@article{Sondo2015-fh,

title = {Dynamic of plasmodium falciparum chloroquine resistance 

 transporter gene Pfcrt K76T mutation five years after 

 withdrawal of chloroquine in Burkina Faso},

author = {Paul Sondo and Karim Derra and Zekiba Tarnagda and Seydou Diallo Nakanabo and Odile Zampa and Adama Kazienga and Innocent Valea and Hermann Sorgho and Jean-Bosco Ouedraogo and Tinga Robert Guiguemde and Halidou Tinto},

year  = {2015},

date = {2015-06-01},

journal = {Pan Afr. Med. J.},

volume = {21},

pages = {101},

publisher = {Pan African Medical Journal},

abstract = {We investigated the evolution of Pfcrt K76T mutation five years 

 after the withdrawal of chloroquine in Burkina Faso. A total of 

 675 clinical isolates collected from October 2010 to September 

 2012 were successfully genotyped. Single nucleotide polymorphism 

 in Pfcrt (codon 76) gene was analyzed. The prevalence of 

 resistant Pfcrt 76T allele was 20.55%. There was a progressive 

 decrease of the proportion of mutant type pfcrt T76 from 2010 to 2012 (X2=5.508 p=0.0189). Our results suggest a progressive 

 return of the wild type Pfcrt K76 in Burkina Faso but the 

 prevalence of the mutants Pfcrt T76 still remains high.},

keywords = {Malaria; chloroquine resistance; pfcrt; plasmodium falciparum},

pubstate = {published},

tppubtype = {article}

}

@article{Tiono2015-cq,

title = {Increased systemic exposures of artemether and 

 dihydroartemisinin in infants under 5 kg with uncomplicated 

 Plasmodium falciparum malaria treated with 

 artemether-lumefantrine (Coartemtextregistered)},

author = {Alfred B Tiono and Halidou Tinto and Maroufou J Alao and Martin Meremikwu and Antoinette Tshefu and Bernhards Ogutu and Alphonse Ouedraogo and Moussa Lingani and Marc Cousin and Gilbert Lef`evre and Jay Prakash Jain and Stephan Duparc and Kamal Hamed},

year  = {2015},

date = {2015-04-01},

journal = {Malar. J.},

volume = {14},

number = {1},

pages = {157},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Artemether-lumefantrine (AL) dispersible formulation 

 was developed for the treatment of uncomplicated Plasmodium 

 falciparum malaria in infants and children weighing 5 to 28 days 

 and \<5 kg of body weight, who were treated with one AL 

 dispersible tablet (20 mg artemether/120 mg lumefantrine) given 

 twice-daily for three days and followed up for six weeks (core 

 follow-up) and at 12 months of age (long-term follow-up). 

 RESULTS: A total of 20 patients were enrolled and completed the 

 six-week core study follow-up. In the per protocol population, 

 PCR-corrected cure rate at days 28 and 42 was 100% (95% CI: 

 79.4, 100). AL dispersible was well tolerated with reported 

 adverse events of mild to moderate severity. Pharmacokinetic 

 data showed that lumefantrine levels were similar, however, 

 artemether and dihydroartemisinin levels were on average two- to 

 three-fold greater than historical values in infants and 

 children $geq$5 kg. CONCLUSIONS: A three-day regimen of AL 

 dispersible formulation was efficacious and generally well 

 tolerated in infants weighing \<5 kg with uncomplicated P. 

 falciparum malaria, but artemether and dihydroartemisinin 

 exposures could not be supported by the preclinical safety 

 margins for neurotoxicity. Hence, dosing recommendations cannot 

 be made in infants \<5 kg as implications for toxicity are 

 unknown. TRIAL REGISTRATION: Clinicaltrials.gov NCT01619878.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Baiden2015-jk,

title = {Prospective observational study to evaluate the clinical safety 

 of the fixed-dose artemisinin-based combination 

 Eurartesimtextregistered (dihydroartemisinin/piperaquine), in 

 public health facilities in Burkina Faso, Mozambique, Ghana, and 

 Tanzania},

author = {Rita Baiden and Abraham Oduro and Tinto Halidou and Margaret Gyapong and Ali Sie and Eusebio Macete and Salim Abdulla and Seth Owusu-Agyei and Abdunoor Mulokozi and Alex Adjei and Esperanca Sevene and Guillaume Compaor\'{e} and Innocent Valea and Isaac Osei and Abena Yawson and Martin Adjuik and Raymond Akparibo and Bernhards Ogutu and Gabriel Leonard Upunda and Peter Smith and Fred Binka},

year  = {2015},

date = {2015-04-01},

journal = {Malar. J.},

volume = {14},

number = {1},

pages = {160},

publisher = {Springer Nature},

abstract = {BACKGROUND: The World Health Organization recommends 

 artemisinin-based combination (ACT) for the treatment of 

 uncomplicated malaria. Post-licensure safety data on newly 

 registered ACT is critical for evaluating their risk/benefit 

 profile in malaria endemic countries. The clinical safety of the 

 newly registered combination, Eurartesimtextregistered, following its introduction into the public health system in four 

 African countries was assessed. METHODS: This was a prospective, 

 observational, open-label, non-comparative, longitudinal, 

 multi-centre study using cohort event monitoring. Patients with 

 confirmed malaria had their first dose observed and instructed 

 on how to take the second and the third doses at home. Patients 

 were contacted on day 5 $pm$ 2 to assess adherence and adverse 

 events (AEs). Spontaneous reporting of AEs was continued till 

 day 28. A nested cohort who completed full treatment course had 

 repeated electrocardiogram (ECG) measurements to assess effect 

 on QTc interval. RESULTS: A total of 10,925 uncomplicated 

 malaria patients were treated with Eurartesimtextregistered. 

 Most patients,95% (10,359/10,925), did not report any adverse 

 event following at least one dose of 

 Eurartesimtextregistered. A total of 797 adverse events were 

 reported. The most frequently reported, by system organ 

 classification, were infections and infestations (3. 24%) and 

 gastrointestinal disorders (1. 37%). In the nested cohort, no 

 patient had QTcF \> 500 ms prior to day 3 pre-dose 3. Three 

 patients had QTcF \> 500 ms (509 ms, 501 ms, 538 ms) three to 

 four hours after intake of the last dose. All the QTcF values in 

 the three patients had returned to \<500 ms at the next scheduled 

 ECG on day 7 (470 ms, 442 ms, 411 ms). On day 3 pre- and 

 post-dose 3, 70 and 89 patients, respectively, had a QTcF 

 increase of $geq$ 60 ms compared to their baseline, but 

 returned to nearly baseline values on day 7. CONCLUSION: 

 Eurartesimtextregistered single course treatment for 

 uncomplicated falciparum malaria is well-tolerated. QT interval 

 prolongation above 500 ms may occur at a rate of three per 1,002 

 patients after the third dose with no association of any 

 clinical symptoms. QT interval prolongation above 60 ms was 

 detected in less than 10% of the patients without any clinical 

 abnormalities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nambozi2015-tz,

title = {Safe and efficacious artemisinin-based combination treatments 

 for African pregnant women with malaria: a multicentre 

 randomized control trial},

author = {Michael Nambozi and Modest Mulenga and Tinto Halidou and Harry Tagbor and Victor Mwapasa and Linda Kalilani Phiri and Gertrude Kalanda and Innocent Valea and Maminata Traore and David Mwakazanga and Yves Claeys and C\'{e}line Schurmans and Maaike De Crop and Joris Menten and Raffaella Ravinetto and Kamala Thriemer and Jean-Pierre Van Geertruyden and Theonest Mutabingwa and Umberto D'Alessandro and Pregact Group},

year  = {2015},

date = {2015-01-01},

journal = {Reprod. Health},

volume = {12},

number = {1},

pages = {5},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Asymptomatic and symptomatic malaria during 

 pregnancy has consequences for both mother and her offspring. 

 Unfortunately, there is insufficient information on the safety 

 and efficacy of most antimalarials in pregnancy. Indeed, 

 clinical trials assessing antimalarial treatments systematically 

 exclude pregnancy for fear of teratogenicity and embryotoxicity. 

 The little available information originates from South East Asia 

 while in sub-Saharan Africa such information is still limited 

 and needs to be provided. DESIGN: A Phase 3, non-inferiority, 

 multicentre, randomized, open-label clinical trial on safety and 

 efficacy of 4 ACT when administered during pregnancy was carried 

 out in 4 African countries: Burkina Faso, Ghana, Malawi and 

 Zambia. This is a four arm trial using a balanced incomplete 

 block design. Pregnant women diagnosed with malaria are 

 randomised to receive either amodiaquine-artesunate (AQ-AS), 

 dihydroartemisinin-piperaquine (DHA-PQ), artemether-lumefantrine 

 (AL), or mefloquine-artesunate (MQAS). They are actively 

 followed up until day 63 post-treatment and then monthly until 

 4-6 weeks post-delivery. The offspring is visited at the time of 

 the first birthday. The primary endpoint is treatment failure 

 (PCR adjusted) at day 63 and safety profiles. Secondary 

 endpoints included PCR unadjusted treatment failure up to day 

 63, gametocyte carriage, Hb changes, placenta malaria, mean 

 birth weight and low birth weight. The primary statistical 

 analysis will use the combined data from all 4 centres, with 

 adjustment for any centre effects, using an additive model for 

 the response rates. This will allow the assessment of all 6 

 possible pair-wise treatment comparisons using all available 

 data. DISCUSSION: The strength of this trial is the involvement 

 of several African countries, increasing the generalisability of 

 the results. In addition, it assesses most ACTs currently 

 available, determining their relative '-value-' compared to 

 others. The balanced incomplete block design was chosen because 

 using all 4-arms in each site would have increased complexity in 

 terms of implementation. Excluding HIV-positive pregnant women 

 on antiretroviral drugs may be seen as a limitation because of 

 the possible interactions between antiretroviral and 

 antimalarial treatments. Nevertheless, the results of this trial 

 will provide the evidence base for the formulation of malaria 

 treatment policy for pregnant women in sub-Saharan Africa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Baraka2015-my,

title = {In vivo selection of Plasmodium falciparum Pfcrt and Pfmdr1 

 variants by artemether-lumefantrine and 

 dihydroartemisinin-piperaquine in Burkina Faso},

author = {Vito Baraka and Halidou Tinto and Innocent Valea and Robert Fitzhenry and Christopher Delgado-Ratto and Martin K Mbonye and Chantal Van Overmeir and Anna Rosanas-Urgell and Jean-Pierre Van Geertruyden and Umberto D'Alessandro and Annette Erhart},

year  = {2015},

date = {2015-01-01},

journal = {Antimicrob. Agents Chemother.},

volume = {59},

number = {1},

pages = {734--737},

abstract = {Plasmodium falciparum Pfcrt-76 and Pfmdr1-86 gene polymorphisms 

 were determined during a clinical trial in Burkina Faso comparing 

 the efficacies of dihydroartemisinin-piperaquine (DHA-PPQ) and 

 artemether-lumefantrine (AL). Significant selection of Pfcrt-K76 

 was observed after exposure to AL and DHA-PPQ, as well as 

 selection of Pfmdr1-N86 after AL but not DHA-PPQ treatment, 

 suggesting reverse selection on the Pfcrt gene by PPQ. These 

 results support the rational use of DHA-PPQ in settings where 

 chloroquine (CQ) resistance is high.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ravinetto2015-et,

title = {Participation in medical research as a resource-seeking strategy 

 in socio-economically vulnerable communities: call for research 

 and action},

author = {Raffaella M Ravinetto and Muhammed O Afolabi and Joseph Okebe and Jennifer Ilo Van Nuil and Pascal Lutumba and Hypolite Muhindo Mavoko and Alain Nahum and Halidou Tinto and Adamu Addissie and Umberto D'Alessandro and Koen Peeters Grietens},

year  = {2015},

date = {2015-01-01},

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

volume = {20},

number = {1},

pages = {63--66},

publisher = {Wiley},

abstract = {The freedom to consent to participate in medical research is a 

 complex subject, particularly in socio-economically vulnerable 

 communities, where numerous factors may limit the efficacy of 

 the informed consent process. Informal consultation among 

 members of the Switching the Poles Clinical Research Network 

 coming from various sub-Saharan African countries, that is 

 Burkina Faso, The Gambia, Rwanda, Ethiopia, the Democratic 

 Republic of Congo (DRC) and Benin, seems to support the 

 hypothesis that in socio-economical vulnerable communities with 

 inadequate access to health care, the decision to participate in 

 research is often taken irrespectively of the contents of the 

 informed consent interview, and it is largely driven by the 

 opportunity to access free or better quality care and other 

 indirect benefits. Populations' vulnerability due to poverty 

 and/or social exclusion should obviously not lead to exclusion 

 from medical research, which is most often crucially needed to 

 address their health problems. Nonetheless, to reduce the 

 possibility of exploitation, there is the need to further 

 investigate the complex links between socio-economical 

 vulnerability, access to health care and individual freedom to 

 decide on participation in medical research. This needs bringing 

 together clinical researchers, social scientists and 

 bioethicists in transdisciplinary collaborative research efforts 

 that require the collective input from researchers, research 

 sponsors and funders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bocoum2014-ci,

title = {Malaria prevention measures in Burkina Faso: distribution and 

 households expenditures},

author = {Fadima Yaya Bocoum and Danielle Belemsaga and Alex Adjagba and Damian Walker and Seni Kouanda and Halidou Tinto},

year  = {2014},

date = {2014-11-01},

journal = {Int. J. Equity Health},

volume = {13},

number = {1},

pages = {108},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: The provision of insecticide-treated nets (ITNs) is 

 widely accepted in Burkina Faso thanks to large-scale national 

 distribution campaigns. However, household also use other 

 methods of prevention. Thus far, there is little knowledge about 

 the expenditures of these malaria prevention methods, 

 particularly in combination with the national interventions. 

 This paper presents the utilization levels and expenditures of 

 malaria prevention tools in Burkina Faso and explores the 

 potential inequality in ownership. METHODS: The analysis is 

 based on a cross-sectional survey, conducted during the 2010 

 high transmission season from July to September in the Nanoro 

 Health and Demographic Surveillance Site. Following a systematic 

 sampling technique, the survey covers 500 households with 

 children under 5 years of age from 24 villages. In the survey, 

 households were asked about expenditures on malaria prevention 

 methods in the month preceding the survey. This includes 

 expenditure on coils, indoor spraying, aerosols, repellents, 

 herbs, cleaning of the environment and clearing of the 

 vegetation. The data analysis was conducted with SPSS taking 

 into account the socio-economic status (SES) of the household to 

 examine any differences in the utilization of the prevention 

 method and expenditure quintiles. An asset-based index, created 

 through principal components analysis (PCA), was used to 

 categorize the households into quintiles. FINDINGS: Of the 

 households surveyed, 45% used one preventive measure in the 

 past month; 29% used two measures; and 25% used three or more 

 measures. A significant association was found between the number 

 of prevention measures and the SES of the household (p \< 0.05). 

 The majority of households owned at least one insecticide 

 treated net (ITN) (98%). Among households that used ITN, 53.8% 

 used methods other than bed nets. The majority of households 

 paid nothing for malaria prevention. CONCLUSION: Most of the 

 households received bed nets and other preventive method for 

 free. There is equity in expenditures across SES groups. Free 

 distribution of ITNs ensured that there was equity in ITN 

 ownership among households. More research on the possibility of 

 increasing access to other locally relevant methods of malaria 

 control that proved to be effective is need.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Valea2014-gm,

title = {Pharmacokinetics of co-formulated mefloquine and artesunate in 

 pregnant and non-pregnant women with uncomplicated Plasmodium 

 falciparum infection in Burkina Faso},

author = {Innocent Valea and Halidou Tinto and Maminata Traore-Coulibaly and Laeticia C Toe and Niklas Lindegardh and Joel Tarning and Jean-Pierre Van Geertruyden and Umberto D'Alessandro and Geraint R Davies and Stephen A Ward},

year  = {2014},

date = {2014-09-01},

journal = {J. Antimicrob. Chemother.},

volume = {69},

number = {9},

pages = {2499--2507},

publisher = {Oxford University Press (OUP)},

abstract = {OBJECTIVES: Mefloquine/artesunate has recently been developed as 

 a fixed-dose combination, providing a promising 

 rescue/alternative treatment for malaria during pregnancy. 

 However, limited data are available on the effect of pregnancy 

 on its pharmacokinetic properties. This study was conducted to 

 assess the pharmacokinetic properties of 

 mefloquine/carboxymefloquine and artesunate/dihydroartemisinin 

 in pregnant and non-pregnant women with uncomplicated malaria. 

 METHODS: Twenty-four women in their second and third trimesters 

 of pregnancy and 24 paired non-pregnant women were enrolled. All 

 patients were treated for uncomplicated Plasmodium falciparum 

 malaria with a standard fixed-dose combination of oral 

 mefloquine and artesunate one daily over 3 days. Frequent blood 

 samples were collected before treatment and at scheduled times 

 post-dose for the drug measurements and pharmacokinetic 

 analyses. The study was registered at www.clinicaltrials.gov 

 (identifier: NCT00701961). RESULTS: The total median exposure to 

 mefloquine and dihydroartemisinin was not significantly 

 different between the pregnant and non-pregnant women (P\>0.05). 

 There was a trend of higher exposure to mefloquine in the 

 pregnant women, but this difference did not reach statistical significance (656700 versus 542400 h $times$ ng/mL; P=0.059). 

 However, the total exposure to carboxymefloquine was 49% lower 

 during pregnancy (735600 versus 1499000 h $times$ ng/mL; 

 P\<0.001) and the total drug exposure to artesunate was 42% 

 higher during pregnancy (89.0 versus 62.9 h $times$ ng/mL; P=0.039) compared with non-pregnant controls. CONCLUSIONS: The 

 plasma levels of mefloquine and dihydroartemisinin appeared to 

 be similar in both pregnant and non-pregnant women, but there 

 were significant differences in carboxymefloquine and artesunate 

 exposure. The data presented here do not warrant a dose 

 adjustment in pregnant patients, but an extensive analysis of 

 the data could provide a better understanding of these findings.},

keywords = {PK; antimalarials; pregnancy},

pubstate = {published},

tppubtype = {article}

}

@article{Scott2014-ew,

title = {Community-based scheduled screening and treatment of malaria in 

 pregnancy for improved maternal and infant health in The Gambia, 

 Burkina Faso and Benin: study protocol for a randomized 

 controlled trial},

author = {Susana Scott and Petra F Mens and Halidou Tinto and Alain Nahum and Esm\'{e}e Ruizendaal and Franco Pagnoni and Koen Peeters Grietens and Lindsay Kendall and Kalifa Bojang and Henk Schallig and Umberto D'Alessandro},

year  = {2014},

date = {2014-08-01},

journal = {Trials},

volume = {15},

number = {1},

pages = {340},

publisher = {Springer Nature},

abstract = {BACKGROUND: In sub-Saharan Africa, malaria continues to cause 

 over 10,000 maternal deaths and 75,000 to 200,000 infant deaths. 

 Successful control of malaria in pregnancy could save lives of 

 mothers and babies and is an essential part of antenatal care in 

 endemic areas. The primary objective is to determine the 

 protective efficacy of community-scheduled screening and 

 treatment (CSST) using community health workers (CHW) against 

 the primary outcome of prevalence of placental malaria. The 

 secondary objectives are to determine the protective efficacy of 

 CSST on maternal anaemia, maternal peripheral infection, low 

 birth weight, selection of sulfadoxine-pyrimethamine (SP) 

 resistance markers, and on antenatal clinic (ANC) attendance and 

 coverage of intermittent preventive treatment during pregnancy 

 (IPTp-SP). METHODS/DESIGN: This is a multi-centre 

 cluster-randomised controlled trial involving three countries 

 with varying malaria endemicity; low (The Gambia) versus high 

 transmission (Burkina Faso and Benin), and varying degrees of SP 

 resistance (high in Benin and moderate in Gambia and Burkina 

 Faso). CHW and their related catchment population who are 

 randomised into the intervention arm will receive specific 

 training on community-based case management of malaria in 

 pregnancy. All women in both study arms will be enrolled at 

 their first ANC visits in their second trimester where they will 

 receive their first dose of IPTp-SP. Thereafter, CHW in the 

 intervention arm will perform scheduled monthly screening and 

 treatment in the womens homes. At time of delivery, a placental 

 biopsy will be collected from all women to determine placental 

 malaria. At each contact point, filter paper and blood slides 

 will be collected for detection of malaria infection and SP 

 resistance markers. DISCUSSION: To reach successful global 

 malaria control, there is an urgent need to access those at 

 greatest risk of malaria infection. The project is designed to 

 develop a low-cost intervention in pregnant women which will 

 have an immediate impact on the malaria burden in 

 resource-limited countries. This will be done by adding to the 

 standard IPTp-SP delivered through the health facilities: an 

 ``extension'' strategy to the communities in rural areas thus 

 bringing health services closer to where women live. TRIAL 

 REGISTRATION: Current Controlled Trials: ISRCTN37259296 (5 July 

 2013), and clinicaltrials.gov: NCT01941264 (10 September 2013).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RTSS_Clinical_Trials_Partnership2014-dl,

title = {Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 

 months after vaccination: a phase 3 randomized, controlled trial 

 in children and young infants at 11 African sites},

author = {S Clinical Trials Partnership RTS},

year  = {2014},

date = {2014-07-01},

journal = {PLoS Med.},

volume = {11},

number = {7},

pages = {e1001685},

abstract = {BACKGROUND: A malaria vaccine could be an important addition to 

 current control strategies. We report the safety and vaccine 

 efficacy (VE) of the RTS,S/AS01 vaccine during 18 mo following 

 vaccination at 11 African sites with varying malaria 

 transmission. METHODS AND FINDINGS: 6,537 infants aged 6-12 wk 

 and 8,923 children aged 5-17 mo were randomized to receive three 

 doses of RTS,S/AS01 or comparator vaccine. VE against clinical 

 malaria in children during the 18 mo after vaccine dose 3 (per 

 protocol) was 46% (95% CI 42% to 50%) (range 40% to 77%; 

 VE, p\<0.01 across all sites). VE during the 20 mo after vaccine 

 dose 1 (intention to treat [ITT]) was 45% (95% CI 41% to 

 49%). VE against severe malaria, malaria hospitalization, and 

 all-cause hospitalization was 34% (95% CI 15% to 48%), 41% 

 (95% CI 30% to 50%), and 19% (95% CI 11% to 27%), 

 respectively (ITT). VE against clinical malaria in infants was 

 27% (95% CI 20% to 32%, per protocol; 27% [95% CI 21% to 

 33%], ITT), with no significant protection against severe 

 malaria, malaria hospitalization, or all-cause hospitalization. 

 Post-vaccination anti-circumsporozoite antibody geometric mean 

 titer varied from 348 to 787 EU/ml across sites in children and 

 from 117 to 335 EU/ml in infants (per protocol). VE waned over 

 time in both age categories (Schoenfeld residuals p\<0.001). The 

 number of clinical and severe malaria cases averted per 1,000 

 children vaccinated ranged across sites from 37 to 2,365 and from 

 -1 to 49, respectively; corresponding ranges among infants were 

 -10 to 1,402 and -13 to 37, respectively (ITT). Meningitis was 

 reported as a serious adverse event in 16/5,949 and 1/2,974 

 children and in 9/4,358 and 3/2,179 infants in the RTS,S/AS01 and 

 control groups, respectively. CONCLUSIONS: RTS,S/AS01 prevented 

 many cases of clinical and severe malaria over the 18 mo after 

 vaccine dose 3, with the highest impact in areas with the 

 greatest malaria incidence. VE was higher in children than in 

 infants, but even at modest levels of VE, the number of malaria 

 cases averted was substantial. RTS,S/AS01 could be an important 

 addition to current malaria control in Africa. TRIAL 

 REGISTRATION: www.ClinicalTrials.gov NCT00866619 Please see later 

 in the article for the Editors' Summary.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2014-zx,

title = {Ex vivo anti-malarial drugs sensitivity profile of Plasmodium 

 falciparum field isolates from Burkina Faso five years after the 

 national policy change},

author = {Halidou Tinto and L\'{e}a N Bonkian and Louis A Nana and Isidore Yerbanga and Moussa Lingani and Adama Kazienga and Innocent Val\'{e}a and Hermann Sorgho and Herv\'{e} Kpoda and Tinga Robert Guiguemd\'{e} and Jean Bosco Ou\'{e}draogo and Petronella F Mens and Henk Schallig and Umberto D'Alessandro},

year  = {2014},

date = {2014-05-01},

journal = {Malar. J.},

volume = {13},

number = {1},

pages = {207},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: The recent reports on the decreasing susceptibility 

 of Plasmodium falciparum to artemisinin derivatives along the 

 Thailand and Myanmar border are worrying. Indeed it may spread 

 to India and then Africa, repeating the same pattern observed 

 for chloroquine resistance. Therefore, it is essential to start 

 monitoring P. falciparum sensitivity to artemisinin derivatives 

 and its partner drugs in Africa. Efficacy of AL and ASAQ were 

 tested by carrying out an in vivo drug efficacy test, with an ex 

 vivo study against six anti-malarial drugs nested into it. 

 Results of the latter are reported here. METHODS: Plasmodium 

 falciparum ex-vivo susceptibility to chloroquine (CQ), quinine 

 (Q), lumefantrine (Lum), monodesethylamodiaquine (MDA), 

 piperaquine (PPQ) and dihydroartemisinin (DHA) was investigated 

 in children (6 months - 15 years) with a parasitaemia of at 

 least $geq$4,000/$mu$l. The modified isotopic microtest 

 technique was used. The results of cellular proliferation were 

 analysed using ICEstimator software to determine the 50% 

 inhibitory concentration (IC50) values. RESULTS: DHA was the 

 most potent among the 6 drugs tested, with IC50 values ranging from 0.8 nM to 0.9 nM (Geometric mean IC50 = 0.8 nM; 95% CI 

 [0.8 - 0.9]). High IC50 values ranged between 0.8 nM to 166.1 nM were reported for lumefantrine (Geometric mean IC50 = 25.1 nM; 

 95% CI [22.4 - 28.2]). MDA and Q IC50s were significantly higher in CQ-resistant than in CQ-sensitive isolates (P = 

 0.0001). However, the opposite occurred for Lum and DHA (P \< 

 0.001). No difference was observed for PPQ. CONCLUSION: 

 Artemisinin derivatives are still very efficacious in Burkina 

 Faso and DHA-PPQ seems a valuable alternative ACT. The high 

 lumefantrine IC50 found in this study is worrying as it may 

 indicate a decreasing efficacy of one of the first-line 

 treatments. This should be further investigated and monitored 

 over time with large in vivo and ex vivo studies that will 

 include also plasma drug measurements.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kajungu2014-md,

title = {Paediatric pharmacovigilance: use of pharmacovigilance data 

 mining algorithms for signal detection in a safety dataset of a 

 paediatric clinical study conducted in seven African countries},

author = {Dan K Kajungu and Annette Erhart and Ambrose Otau Talisuna and Quique Bassat and Corine Karema and Carolyn Nabasumba and Michael Nambozi and Halidou Tinto and Peter Kremsner and Martin Meremikwu and Umberto D'Alessandro and Niko Speybroeck},

year  = {2014},

date = {2014-05-01},

journal = {PLoS One},

volume = {9},

number = {5},

pages = {e96388},

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

abstract = {BACKGROUND: Pharmacovigilance programmes monitor and help 

 ensuring the safe use of medicines which is critical to the 

 success of public health programmes. The commonest method used 

 for discovering previously unknown safety risks is spontaneous 

 notifications. In this study we examine the use of data mining 

 algorithms to identify signals from adverse events reported in a 

 phase IIIb/IV clinical trial evaluating the efficacy and safety 

 of several Artemisinin-based combination therapies (ACTs) for 

 treatment of uncomplicated malaria in African children. METHODS: 

 We used paediatric safety data from a multi-site, multi-country 

 clinical study conducted in seven African countries (Burkina 

 Faso, Gabon, Nigeria, Rwanda, Uganda, Zambia, and Mozambique). 

 Each site compared three out of four ACTs, namely 

 amodiaquine-artesunate (ASAQ), dihydroartemisinin-piperaquine 

 (DHAPQ), artemether-lumefantrine (AL) or chlorproguanil/dapsone 

 and artesunate (CD+A). We examine two pharmacovigilance signal 

 detection methods, namely proportional reporting ratio and 

 Bayesian Confidence Propagation Neural Network on the clinical 

 safety dataset. RESULTS: Among the 4,116 children (6-59 months 

 old) enrolled and followed up for 28 days post treatment, a 

 total of 6,238 adverse events were reported resulting into 346 

 drug-event combinations. Nine signals were generated both by 

 proportional reporting ratio and Bayesian Confidence Propagation 

 Neural Network. A review of the manufacturer package leaflets, 

 an online Multi-Drug Symptom/Interaction Checker (DoubleCheckMD) 

 and further by therapeutic area experts reduced the number of 

 signals to five. The ranking of some drug-adverse reaction pairs 

 on the basis of their signal index differed between the two 

 methods. CONCLUSIONS: Our two data mining methods were equally 

 able to generate suspected signals using the pooled safety data 

 from a phase IIIb/IV clinical trial. This analysis demonstrated 

 the possibility of utilising clinical studies safety data for 

 key pharmacovigilance activities like signal detection and 

 evaluation. This approach can be applied to complement the 

 spontaneous reporting systems which are limited by under 

 reporting.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2014-hc,

title = {Effectiveness of artesunate-amodiaquine vs. 

 artemether-lumefantrine for the treatment of uncomplicated 

 falciparum malaria in Nanoro, Burkina Faso: a non-inferiority 

 randomised trial},

author = {Halidou Tinto and Salou Diallo and Issaka Zongo and Issa Guiraud and Innocent Valea and Adama Kazienga and Herv\'{e} Kpoda and Hermann Sorgho and Jean-Bosco Ou\'{e}draogo and Tinga Robert Guiguemd\'{e} and Umberto D'Alessandro},

year  = {2014},

date = {2014-04-01},

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

volume = {19},

number = {4},

pages = {469--475},

publisher = {Wiley},

abstract = {OBJECTIVES: Artemisinin-based combination therapies (ACTs) are 

 essential for the effective control of falciparum malaria in 

 endemic countries. However, in most countries, such choice has 

 been carried out without knowing their effectiveness when 

 deployed in real-life conditions, that is, when treatment is not 

 directly observed. We report here the results of a study 

 assessing the effectiveness of the two ACTs currently 

 recommended in Burkina Faso for the treatment of uncomplicated 

 malaria, that is, artemether-lumefantrine (AL) and 

 artesunate-amodiaquine (ASAQ). METHODS: Between September 2008 

 and January 2010, 340 children were randomised to one of the two 

 study arms and followed up for 42 days. Treatment was 

 administered according to routine practices, that is, the first 

 dose was given by study nurses who explained to the 

 parent/guardian how to administer the other doses at home during 

 the following 2 days. RESULTS: The results showed a 

 significantly higher unadjusted adequate clinical and 

 parasitological response in the ASAQ (58.4%) than in the AL arm 

 (46.1%) at day 28 but these trends were similar after 

 correction with PCR data (ASAQ (89.7%) and AL (89.8%)). New 

 infections started to appear after day 14, first in the AL and 

 then in the ASAQ arm but at day 42 day of follow-up we observed 

 no difference in the occurrence of recrudescent infection. 

 CONCLUSION: Despite a lower cure rate than those reported in 

 efficacy studies in which the treatment administration was 

 directly observed, both AL and ASAQ can still be used for the 

 treatment of uncomplicated malaria in Burkina Faso.},

keywords = {Burkina Faso; artemisinin-based combination therapies;   effectiveness; uncomplicated malaria},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2014-of,

title = {The impact of clinical research activities on communities in 

 rural Africa: the development of the Clinical Research Unit of 

 Nanoro (CRUN) in Burkina Faso},

author = {Halidou Tinto and Innocent Valea and Hermann Sorgho and Marc Christian Tahita and Maminata Traore and Bi\'{e}bo Bihoun and Issa Guiraud and Herv\'{e} Kpoda and J\'{e}r\'{e}mi Rouamba and Sayouba Ou\'{e}draogo and Palpouguini Lompo and Sandrine Yara and William Kabore and Jean-Bosco Ou\'{e}draogo and Robert Tinga Guiguemd\'{e} and Fred N Binka and Bernhards Ogutu},

year  = {2014},

date = {2014-03-01},

journal = {Malar. J.},

volume = {13},

number = {1},

pages = {113},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: The opportunities for developing new drugs and 

 vaccines for malaria control look brighter now than ten years 

 ago. However, there are few places in sub-Saharan Africa with 

 the necessary infrastructure and expertise to support such 

 research in compliance to international standards of clinical 

 research (ICH-GCP). The Clinical Research Unit of Nanoro (CRUN) 

 was founded in 2008 to provide a much-needed GCP-compliant 

 clinical trial platform for an imminent large-scale Phase 3 

 malaria vaccine trial. A dynamic approach was used that entailed 

 developing the required infrastructure and human resources, 

 while engaging local communities in the process as key 

 stakeholders. This provided a better understanding and ownership 

 of the research activities by the local population. CASE 

 DESCRIPTION: Within five years (2008-2013), the CRUN set up a 

 fully and well-equipped GCP-compliant clinical trial research 

 facility, which enabled to attract 25 grants. The research team 

 grew from ten health workers prior to 2008 to 254 in 2013. A 

 Health and Demographic Surveillance System (HDSS), which covers 

 a total population of about 60,000 people in 24 villages was set 

 up in the district. The local community contributed to the 

 development of the facility through the leadership of the king 

 and the mayor of Nanoro. As a result of their active advocacy, 

 the government extended the national electrical grid to the new 

 research center, and later to the entire village. This produced 

 a positive impact on the community's quality of life. The 

 quality of health care improved substantially, due to the 

 creation of more elaborate clinical laboratory services and the 

 acquisition of state-of-the-art equipment. CONCLUSION: Involving 

 the community in the key steps of establishing the centre 

 provided the foundation for what was to become the CRUN success 

 story. This experience demonstrates that when clinical trials 

 research sites are carefully developed and implemented, they can 

 have a positive and powerful impact on local communities in 

 resource-poor settings, well beyond the task of generating 

 expected study data.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Samadoulougou2014-dk,

title = {Parachecktextregistered rapid diagnostic test for detecting 

 malaria infection in under five children: a population-based 

 survey in Burkina Faso},

author = {Sekou Samadoulougou and Fati Kirakoya-Samadoulougou and Sophie Sarrassat and Halidou Tinto and Fid`ele Bakiono and Issa Nebi\'{e} and Annie Robert},

year  = {2014},

date = {2014-03-01},

journal = {Malar. J.},

volume = {13},

number = {1},

pages = {101},

publisher = {Springer Nature},

abstract = {BACKGROUND: Over the past ten years, Rapid Diagnostic Tests 

 (RDT) played a major role in improving the use of biological 

 malaria diagnosis, in particular in poor-resources settings. In 

 Burkina Faso, a recent Demography and Health Survey (DHS) gave 

 the opportunity to assess the performance of the 

 Parachecktextregistered test in under five children 

 nationwide at community level. METHODS: A national 

 representative sample of 14,947 households was selected using a 

 stratified two-stage cluster sampling. In one out of two 

 households, all under five children were eligible to be tested 

 for malaria using both RDT and microscopy diagnosis. 

 Parachecktextregistered performance was assessed using 

 miscroscopy as the gold standard. Sensitivity and specificity 

 were calculated as well as the diagnosis accuracy (DA) and the 

 Youden index. RESULTS: The malaria infection prevalence was 

 estimated at 66% (95% CI: 64.8-67.2) according to microscopy 

 and at 76.2% (95% CI: 75.1-77.3) according to 

 Parachecktextregistered. The sensitivity and specificity were 

 estimated at 89.9% (95% CI: 89.0-90.8) and 50.4% (95% CI: 

 48.3-52.6) respectively with a Diagnosis Accuracy of 77% and a 

 Youden index of 40%. The positive predictive value for malaria 

 infection was 77.9% (95% CI: 76.7-79.1) and the negative 

 predictive value was 72.1% (95% CI: 69.7-74.3). Variations 

 were found by age group, period of the year and urban and rural 

 areas, as well as across the 13 regions of the country. 

 CONCLUSION: While the sensitivity of the 

 Parachecktextregistered test was high, its specificity was 

 poor in the general under five population of Burkina Faso. These 

 results suggest that Parachecktextregistered is not suitable 

 to assess malaria infection prevalence at community level in 

 areas with high malaria transmission. In such settings, malaria 

 prevalence in the general population could be estimated using 

 microscopy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Maltha2014-wh,

title = {Frequency of severe malaria and invasive bacterial infections 

 among children admitted to a rural hospital in Burkina Faso},

author = {Jessica Maltha and Issa Guiraud and B\'{e}renger Kabor\'{e} and Palpouguini Lompo and Benedikt Ley and Emmanuel Bottieau and Chris Van Geet and Halidou Tinto and Jan Jacobs},

year  = {2014},

date = {2014-02-01},

journal = {PLoS One},

volume = {9},

number = {2},

pages = {e89103},

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

abstract = {BACKGROUND: Although severe malaria is an important cause of 

 mortality among children in Burkina Faso, data on 

 community-acquired invasive bacterial infections (IBI, 

 bacteremia and meningitis) are lacking, as well as data on the 

 involved pathogens and their antibiotic resistance rates. 

 METHODS: The present study was conducted in a rural hospital and 

 health center in Burkina Faso, in a seasonal malaria 

 transmission area. Hospitalized children (\<15 years) presenting 

 with T$geq$38.0°C and/or signs of severe illness were enrolled 

 upon admission. Malaria diagnosis and blood culture were 

 performed for all participants, lumbar puncture when clinically 

 indicated. We assessed the frequency of severe malaria 

 (microscopically confirmed, according to World Health 

 Organization definitions) and IBI, and the species distribution 

 and antibiotic resistance of the bacterial pathogens causing 

 IBI. RESULTS: From July 2012 to July 2013, a total of 711 

 patients were included. Severe malaria was diagnosed in 292 

 (41.1%) children, including 8 (2.7%) with IBI co-infection. IBI was demonstrated in 67 (9.7%) children (bacteremi},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Maltha2014-xp,

title = {Accuracy of PfHRP2 versus Pf-pLDH antigen detection by 

 malaria rapid diagnostic tests in hospitalized children in a 

 seasonal hyperendemic malaria transmission area in Burkina Faso},

author = {Jessica Maltha and Issa Guiraud and Palpouguini Lompo and B\'{e}renger Kabor\'{e} and Philippe Gillet and Chris Van Geet and Halidou Tinto and Jan Jacobs},

year  = {2014},

date = {2014-01-01},

journal = {Malar. J.},

volume = {13},

number = {1},

pages = {20},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: In most sub-Saharan African countries malaria rapid 

 diagnostic tests (RDTs) are now used for the diagnosis of 

 malaria. Most RDTs used detect Plasmodium falciparum 

 histidine-rich protein-2 (PfHRP2), though P. falciparum-specific 

 parasite lactate dehydrogenase (Pf-pLDH)-detecting RDTs may have 

 advantages over PfHRP2-detecting RDTs. Only few data are 

 available on the use of RDTs in severe illness and the present 

 study compared Pf-pLDH to PfHRP2-detection. METHODS: 

 Hospitalized children aged one month to 14 years presenting with 

 fever or severe illness were included over one year. Venous 

 blood samples were drawn for malaria diagnosis (microscopy and 

 RDT), culture and complete blood count. Leftovers were stored at 

 -80 °C and used for additional RDT analysis and PCR. An RDT 

 targeting both PfHRP2 and Pf-pLDH was performed on all samples 

 for direct comparison of diagnostic accuracy with microscopy as 

 reference method. PCR was performed to explore false-positive 

 RDT results. RESULTS: In 376 of 694 (54.2%) included children, 

 malaria was microscopically confirmed. Sensitivity, specificity, 

 positive predictive value (PPV) and negative predictive value 

 were 100.0, 70.9, 69.4 and 100.0%, respectively for 

 PfHRP2-detection and 98.7, 94.0, 91.6 and 99.1%, respectively 

 for Pf-pLDH-detection. Specificity and PPV were significantly 

 lower for PfHRP2-detection (p \<0.001). For both detection 

 antigens, specificity was lowest for children one to five years 

 and in the rainy season. PPV for both antigens was highest in 

 the rainy season, because of higher malaria prevalence. False 

 positive PfHRP2 results were associated with prior anti-malarial 

 treatment and positive PCR results (98/114 (86.0%) samples 

 tested). CONCLUSION: Among children presenting with severe 

 febrile illness in a seasonal hyperendemic malaria transmission 

 area, the present study observed similar sensitivity but lower 

 specificity and PPV of PfHRP2 compared to Pf-pLDH-detection. 

 Further studies should assess the diagnostic accuracy and safety 

 of an appropriate Pf-pLDH-detecting RDT in field settings and if 

 satisfying, replacement of PfHRP2 by Pf-pLDH-detecting RDTs 

 should be considered.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tahita2013-vk,

title = {Clinical signs and symptoms cannot reliably predict Plasmodium 

 falciparum malaria infection in pregnant women living in an area 

 of high seasonal transmission},

author = {Marc C Tahita and Halidou Tinto and Joris Menten and Jean-Bosco Ouedraogo and Robert T Guiguemde and Jean Pierre Geertruyden and Annette Erhart and Umberto D'Alessandro},

year  = {2013},

date = {2013-12-01},

journal = {Malar. J.},

volume = {12},

number = {1},

pages = {464},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Malaria in pregnancy is a major public health 

 problem in endemic countries. Though the signs and symptoms of 

 malaria among pregnant women have been already described, 

 clinical presentation may vary according to intensity of 

 transmission and local perceptions. Therefore, determining 

 common signs and symptoms among pregnant women with a malaria 

 infection may be extremely useful to identify those in need of 

 further investigation by rapid diagnostic test or microscopy. 

 METHODS: Six hundred pregnant women attending the maternity 

 clinic of Nanoro District Hospital, Burkina Faso were recruited, 

 200 with suspected clinical malaria and 400 as controls. Cases 

 were matched with controls by gestational age and parity. Signs 

 and symptoms were collected and a blood sample taken for rapid 

 diagnostic test, microscopy and haemoglobin measurement. A 

 multivariate model was used to assess the predictive value of 

 signs and symptoms for malaria infection. RESULTS: The overall 

 prevalence of malaria was 42.6% (256/600) while anaemia was 

 found in 60.8% (365/600) of the women. Nearly half (49%) of 

 the cases and 39.5% of the controls had a malaria infection (p = 0.03). The most common signs and symptoms among the cases were 

 fever (36%,72/200), history of fever (29%,58/200) and headache 

 (52%,104/200). The positive predictive value for fever was 53% 

 (95% CI:41-64), history of fever 58% (95% CI:37-63) and 

 headache 51% (95% CI:41-61). CONCLUSION: Signs and symptoms 

 suggestive of malaria are frequent among pregnant women living 

 in areas of intense transmission. Common malaria symptoms are 

 not strong predictors of infection. For a better management of 

 malaria in pregnancy, active screening to detect and treat 

 malaria infection early should be performed on all pregnant 

 women attending a health facility.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Pare_Toe2013-vh,

title = {Could the decision of trial participation precede the informed 

 consent process? Evidence from Burkina Faso},

author = {Lea Par\'{e} Toe and Raffaella M Ravinetto and Susan Dierickx and Charlotte Gryseels and Halidou Tinto and No`el Rouamba and Ibrahim Diallo and Yacouba Cissao and Korotimi Bayala and Susanna Hausmann and Joan Muela and Umberto D'Alessandro and Koen Peeters Grietens},

year  = {2013},

date = {2013-11-01},

journal = {PLoS One},

volume = {8},

number = {11},

pages = {e80800},

abstract = {BACKGROUND: Over the last years, the number of clinical trials 

 carried out in low-income countries with poor medical 

 infrastructure and limited access to health care has increased. 

 In these settings, the decision of participating in a clinical 

 study may be influenced by factors related to participants' 

 vulnerability that limit the efficacy of the informed consent. 

 METHODS: A mixed methods social science study, based on the 

 triangulation of qualitative and quantitative data, was carried 

 out in a socio-economically disadvantaged and semi-urban area of 

 Bobo Dioulasso, Burkina Faso. The study aimed at assessing the 

 relevance of the informed consent procedure on the 

 decision-making process of the parents and/or guardians of 

 potential participants in a pediatric malaria trial. RESULTS: For 

 most parents (70.4%), the decision of participating had already 

 been taken before undergoing the informed consent process and was 

 based on the information conveyed through the community. Access 

 to free and good quality health care often inspired this 

 decision. In addition, the parents' willingness to have their 

 child included in the trial made them develop active strategies 

 to achieve this purpose. DISCUSSION: In a context of 

 socio-economic vulnerability and poor access to free health care, 

 the process of informed consent does not always accomplish its 

 goal of informing people and enabling them to make a free and 

 informed decision. This information role is somehow anticipated 

 by the community and trial participation becomes a strategic 

 action to secure otherwise unavailable health resources leading 

 community members to decide on participation even prior to the 

 informed consent process.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Muhindo_Mavoko2013-hc,

title = {Impact of retreatment with an artemisinin-based combination on 

 malaria incidence and its potential selection of resistant 

 strains: study protocol for a randomized controlled clinical 

 trial},

author = {Hypolite Muhindo Mavoko and Carolyn Nabasumba and Halidou Tinto and Umberto D'Alessandro and Martin Peter Grobusch and Pascal Lutumba and Jean-Pierre Van Geertruyden},

year  = {2013},

date = {2013-09-01},

journal = {Trials},

volume = {14},

number = {1},

pages = {307},

publisher = {Springer Nature},

abstract = {BACKGROUND: Artemisinin-based combination therapy is currently 

 recommended by the World Health Organization as first-line 

 treatment of uncomplicated malaria. Recommendations were adapted 

 in 2010 regarding rescue treatment in case of treatment failure. 

 Instead of quinine monotherapy, it should be combined with an 

 antibiotic with antimalarial properties; alternatively, another 

 artemisinin-based combination therapy may be used. However, for 

 informing these policy changes, no clear evidence is yet 

 available. The need to provide the policy makers with hard data 

 on the appropriate rescue therapy is obvious. We hypothesize 

 that the efficacy of the same artemisinin-based combination 

 therapy used as rescue treatment is as efficacious as quinine + 

 clindamycin or an alternative artemisinin-based combination 

 therapy, without the risk of selecting drug resistant strains. 

 DESIGN: We embed a randomized, open label, three-arm clinical 

 trial in a longitudinal cohort design following up children with 

 uncomplicated malaria until they are malaria parasite free for 4 

 weeks. The study is conducted in both the Democratic Republic of 

 Congo and Uganda and performed in three steps. In the first 

 step, the pre-randomized controlled trial (RCT) phase, children 

 aged 12 to 59 months with uncomplicated malaria are treated with 

 the recommended first-line drug and constitute a cohort that is 

 passively followed up for 42 days. If the patients experience an 

 uncomplicated malaria episode between days 14 and 42 of 

 follow-up, they are randomized either to quinine + clindamycin, 

 or an alternative artemisinin-based combination therapy, or the 

 same first-line artemisinin-based combination therapy to be 

 followed up for 28 additional days. If between days 14 and 28 

 the patients experience a recurrent parasitemia, they are 

 retreated with the recommended first-line regimen and actively 

 followed up for another 28 additional days (step three; post-RCT 

 phase). The same methodology is followed for each subsequent 

 failure. In any case, all patients without an infection at day 

 28 are classified as treatment successes and reach a study 

 endpoint. The RCT phase allows the comparison of the safety and 

 efficacy of three rescue treatments. The prolonged follow-up of 

 all children until they are 28 days parasite-free allows us to 

 assess epidemiological-, host- and parasite-related predictors 

 for repeated malaria infection. TRIAL REGISTRATION: NCT01374581 

 and PACTR201203000351114.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}