Clonorchis sinensis is a liver fluke that causes clonorchiasis, a significant public health concern in East Asia, closely associated with hepatobiliary diseases. Dopamine is an essential neurotransmitter involved in neuromuscular signaling, and its uptake by trematodes may contribute to parasite physiology and survival. This study aimed to characterize the dopamine transporter CsDAT in C. sinensis by synthesizing cDNA from adult worms and expressing it in Xenopus laevis oocytes; subsequently, uptake assays were conducted using radiolabeled dopamine. Functional assays confirmed that CsDAT mediates dopamine uptake in a sodium-dependent manner. The uptake was saturable and exhibited Michaelis-Menten kinetics with a Michaelis constant of 454.5 nM and a maximum uptake rate of 1,422.5 fmol/oocyte/h. CsDAT efficiently transported dopamine with high affinity, indicating its physiological relevance in the parasite. A 3-dimensional model of CsDAT was constructed to examine its structural features. The predicted structure contained a conserved substrate-binding pocket similar to that of other known neurotransmitter transporters. Molecular docking simulations showed that dopamine stably fits within the binding pocket. The key amino acid residues formed hydrogen bonds and hydrophobic interactions with dopamine. Interestingly, dopamine and several inhibitors demonstrated higher binding affinity to CsDAT than the human dopamine transporter. This study provides the first functional and structural insights into CsDAT. The higher inhibitor-binding affinity of CsDAT compared to human dopamine transporter suggests its potential for use in therapeutic exploration. Targeting CsDAT may facilitate the development of new therapeutic agents against clonorchiasis with minimal off-target effects on the human nervous system.

As many countries implement different programs aimed at eliminating malaria, attention should be given to asymptomatic carriers that may interrupt the progress. This was a community-based cross-sectional study conducted in Tanzania from December 2022 to July 2023 within 4 villages from each of the 3 regions, Geita and Kigoma, which are high malaria transmission, and Arusha, which is low transmission. Malaria was diagnosed in asymptomatic individuals aged 1 year and older using the malaria rapid diagnostic test and light microscope. A total of 2,365 of 3,489 (67.9%) participants were enrolled from high-transmission villages. The overall prevalence was 25.5% and 15.8% by malaria rapid diagnostic test and light microscope, respectively. Using the respective tools, the prevalence was significantly higher at 35.6% (confidence interval (CI)=23.6–49.9) and 23.1% (CI=16.2–35.1) in the high-transmission regions (Geita and Kigoma) compared with 2.9% (CI=1.1–3.5) and 1.1% (CI=0.7–1.8) in the low-transmission region (Arusha). Children younger than 15 years and males accounted for the greatest proportion of infections. In the study area, the prevalence of asymptomatic cases was higher than that of reported symptomatic cases in health facilities. We hypothesize that these parasite reservoirs may contribute to the persistence of malaria in the country. Therefore, to achieve comprehensive malaria control in the country, the surveillance and screening of asymptomatic malaria cases are vital.

Clonorchis sinensis, which causes clonorchiasis, is prevalent in East Asian countries and poses notable health risks, including bile duct complications. Although praziquantel is the primary treatment for the disease, the emerging resistance among trematodes highlights the need for alternative strategies. Understanding the nutrient uptake mechanisms in trematodes, including C. sinensis, is crucial for developing future effective treatments. This study aimed to characterize the function of C. sinensis glucose transporter 4 (CsGTP4) and determine its role in nutrient uptake employing synthesized cDNA of adult C. sinensis worms. The functional characterization of CsGTP4 involved injecting its cRNA into Xenopus laevis oocytes and analyzing the deoxy-D-glucose uptake levels. The results demonstrated that deoxy-D-glucose uptake depended on the deoxy-D-glucose incubation and CsGTP4 expression time, but not sodium-dependent. The concentration-dependent uptake followed the Michaelis–Menten equation, with a Km value of 2.7 mM and a Vmax value of 476 pmol/oocyte/h based on the Lineweaver–Burk analysis. No uptake of radiolabeled α-ketoglutarate, p-aminohippurate, taurocholate, arginine, or carnitine was observed. The uptake of deoxy-D-glucose by CsGTP4 was significantly inhibited by unlabeled glucose and galactose in a concentration-dependent manner. It was significantly inhibited under strongly acidic and basic conditions. These insights into the glucose uptake kinetics and pH dependency of CsGTP4 provide a deeper understanding of nutrient acquisition in trematodes. This study contributes to the development of novel antiparasitic agents, addressing a considerable socioeconomic challenge in affected regions.