Fishermen in Southeast Asia have been found to be highly vulnerable to HIV, with research evidence highlighting the role of sexual risk behaviors. This study aims to estimate the rate of HIV as well as hepatitis C virus (HCV) infections among Malaysian fishermen, and the risky sexual and injection drug use behaviors that may contribute to these infections. The study also includes an assessment of socio-demographic, occupational and behavioral correlates of testing positive for HIV or HCV, and socio-demographic and occupational correlates of risk behaviors. The study had a cross-sectional design and recruited 406 fishermen through respondent-driven sampling (RDS). Participants self-completed a questionnaire and provided biological specimens for HIV and HCV testing. We conducted and compared results of analyses of both unweighted data and data weighted with the Respondent-Driven Sampling Analysis Tool (RDSAT). Of the participating fishermen, 12.4% were HIV positive and 48.6% had HCV infection. Contrary to expectations and findings from previous research, most fishermen (77.1%) were not sexually active. More than a third had a history of injection drug use, which often occurred during fishing trips on commercial vessels and during longer stays at sea. Of the fishermen who injected drugs, 42.5% reported unsafe injection practices in the past month. Reporting a history of injection drug use increased the odds of testing HIV positive by more than 6 times (AOR = 6.22, 95% CIs [2.74, 14.13]). Most fishermen who injected drugs tested positive for HCV. HCV infection was significantly associated with injection drug use, being older than 25 years, working on a commercial vessel and spending four or more days at sea per fishing trip. There is an urgent need to strengthen current harm reduction and drug treatment programs for Malaysian fishermen who inject drugs, especially among fishermen who work on commercial vessels and engage in deep-sea fishing.
The post-transcriptional modification of tRNAs plays a crucial role in tRNA structure and function. Pathogenic variants in tRNA-modification enzymes have been implicated in a wide range of human neurodevelopmental and neurological disorders. However, the molecular basis for many of these disorders remains unknown. Here, we describe a comprehensive cohort of 43 individuals from 31 unrelated families with bi-allelic variants in tRNA methyltransferase 1 (TRMT1). These individuals present with a neurodevelopmental disorder universally characterized by developmental delay and intellectual disability, accompanied by variable behavioral abnormalities, epilepsy, and facial dysmorphism. The identified variants include ultra-rare TRMT1 variants, comprising missense and predicted loss-of-function variants, which segregate with the observed clinical pathology. Our findings reveal that several variants lead to mis-splicing and a consequent loss of TRMT1 protein accumulation. Moreover, cells derived from individuals harboring TRMT1 variants exhibit a deficiency in tRNA modifications catalyzed by TRMT1. Molecular analysis reveals distinct regions of TRMT1 required for tRNA-modification activity and binding. Notably, depletion of Trmt1 protein in zebrafish is sufficient to induce developmental and behavioral phenotypes along with gene-expression changes associated with disrupted cell cycle, immune response, and neurodegenerative disorders. Altogether, these findings demonstrate that loss of TRMT1-catalyzed tRNA modifications leads to intellectual disability and provides insight into the molecular underpinnings of tRNA-modification deficiency caused by pathogenic TRMT1 variants.