Different methodological approaches to the assessment of in vivo efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children.

BACKGROUND: Use of different methods for assessing the efficacy of artemisinin-based combination antimalarial treatments (ACTs) will result in different estimates being reported, with implications for changes in treatment policy. METHODS: Data from different in vivo studies of ACT treatment of uncomplicated falciparum malaria were combined in a single database. Efficacy at day 28 corrected by PCR genotyping was estimated using four methods. In the first two methods, failure rates were calculated as proportions with either (1a) reinfections excluded from the analysis (standard WHO per-protocol analysis) or (1b) reinfections considered as treatment successes. In the second two methods, failure rates were estimated using the Kaplan-Meier product limit formula using either (2a) WHO (2001) definitions of failure, or (2b) failure defined using parasitological criteria only. RESULTS: Data analysed represented 2926 patients from 17 studies in nine African countries. Three ACTs were studied: artesunate-amodiaquine (AS+AQ, N = 1702), artesunate-sulphadoxine-pyrimethamine (AS+SP, N = 706) and artemether-lumefantrine (AL, N = 518).Using method (1a), the day 28 failure rates ranged from 0% to 39.3% for AS+AQ treatment, from 1.0% to 33.3% for AS+SP treatment and from 0% to 3.3% for AL treatment. The median [range] difference in point estimates between method 1a (reference) and the others were: (i) method 1b = 1.3% [0 to 24.8], (ii) method 2a = 1.1% [0 to 21.5], and (iii) method 2b = 0% [-38 to 19.3].The standard per-protocol method (1a) tended to overestimate the risk of failure when compared to alternative methods using the same endpoint definitions (methods 1b and 2a). It either overestimated or underestimated the risk when endpoints based on parasitological rather than clinical criteria were applied. The standard method was also associated with a 34% reduction in the number of patients evaluated compared to the number of patients enrolled. Only 2% of the sample size was lost when failures were classified on the first day of parasite recurrence and survival analytical methods were used. CONCLUSION: The primary purpose of an in vivo study should be to provide a precise estimate of the risk of antimalarial treatment failure due to drug resistance. Use of survival analysis is the most appropriate way to estimate failure rates with parasitological recurrence classified as treatment failure on the day it occurs

Epilepsy and traditional medicine in Bobo-Dioulasso (Burkina Faso).

OBJECTIVES: To contribute to a better knowledge of how epilepsy is perceived by traditional healers in Burkina Faso; what means they use to treat it, and how they think about modern treatment. MATERIAL AND METHODS: Individual interviews with 65 traditional healers chosen at random from members of the Reelwende Association. RESULTS: All traditional practitioners were of male gender. Most of them were above 50 years of age, and 75% had more than 10 years' experience. Epilepsy was considered to be contagious by 44% of the traditional practitioners, and hereditary according to 40% of them. Roughly, 15% of the healers think that the problem is localized in the head of a person and 7.8% think that they have worms in their head. Thirty-one per cent of them diagnose epilepsy if there is a combination of 'convulsions, sudden fall, dribbling and amnesia'. Another 15% require a combination of 'convulsions, amnesia and dribbling', the remaining 54% make the diagnosis based on one symptom or various combinations of two symptoms of 'grand mal' (generalized tonic clonic) seizures and most claim they have a treatment for it. For a quarter of them, therapeutic-means include concoctions of herbs or roots, baths and infusions. During the fit, 31% of the traditional practitioners think that nothing should be performed. According to 75% of them, traditional and modern treatments are complementary. CONCLUSION: Notwithstanding important differences in culture and religions (Muslim, Christian and Original), there is great similarity between the knowledge and beliefs about epilepsy reported from other parts of Africa and those presented by our study-group, suggesting an ancient origin of the concepts. Further study is needed to find out how other facets of epilepsy (e.g. complex partial seizures, absences) are perceived and how these are being treated. Ways need to be found to raise awareness about epilepsy without interfering with religious and cultural beliefs

Randomized comparison of amodiaquine plus sulfadoxine-pyrimethamine, artemether-lumefantrine, and dihydroartemisinin-piperaquine for the treatment of uncomplicated Plasmodium falciparum malaria in Burkina Faso.

BACKGROUND: Combination antimalarial therapy is advocated to improve treatment efficacy and limit selection of drug-resistant parasites. We compared the efficacies of 3 combination regimens in Bobo-Dioulasso, Burkina Faso: amodiaquine plus sulfadoxine-pyrimethamine, which was recently shown to be highly efficacious at this site; artemether-lumefantrine, the new national first-line antimalarial regimen; and dihydroartemisinin-piperaquine (DP), a newer regimen. METHODS: We enrolled 559 patients >or=6 months of age with uncomplicated Plasmodium falciparum malaria and randomized them to the 3 regimens. We analyzed the risk of recurrent parasitemia by day 28 and day 42, both unadjusted and adjusted by PCR methods to distinguish recrudescence and new infection. RESULTS: Complete data were available for 517 (92.5%) of the enrolled subjects. Early treatment failures occurred in 5 patients treated with amodiaquine plus sulfadoxine-pyrimethamine and in 2 patients each treated with the other regimens. The day 28 risk of recurrent parasitemia, unadjusted by genotyping, was significantly higher for patients receiving artemether-lumefantrine than for patients receiving amodiaquine plus sulfadoxine-pyrimethamine (20.1% vs. 6.2%; risk difference, 13.8%; 95% confidence interval, 7.0%-20.7%) or dihydroartemisinin-piperaquine (20.1% vs. 2.2%; risk difference, 17.9%; 95% confidence interval, 11.6%-24.1%). Similar differences were seen for children <5 years of age (54% of the study population) and when outcomes were extended to 42 days. Significant differences were not seen between outcomes for patients receiving amodiaquine plus sulfadoxine-pyrimethamine and outcomes for those receiving dihydroartemisinin-piperaquine. Recrudescences were uncommon (occurring in <5% of patients) in all treatment groups. No serious adverse events were noted. CONCLUSIONS: All regimens were highly efficacious in clearing infection, but considering the risks of recurrent malaria after therapy, the amodiaquine plus sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine regimens were more efficacious than the artemether-lumefantrine regimen (the new national regimen in Burkina Faso) for the treatment of uncomplicated P. falciparum malaria

Host candidate gene polymorphisms and clearance of drug-resistant parasites

Resistance to anti-malarial drugs is a widespread problem for control programmes for this devastating disease. Molecular tests are available for many anti-malarial drugs and are useful tools for the surveillance of drug resistance. However, the correlation of treatment outcome and molecular tests with particular parasite markers is not perfect, due in part to individuals who are able to clear genotypically drug-resistant parasites. This study aimed to identify molecular markers in the human genome that correlate with the clearance of malaria parasites after drug treatment, despite the drug resistance profile of the protozoan as predicted by molecular approaches

Etat des lieux de la reproduction sexuée des ignames africaines Dioscorea cayenensis – Dioscorea rotundata cultivées au Bénin

Les ignames sont d’importantes plantes alimentaires à multiplication végétative dont l’amélioration et la création variétale dépendent, comme chez les végétaux, de la maîtrise de la biologie de la reproduction sexuée. L’état des lieux des cultivars florifères des ignames africaines Dioscorea cayenensis – D. rotundata a été  réalisé à Djidja et à Ouaké, deux communes productrices du Bénin par une approche participative, à travers des focus-groups, des enquêtes individuelles et des visites de champs. Ainsi, à Ouaké, vingt quatre (24) cultivars ont été recensés, dont dix-neuf (19), soit 79% florifères avec 74% de mâles, 21% de femelles et 5% sont monoïques. Le taux de fructification est d’environ 15 fruits par pied. A Djidja, vingt-six (26) cultivars sont recensés dont vingt-trois (23), soit 88% florifères avec 57% de femelle et 43% de mâle. Le taux de fructification à Djidja est élevé 102 fruits par pied en moyenne. Le taux de floraison femelle et le taux de  fructification sont beaucoup plus importants à Djidja qu’à Ouaké. Dans le but de l’amélioration et de la création variétale, le site de Djidja semble être plus propice à l’utilisation de la reproduction sexuée chez les ignames cultivées que celui de Ouaké.Mots clés : Igname, floraison, fructification, Djidja, Ouaké

Globally prevalent PfMDR1 mutations modulate Plasmodium falciparum susceptibility to artemisinin-based combination therapies

Antimalarial chemotherapy, globally reliant on artemisinin-based combination therapies (ACTs), is threatened by the spread of drug resistance in Plasmodium falciparum parasites. Here we use zinc-finger nucleases to genetically modify the multidrug resistance-1 transporter PfMDR1 at amino acids 86 and 184, and demonstrate that the widely prevalent N86Y mutation augments resistance to the ACT partner drug amodiaquine and the former first-line agent chloroquine. In contrast, N86Y increases parasite susceptibility to the partner drugs lumefantrine and mefloquine, and the active artemisinin metabolite dihydroartemisinin. The PfMDR1 N86 plus Y184F isoform moderately reduces piperaquine potency in strains expressing an Asian/African variant of the chloroquine resistance transporter PfCRT. Mutations in both digestive vacuole-resident transporters are thought to differentially regulate ACT drug interactions with host haem, a product of parasite-mediated haemoglobin degradation. Global mapping of these mutations illustrates where the different ACTs could be selectively deployed to optimize treatment based on regional differences in PfMDR1 haplotypes.This work was funded in part by the National Institutes of Health (R01 AI50234, AI124678 and AI109023) and a Burroughs Wellcome Fund Investigator in Pathogenesis of Infectious Diseases award to D.A.F. This research also received funding from the Portuguese Fundacao para a Ciencia e Tecnologia (FCT), cofunded by Programa Operacional Regional do Norte (ON.2-O Novo Norte); from the Quadro de Referencia Estrategico Nacional (QREN) through the Fundo Europeu de Desenvolvimento Regional (FEDER) and from the Projeto Estrategico - LA 26 - 2013-2014 (PEst-C/SAU/LA0026/2013). M.I.V. is the recipient of a postdoctoral fellowship from FCT/Ministerio da Ciencia e Ensino Superior, Portugal-MCES (SFRH/BPD/76614/2011). A.M.L. was supported by an Australian National Health and Medical Research Council (NHMRC) Overseas Biomedical Fellowship (585519). R.E.M. was supported by an NHMRC RD Wright Biomedical Fellowship (1053082). A.C.U. was supported by an Irving scholarship from Columbia University. We thank Dr Andrea Ecker for her help with plasmid design and Pedro Ferreira for his expert help with Fig. 6.info:eu-repo/semantics/publishedVersio

First detection of bla TEM, SHV and CTX-M among Gram negative bacilli exhibiting extended spectrum &#946;- lactamase phenotype isolated at University Hospital Center, Yalgado Ouedraogo, Ouagadougou, Burkina Faso

Resistance to a wide variety of common antimicrobials is observed among clinical strains designed as extended spectrum β-lactmase (ESBL)  producers. They produce enzymatic protein which inactivates efficiently oxyimino cephalosporin and constitutes a serious global health concern that has complicated treatment strategies. Many studies report high prevalence of ESBL producers among Gram negative bacilli. The aim of this work was to identify the presence of TEM, SHV and CTX-M families in thesestrains which were initially screened by phenotypic method. Gram negative bacilli resisting third or four generation cephalosporin were isolated during anti-biogram study. The presence of ESBL positivity was detected using the double disk synergy test. Minimal inhibitory concentrations (MICs) of ceftriazon for any strain were determined using E-test manufacturing protocol. Polymerase chain reaction (PCR) analysis for β-lactamase (bla) genes of TEM, SHV and CTX-M family was carried out using designed primers in 171 ESBL isolates producers. Among 259 Gram negative bacilli collected, 171 (66, 02%) exhibited ESBL producers’ profile. Urine samples constitute major source of ESBL producers. The highest prevalence of ESBL was observed in Escherichia coli (75, 50%). Among ESBL isolates producers, gene prevalence of bla-CTX-M (65, 49%) was highest, followed by bla-TEM (25, 73%) and bla-SHV (18, 71%) in the present study. The frequency of ESBL producing strains among clinical isolates has been steadily increased. Continual drug resistance surveillance and molecular characteristics of ESBL isolates are necessary to guide the appropriate and judicious antibiotic use.Key words: Extended spectrum β-lactamase (ESBL), double disk synergy test, blaTEM, blaSHV, blaCTX-M, PCR

Microbiological and kinetic detection of gram negative bacilli producing extended-spectrum- β-lactamases (esbl) in emergencies and reanimation units of university hospital center, Yalgadoouedraogo, Burkina Faso

Background: Epidemiology of extended-Spectrum- β-lactamases has become worldwide, and our aim was to establish the prevalence of isolates producer in university hospital center Yalgado OUEDRAOGO particularly in reanimation and emergencies units.Material and methods: Prospective study was drive during July 2009 to march 2012 in order to collect strains resisting to third generation of cephalosporin during diagnosis analysis of biological specimens. Susceptibility of bacteria to antimicrobial agents was evaluated by disc diffusion method. Production of extended-spectrum β-lactamases has been investigated by double disc diffusion and kinetic methods.Results: 259 isolates which resisted at least to one of third generation of cephalosporins were collected. Among them 188 (72, 58 %) were positive to synergy test by a double disc diffusion method. The MICs of ceftriaxone determined by E-test were under than 50kg/ml, 100kg/ml et 256kg/ml for respect 81,57°/° ; 55,26°/° et 39,74°/° of isolates. Hydrolyze of β-lactam ring by bacterial extract followed at spectrophotometer showed speeds running at 0 to 0,090UAb.mn-1 for both isolates. Extract of 171 bacterial strains positives to synergy test had hydrolyzed at least one of oxy-iminocephalosporins and were identified as producing extended- spectrum β-lactamases. Spices reported by this study were 99 Escherichia coli (57,89%) ; 28 Klebsisella pneumonia (16,37%) ; 15 Enterobactersp (8,77%) ; 19 Pseudomonas aeruginosa (11,11%) ; 4 Citrobactersp (2,33%) 2 Acinetobactersp (1,16%), 3 Proteus mirabilis (1,75%) and 1 Salmonella typhi (0,05%).Conclusion: This study showed that bacterial resistances by extended- spectrum β-lactamases are a reality in University Hospital center YalgadoOuedraogo. It calls about antibiotics prescription and hospital hygiene in order to reduce emergence and propagation of new resisting bacterial.Keywords: microbial and kinetic analysis, Gram negative bacilli, extended-Spectrum- β-lactamase, emergencies, reanimatio

Prevalence of Escherichia coli virulence genes in patients with diarrhoea in Ouagadougou, Burkina Faso

Objective: Diarrhoeagenic E. coli (DEC) strains are important causes of diarrhoea in the developing world and, to a lesser extent, inthe developed world. In this study, we investigated the prevalence of the virulence genes specific for five major pathogroups of diarrheagenic Escherichia coli (DEC) in primary cultures from diarrhoeagenic patients in Burkina Faso.Methodology: From September 2016 to Mars 2017, a total of 211 faecal samples from diarrhoeagenic patients from urban hospitals of Ouagadou, Burkina Faso have been analysed. A 16-plex PCR was used to detect simultaneously, the five major DEC pathotypes (enteropathogenic E. coli (EPEC), enterotoxigenic E. coli (ETEC), Shiga toxin-producing E. coli (STEC), enteroaggregative E. coli (EAEC) and enteroinvasive E. coli (EIEC)).Results: At least one diarrhoeagenic E. Coli pathotype was detected in 31 samples (14.7%) in children and adults with diarrhoea. EAEC was the most common pathotype detected 9.5% (20/211), followed by EIEC2.4% (05/211) and STEC 0.5% (01/211). More than one DEC pathotype were detected in 2.4% (05/211) patients. EPEC and ETEC were not detected in single infection but in co-infection with others pathotypes.Conclusion: DEC, especially enteroaggregative, may be important responsible of diarrhoeas in Burkina Faso from all ages patient.Key Words: Diarrhoeagenic Escherichia coli, 16-plex PCR, Burkina Faso, human diarrhoeas stool

The effect of dose on the antimalarial efficacy of artemether-lumefantrine: a systematic review and pooled analysis of individual patient data

Background: Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria, although treatment failures occur in some regions. We investigated the effect of dosing strategy on efficacy in a pooled analysis from trials done in a wide range of malaria-endemic settings. Methods: We searched PubMed for clinical trials that enrolled and treated patients with artemether-lumefantrine and were published from 1960 to December, 2012. We merged individual patient data from these trials by use of standardised methods. The primary endpoint was the PCR-adjusted risk of Plasmodium falciparum recrudescence by day 28. Secondary endpoints consisted of the PCR-adjusted risk of P falciparum recurrence by day 42, PCR-unadjusted risk of P falciparum recurrence by day 42, early parasite clearance, and gametocyte carriage. Risk factors for PCR-adjusted recrudescence were identified using Cox's regression model with frailty shared across the study sites. Findings: We included 61 studies done between January, 1998, and December, 2012, and included 14 327 patients in our analyses. The PCR-adjusted therapeutic efficacy was 97·6% (95% CI 97·4-97·9) at day 28 and 96·0% (95·6-96·5) at day 42. After controlling for age and parasitaemia, patients prescribed a higher dose of artemether had a lower risk of having parasitaemia on day 1 (adjusted odds ratio [OR] 0·92, 95% CI 0·86-0·99 for every 1 mg/kg increase in daily artemether dose; p=0·024), but not on day 2 (p=0·69) or day 3 (0·087). In Asia, children weighing 10-15 kg who received a total lumefantrine dose less than 60 mg/kg had the lowest PCR-adjusted efficacy (91·7%, 95% CI 86·5-96·9). In Africa, the risk of treatment failure was greatest in malnourished children aged 1-3 years (PCR-adjusted efficacy 94·3%, 95% CI 92·3-96·3). A higher artemether dose was associated with a lower gametocyte presence within 14 days of treatment (adjusted OR 0·92, 95% CI 0·85-0·99; p=0·037 for every 1 mg/kg increase in total artemether dose). Interpretation: The recommended dose of artemether-lumefantrine provides reliable efficacy in most patients with uncomplicated malaria. However, therapeutic efficacy was lowest in young children from Asia and young underweight children from Africa; a higher dose regimen should be assessed in these groups. Funding: Bill and Melinda Gates Foundation