scholarly journals Within-Household Clustering of Genetically Related Plasmodium Falciparum Infections In A Moderate Transmission Area of Uganda

2020 ◽  
Author(s):  
Jessica Briggs ◽  
Alison Kuchta ◽  
Max Murphy ◽  
Sofonias Tessema ◽  
Emmanuel Arinaitwe ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Genetic Relatedness ◽  
Malaria Incidence ◽  
Spatial Scales ◽  
Genetic Data ◽  
Fine Scale ◽  
Lower Elevation ◽  
Significant Difference

Abstract Background: Evaluation of genetic relatedness of malaria parasites is a useful tool for understanding transmission patterns, but patterns are not easily detectable in areas with moderate to high malaria transmission. To evaluate the feasibility of detecting genetic relatedness in a moderate malaria transmission setting, we measured relatedness of Plasmodium falciparum infections in cohort participants from randomly selected households in the Kihihi sub-county of Uganda (annual entomological inoculation rate of 27 infectious bites per person). Methods: All infections detected via microscopy or Plasmodium-specific loop mediated isothermal amplification from passive and active case detection during August 2011-March 2012 were genotyped at 26 microsatellite loci, providing data for 349 samples from 230 participants living in 80 households. Pairwise genetic relatedness was calculated using identity by state (IBS).Results: As expected, genetic diversity was high (mean heterozygosity [He]=0.73), and the majority (76.5%) of samples were polyclonal. Despite the high genetic diversity, fine-scale population structure was detectable, with significant spatiotemporal clustering of highly related infections. Although the difference in malaria incidence between households at higher (mean 1127 meters) vs. lower elevation (mean 1015 meters) was modest (1.4 malaria cases per person-year versus 1.9 per person-year, respectively), we found a significant difference in multiplicity of infection (2.2 versus 2.6, p = 0.008) and, more strikingly, a higher proportion of highly related infections within households (6.3% vs 0.9%, p = 0.0005) at higher elevation compared to lower elevation. Conclusions: Genetic data from a relatively small number of diverse, multiallelic loci reflected fine scale patterns of malaria transmission. Given the increasing interest in applying genetic data to augment malaria surveillance, our study provides evidence that genetic data can be used to inform transmission patterns at local spatial scales even in moderate transmission areas.

scholarly journals Within-household clustering of genetically related Plasmodium falciparum infections in a moderate transmission area of Uganda

2021 ◽  
Author(s):  
Jessica Briggs ◽  
Alison Kuchta ◽  
Max Murphy ◽  
Sofonias Tessema ◽  
Emmanuel Arinaitwe ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Genetic Relatedness ◽  
Malaria Incidence ◽  
Spatial Scales ◽  
Genetic Data ◽  
Fine Scale ◽  
Lower Elevation ◽  
Significant Difference

Abstract Background Evaluation of genetic relatedness of malaria parasites is a useful tool for understanding transmission patterns, but patterns are not easily detectable in areas with moderate to high malaria transmission. To evaluate the feasibility of detecting genetic relatedness in a moderate malaria transmission setting, relatedness of Plasmodium falciparum infections was measured in cohort participants from randomly selected households in the Kihihi sub-county of Uganda (annual entomological inoculation rate of 27 infectious bites per person). Methods All infections detected via microscopy or Plasmodium-specific loop mediated isothermal amplification from passive and active case detection during August 2011-March 2012 were genotyped at 26 microsatellite loci, providing data for 349 samples from 230 participants living in 80 households. Pairwise genetic relatedness was calculated using identity by state (IBS).Results As expected, genetic diversity was high (mean heterozygosity [He]=0.73), and the majority (76.5%) of samples were polyclonal. Despite the high genetic diversity, fine-scale population structure was detectable, with significant spatiotemporal clustering of highly related infections. Although the difference in malaria incidence between households at higher (mean 1127 metres) versus lower elevation (mean 1015 metres) was modest (1.4 malaria cases per person-year versus 1.9 per person-year, respectively), there was a significant difference in multiplicity of infection (2.2 versus 2.6, p = 0.008) and, more strikingly, a higher proportion of highly related infections within households (6.3% vs 0.9%, p = 0.0005) at higher elevation compared to lower elevation. Conclusions Genetic data from a relatively small number of diverse, multiallelic loci reflected fine scale patterns of malaria transmission. Given the increasing interest in applying genetic data to augment malaria surveillance, this study provides evidence that genetic data can be used to inform transmission patterns at local spatial scales even in moderate transmission areas.

scholarly journals Within‐household clustering of genetically related Plasmodium falciparum infections in a moderate transmission area of Uganda

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jessica Briggs ◽  
Alison Kuchta ◽  
Max Murphy ◽  
Sofonias Tessema ◽  
Emmanuel Arinaitwe ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Genetic Relatedness ◽  
Malaria Incidence ◽  
Spatial Scales ◽  
Genetic Data ◽  
Fine Scale ◽  
Lower Elevation ◽  
Significant Difference

Abstract Background Evaluation of genetic relatedness of malaria parasites is a useful tool for understanding transmission patterns, but patterns are not easily detectable in areas with moderate to high malaria transmission. To evaluate the feasibility of detecting genetic relatedness in a moderate malaria transmission setting, relatedness of Plasmodium falciparum infections was measured in cohort participants from randomly selected households in the Kihihi sub-county of Uganda (annual entomological inoculation rate of 27 infectious bites per person). Methods All infections detected via microscopy or Plasmodium-specific loop mediated isothermal amplification from passive and active case detection during August 2011-March 2012 were genotyped at 26 microsatellite loci, providing data for 349 samples from 230 participants living in 80 households. Pairwise genetic relatedness was calculated using identity by state (IBS). Results As expected, genetic diversity was high (mean heterozygosity [He] = 0.73), and the majority (76.5 %) of samples were polyclonal. Despite the high genetic diversity, fine-scale population structure was detectable, with significant spatiotemporal clustering of highly related infections. Although the difference in malaria incidence between households at higher (mean 1127 metres) versus lower elevation (mean 1015 metres) was modest (1.4 malaria cases per person-year vs. 1.9 per person-year, respectively), there was a significant difference in multiplicity of infection (2.2 vs. 2.6, p = 0.008) and, more strikingly, a higher proportion of highly related infections within households (6.3 % vs. 0.9 %, p = 0.0005) at higher elevation compared to lower elevation. Conclusions Genetic data from a relatively small number of diverse, multiallelic loci reflected fine scale patterns of malaria transmission. Given the increasing interest in applying genetic data to augment malaria surveillance, this study provides evidence that genetic data can be used to inform transmission patterns at local spatial scales even in moderate transmission areas.

scholarly journals Fine-Scale Population Genetic Structure and Within-Tree Distribution of Mating Types of Venturia effusa, Cause of Pecan Scab in the United States

2018 ◽  
Vol 108 (11) ◽  
pp. 1326-1336 ◽  
Author(s):  
Clive H. Bock ◽  
Carolyn A. Young ◽  
Katherine L. Stevenson ◽  
Nikki D. Charlton
Keyword(s):  
United States ◽  
Genetic Diversity ◽  
Asexual Reproduction ◽  
Population Genetic ◽  
Spatial Scales ◽  
The United States ◽  
Source Population ◽  
Mating Types ◽  
Fine Scale ◽  
Scale Population

Scab (caused by Venturia effusa) is the major disease of pecan in the southeastern United States. There is no information available on the fine-scale population genetic diversity or the occurrence of clonal types at small spatial scales that provides insight into inoculum sources and dispersal mechanisms, and potential opportunity for sexual reproduction. To investigate fine-scale genetic diversity, four trees of cultivar Wichita (populations) were sampled hierarchically: within each tree canopy, four approximately evenly spaced terminals (subpopulations) were selected and up to six leaflets (sub-subpopulations) were sampled from different compound leaves on each terminal. All lesions (n = 1 to 8) on each leaflet were sampled. The isolates were screened against a panel of 29 informative microsatellite markers and the resulting multilocus genotypes (MLG) subject to analysis. Mating type was also determined for each isolate. Of 335 isolates, there were 165 MLG (clonal fraction 49.3%). Nei’s unbiased measure of genetic diversity for the clone-corrected data were moderate to high (0.507). An analysis of molecular variance demonstrated differentiation (P = 0.001) between populations on leaflets within individual terminals and between terminals within trees in the tree canopies, with 93.8% of variance explained among isolates within leaflet populations. Other analyses (minimum-spanning network, Bayesian, and discriminant analysis of principal components) all indicated little affinity of isolate for source population. Of the 335 isolates, most unique MLG were found at the stratum of the individual leaflets (n = 242), with similar total numbers of unique MLG observed at the strata of the terminal (n = 170), tree (n = 166), and orchard (n = 165). Thus, the vast majority of shared clones existed on individual leaflets on a terminal at the scale of 10s of centimeters or less, indicating a notable component of short-distance dispersal. There was significant linkage disequilibrium (P < 0.001), and an analysis of Psex showed that where there were multiple encounters of an MLG, they were most probably the result of asexual reproduction (P < 0.05) but there was no evidence that asexual reproduction was involved in single or first encounters of an MLG (P > 0.05). Overall, the MAT1-1-1 and MAT1-2-1 idiomorphs were at equilibrium (73:92) and in most populations, subpopulations, and sub-subpopulations. Both mating types were frequently observed on the same leaflet. The results provide novel information on the characteristics of populations of V. effusa at fine spatial scales, and provide insights into the dispersal of the organism within and between trees. The proximity of both mating idiomorphs on single leaflets is further evidence of opportunity for development of the sexual stage in the field.

scholarly journals Molecular epidemiology of Plasmodium falciparum by multiplexed amplicon deep sequencing in Senegal

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Tolla Ndiaye ◽  
Mouhamad Sy ◽  
Amy Gaye ◽  
Katherine J. Siddle ◽  
Daniel J. Park ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Molecular Epidemiology ◽  
Deep Sequencing ◽  
Haplotype Diversity ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
The South ◽  
The North ◽  
Significant Difference

Abstract Background Molecular epidemiology can provide important information regarding the genetic diversity and transmission of Plasmodium falciparum, which can assist in designing and monitoring elimination efforts. However, malaria molecular epidemiology including understanding the genetic diversity of the parasite and performing molecular surveillance of transmission has been poorly documented in Senegal. Next Generation Sequencing (NGS) offers a practical, fast and high-throughput approach to understand malaria population genetics. This study aims to unravel the population structure of P. falciparum and to estimate the allelic diversity, multiplicity of infection (MOI), and evolutionary patterns of the malaria parasite using the NGS platform. Methods Multiplex amplicon deep sequencing of merozoite surface protein 1 (PfMSP1) and merozoite surface protein 2 (PfMSP2) in fifty-three P. falciparum isolates from two epidemiologically different areas in the South and North of Senegal, was carried out. Results A total of 76 Pfmsp1 and 116 Pfmsp2 clones were identified and 135 different alleles were found, 56 and 79 belonged to the pfmsp1 and pfmsp2 genes, respectively. K1 and IC3D7 allelic families were most predominant in both sites. The local haplotype diversity (Hd) and nucleotide diversity (π) were higher in the South than in the North for both genes. For pfmsp1, a high positive Tajima’s D (TD) value was observed in the South (D = 2.0453) while negative TD value was recorded in the North (D = − 1.46045) and F-Statistic (Fst) was 0.19505. For pfmsp2, non-directional selection was found with a highly positive TD test in both areas and Fst was 0.02111. The mean MOI for both genes was 3.07 and 1.76 for the South and the North, respectively, with a statistically significant difference between areas (p = 0.001). Conclusion This study revealed a high genetic diversity of pfmsp1 and pfmsp2 genes and low genetic differentiation in P. falciparum population in Senegal. The MOI means were significantly different between the Southern and Northern areas. Findings also showed that multiplexed amplicon deep sequencing is a useful technique to investigate genetic diversity and molecular epidemiology of P. falciparum infections.

scholarly journals The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Christina Salgado ◽  
George Ayodo ◽  
Michael D. Macklin ◽  
Meetha P. Gould ◽  
Srinivas Nallandhighal ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Malaria Incidence ◽  
Experimental Studies ◽  
Low Density ◽  
Healthy Children ◽  
Cross Sectional Survey ◽  
Western Kenya ◽  
Transcriptional Pattern ◽  
Asymptomatic Infections

Abstract Background Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission. Methods In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa–Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals. Results The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11–15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR. Conclusions This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission.

scholarly journals Malaria Incidence and Associated Risk Factors in and Around Anger Gute Town, Western Ethiopia

2020 ◽  
Author(s):  
Mebrate Dufera ◽  
Oljira Kenea ◽  
Geleta Tadele
Keyword(s):  
Risk Factors ◽  
At Risk ◽  
Malaria Transmission ◽  
Health Center ◽  
Trend Analysis ◽  
Malaria Incidence ◽  
Sub Saharan Africa ◽  
Significant Difference ◽  
Associated Risk Factors ◽  
Western Ethiopia

Abstract Background: Malaria is one of the most important causes of morbidity and mortality in sub-Saharan Africa including Ethiopia. About 75% of the total area of the country is an area of malaria transmission and an estimated 68% of the Ethiopian population is at risk from malaria. Therfore, this study was aimed to evaluate local malaria incidence and associated risk factors in and around Anger Gute town, East Wollega Zone,Oromia Regional State, Western Ethiopia. Methods: Health-facility based cross-sectional study was carried out from June to December 2018. 462 malaria suspected patients attending three health posts and one health center were included in the study. Data were collected using structured questionnaire and laboratory diagnosis of malaria. Data analysis was performed using SPSS version 20.0 for windows. Logistic regression was used to examine the effect of each independent variable on incidence of malaria. P values of less or equal to 0.05 were considered significant. Results : Of 462 malaria suspected cases, 122 (26.4%) had Plasmodium infection which was confirmed by microscopy or RDT. 64.75 %, 32 % and 3.75% of malaria was caused by P. falciparum, P. vivax and mixed infections respectively. Malaria incidence in and around Anger Gute town from June to December 2018 was found to be 0.343 % (122/ 35, 585). No significant difference in incidence of malaria was found by sex and age categories of study participants (P>0.05). Incidence of malaria was significantly lower in urban kebeles compared to rural kebeles (COR= 0.359, P=0.00). Incidence of malaria was significantly associated with presence of stagnant water nearby living house (AOD=186.3, P=0.000), utilization of bed net (AOD=0.08, P=0.000), and IRS (AOD=0.056,P=0.03). Six years malaria trend analysis at Anger Gute Health Center showed that number of confirmed malaria cases was significantly decreased in 2014 - 2018 as compared to 2013. Since 2014; numbers of confirmed malaria cases have been more or less constant in Anger Gute health center. Conclusions: Incidence of malaria in and around Anger Gute town was 3.43 per 1000 population at risk of the disease during the study period and was lower than recent incidence of malaria reported from Ethiopia. Trend analysis of malaria from 2014 to 2018 indicated nearly unchanged numbers of malaria cases. This shows presence of low sustained malaria transmission. Integrated vector control efforts are needed to suppress transmission that lead to elimination of the disease in the study setting. Key words: Anger Gute, malaria, malaria incidence

scholarly journals Molecular epidemiology of Plasmodium falciparum by multiplexed amplicon deep sequencing in Senegal

2020 ◽  
Author(s):  
Tolla NDIAYE ◽  
Mouhamad Sy ◽  
Amy Gaye ◽  
Katherine J. Siddle ◽  
Daniel J. Park ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Molecular Epidemiology ◽  
Deep Sequencing ◽  
Haplotype Diversity ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
The South ◽  
The North ◽  
Significant Difference

Abstract Background Molecular epidemiology can provide important information regarding the genetic diversity and transmission of Plasmodium falciparum , which can assist in designing and monitoring elimination efforts. However, malaria molecular epidemiology including understanding the genetic diversity of the parasite and performing molecular surveillance of transmission has been poorly documented in Senegal. Next Generation Sequencing (NGS) offers a practical, fast and high-throughput approach to understand malaria population genetics. This study aims to unravel the population structure of P. falciparum and to estimate the allelic diversity, multiplicity of infection (MOI), and evolutionary patterns of the malaria parasite using the NGS platform. Methods Multiplex amplicon deep sequencing of merozoite surface protein 1 (PfMSP1) and merozoite surface protein 2 (PfMSP2) genes in fifty-three P. falciparum isolates from two epidemiologically different areas in the South and North of Senegal, was carried out. Results A total of 76 Pfmsp1 and 116 Pfmsp2 clones were identified and 135 different alleles were found, 56 and 79 belonged to the pfmsp1 and pfmsp2 genes, respectively. K1 and IC3D7 allelic families were most predominant in both sites. The local haplotype diversity (Hd) and nucleotide diversity (π) were higher in the South than in the North for both genes. For pfmsp1 , a high positive Tajima’s D (TD) value was observed in the South (D=2.0453) while negative TD value was recorded in the North (D=-1.46045) and F-Statistic (Fst) was 0.19505. For pfmsp2 , non-directional selection was found with a highly positive TD test in both areas and Fst was 0.02111. The mean MOI for both genes was 3.07 and 1.76 for the South and the North, respectively, with a statistically significant difference between areas ( p=0.001 ). Conclusion This study revealed a high genetic diversity of pfmsp1 and pfmsp2 genes and low genetic differentiation in P. falciparum population in Senegal. The MOI means were significantly different between the Southern and Northern areas. Findings also showed that multiplexed amplicon deep sequencing is a useful technique to investigate genetic diversity and molecular epidemiology of P. falciparum infections.

scholarly journals Genetic diversity of Plasmodium falciparum and genetic profile after artemisinin-based combination therapy (ACTs) deployment in Cameroon for the management of uncomplicated malaria in Children

2019 ◽  
Author(s):  
Metoh Theresia Njuabe ◽  
Jun-Hu Chen ◽  
Philip Fon Gah ◽  
Zhou Xia ◽  
Somo.Roger Moyou ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Genetic Profile ◽  
High Identity ◽  
West Region ◽  
Control Intervention ◽  
Allelic Type ◽  
The Impact ◽  
Region Ii

Abstract Background Plasmodium falciparum is the number one cause of malaria morbidity and mortality. Several methods of intervention have been deployed in Cameroon with an attempt to reduce malaria transmission. But evaluation methods mostly based on microscopy and immunology have proven to be cumbersome and expensive. This study aimed at analyzing the genetic diversity of P.falciparum and the impact of ACTs deployment on MOI Method 350 clinical isolates were collected between 2012 and 2013 and, three P. falciparum loci namely, msp-1(block2), msp-2 (block3), and glurp, (region II) characterized by nested PCR and DNA sequencing. Results From this study, a total of 16 different pfmsp1 were identified, including K1, MAD20 and RO33 allelic families. The K1 and MAD20 were the predominant polymorphic allelic types at the msp-1 gene, whereas alleles belonging to 3D7/IC were more frequent at the msp-2 gene. A peculiarity of this study is that RO33 revealed a monomorphic pattern among the msp-1 allelic type. Msp-1 and msp-2 revealed considerably greater parasite diversity than glurp. A total of 27 different msp-2 genotypes were recorded of which 15 belonged to the 3D7-type and 12 to the FC27 allelic families. Alignment of peptides encoded by pfmsp1 and Pfmsp2 reveals that K1 polymorphism had the highest similarity in the P.fmsp1 and Pfmsp2 clade followed by MAD20 with 93% to 100% homology. Indicating that P. falciparum isolates from Cameroon present high identity with allelic sequences from other areas in Africa, suggesting that vaccine developed with k1 and MAD20 of Pfmsp1 allelic variant could be protective for Africa children. The MOI ranged from 2.51 for msp1 to 3.82 for msp2. The overall heterozygosity ranged from 0.55 for msp-1 to 0.96 for msp-2 consistent with the genetic pattern observed in hyperendemic areas. Conclusion The present study reveals that isolates from South West Region of Cameroon are mainly polyclonal with high MOI and highly diverse in respect to both msp-1 and msp-2 despite ACTs deployment aiming at reducing malaria transmission. This study lays emphasis on the use of MOI and genotyping of both msp-1 and msp-2 in the evaluation of malaria control intervention in malaria endemics countries.

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