Publications

@article{Kattenberg2012-hg,

title = {Antigen persistence of rapid diagnostic tests in pregnant women 

 in Nanoro, Burkina Faso, and the implications for the diagnosis 

 of malaria in pregnancy},

author = {Johanna H Kattenberg and Christian M Tahita and Inge A J Versteeg and Halidou Tinto and Maminata Traor\'{e}-Coulibaly and Henk D F H Schallig and Petra F Mens},

year  = {2012},

date = {2012-05-01},

journal = {Trop. Med. Int. Health},

volume = {17},

number = {5},

pages = {550--557},

publisher = {Wiley},

abstract = {OBJECTIVES: To evaluate persistence of several Plasmodium 

 antigens in pregnant women after treatment and compare 

 diagnostics during treatment follow-up. METHODS: Thirty-two pregnant women (N = 32) with confirmed malaria infection by a 

 histidine-rich protein 2 (HRP2)-based rapid diagnostic test 

 (RDT) and microscopy were followed for 28 days after 

 artemisinin-based combination therapy (ACT). A Plasmodium 

 lactate dehydrogenase (pLDH)-based RDT and two ELISAs based on 

 the detection of dihydrofolate reductase-thymidylate synthase 

 (DHFR-TS) and haeme detoxification protein (HDP) were compared 

 with each other and to RT-PCR at each visit. RESULTS: The mean 

 visit number (95% confidence interval) on which the HRP2-based 

 RDT was still positive after treatment was 3.4 (2.7-4.1) visits 

 with some patients still positive at day 28. This is 

 significantly later than the pLDH-based RDT [0.84 (0.55-1.1)], 

 microscopy (median 1, range 1-3), DHFR-TS-ELISA [1.7 (1.1-2.3)] 

 and RT-PCR (median 2, range 1-5) (P < 0.05), but not 

 significantly later than HDP-ELISA [2.1 (1.6-2.7)]. Lower 

 gravidity and higher parasite density at day 0 resulted in 

 significantly longer positive results with most tests (P < 

 0.05). CONCLUSIONS: HRP2 can persist up to 28 days after ACT 

 treatment; therefore, this test is not suitable for treatment 

 follow-up in pregnant women and can generate problems when using 

 this test during intermittent preventive treatment (IPTp). 

 DHFR-TS is less persistent than HRP2, making it a potentially 

 interesting target for diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rueangweerayut2012-is,

title = {Pyronaridine-artesunate versus mefloquine plus artesunate for 

 malaria},

author = {Ronnatrai Rueangweerayut and Aung Pyae Phyo and Chirapong Uthaisin and Yi Poravuth and Tran Quang Binh and Halidou Tinto and Louis K P\'{e}nali and Neena Valecha and Nong Thi Tien and Salim Abdulla and Isabelle Borghini-Fuhrer and Stephan Duparc and Chang-Sik Shin and Lawrence Fleckenstein and Pyronaridine-Artesunate Study Team},

year  = {2012},

date = {2012-04-01},

journal = {N. Engl. J. Med.},

volume = {366},

number = {14},

pages = {1298--1309},

abstract = {BACKGROUND: Pyronaridine-artesunate is an artemisinin-based 

 combination therapy under evaluation for the treatment of 

 Plasmodium falciparum and P. vivax malaria. METHODS: We conducted 

 a phase 3, open-label, multicenter, noninferiority trial that 

 included 1271 patients between 3 and 60 years of age from Asia 

 (81.3%) or Africa (18.7%) with microscopically confirmed, 

 uncomplicated P. falciparum malaria. Patients underwent 

 randomization for treatment with a fixed-dose combination of 180 

 mg of pyronaridine and 60 mg of artesunate or with 250 mg of 

 mefloquine plus 100 mg of artesunate. Doses were calculated 

 according to body weight and administered once daily for 3 days. 

 RESULTS: Pyronaridine-artesunate was noninferior to mefloquine 

 plus artesunate for the primary outcome: adequate clinical and 

 parasitologic response in the per-protocol population on day 28, 

 corrected for reinfection with the use of 

 polymerase-chain-reaction (PCR) genotyping. For this outcome, 

 efficacy in the group receiving pyronaridine-artesunate was 

 99.2% (743 of 749 patients; 95% confidence interval [CI], 98.3 

 to 99.7) and that in the group receiving mefloquine plus 

 artesunate was 97.8% (360 of 368 patients; 95% CI, 95.8 to 

 99.1), with a treatment difference of 1.4 percentage points (95% CI, 0.0 to 3.5; P=0.05). In the intention-to-treat population, 

 efficacy on day 42 in the group receiving pyronaridine-artesunate 

 was 83.1% (705 of 848 patients; 95% CI, 80.4 to 85.6) and that 

 in the group receiving mefloquine plus artesunate was 83.9% (355 

 of 423 patients; 95% CI, 80.1 to 87.3). In Cambodia, where there 

 were 211 study patients, the median parasite clearance time was 

 prolonged for both treatments: 64 hours versus 16.0 to 38.9 hours 

 in other countries (P<0.001, on the basis of Kaplan-Meier 

 estimates). Kaplan-Meier estimates of the recrudescence rate in 

 the intention-to-treat population in Cambodia until day 42 were 

 higher with pyronaridine-artesunate than with mefloquine plus artesunate (10.2% [95% CI, 5.4 to 18.6] vs. 0%; P=0.04 as 

 calculated with the log-rank test), but similar for the other 

 countries combined (4.7% [95% CI, 3.3 to 6.7] and 2.8% [95% CI, 1.5 to 5.3], respectively; P=0.24). Elevated levels of 

 aminotransferases were observed in those receiving 

 pyronaridine-artesunate. Two patients receiving mefloquine plus 

 artesunate had seizures. CONCLUSIONS: Fixed-dose 

 pyronaridine-artesunate was efficacious in the treatment of 

 uncomplicated P. falciparum malaria. In Cambodia, extended 

 parasite clearance times were suggestive of in vivo resistance to 

 artemisinin. (Funded by Shin Poong Pharmaceutical Company and the 

 Medicines for Malaria Venture; ClinicalTrials.gov number, 

 NCT00403260.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Valea2012-pp,

title = {An analysis of timing and frequency of malaria infection during 

 pregnancy in relation to the risk of low birth weight, anaemia 

 and perinatal mortality in Burkina Faso},

author = {Innocent Valea and Halidou Tinto and Maxime K Drabo and Lieven Huybregts and Hermann Sorgho and Jean-Bosco Ouedraogo and Robert T Guiguemde and Jean Pierre Geertruyden and Patrick Kolsteren and Umberto D'Alessandro and FSP/MISAME Group},

year  = {2012},

date = {2012-03-01},

journal = {Malar. J.},

volume = {11},

number = {1},

pages = {71},

publisher = {Springer Nature},

abstract = {BACKGROUND: A prospective study aiming at assessing the effect 

 of adding a third dose sulphadoxine-pyrimethamine (SP) to the 

 standard two-dose intermittent preventive treatment for pregnant 

 women was carried out in Hounde, Burkina Faso, between March 

 2006 and July 2008. Pregnant women were identified as earlier as 

 possible during pregnancy through a network of home visitors, 

 referred to the health facilities for inclusion and followed up 

 until delivery. METHODS: Study participants were enrolled at 

 antenatal care (ANC) visits and randomized to receive either two 

 or three doses of SP at the appropriate time. Women were visited 

 daily and a blood slide was collected when there was fever (body 

 temperature > 37.5°C) or history of fever. Women were encouraged 

 to attend ANC and deliver in the health centre, where the 

 new-born was examined and weighed. The timing and frequency of 

 malaria infection was analysed in relation to the risk of low 

 birth weight, maternal anaemia and perinatal mortality. RESULTS: 

 Data on birth weight and haemoglobin were available for 1,034 

 women. The incidence of malaria infections was significantly 

 lower in women having received three instead of two doses of SP. 

 Occurrence of first malaria infection during the first or second 

 trimester was associated with a higher risk of low birth weight: incidence rate ratios of 3.56 (p < 0.001) and 1.72 (p = 0.034), 

 respectively. After adjusting for possible confounding factors, 

 the risk remained significantly higher for the infection in the first trimester of pregnancy (adjusted incidence rate ratio = 2.0},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RTSS_Clinical_Trials_Partnership2011-gv,

title = {First results of phase 3 trial of RTS,S/AS01 malaria vaccine 

 in African children},

author = {S Clinical Trials Partnership RTS and Selidji Todagbe Agnandji and Bertrand Lell and Solange Solmeheim Soulanoudjingar and Jos\'{e} Francisco Fernandes and B\'{e}atrice Peggy Abossolo and Cornelia Conzelmann and Barbara Gaelle Nfono Ondo Methogo and Yannick Doucka and Arnaud Flamen and Benjamin Mordm\"{u}ller and Saadou Issifou and Peter Gottfried Kremsner and Jahit Sacarlal and Pedro Aide and Miguel Lanaspa and John J Aponte and Arlindo Nhamuave and Diana Quelhas and Quique Bassat and Sofia Mandjate and Eus\'{e}bio Macete and Pedro Alonso and Salim Abdulla and Nahya Salim and Omar Juma and Mwanajaa Shomari and Kafuruki Shubis and Francisca Machera and Ali Said Hamad and Rose Minja and Ali Mtoro and Alma Sykes and Saumu Ahmed and Alwisa Martin Urassa and Ali Mohammed Ali and Grace Mwangoka and Marcel Tanner and Halidou Tinto and Umberto D'Alessandro and Hermann Sorgho and Innocent Valea and Marc Christian Tahita and William Kabor\'{e} and Sayouba Ou\'{e}draogo and Yara Sandrine and Robert Tinga Guiguemd\'{e} and Jean Bosco Ou\'{e}draogo and Mary J Hamel and Simon Kariuki and Chris Odero and Martina Oneko and Kephas Otieno and Norbert Awino and Jackton Omoto and John Williamson and Vincent Muturi-Kioi and Kayla F Laserson and Laurence Slutsker and Walter Otieno and Lucas Otieno and Otsyula Nekoye and Stacey Gondi and Allan Otieno and Bernhards Ogutu and Ruth Wasuna and Victorine Owira and David Jones and Agnes Akoth Onyango and Patricia Njuguna and Roma Chilengi and Pauline Akoo and Christine Kerubo and Jesse Gitaka and Charity Maingi and Trudie Lang and Ally Olotu and Benjamin Tsofa and Philip Bejon and Norbert Peshu and Kevin Marsh and Seth Owusu-Agyei and Kwaku Poku Asante and Kingsley Osei-Kwakye and Owusu Boahen and Samuel Ayamba and Kingsley Kayan and Ruth Owusu-Ofori and David Dosoo and Isaac Asante and George Adjei and George Adjei and Daniel Chandramohan and Brian Greenwood and John Lusingu and Samwel Gesase and Anangisye Malabeja and Omari Abdul and Hassan Kilavo and Coline Mahende and Edwin Liheluka and Martha Lemnge and Thor Theander and Chris Drakeley and Daniel Ansong and Tsiri Agbenyega and Samuel Adjei and Harry Owusu Boateng and Theresa Rettig and John Bawa and Justice Sylverken and David Sambian and Alex Agyekum and Larko Owusu and Francis Martinson and Irving Hoffman and Tisungane Mvalo and Portia Kamthunzi and Ruthendo Nkomo and Albans Msika and Allan Jumbe and Nelecy Chome and Dalitso Nyakuipa and Joseph Chintedza and W Ripley Ballou and Myriam Bruls and Joe Cohen and Yolanda Guerra and Erik Jongert and Didier Lapierre and Amanda Leach and Marc Lievens and Opokua Ofori-Anyinam and Johan Vekemans and Terrell Carter and Didier Leboulleux and Christian Loucq and Afiya Radford and Barbara Savarese and David Schellenberg and Marla Sillman and Preeti Vansadia},

year  = {2011},

date = {2011-11-01},

journal = {N. Engl. J. Med.},

volume = {365},

number = {20},

pages = {1863--1875},

publisher = {New England Journal of Medicine (NEJM/MMS)},

abstract = {BACKGROUND: An ongoing phase 3 study of the efficacy, safety, 

 and immunogenicity of candidate malaria vaccine RTS,S/AS01 is 

 being conducted in seven African countries. METHODS: From March 

 2009 through January 2011, we enrolled 15,460 children in two 

 age categories--6 to 12 weeks of age and 5 to 17 months of 

 age--for vaccination with either RTS,S/AS01 or a non-malaria 

 comparator vaccine. The primary end point of the analysis was 

 vaccine efficacy against clinical malaria during the 12 months 

 after vaccination in the first 6000 children 5 to 17 months of 

 age at enrollment who received all three doses of vaccine 

 according to protocol. After 250 children had an episode of 

 severe malaria, we evaluated vaccine efficacy against severe 

 malaria in both age categories. RESULTS: In the 14 months after 

 the first dose of vaccine, the incidence of first episodes of 

 clinical malaria in the first 6000 children in the older age 

 category was 0.32 episodes per person-year in the RTS,S/AS01 

 group and 0.55 episodes per person-year in the control group, 

 for an efficacy of 50.4% (95% confidence interval [CI], 45.8 

 to 54.6) in the intention-to-treat population and 55.8% (97.5% 

 CI, 50.6 to 60.4) in the per-protocol population. Vaccine 

 efficacy against severe malaria was 45.1% (95% CI, 23.8 to 

 60.5) in the intention-to-treat population and 47.3% (95% CI, 

 22.4 to 64.2) in the per-protocol population. Vaccine efficacy 

 against severe malaria in the combined age categories was 34.8% 

 (95% CI, 16.2 to 49.2) in the per-protocol population during an 

 average follow-up of 11 months. Serious adverse events occurred 

 with a similar frequency in the two study groups. Among children 

 in the older age category, the rate of generalized convulsive 

 seizures after RTS,S/AS01 vaccination was 1.04 per 1000 doses 

 (95% CI, 0.62 to 1.64). CONCLUSIONS: The RTS,S/AS01 vaccine 

 provided protection against both clinical and severe malaria in 

 African children. (Funded by GlaxoSmithKline Biologicals and the 

 PATH Malaria Vaccine Initiative; RTS,S ClinicalTrials.gov 

 number, NCT00866619 .).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bisoffi2011-dn,

title = {Strict adherence to malaria rapid test results might lead to a 

 neglect of other dangerous diseases: a cost benefit analysis 

 from Burkina Faso},

author = {Zeno Bisoffi and Sodiomon B Sirima and Filip Meheus and Claudia Lodesani and Federico Gobbi and Andrea Angheben and Halidou Tinto and Bouma Neya and Klara Van den Ende and Annalisa Romeo and Jef Van den Ende},

year  = {2011},

date = {2011-08-01},

journal = {Malar. J.},

volume = {10},

number = {1},

pages = {226},

publisher = {Springer Nature},

abstract = {BACKGROUND: Malaria rapid diagnostic tests (RDTs) have generally 

 been found reliable and cost-effective. In Burkina Faso, the 

 adherence of prescribers to the negative test result was found 

 to be poor. Moreover, the test accuracy for malaria-attributable 

 fever (MAF) is not the same as for malaria infection. This paper 

 aims at determining the costs and benefits of two competing 

 strategies for the management of MAF: presumptive treatment for 

 all or use of RDTs. METHODS: A cost benefit analysis was carried 

 out using a decision tree, based on data previously obtained, 

 including a randomized controlled trial (RCT) recruiting 852 

 febrile patients during the dry season and 1,317 in the rainy 

 season. Cost and benefit were calculated using both the real 

 adherence found by the RCT and assuming an ideal adherence of 

 90% with the negative result. The main parameters were 

 submitted to sensitivity analysis. RESULTS AND DISCUSSION: At 

 real adherence, the test-based strategy was dominated. Assuming 

 ideal adherence, at the value of 525 € for a death averted, the 

 total cost of managing 1,000 febrile children was 1,747 vs. 

 1,862 € in the dry season and 1,372 vs. 2,138 in the rainy 

 season for the presumptive vs. the test-based strategy. For 

 adults it was 2,728 vs. 1,983 and 2,604 vs. 2,225, respectively. 

 At the subsidized policy adopted locally, assuming ideal 

 adherence, the RDT would be the winning strategy for adults in 

 both seasons and for children in the dry season.At sensitivity 

 analysis, the factors most influencing the choice of the better 

 strategy were the value assigned to a death averted and the 

 proportion of potentially severe NMFI treated with antibiotics 

 in patients with false positive RDT results. The test-based 

 strategy appears advantageous for adults if a satisfactory 

 adherence could be achieved. For children the presumptive 

 strategy remains the best choice for a wide range of scenarios. 

 CONCLUSIONS: For RDTs to be preferred, a positive result should 

 not influence the decision to treat a potentially severe NMFI 

 with antibiotics. In the rainy season the presumptive strategy 

 always remains the better choice for children.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Swysen2011-lr,

title = {Development of standardized laboratory methods and quality 

 processes for a phase III study of the RTS, S/AS01 

 candidate malaria vaccine},

author = {Christine Swysen and Johan Vekemans and Myriam Bruls and Sunny Oyakhirome and Chris Drakeley and Peter Kremsner and Brian Greenwood and Opokua Ofori-Anyinam and Brenda Okech and Tonya Villafana and Terrell Carter and Barbara Savarese and Adriano Duse and Andrea Reijman and Charlotte Ingram and John Frean and Bernhards Ogutu and Clinical Trials Partnership Committee},

year  = {2011},

date = {2011-08-01},

journal = {Malar. J.},

volume = {10},

number = {1},

pages = {223},

publisher = {Springer Nature},

abstract = {BACKGROUND: A pivotal phase III study of the RTS,S/AS01 malaria 

 candidate vaccine is ongoing in several research centres across 

 Africa. The development and establishment of quality systems was 

 a requirement for trial conduct to meet international regulatory 

 standards, as well as providing an important capacity 

 strengthening opportunity for study centres. METHODS: 

 Standardized laboratory methods and quality assurance processes 

 were implemented at each of the study centres, facilitated by 

 funding partners. RESULTS: A robust protocol for determination 

 of parasite density based on actual blood cell counts was set up 

 in accordance with World Health Organization recommendations. 

 Automated equipment including haematology and biochemistry 

 analyzers were put in place with standard methods for bedside 

 testing of glycaemia, base excess and lactacidaemia. Facilities 

 for X-rays and basic microbiology testing were also provided or 

 upgraded alongside health care infrastructure in some centres. 

 External quality assurance assessment of all major laboratory 

 methods was established and method qualification by each 

 laboratory demonstrated. The resulting capacity strengthening 

 has ensured laboratory evaluations are conducted locally to the 

 high standards required in clinical trials. CONCLUSION: Major 

 efforts by study centres, together with support from 

 collaborating parties, have allowed standardized methods and 

 robust quality assurance processes to be put in place for the 

 phase III evaluation of the RTS, S/AS01 malaria candidate 

 vaccine. Extensive training programmes, coupled with continuous 

 commitment from research centre staff, have been the key 

 elements behind the successful implementation of quality 

 processes. It is expected these activities will culminate in 

 healthcare benefits for the subjects and communities 

 participating in these trials. TRIAL REGISTRATION: 

 Clinicaltrials.gov NCT00866619.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ravinetto2011-tb,

title = {Double ethical review of North-South collaborative clinical 

 research: hidden paternalism or real partnership?},

author = {Raffaella Ravinetto and Anne Buv\'{e} and Tinto Halidou and Pascal Lutumba and Ambrose Talisuna and Mohammad Juffrie and Umberto D'Alessandro and Marleen Boelaert},

year  = {2011},

date = {2011-04-01},

journal = {Trop. Med. Int. Health},

volume = {16},

number = {4},

pages = {527--530},

publisher = {Wiley},

abstract = {Despite their universal character, the ethical principles 

 governing clinical research need to be translated into 

 procedures and practices, which will vary among countries and 

 regions because of differences in local cultural norms and in 

 the available resources. Double ethical review, by which a 

 research protocol is submitted for ethical clearance both in the 

 country or countries where the research takes place and in the 

 country of the sponsor or funding agency, will then help ensure 

 that all relevant perspectives are taken into account. In 

 addition, a geographically and culturally close ethics committee 

 can do a much better informed and comprehensive assessment of 

 the respective skills of the clinical sites and of the sponsor. 

 But the practical implementation of double ethical review can 

 bring significant difficulties and delays, especially in 

 multi-site and multi-country researches. Currently, most ethics 

 committees do not proactively seek communication with others 

 evaluating the same research protocol in different 

 socio-economical and cultural contexts, so in practice there is 

 no mutual learning process. Proactive communication would help 

 to build collaborative partnership among ethical bodies, 

 promoting common practices and resolving conflicting opinions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Valea2010-af,

title = {Intermittent preventive treatment of malaria with 

 sulphadoxine-pyrimethamine during pregnancy in Burkina Faso: 

 effect of adding a third dose to the standard two-dose regimen 

 on low birth weight, anaemia and pregnancy outcomes},

author = {Innocent Valea and Halidou Tinto and Maxime K Drabo and Lieven Huybregts and Marie-Claire Henry and Dominique Roberfroid and Robert T Guiguemde and Patrick Kolsteren and Umberto D'Alessandro and FSP/MISAME Group},

year  = {2010},

date = {2010-11-01},

journal = {Malar. J.},

volume = {9},

number = {1},

pages = {324},

publisher = {Springer Nature},

abstract = {BACKGROUND: Intermittent preventive treatment with 

 sulphadoxine-pyrimethamine (IPTp-SP) is being implemented in 

 most malaria endemic countries as a standard two-doses regimen 

 as it reduces the risk of low birth weight (LBW) and the 

 prevalence of maternal anaemia. Nevertheless, where the risk of 

 infection close to delivery is high because of intense 

 transmission, a third IPTp-SP dose may further reduce the 

 negative effects of malaria on pregnancy outcome. METHODS: 

 Pregnant women in the 2nd or 3rd trimester were randomized to 

 receive either 2 (SP2) or 3 doses (SP3) of SP. Trained field 

 workers paid home visits to the women for drug administration 

 according to a predefined drug delivery schedule. Women were 

 encouraged to attend their scheduled ANC visits and to deliver 

 at the health facilities where the new-born was weighed. The 

 prevalence of LBW (<2500 g), severe anaemia (Hb < 8 g/dL) and 

 premature birth was analysed using intention-to-treat (ITT) and 

 per-protocol (PP) analysis. RESULTS: Data from 1274 singleton 

 pregnancies were analysed (641 in the SP3 and 633 in the SP2 

 group). The uptake of the intervention appeared to be low. 

 Though the prevalence of LBW in both intervention groups was similar (adjusted Incident Rate Rati},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bisoffi2010-jd,

title = {Accuracy of a rapid diagnostic test on the diagnosis of malaria 

 infection and of malaria-attributable fever during low and high 

 transmission season in Burkina Faso},

author = {Zeno Bisoffi and Sodiomon B Sirima and Joris Menten and Cristian Pattaro and Andrea Angheben and Federico Gobbi and Halidou Tinto and Claudia Lodesani and Bouma Neya and Maria Gobbo and Jef Van den Ende},

year  = {2010},

date = {2010-07-01},

journal = {Malar. J.},

volume = {9},

number = {1},

pages = {192},

publisher = {Springer Nature},

abstract = {BACKGROUND: Malaria management policies currently recommend that 

 the treatment should only be administered after laboratory 

 confirmation. Where microscopy is not available, rapid 

 diagnostic tests (RDTs) are the usual alternative. Conclusive 

 evidence is still lacking on the safety of a test-based strategy 

 for children. Moreover, no formal attempt has been made to 

 estimate RDTs accuracy on malaria-attributable fever. This study 

 aims at estimating the accuracy of a RDT for the diagnosis of 

 both malaria infection and malaria - attributable fever, in a 

 region of Burkina Faso with a typically seasonal malaria 

 transmission pattern. METHODS: Cross-sectional study. SUBJECTS: 

 all patients aged > 6 months consulting during the study 

 periods. Gold standard for the diagnosis of malaria infection 

 was microscopy. Gold standard for malaria-attributable fever was 

 the number of fevers attributable to malaria, estimated by 

 comparing parasite densities of febrile versus non-febrile 

 subjects. EXCLUSION CRITERIA: severe clinical condition needing 

 urgent care. RESULTS: In the dry season, 186/852 patients with 

 fever (22%) and 213/1,382 patients without fever (15%) had a 

 Plasmodium falciparum infection. In the rainy season, this 

 proportion was 841/1,317 (64%) and 623/1,669 (37%), 

 respectively. The attributable fraction of fever to malaria was 

 11% and 69%, respectively. The RDT was positive in 113/400 

 (28.3%) fever cases in the dry season, and in 443/650 (68.2%) 

 in the rainy season. In the dry season, the RDT sensitivity and 

 specificity for malaria infection were 86% and 90% 

 respectively. In the rainy season they were 94% and 78% 

 respectively. In the dry season, the RDT sensitivity and 

 specificity for malaria-attributable fever were 94% and 75%, 

 the positive predictive value (PPV) was 9% and the negative 

 predictive value (NPV) was 99.8%. In the rainy season the test 

 sensitivity for malaria-attributable fever was 97% and 

 specificity was 55%. The PPV ranged from 38% for adults to 

 82% for infants, while the NPV ranged from 84% for infants to 

 over 99% for adults. CONCLUSIONS: In the dry season the RDT has 

 a low positive predictive value, but a very high negative 

 predictive value for malaria-attributable fever. In the rainy 

 season the negative test safely excludes malaria in adults but 

 not in children.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bassat2009-xq,

title = {Dihydroartemisinin-piperaquine and artemether-lumefantrine for 

 treating uncomplicated malaria in African children: a 

 randomised, non-inferiority trial},

author = {Quique Bassat and Modest Mulenga and Halidou Tinto and Patrice Piola and Steffen Borrmann and Clara Men\'{e}ndez and Michael Nambozi and Innocent Val\'{e}a and Carolyn Nabasumba and Philip Sasi and Antonella Bacchieri and Marco Corsi and David Ubben and Ambrose Talisuna and Umberto D'Alessandro},

year  = {2009},

date = {2009-11-01},

journal = {PLoS One},

volume = {4},

number = {11},

pages = {e7871},

publisher = {Public Library of Science (PLoS)},

abstract = {BACKGROUND: Artemisinin combination therapies (ACTs) are 

 currently the preferred option for treating uncomplicated 

 malaria. Dihydroartemisinin-piperaquine (DHA-PQP) is a promising 

 fixed-dose ACT with limited information on its safety and 

 efficacy in African children. METHODOLOGY/PRINCIPAL FINDINGS: 

 The non-inferiority of DHA-PQP versus artemether-lumefantrine 

 (AL) in children 6-59 months old with uncomplicated P. 

 falciparum malaria was tested in five African countries (Burkina 

 Faso, Kenya, Mozambique, Uganda and Zambia). Patients were 

 randomised (2:1) to receive either DHA-PQP or AL. 

 Non-inferiority was assessed using a margin of -5% for the 

 lower limit of the one-sided 97.5% confidence interval on the 

 treatment difference (DHA-PQP vs. AL) of the day 28 polymerase 

 chain reaction (PCR) corrected cure rate. Efficacy analysis was 

 performed in several populations, and two of them are presented 

 here: intention-to-treat (ITT) and enlarged per-protocol (ePP). 

 1553 children were randomised, 1039 receiving DHA-PQP and 514 

 AL. The PCR-corrected day 28 cure rate was 90.4% (ITT) and 

 94.7% (ePP) in the DHA-PQP group, and 90.0% (ITT) and 95.3% 

 (ePP) in the AL group. The lower limits of the one-sided 97.5% 

 CI of the difference between the two treatments were -2.80% and 

 -2.96%, in the ITT and ePP populations, respectively. In the 

 ITT population, the Kaplan-Meier estimate of the proportion of 

 new infections up to Day 42 was 13.55% (95% CI: 

 11.35%-15.76%) for DHA-PQP vs 24.00% (95% CI: 

 20.11%-27.88%) for AL (p<0.0001). CONCLUSIONS/SIGNIFICANCE: 

 DHA-PQP is as efficacious as AL in treating uncomplicated 

 malaria in African children from different endemicity settings, 

 and shows a comparable safety profile. The occurrence of new 

 infections within the 42-day follow up was significantly lower 

 in the DHA-PQP group, indicating a longer post-treatment 

 prophylactic effect. TRIAL REGISTRATION: Controlled-trials.com 

 ISRCTN16263443.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bisoffi2009-zh,

title = {Rapid malaria diagnostic tests vs. clinical management of 

 malaria in rural Burkina Faso: safety and effect on clinical 

 decisions. A randomized trial},

author = {Zeno Bisoffi and Bienvenu Sodiomon Sirima and Andrea Angheben and Claudia Lodesani and Federico Gobbi and Halidou Tinto and Jef Van den Ende},

year  = {2009},

date = {2009-05-01},

journal = {Trop. Med. Int. Health},

volume = {14},

number = {5},

pages = {491--498},

publisher = {Wiley},

abstract = {OBJECTIVES: To assess if the clinical outcome of patients 

 treated after performing a Rapid Diagnostic Test for malaria 

 (RDT) is at least equivalent to that of controls (treated 

 presumptively without test) and to determine the impact of the 

 introduction of a malaria RDT on clinical decisions. METHODS: 

 Randomized, multi-centre, open clinical trial in two arms in 

 2006 at the end of the dry and of the rainy season in 10 

 peripheral health centres in Burkina Faso: one arm with use of 

 RDT before treatment decision, one arm managed clinically. 

 Primary endpoint: persistence of fever at day 4. Secondary 

 endpoints: frequency of malaria treatment and of antibiotic 

 treatment. RESULTS: A total of 852 febrile patients were 

 recruited in the dry season and 1317 febrile patients in the 

 rainy season, and randomized either to be submitted to RDT 

 (P_RTD) or to be managed presumptively (P_CLIN). In both 

 seasons, no significant difference was found between the two 

 randomized groups in the frequency of antimalarial treatment, 

 nor of antibiotic prescription. In the dry season, 80.8% and 

 79.8% of patients with a negative RDT were nevertheless 

 diagnosed and treated for malaria, and so were 85.0% and 82.6% 

 negative patients in the rainy season. In the rainy season only, 

 both diagnosis and treatment of other conditions were 

 significantly less frequent in RDT positive vs. negative patients (48.3% vs. 61.4% and 46.2% vs. 59.9},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Valea2009-ip,

title = {Performance of OptiMAL-IT compared to microscopy, for malaria 

 detection in Burkina Faso},

author = {Innocent Val\'{e}a and Halidou Tinto and Madi Nikiema and Lawrence Yamuah and Noel Rouamba and Maxime Drabo and Robert T Guiguemde and Umberto d'Alessandro},

year  = {2009},

date = {2009-03-01},

journal = {Trop. Med. Int. Health},

volume = {14},

number = {3},

pages = {338--340},

publisher = {Wiley},

abstract = {OBJECTIVE: To compare the performance of OptiMAL-IT, a rapid 

 diagnostic test for malaria, with that of microscopy in Burkina 

 Faso. METHOD: Finger-prick blood samples of 464 children 

 attending hospital for suspected malaria were tested for malaria 

 by microscopy and OptiMAL-IT. RESULTS: The sensitivity and specificity of OptiMAL-IT were 98.7% (CI 95% = 97.6-99.8) and 96.2% (CI 95% = 94.3-98.1) respectively, with a high positive 

 likelihood ratio (25.97). CONCLUSION: OptiMAL-IT can be 

 considered a good method to diagnose malaria in Burkina Faso, 

 particularly in remote areas with little or no access to 

 microscopy services.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Culleton2008-pj,

title = {Failure to detect Plasmodium vivax in West and Central Africa by 

 PCR species typing},

author = {Richard L Culleton and Toshihiro Mita and Mathieu Ndounga and Holger Unger and Pedro V L Cravo and Giacomo M Paganotti and Nobuyuki Takahashi and Akira Kaneko and Hideaki Eto and Halidou Tinto and Corine Karema and Umberto D'Alessandro and Virgilio Ros\'{a}rio and Takatoshi Kobayakawa and Francine Ntoumi and Richard Carter and Kazuyuki Tanabe},

year  = {2008},

date = {2008-09-01},

journal = {Malar. J.},

volume = {7},

number = {1},

pages = {174},

publisher = {Springer Nature},

abstract = {BACKGROUND: Plasmodium vivax is estimated to affect 75 million 

 people annually. It is reportedly absent, however, from west and 

 central Africa due to the high prevalence of the Duffy negative 

 phenotype in the indigenous populations. Despite this, 

 non-African travellers consistently return to their own 

 countries with P. vivax malaria after visiting this region. An 

 attempt was made, therefore, to detect the presence of P. vivax 

 parasites in blood samples collected from the indigenous 

 populations of west and central Africa. METHODS: Parasite 

 species typing (for all four human malaria parasites) was 

 carried out by PCR on 2,588 blood samples collected from 

 individuals from nine African malaria-endemic countries. 

 RESULTS: Most infections (98.5%) were Plasmodium falciparum, 

 Plasmodium malariae was identified in 8.5% of all infections, 

 and Plasmodium ovale in 3.9%. The prevalence of both parasites 

 varied greatly by country. Only one case of P. vivax was 

 detected from Sao Tome, an island off the west coast of Africa, 

 confirming the scarcity of this parasite in Africa. CONCLUSION: 

 The prevalence of P. vivax in local populations in sub-Saharan 

 Africa is very low, despite the frequent identification of this 

 parasite in non-African travellers.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2008-bs,

title = {Chloroquine-resistance molecular markers (Pfcrt T76 and 

 Pfmdr-1 Y86) and amodiaquine resistance in Burkina Faso},

author = {Halidou Tinto and Lougu\'{e} Guekoun and Issaka Zongo and Robert Tinga Guiguemd\'{e} and Umberto D'Alessandro and Jean Bosco Ou\'{e}draogo},

year  = {2008},

date = {2008-02-01},

journal = {Trop. Med. Int. Health},

volume = {13},

number = {2},

pages = {238--240},

publisher = {Wiley},

abstract = {We investigated the relationship between the two main molecular 

 markers for chloroquine resistance (Pfcrt T76 and Pfmdr-1 Y86) 

 and the clinical efficacy of amodiaquine in Burkina Faso. Before 

 treatment, the prevalence of Pfcrt T76, Pfmdr-1 Y86 or both 

 mutations in the same infection was significantly higher in 

 patients who experienced a recrudescence than in those who 

 successfully responded to the treatment. Therefore, these two 

 molecular markers could be useful in monitoring amodiaquine 

 resistance, particularly in countries where this drug is used in 

 combination with artesunate as first- or second-line treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2007-yx,

title = {Sulfadoxine-pyrimethamine efficacy and selection of Plasmodium 

 falciparum DHFR mutations in Burkina Faso before its 

 introduction as intermittent preventive treatment for pregnant 

 women},

author = {Halidou Tinto and Jean Bosco Ou\'{e}draogo and Issaka Zongo and Chantal Overmeir and Eric Marck and Tinga Robert Guiguemd\'{e} and Umberto D'Alessandro},

year  = {2007},

date = {2007-04-01},

journal = {Am. J. Trop. Med. Hyg.},

volume = {76},

number = {4},

pages = {608--613},

publisher = {American Society of Tropical Medicine and Hygiene},

abstract = {Sulfadoxine-pyrimethamine efficacy was determined with a 28-day 

 follow-up in 97 children between 6 months and 15 years of age. 

 The polymerase chain reaction (PCR)-corrected treatment failure 

 was 8.2% and the uncorrected was 21.6%. The presence of the 

 dihydrofolate reductase (DHFR) and dihydropteroate synthetase 

 (DHPS) mutations linked to sulfadoxine-pyrimethamine resistance 

 before and after treatment was determined by PCR-restriction 

 fragment length polymorphism (RFLP) and by a fluorogenic PCR 

 assay. Before treatment, the prevalence of the triple DHFR 

 mutations was higher among the patients having had a recurrent 

 parasitemia (either recrudescence or new infection; 28.6% versus 9.3%), although the difference was not significant (P = 

 0.1). The double mutation Ala-436/Gly-437 was observed in 67% 

 of samples, whereas no Glu-540 mutation was found. After 

 treatment, the triple DHFR mutation was found in 76.2% of 

 patients with recurrent parasitemia, recrudescence, and new 

 infection alike. Such high prevalence of mutant parasites 

 indicates that sulfadoxine-pyrimethamine should not be used as 

 monotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zongo2007-uv,

title = {Artemether-lumefantrine versus amodiaquine plus 

 sulfadoxine-pyrimethamine for uncomplicated falciparum malaria 

 in Burkina Faso: a randomised non-inferiority trial},

author = {Issaka Zongo and Grant Dorsey and Noel Rouamba and Halidou Tinto and Christian Dokomajilar and Robert T Guiguemde and Philip J Rosenthal and Jean Bosco Ouedraogo},

year  = {2007},

date = {2007-02-01},

journal = {Lancet},

volume = {369},

number = {9560},

pages = {491--498},

publisher = {Elsevier BV},

abstract = {BACKGROUND: Artemisinin-based combination regimens are widely 

 advocated for malarial treatment, but other effective regimens 

 might be cheaper and more readily available. Our aim was to 

 compare the risk of recurrent parasitaemia in patients given 

 artemether-lumefantrine with that in those given amodiaquine 

 plus sulfadoxine-pyrimethamine for uncomplicated malaria. 

 METHODS: We enrolled 521 patients aged 6 months or older with 

 uncomplicated falciparum malaria in Bobo-Dioulasso, Burkina 

 Faso. Patients were randomly assigned to receive standard doses 

 of either artemether-lumefantrine (261) or amodiaquine plus 

 sulfadoxine-pyrimethamine (260) for 3 days. Primary endpoints 

 were the risks of treatment failure within 28 days, either 

 unadjusted or adjusted by genotyping to distinguish 

 recrudescence from new infection. The study is registered at 

 controlled-trials.gov with the identifier ISRCTN54261005. 

 FINDINGS: Of enrolled patients, 478 (92%) completed the 28-day 

 study. The risk of recurrent symptomatic malaria was lowest in 

 the group given amodiaquine plus sulfadoxine-pyrimethamine 

 (1.7%vs 10.2%; risk difference 8.5%; 95% CI 4.3-12.6; p=0.0001); as was the risk of recurrent parasitaemia (4.7%vs 15.1%; 10.4%; 5.1-15.6; p=0.0002). Nearly all recurrences were 

 due to new infections. Recrudescences were four late treatment 

 failures with artemether-lumefantrine and one early treatment 

 failure with amodiaquine plus sulfadoxine-pyrimethamine. Both 

 regimens were safe and well tolerated, with pruritus more common 

 with amodiaquine plus sulfadoxine-pyrimethamine than with 

 artemether-lumefantrine. Each regimen selected for new isolates 

 with mutations that have been associated with decreased drug 

 susceptibility. INTERPRETATION: Amodiaquine plus 

 sulfadoxine-pyrimethamine was more effective than was 

 artemether-lumefantrine for the treatment of uncomplicated 

 malaria. For regions of Africa where amodiaquine plus 

 sulfadoxine-pyrimethamine continues to be effective, this less 

 expensive and more available regimen should be considered as an 

 alternative to blanket recommendations for artemisinin-based 

 combination treatment for malaria.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2006-iz,

title = {In-vitro susceptibility of Plasmodium falciparum to 

 monodesethylamodiaquine, dihydroartemisinin and quinine in an 

 area of high chloroquine resistance in Rwanda},

author = {Halidou Tinto and Claude Rwagacondo and Corinne Karema and Denise Mupfasoni and Waltruda Vandoren and Emmanuel Rusanganwa and Annette Erhart and Chantal Van Overmeir and Eric Van Marck and Umberto D'Alessandro},

year  = {2006},

date = {2006-06-01},

journal = {Trans. R. Soc. Trop. Med. Hyg.},

volume = {100},

number = {6},

pages = {509--514},

publisher = {Oxford University Press (OUP)},

abstract = {Plasmodium falciparum in-vitro susceptibility to chloroquine 

 (CQ), monodesethylamodiaquine, quinine and dihydroartemisinin 

 was investigated in Rwandan patients with a parasitaemia of at least >or=4000/microl. The study was carried out in 

 November-December 2003. Dihydroartemisinin was the most potent (GM IC(50)=2.6nmol/l, 95% CI 2.2-3.2) among the drugs tested. 

 Resistance to chloroquine was 45% (33/74) and that to 

 monodesethylamodiaquine 7% (5/74). All the tested isolates were 

 susceptible to quinine. The mean IC(50) of 

 monodesethylamodiaquine, quinine and dihydroartemisinin was 

 significantly higher for chloroquine-resistant than for 

 chloroquine-sensitive strains (P<0.05). The IC(50) of each drug 

 was significantly and positively correlated to that of the other 

 three drugs (P<0.005), and this correlation was higher between CQ and monodesethylamodiaquine (r=0.8). In-vitro CQ resistance 

 is linked to that of the other drugs tested. Most worrying is 

 the positive correlation between the IC(50) of 

 dihydroartemisinin and the other drugs, more particularly with 

 CQ, suggesting an increased tolerance of the parasites to all 

 drugs.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2005-vz,

title = {Usefulness of the Plasmodium falciparum chloroquine resistance 

 transporter T76 genotype failure index for the estimation of 

 in vivo chloroquine resistance in Burkina Faso},

author = {Halidou Tinto and Boroma Sanou and Jean-Claude Dujardin and Jean Bosco Ou\'{e}draogo and Chantal VAN Overmeir and Annette Erhart and Eric VAN Marck and Tinga Robert Guiguemd\'{e} and Umberto D'Alessandro},

year  = {2005},

date = {2005-07-01},

journal = {Am. J. Trop. Med. Hyg.},

volume = {73},

number = {1},

pages = {171--173},

publisher = {American Society of Tropical Medicine and Hygiene},

abstract = {The prevalence of chloroquine (CQ) treatment failure and the 

 genotype failure index was determined in four sentinel sites in 

 Burkina Faso. In three sites, the genotype failure index varied 

 between 1.7 and 3, a result confirming the relationship between 

 the Plasmodium falciparum CQ resistance transporter (Pfcrt) T76 

 mutation and CQ resistance. In the remaining site, the genotype 

 failure index was unusually low, 1.1, which was significantly 

 different than that in the other sites (P < 0.00001). These 

 findings are discussed. Often but not always, the prevalence of 

 CQ resistance can be correctly estimated by the Pfcrt T76 

 genotype failure index.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2004-sw,

title = {Parasitological resistance of Plasmodium falciparum to 

 antimalarial drugs: what physicians should keep in mind},

author = {Halidou Tinto and Jean Bosco Ou\'{e}draogo and Maminata Traor\'{e} and Tinga Robert Guiguemd\'{e}},

year  = {2004},

date = {2004-04-01},

journal = {Sante},

volume = {14},

number = {2},

pages = {69--73},

abstract = {Plasmodium falciparum drug resistance has considerably modified 

 the attitude of physicians in terms of malaria case management. 

 However, a bad understanding of the resistance phenomenon can 

 lead to non-appropriate therapeutic and/or public health 

 practices. The objective of this paper was to contribute to 

 clarify the concept of parasitological resistance by analysing 

 the different types of resistance observed in vivo. We showed 

 through some examples that the precision of in vivo 

 parasitological results depends on the type of microscopical 

 technique used. We also showed that the classification system 

 into resistance levels RI, RII, and RIII does not correspond to 

 an increase in the resistance of the parasite itself but rather 

 to an increase in the proportion of the resistant strains 

 compared to the sensitive ones circulating in a given population. 

 Mutant strains are circulating in low proportions as long as 

 there is no selective drug pressure. They can be first detected 

 in vitro and, later on, when their proportion increase, they are 

 detected in vivo, first in non-immune subjects and later in 

 semi-immune subjects. Therefore, the role of the host immunity is 

 important in malaria drug resistance. To conclude, increasing use 

 of antimalarial drugs (especially in monotherapy) cannot thwart 

 the resistance, but rather leads to the selection of mutants 

 strains. As the proportion of the mutant strains increases 

 compared to the sensitive (wild) ones, it will reach the 

 microscopic detection level and then, the clinical level. It is 

 important that physicians involved in malaria case management 

 understand these notions in order to avoid non-appropriate 

 therapeutic decisions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2003-pn,

title = {Relationship between the Pfcrt T76 and the Pfmdr-1 Y86 

 mutations in Plasmodium falciparum and in vitro/in vivo 

 chloroquine resistance in Burkina Faso, West Africa},

author = {Halidou Tinto and Jean Bosco Ou\'{e}draogo and Annette Erhart and Chantal Van Overmeir and Jean-Claude Dujardin and Eric Van Marck and Tinga Robert Guiguemd\'{e} and Umberto D'Alessandro},

year  = {2003},

date = {2003-11-01},

journal = {Infect. Genet. Evol.},

volume = {3},

number = {4},

pages = {287--292},

publisher = {Elsevier BV},

abstract = {The relationship between Pfcrt T76 and Pfmdr-1 Y86 mutations in 

 Plasmodium falciparum was explored in samples from patients with 

 uncomplicated malaria and tested in vitro and in vivo with 

 chloroquine (CQ) in Burkina Faso. The two mutations were 

 strongly related. The Pfcrt T76 mutation was found in 82% of 

 the samples having the Pfmdr-1 Y86 mutation too (odds ratio (OR)=4.8 [95% CI: 1.7-13.3]; P=0.002). However, only half 

 (16/34) of samples with Pfcrt T76 mutation had also the Pfmdr-1 

 Y86 mutation. The latter was apparently associated with in vitro resistance (OR=4.8 [95% CI: 1.4-16.5]; P=0.01) but such association disappeared (P=0.77) after adjusting for the 

 presence of the Pfcrt T76 mutation. This suggests that the 

 occurrence of the Pfmdr-1 Y86 mutation is dependent on that of 

 Pfcrt T76 mutation and could explain previous reports linking 

 the Pfmdr-1 Y86 mutation with CQ resistance (CQR). The isolates 

 carrying both the Pfcrt K76 and Pfmdr-1 N86 alleles (wild/wild 

 (WW)) and the single mutant Pfmdr-1 Y86 (WM) had the lowest IC50 

 geometric mean (GMIC50) values, while those carrying both Pfcrt 

 T76/Pfmdr-1 Y86 alleles (mutant/mutant (MM)), and the single 

 mutant Pfcrt T76 (MW) had the highest. Among pre-treatment 

 samples there was a strong linkage disequilibrium with an excess 

 of MM and WW and a deficit of single mutants (MW and WM), 

 suggesting that parasite fitness is higher for the former and 

 lower for the latter.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}