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Travelers’ diarrhea has a high incidence rate among deployed US military personnel and can hinder operational readiness. The Global Travelers’ Diarrhea study is a US Department of Defense­–funded multisite surveillance effort to investigate the etiology and epidemiology of travelers’ diarrhea. During 2018–2023, we enrolled 512 participants at partner institutions in 6 countries: Djibouti, Georgia, Egypt, Honduras, Nepal, and Peru. Harmonized laboratory methods conducted at each partner institution identified >1 pathogens, including Escherichia coli (67%–82%), norovirus (4%–29%), and Campylobacter jejuni (2%–20%), in 403 (79%) cases. Among cases, 79.7% were single infections, 19.6% were double infections, and 0.7% were triple infections. The most common enterotoxigenic E. coli colonization factors identified were CS3 (25%) and CS21 (25%), followed by CS2 (18%) and CS6 (15%). These data can inform best treatment practices for travelers’ diarrhea and support US military health readiness.

IntroductionCataract is the leading cause of blindness among the elderly worldwide. Twin and family studies support an important role for genetic factors in cataract susceptibility with heritability estimates up to 58%. To date, 55 loci for cataract have been identified by genome-wide association studies (GWAS), however, much work remains to identify the causal genes. Here, we conducted a transcriptome-wide association study (TWAS) of cataract to prioritize causal genes and identify novel ones, and examine the impact of their expression.MethodsWe performed tissue-specific and multi-tissue TWAS analyses to assess associations between imputed gene expression from 54 tissues (including 49 from the Genotype Tissue Expression (GTEx) Project v8) with cataract using FUSION software. Meta-analyzed GWAS summary statistics from 59,944 cataract cases and 478,571 controls, all of European ancestry and from two cohorts (GERA and UK Biobank) were used. We then examined the expression of the novel genes in the lens tissue using the iSyTE database.ResultsAcross tissue-specific and multi-tissue analyses, we identified 99 genes for which genetically predicted gene expression was associated with cataract after correcting for multiple testing. Of these 99 genes, 20 (AC007773.1, ANKH, ASIP, ATP13A2, CAPZB, CEP95, COQ6, CREB1, CROCC, DDX5, EFEMP1, EIF2S2, ESRRB, GOSR2, HERC4, INSRR, NIPSNAP2, PICALM, SENP3, and SH3YL1) did not overlap with previously reported cataract-associated loci. Tissue-specific analysis identified 202 significant gene-tissue associations for cataract, of which 166 (82.2%), representing 9 unique genes, were attributed to the previously reported 11q13.3 locus. Tissue-enrichment analysis revealed that gastrointestinal tissues represented one of the highest proportions of the Bonferroni-significant gene-tissue associations (21.3%). Moreover, this gastrointestinal tissue type was the only anatomical category significantly enriched in our results, after correcting for the number of tissue donors and imputable genes for each reference panel. Finally, most of the novel cataract genes (e.g., Capzb) were robustly expressed in iSyTE lens data.DiscussionOur results provide evidence of the utility of imputation-based TWAS approaches to characterize known GWAS risk loci and identify novel candidate genes that may increase our understanding of cataract etiology. Our findings also highlight the fact that expression of genes associated with cataract susceptibility is not necessarily restricted to lens tissue.

Acute gastroenteritis (AGE) has a major impact on morbidity and mortality worldwide. The viral aetiology of diarrhoeal diseases may remain unknown due to limited diagnostic facilities. Non-polio enteroviruses (NPEVs) are the third most frequent pathogen detected in stool specimens from AGE cases, yet their potential role in AGE is uncertain. In Nepal, limited data are available on NPEVs, due to both the lack of an adequate surveillance program and the availability of tests. The global polio eradication initiative effort of the WHO has eradicated the incidence of poliomyelitis and acute flaccid paralysis (AFP) from many parts of the world, including Nepal. However, cases of AFP associated with NPEVs have been reported in different countries, including the neighbouring India. This study aims to investigate the diarrhoeal stool samples from a birth cohort until the age of 36 months for NPEVs and the genotype diversity of NPEV in community children with diarrhoea. A total of 280 longitudinal diarrhoeal stool samples that were negative for other enteric pathogens were tested using RT-PCRs. NPEVs was detected in 97 stool specimens (34.6%) and were significantly more frequent in infants up to one year of age. This study identified 17 various NPEV types, with the dominating species being Enterovirus B (EV-B). Ten different types of echoviruses were recorded in this study, with the two rare NPEVs B74 and A120. Based on prevalence, seasonality, and diversity, further studies are warranted to investigate the role of enterovirus in diarrhoeal disease.

Background: Globally, rotavirus A (RV) is a leading cause of acute gastroenteritis (AGE) in young children under 5 years. The main aim of this study was to describe the prevalence of RV in children with and without diarrhea whose age ranged from 3 months to 5 years from two different hospitals of Nepal. We also described the diversity of rotavirus circulating during the pre-vaccination period in Nepal between 2006–2009. Materials and methods: A total of 2400 stool samples collected from children's years with diarrhea (cases, N = 1200) and without diarrhea (controls, N = 1200) were tested for the presence of RV by both enzyme-linked immunosorbent assay and real-time reverse transcription polymerase chain reaction (RT-PCR). All samples positive for RT PCR and/or ELISA were further characterized for G and P genotypes by conventional RT-PCR. Results: In total, 500 of the 2398 (20.8 %) samples (424 cases and 76 controls), were positive for RV. The most frequently detected G-types were G12, G1, and G9 and P-types were P[8] and P[6]. The predominant genotypes G12P[6], G12P[8], G1P[8] and G9P[8] were identified in 27.8 %, 24.2 %, 11.8 % and 10.8 % of the samples, respectively. Conclusion: This study observed high prevalence of G12P[6] rotavirus circulating in Nepal before vaccine introduction and they may pose an emerging challenge to current and future vaccine. Therefore, continuous molecular surveillance of circulating genotypes and emerging rotavirus strain should be carried out to better understand the effectiveness of vaccination program.