Health risk assessment of residential exposure to cypermethrin among young children in agricultural communities in northeastern Thailand

This study aimed to identify factors associated with dermal exposure to cypermethrin and assess the health risks among young children in an agricultural community in Thailand. Face-to-face interviews were conducted with the parents/caregivers of 58 children (aged 1–3 years). Wipe samples were analyzed for cypermethrin by gas chromatography-microelectron capture detection (GC-µECD). Health risk assessments were based on the cypermethrin concentration on the children’s hands and feet. Spearman’s correlation indicated significant associations among cypermethrin concentrations on the hands, feet, floors/wooden beds, and toys (rho?=?0.438–0.613, p-value <0.001). Cypermethrin concentrations on the hands were significantly and inversely correlated with the child’s caregiver being the child’s mother and insecticide use (p?<?0.01). Concentrations on the feet were significantly correlated with insecticide use (p?<?0.05) and showering (p?<?0.01). The hazard quotient calculated from dermal exposure via the hands and feet showed no risk for potential noncarcinogenic effects (5.586?×?10^?5 in the dry season and 4.301?×?10^?4 in the wet season). These findings suggest that young children might not be at risk for cypermethrin exposure through the dermal route. Residential exposure among young children may be reduced by improved hygiene. Health risk assessments of environmental insecticide exposure via the oral and inhalation routes require further investigation.     

Transgenic pyrimethamine-resistant plasmodium falciparum reveals transmission-blocking potency of P218, a novel antifolate candidate drug

Antimalarial drugs capable of targeting multiple parasite stages, particularly the transmissible stages, can be valuable tools for advancing the malaria elimination agenda. Current antifolate drugs such as pyrimethamine can inhibit replicative parasite stages in both humans and mosquitoes, but antifolate resistance remains a challenge. The lack of reliable gametocyte-producing, antifolate-resistant Plasmodium falciparum laboratory strain hinders the study of new antifolate compounds that can overcome antifolate resistance including development stages in the mosquito. We used clustered regularly interspaced short palindromic repeats-Cas9 genome editing to develop a transgenic gametocyte-producing strain of P. falciparum with quadruple mutations (N51I, C59R, S108N, I164L) in the dihydrofolate reductase (dhfr) gene, using NF54 as a parental strain. The transgenic parasites exhibited pyrimethamine resistance while maintaining their gametocyte-producing activity. We then demonstrated that pyrimethamine could no longer inhibit male gametocyte exflagellation in the transgenic parasite. In contrast, P218, the novel antifolate, designed to overcome antifolate resistance, potently inhibited exflagellation. The exflagellation IC₅₀ of P218 was five times lower than the asexual stage half maximal inhibitory concentration (IC₅₀), suggesting a strong barrier for transmission of P218-resistant parasites. The transgenic gametocyte-producing, pyrimethamine-resistant parasite is a robust system for evaluating novel antifolate compounds against non-asexual stage development.