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  1. Article: Selection of artemisinin partial resistance Kelch13 mutations in Uganda in 2016-22 was at a rate comparable to that seen previously in South-East Asia.

    Meier-Scherling, Cecile P G / Watson, Oliver J / Asua, Victor / Ghinai, Isaac / Katairo, Thomas / Garg, Shreeya / Conrad, Melissa / Rosenthal, Philip J / Okell, Lucy C / Bailey, Jeffrey A

    medRxiv : the preprint server for health sciences

    2024  

    Abstract: Background: Artemisinin partial resistance, mediated by mutations in the : Methods: We investigated K13 mutation prevalence at 16 sites in Uganda (2016-2022, 6586 samples), and five sites in SEA (2003-2018, 5465 samples) by calculating selection ... ...

    Abstract Background: Artemisinin partial resistance, mediated by mutations in the
    Methods: We investigated K13 mutation prevalence at 16 sites in Uganda (2016-2022, 6586 samples), and five sites in SEA (2003-2018, 5465 samples) by calculating selection coefficients using Bayesian mixed-effect linear models. We then tested whether SEA K13 mutation prevalence could have been forecast accurately using up to the first five years of available data and forecast future K13 mutation prevalence in Uganda.
    Findings: The selection coefficient for the prevalence of relevant K13 mutations (441L, 469F/Y, 561H, 675V) was estimated at s=0·383 (95% CrI: 0·247 - 0·528) per year, a 38% relative prevalence increase. Selection coefficients across Uganda were s=0·968 (0·463 - 1·569) for 441L, s=0·153 (-0·445 - 0·727) for 469F, s=0·222 (-0·011 - 0·398) for 469Y, and s=0·152 (-0·023 - 0·312) for 675V. In SEA, the selection coefficient was s=-0·005 (-0·852 - 0·814) for 539T, s=0·574 (-0·092 - 1·201) for 580Y, and s=0·308 (0·089 - 0·536) for all validated K13 mutations. Forecast prevalences for Uganda assuming constant selection neared fixation (>95% prevalence) within a decade (2028-2033) for combined K13 mutations.
    Interpretation: The selection of K13 mutations in Uganda was at a comparable rate to that observed in SEA, suggesting K13 mutations may continue to increase quickly in Uganda.
    Funding: NIH R01AI156267, R01AI075045, and R01AI089674.
    Language English
    Publishing date 2024-02-04
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2024.02.03.24302209
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Persistence of the ground beetle (Coleoptera: Carabidae) microbiome to diet manipulation.

    Silver, Anita / Perez, Sean / Gee, Melanie / Xu, Bethany / Garg, Shreeya / Will, Kipling / Gill, Aman

    PloS one

    2021  Volume 16, Issue 3, Page(s) e0241529

    Abstract: Host-associated microbiomes can play important roles in the ecology and evolution of their insect hosts, but bacterial diversity in many insect groups remains poorly understood. Here we examine the relationship between host environment, host traits, and ... ...

    Abstract Host-associated microbiomes can play important roles in the ecology and evolution of their insect hosts, but bacterial diversity in many insect groups remains poorly understood. Here we examine the relationship between host environment, host traits, and microbial diversity in three species in the ground beetle family (Coleoptera: Carabidae), a group of roughly 40,000 species that synthesize a wide diversity of defensive compounds. This study used 16S amplicon sequencing to profile three species that are phylogenetically distantly related, trophically distinct, and whose defensive chemical secretions differ: Anisodactylus similis LeConte, 1851, Pterostichus serripes (LeConte, 1875), and Brachinus elongatulus Chaudoir, 1876. Wild-caught beetles were compared to individuals maintained in the lab for two weeks on carnivorous, herbivorous, or starvation diets (n = 3 beetles for each species-diet combination). Metagenomic samples from two highly active tissue types-guts, and pygidial gland secretory cells (which produce defensive compounds)-were processed and sequenced separately from those of the remaining body. Bacterial composition and diversity of these ground beetles were largely resilient to controlled changes to host diet. Different tissues within the same beetle harbor unique microbial communities, and secretory cells in particular were remarkably similar across species. We also found that these three carabid species have patterns of microbial diversity similar to those previously found in carabid beetles. These results provide a baseline for future studies of the role of microbes in the diversification of carabids.
    MeSH term(s) Animals ; Bacteria/classification ; Bacteria/isolation & purification ; Coleoptera/classification ; Coleoptera/microbiology ; DNA/chemistry ; DNA/metabolism ; Diet ; Intestines/microbiology ; Metagenomics ; Microbiota ; Phylogeny ; Sequence Analysis, DNA
    Chemical Substances DNA (9007-49-2)
    Language English
    Publishing date 2021-03-19
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0241529
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Ex vivo

    Somé, A Fabrice / Conrad, Melissa D / Kabré, Zachari / Fofana, Aminata / Yerbanga, R Serge / Bazié, Thomas / Neya, Catherine / Somé, Myreille / Kagambega, Tegawinde Josue / Legac, Jenny / Garg, Shreeya / Bailey, Jeffrey A / Ouédraogo, Jean-Bosco / Rosenthal, Philip J / Cooper, Roland A

    Antimicrobial agents and chemotherapy

    2024  Volume 68, Issue 4, Page(s) e0153423

    Abstract: Malaria remains a leading cause of morbidity and mortality in Burkina Faso, which utilizes artemether-lumefantrine as the principal therapy to treat uncomplicated malaria and seasonal malaria chemoprevention with monthly sulfadoxine-pyrimethamine plus ... ...

    Abstract Malaria remains a leading cause of morbidity and mortality in Burkina Faso, which utilizes artemether-lumefantrine as the principal therapy to treat uncomplicated malaria and seasonal malaria chemoprevention with monthly sulfadoxine-pyrimethamine plus amodiaquine in children during the transmission season. Monitoring the activities of available antimalarial drugs is a high priority. We assessed the
    MeSH term(s) Child ; Humans ; Antimalarials/pharmacology ; Antimalarials/therapeutic use ; Plasmodium falciparum ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/parasitology ; Artemether, Lumefantrine Drug Combination/therapeutic use ; Folic Acid Antagonists/pharmacology ; Burkina Faso ; Artemether/therapeutic use ; Pyrimethamine/pharmacology ; Pyrimethamine/therapeutic use ; Malaria/drug therapy ; Lumefantrine/pharmacology ; Lumefantrine/therapeutic use ; Drug Combinations ; Polymorphism, Genetic/genetics ; Drug Resistance/genetics ; Protozoan Proteins/genetics ; Protozoan Proteins/therapeutic use
    Chemical Substances Antimalarials ; Artemether, Lumefantrine Drug Combination ; Folic Acid Antagonists ; Artemether (C7D6T3H22J) ; Pyrimethamine (Z3614QOX8W) ; Lumefantrine (F38R0JR742) ; Drug Combinations ; Protozoan Proteins
    Language English
    Publishing date 2024-02-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/aac.01534-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Evolution of Partial Resistance to Artemisinins in Malaria Parasites in Uganda.

    Conrad, Melissa D / Asua, Victor / Garg, Shreeya / Giesbrecht, David / Niaré, Karamoko / Smith, Sawyer / Namuganga, Jane F / Katairo, Thomas / Legac, Jennifer / Crudale, Rebecca M / Tumwebaze, Patrick K / Nsobya, Samuel L / Cooper, Roland A / Kamya, Moses R / Dorsey, Grant / Bailey, Jeffrey A / Rosenthal, Philip J

    The New England journal of medicine

    2023  Volume 389, Issue 8, Page(s) 722–732

    Abstract: Background: Partial resistance of : Methods: We performed annual surveillance among patients who presented with uncomplicated malaria at 10 to 16 sites across Uganda from 2016 through 2022. We sequenced the gene encoding kelch 13 (: Results: By ... ...

    Abstract Background: Partial resistance of
    Methods: We performed annual surveillance among patients who presented with uncomplicated malaria at 10 to 16 sites across Uganda from 2016 through 2022. We sequenced the gene encoding kelch 13 (
    Results: By 2021-2022, the prevalence of parasites with validated or candidate resistance markers reached more than 20% in 11 of the 16 districts where surveillance was conducted. The PfK13 469Y and 675V mutations were seen in far northern Uganda in 2016-2017 and increased and spread thereafter, reaching a combined prevalence of 10 to 54% across much of northern Uganda, with spread to other regions. The 469F mutation reached a prevalence of 38 to 40% in one district in southwestern Uganda in 2021-2022. The 561H mutation, previously described in Rwanda, was first seen in southwestern Uganda in 2021, reaching a prevalence of 23% by 2022. The 441L mutation reached a prevalence of 12 to 23% in three districts in western Uganda in 2022. Genetic analysis indicated local emergence of mutant parasites independent of those in Southeast Asia. The emergence of resistance was observed predominantly in areas where effective malaria control had been discontinued or transmission was unstable.
    Conclusions: Data from Uganda showed the emergence of partial resistance to artemisinins in multiple geographic locations, with increasing prevalence and regional spread over time. (Funded by the National Institutes of Health.).
    MeSH term(s) Animals ; Humans ; Artemisinins/pharmacology ; Artemisinins/therapeutic use ; Benchmarking ; Parasites/drug effects ; Parasites/genetics ; Uganda/epidemiology ; Drug Resistance/genetics ; Malaria/drug therapy ; Malaria/genetics ; Malaria/parasitology ; Protozoan Proteins/genetics
    Chemical Substances artemisinin (9RMU91N5K2) ; Artemisinins ; Protozoan Proteins
    Language English
    Publishing date 2023-08-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 207154-x
    ISSN 1533-4406 ; 0028-4793
    ISSN (online) 1533-4406
    ISSN 0028-4793
    DOI 10.1056/NEJMoa2211803
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  5. Article ; Online: Decreased susceptibility of Plasmodium falciparum to both dihydroartemisinin and lumefantrine in northern Uganda.

    Tumwebaze, Patrick K / Conrad, Melissa D / Okitwi, Martin / Orena, Stephen / Byaruhanga, Oswald / Katairo, Thomas / Legac, Jennifer / Garg, Shreeya / Giesbrecht, David / Smith, Sawyer R / Ceja, Frida G / Nsobya, Samuel L / Bailey, Jeffrey A / Cooper, Roland A / Rosenthal, Philip J

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 6353

    Abstract: Artemisinin partial resistance may facilitate selection of Plasmodium falciparum resistant to combination therapy partner drugs. We evaluated 99 P. falciparum isolates collected in 2021 from northern Uganda, where resistance-associated PfK13 C469Y and ... ...

    Abstract Artemisinin partial resistance may facilitate selection of Plasmodium falciparum resistant to combination therapy partner drugs. We evaluated 99 P. falciparum isolates collected in 2021 from northern Uganda, where resistance-associated PfK13 C469Y and A675V mutations have emerged, and eastern Uganda, where these mutations are uncommon. With the ex vivo ring survival assay, isolates with the 469Y mutation (median survival 7.3% for mutant, 2.5% mixed, and 1.4% wild type) and/or mutations in Pfcoronin or falcipain-2a, had significantly greater survival; all isolates with survival >5% had mutations in at least one of these proteins. With ex vivo growth inhibition assays, susceptibility to lumefantrine (median IC
    MeSH term(s) Humans ; Plasmodium falciparum/genetics ; Plasmodium falciparum/metabolism ; Antimalarials/pharmacology ; Antimalarials/therapeutic use ; Lumefantrine/pharmacology ; Lumefantrine/therapeutic use ; Artemether, Lumefantrine Drug Combination/pharmacology ; Artemether, Lumefantrine Drug Combination/therapeutic use ; Uganda ; Malaria, Falciparum/drug therapy ; Drug Resistance/genetics ; Artemether/pharmacology ; Artemether/therapeutic use ; Artemisinins/pharmacology ; Artemisinins/therapeutic use ; Chloroquine/pharmacology ; Drug Combinations ; Protozoan Proteins/metabolism
    Chemical Substances Antimalarials ; Lumefantrine (F38R0JR742) ; Artemether, Lumefantrine Drug Combination ; artenimol (6A9O50735X) ; Artemether (C7D6T3H22J) ; Artemisinins ; Chloroquine (886U3H6UFF) ; Drug Combinations ; Protozoan Proteins
    Language English
    Publishing date 2022-10-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-33873-x
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  6. Article ; Online: Susceptibilities of Ugandan Plasmodium falciparum Isolates to Proteasome Inhibitors.

    Garg, Shreeya / Kreutzfeld, Oriana / Chelebieva, Sevil / Tumwebaze, Patrick K / Byaruhanga, Oswald / Okitwi, Martin / Orena, Stephen / Katairo, Thomas / Nsobya, Samuel L / Conrad, Melissa D / Aydemir, Ozkan / Legac, Jennifer / Gould, Alexandra E / Bayles, Brett R / Bailey, Jeffrey A / Duffey, Maelle / Lin, Gang / Kirkman, Laura A / Cooper, Roland A /
    Rosenthal, Philip J

    Antimicrobial agents and chemotherapy

    2022  Volume 66, Issue 10, Page(s) e0081722

    Abstract: The proteasome is a promising target for antimalarial chemotherapy. We ... ...

    Abstract The proteasome is a promising target for antimalarial chemotherapy. We assessed
    MeSH term(s) Humans ; Antimalarials/pharmacology ; Antimalarials/chemistry ; Asparagine ; Drug Resistance/genetics ; Ethylenediamines/pharmacology ; Malaria, Falciparum/drug therapy ; Malaria, Falciparum/parasitology ; Peptides/pharmacology ; Plasmodium falciparum/drug effects ; Plasmodium falciparum/genetics ; Proteasome Endopeptidase Complex/genetics ; Proteasome Inhibitors/chemistry ; Proteasome Inhibitors/pharmacology ; Uganda
    Chemical Substances Antimalarials ; Asparagine (7006-34-0) ; divinyl sulfone (5PFN71LP8M) ; Ethylenediamines ; Peptides ; Proteasome Endopeptidase Complex (EC 3.4.25.1) ; Proteasome Inhibitors
    Language English
    Publishing date 2022-09-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 217602-6
    ISSN 1098-6596 ; 0066-4804
    ISSN (online) 1098-6596
    ISSN 0066-4804
    DOI 10.1128/aac.00817-22
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    In stock of ZB MED Cologne/Königswinter

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