Temporal and spatial dynamics of Plasmodium falciparum clonal lineages in Guyana.

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.

Temporal and spatial dynamics of Plasmodium falciparum clonal lineages in Guyana.

Plasmodium parasites, the causal agents of malaria, are eukaryotic organisms that obligately undergo sexual recombination within mosquitoes. However, in low transmission settings where most mosquitoes become infected with only a single parasite clone, 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. To investigate whether this clonality was potentially associated with the persistence and spatial spread of the mutation, 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 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 report polymorphisms exhibiting evidence of selection for drug resistance or other phenotypes and reported a novel pfk13 mutation (G718S) as well as 61 nonsynonymous substitutions that increased markedly in frequency. However, P. falciparum clonal dynamics in Guyana appear to be largely driven by stochastic factors, in contrast to other geographic regions. The use of multiple artemisinin combination therapies in Guyana may have contributed to the disappearance of the pfk13 C580Y mutation.

Caring for Young Children with Asthma: Perspectives from Urban Community Health Centers.

Asthma disproportionately affects low-income, minority youth, with notable disparities among children <5 years of age. Understanding the perceptions of urban community health centers (CHCs) regarding treating young children with asthma could improve care for these patients. This study uses data from semi-structured focus groups with staff from eight urban CHCs. Themes emerged in three domains. Within the parent/family domain, providers noted low rates of follow-up visits, low health literacy, and-for young children specifically-misunderstanding about the diagnosis. At the CHC level, providers needed more staff, space, and comfort with applying the guidelines to infants and young children. CHCs reported asthma registries, population health oversight, and an asthma champion improved care. At the system level, providers wanted improved communication with emergency departments and community outreach programs. Reducing these multi-level barriers may improve care.

LEAP: A randomized-controlled trial of a lay-educator inpatient asthma education program.

OBJECTIVE: To evaluate the impact of LEAP, a volunteer-based, inpatient asthma education program for families of inner-city children with asthma. METHODS: 711 children ages 2-17 years admitted with status asthmaticus were randomized to receive usual care or usual care plus a supplemental education intervention. Both groups completed a baseline interview. Trained volunteer lay educators conducted individualized bedside education with the intervention group. Primary outcome was attendance at a post-hospitalization follow-up visit 7-10 days after discharge. Secondary outcomes included parent-reported asthma management behaviors, symptoms, and self-efficacy scores from a one month follow-up interview. RESULTS: Post-hospitalization asthma clinic attendance was poor (38%), with no difference between groups. Families randomized to the intervention group were more likely to report use of a controller (OR 2.4, 95% CI 1.3-4.2, p<0.01) and a valved-holding chamber (OR 2.9, 95% CI 1.1-7.4, p=0.03), and were more likely to have an asthma action plan at follow up (OR 2.0, 95% CI 1.3-3.0, p<0.01). Asthma self-efficacy scores were significantly improved among those who received the intervention (p=0.04). CONCLUSIONS: Inpatient asthma education by trained lay volunteers was associated with improved asthma management behaviors. PRACTICE IMPLICATIONS: This novel volunteer-based program could have widespread implications as a sustainable model for asthma education.

The emergence of retail-based clinics in the United States: early observations.

Retail-based clinics have proliferated rapidly in the past two years, with approximately 1,000 sites in thirty-seven states representing almost three million cumulative visits. Clinic operators have evolved from a dispersed group of privately financed concerns to a concentrated, largely corporate-owned group. A major development has been the move to large-scale acceptance of insurance, deviating from the initial cash-pay model. Consumers' acceptance and the fact that the clinics appear to increase access for both the uninsured and the insured has encouraged providers and policymakers to consider this approach to basic, acute care while seeking a better understanding of these clinics.