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

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.

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

10.21203/rs.3.rs-37125/v1 ◽

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.

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

10.21203/rs.3.rs-37125/v3 ◽

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.

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Micro-epidemiological structuring of Plasmodium falciparum parasite populations in regions with varying transmission intensities in Africa

Wellcome Open Research ◽

10.12688/wellcomeopenres.10784.2 ◽

2017 ◽

Vol 2 ◽

pp. 10 ◽

Cited By ~ 4

Author(s):

Irene Omedo ◽

Polycarp Mogeni ◽

Teun Bousema ◽

Kirk Rockett ◽

Alfred Amambua-Ngwa ◽

...

Keyword(s):

Genetic Relatedness ◽

Temporal Structure ◽

Principal Component ◽

Nucleotide Polymorphisms ◽

Homogeneous Population ◽

Space And Time ◽

Plasmodium Falciparum Parasite ◽

Spatio Temporal ◽

Parasite Populations ◽

The Relationship

Background: The first models of malaria transmission assumed a completely mixed and homogeneous population of parasites. Recent models include spatial heterogeneity and variably mixed populations. However, there are few empiric estimates of parasite mixing with which to parametize such models. Methods: Here we genotype 276 single nucleotide polymorphisms (SNPs) in 5199 P. falciparum isolates from two Kenyan sites (Kilifi county and Rachuonyo South district) and one Gambian site (Kombo coastal districts) to determine the spatio-temporal extent of parasite mixing, and use Principal Component Analysis (PCA) and linear regression to examine the relationship between genetic relatedness and distance in space and time for parasite pairs. Results: Using 107, 177 and 82 SNPs that were successfully genotyped in 133, 1602, and 1034 parasite isolates from The Gambia, Kilifi and Rachuonyo South district, respectively, we show that there are no discrete geographically restricted parasite sub-populations, but instead we see a diffuse spatio-temporal structure to parasite genotypes. Genetic relatedness of sample pairs is predicted by relatedness in space and time. Conclusions: Our findings suggest that targeted malaria control will benefit the surrounding community, but unfortunately also that emerging drug resistance will spread rapidly through the population.

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Micro-epidemiological structuring of Plasmodium falciparum parasite populations in regions with varying transmission intensities in Africa.

Wellcome Open Research ◽

10.12688/wellcomeopenres.10784.1 ◽

2017 ◽

Vol 2 ◽

pp. 10 ◽

Cited By ~ 5

Author(s):

Irene Omedo ◽

Polycarp Mogeni ◽

Teun Bousema ◽

Kirk Rockett ◽

Alfred Amambua-Ngwa ◽

...

Keyword(s):

Genetic Relatedness ◽

Temporal Structure ◽

Principal Component ◽

Nucleotide Polymorphisms ◽

Homogeneous Population ◽

Space And Time ◽

Plasmodium Falciparum Parasite ◽

Spatio Temporal ◽

Parasite Populations ◽

The Relationship

Background: The first models of malaria transmission assumed a completely mixed and homogeneous population of parasites. Recent models include spatial heterogeneity and variably mixed populations. However, there are few empiric estimates of parasite mixing with which to parametize such models. Methods: Here we genotype 276 single nucleotide polymorphisms (SNPs) in 5199 P. falciparum isolates from two Kenyan sites and one Gambian site to determine the spatio-temporal extent of parasite mixing, and use Principal Component Analysis (PCA) and linear regression to examine the relationship between genetic relatedness and relatedness in space and time for parasite pairs. Results: We show that there are no discrete geographically restricted parasite sub-populations, but instead we see a diffuse spatio-temporal structure to parasite genotypes. Genetic relatedness of sample pairs is predicted by relatedness in space and time. Conclusions: Our findings suggest that targeted malaria control will benefit the surrounding community, but unfortunately also that emerging drug resistance will spread rapidly through the population.

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Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant genotype frequencies in African Plasmodium falciparum parasite populations

Malaria Journal ◽

10.1186/1475-2875-9-247 ◽

2010 ◽

Vol 9 (1) ◽

pp. 247 ◽

Cited By ~ 63

Author(s):

Sankar Sridaran ◽

Shannon K McClintock ◽

Luke M Syphard ◽

Karen M Herman ◽

John W Barnwell ◽

...

Keyword(s):

Drug Resistance ◽

Plasmodium Falciparum ◽

Dihydrofolate Reductase ◽

Meta Analysis ◽

Mutant Genotype ◽

Dihydropteroate Synthase ◽

Genotype Frequencies ◽

Plasmodium Falciparum Parasite ◽

Parasite Populations ◽

Falciparum Parasite

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Prevalence and factors associated with carriage of Pfmdr1 polymorphisms among pregnant women receiving intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and artemether-lumefantrine for malaria treatment in Burkina Faso

Malaria Journal ◽

10.1186/s12936-020-03473-5 ◽

2020 ◽

Vol 19 (1) ◽

Author(s):

Hamtandi Magloire Natama ◽

Rouamba Toussaint ◽

Djamina Line Cerine Bazié ◽

Sékou Samadoulougou ◽

Maminata Coulibaly-Traoré ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Burkina Faso ◽

Pregnant Women ◽

Mutant Allele ◽

Intermittent Preventive Treatment ◽

Preventive Treatment ◽

Dried Blood Spots ◽

Nucleotide Polymorphisms ◽

High Coverage ◽

Factors Associated

Abstract Background Single nucleotide polymorphisms occurring in the Plasmodium falciparum multidrug resistant gene 1 (pfmdr1) are known to be associated with aminoquinoline resistance and, therefore, represent key P. falciparum markers for monitoring resistance both in susceptible groups (children under 5 years old and pregnant women) and in the general population. This study aimed to determine prevalence and factors associated with the carriage of pfmdr1 N86Y, Y184F and D1246Y polymorphisms among pregnant women in a setting of high malaria transmission in Burkina Faso. Methods Plasmodium falciparum isolates were collected at the first antenatal care visit (ANC-1) as well as at delivery from pregnant women participating in the COSMIC trial (NTC01941264), which assessed malaria preventive interventions during pregnancy in the Nanoro Health District. Here, pregnant women received intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) and malaria infections and/or diseases were treated using artemether-lumefantrine (AL) during the trial. Parasite DNA was extracted from dried blood spots and the presence of pfmdr1 mutations at positions 86, 184 and 1246 was determined using nested PCR, followed by restriction fragment length polymorphism (RFLP) analysis. Results A prevalence of 13.2% (20/151) and 12.1% (14/116) of the pfmdr1 86Y mutant allele was found at ANC-1 and at delivery, respectively, while no mutant allele was observed for Y184F and D1246Y codons at both ANC-1 and at delivery. There were no significant factors associated with pfmdr1 86Y mutant allele carriage at ANC-1. However, malaria infections at delivery with a parasite density above the median (2237.2 (IQR: 613.5–11,425.7) parasites/µl) was associated with an increase risk of pfmdr1 86Y mutant allele carriage (AOR = 5.5 (95% CI 1.07–28.0); P = 0.04). In contrast, both three or more IPTp-SP doses (AOR = 0.25 (95% CI 0.07–0.92); P = 0.04) and one or more AL treatment (AOR = 0.25 (95% CI 0.07–0.89); P = 0.03) during pregnancy were associated with a significant reduce risk of pfmdr1 86Y mutant allele carriage at delivery. Conclusion These findings suggest that both high coverage of IPTp-SP and the use of AL for the treatment of malaria infection/disease during pregnancy select for pfmdr1 N86 wild-type allele at delivery.

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