Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali.

Plasmodium falciparum malaria cases in Africa represent over 90% of the global burden with Mali being amongst the 11 highest burden countries that account for 70% of this annual incidence. The persistence of P. falciparum despite massive global interventions is because of its genetic diversity that drives its ability to adapt to environmental changes, develop resistance to drugs, and evade the host immune system. Knowledge on P. falciparum genetic diversity across populations and intervention landscape is thus critical for the implementation of new strategies to eliminate malaria. This study assessed genetic variation with 12,177 high-quality SNPs from 830 Malian P. falciparum isolates collected between 2007 and 2017 from seven locations. The complexity of infections remained high, varied between sites, and showed a trend toward overall decreasing complexity over the decade. Though there was no significant substructure, allele frequencies varied geographically, partly driven by temporal variance in sampling, particularly for drug resistance and antigen loci. Thirty-two mutations in known drug resistance markers (pfcrt, pfdhps, pfdhfr, pfmdr1, pfmdr2, and pfk13) attained a frequency of at least 2% in the populations. SNPs within and around the major markers of resistance to quinolines (pfmdr1 and pfcrt) and antifolates (pfdhfr and pfdhps) varied temporally and geographically, with strong linkage disequilibrium and signatures of directional selection in the genome. These geo-temporal populations also differentiated at alleles in immune-related loci, including, protein E140, pfsurfin8, pfclag8, and pfceltos, as well as pftrap, which showed signatures of haplotype differentiation between populations. Several regions across the genomes, including five known drug resistance loci, showed signatures of differential positive selection. These results suggest that drugs and immune pressure are dominant selective forces against P. falciparum in Mali, but their effect on the parasite genome varies temporally and spatially. Interventions interacting with these genomic variants need to be routinely evaluated as malaria elimination strategies are implemented

Different Plasmodium falciparum clearance times in two Malian villages following artesunate monotherapy.

BACKGROUND: Artemisinin resistance described as increased parasite clearance time (PCT) is rare in Africa. More sensitive methods such as qPCR might better characterize the clearance phenotype in sub-Saharan Africa. METHODS: PCT is explored in Mali using light microscopy and qPCR after artesunate for uncomplicated malaria. In two villages, patients were followed for 28 days. Blood smears and spots were collected respectively for microscopy and qPCR. Parasitemia slope half-life was calculated after microscopy. Patient residual parasitemia were measured by qPCR. RESULTS: Uncorrected adequate clinical and parasitological responses (ACPR) observed in Faladje and Bougoula-Hameau were 78% and 92%, respectively (p=0.01). This reached 100% for both after molecular correction. Proportions of 24H microscopy positive patients in Faladje and Bougoula-Hameau were 97.2% and 72%, respectively (p<0.0001). Slope half-life was 2.8h in Faladje vs 2H in Bougoula-Hameau (p<0.001) and Proportions of 72H patients with residual parasitemia were 68.5% and 40% in Faladje and Bougoula-Hameau, respectively (p=0.003). The mean residual parasitemia was 2.9 in Faladje vs. 0.008 in Bougoula-Hameau (p=0.002). Although artesunate is efficacious in Mali, the longer parasite clearance time with submicroscopic parasitemia observed may represent early signs of developing P. falciparum resistance to artemisinins

Table1_Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali

Plasmodium falciparum malaria cases in Africa represent over 90% of the global burden with Mali being amongst the 11 highest burden countries that account for 70% of this annual incidence. The persistence of P. falciparum despite massive global interventions is because of its genetic diversity that drives its ability to adapt to environmental changes, develop resistance to drugs, and evade the host immune system. Knowledge on P. falciparum genetic diversity across populations and intervention landscape is thus critical for the implementation of new strategies to eliminate malaria. This study assessed genetic variation with 12,177 high-quality SNPs from 830 Malian P. falciparum isolates collected between 2007 and 2017 from seven locations. The complexity of infections remained high, varied between sites, and showed a trend toward overall decreasing complexity over the decade. Though there was no significant substructure, allele frequencies varied geographically, partly driven by temporal variance in sampling, particularly for drug resistance and antigen loci. Thirty-two mutations in known drug resistance markers (pfcrt, pfdhps, pfdhfr, pfmdr1, pfmdr2, and pfk13) attained a frequency of at least 2% in the populations. SNPs within and around the major markers of resistance to quinolines (pfmdr1 and pfcrt) and antifolates (pfdhfr and pfdhps) varied temporally and geographically, with strong linkage disequilibrium and signatures of directional selection in the genome. These geo-temporal populations also differentiated at alleles in immune-related loci, including, protein E140, pfsurfin8, pfclag8, and pfceltos, as well as pftrap, which showed signatures of haplotype differentiation between populations. Several regions across the genomes, including five known drug resistance loci, showed signatures of differential positive selection. These results suggest that drugs and immune pressure are dominant selective forces against P. falciparum in Mali, but their effect on the parasite genome varies temporally and spatially. Interventions interacting with these genomic variants need to be routinely evaluated as malaria elimination strategies are implemented

Thoracotomies à l’Hôpital General de Douala : Indications et résultats

Introduction : La thoracotomie est une procédure chirurgicale majeure pouvant être conduite dans un contexte d’urgence ou électif. Celle-ci peut avoir diverses indications et comme tout acte chirurgical conduire à de nombreuses complications avec un taux de mortalité relativement élevé dans notre contexte où le plateau technique est souvent limité. Objectif : Le but de notre étude était de déterminer les indications et les résultats des thoracotomies à l’hôpital général de Douala entre 2006 et 2017. Patients et Méthode : Il s’agissait d’une étude rétrospective qui s’est déroulée dans le service de chirurgie de l’hôpital général de Douala dans la période allant du 1er Janvier 2006 au 31 Décembre 2017. Au total 35 dossiers de patients ayant bénéficié d’une thoracotomie ont été inclus. Résultats : Les principales indications retrouvées étaient les traumatismes thoraciques avec 37 % de cas suivies de la persistance du canal artériel 14 % et les séquelles de tuberculose 11 %. Les complications étaient retrouvées dans 17 % des cas (n=5) avec comme principale complication l’empyème avec 11% de cas. Le taux de mortalité était de 6 %.Conclusion : Au terme de notre étude, nous avons observé que les indications de thoracotomies étaient aussi bien traumatiques que non traumatiques avec une légère prédominance pour les indications traumatiques. Le taux de mortalité bien qu’acceptable était non négligeable. Mots clés : Thoracotomie, indications, complications, Douala English title: Thoracotomies at Douala General Hospital: Indications and resultsIntroduction: thoracotomy is a major surgical procedure that can be done in the context of an emergency or as elective. It can have diverse indication and like every other surgical act, has numerous complications with a relatively high mortality rate in limited technical facilities settings. Objective: The aim of our study was to determine the indication and results of thoracotomies at the Douala General Hospital between 2006 and 2017. Patients and Methods: We conducted a retrospective study in the surgical unit of the Douala General Hospital. The file of 37 patients who underwent thoracotomy between 1st January 2006 to the 31st of December 2017 were included Results: The main indication found were thoracic trauma with 37% of cases, following patient by ductus arteriosus closure 14% and tuberculosis sequels (11%). Complications were found in 17% of the case (n = 5) with main complication being empyema. The mortality rate was of 6%. Conclusion: The present study showed that the indication for thoracotomy could be traumatic as well as not traumatic with a predominance of traumatic indications. The mortality rate was 6%. Keywords : Thoracotomy, indication, complications, Doual