scholarly journals Temporal and spatial analysis of Plasmodium falciparum genomics reveals patterns of connectivity in a low-transmission district in Southern Province, Zambia

2021 ◽  
Author(s):  
Kara A Moser ◽  
Ozkan Aydemir ◽  
Chris Hennelly ◽  
Tamaki Kobayashi ◽  
Timothy Shields ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Genetic Relatedness ◽  
Spatial Dynamics ◽  
Epidemiological Data ◽  
Dried Blood Spots ◽  
Health Centers ◽  
Low Transmission ◽  
Southern Province ◽  
Temporal And Spatial

Understanding temporal and spatial dynamics of ongoing malaria transmission will be critical to inform effective interventions and elimination strategies in low transmission regions approaching elimination. Parasite genomics are being used as a tool to monitor epidemiologic trends, including assessing residual transmission across seasons or importation of malaria into these regions. Southern Province, Zambia is a low-transmission setting with seasonal malaria. We genotyped 441 Plasmodium falciparum samples using molecular inversion probes at 1,832 positions across the genome, using dried blood spots collected from 2012-2018 from 8 health centers in the catchment area of Macha Hospital in Choma District. We show that highly related parasites persist across multiple seasons, suggesting that the persistence of malaria is at least in part fueled by parasites seeding across the dry season. In addition, we identify clusters of clonal parasites that are dissimilar to the general population, suggesting that introduction of parasites from elsewhere may contribute to the continued malaria burden. We identified signals of population size fluctuation over the course of individual transmission seasons, suggesting a ramp-up of malaria transmission from a seasons beginning. Despite the small spatial scale of the study (2,000 sq km), we identified an inverse relationship between genetic relatedness of parasite pairs and distance between health centers, as well as increased relatedness between specific health centers. These results, leveraging both genomic and epidemiological data, provide a comprehensive picture of fluctuations in parasite populations in this pre-elimination setting of southern Zambia.

scholarly journals Genetic analysis reveals unique characteristics of Plasmodium falciparum parasite populations in Haiti

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Rachel F. Daniels ◽  
Stella Chenet ◽  
Eric Rogier ◽  
Naomi Lucchi ◽  
Camelia Herman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Relatedness ◽  
Dried Blood Spots ◽  
Caribbean Region ◽  
Nucleotide Polymorphisms ◽  
Single Genome ◽  
Plasmodium Falciparum Parasite ◽  
Genetic Signatures ◽  
Parasite Populations

Abstract Background With increasing interest in eliminating malaria from the Caribbean region, Haiti is one of the two countries on the island of Hispaniola with continued malaria transmission. While the Haitian population remains at risk for malaria, there are a limited number of cases annually, making conventional epidemiological measures such as case incidence and prevalence of potentially limited value for fine-scale resolution of transmission patterns and trends. In this context, genetic signatures may be useful for the identification and characterization of the Plasmodium falciparum parasite population in order to identify foci of transmission, detect outbreaks, and track parasite movement to potentially inform malaria control and elimination strategies. Methods This study evaluated the genetic signals based on analysis of 21 single-nucleotide polymorphisms (SNPs) from 462 monogenomic (single-genome) P. falciparum DNA samples extracted from dried blood spots collected from malaria-positive patients reporting to health facilities in three southwestern Haitian departments (Nippes, Grand’Anse, and Sud) in 2016. Results Assessment of the parasite genetic relatedness revealed evidence of clonal expansion within Nippes and the exchange of parasite lineages between Nippes, Sud, and Grand'Anse. Furthermore, 437 of the 462 samples shared high levels of genetic similarity–at least 20 of 21 SNPS–with at least one other sample in the dataset. Conclusions These results revealed patterns of relatedness suggestive of the repeated recombination of a limited number of founding parasite types without significant outcrossing. These genetic signals offer clues to the underlying relatedness of parasite populations and may be useful for the identification of the foci of transmission and tracking of parasite movement in Haiti for malaria elimination.

scholarly journals Genetic analysis reveals unique characteristics of Plasmodium falciparum parasite populations in Haiti

2020 ◽  
Author(s):  
Rachel Daniels ◽  
Stella Chenet ◽  
Eric Rogier ◽  
Naomi Lucchi ◽  
Camelia Herman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Relatedness ◽  
Dried Blood Spots ◽  
Caribbean Region ◽  
Nucleotide Polymorphisms ◽  
Single Genome ◽  
Plasmodium Falciparum Parasite ◽  
Genetic Signatures ◽  
Parasite Populations

Abstract Background: With increasing interest in eliminating malaria from the Caribbean region, Haiti is one of the two countries on the island of Hispaniola with continued malaria transmission. While the Haitian populace remains at risk for malaria, there are a limited number of cases annually, making conventional epidemiological measures such as case incidence and prevalence of potentially limited value for fine-scale resolution of transmission patterns and trends. In this context, genetic signatures may be useful for the identification and characterization of the Plasmodium falciparum parasite population in order to identify foci of transmission, detect outbreaks, and track parasite movement to potentially inform malaria control and elimination strategies. Methods: This study evaluated the genetic signals based on analysis of 21 single-nucleotide polymorphisms (SNPs) from 462 monogenomic (single-genome) P. falciparum DNA samples extracted from dried blood spots collected from malaria-positive patients reporting to health facilities in three southwestern Haitian departments (Nippes, Grand’Anse, and Sud) in 2016. Results: Assessment of the parasite genetic relatedness revealed evidence of clonal expansion within Nippes and the exchange of parasite lineages between Nippes, Sud, and Grand'Anse. Furthermore, 437 of the 462 samples shared high levels of genetic similarity­­—at least 20 of 21 SNPS—with at least one other sample in the dataset. Conclusions: These results revealed patterns of relatedness suggestive of the repeated recombination of a limited number of founding parasite types without significant outcrossing. These genetic signals offer clues to the underlying relatedness of parasite populations and may be useful for the identification of the foci of transmission and tracking of parasite movement in Haiti for malaria elimination.

scholarly journals Genetic Analysis Reveals Unique Characteristics of Plasmodium Falciparum Parasite Populations in Haiti

2020 ◽  
Author(s):  
Rachel Daniels ◽  
Stella Chenet ◽  
Eric Rogier ◽  
Naomi Lucchi ◽  
Camelia Herman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Relatedness ◽  
Dried Blood Spots ◽  
Caribbean Region ◽  
Nucleotide Polymorphisms ◽  
Single Genome ◽  
Plasmodium Falciparum Parasite ◽  
Genetic Signatures ◽  
Parasite Populations

Abstract Background: With increasing interest in eliminating malaria from the Caribbean region, Haiti is one of the two countries on the island of Hispaniola with continued malaria transmission. While the Haitian populace remains at risk for malaria, there are a limited number of cases annually, making conventional epidemiological measures such as case incidence and prevalence of potentially limited value for fine-scale resolution of transmission patterns and trends. In this context, genetic signatures may be useful for the identification and characterization of the Plasmodium falciparum parasite population in order to identify foci of transmission, detect outbreaks, and track parasite movement to potentially inform malaria control and elimination strategies. Methods: This study evaluated the genetic signals based on analysis of 21 single-nucleotide polymorphisms (SNPs) from 462 monogenomic (single-genome) P. falciparum DNA samples extracted from dried blood spots collected from malaria-positive patients reporting to health facilities in three southwestern Haitian departments (Nippes, Grand’Anse, and Sud) in 2016. Results: Assessment of the parasite genetic relatedness revealed evidence of clonal expansion within Nippes and the exchange of parasite lineages between Nippes, Sud, and Grand'Anse. Furthermore, 437 of the 462 samples shared high levels of genetic similarity­­—at least 20 of 21 SNPS—with at least one other sample in the dataset. Conclusions: These results revealed patterns of relatedness suggestive of the repeated recombination of a limited number of founding parasite types without significant outcrossing. These genetic signals offer clues to the underlying relatedness of parasite populations and may be useful for the identification of the foci of transmission and tracking of parasite movement in Haiti for malaria elimination.

scholarly journals Ultrasensitive diagnostics for low density asymptomatic Plasmodium falciparum infections in low transmission settings

2020 ◽  
Author(s):  
Kayvan Zainabadi
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Elimination ◽  
Field Performance ◽  
Dried Blood Spots ◽  
Multidrug Resistant ◽  
Current Status ◽  
Malaria Surveillance ◽  
Low Transmission ◽  
Large Populations ◽  
Asymptomatic Individuals

The emergence of multidrug resistant Plasmodium falciparum malaria in Southeast Asia has accelerated regional malaria elimination efforts. Most malaria in this and other low transmission settings exists in asymptomatic individuals, which conventional diagnostic tests lack the sensitivity to detect. This has led to the development of new ultrasensitive diagnostics that are capable of detecting these low parasitemic infections. This review summarizes the current status of ultrasensitive technologies, including PCR and LAMP-based methods, as well as a newly developed ultrasensitive rapid diagnostic test (uRDT). The sensitivity, specificity, and field performance of these platforms will be examined, as well as their suitability for use in resource limited settings to aid in malaria elimination efforts. uRDTs, with their improved sensitivity, are now able to detect approximately half of asymptomatic infections, providing a useful point of contact tool for malaria surveillance. The increased sensitivity and high-throughput nature of PCR-based tests make them ideal for screening large populations in places where laboratory capacity exists, and the recent commercialization of malaria LAMP kits should facilitate their adoption as a public health tool in places where such infrastructure is lacking. Finally, recent advances with dried blood spots may enable the utilization of the extensive laboratory infrastructure of higher income countries to assist with molecular surveillance in support of malaria elimination. If malaria is to be eliminated in SEA and other low endemic regions, then ultrasensitive diagnostics may play a key role in identifying and clearing the vast asymptomatic pool of infections that are common to these regions.

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 Genetic Diversity of Plasmodium Falciparum Populations in three Malaria Transmission Settings in Madagascar

2021 ◽  
Author(s):  
Fanomezantsoa Ralinoro ◽  
Tovonahary Angelo Rakotomanga ◽  
Riana Rakotosaona ◽  
Danielle A. Doll Rakoto ◽  
Didier Menard ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Drug Efficacy ◽  
Control Measures ◽  
Health Centers ◽  
Allele Specific ◽  
Genetic Profiles ◽  
The Impact ◽  
Pcr Targeting

Abstract BackgroundThe assessment of the genetic diversity of Plasmodium falciparum parasites from various malaria transmission settings could help to define tailored and dedicated local strategies for malaria control and elimination. To date, this information is scarce in Madagascar. To fill this gap, a study aiming at investigating the genetic diversity of P. falciparum populations in three epidemiological facies (Equatorial, Tropical and Fringes) in Madagascar was conducted.MethodsTwo hundred sixty-six P. falciparum isolates were obtained from patients with uncomplicated malaria enrolled in clinical drug efficacy studies conducted in health centers at Tsaratanana (Equatorial facies), Antanimbary (Tropical facies) and Anjoma Ramartina (Fringes) in 2013 and 2016. Parasite DNA was extracted from blood samples collected prior antimalarial treatment. Plasmodium species were identified by nested-PCR targeting 18S rRNA gene. The genetic profiles of P. falciparum parasites were defined by assessing the polymorphic regions of the msp-1 and msp-2 genes using allele-specific nested-PCR.ResultsA total of 58 alleles were detected for msp-1 (18 alleles) and msp-2 (40 alleles) among P. falciparum samples tested. K1 (62.9%, 139/221) and FC27 (69.5%, 114/164) were the most predominant msp-1 and msp-2 allelic families, although the proportions of the msp-1 and msp-2 alleles varied significantly between sites. Polyclonal infections were more frequent in site located in the Equatorial facies (69.8%) compared to sites in the Tropical facies (60.5%) and Fringes (58.1%). Population genetic measures showed that the genetic diversity was similar between sites and the parasite flow within sites was limited.ConclusionThis study provides recent information on the genetic diversity of P. falciparum populations in three transmission facies in Madagascar and valuable baseline data to further evaluate the impact of the control measures implemented in Madagascar.

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 Genetic analysis reveals unique characteristics of Plasmodium falciparum parasite populations in Haiti

2020 ◽  
Author(s):  
Rachel Daniels ◽  
Stella Chenet ◽  
Eric Rogier ◽  
Naomi Lucchi ◽  
Camelia Herman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Genetic Relatedness ◽  
Dried Blood Spots ◽  
Caribbean Region ◽  
Nucleotide Polymorphisms ◽  
Single Genome ◽  
Plasmodium Falciparum Parasite ◽  
Genetic Signatures ◽  
Parasite Populations

Abstract Background With increasing interest in eliminating malaria from the Caribbean region, Haiti is one of the two countries on the island of Hispaniola with continued malaria transmission. While the Haitian population remains at risk for malaria, there are a limited number of cases annually, making conventional epidemiological measures such as case incidence and prevalence of potentially limited value for fine-scale resolution of transmission patterns and trends. In this context, genetic signatures may be useful for the identification and characterization of the Plasmodium falciparum parasite population in order to identify foci of transmission, detect outbreaks, and track parasite movement to potentially inform malaria control and elimination strategies. Methods This study evaluated the genetic signals based on analysis of 21 single-nucleotide polymorphisms (SNPs) from 462 monogenomic (single-genome) P. falciparum DNA samples extracted from dried blood spots collected from malaria-positive patients reporting to health facilities in three southwestern Haitian departments (Nippes, Grand’Anse, and Sud) in 2016. Results Assessment of the parasite genetic relatedness revealed evidence of clonal expansion within Nippes and the exchange of parasite lineages between Nippes, Sud, and Grand'Anse. Furthermore, 437 of the 462 samples shared high levels of genetic similarity–at least 20 of 21 SNPS–with at least one other sample in the dataset. Conclusions These results revealed patterns of relatedness suggestive of the repeated recombination of a limited number of founding parasite types without significant outcrossing. These genetic signals offer clues to the underlying relatedness of parasite populations and may be useful for the identification of the foci of transmission and tracking of parasite movement in Haiti for malaria elimination.

scholarly journals Long-distance transmission patterns modelled from SNP barcodes of Plasmodium falciparum infections in The Gambia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alfred Amambua-Ngwa ◽  
David Jeffries ◽  
Julia Mwesigwa ◽  
Aminata Seedy-Jawara ◽  
Joseph Okebe ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Genetic Relatedness ◽  
Malaria Prevalence ◽  
The Gambia ◽  
Long Distance ◽  
Travel History ◽  
Transmission Season ◽  
Malaria Transmission Season ◽  
Likelihood Model

Abstract Malaria has declined significantly in The Gambia and determining transmission dynamics of Plasmodium falciparum can help targeting control interventions towards elimination. This can be inferred from genetic similarity between parasite isolates from different sites and timepoints. Here, we imposed a P. falciparum life cycle time on a genetic distance likelihood model to determine transmission paths from a 54 SNP barcode of 355 isolates. Samples were collected monthly during the 2013 malaria season from six pairs of villages spanning 300 km from western to eastern Gambia. There was spatial and temporal hierarchy in pairwise genetic relatedness, with the most similar barcodes from isolates within the same households and village. Constrained by travel data, the model detected 60 directional transmission events, with 27% paths linking persons from different regions. We identified 13 infected individuals (4.2% of those genotyped) responsible for 2 to 8 subsequent infections within their communities. These super-infectors were mostly from high transmission villages. When considering paths between isolates from the most distant regions (west vs east) and travel history, there were 3 transmission paths from eastern to western Gambia, all at the peak (October) of the malaria transmission season. No paths with known travel originated from the extreme west to east. Although more than half of all paths were within-village, parasite flow from east to west may contribute to maintain transmission in western Gambia, where malaria transmission is already low. Therefore, interrupting malaria transmission in western Gambia would require targeting eastern Gambia, where malaria prevalence is substantially higher, with intensified malaria interventions.

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