As an efficient drug for alveolar echinococcosis (AE) is still not available, new chemotherapy targets are necessary. The mitochondrial respiratory chain may be a good drug candidate because parasite respiratory chains are quite different from those of mammalian hosts. For example, Ascaris suum possesses an NADH‐fumarate reductase system (fumarate respiration) that is highly adapted to anaerobic environments such as the small intestine. It is composed of mitochondrial complex I (NADH‐ubiquinone reductase), complex II (succinate‐ubiquinone reductase), and rhodoquinone. We previously demonstrated that fumarate respiration is also essential in E. multilocularis. Quinazoline, a complex I inhibitor, inhibited growth of E. multilocularis larvae in vitro. These results indicate that fumarate respiration could be a target for E. multilocularis therapy. In the current chapter, we focused on complex II, which is another component of this system, because quinazoline exhibited strong toxicity to mammalian mitochondria. We evaluated the molecular and biochemical characterization of E. multilocularis complex II as a potential drug target. In addition, we found that ascofuranone, a trypanosome cyanide‐insensitive alternative oxidase inhibitor, inhibited E. multilocularis complex II at the nanomolar order. Our findings demonstrate the potential development of targeted therapy against Echinococcus complex II.
Background/Objectives: Sporadic Creutzfeldt–Jakob disease (sCJD) is a fatal neurodegenerative disorder traditionally diagnosed based on the World Health Organization (WHO) criteria in 1998. Recently, Hermann et al. proposed updated diagnostic criteria incorporating advanced biomarkers to enhance early detection of sCJD. This study aimed to evaluate the sensitivity and specificity of Hermann’s criteria compared with those of the WHO criteria in a large cohort of patients suspected of prion disease in Japan. Methods: In this retrospective cohort study, we examined the new criteria using data of 2004 patients with suspected prion disease registered with the Japanese Prion Disease Surveillance (JPDS) between January 2009 and May 2023. Patients with genetic or acquired prion diseases or incomplete data necessary for the diagnostic criteria were excluded, resulting in 786 eligible cases. The sensitivity and specificity of the WHO and Hermann’s criteria were calculated by comparing diagnoses with those made by the JPDS Committee. Results: Of the 786 included cases, Hermann’s criteria helped identify 572 probable cases compared with 448 by the WHO criteria. The sensitivity and specificity of the WHO criteria were 96.4% and 96.6%, respectively. Hermann’s criteria demonstrated a sensitivity of 99.3% and a specificity of 95.2%, indicating higher sensitivity but slightly lower specificity. Fifty-five cases were classified as “definite” by both criteria. Conclusions: The findings suggest that Hermann’s criteria could offer improved sensitivity for detecting sCJD, potentially reducing diagnostic oversight. However, caution is advised in clinical practice to avoid misdiagnosis, particularly in treatable neurological diseases, by ensuring thorough exclusion of other potential conditions.
In parts of Asia, including Vietnam, Rotavirus alphagastroenteritidis (formerly known as Rotavirus A ; RVA) strains of porcine origin, particularly G4P[6] strains, have been detected in humans at relatively high frequencies. This study investigated the origins of G4P[6] strains identified in Vietnamese children and examined possible factors underlying their frequent detection, based on molecular epidemiological analyses. Among the 1,252 RVA-positive faecal specimens collected over a 2-year period, 28 (2.2%) contained only the G4P[6] strain. Of these, 23 (1.8%) G4P[6] strains were successfully sequenced for their whole genomes, all of which were confirmed to be entirely of porcine RVA origin, with no evidence of genomic reassortment with human RVA strains. Two distinct clusters of G4P[6] strains (comprising two and three strains, respectively) shared identical genome sequences, suggesting the possibility of limited human-to-human transmission. In contrast, the remaining 18 G4P[6] strains were genetically distinct from one another, indicating multiple, independent interspecies transmission events from pigs to humans. Phylogenetic analysis revealed that the P[6] genome segments of porcine RVA or porcine-like human RVA strains, including those identified in this study, were genetically distinct from those of typical human RVA strains and showed notable geographic variation in detection frequency. Comparative analysis of the variable regions of P[6] amino acid sequences identified characteristic residues that distinguish porcine RVA-like P[6] from human RVA-like P[6], some of which correspond to known glycan-binding sites. This study revealed a high frequency of pig-to-human spillover transmission of porcine-derived G4P[6] rotavirus strains in Vietnamese children. The findings suggest that these cases were not the result of newly emerging strains capable of sustained human-to-human transmission. Furthermore, distinct amino acid characteristics in the porcine RVA P[6] protein were identified that may play a role in facilitating the cross-species transmission of rotavirus from pigs to humans.