@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}

}

@article{Henriques2013-ee,

title = {Artemisinin resistance in rodent malaria--mutation in the AP2 

 adaptor $mu$-chain suggests involvement of endocytosis and 

 membrane protein trafficking},

author = {Gisela Henriques and Axel Martinelli and Louise Rodrigues and Katarzyna Modrzynska and Richard Fawcett and Douglas R Houston and Sofia T Borges and Umberto d'Alessandro and Halidou Tinto and Corine Karema and Paul Hunt and Pedro Cravo},

year  = {2013},

date = {2013-04-01},

journal = {Malar. J.},

volume = {12},

number = {1},

pages = {118},

publisher = {Springer Nature},

abstract = {BACKGROUND: The control of malaria, caused by Plasmodium 

 falciparum, is hampered by the relentless evolution of drug 

 resistance. Because artemisinin derivatives are now used in the 

 most effective anti-malarial therapy, resistance to artemisinin 

 would be catastrophic. Indeed, studies suggest that artemisinin 

 resistance has already appeared in natural infections. 

 Understanding the mechanisms of resistance would help to prolong 

 the effective lifetime of these drugs. Genetic markers of 

 resistance are therefore required urgently. Previously, a 

 mutation in a de-ubiquitinating enzyme was shown to confer 

 artemisinin resistance in the rodent malaria parasite Plasmodium 

 chabaudi. METHODS: Here, for a mutant P. chabaudi malaria 

 parasite and its immediate progenitor, the in vivo artemisinin 

 resistance phenotypes and the mutations arising using Illumina 

 whole-genome re-sequencing were compared. RESULTS: An increased 

 artemisinin resistance phenotype is accompanied by one 

 non-synonymous substitution. The mutated gene encodes the 

 $mu$-chain of the AP2 adaptor complex, a component of the 

 endocytic machinery. Homology models indicate that the mutated 

 residue interacts with a cargo recognition sequence. In natural 

 infections of the human malaria parasite P. falciparum, 12 

 polymorphisms (nine SNPs and three indels) were identified in 

 the orthologous gene. CONCLUSION: An increased 

 artemisinin-resistant phenotype occurs along with a mutation in 

 a functional element of the AP2 adaptor protein complex. This 

 suggests that endocytosis and trafficking of membrane proteins 

 may be involved, generating new insights into possible 

 mechanisms of resistance. The genotypes of this adaptor protein 

 can be evaluated for its role in artemisinin responses in human 

 infections of P. falciparum.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2013-rv,

title = {Good clinical practice in resource-limited settings: translating 

 theory into practice},

author = {Halidou Tinto and Ramadhani A Noor and Charles L Wanga and Innocent Valea and Maimouna Ndour Mbaye and Umberto D'Alessandro and Raffaella M Ravinetto},

year  = {2013},

date = {2013-04-01},

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

volume = {88},

number = {4},

pages = {608--613},

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

abstract = {A Good Clinical Practices (GCPs) course, based on the 

 combination of theoretical modules with a practical training in 

 real-life conditions, was held in 2010 in Burkina Faso. It was 

 attended by 15 trainees from nine African, Asian, and Latin 

 American countries. There were some discrepancies between the 

 average good results at the end of the theoretical phase and the 

 GCP application during the first days of the practical phase, 

 underlying the difficulties of translating theoretical knowledge 

 into good practices. Most of the findings were not unexpected 

 and reflected the challenges commonly faced by clinical 

 investigators in resource-poor contexts (i.e., the high workload 

 at peripheral health facilities, the need to conciliate routine 

 clinical activities with clinical research, and the risk of 

 creating a double standard among patients attending the same 

 health facility [free care for recruited patients versus user 

 fees for non-recruited patients with the same medical 

 condition]). Even if limited in number and time, these 

 observations suggest that a theoretical training alone may not 

 be sufficient to prepare trainees for the challenges of medical 

 research in real-life settings. Conversely, when a practical 

 phase immediately follows a theoretical one, trainees can 

 immediately experience what the research methodology implicates 

 in terms of work organization and relationship with recruited 

 and non-recruited patients. This initial experience shows the 

 complexity of translating GCP into practice and suggests the 

 need to rethink the current conception of GCP training.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bamba2013-ua,

title = {Traitement pr\'{e}ventif intermittent `a la sulfadoxine -- 

 pyrim\'{e}thamine du paludisme chez les femmes enceintes: 

 efficacit\'{e} et observance dans deux h^opitaux urbains du 

 Burkina Faso},

author = {Sanata Bamba and Adama S\'{e}r\'{e} and Rodrigues Niki\'{e}ma and Tinto Halidou and Blandine Thi\'{e}ba and Blami Dao and Robert Tinga Guiguemd\'{e}},

year  = {2013},

date = {2013-03-01},

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

volume = {14},

pages = {105},

publisher = {Pan African Medical Journal},

keywords = {Burkina Faso; Grossesse; Intermittent Preventive Treatment;   Malaria; effectiveness; observance; pyrimethamine; sulfadoxine;   woman},

pubstate = {published},

tppubtype = {article}

}

@article{Bisoffi2013-bz,

title = {Should malaria treatment be guided by a point of care rapid 

 test? A threshold approach to malaria management in rural 

 Burkina Faso},

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

year  = {2013},

date = {2013-03-01},

journal = {PLoS One},

volume = {8},

number = {3},

pages = {e58019},

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

abstract = {BACKGROUND: In Burkina Faso, rapid diagnostic tests for malaria 

 have been made recently available. Previously, malaria was 

 managed clinically. This study aims at assessing which is the 

 best management option of a febrile patient in a hyperendemic 

 setting. Three alternatives are: treating presumptively, 

 testing, or refraining from both test and treatment. The test 

 threshold is the tradeoff between refraining and testing, the 

 test-treatment threshold is the tradeoff between testing and 

 treating. Only if the disease probability lies between the two 

 should the test be used. METHODS AND FINDINGS: Data for this 

 analysis was obtained from previous studies on malaria rapid 

 tests, involving 5220 patients. The thresholds were calculated, 

 based on disease risk, treatment risk and cost, test accuracy 

 and cost. The thresholds were then matched against the disease 

 probability. For a febrile child under 5 in the dry season, the 

 pre-test probability of clinical malaria (3.2%), was just above 

 the test/treatment threshold. In the rainy season, that 

 probability was 63%, largely above the test/treatment 

 threshold. For febrile children \>5 years and adults in the dry 

 season, the probability was 1.7%, below the test threshold, 

 while in the rainy season it was higher (25.1%), and situated 

 between the two thresholds (3% and 60.9%), only if costs were 

 not considered. If they were, neither testing nor treating with 

 artemisinin combination treatments (ACT) would be recommended. 

 CONCLUSIONS: A febrile child under 5 should be treated 

 presumptively. In the dry season, the probability of clinical 

 malaria in adults is so low, that neither testing nor treating 

 with any regimen should be recommended. In the rainy season, if 

 costs are considered, a febrile adult should not be tested, nor 

 treated with ACT, but a possible alternative would be a 

 presumptive treatment with amodiaquine plus 

 sulfadoxine-pyrimethamine. If costs were not considered, testing 

 would be recommended.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ravinetto2013-hg,

title = {Challenges of non-commercial multicentre North-South 

 collaborative clinical trials},

author = {Raffaella M Ravinetto and Ambrose Talisuna and Maaike De Crop and Harry Loen and Joris Menten and Chantal Van Overmeir and Halidou Tinto and Raquel Gonzalez and Martin Meremikwu and Carolyn Nabasuma and Ghyslain M Ngoma and Corine Karema and Yeka Adoke and Mike Chaponda and Jean-Pierre Van Geertruyden and Umberto D'Alessandro},

year  = {2013},

date = {2013-02-01},

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

volume = {18},

number = {2},

pages = {237--241},

publisher = {Wiley},

abstract = {The last decade has witnessed a substantial increase of 

 multi-centre, public health-oriented clinical trials in poor 

 countries. However, non-commercial research groups have less 

 staff and financial resources than traditional commercial 

 sponsors, so the trial teams have to be creative to comply with 

 Good Clinical Practices (GCP) requirements. According to the 

 recent experience of a large multicentre trial on antimalarials, 

 major challenges result from the complexity of multiple ethical 

 review, the costs of in-depth monitoring at several sites, 

 setting up an adequate Good Clinical Laboratory Practices (GCLP) 

 framework, lack of insurers in host countries, and lack of 

 adequate non-commercial data management software. Public 

 research funding agencies need to consider these challenges in 

 their funding policies. They also could support common spaces 

 where North-South collaborative research groups may share 

 critical information, such as on research insurance and 

 open-source, GCP-compliant software. WHO should update its GCP 

 guidelines, which date back to 1995, to incorporate the 

 perspectives and needs of non-commercial clinical research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ye2013-vs,

title = {Malaria mortality estimates: need for agreeable approach},

author = {Yazoume Ye and Catherine Kyobutungi and Bernhards Ogutu and Leopoldo Villegas and Diadier Diallo and Halidou Tinto and Abraham Oduro and Osman Sankoh},

year  = {2013},

date = {2013-02-01},

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

volume = {18},

number = {2},

pages = {219--221},

publisher = {Wiley},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RTSS_Clinical_Trials_Partnership2012-am,

title = {A phase 3 trial of RTS,S/AS01 malaria vaccine in African 

 infants},

author = {S Clinical Trials Partnership RTS and Selidji Todagbe Agnandji and Bertrand Lell and Jos\'{e} Francisco Fernandes and B\'{e}atrice Peggy Abossolo and Barbara Gaelle Nfono Ondo Methogo and Anita Lumeka Kabwende and Ayola Akim Adegnika 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 Sonia Machevo and Sozinho Acacio and Helder Bulo and Betuel Sigauque and Eus\'{e}bio Macete and Pedro Alonso and Salim Abdulla and Nahya Salim and Rose Minja and Maxmillian Mpina and Saumu Ahmed and Ali Mohammed Ali and Ali Takadir Mtoro and Ali Said Hamad and Paul Mutani and Marcel Tanner and Halidou Tinto and Umberto D'Alessandro and Hermann Sorgho and Innocent Valea and Bi\'{e}bo Bihoun and Issa Guiraud and Berenger Kabor\'{e} and Olivier Sombi\'{e} and Robert Tinga Guiguemd\'{e} and Jean Bosco Ou\'{e}draogo and Mary J Hamel and Simon Kariuki and Martina Oneko and Chris Odero and Kephas Otieno and Norbert Awino and Meredith McMorrow and Vincent Muturi-Kioi and Kayla F Laserson and Laurence Slutsker and Walter Otieno and Lucas Otieno and Nekoye Otsyula and Stacey Gondi and Allan Otieno and Victorine Owira and Esther Oguk and George Odongo and Jon Ben Woods and Bernhards Ogutu and Patricia Njuguna and Roma Chilengi and Pauline Akoo and Christine Kerubo and Charity Maingi and Trudie Lang and Ally Olotu and Philip Bejon and Kevin Marsh and Gabriel Mwambingu and Seth Owusu-Agyei and Kwaku Poku Asante and Kingsley Osei-Kwakye and Owusu Boahen and David Dosoo and Isaac Asante and George Adjei and Evans Kwara and Daniel Chandramohan and Brian Greenwood and John Lusingu and Samwel Gesase and Anangisye Malabeja and Omari Abdul and Coline Mahende and Edwin Liheluka and Lincoln Malle and Martha Lemnge and Thor G 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 Anima Sarfo and Alex Agyekum and Francis Martinson and Irving Hoffman and Tisungane Mvalo and Portia Kamthunzi and Rutendo Nkomo and Tapiwa Tembo and Gerald Tegha and Mercy Tsidya and Jane Kilembe and Chimwemwe Chawinga and W Ripley Ballou and Joe Cohen and Yolanda Guerra and Erik Jongert and Didier Lapierre and Amanda Leach and Marc Lievens and Opokua Ofori-Anyinam and Aur\'{e}lie Olivier and Johan Vekemans and Terrell Carter and David Kaslow and Didier Leboulleux and Christian Loucq and Afiya Radford and Barbara Savarese and David Schellenberg and Marla Sillman and Preeti Vansadia},

year  = {2012},

date = {2012-12-01},

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

volume = {367},

number = {24},

pages = {2284--2295},

abstract = {BACKGROUND: The candidate malaria vaccine RTS,S/AS01 reduced 

 episodes of both clinical and severe malaria in children 5 to 17 

 months of age by approximately 50% in an ongoing phase 3 trial. 

 We studied infants 6 to 12 weeks of age recruited for the same 

 trial. METHODS: We administered RTS,S/AS01 or a comparator 

 vaccine to 6537 infants who were 6 to 12 weeks of age at the time 

 of the first vaccination in conjunction with Expanded Program on 

 Immunization (EPI) vaccines in a three-dose monthly schedule. 

 Vaccine efficacy against the first or only episode of clinical 

 malaria during the 12 months after vaccination, a coprimary end 

 point, was analyzed with the use of Cox regression. Vaccine 

 efficacy against all malaria episodes, vaccine efficacy against 

 severe malaria, safety, and immunogenicity were also assessed. 

 RESULTS: The incidence of the first or only episode of clinical 

 malaria in the intention-to-treat population during the 14 months 

 after the first dose of vaccine was 0.31 per person-year in the 

 RTS,S/AS01 group and 0.40 per person-year in the control group, 

 for a vaccine efficacy of 30.1% (95% confidence interval [CI], 

 23.6 to 36.1). Vaccine efficacy in the per-protocol population 

 was 31.3% (97.5% CI, 23.6 to 38.3). Vaccine efficacy against 

 severe malaria was 26.0% (95% CI, -7.4 to 48.6) in the 

 intention-to-treat population and 36.6% (95% CI, 4.6 to 57.7) 

 in the per-protocol population. Serious adverse events occurred 

 with a similar frequency in the two study groups. One month after 

 administration of the third dose of RTS,S/AS01, 99.7% of 

 children were positive for anti-circumsporozoite antibodies, with 

 a geometric mean titer of 209 EU per milliliter (95% CI, 197 to 

 222). CONCLUSIONS: The RTS,S/AS01 vaccine coadministered with EPI 

 vaccines provided modest protection against both clinical and 

 severe malaria in young infants. (Funded by GlaxoSmithKline 

 Biologicals and the PATH Malaria Vaccine Initiative; RTS,S 

 ClinicalTrials.gov number, NCT00866619.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Derra2012-bz,

title = {Profile: Nanoro Health and Demographic Surveillance System},

author = {Karim Derra and Eli Rouamba and Adama Kazienga and Sayouba Ouedraogo and Marc C Tahita and Hermann Sorgho and Innocent Valea and Halidou Tinto},

year  = {2012},

date = {2012-10-01},

journal = {Int. J. Epidemiol.},

volume = {41},

number = {5},

pages = {1293--1301},

publisher = {Oxford University Press (OUP)},

abstract = {The Nanoro Health and Demographic Surveillance System (HDSS), 

 located in the rural centre of Burkina Faso, was established in 

 2009 by the Clinical Research Unit of Nanoro with the aim of 

 providing a core framework for clinical trials and also to 

 support the Burkina Faso health authorities in generating 

 epidemiological data that can contribute to the setup and 

 assessment of health interventions. In the baseline of initial 

 census, 54 781 individuals were recorded of whom 56.1% are 

 female. After the initial census, vital events such as 

 pregnancies, births, migrations and deaths have been monitored, 

 and data on individuals and household characteristics are 

 updated during regular 4-monthly household visits. The available 

 data are categorized into demographic, cultural, socio-economic 

 and health information, and are used for monitoring and 

 evaluation of population development issues. As a young site, 

 our objective has been to strengthen our skills and knowledge 

 and share new scientific experiences with INDEPTH and HDSS sites 

 in Burkina Faso. In addition, all data produced by the Nanoro 

 HDSS will be made publicly available through the INDEPTH data 

 sharing system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kattenberg2012-oz,

title = {Evaluation of antigen detection tests, microscopy, and 

 polymerase chain reaction for diagnosis of malaria in peripheral 

 blood in asymptomatic pregnant women in Nanoro, Burkina Faso},

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

year  = {2012},

date = {2012-08-01},

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

volume = {87},

number = {2},

pages = {251--256},

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

abstract = {Rapid diagnostics tests (RDTs) detect malaria specific 

 antigen(s) in the circulation, even when parasites are 

 sequestered in the placenta and not visible by microscopy. 

 However, research on their diagnostic accuracy during pregnancy is limited. Pregnant women (n = 418) were screened for malaria 

 during routine antenatal care by using two RDTs that detect 

 histidine-rich protein 2 (HRP2) or Plasmodium lactate 

 dehydrogenase, and enzyme-linked immunosorbent assays with 

 antibodies that detect dihydrofolate reductase-thymidylate 

 synthase or heme-detoxification protein, and compared with 

 real-time polymerase chain reaction (RT-PCR) and microscopy for 

 evaluation of their diagnostic accuracy. Prevalence of malaria 

 infection was high (53% by PCR). The RT-PCR and the HRP2 RDT 

 detected most cases of malaria during pregnancy, whereas 

 microscopy, the Plasmodium lactate dehydrogenase RDT, and 

 enzyme-linked immunosorbent assays for dihydrofolate 

 reductase-thymidylate synthase and heme-detoxification protein 

 antibodies did not detect several low-density infections. 

 Therefore, the HRP2 RDT could be a useful tool in 

 high-transmission areas for diagnosis of malaria in asymptomatic 

 pregnant women.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}