@article{PREGACT_Study_Group2016-hk,

title = {Four artemisinin-based treatments in African pregnant women with 

 malaria},

author = {PREGACT Study Group and Divine Pekyi and Akua A Ampromfi and Halidou Tinto and Maminata Traor\'{e}-Coulibaly and Marc C Tahita and Innocent Val\'{e}a and Victor Mwapasa and Linda Kalilani-Phiri and Gertrude Kalanda and Mwayiwawo Madanitsa and Raffaella Ravinetto and Theonest Mutabingwa and Prosper Gbekor and Harry Tagbor and Gifty Antwi and Joris Menten and Maaike De Crop and Yves Claeys and Celine Schurmans and Chantal Van Overmeir and Kamala Thriemer and Jean-Pierre Van Geertruyden and Umberto D'Alessandro and Michael Nambozi and Modest Mulenga and Sebastian Hachizovu and Jean-Bertin B Kabuya and Joyce Mulenga},

year  = {2016},

date = {2016-09-01},

journal = {Malawi Med. J.},

volume = {28},

number = {3},

pages = {139--149},

abstract = {BACKGROUND: Information regarding the safety and efficacy of 

 artemisinin combination treatments for malaria in pregnant women 

 is limited, particularly among women who live in sub-Saharan 

 Africa. METHODS: We conducted a multicenter, randomized, 

 open-label trial of treatments for malaria in pregnant women in 

 four African countries. A total of 3428 pregnant women in the 

 second or third trimester who had falciparum malaria (at any 

 parasite density and regardless of symptoms) were treated with 

 artemether-lumefantrine, amodiaquine-artesunate, 

 mefloquine-artesunate, or dihydroartemisinin-piperaquine. The 

 primary end points were the polymerase-chain-reaction 

 (PCR)-adjusted cure rates (i.e., cure of the original infection; 

 new infections during follow-up were not considered to be 

 treatment failures) at day 63 and safety outcomes. RESULTS: The 

 PCR-adjusted cure rates in the per-protocol analysis were 94.8% 

 in the artemether-lumefantrine group, 98.5% in the 

 amodiaquine-artesunate group, 99.2% in the 

 dihydroartemisinin-piperaquine group, and 96.8% in the 

 mefloquine-artesunate group; the PCR-adjusted cure rates in the 

 intention-to-treat analysis were 94.2%, 96.9%, 98.0%, and 

 95.5%, respectively. There was no significant difference among 

 the amodiaquine-artesunate group, dihydroartemisinin-piperaquine 

 group, and the mefloquine-artesunate group. The cure rate in the 

 artemether-lumefantrine group was significantly lower than that 

 in the other three groups, although the absolute difference was 

 within the 5-percentage-point margin for equivalence. The 

 unadjusted cure rates, used as a measure of the post-treatment 

 prophylactic effect, were significantly lower in the 

 artemether-lumefantrine group (52.5%) than in groups that 

 received amodiaquine-artesunate (82.3%), 

 dihydroartemisinin-piperaquine (86.9%), or mefloquine-artesunate 

 (73.8%). No significant difference in the rate of serious 

 adverse events and in birth outcomes was found among the 

 treatment groups. Drug-related adverse events such as asthenia, 

 poor appetite, dizziness, nausea, and vomiting occurred 

 significantly more frequently in the mefloquine-artesunate group 

 (50.6%) and the amodiaquine-artesunate group (48.5%) than in 

 the dihydroartemisinin-piperaquine group (20.6%) and the 

 artemether-lumefantrine group (11.5%) (P\<0.001 for comparison 

 among the four groups). CONCLUSIONS: Artemether-lumefantrine was 

 associated with the fewest adverse effects and with acceptable 

 cure rates but provided the shortest posttreatment prophylaxis, 

 whereas dihydroartemisinin-piperaquine had the best efficacy and 

 an acceptable safety profile. (Funded by the European and 

 Developing Countries Clinical Trials Partnership and others; 

 ClinicalTrials.gov number, NCT00852423.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kiemde2016-qv,

title = {Aetiologies of non-malaria febrile episodes in children under 5 

 years in sub-Saharan Africa},

author = {Francois Kiemde and Ren\'{e} Spijker and Petra F Mens and Halidou Tinto and Michael Boele and Henk D F H Schallig},

year  = {2016},

date = {2016-08-01},

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

volume = {21},

number = {8},

pages = {943--955},

publisher = {Wiley},

abstract = {OBJECTIVES: To provide an overview of the most frequent 

 aetiologies found in febrile episodes of children under 5 years 

 from sub-Saharan Africa. METHODS: MEDLINE and EMBASE were 

 searched for publications in English and French on non-malaria 

 fever episodes in African children under 5 years of age, which 

 were published between January 1990 and July 2015. Case reports 

 and conference abstracts were excluded. RESULTS: In total, 3851 

 titles and abstracts were reviewed, and 153 were selected for 

 full screening of which 18 were included in the present review. 

 Bloodstream infection (BSI) was most commonly investigated (nine 

 of 18) followed by urinary tract infection (UTI) (four of 18) 

 and respiratory tract infection (RTI) (two of 18). Few studies 

 investigated BSI and UTI in the same children (two of 18), or 

 BSI and gastrointestinal infection (GII) (one of 18). As for 

 BSI, the most frequently isolated bacteria were E. coli (four of 

 12), Streptococcus pneumonia (four of 12), Salmonella spp (three 

 of 12) and Staphylococcus aureus (two of 12) with a positive 

 identification rate of 19.7-33.3%, 5.2-27.6%, 11.7-65.4% and 

 23.5-42.0%, respectively. As for UTI, the main bacteria 

 isolated were E. coli (six of six) and Klebsiella spp (six of 

 six) with a positive rate of 20.0-72.3% and 10.0-28.5%, 

 respectively. No bacterium was isolated in RTI group, but Human 

 influenzae A and B were frequently found, with the highest 

 positive identification rate in Tanzania (75.3%). Dengue virus 

 (two of 12) was the most frequently reported viral infection 

 with a positive identification rate of 16.7-30.8%. Finally, 

 only rotavirus/adenovirus (69.2% positive identification rate) 

 was found in GII and no bacterium was isolated in this group. 

 CONCLUSIONS: The high prevalence of treatable causes of 

 non-malaria fever episodes requires a proper diagnosis of the 

 origin of fever followed by an appropriate treatment, thereby 

 reducing the under-5 mortality in sub-Saharan Africa and 

 preventing the overprescription of antibiotics and thus 

 circumventing the rise of antibiotic resistance.},

keywords = {Afrique subsaharienne; aetiology; children; enfants;   etiolog{'i}a; fever; fiebre; fi{`e}vre; malaria; ni{~n}os;   paludisme; sub-Saharan Africa; {\'{A}}frica subsahariana;   {\'{e}}tiologie},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Aetiologies of non-malaria febrile episodes in children under 5 years in sub-Saharan Africa.},

author = {Francois Kiemde and Ren\'{e} Spijker and Petra F. Mens and Halidou Tinto and Michael Boele and Henk D. F. H. Schallig},

year  = {2016},

date = {2016-08-01},

journal = {Tropical medicine \& international health : TM \& IH},

volume = {21},

issue = {8},

pages = {943-955},

address = {England},

abstract = {OBJECTIVES: To provide an overview of the most frequent aetiologies found in febrile episodes of children under 5 years from sub-Saharan Africa. METHODS: MEDLINE and EMBASE were searched for publications in English and French on non-malaria fever episodes in African children under 5 years of age, which were published between January 1990 and July 2015. Case reports and conference abstracts were excluded. RESULTS: In total, 3851 titles and abstracts were reviewed, and 153 were selected for full screening of which 18 were included in the present review. Bloodstream infection (BSI) was most commonly investigated (nine of 18) followed by urinary tract infection (UTI) (four of 18) and respiratory tract infection (RTI) (two of 18). Few studies investigated BSI and UTI in the same children (two of 18), or BSI and gastrointestinal infection (GII) (one of 18). As for BSI, the most frequently isolated bacteria were E. coli (four of 12), Streptococcus pneumonia (four of 12), Salmonella spp (three of 12) and Staphylococcus aureus (two of 12) with a positive identification rate of 19.7-33.3%, 5.2-27.6%, 11.7-65.4% and 23.5-42.0%, respectively. As for UTI, the main bacteria isolated were E. coli (six of six) and Klebsiella spp (six of six) with a positive rate of 20.0-72.3% and 10.0-28.5%, respectively. No bacterium was isolated in RTI group, but Human influenzae A and B were frequently found, with the highest positive identification rate in Tanzania (75.3%). Dengue virus (two of 12) was the most frequently reported viral infection with a positive identification rate of 16.7-30.8%. Finally, only rotavirus/adenovirus (69.2% positive identification rate) was found in GII and no bacterium was isolated in this group. CONCLUSIONS: The high prevalence of treatable causes of non-malaria fever episodes requires a proper diagnosis of the origin of fever followed by an appropriate treatment, thereby reducing the under-5 mortality in sub-Saharan Africa and preventing the overprescription of antibiotics and thus circumventing the rise of antibiotic resistance.},

keywords = {aetiology, \'{A}frica subsahariana, Afrique subsaharienne, Children, enfants, etiolog\'{i}a, \'{e}tiologie, Fever, fiebre, fi\`{e}vre, Malaria, ni\~{n}os, paludisme, sub-Saharan Africa},

pubstate = {Publisher},

tppubtype = {article}

}

@article{Kuijpers2016-yp,

title = {Severe anaemia associated with Plasmodium falciparum infection in 

 children: consequences for additional blood sampling for research},

author = {Laura Maria Francisca Kuijpers and Jessica Maltha and Issa Guiraud and B\'{e}renger Kabor\'{e} and Palpouguini Lompo and Hugo Devlieger and Chris Van Geet and Halidou Tinto and Jan Jacobs},

year  = {2016},

date = {2016-06-01},

journal = {Malar. J.},

volume = {15},

pages = {304},

abstract = {BACKGROUND: Plasmodium falciparum infection may cause severe 

 anaemia, particularly in children. When planning a diagnostic 

 study on children suspected of severe malaria in sub-Saharan 

 Africa, it was questioned how much blood could be safely sampled; 

 intended blood volumes (blood cultures and EDTA blood) were 6 mL 

 (children aged 2 months to \<12 years, data of age, weight and 

 haemoglobin value (Hb) were available. For each child, the 

 estimated TBV (TBVe) (mL) was calculated by multiplying the body 

 weight (kg) by the factor 80 (ml/kg). Next, TBVe was corrected 

 for the degree of anaemia to obtain the functional TBV (TBVf). 

 The correction factor consisted of the rate 'Hb of the child 

 divided by the reference Hb'; both the lowest ('best case') and 

 highest ('worst case') reference Hb values were used. Next, the 

 exact volume that a 3.8 % proportion of this TBVf would present 

 was calculated and this volume was compared to the blood volumes 

 that were intended to be sampled. RESULTS: When applied to the 

 Burkina Faso cohort, the simulation exercise pointed out that in 

 5.3 % (best case) and 11.4 % (worst case) of children the blood 

 volume intended to be sampled would exceed the volume as defined 

 by the 3.8 % safety guideline. Highest proportions would be in 

 the age groups 2-6 months (19.0 %; worst scenario) and 6 

 months-2 years (15.7 %; worst case scenario). A positive rapid 

 diagnostic test for P. falciparum was associated with an 

 increased risk of violating the safety guideline in the worst case scenario (p = 0.016). CONCLUSIONS: Blood sampling in 

 children for research in P. falciparum endemic settings may 

 easily violate the proposed safety guideline when applied to 

 TBVf. Ethical committees and researchers should be wary of this 

 and take appropriate precautions.},

keywords = {Blood specimen collection; Blood volume; Child; Practice   guidelines as topic},

pubstate = {published},

tppubtype = {article}

}

@article{WWARN_Gametocyte_Study_Group2016-xr,

title = {Gametocyte carriage in uncomplicated Plasmodium falciparum 

 malaria following treatment with artemisinin combination therapy: 

 a systematic review and meta-analysis of individual patient data},

author = {WWARN Gametocyte Study Group},

year  = {2016},

date = {2016-05-01},

journal = {BMC Med.},

volume = {14},

pages = {79},

abstract = {BACKGROUND: Gametocytes are responsible for transmission of 

 malaria from human to mosquito. Artemisinin combination therapy 

 (ACT) reduces post-treatment gametocyte carriage, dependent upon 

 host, parasite and pharmacodynamic factors. The gametocytocidal 

 properties of antimalarial drugs are important for malaria 

 elimination efforts. An individual patient clinical data 

 meta-analysis was undertaken to identify the determinants of 

 gametocyte carriage and the comparative effects of four ACTs: 

 artemether-lumefantrine (AL), artesunate/amodiaquine (AS-AQ), 

 artesunate/mefloquine (AS-MQ), and dihydroartemisinin-piperaquine 

 (DP). METHODS: Factors associated with gametocytaemia prior to, 

 and following, ACT treatment were identified in multivariable 

 logistic or Cox regression analysis with random effects. All 

 relevant studies were identified through a systematic review of 

 PubMed. Risk of bias was evaluated based on study design, 

 methodology, and missing data. RESULTS: The systematic review 

 identified 169 published and 9 unpublished studies, 126 of which 

 were shared with the WorldWide Antimalarial Resistance Network 

 (WWARN) and 121 trials including 48,840 patients were included in 

 the analysis. Prevalence of gametocytaemia by microscopy at 

 enrolment was 12.1 % (5887/48,589), and increased with 

 decreasing age, decreasing asexual parasite density and 

 decreasing haemoglobin concentration, and was higher in patients 

 without fever at presentation. After ACT treatment, 

 gametocytaemia appeared in 1.9 % (95 % CI, 1.7-2.1) of 

 patients. The appearance of gametocytaemia was lowest after AS-MQ 

 and AL and significantly higher after DP (adjusted hazard ratio (AHR), 2.03; 95 % CI, 1.24-3.12; P = 0.005 compared to AL) and 

 AS-AQ fixed dose combination (FDC) (AHR, 4.01; 95 % CI, 

 2.40-6.72; P \< 0.001 compared to AL). Among individuals who had 

 gametocytaemia before treatment, gametocytaemia clearance was 

 significantly faster with AS-MQ (AHR, 1.26; 95 % CI, 1.00-1.60; P = 0.054) and slower with DP (AHR, 0.74; 95 % CI, 0.63-0.88; P = 0.001) compared to AL. Both recrudescent (adjusted odds ratio 

 (AOR), 9.05; 95 % CI, 3.74-21.90; P \< 0.001) and new (AOR, 3.03; 

 95 % CI, 1.66-5.54; P \< 0.001) infections with asexual-stage 

 parasites were strongly associated with development of 

 gametocytaemia after day 7. CONCLUSIONS: AS-MQ and AL are more 

 effective than DP and AS-AQ FDC in preventing gametocytaemia 

 shortly after treatment, suggesting that the non-artemisinin 

 partner drug or the timing of artemisinin dosing are important 

 determinants of post-treatment gametocyte dynamics.},

keywords = {Drug resistance; Gametocyte; Malaria; Plasmodium falciparum},

pubstate = {published},

tppubtype = {article}

}

@article{Sondo2016-wt,

title = {Artesunate-amodiaquine and artemether-lumefantrine therapies and 

 selection of Pfcrt and Pfmdr1 alleles in Nanoro, Burkina Faso},

author = {Paul Sondo and Karim Derra and Seydou Diallo Nakanabo and Zekiba Tarnagda and Adama Kazienga and Odile Zampa and Innocent Val\'{e}a and Hermann Sorgho and Ellis Owusu-Dabo and Jean-Bosco Ou\'{e}draogo and Tinga Robert Guiguemd\'{e} and Halidou Tinto},

year  = {2016},

date = {2016-03-01},

journal = {PLoS One},

volume = {11},

number = {3},

pages = {e0151565},

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

abstract = {The adoption of Artemisinin based combination therapies (ACT) 

 constitutes a basic strategy for malaria control in sub-Saharan 

 Africa. Moreover, since cases of ACT resistance have been 

 reported in South-East Asia, the need to understand P. 

 falciparum resistance mechanism to ACT has become a global 

 research goal. The selective pressure of ACT and the possibility 

 that some specific Pfcrt and Pfmdr1 alleles are associated with 

 treatment failures was assessed in a clinical trial comparing 

 ASAQ to AL in Nanoro. Dried blood spots collected on Day 0 and 

 on the day of recurrent parasitaemia during the 28-day follow-up 

 were analyzed using the restriction fragments length 

 polymorphism (PCR-RFLP) method to detect single nucleotide 

 polymorphisms (SNPs) in Pfcrt (codon76) and Pfmdr1 (codons 86, 

 184, 1034, 1042, and 1246) genes. Multivariate analysis of the 

 relationship between the presence of Pfcrt and Pfmdr1 alleles 

 and treatment outcome was performed. AL and ASAQ exerted 

 opposite trends in selecting Pfcrt K76T and Pfmdr1-N86Y alleles, 

 raising the potential beneficial effect of using diverse ACT at 

 the same time as first line treatments to reduce the selective 

 pressure by each treatment regimen. No clear association between 

 the presence of Pfcrt and Pfmdr1 alleles carried at baseline and 

 treatment failure was observed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{PREGACT_Study_Group2016-ed,

title = {Four artemisinin-based treatments in African pregnant women with 

 malaria},

author = {PREGACT Study Group and Divine Pekyi and Akua A Ampromfi and Halidou Tinto and Maminata Traor\'{e}-Coulibaly and Marc C Tahita and Innocent Val\'{e}a and Victor Mwapasa and Linda Kalilani-Phiri and Gertrude Kalanda and Mwayiwawo Madanitsa and Raffaella Ravinetto and Theonest Mutabingwa and Prosper Gbekor and Harry Tagbor and Gifty Antwi and Joris Menten and Maaike De Crop and Yves Claeys and Celine Schurmans and Chantal Van Overmeir and Kamala Thriemer and Jean-Pierre Van Geertruyden and Umberto D'Alessandro and Michael Nambozi and Modest Mulenga and Sebastian Hachizovu and Jean-Bertin B Kabuya and Joyce Mulenga},

year  = {2016},

date = {2016-03-01},

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

volume = {374},

number = {10},

pages = {913--927},

abstract = {BACKGROUND: Information regarding the safety and efficacy of 

 artemisinin combination treatments for malaria in pregnant women 

 is limited, particularly among women who live in sub-Saharan 

 Africa. METHODS: We conducted a multicenter, randomized, 

 open-label trial of treatments for malaria in pregnant women in 

 four African countries. A total of 3428 pregnant women in the 

 second or third trimester who had falciparum malaria (at any 

 parasite density and regardless of symptoms) were treated with 

 artemether-lumefantrine, amodiaquine-artesunate, 

 mefloquine-artesunate, or dihydroartemisinin-piperaquine. The 

 primary end points were the polymerase-chain-reaction 

 (PCR)-adjusted cure rates (i.e., cure of the original infection; 

 new infections during follow-up were not considered to be 

 treatment failures) at day 63 and safety outcomes. RESULTS: The 

 PCR-adjusted cure rates in the per-protocol analysis were 94.8% 

 in the artemether-lumefantrine group, 98.5% in the 

 amodiaquine-artesunate group, 99.2% in the 

 dihydroartemisinin-piperaquine group, and 96.8% in the 

 mefloquine-artesunate group; the PCR-adjusted cure rates in the 

 intention-to-treat analysis were 94.2%, 96.9%, 98.0%, and 

 95.5%, respectively. There was no significant difference among 

 the amodiaquine-artesunate group, dihydroartemisinin-piperaquine 

 group, and the mefloquine-artesunate group. The cure rate in the 

 artemether-lumefantrine group was significantly lower than that 

 in the other three groups, although the absolute difference was 

 within the 5-percentage-point margin for equivalence. The 

 unadjusted cure rates, used as a measure of the post-treatment 

 prophylactic effect, were significantly lower in the 

 artemether-lumefantrine group (52.5%) than in groups that 

 received amodiaquine-artesunate (82.3%), 

 dihydroartemisinin-piperaquine (86.9%), or mefloquine-artesunate 

 (73.8%). No significant difference in the rate of serious 

 adverse events and in birth outcomes was found among the 

 treatment groups. Drug-related adverse events such as asthenia, 

 poor appetite, dizziness, nausea, and vomiting occurred 

 significantly more frequently in the mefloquine-artesunate group 

 (50.6%) and the amodiaquine-artesunate group (48.5%) than in 

 the dihydroartemisinin-piperaquine group (20.6%) and the 

 artemether-lumefantrine group (11.5%) (P\<0.001 for comparison 

 among the four groups). CONCLUSIONS: Artemether-lumefantrine was 

 associated with the fewest adverse effects and with acceptable 

 cure rates but provided the shortest post-treatment prophylaxis, 

 whereas dihydroartemisinin-piperaquine had the best efficacy and 

 an acceptable safety profile. (Funded by the European and 

 Developing Countries Clinical Trials Partnership and others; 

 ClinicalTrials.gov number, NCT00852423.).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sarovich2016-ww,

title = {Phylogenomic analysis reveals an Asian origin for African 

 Burkholderia pseudomallei and further supports melioidosis 

 endemicity in Africa},

author = {Derek S Sarovich and Benoit Garin and Birgit De Smet and Mirjam Kaestli and Mark Mayo and Peter Vandamme and Jan Jacobs and Palpouguini Lompo and Marc C Tahita and Halidou Tinto and Innocente Djaomalaza and Bart J Currie and Erin P Price},

year  = {2016},

date = {2016-03-01},

journal = {mSphere},

volume = {1},

number = {2},

publisher = {American Society for Microbiology},

abstract = {Burkholderia pseudomallei, an environmental bacterium that 

 causes the deadly disease melioidosis, is endemic in northern 

 Australia and Southeast Asia. An increasing number of 

 melioidosis cases are being reported in other tropical regions, 

 including Africa and the Indian Ocean islands. B. pseudomallei 

 first emerged in Australia, with subsequent rare dissemination 

 event(s) to Southeast Asia; however, its dispersal to other 

 regions is not yet well understood. We used large-scale 

 comparative genomics to investigate the origins of three B. 

 pseudomallei isolates from Madagascar and two from Burkina Faso. 

 Phylogenomic reconstruction demonstrates that these African B. 

 pseudomallei isolates group into a single novel clade that 

 resides within the more ancestral Asian clade. Intriguingly, 

 South American strains reside within the African clade, 

 suggesting more recent dissemination from West Africa to the 

 Americas. Anthropogenic factors likely assisted in B. 

 pseudomallei dissemination to Africa, possibly during migration 

 of the Austronesian peoples from Indonesian Borneo to Madagascar 

 ~2,000 years ago, with subsequent genetic diversity driven by 

 mutation and recombination. Our study provides new insights into 

 global patterns of B. pseudomallei dissemination and adds to the 

 growing body of evidence of melioidosis endemicity in Africa. 

 Our findings have important implications for melioidosis 

 diagnosis and management in Africa. IMPORTANCE Sporadic 

 melioidosis cases have been reported in the African mainland and 

 Indian Ocean islands, but until recently, these regions were not 

 considered areas where B. pseudomallei is endemic. Given the 

 high mortality rate of melioidosis, it is crucial that this 

 disease be recognized and suspected in all regions of 

 endemicity. Previous work has shown that B. pseudomallei 

 originated in Australia, with subsequent introduction into Asia; 

 however, the precise origin of B. pseudomallei in other tropical 

 regions remains poorly understood. Using whole-genome 

 sequencing, we characterized B. pseudomallei isolates from 

 Madagascar and Burkina Faso. Next, we compared these strains to 

 a global collection of B. pseudomallei isolates to identify 

 their evolutionary origins. We found that African B. 

 pseudomallei strains likely originated from Asia and were 

 closely related to South American strains, reflecting a 

 relatively recent shared evolutionary history. We also 

 identified substantial genetic diversity among African strains, 

 suggesting long-term B. pseudomallei endemicity in this region.},

keywords = {Burkholderia; epidemiology; infectious disease; melioidosis;   phylogeography; population genetics},

pubstate = {published},

tppubtype = {article}

}

@article{Decuypere2016-jf,

title = {Towards improving point-of-care diagnosis of non-malaria febrile 

 illness: A metabolomics approach},

author = {Saskia Decuypere and Jessica Maltha and Stijn Deborggraeve and Nicholas J W Rattray and Guiraud Issa and Kabor\'{e} B\'{e}renger and Palpouguini Lompo and Marc C Tahita and Thusitha Ruspasinghe and Malcolm McConville and Royston Goodacre and Halidou Tinto and Jan Jacobs and Jonathan R Carapetis},

year  = {2016},

date = {2016-03-01},

journal = {PLoS Negl. Trop. Dis.},

volume = {10},

number = {3},

pages = {e0004480},

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

abstract = {INTRODUCTION: Non-malaria febrile illnesses such as bacterial 

 bloodstream infections (BSI) are a leading cause of disease and 

 mortality in the tropics. However, there are no reliable, simple 

 diagnostic tests for identifying BSI or other severe non-malaria 

 febrile illnesses. We hypothesized that different infectious 

 agents responsible for severe febrile illness would impact on 

 the host metabolome in different ways, and investigated the 

 potential of plasma metabolites for diagnosis of non-malaria 

 febrile illness. METHODOLOGY: We conducted a comprehensive 

 mass-spectrometry based metabolomics analysis of the plasma of 

 61 children with severe febrile illness from a malaria-endemic 

 rural African setting. Metabolite features characteristic for 

 non-malaria febrile illness, BSI, severe anemia and poor 

 clinical outcome were identified by receiver operating curve 

 analysis. PRINCIPAL FINDINGS: The plasma metabolome profile of 

 malaria and non-malaria patients revealed fundamental 

 differences in host response, including a differential 

 activation of the hypothalamic-pituitary-adrenal axis. A simple 

 corticosteroid signature was a good classifier of severe malaria 

 and non-malaria febrile patients (AUC 0.82, 95% CI: 0.70-0.93). 

 Patients with BSI were characterized by upregulated plasma bile 

 metabolites; a signature of two bile metabolites was estimated 

 to have a sensitivity of 98.1% (95% CI: 80.2-100) and a 

 specificity of 82.9% (95% CI: 54.7-99.9) to detect BSI in 

 children younger than 5 years. This BSI signature demonstrates 

 that host metabolites can have a superior diagnostic sensitivity 

 compared to pathogen-detecting tests to identify infections 

 characterized by low pathogen load such as BSI. CONCLUSIONS: 

 This study demonstrates the potential use of plasma metabolites 

 to identify causality in children with severe febrile illness in 

 malaria-endemic settings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Decuypere2016-fa,

title = {Diagnosis of bacterial bloodstream infections: A 16S 

 metagenomics approach},

author = {Saskia Decuypere and Conor J Meehan and Sandra Van Puyvelde and Tessa De Block and Jessica Maltha and Lompo Palpouguini and Marc Tahita and Halidou Tinto and Jan Jacobs and Stijn Deborggraeve},

year  = {2016},

date = {2016-02-01},

journal = {PLoS Negl. Trop. Dis.},

volume = {10},

number = {2},

pages = {e0004470},

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

abstract = {BACKGROUND: Bacterial bloodstream infection (bBSI) is one of the 

 leading causes of death in critically ill patients and accurate 

 diagnosis is therefore crucial. We here report a 16S 

 metagenomics approach for diagnosing and understanding bBSI. 

 METHODOLOGY/PRINCIPAL FINDINGS: The proof-of-concept was 

 delivered in 75 children (median age 15 months) with severe 

 febrile illness in Burkina Faso. Standard blood culture and 

 malaria testing were conducted at the time of hospital 

 admission. 16S metagenomics testing was done retrospectively and 

 in duplicate on the blood of all patients. Total DNA was 

 extracted from the blood and the V3-V4 regions of the bacterial 

 16S rRNA genes were amplified by PCR and deep sequenced on an 

 Illumina MiSeq sequencer. Paired reads were curated, 

 taxonomically labeled, and filtered. Blood culture diagnosed 

 bBSI in 12 patients, but this number increased to 22 patients 

 when combining blood culture and 16S metagenomics results. In 

 addition to superior sensitivity compared to standard blood 

 culture, 16S metagenomics revealed important novel insights into 

 the nature of bBSI. Patients with acute malaria or recovering 

 from malaria had a 7-fold higher risk of presenting 

 polymicrobial bloodstream infections compared to patients with no recent malaria diagnosis (p-value = 0.046). Malaria is known 

 to affect epithelial gut function and may thus facilitate 

 bacterial translocation from the intestinal lumen to the blood. 

 Importantly, patients with such polymicrobial blood infections 

 showed a 9-fold higher risk factor for not surviving their febrile illness (p-value = 0.030). CONCLUSIONS/SIGNIFICANCE: Our 

 data demonstrate that 16S metagenomics is a powerful approach 

 for the diagnosis and understanding of bBSI. This 

 proof-of-concept study also showed that appropriate control 

 samples are crucial to detect background signals due to 

 environmental contamination.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Brabin2016-lp,

title = {Perspectives on the design and methodology of periconceptional 

 nutrient supplementation trials},

author = {Bernard J Brabin and Sabine Gies and Stephen Owens and Yves Claeys and Umberto D'Alessandro and Halidou Tinto and Loretta Brabin},

year  = {2016},

date = {2016-01-01},

journal = {Trials},

volume = {17},

number = {1},

pages = {58},

publisher = {Springer Science and Business Media LLC},

abstract = {Periconceptional supplementation could extend the period over 

 which maternal and fetal nutrition is improved, but there are 

 many challenges facing early-life intervention studies. 

 Periconceptional trials differ from pregnancy supplementation 

 trials, not only because of the very early or pre-gestational 

 timing of nutrient exposure but also because they generate 

 subsidiary information on participants who remain non-pregnant. 

 The methodological challenges are more complex although, if well 

 designed, they provide opportunities to evaluate concurrent 

 hypotheses related to the health of non-pregnant women, 

 especially nulliparous adolescents. This review examines the 

 framework of published and ongoing randomised trial designs. 

 Four cohorts typically arise from the periconceptional trial 

 design--two of which are non-pregnant and two are pregnant--and 

 this structure provides assessment options related to 

 pre-pregnant, maternal, pregnancy and fetal outcomes. 

 Conceptually the initial decision for single or micronutrient 

 intervention is central--as is the choice of dosage and 

 content--in order to establish a comparative framework across 

 trials, improve standardisation, and facilitate interpretation 

 of mechanistic hypotheses. Other trial features considered in 

 the review include: measurement options for baseline and outcome 

 assessments; adherence to long-term supplementation; sample size 

 considerations in relation to duration of nutrient 

 supplementation; cohort size for non-pregnant and pregnant 

 cohorts as the latter is influenced by parity selection; 

 integrating qualitative studies and data management issues. 

 Emphasis is given to low resource settings where high infection 

 rates and the possibility of nutrient-infection interactions may 

 require appropriate safety monitoring. The focus is on pragmatic 

 issues that may help investigators planning a periconceptional 

 trial.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Adjei2016-zp,

title = {Treatment outcomes in a safety observational study of 

 dihydroartemisinin/piperaquine (Eurartesim(textregistered)) 

 in the treatment of uncomplicated malaria at public health 

 facilities in four African countries},

author = {Alexander Adjei and Solomon Narh-Bana and Alberta Amu and Vida Kukula and Richard Afedi Nagai and Seth Owusu-Agyei and Abraham Oduro and Eusebio Macete and Salim Abdulla and Tinto Halidou and Ali Sie and Isaac Osei and Esperance Sevene and Kwaku-Poku Asante and Abdunoor Mulokozi and Guillaume Compaore and Innocent Valea and Martin Adjuik and Rita Baiden and Bernhards Ogutu and Fred Binka and Margaret Gyapong},

year  = {2016},

date = {2016-01-01},

journal = {Malar. J.},

volume = {15},

number = {1},

pages = {43},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Dihydroartemisinin-piperaquine (DHA-PQ) is one of 

 five WHO recommended artemisinin combination therapy (ACT) for 

 the treatment of uncomplicated malaria. However, little was 

 known on its post-registration safety and effectiveness in 

 sub-Saharan Africa. DHA-PQ provides a long post-treatment 

 prophylactic effect against re-infection; however, new 

 infections have been reported within a few weeks of treatment, 

 especially in children. This paper reports the clinical outcomes 

 following administration of DHQ-PQ in real-life conditions in 

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

 Tanzania for the treatment of confirmed uncomplicated malaria. 

 METHODS: An observational, non-comparative, longitudinal study 

 was conducted on 10,591 patients with confirmed uncomplicated 

 malaria visiting public health facilities within seven health 

 and demographic surveillance system sites in four African 

 countries (Ghana, Tanzania, Burkina Faso, Mozambique) between 

 September 2013 and April 2014. Patients were treated with DHA-PQ 

 based on body weight and followed up for 28 days to assess the 

 clinical outcome. A nested cohort of 1002 was intensely followed 

 up. Clinical outcome was assessed using the proportion of 

 patients who reported signs and symptoms of malaria after 

 completing 3 days of treatment. RESULTS: A total of 11,097 

 patients were screened with 11,017 enrolled, 94 were lost to 

 follow-up, 332 withdrew and 10,591 (96.1%) patients aged 6 

 months-85 years met protocol requirements for analysis. Females 

 were 52.8 and 48.5% were \<5 years of age. Malaria was diagnosed 

 by microscopy and rapid diagnostic test in 69.8% and 29.9%, 

 respectively. At day 28, the unadjusted risk of recurrent 

 symptomatic parasitaemia was 0.5% (51/10,591). Most of the 

 recurrent symptomatic malaria patients (76%) were children \<5 

 years. The mean haemoglobin level decreased from 10.6 g/dl on 

 day 1 to 10.2 g/dl on day 7. There was no significant renal 

 impairment in the nested cohort during the first 7 days of 

 follow-up with minimal non-clinically significant changes noted 

 in the liver enzymes. CONCLUSION: DHA-PQ was effective and well 

 tolerated in the treatment of uncomplicated malaria and provides 

 an excellent alternative first-line ACT in sub-Saharan Africa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2016-ie,

title = {Lessons learnt from 20 years surveillance of malaria drug 

 resistance prior to the policy change in Burkina Faso},

author = {Halidou Tinto and Innocent Valea and Jean-Bosco Ou\'{e}draogo and Tinga Robert Guiguemd\'{e}},

year  = {2016},

date = {2016-01-01},

journal = {Ann. Parasitol.},

volume = {62},

number = {1},

pages = {17--24},

abstract = {The history of drug resistance to the previous antimalarial 

 drugs, and the potential for resistance to evolve to 

 Artemisinin-based combination therapies, demonstrates the 

 necessity to set-up a good surveillance system in order to 

 provide early warning of the development of resistance. Here we 

 report a review summarizing the history of the surveillance of 

 drug resistance that led to the policy change in Burkina Faso. 

 The first Plasmodium falciparum Chloroquine-Resistance strain 

 identified in Burkina Faso was detected by an in vitro test 

 carried out in Koudougou in 1983. Nevertheless, no further cases 

 were reported until 1987, suggesting that resistant strains had 

 been circulating at a low prevalence before the beginning of the 

 systematic surveillance system from 1984. We observed a marked 

 increase of Chloroquine-Resistance in 2002-2003 probably due to 

 the length of follow-up as the follow-up duration was 7 or 14 

 days before 2002 and 28 days from 2002 onwards. Therefore, 

 pre-2002 studies have probably under-estimated the real 

 prevalence of Chloroquine-Resistance by not detecting the late 

 recrudescence. With a rate of 8.2% treatment failure reported in 

 2003, Sulfadoxine-Pyrimethamine was still efficacious for the 

 treatment of uncomplicated malaria in Burkina Faso but this rate 

 might rapidly increase as the result of its spreading from 

 neighboring countries and due to its current use for both the 

 Intermittent Preventive Treatment in pregnant women and Seasonal 

 Malaria Chemoprophylaxis. The current strategy for the 

 surveillance of the Artemisinin-based combination treatments 

 resistance should build on lessons learnt under the previous 

 period of 20 years surveillance of Chloroquine and 

 Sulfadoxine-Pyrimethamine resistance (1994-2004). The most 

 important aspect being to extend the number of sentinel sites so 

 that data would be less patchy and could help understanding the 

 dynamic of the resistance.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tinto2015-xp,

title = {Assessment of the safety of antimalarial drug use during early 

 pregnancy (ASAP): protocol for a multicenter prospective 

 cohort study in Burkina Faso, Kenya and Mozambique},

author = {Halidou Tinto and Esperanc ca Sevene and Stephanie Dellicour and Gregory S Calip and Umberto d'Alessandro and Eus\'{e}bio Macete and Seydou Nakanabo-Diallo and Adama Kazienga and Innocent Valea and Hermann Sorgho and Anifa Val\'{a} and Orvalho Augusto and Maria Ruperez and Clara Menendez and Peter Ouma and Meghna Desai and Feiko Ter Kuile and Andy Stergachis},

year  = {2015},

date = {2015-12-01},

journal = {Reprod. Health},

volume = {12},

number = {1},

pages = {112},

publisher = {Springer Nature},

abstract = {BACKGROUND: A major unresolved safety concern for malaria case 

 management is the use of artemisinin combination therapies 

 (ACTs) in the first trimester of pregnancy. There is a need for 

 human data to inform policy makers and treatment guidelines on 

 the safety of artemisinin combination therapies (ACT) when used 

 during early pregnancy. METHODS: The overall goal of this paper 

 is to describe the methods and implementation of a study aimed 

 at developing surveillance systems for identifying exposures to 

 antimalarials during early pregnancy and for monitoring 

 pregnancy outcomes using health and demographic surveillance 

 platforms. This was a multi-center prospective observational 

 cohort study involving women at health and demographic 

 surveillance sites in three countries in Africa: Burkina Faso, 

 Kenya and Mozambique [(ClinicalTrials.gov Identifier: 

 NCT01232530)]. The study was designed to identify pregnant women 

 with artemisinin exposure in the first trimester and compare 

 them to: 1) pregnant women without malaria, 2) pregnant women 

 treated for malaria, but exposed to other antimalarials, and 3) 

 pregnant women with malaria and treated with artemisinins in the 

 2nd or 3rd trimesters from the same settings. Pregnant women 

 were recruited through community-based surveys and attendance at 

 health facilities, including antenatal care clinics and followed 

 until delivery. Data from the three sites will be pooled for 

 analysis at the end of the study. Results are forthcoming. 

 DISCUSSION: Despite few limitations, the methods described here 

 are relevant to the development of sustainable pharmacovigilance 

 systems for drugs used by pregnant women in the tropics using 

 health and demographic surveillance sites to prospectively 

 ascertain drug safety in early pregnancy. TRIAL REGISTRATION: 

 NCT01232530.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sankoh2015-fw,

title = {CHESS: an innovative concept for a new generation of population 

 surveillance},

author = {Osman Sankoh and INDEPTH Network},

year  = {2015},

date = {2015-12-01},

journal = {Lancet Glob. Health},

volume = {3},

number = {12},

pages = {e742},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Held2015-hx,

title = {Ferroquine and artesunate in African adults and children with 

 Plasmodium falciparum malaria: a phase 2, multicentre, 

 randomised, double-blind, dose-ranging, non-inferiority study},

author = {Jana Held and Christian Supan and Carmen L O Salazar and Halidou Tinto and L\'{e}a N Bonkian and Alain Nahum and Bancole Moulero and Ali Si\'{e} and Boubacar Coulibaly and Sodiomon B Sirima and Mohamadou Siribie and Nekoye Otsyula and Lucas Otieno and Ahmed M Abdallah and Robert Kimutai and Marielle Bouyou-Akotet and Maryvonne Kombila and Kimiko Koiwai and Cathy Cantalloube and Chantal Din-Bell and Elhadj Djeriou and John Waitumbi and Benjamin Mordm\"{u}ller and Daniel Ter-Minassian and Bertrand Lell and Peter G Kremsner},

year  = {2015},

date = {2015-12-01},

journal = {Lancet Infect. Dis.},

volume = {15},

number = {12},

pages = {1409--1419},

publisher = {Elsevier BV},

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

 the recommended first-line treatment for uncomplicated 

 Plasmodium falciparum malaria. Ferroquine is a new combination 

 partner for fast-acting ACTs such as artesunate. We aimed to 

 assess different doses of ferroquine in combination with 

 artesunate against uncomplicated P falciparum malaria in a 

 heterogeneous population in Africa. METHODS: We did a phase 2, 

 multicentre, parallel-group, double-blind, randomised, 

 dose-ranging non-inferiority trial at eight African hospitals 

 (two in Gabon, three in Burkina Faso, one in Benin, and two in 

 Kenya). We recruited patients presenting with acute P falciparum 

 monoinfection (1000-200,000 parasites per $mu$L), and a central 

 body temperature of at least 37·5°C or history of fever in the 

 past 24 h. We assessed patients in two sequential cohorts: 

 cohort 1 contained adults (bodyweight \>50 kg) and adolescents 

 (aged $geq$14 years, \>30 kg), and cohort 2 contained children 

 (aged 2-13 years, 15-30 kg). We randomly assigned patients 

 (1:1:1:1) to receive artesunate 4 mg/kg per day plus ferroquine 

 2 mg/kg, 4 mg/kg, or 6 mg/kg, given double-blind once per day 

 for 3 days, or ferroquine monotherapy 4 mg/kg per day given 

 single-blind (ie, allocation was only masked from the patient) 

 once per day for 3 days. We did 14 patient visits (screening, 3 

 treatment days and 48 h post-treatment surveillance, a visit on 

 day 7, then one follow-up visit per week until day 63). The 

 primary endpoint was non-inferiority of treatment in terms of 

 PCR-corrected cure rate against a reference value of 90%, with 

 a 10% non-inferiority margin, assessed in patients treated 

 without major protocol deviations for parasitologically 

 confirmed malaria. We assessed safety in all treated patients. 

 This study is registered with ClinicalTrials.gov, number 

 NCT00988507, and is closed. FINDINGS: Between Oct 16, 2009, and 

 Sept 22, 2010, we randomly assigned 326 eligible patients to 

 treatment groups, with last follow-up visit on Dec 1, 2010. 284 

 patients (87%) were available for per-protocol analyses. At day 

 28, PCR-confirmed cure was noted in 68 (97%, 95% CI 90-100) of 

 70 patients treated with ferroquine 2 mg/kg plus artesunate, 73 

 (99%, 93-100) of 74 with ferroquine 4 mg/kg plus artesunate, 71 

 (99%, 93-100) of 72 with ferroquine 6 mg/kg plus artesunate, 

 and 54 (79%, 68-88) of 68 with ferroquine 4 mg/kg monotherapy. 

 The three dose groups of ferroquine plus artesunate met the 

 non-inferiority hypothesis. The most common adverse events were 

 headache in cohort 1 (30 [19%] of 162 patients) and worsening 

 malaria in cohort 2 (23 [14%] of 164 patients); occurrences 

 were similar between treatment groups. INTERPRETATION: 

 Ferroquine combined with artesunate was associated with high 

 cure rates and was safe at all doses tested, and could be a 

 promising new drug combination for the treatment of P falciparum 

 malaria. Ferroquine could also partner other drugs to establish 

 a new generation of antimalarial combinations, especially in 

 regions that have developed resistance to ACTs. FUNDING: Sanofi.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{White2015-cw,

title = {Immunogenicity of the RTS,S/AS01 malaria vaccine and 

 implications for duration of vaccine efficacy: secondary analysis 

 of data from a phase 3 randomised controlled trial},

author = {Michael T White and Robert Verity and Jamie T Griffin and Kwaku Poku Asante and Seth Owusu-Agyei and Brian Greenwood and Chris Drakeley and Samwel Gesase and John Lusingu and Daniel Ansong and Samuel Adjei and Tsiri Agbenyega and Bernhards Ogutu and Lucas Otieno and Walter Otieno and Selidji T Agnandji and Bertrand Lell and Peter Kremsner and Irving Hoffman and Francis Martinson and Portia Kamthunzu and Halidou Tinto and Innocent Valea and Hermann Sorgho and Martina Oneko and Kephas Otieno and Mary J Hamel and Nahya Salim and Ali Mtoro and Salim Abdulla and Pedro Aide and Jahit Sacarlal and John J Aponte and Patricia Njuguna and Kevin Marsh and Philip Bejon and Eleanor M Riley and Azra C Ghani},

year  = {2015},

date = {2015-12-01},

journal = {Lancet Infect. Dis.},

volume = {15},

number = {12},

pages = {1450--1458},

abstract = {BACKGROUND: The RTS,S/AS01 malaria vaccine targets the 

 circumsporozoite protein, inducing antibodies associated with the 

 prevention of Plasmodium falciparum infection. We assessed the 

 association between anti-circumsporozoite antibody titres and the 

 magnitude and duration of vaccine efficacy using data from a 

 phase 3 trial done between 2009 and 2014. METHODS: Using data 

 from 8922 African children aged 5-17 months and 6537 African 

 infants aged 6-12 weeks at first vaccination, we analysed the 

 determinants of immunogenicity after RTS,S/AS01 vaccination with 

 or without a booster dose. We assessed the association between 

 the incidence of clinical malaria and anti-circumsporozoite 

 antibody titres using a model of anti-circumsporozoite antibody 

 dynamics and the natural acquisition of protective immunity over 

 time. FINDINGS: RTS,S/AS01-induced anti-circumsporozoite antibody 

 titres were greater in children aged 5-17 months than in those 

 aged 6-12 weeks. Pre-vaccination anti-circumsporozoite titres 

 were associated with lower immunogenicity in children aged 6-12 

 weeks and higher immunogenicity in those aged 5-17 months. The 

 immunogenicity of the booster dose was strongly associated with 

 immunogenicity after primary vaccination. Anti-circumsporozoite 

 titres wane according to a biphasic exponential distribution. In 

 participants aged 5-17 months, the half-life of the short-lived 

 component of the antibody response was 45 days (95% credible 

 interval 42-48) and that of the long-lived component was 591 days 

 (557-632). After primary vaccination 12% (11-13) of the response 

 was estimated to be long-lived, rising to 30% (28-32%) after a 

 booster dose. An anti-circumsporozoite antibody titre of 121 

 EU/mL (98-153) was estimated to prevent 50% of infections. 

 Waning anti-circumsporozoite antibody titres predict the duration 

 of efficacy against clinical malaria across different age 

 categories and transmission intensities, and efficacy wanes more 

 rapidly at higher transmission intensity. INTERPRETATION: 

 Anti-circumsporozoite antibody titres are a surrogate of 

 protection for the magnitude and duration of RTS,S/AS01 efficacy, 

 with or without a booster dose, providing a valuable surrogate of 

 effectiveness for new RTS,S formulations in the age groups 

 considered. FUNDING: UK Medical Research Council.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tahita2015-pv,

title = {Prevalence of the dhfr and dhps mutations among pregnant women 

 in rural Burkina Faso five years after the introduction of 

 intermittent preventive treatment with sulfadoxine-pyrimethamine},

author = {Marc C Tahita and Halidou Tinto and Annette Erhart and Adama Kazienga and Robert Fitzhenry and Chantal VanOvermeir and Anna Rosanas-Urgell and Jean-Bosco Ouedraogo and Robert T Guiguemde and Jean-Pierre Van Geertruyden and Umberto D'Alessandro},

year  = {2015},

date = {2015-09-01},

journal = {PLoS One},

volume = {10},

number = {9},

pages = {e0137440},

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

abstract = {BACKGROUND: The emergence and spread of drug resistance 

 represents one of the biggest challenges for malaria control in 

 endemic regions. Sulfadoxine-pyrimethamine (SP) is currently 

 deployed as intermittent preventive treatment in pregnancy 

 (IPTp) to prevent the adverse effects of malaria on the mother 

 and her offspring. Nevertheless, its efficacy is threatened by 

 SP resistance which can be estimated by the prevalence of 

 dihydropteroate synthase (dhps) and dihydrofolate reductase 

 (dhfr) mutations. This was measured among pregnant women in the 

 health district of Nanoro, Burkina Faso. METHODS: From June to 

 December 2010, two hundred and fifty six pregnant women in the 

 second and third trimester, attending antenatal care with 

 microscopically confirmed malaria infection were invited to 

 participate, regardless of malaria symptoms. A blood sample was 

 collected on filter paper and analyzed by PCR-RFLP for the 

 alleles 51, 59, 108, 164 in the pfdhfr gene and 437, 540 in the 

 pfdhps gene. RESULTS: The genes were successfully genotyped in 

 all but one sample (99.6%; 255/256) for dhfr and in 90.2% 

 (231/256) for dhps. The dhfr C59R and S108N mutations were the 

 most common, with a prevalence of 61.2% (156/255) and 55.7% 

 (142/255), respectively; 12.2% (31/255) samples had also the 

 dhfr N51I mutation while the I164L mutation was absent. The dhps 

 A437G mutation was found in 34.2% (79/231) isolates, but none 

 of them carried the codon K540E. The prevalence of the dhfr 

 double mutations NRNI and the triple mutations IRNI was 35.7% 

 (91/255) and 11.4% (29/255), respectively. CONCLUSION: Though 

 the mutations in the pfdhfr and pfdhps genes were relatively 

 common, the prevalence of the triple pfdhfr mutation was very 

 low, indicating that SP as IPTp is still efficacious in Burkina 

 Faso.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Sondo2015-ka,

title = {Effectiveness and safety of artemether-lumefantrine versus 

 artesunate-amodiaquine for unsupervised treatment of 

 uncomplicated falciparum malaria in patients of all age groups 

 in Nanoro, Burkina Faso: a randomized open label trial},

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

year  = {2015},

date = {2015-08-01},

journal = {Malar. J.},

volume = {14},

number = {1},

pages = {325},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Several studies have reported high efficacy and 

 safety of artemisinin-based combination therapy (ACT) mostly 

 under strict supervision of drug intake and limited to children 

 less than 5 years of age. Patients over 5 years of age are 

 usually not involved in such studies. Thus, the findings do not 

 fully reflect the reality in the field. This study aimed to 

 assess the effectiveness and safety of ACT in routine treatment 

 of uncomplicated malaria among patients of all age groups in 

 Nanoro, Burkina Faso. METHODS: A randomized open label trial 

 comparing artesunate-amodiaquine (ASAQ) and 

 artemether-lumefantrine (AL) was carried out from September 2010 

 to October 2012 at two primary health centres (Nanoro and 

 Nazoanga) of Nanoro health district. A total of 680 patients 

 were randomized to receive either ASAQ or AL without any 

 distinction by age. Drug intake was not supervised as pertains 

 in routine practice in the field. Patients or their 

 parents/guardians were advised on the time and mode of 

 administration for the 3 days treatment unobserved at home. 

 Follow-up visits were performed on days 3, 7, 14, 21, and 28 to 

 evaluate clinical and parasitological resolution of their 

 malaria episode as well as adverse events. PCR genotyping of 

 merozoite surface proteins 1 and 2 (msp-1, msp-2) was used to 

 differentiate recrudescence and new infection. RESULTS: By day 

 28, the PCR corrected adequate clinical and parasitological 

 response was 84.1 and 77.8 % respectively for ASAQ and AL. The 

 cure rate was higher in older patients than in children under 5 

 years old. The risk of re-infection by day 28 was higher in AL 

 treated patients compared with those receiving ASAQ (p \< 

 0.00001). Both AL and ASAQ treatments were well tolerated. 

 CONCLUSION: This study shows a lowering of the efficacy when 

 drug intake is not directly supervised. This is worrying as both 

 rates are lower than the critical threshold of 90 % required by 

 the WHO to recommend the use of an anti-malarial drug in a 

 treatment policy. TRIAL REGISTRATION: NCT01232530.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tahita2015-on,

title = {Ex vivo anti-malarial drug susceptibility of Plasmodium 

 falciparum isolates from pregnant women in an area of highly 

 seasonal transmission in Burkina Faso},

author = {Marc C Tahita and Halidou Tinto and Sibiri Yarga and Adama Kazienga and Maminata Traore Coulibaly and Innocent Valea and Chantal Van Overmeir and Anna Rosanas-Urgell and Jean-Bosco Ouedraogo and Robert T Guiguemde and Jean-Pierre Geertruyden and Annette Erhart and Umberto D'Alessandro},

year  = {2015},

date = {2015-06-01},

journal = {Malar. J.},

volume = {14},

number = {1},

pages = {251},

publisher = {Springer Science and Business Media LLC},

abstract = {BACKGROUND: Ex vivo assays are usually carried out on parasite 

 isolates collected from patients with uncomplicated Plasmodium 

 falciparum malaria, from which pregnant women are usually 

 excluded as they are often asymptomatic and with relatively low 

 parasite densities. Nevertheless, P. falciparum parasites 

 infecting pregnant women selectively sequester in the placenta 

 and may have a different drug sensitivity profile compared to 

 those infecting other patients. The drug sensitivity profile of 

 P. falciparum isolates from infected pregnant women recruited in 

 a treatment efficacy trial conducted in Burkina Faso was 

 determined in an ex vivo study. METHODS: The study was conducted 

 between October 2010 and December 2012. Plasmodium falciparum 

 isolates were collected before treatment and at the time of any 

 recurrent infection whose parasite density was at least 100/µl. 

 A histidine-rich protein-2 assay was used to assess their 

 susceptibility to a panel of seven anti-malarial drugs. The 

 concentration of anti-malarial drug inhibiting 50% of the 

 parasite maturation to schizonts (IC(50)) for each drug was 

 determined with the IC Estimator version 1.2. RESULTS: The 

 prevalence of resistant isolates was 23.5% for chloroquine, 

 9.2% for mefloquine, 8.0% for monodesethylamodiaquine, and 

 4.4% for quinine. Dihydroartemisinin, mefloquine, lumefantrine, 

 and monodesethylamodiaquine had the lowest mean IC(50) ranging 

 between 1.1 and 1.5 nM respectively. The geometric mean IC(50) 

 of the tested drugs did not differ between chloroquine-sensitive 

 and resistant parasites, with the exception of quinine, for 

 which the IC(50) was higher for chloroquine-resistant isolates. 

 The pairwise comparison between the IC(50) of the tested drugs 

 showed a positive and significant correlation between 

 dihydroartemisinin and both mefloquine and chloroquine, between 

 chloroquine and lumefantrine and between monodesethylamodiaquine 

 and mefloquine. CONCLUSION: These ex vivo results suggest that 

 treatment with the currently available artemisinin-based 

 combinations is efficacious for the treatment of malaria in 

 pregnancy in Burkina Faso. TRIAL REGISTRATION: 

 ClinicalTrials.gov ID: NCT00852423.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}