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Plasmodium parasites, the causal agents of malaria, are eukaryotic organisms that obligately undergo sexual recombination within mosquitoes. In low transmission settings, parasites recombine with themselves, and the clonal lineage is propagated rather than broken up by outcrossing. We investigated whether stochastic/neutral factors drive the persistence and abundance of Plasmodium falciparum clonal lineages in Guyana, a country with relatively low malaria transmission, but the only setting in the Americas in which an important artemisinin resistance mutation (pfk13 C580Y) has been observed. We performed whole genome sequencing on 1,727 Plasmodium falciparum samples collected from infected patients across a five-year period (2016–2021). We characterized the relatedness between each pair of monoclonal infections (n = 1,409) through estimation of identity-by-descent (IBD) and also typed each sample for known or candidate drug resistance mutations. A total of 160 multi-isolate clones (mean IBD ≥ 0.90) were circulating in Guyana during the study period, comprising 13 highly related clusters (mean IBD ≥ 0.40). In the five-year study period, we observed a decrease in frequency of a mutation associated with artemisinin partner drug (piperaquine) resistance (pfcrt C350R) and limited co-occurence of pfcrt C350R with duplications of plasmepsin 2/3, an epistatic interaction associated with piperaquine resistance. We additionally observed 61 nonsynonymous substitutions that increased markedly in frequency over the study period as well as a novel pfk13 mutation (G718S). However, P. falciparum clonal dynamics in Guyana appear to be largely driven by stochastic factors, in contrast to other geographic regions, given that clones carrying drug resistance polymorphisms do not demonstrate enhanced persistence or higher abundance than clones carrying polymorphisms of comparable frequency that are unrelated to resistance. The use of multiple artemisinin combination therapies in Guyana may have contributed to the disappearance of the pfk13 C580Y mutation. Author summary: Malaria is caused by eukaryotic Plasmodium parasites, which undergo sexual recombination within mosquitoes. In settings with low transmission, such as Guyana, these parasites often recombine with themselves, leading to the propagation of identical clones. We explored the population genomics of Plasmodium falciparum malaria parasites in Guyana over five years to characterize clonal transmission dynamics and understand whether they were influenced by local drug resistance mutations under strong selection, including pfk13 C580Y, which confers resistance to artemisinin, and pfcrt C350R, which confers resistance to piperaquine. Based on whole genome sequencing results from 1,409 monoclonal (single-strain) samples, we identified 160 multi-isolate clones, in which all parasites share at least 90% of their genomes through recent common ancestry. We observed a decrease in frequency of the pfcrt C350R mutation, as well as the disappearance of pfk13 C580Y. Our findings contrast with the deterministic rise of drug resistance mutations observed in other geographic regions, sometimes associated with clonality. The simultaneous use of at least two different artemisinin combination therapies may have prevented the spread of an artemisinin-resistant clone in Guyana, suggesting a strategy for resistance management in other geographic regions. [ABSTRACT FROM AUTHOR]

Objective: To identify challenges that may raise pathogens' resistance to antimicrobial drugs by exploring the private market for antimicrobials in two selected mining and frontier areas of Guyana., Methods: The private sector supply was mapped by approaching all authorized pharmacies and informal outlets, e.g., street vendors and grocery stores, around the two selected towns. Interviews were conducted with a) sellers on the availability of drugs, expiration dates, prices, and main producers; and b) customers on purchased drugs, diagnoses, and prescriptions received before purchasing drugs, and intention to complete the treatment. The information collected was described, and the determinants of the self-reported intention of customers to complete the whole treatment were identified., Results: From the perspective of the supply of antimicrobials, essential medicines faced low and insecure availability, and prescriptions frequently deviated from diagnoses. From the perspective of the demand for antimicrobials, one-third of purchased antibiotics had a high potential for antimicrobial resistance as per the World Health Organization AWaRe classification. A high price reduced the self-reported intention to complete the treatment among those who had a prescription, while buying the medication in a licensed pharmacy increased such intention., Conclusions: In Guyana, there persists a need to establish and revise policies addressing both supply and demand, such as restricting the sale of antimicrobials to licensed pharmacies and upon prescription, improving prescription practices while reducing the financial burden to patients, guaranteeing access to first-line treatment drugs, and instructing patients on appropriate use of antimicrobials. Revising such policies is an essential step to contain antimicrobial resistance in the analyzed areas and across Guyana., Competing Interests: Conflict of interest. None declared.

Guyana remains one of four countries in the Americas endemic for lymphatic filariasis (LF). Elimination of LF requires repeated annual mass drug administration (MDA) with sufficient levels of coverage for success. This study assesses the acceptability and never treatment of LF MDA using data from a routine assessment survey in 2021. A subset of individuals, over 20 years of age (n = 2498), were selected to receive an expanded questionnaire to examine factors associated with acceptability and never treatment. Assessed factors include respondent demographics, knowledge, risk perceptions of LF, and opinions on the MDA programme. The majority (73%) of those with scores above the acceptability threshold (score ≥22.5) reported participating in MDA two or more times. Factors strongly and positively associated with scoring above the acceptability threshold include beliefs in importance of participation in MDA for their community (aOR = 2.8, 95%CI (1.1-7.2)), perception of importance of LF treatment (6.9 (3.2-14.7)), receiving treatment in 2021 (2.9 (1.5-5.4)), and the number of self-reported times taking treatment for LF (2.2 (1.1-4.4)). Ten percent of respondents participated in the MDA for the first time in 2021, while 15% reported never treatment during any round of LF MDA. Three factors were statistically associated with participation in MDA across the two levels of the models (level 1: took LF treatment once versus never, and level 2: took LF treatment twice versus never) included: 1) scoring above the acceptability threshold (aOR = 6.2, 95%CI(3.8-10.0)), 2) self-reported importance of participation in MDA for their community (7.1 (2.9-17.8)), and 3) personal beliefs that they should take LF treatment even if they are not sick (2.6 (1.7-3.9)). As Guyana moves closer to LF elimination, these results provide further insight and understanding into programmatic results and could inform further action following MDA activities-particularly if an approach is needed to address never treatment during MDA., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Duguay et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)