Variation in biting frequency by Anopheles mosquitoes can explain some of the heterogeneity in malaria transmission in endemic areas. In this study in Burkina Faso, we assessed natural exposure to mosquitoes by matching the genotype of blood meals from 1066 mosquitoes with blood from residents of local households. We observed that the distribution of mosquito bites exceeded the Pareto rule (20/80) in two of the three surveys performed (20/85, 76, and 96) and, at its most pronounced, is estimated to have profound epidemiological consequences, inflating the basic reproduction number of malaria by 8-fold. The distribution of bites from sporozoite-positive mosquitoes followed a similar pattern, with a small number of individuals within households receiving multiple potentially infectious bites over the period of a few days. Together, our findings indicate that heterogeneity in mosquito exposure contributes considerably to heterogeneity in infection risk and suggest significant variation in malaria transmission potential.
Plasmodium falciparum gametocyte kinetics and infectivity may differ between chronic and incident infections. In the current study, we assess parasite kinetics and infectivity to mosquitoes among children (aged 5–10 years) from Burkina Faso with (a) incident infections following parasite clearance (n = 48) and (b) chronic asymptomatic infections (n = 60). In the incident infection cohort, 92% (44/48) of children develop symptoms within 35 days, compared to 23% (14/60) in the chronic cohort. All individuals with chronic infection carried gametocytes or developed them during follow-up, whereas only 35% (17/48) in the incident cohort produce gametocytes before becoming symptomatic and receiving treatment. Parasite multiplication rate (PMR) and the relative abundance of ap2-g and gexp-5 transcripts are positively associated with gametocyte production. Antibody responses are higher and PMR lower in chronic infections. The presence of symptoms and sexual stage immune responses are associated with reductions in gametocyte infectivity to mosquitoes. We observe that most incident infections require treatment before the density of mature gametocytes is sufficient to infect mosquitoes. In contrast, chronic, asymptomatic infections represent a significant source of mosquito infections. Our observations support the notion that malaria transmission reduction may be expedited by enhanced case management, involving both symptom-screening and infection detection.
Diarrheagenic Escherichia coli (DEC) is important bacteria of children’s endemic and epidemic diarrhea worldwide. The aim of this study was to determine the prevalence of DEC isolated from stool samples collected from children with acute diarrhea living in Ouagadougou, Burkina Faso. From August 2013 to October 2015, stool samples were collected from 315 children under 5 years of age suffering from diarrhea in the “Centre Médical avec Antenne Chirurgicale (CMA)” Paul VI and the CMA of Schiphra. E. coli were isolated and identified by standard microbiological methods, and the 16-plex PCR method was used to further characterize them. Four hundred and nineteen (419) E. coli strains were characterized, of which 31 (7.4%) DEC pathotypes were identified and classified in five E. coli pathotypes: 15 enteroaggregative E. coli (EAEC) (48.4%), 8 enteropathogenic E. coli (EPEC) (25.8%) with 4 typical EPEC and 4 atypical EPEC, 4 enteroinvasive E. coli (EIEC) (12.9%), 3 enterohemorrhagic E. coli (EHEC) 9.67%, and 1 enterotoxigenic E. coli (ETEC) 3.2%. The use of multiplex PCR as a routine in clinical laboratory for the detection of DEC would be a useful mean for a rapid management of an acute diarrhea in children.
While significant advances have been made in understanding Plasmodium falciparum gametocyte biology and its relationship with malaria parasite transmission, the gametocyte sex ratio contribution to this process still remains a relevant research question. The present review discusses the biology of sex determination in P. falciparum, the underlying host and parasite factors, the sex specific susceptibility to drugs, the effect of sex ratio dynamics on malaria parasite transmission and the development of gametocyte sex specific diagnosis tools. Despite the inherent differences across several studies and approaches, the emerging picture highlights a potentially relevant contribution of the P. falciparum gametocyte sex ratio in the modulation of malaria parasite transmission. The increasing availability of molecular methods to measure gametocyte sex ratio will enable evaluation of important parameters, such as the impact of drug treatment on gametocyte sex ratio in vitro and in vivo as well as the changes of gametocyte sex ratios in natural infections, key steps towards elucidating how these parameters affect parasite infectiousness to the mosquito vectors.
The mechanisms behind the ability of Plasmodium falciparum to evade host immune system are poorly understood and are a major roadblock in achieving malaria elimination. Here, we use integrative genomic profiling and a longitudinal pediatric cohort in Burkina Faso to demonstrate the role of post-transcriptional regulation in host immune response in malaria. We report a strong signature of miRNA expression differentiation associated with P. falciparum infection (127 out of 320 miRNAs, B-H FDR 5%) and parasitemia (72 miRNAs, B-H FDR 5%). Integrative miRNA-mRNA analysis implicates several infection-responsive miRNAs (e.g., miR-16-5p, miR-15a-5p and miR-181c-5p) promoting lymphocyte cell death. miRNA cis-eQTL analysis using whole-genome sequencing data identified 1,376 genetic variants associated with the expression of 34 miRNAs (B-H FDR 5%). We report a protective effect of rs114136945 minor allele on parasitemia mediated through miR-598-3p expression. These results highlight the impact of post-transcriptional regulation, immune cell death processes and host genetic regulatory control in malaria.
Aims: The aim of this study is to assess the prevalence of hemoglobin abnormalities and G6PD deficiency and their respective influence on anemia occurring in less than five years old children with clinical P. falciparum malaria living in Burkina Faso. Study Design: The study was a cross-sectional survey with descriptive focus conducted from December 2010 to January 2013 in Saponé health district and from May to October 2011 in Banfora health district. Clinical and laboratory data were collected. Blood smears on slides for malaria diagnosis by microscopy, hemoglobin level and filter paper for the detection of human genetic factors were performed. Methodology: A total of 386 subjects from Saponé (131) and Banfora (255) were enrolled. DNA collected from each sample was extracted using chelex-100 method and the human genetic resistance factors background was assessed by RFLP-PCR. Abnormal hemoglobin patients were classified as NonAA while AA was defined the normal hemoglobin. Results: In this study, 70.98% (274/386) were classified normal hemoglobin (AA) while 29.02% (112/386) of subjects were carrying at least one abnormal (NonAA) allele: 24.35%AC, 3.63% AS, 0.78%CC and 0.26%SC. G6PD deficiency was 9.59% (37/386) among which, 4.92% for male and 4.66% in female. However, this gender difference was not statistically significant (p=1.00). 319/367 (86.92%) of the patients were anemic (59.4% with moderate anemia and 20.98% with mild anemia). The prevalence of anemia in G6PD deficient subjects was 83.33% (of which 58.33% were moderate anemia and 22.22% mild anemia). The difference between types of hemoglobin (p=0.64) in the occurrence of anemia (AA 87.64% and Non AA 85.18%) was not statistically significant. Conclusion: This study showed that the prevalence of these genetic factors was relatively low among children with clinical falciparum malaria with high parasite density. In addition, these factors appear to have no effect on anemia.
30We longitudinally assessed P. falciparum parasite kinetics, gametocyte production and infectivity 31 in incident infections that were naturally acquired following infection clearance and in chronic 32 asymptomatic infections in Burkina Faso. 92% (44/48) of the incident cohort developed symptoms 33 and were treated within 35 days, compared to 23% (14/60) of the chronic cohort. All but two 34 individuals with chronic infection were gametocytaemic at enrollment, whereas only 35% (17/48) 35in the incident cohort developed gametocytes within 35 days. The relative abundance of ap2-g 36 transcripts was positively associated with conversion to gametocyte production (i.e. the ratio of 37 gametocytes at day 14 to ring stage parasites at baseline) and was higher in chronic infections. 38Parasite multiplication rate, assessed by daily molecular parasite quantification, was positively 39 associated with prospective gametocyte production. Most incident infections were cleared before 40 gametocyte density was sufficiently high to infect mosquitoes. In contrast, chronic, asymptomatic 41 infections represented a significant source of mosquito infections. If present, gametocytes were 42 significantly less infectious if concurrent with malaria symptoms. Our observations support the 43 notion that malaria transmission reduction may be expediated by enhanced case management, 44 involving both symptom-screening and infection detection.45 46 47 48The epidemiology of P. falciparum transmission stages, gametocytes, is poorly understood. 50Molecular diagnostics show that low density gametocyte carriage is highly prevalent in endemic 51 populations 1 and that many low density infections are infectious to mosquitoes 2 , explaining 52 observations from the 1950s that gametocyte free individuals (as determined by microscopy) 53 frequently infected mosquitoes 3 . Few assessments of the population infectious reservoir of 54 malaria parasites have been undertaken 4,5 , particularly with tools capable of detecting low 55 parasite and gametocyte densities 6,7 . Fewer still have been able to assess the association of 56 infectivity with factors other than parasite density, despite clear evidence that gametocyte 57 maturity 8,9 , intrinsic parasite factors 10,11 , human genetic factors 12 , and human clinical and immune 58 responses 13-15 can have significant influence on the effectiveness of parasite transmission. 59The association between malaria symptoms and gametocyte dynamics is particularly poorly 60 understood. Among similarly immune individuals, higher densities of pathogenic, asexual stage 61 malaria parasites are commonly associated with the presentation of symptoms 16 . Because 62 gametocytes develop from asexual parasites, individuals with clinical malaria and higher parasite 63 densities may have more gametocytes and be more likely to infect mosquitoes 17,18 . On the other 64 hand, the slower development of gametocytes may result in higher densities later in infections. 65This would result in higher gametocyte densities in infecti...
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