Abstract Plasmodium vivax malaria remains a significant global health burden, with recurrent relapses contributing to morbidity and complicating elimination efforts. While traditionally considered less severe than P. falciparum , emerging evidence has indicated that P. vivax can affect the central nervous system (CNS). Neurological effects range from subtle cognitive and attention deficits to severe complications such as diffuse encephalopathy, seizures and cerebral involvement. The pathophysiology of brain involvement is multifactorial, involving microvascular obstruction, systemic inflammation, cytokine-mediated neurotoxicity and oxidative stress, which collectively contribute to neuronal injury and altered brain function. Antimalarial agents used in the treatment and radical cure of P. vivax , including chloroquine, primaquine and tafenoquine, differ in their pharmacological and neuropharmacological properties. Radical cure requires 8-aminoquinolines (primaquine or tafenoquine) to eliminate dormant hepatic hypnozoites, as chloroquine is limited to blood-stage activity and does not prevent relapse. These agents exhibit distinct neuropharmacological profiles, influenced by factors such as blood-brain barrier penetration, metabolic activation and receptor interactions. In silico analyses and clinical data suggest that primaquine and its metabolites have the highest potential for CNS interactions, with tafenoquine showing a comparatively generally acceptable neuropsychiatric safety profile, and chloroquine with identifiable CNS and cardiac risks. These findings underscore the importance of glucose-6-phosphate dehydrogenase deficiency and psychiatric screening, monitoring for neuropsychiatric adverse effects and tailoring therapy to patient-specific risk factors. Integrating pharmacogenetic insights and neurotoxicity considerations into treatment strategies may optimize efficacy and safety in the management of P. vivax malaria.
Tritrichomonas foetus is the causative agent of bovine trichomonosis, a venereal disease that compromises cattle fertility and causes major economic losses. We report a chromosome-scale genome assembly of T. foetus isolate, TfOz5, from Queensland, Australia generated using Oxford Nanopore long-read sequencing and Pore-C chromatin conformation capture. The 137.7 Mb assembly spans 5 chromosomes with an N50 of 24 Mb. Repeat analysis revealed 43.6% repetitive content dominated by DNA transposons. Gene prediction identified 32 104 protein-coding genes of which 98.3% were assigned to orthogroups. Comparative analysis with the KV-1 genome detected 160 structural variants, including deletions (40.6%), insertions (22.5%), duplications (16.3%), inversions (13.1%) and translocations (7.5%). Across 9 Parabasalia species, we observed high gene family conservation and 305 species-specific orthogroups in TfOz5. Phylogenetic analysis confirmed the monophyletic cluster of T. foetus strains (K, KV-1 and TfOz5). Inter-species comparison with the human urogenital parasite Trichomonas vaginalis G3 revealed conserved gene sets between T. foetus TfOz5 and T. vaginalis G3 that were significantly enriched for core cellular functions (translation, cell cycle and mitochondria-related homology hits), while divergent genes highlighted species-specific host interactions. Trichomonas vaginalis G3 showed enrichment for proteolysis, regulation of DNA-templated transcription and symbiont-host adhesion, traits consistent with persistence in the human genital tract. Similarly, T. foetus TfOz5 host interactions align with long-term survival in the bovine reproductive niche. This chromosome-scale assembly provides a valuable genomic framework for investigating parasite evolution, identifying candidate genetic features associated with host adaptation and supporting the development of next-generation recombinant vaccines to control bovine trichomonosis.
The life cycles of trematodes infecting crocodilians remain poorly understood, with most species known exclusively from adult stages recovered from definitive hosts. The present study elucidates the life cycle of Neofibricola smiti Achatz, Martens, Kudlai, Junker, Boe et Tkach, 2022, from South Africa and identifies Bulinus sp. as first intermediate host, representing the first confirmed first intermediate host association for a crocodilian-infecting diplostomid. In addition, a metacercaria recovered from the eye viscera of Clarias gariepinus (Burchell, 1822) expands the known range of second intermediate hosts for N. smiti to include a clariid fish. Phylogenetic analyses of partial 28S rDNA, ITS2 rDNA and COI mtDNA sequences generated from sporocysts, cercariae and a metacercaria confirmed conspecificity with the sexual adult specimens previously described from the Nile crocodile, Crocodylus niloticus Laurenti, 1768, and metacercariae identified from M & uuml;ller's clawed frog, Xenopus muelleri (Peters, 1844). The occurrence of metacercariae in both amphibian and fish hosts suggests either a broader second intermediate host range or more complex transmission pathways including paratenic host use, as has been demonstrated in other diplostomids. This study thus presents the first fully elucidated and molecularly characterized life cycle for a crocodilian-infecting diplostomid and advances our current understanding of host associations and transmission pathways within the Diplostomidae.
International collaborations enhance research outcomes by providing partners with increased access to resources, training and multidisciplinary expertise. These partnerships facilitate knowledge exchange and infrastructure development, promoting sustainable research ecosystems. The development of early career researchers (ECRs) is particularly important in strengthening research capacity within international research networks. However, literature regarding their experiences is limited. Here, we present a qualitative study of one international research network, the UK Global Challenges Research Fund-supported Global Network for Neglected Tropical Diseases (2018-2022) and its impact on ECR career development. Semi-structured interviews were conducted with 19 ECRs previously supported by the Network; these were then thematically analysed. Key themes were identified relating to ECR experiences with the Network. Findings indicate that the Network provided valuable opportunities for professional development, knowledge exchange and collaborative research, which participants described as transformative for their careers. However, ECRs stressed that structural barriers such as insufficient funding and job insecurity limited the Network's longer-term impact, severely affecting ECR retention and development. These results highlight the benefits of international research collaborations and the need for targeted support and sustainable research funding to retain and develop ECRs, particularly in disease-endemic countries.
