parasite-free phase were used to measure P. falciparum antigen-specific antibody and cytokine activity. We found evidence of intra- and inter-individual variation in the number of parasite genotypes present in different malaria episodes, although in 72% of isolates no more than 2 parasite genotypes were detectable. Samples with the highest multiplicity were from children with significantly lower (p < 0.03) antibody responses to specific asexual stage antigens. Additionally, the whole blood interferon-gamma production capacity was significantly higher (p < 0.02) in those with lower infection multiplicity. Malaria episodes with multiple clones indeed reflect a low level of acquired immunity and a consequently poor capacity to control the infection. These findings suggest that the multiplicity of falciparum infection may be a potentially useful parameter in the evaluation of malaria control interventions.
Christelle Pomares-Estran, Pascal Delaunay, Annie Mottard, Eric Cua, Pierre-Marie Roger, Bruno Pradines, Daniel Parzy, Hervé Bogreau, Christophe Rogier, Charles Jeannin, Saïd Karch, Didier Fontenille, Dominique Dejour-Salamanca, Fabrice Legros, Pierre Marty (2009)  Atypical aetiology of a conjugal fever: autochthonous airport malaria between Paris and French Riviera: a case report.   Malar J 8: 08  
Abstract: Endemic malaria has been eradicated from France, but some falciparum malaria cases have been described in patients who have never travelled outside the country. Ms. V. 21 year-old and Mr. M. 23 year-old living together in Paris were on holiday in Saint Raphaël (French Riviera). They presented with fever, vertigo and nausea. A blood smear made to control thrombocytopaenia revealed intra-erythrocytic forms of Plasmodium falciparum. The parasitaemia level was 0.15% for Ms. V and 3.2% for Mr. M. This couple had no history of blood transfusion or intravenous drug use. They had never travelled outside metropolitan France, but had recently travelled around France: to Saint Mard (close to Paris Charles de Gaulle (CdG) airport), to Barneville plage (in Normandy) and finally to Saint Raphaël. The most probable hypothesis is an infection transmitted in Saint Mard by an imported anopheline mosquito at CdG airport. The DNA analysis of parasites from Ms. V.'s and Mr. M.'s blood revealed identical genotypes. Because it is unlikely that two different anopheline mosquitoes would be infected by exactly the same clones, the two infections must have been caused by the infective bites of the same infected mosquito.
Manuela Oliver, Marc Grandadam, Catherine Marimoutou, Christophe Rogier, Elisabeth Botelho-Nevers, Hugues Tolou, Jean-Luc Moalic, Philippe Kraemer, Marc Morillon, Jean-Jacques Morand, Pierre Jeandel, Philippe Parola, Fabrice Simon (2009)  Persisting mixed cryoglobulinemia in Chikungunya infection.   PLoS Negl Trop Dis 3: 2. 02  
Abstract: BACKGROUND: Chikungunya virus (CHIKV), an arbovirus, is responsible for a two-stage disabling disease, consisting of an acute febrile polyarthritis for the first 10 days, frequently followed by chronic rheumatisms, sometimes lasting for years. Up to now, the pathophysiology of the chronic stage has been elusive. Considering the existence of occasional peripheral vascular disorders and some unexpected seronegativity during the chronic stage of the disease, we hypothesized the role of cryoglobulins. METHODS: From April 2005 to May 2007, all travelers with suspected CHIKV infection were prospectively recorded in our hospital department. Demographic, clinical and laboratory findings (anti-CHIKV IgM and IgG, cryoglobulin) were registered at the first consultation or hospitalization and during follow-up. RESULTS: Among the 66 travelers with clinical suspicion of CHIKV infection, 51 presented anti-CHIKV IgM. There were 45 positive with the serological assay tested at room temperature, and six more, which first tested negative when sera were kept at 4 degrees C until analysis, became positive after a 2-hour incubation of the sera at 37 degrees C. Forty-eight of the 51 CHIKV-seropositive patients were screened for cryoglobulinemia; 94% were positive at least once during their follow-up. Over 90% of the CHIKV-infected patients had concomitant arthralgias and cryoglobulinemia. Cryoglobulin prevalence and level drop with time as patients recover, spontaneously or after short-term corticotherapy. In some patients cryoglobulins remained positive after 1 year. CONCLUSION: Prevalence of mixed cryoglobulinemia was high in CHIKV-infected travelers with long-lasting symptoms. No significant association between cryoglobulinemia and clinical manifestations could be evidenced. The exact prognostic value of cryoglobulin levels has yet to be determined. Responsibility of cryoglobulinemia was suspected in unexpected false negativity of serological assays at room temperature, leading us to recommend performing serology on pre-warmed sera.
Aissatou Toure-Balde, Blanca-Liliana Perlaza, Jean-Pierre Sauzet, Mouhamadou Ndiaye, Georgette Aribot, Adama Tall, Cheikh Sokhna, Christophe Rogier, Giampietro Corradin, Christian Roussilhon, Pierre Druilhe (2009)  Evidence for multiple B- and T-cell epitopes in Plasmodium falciparum liver-stage antigen 3.   Infect Immun 77: 3. 1189-1196 Mar  
Abstract: Liver-stage antigen 3 (LSA-3) is a new vaccine candidate that can induce protection against Plasmodium falciparum sporozoite challenge. Using a series of long synthetic peptides (LSP) encompassing most of the 210-kDa LSA-3 protein, a study of the antigenicity of this protein was carried out in 203 inhabitants from the villages of Dielmo (n = 143) and Ndiop (n = 60) in Senegal (the level of malaria transmission differs in these two villages). Lymphocyte responses to each individual LSA-3 peptide were recorded, some at high prevalences (up to 43%). Antibodies were also detected to each of the 20 peptides, many at high prevalence (up to 84% of responders), and were directed to both nonrepeat and repeat regions. Immune responses to LSA-3 were detectable even in individuals of less than 5 years of age and increased with age and hence exposure to malaria, although they were not directly related to the level of malaria transmission. Thus, several valuable T- and B-cell epitopes were characterized all along the LSA-3 protein, supporting the antigenicity of this P. falciparum vaccine candidate. Finally, antibodies specific for peptide LSP10 located in a nonrepeat region of LSA-3 were found significantly associated with a lower risk of malaria attack over 1 year of daily clinical follow-up in children between the ages of 7 and 15 years, but not in older individuals.
Maud Henry, Sébastien Briolant, Agnès Zettor, Stéphane Pelleau, Meili Baragatti, Eric Baret, Joel Mosnier, Rémy Amalvict, Thierry Fusai, Christophe Rogier, Bruno Pradines (2009)  Plasmodium falciparum Na+/H+ exchanger 1 transporter is involved in reduced susceptibility to quinine.   Antimicrob Agents Chemother 53: 5. 1926-1930 May  
Abstract: Polymorphisms in the Plasmodium falciparum crt (Pfcrt), Pfmdr1, and Pfmrp genes were not significantly associated with quinine (QN) 50% inhibitory concentrations (IC(50)s) in 23 strains of Plasmodium falciparum. An increased number of DNNND repeats in Pfnhe-1 microsatellite ms4760 was associated with an increased IC(50) of QN (P = 0.0007). Strains with only one DNNND repeat were more susceptible to QN (mean IC(50) of 154 nM). Strains with two DNNND repeats had intermediate susceptibility to QN (mean IC(50) of 548 nM). Strains with three DNNND repeats had reduced susceptibility to QN (mean IC(50) of 764 nM). Increased numbers of NHNDNHNNDDD repeats were associated with a decreased IC(50) of QN (P = 0.0020). Strains with profile 7 for Pfnhe-1 ms4760 (ms4760-7) were significantly associated with reduced QN susceptibility (mean IC(50) of 764 nM). The determination of DNNND and NHNDNHNNDDD repeats in Pfnhe-1 ms4760 could be a good marker of QN resistance and provide an attractive surveillance method to monitor temporal trends in P. falciparum susceptibility to QN. The validity of the markers should be further supported by analyzing more isolates.
Eve Orlandi-Pradines, Christophe Rogier, Bernard Koffi, Fanny Jarjaval, Melissa Bell, Vanessa Machault, Christophe Pons, Romain Girod, Jean-Paul Boutin, Frédéric Pagès (2009)  Major variations in malaria exposure of travellers in rural areas: an entomological cohort study in western Côte d'Ivoire.   Malar J 8: 07  
Abstract: BACKGROUND: Malaria remains a major threat, to both travellers and military personnel deployed to endemic areas. The recommendations for travellers given by the World Health Organization is based on the incidence of malaria in an area and do not take the degree of exposure into account. The aim of this article is to evaluate the exposure of travellers by entomologic methods, which are the commonly used measures of the intensity of malaria transmission. METHODS: From February 2004 to June 2004, five groups of 30 military personnel were stationed in up to 10 sites in western Côte d'Ivoire, from one week to several months. Adult mosquitoes were collected by human landing catches at each site during the five months and the level of exposure to malaria transmission of each group was estimated. RESULTS: The level of transmission varied from one site to another one from less than one to approximately more than 100 infective bites per month. In the majority of sites, at least two anopheline species were involved in transmission. The cumulative EIR over the study period varied according to the groups from 29 infected bites per person/per mission to 324. CONCLUSION: The level of malaria transmission and malaria risk varies widely (varying by a factor of eleven) between groups of travellers travelling in the same region and at the same time. Physicians involved in travel medicine or supporting expatriated populations or refugees should consider this heterogeneity and emphasize the importance of combining appropriate measures, such as chemoprophylaxis and protective measures against mosquitoes.
Adama Tall, Cheikh Sokhna, Ronald Perraut, Didier Fontenille, Laurence Marrama, Alioune B Ly, Fatoumata D Sarr, Aïssatou Toure, Jean-François Trape, André Spiegel, Christophe Rogier, Pierre Druilhe (2009)  Assessment of the relative success of sporozoite inoculations in individuals exposed to moderate seasonal transmission.   Malar J 8: 07  
Abstract: BACKGROUND: The time necessary for malaria parasite to re-appear in the blood following treatment (re-infection time) is an indirect method for evaluating the immune defences operating against pre-erythrocytic and early erythrocytic malaria stages. Few longitudinal data are available in populations in whom malaria transmission level had also been measured. METHODS: One hundred and ten individuals from the village of Ndiop (Senegal), aged between one and 72 years, were cured of malaria by quinine (25 mg/day oral Quinimax in three equal daily doses, for seven days). Thereafter, thick blood films were examined to detect the reappearance of Plasmodium falciparum every week, for 11 weeks after treatment. Malaria transmission was simultaneously measured weekly by night collection of biting mosquitoes. RESULTS: Malaria transmission was on average 15.3 infective bites per person during the 77 days follow up. The median reappearance time for the whole study population was 46.8 days, whereas individuals would have received an average one infective bite every 5 days. At the end of the follow-up, after 77 days, 103 of the 110 individuals (93.6%; CI 95% [89.0-98.2]) had been re-infected with P. falciparum. The median reappearance time ('re-positivation') was longer in subjects with patent parasitaemia at enrolment than in parasitologically-negative individuals (58 days vs. 45.9; p = 0.03) and in adults > 30 years than in younger subjects (58.6 days vs. 42.7; p = 0.0002). In a multivariate Cox PH model controlling for the sickle cell trait, G6PD deficiency and the type of habitat, the presence of parasitaemia at enrolment and age >/= 30 years were independently predictive of a reduced risk of re-infection (PH = 0.5 [95% CI: 0.3-0.9] and 0.4; [95% CI: 0.2-0.6] respectively). CONCLUSION: Results indicate the existence of a substantial resistance to sporozoites inoculations, but which was ultimately overcome in almost every individual after 2 1/2 months of natural challenges. Such a study design and the results obtained suggest that, despite a small sample size, this approach can contribute to assess the impact of intervention methods, such as the efficacy vector-control measures or of malaria pre-erythrocytic stages vaccines.
Céline Barnadas, Lise Musset, Eric Legrand, Magali Tichit, Sébastien Briolant, Thierry Fusai, Christophe Rogier, Christiane Bouchier, Stéphane Picot, Didier Ménard (2009)  High prevalence and fixation of Plasmodium vivax dhfr/dhps mutations related to sulfadoxine/pyrimethamine resistance in French Guiana.   Am J Trop Med Hyg 81: 1. 19-22 Jul  
Abstract: Plasmodium vivax isolates from French Guiana were studied for the presence of mutations associated with sulfadoxine/pyrimethamine (SP) drug resistance. Ninety-six blood samples were collected from 2000 to 2005 from symptomatic malaria patients. SP drug resistance was predicted by determining point mutations in the dihydrofolate reductase (pvdhfr) and dihydropteroate synthase (pvdhps) genes. All samples showed mutant genotypes in both genes with a prevalence > 90% for the 58R, 117N, 382C, and 383G. A new mutation (116G) in pvdhfr was found at a frequency of 3.3%. Six different pvdhfr/dhps multilocus genotypes were observed with the predominance of the quintuple mutant-type 58R/117N/173L-382C/383G (59.3%). No significant differences were observed between the prevalence of haplotypes and the year of collection. Our results indicate that, in this area, the fixation of SP drug-resistant parasites in the P. vivax population is stable.
Benjamin Queyriaux, Bruno Pradines, Lilia Hasseine, Sébastien Coste, Patrick Rodriguez, Thierry Coffinet, Rachel Haus-Cheymol, Christophe Rogier (2009)  Airport malaria   Presse Med 38: 7-8. 1106-1109 Jul/Aug  
Abstract: Airport malaria is a particular form of autochthonous malaria: it happens when the Plasmodium infected Anopheles genus mosquito travels from an endemic area to a malaria free airport. Since 1969, 30 cases of airport malaria have been reported in France, 2 during summer 2008. The severity of airport malaria is explained by the frequency of Plasmodium falciparum infecting non immune individuals and an often important diagnosis delay. It is a compulsory notification disease in France. The International Health Regulations (IHR) require states to check that airplanes coming from malaria or arboviral endemic area are systematically disinsected. Vector control measures have to be implemented within a distance of at least 400 meters around the perimeter of airports in malaria or arboviral endemic areas. In France, this measure applies to all airports of French overseas territories, except for the island of Saint-Pierre and Miquelon.
S Badiaga, C Foucault, C Rogier, B Doudier, C Rovery, H T Dupont, P Castro, D Raoult, P Brouqui (2008)  The effect of a single dose of oral ivermectin on pruritus in the homeless   J Antimicrob Chemother 62: 2. 404-9  
Abstract: BACKGROUND: Homeless people commonly present with ectoparasite-based pruritus. We evaluated the efficacy of a single dose of ivermectin to reduce the pruritus prevalence in a homeless population. METHODS: We conducted a randomized, double-blind, placebo-controlled trial from January 2006 to April 2006 in two homeless shelters in the city of Marseille, France. Homeless people complaining of pruritus were randomized to receive either ivermectin (24 mg) or placebo. Follow-up visits were planned at day 14 and day 28 after the inclusion to assess the outcome of pruritus. RESULTS: Forty-two subjects with pruritus were randomized to the ivermectin group and 40 to the placebo group. On day 14, pruritus was reported by significantly more subjects in the placebo group than those in the ivermectin group for both the per-protocol (PP) population (91.42% versus 68.57%, P = 0.014) and the intention-to-treat (ITT) population (92.5% versus 73.80%, P = 0.038). No significant effect was observed at day 28. Ivermectin was the only independent factor associated with the absence of pruritus at day 14 in both PP population [OR: 4.60 (95% CI:1.13; 18.73), P = 0.033] and ITT population [OR: 4.38 (95% CI: 1.07; 17.77), P = 0.039]. CONCLUSIONS: A single dose of oral ivermectin has a transient beneficial effect on the reduction of the prevalence of pruritus in the homeless population. More studies are required to assess the efficacy of multiple repeated treatments with ivermectin to reduce scabies and body lice endemic among homeless people with pruritus and the impact of such treatment on this population.
Notes: 1460-2091 (Electronic) xD;Journal Article xD;Research Support, Non-U.S. Gov't
A Sakuntabhai, R Ndiaye, I Casademont, C Peerapittayamonkol, C Rogier, P Tortevoye, A Tall, R Paul, C Turbpaiboon, W Phimpraphi, J F Trape, A Spiegel, S Heath, O Mercereau-Puijalon, A Dieye, C Julier (2008)  Genetic determination and linkage mapping of Plasmodium falciparum malaria related traits in Senegal   PLoS ONE 3: 4.  
Abstract: Plasmodium falciparum malaria episodes may vary considerably in their severity and clinical manifestations. There is good evidence that host genetic factors contribute to this variability. To date, most genetic studies aiming at the identification of these genes have used a case/control study design for severe malaria, exploring specific candidate genes. Here, we performed a family-based genetic study of falciparum malaria related phenotypes in two independent longitudinal survey cohorts, as a first step towards the identification of genes and mechanisms involved in the outcome of infection. We studied two Senegalese villages, Dielmo and Ndiop that differ in ethnicity, malaria transmission and endemicity. We performed genome-scan linkage analysis of several malaria-related phenotypes both during clinical attacks and asymptomatic infection. We show evidence for a strong genetic contribution to both the number of clinical falciparum malaria attacks and the asymptomatic parasite density. The asymptomatic parasite density showed linkage to chromosome 5q31 (LOD = 2.26, empirical p = 0.0014, Dielmo), confirming previous findings in other studies. Suggestive linkage values were also obtained at three additional chromosome regions: the number of clinical malaria attacks on chromosome 5p15 (LOD = 2.57, empirical p = 0.001, Dielmo) and 13q13 (LOD = 2.37, empirical p = 0.0014 Dielmo), and the maximum parasite density during asymptomatic infection on chromosome 12q21 (LOD = 3.1, empirical p<10(-4), Ndiop). While regions of linkage show little overlap with genes known to be involved in severe malaria, the four regions appear to overlap with regions linked to asthma or atopy related traits, suggesting that common immune related pathways may be involved.
Notes: 1932-6203 (Electronic) xD;Journal Article xD;Research Support, Non-U.S. Gov't
V Machault, E Orlandi-Pradines, R Michel, F Pages, G Texier, B Pradines, T Fusai, J P Boutin, C Rogier (2008)  Remote sensing and malaria risk for military personnel in Africa   J Travel Med 15: 4. 216-20  
Abstract: BACKGROUND: Nonimmune travelers in malaria-endemic areas are exposed to transmission and may experience clinical malaria attacks during or after their travel despite using antivectorial devices or chemoprophylaxis. Environment plays an essential role in the epidemiology of this disease. Remote-sensed environmental information had not yet been tested as an indicator of malaria risk among nonimmune travelers. METHODS: A total of 1,189 personnel from 10 French military companies traveling for a short-duration mission (about 4 mo) in sub-Saharan Africa from February 2004 to February 2006 were enrolled in a prospective longitudinal cohort study. Incidence rate of clinical malaria attacks occurring during or after the mission was analyzed according to individual characteristics, compliance with antimalaria prophylactic measures, and environmental information obtained from earth observation satellites for all the locations visited during the missions. RESULTS: Age, the lack of compliance with the chemoprophylaxis, and staying in areas with an average Normalized Difference Vegetation Index higher than 0.35 were risk factors for clinical malaria. CONCLUSIONS: Remotely sensed environmental data can provide important planning information on the likely level of malaria risk among nonimmune travelers who could be briefly exposed to malaria transmission and could be used to standardize for the risk of malaria transmission when evaluating the efficacy of antimalaria prophylactic measures.
Notes: 1708-8305 (Electronic) xD;Journal Article xD;Research Support, Non-U.S. Gov't
M Henry, S Alibert, C Rogier, J Barbe, B Pradines (2008)  Inhibition of efflux of quinolines as new therapeutic strategy in malaria   Curr Top Med Chem 8: 7. 563-78  
Abstract: Plasmodium falciparum is one of the most lethal parasite responsible for human malaria. Until now, the only one solution to counter malaria is the use of antimalarial drugs. Unfortunately, the extensively use of drugs, such as quinolines (i.e. chloroquine, quinine or mefloquine), have led to the emergence of drug resistance. Chloroquine and probably other quinolines act in interfering in the detoxification of hematin in the digestive vacuole. Quinolines are accumulated in P. falciparum digestive vacuole and the accumulation varies from a susceptible strain to a resistant one. Nevertheless, the mechanisms of quinoline resistance are still investigating. Genetic polymorphisms in some strains have been linked to drug resistance. The modifications observed are mutations on genes that encode transport proteins localized in the membrane of digestive vacuole. Three transporters were involved in quinoline resistance: PfCRT (Plasmodium falciparum chloroquine resistance transporter), Pgh1 (P-glycoprotein homologue 1) and PfMRP (Plasmodium falciparum multidrug resistance protein). They could be involved in accumulation or efflux mechanisms of drugs. In order to understand their role in resistance, localization, encoding gene structure, protein structure and endogenous function of these three transporters are reported. Some molecules that have no intrinsic antimalarial effect have been shown to reverse drug resistance when they are combined to chloroquine, quinine or mefloquine. These molecules are a solution to counter resistance but also they are precious tools to elucidate the resistance mechanisms. The molecules that have already shown a capacity to reverse chloroquine, quinine or mefloquine resistances were reported. Some of them could act on one of the three transporters involved in drug resistance, by confirming their role in quinoline resistance. Here we summarize the main elements of quinoline resistance and reversion of quinoline resistance related to malaria.
Notes: 1873-4294 (Electronic) xD;Journal Article xD;Review
F S Toure, O Ouwe-Missi-Oukem-Boyer, U Bisvigou, O Moussa, C Rogier, P Pino, D Mazier, S Bisser (2008)  Apoptosis : a potential triggering mechanism of neurological manifestation in Plasmodium falciparum malaria   Parasite Immunol 30: 1. 47-51  
Abstract: Plasmodium falciparum infection can lead to a life threatening disease and the pathogenetic mechanisms of severe manifestations are not fully understood. Here, we investigated the capacity of P. falciparum-parasitized red blood cells (PRBC) from 45 children with clinical malaria to induce endothelial cell (EC) apoptosis. In all subjects, PRBC that cytoadhered to ECs could be found albeit to a variable degree. By contrast, PRBC that induce EC apoptosis were found only in nine (20%) subjects. Interestingly, children with neurological manifestations were significantly more likely to harbour apoptogenic strains. There was no quantitative relationship between the capacity of these isolates to cytoadhere and apoptosis induction. We hypothesize that P. falciparum-encoded molecules could be responsible for apoptosis induction and therefore suggest new insights in the pathogenesis of P. falciparum malaria. Further investigations are currently in progress to determine whether these results can be confirmed and to identify putative parasite apoptogenic factors.
Notes: 0141-9838 (Print) xD;Journal Article xD;Research Support, Non-U.S. Gov't
E Israelsson, H Balogun, N M Vasconcelos, J Beser, C Roussilhon, C Rogier, J F Trape, K Berzins (2008)  Antibody responses to a C-terminal fragment of the Plasmodium falciparum blood-stage antigen Pf332 in Senegalese individuals naturally primed to the parasite   Clin Exp Immunol 152: 1. 64-71  
Abstract: Previous studies have shown that antibodies from humans exposed continuously to malaria recognize the Plasmodium falciparum asexual blood-stage antigen Pf332. Here we analysed the antibody responses to a C-terminal fragment of Pf332, designated C231, in individuals from Senegal, by measuring the serum levels of immunoglobulin M (IgM), IgG class and subclass and IgE antibodies. IgG antibody reactivity with crude P. falciparum antigen was detected in all the donors, while many of the children lacked or had low levels of such antibodies against C231. The antibody levels increased significantly with age for both crude P. falciparum antigen and C231, and in the older age groups most of the donors displayed antibodies to C231. This was also true for IgM, IgE and IgG subclass reactivity against C231. Moreover, the ratio of IgG1/IgG2 was considerably lower for C231 than for crude P. falciparum antigen, and in age groups 10-14 and 15-19 years the levels of IgG2 against C231 even exceeded that of IgG1. The IgG2/IgG3 ratios suggest that C231 gives similar levels of IgG2 and IgG3, except for children aged 4-9 years, where IgG3 was higher. Raw IgM, IgG class and subclass and IgE antibody levels to C231 tended to be higher in those who did not experience a malaria attack, but following linear multivariate analysis the trends were not significant.
Notes: 1365-2249 (Electronic) xD;Journal Article xD;Research Support, Non-U.S. Gov't