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  1. Article ; Online: coiaf

    Aris Paschalidis / Oliver J Watson / Ozkan Aydemir / Robert Verity / Jeffrey A Bailey

    PLoS Computational Biology, Vol 19, Iss 6, p e

    Directly estimating complexity of infection with allele frequencies.

    2023  Volume 1010247

    Abstract: In malaria, individuals are often infected with different parasite strains. The complexity of infection (COI) is defined as the number of genetically distinct parasite strains in an individual. Changes in the mean COI in a population have been shown to ... ...

    Abstract In malaria, individuals are often infected with different parasite strains. The complexity of infection (COI) is defined as the number of genetically distinct parasite strains in an individual. Changes in the mean COI in a population have been shown to be informative of changes in transmission intensity with a number of probabilistic likelihood and Bayesian models now developed to estimate the COI. However, rapid, direct measures based on heterozygosity or FwS do not properly represent the COI. In this work, we present two new methods that use easily calculated measures to directly estimate the COI from allele frequency data. Using a simulation framework, we show that our methods are computationally efficient and comparably accurate to current approaches in the literature. Through a sensitivity analysis, we characterize how the distribution of parasite densities, the assumed sequencing depth, and the number of sampled loci impact the bias and accuracy of our two methods. Using our developed methods, we further estimate the COI globally from Plasmodium falciparum sequencing data and compare the results against the literature. We show significant differences in the estimated COI globally between continents and a weak relationship between malaria prevalence and COI.
    Keywords Biology (General) ; QH301-705.5
    Subject code 310
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Immediate pools of malaria infections at diagnosis combined with targeted deep sequencing accurately quantifies frequency of drug resistance mutations

    Ozkan Aydemir / Benedicta Mensah / Patrick W. Marsh / Benjamin Abuaku / James Leslie Myers-Hansen / Jeffrey A. Bailey / Anita Ghansah

    PeerJ, Vol 9, p e

    2021  Volume 11794

    Abstract: Antimalarial resistance surveillance in sub-Saharan Africa is often constrained by logistical and financial challenges limiting its breadth and frequency. At two sites in Ghana, we have piloted a streamlined sample pooling process created immediately by ... ...

    Abstract Antimalarial resistance surveillance in sub-Saharan Africa is often constrained by logistical and financial challenges limiting its breadth and frequency. At two sites in Ghana, we have piloted a streamlined sample pooling process created immediately by sequential addition of positive malaria cases at the time of diagnostic testing. This streamlined process involving a single tube minimized clinical and laboratory work and provided accurate frequencies of all known drug resistance mutations after high-throughput targeted sequencing using molecular inversion probes. Our study validates this method as a cost-efficient, accurate and highly-scalable approach for drug resistance mutation monitoring that can potentially be applied to other infectious diseases such as tuberculosis.
    Keywords Malaria ; Plasmodium falciparum ; Drug resistance ; Molecular inversion probes ; Molecular surveillance ; Medicine ; R ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2021-11-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Temporal and spatial analysis of Plasmodium falciparum genomics reveals patterns of parasite connectivity in a low-transmission district in Southern Province, Zambia

    Abebe A. Fola / Kara A. Moser / Ozkan Aydemir / Chris Hennelly / Tamaki Kobayashi / Timothy Shields / Harry Hamapumbu / Michael Musonda / Ben Katowa / Japhet Matoba / Jennifer C. Stevenson / Douglas E. Norris / Philip E. Thuma / Amy Wesolowski / William J. Moss / Jeffrey A. Bailey / Jonathan J. Juliano / the Southern

    Malaria Journal, Vol 22, Iss 1, Pp 1-

    2023  Volume 11

    Abstract: Abstract Background Understanding temporal and spatial dynamics of malaria transmission will help to inform effective interventions and strategies in regions approaching elimination. Parasite genomics are increasingly used to monitor epidemiologic trends, ...

    Abstract Abstract Background Understanding temporal and spatial dynamics of malaria transmission will help to inform effective interventions and strategies in regions approaching elimination. Parasite genomics are increasingly used to monitor epidemiologic trends, including assessing residual transmission across seasons and importation of malaria into these regions. Methods In a low and seasonal transmission setting of southern Zambia, a total of 441 Plasmodium falciparum samples collected from 8 neighbouring health centres between 2012 and 2018 were genotyped using molecular inversion probes (MIPs n = 1793) targeting a total of 1832 neutral and geographically informative SNPs distributed across the parasite genome. After filtering for quality and missingness, 302 samples and 1410 SNPs were retained and used for downstream population genomic analyses. Results The analyses revealed most (67%, n = 202) infections harboured one clone (monogenomic) with some variation at local level suggesting low, but heterogenous malaria transmission. Relatedness identity-by-descent (IBD) analysis revealed variable distribution of IBD segments across the genome and 6% of pairs were highly-related (IBD ≥ 0.25). Some of the highly-related parasite populations persisted across multiple seasons, suggesting that persistence of malaria in this low-transmission region is fueled by parasites “seeding” across the dry season. For recent years, clusters of clonal parasites were identified that were dissimilar to the general parasite population, suggesting parasite populations were increasingly fragmented at small spatial scales due to intensified control efforts. Clustering analysis using PCA and t-SNE showed a lack of substantial parasite population structure. Conclusion Leveraging both genomic and epidemiological data provided comprehensive picture of fluctuations in parasite populations in this pre-elimination setting of southern Zambia over 7 years.
    Keywords Plasmodium falciparum ; Transmission ; Zambia ; Genomics ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
    Subject code 572
    Language English
    Publishing date 2023-07-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Spatial and epidemiological drivers of Plasmodium falciparum malaria among adults in the Democratic Republic of the Congo

    Jonathan J Juliano / Jonathan B Parr / Steven R Meshnick / Molly Deutsch-Feldman / Nicholas F Brazeau / Kyaw L Thwai / Jeremie Muwonga / Melchior Kashamuka / Antoinette Tshefu Kitoto / Ozkan Aydemir / Jeffrey A Bailey / Jessie K Edwards / Robert Verity / Michael Emch / Emily W Gower

    BMJ Global Health, Vol 5, Iss

    2020  Volume 6

    Abstract: Background Adults are frequently infected with malaria and may serve as a reservoir for further transmission, yet we know relatively little about risk factors for adult infections. In this study, we assessed malaria risk factors among adults using ... ...

    Abstract Background Adults are frequently infected with malaria and may serve as a reservoir for further transmission, yet we know relatively little about risk factors for adult infections. In this study, we assessed malaria risk factors among adults using samples from the nationally representative, cross-sectional 2013–2014 Demographic and Health Survey (DHS) conducted in the Democratic Republic of the Congo (DRC). We further explored differences in risk factors by urbanicity.Methods Plasmodium falciparum infection was determined by PCR. Covariates were drawn from the DHS to model individual, community and environmental-level risk factors for infection. Additionally, we used deep sequencing data to estimate the community-level proportions of drug-resistant infections and included these estimates as potential risk factors. All identified factors were assessed for differences in associations by urbanicity.Results A total of 16 126 adults were included. Overall prevalence of malaria was 30.3% (SE=1.1) by PCR; province-level prevalence ranged from 6.7% to 58.3%. Only 17% of individuals lived in households with at least one bed-net for every two people, as recommended by the WHO. Protective factors included increasing within-household bed-net coverage (Prevalence Ratio=0.85, 95% CI=0.76–0.95) and modern housing (PR=0.58, 95% CI=0.49–0.69). Community-level protective factors included increased median wealth (PR=0.87, 95% CI=0.83–0.92). Education, wealth, and modern housing showed protective associations in cities but not in rural areas.Conclusions The DRC continues to suffer from a high burden of malaria; interventions that target high-risk groups and sustained investment in malaria control are sorely needed. Areas of high prevalence should be prioritised for interventions to target the largest reservoirs for further transmission.
    Keywords Medicine (General) ; R5-920 ; Infectious and parasitic diseases ; RC109-216
    Subject code 610
    Language English
    Publishing date 2020-06-01T00:00:00Z
    Publisher BMJ Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Falciparum malaria from coastal Tanzania and Zanzibar remains highly connected despite effective control efforts on the archipelago

    Andrew P. Morgan / Nicholas F. Brazeau / Billy Ngasala / Lwidiko E. Mhamilawa / Madeline Denton / Mwinyi Msellem / Ulrika Morris / Dayne L. Filer / Ozkan Aydemir / Jeffrey A. Bailey / Jonathan B. Parr / Andreas Mårtensson / Anders Bjorkman / Jonathan J. Juliano

    Malaria Journal, Vol 19, Iss 1, Pp 1-

    2020  Volume 14

    Abstract: Abstract Background Tanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been ... ...

    Abstract Abstract Background Tanzania’s Zanzibar archipelago has made significant gains in malaria control over the last decade and is a target for malaria elimination. Despite consistent implementation of effective tools since 2002, elimination has not been achieved. Importation of parasites from outside of the archipelago is thought to be an important cause of malaria’s persistence, but this paradigm has not been studied using modern genetic tools. Methods Whole-genome sequencing (WGS) was used to investigate the impact of importation, employing population genetic analyses of Plasmodium falciparum isolates from both the archipelago and mainland Tanzania. Ancestry, levels of genetic diversity and differentiation, patterns of relatedness, and patterns of selection between these two populations were assessed by leveraging recent advances in deconvolution of genomes from polyclonal malaria infections. Results Significant decreases in the effective population sizes were inferred in both populations that coincide with a period of decreasing malaria transmission in Tanzania. Identity by descent analysis showed that parasites in the two populations shared long segments of their genomes, on the order of 5 cM, suggesting shared ancestry within the last 10 generations. Even with limited sampling, two of isolates between the mainland and Zanzibar were identified that are related at the expected level of half-siblings, consistent with recent importation. Conclusions These findings suggest that importation plays an important role for malaria incidence on Zanzibar and demonstrate the value of genomic approaches for identifying corridors of parasite movement to the island.
    Keywords Plasmodium ; Malaria ; Population genetics ; Arctic medicine. Tropical medicine ; RC955-962 ; Infectious and parasitic diseases ; RC109-216
    Subject code 616
    Language English
    Publishing date 2020-01-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Drug susceptibility of Plasmodium falciparum in eastern Uganda

    Patrick K Tumwebaze, MS / Thomas Katairo, MS / Martin Okitwi, BS / Oswald Byaruhanga, Dip / Stephen Orena, BS / Victor Asua, MS / Marvin Duvalsaint, PhD / Jennifer Legac, BS / Sevil Chelebieva, BS / Frida G Ceja, BS / Stephanie A Rasmussen, MS / Melissa D Conrad, PhD / Samuel L Nsobya, PhD / Ozkan Aydemir, PhD / Jeffrey A Bailey, PhD / Brett R Bayles, PhD / Philip J Rosenthal, ProfMD / Roland A Cooper, ProfPhD

    The Lancet Microbe, Vol 2, Iss 9, Pp e441-e

    a longitudinal phenotypic and genotypic study

    2021  Volume 449

    Abstract: Summary: Background: Treatment and control of malaria depends on artemisinin-based combination therapies (ACTs) and is challenged by drug resistance, but thus far resistance to artemisinins and partner drugs has primarily occurred in southeast Asia. The ... ...

    Abstract Summary: Background: Treatment and control of malaria depends on artemisinin-based combination therapies (ACTs) and is challenged by drug resistance, but thus far resistance to artemisinins and partner drugs has primarily occurred in southeast Asia. The aim of this study was to characterise antimalarial drug susceptibility of Plasmodium falciparum isolates from Tororo and Busia districts in Uganda. Methods: In this prospective longitudinal study, P falciparum isolates were collected from patients aged 6 months or older presenting at the Tororo District Hospital (Tororo district, a site with relatively low malaria incidence) or Masafu General Hospital (Busia district, a high-incidence site) in eastern Uganda with clinical symptoms of malaria, a positive Giemsa-stained blood film for P falciparum, and no signs of severe disease. Ex-vivo susceptibilities to ten antimalarial drugs were measured using a 72-h microplate growth inhibition assay with SYBR Green detection. Relevant P falciparum genetic polymorphisms were characterised by molecular methods. We compared results with those from earlier studies in this region and searched for associations between drug susceptibility and parasite genotypes. Findings: From June 10, 2016, to July 29, 2019, 361 P falciparum isolates were collected in the Busia district and 79 in the Tororo district from 440 participants. Of 440 total isolates, 392 (89%) successfully grew in culture and showed excellent drug susceptibility for chloroquine (median half-maximal inhibitory concentration [IC50] 20·0 nM [IQR 12·0–26·0]), monodesethylamodiaquine (7·1 nM [4·3–8·9]), pyronaridine (1·1 nM [0·7–2·3]), piperaquine (5·6 nM [3·3–8·6]), ferroquine (1·8 nM [1·5–3·3]), AQ-13 (24·0 nM [17·0–32·0]), lumefantrine (5·1 nM [3·2–7·7]), mefloquine (9·5 nM [6·6–13·0]), dihydroartemisinin (1·5 nM [1·0–2·0]), and atovaquone (0·3 nM [0·2–0·4]). Compared with results from our study in 2010–13, significant improvements in susceptibility were seen for chloroquine (median IC50 288·0 nM [IQR 122·0–607·0]; ...
    Keywords Medicine (General) ; R5-920 ; Microbiology ; QR1-502
    Subject code 572
    Language English
    Publishing date 2021-09-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC

    Robert Verity / Ozkan Aydemir / Nicholas F. Brazeau / Oliver J. Watson / Nicholas J. Hathaway / Melchior Kashamuka Mwandagalirwa / Patrick W. Marsh / Kyaw Thwai / Travis Fulton / Madeline Denton / Andrew P. Morgan / Jonathan B. Parr / Patrick K. Tumwebaze / Melissa Conrad / Philip J. Rosenthal / Deus S. Ishengoma / Jeremiah Ngondi / Julie Gutman / Modest Mulenga /
    Douglas E. Norris / William J. Moss / Benedicta A. Mensah / James L. Myers-Hansen / Anita Ghansah / Antoinette K. Tshefu / Azra C. Ghani / Steven R. Meshnick / Jeffrey A. Bailey / Jonathan J. Juliano

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 10

    Abstract: The genome of the malaria parasite Plasmodium falciparum contains a record of past evolutionary forces. Here, using 2537 parasite sequences from the Democratic Republic of the Congo, the authors demonstrate how drug pressure and human movement have ... ...

    Abstract The genome of the malaria parasite Plasmodium falciparum contains a record of past evolutionary forces. Here, using 2537 parasite sequences from the Democratic Republic of the Congo, the authors demonstrate how drug pressure and human movement have shaped the present-day parasite population.
    Keywords Science ; Q
    Language English
    Publishing date 2020-04-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC

    Robert Verity / Ozkan Aydemir / Nicholas F. Brazeau / Oliver J. Watson / Nicholas J. Hathaway / Melchior Kashamuka Mwandagalirwa / Patrick W. Marsh / Kyaw Thwai / Travis Fulton / Madeline Denton / Andrew P. Morgan / Jonathan B. Parr / Patrick K. Tumwebaze / Melissa Conrad / Philip J. Rosenthal / Deus S. Ishengoma / Jeremiah Ngondi / Julie Gutman / Modest Mulenga /
    Douglas E. Norris / William J. Moss / Benedicta A. Mensah / James L. Myers-Hansen / Anita Ghansah / Antoinette K. Tshefu / Azra C. Ghani / Steven R. Meshnick / Jeffrey A. Bailey / Jonathan J. Juliano

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 10

    Abstract: The genome of the malaria parasite Plasmodium falciparum contains a record of past evolutionary forces. Here, using 2537 parasite sequences from the Democratic Republic of the Congo, the authors demonstrate how drug pressure and human movement have ... ...

    Abstract The genome of the malaria parasite Plasmodium falciparum contains a record of past evolutionary forces. Here, using 2537 parasite sequences from the Democratic Republic of the Congo, the authors demonstrate how drug pressure and human movement have shaped the present-day parasite population.
    Keywords Science ; Q
    Language English
    Publishing date 2020-04-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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