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Abstract Background Type 2 diabetes mellitus (T2DM) is becoming one of the leading causes of morbidity and mortality worldwide, including among Africans. Knowledge of the association between traditional risk factors and both diabetes and pre-diabetes, and whether these differ by age and sex, is important for designing targeted interventions. However, little is known about these associations for African populations. Methods The study used data from WHO STEPS surveys, comprising 15,520 participants (6,774 men and 8,746 women) aged 25–64 years, from 5 different West African countries, namely Burkina Faso (4,711), Benin (3,816), Mali (1,772), Liberia (2,594), and Ghana (2,662). T-test and chi-square tests were used to compare differences in the prevalence of traditional risk factors for both sexes. Multinomial logistic regression was conducted to ascertain the relative risks (RR) and 95% confidence intervals (CI) for both T2DM and impaired fasting glucose (IFG) relating to each risk factor, including obesity [defined by BMI, waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR)], high blood pressure (HBP), fruit and vegetable consumption, physical inactivity, alcohol consumption, and smoking. Models for each of these traditional risk factors and interactions with age and sex were fitted. Results Factors associated with T2DM and IFG were age, obesity [defined by BMI, WC, WHtR, and WHR], HBP, smoking, physical inactivity, and fruit and vegetable consumption (p

Abstract Background Leisure-time physical activity (LTPA) is an important contributor to total physical activity and the focus of many interventions promoting activity in high-income populations. Little is known about LTPA in sub-Saharan Africa (SSA), and with expected declines in physical activity due to rapid urbanisation and lifestyle changes we aimed to assess the sociodemographic differences in the prevalence of LTPA in the adult populations of this region to identify potential barriers for equitable participation. Methods A two-step individual participant data meta-analysis was conducted using data collected in SSA through 10 population health surveys that included the Global Physical Activity Questionnaire. For each sociodemographic characteristic, the pooled adjusted prevalence and risk ratios (RRs) for participation in LTPA were calculated using the random effects method. Between-study heterogeneity was explored through meta-regression analyses and tests for interaction. Results Across the 10 populations (N = 26,022), 18.9% (95%CI: 14.3, 24.1; I 2 = 99.0%) of adults (≥ 18 years) participated in LTPA. Men were more likely to participate in LTPA compared with women (RR for women: 0.43; 95%CI: 0.32, 0.60; P

Background: Cambodia strives to eliminate all species of human malaria by 2025, requiring that foci among forest-exposed populations in remote settings be addressed. This study explores malaria risks amongst forest-exposed groups in Mondulkiri and Kampong Speu Provinces, Cambodia as part of a multi-stage study on novel mosquito bite prevention tools (Project BITE)., Methods: A serial cross-sectional survey explored the demographics, housing structure openness, mosquito bite prevention habits, and protection from malaria amongst three target groups: forest goers who work in the forest, forest dwellers who live in the forest, and forest rangers who patrol forested regions. Malaria prevalence data was collected at three time points using rapid diagnostic tests (RDTs) for febrile individuals and qPCR for all participants. Infection locations and travel patterns of Plasmodium falciparum-infected individuals were analysed for clustering and the potential movement of infections., Results: 2935 participants were enrolled between October 2022 and February 2023, consisting of 1093 (37%) forest goers and 1787 (61%) forest dwellers across both provinces, and 55 (5%) forest rangers in Mondulkiri province. Most worked outdoors as farmers, day labourers, and forest collectors, and reported going to the forest five to seven days a week. For housing, 29% and 39% of participants reported living in partially open primary and secondary structures, respectively. The main methods of mosquito bite protection used were insecticide-treated nets, wearing long sleeves, and burning mosquito coils, with limited protection during the daytime and outside at night. All febrile individuals had negative RDT test results. For qPCR, 24 P. falciparum infections (< 1%) were detected among forest goers and dwellers, clustered in Pu Trom and Pu Nhav villages in Mondulkiri Province, and Banteay Roka and Banteay Roka Kirisenchey (M) villages in Kampong Speu Province. Plasmodium vivax cases were detected (216 cases, 5%) across all enrolled villages. Only two infections were found in forest rangers., Conclusion: Malaria elimination strategies for forest-exposed populations in Cambodia should focus on vector intervention strategies that offer protection during the day and outside at night, and drug-based strategies to clear subpatent infections, targeting forest goers and dwellers in villages where cases are detected., Competing Interests: Declarations. Ethics approval and consent to participate: The study protocol was approved by the University of California’s Human Research Protection Program Institutional Review Board (IRB 22-36956) and the Cambodia Ministry of Health National Ethics Committee for Health Research (NECHR 296). Informed consent was sought by each participant prior to enrolment. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Background: Seroprevalence studies are the standard for disease surveillance, and serology determined eligibility for the first dengue vaccine. Expanding flavivirus co-circulation and vaccination complicate testing. We evaluate the accuracy of a common dengue virus serological assay, examine immunity to non-dengue flaviviruses as a contributor to decreased performance, and assess whether alternative cut points may improve assay performance., Methods: Children (n = 770) aged 2-9 years in Kampong Speu, Cambodia were enrolled in a prospective longitudinal study, and PanBio indirect dengue virus immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) was performed. Plaque reduction neutralization tests (PRNTs) using dengue viruses were performed on a subset to assess the accuracy of the IgG ELISA, and PRNTs with Zika, Japanese encephalitis, and West Nile viruses evaluated immunity to non-dengue flaviviruses. Receiver operating curve analysis identified an alternative cut point to improve IgG ELISA accuracy., Results: The dengue IgG ELISA had a lower specificity than previously reported (58% vs 93%-100%). Of those with false-positive IgG results, 46% had detectable neutralizing antibodies against other flaviviruses including 14% against West Nile virus. A higher IgG cut point improved the test accuracy in this population., Conclusions: Physicians and public health authorities should be alert for West Nile in Cambodia. Immunity to non-dengue flaviviruses can impact dengue surveillance., Clinical Trials Registration: NCT03534245., Competing Interests: Potential conflicts of interest. J. E. M. is now a Clinical Franchise Leader of Influenza in Vaccines Research and Development at Sanofi Pasteur. The work reported in this manuscript was conducted prior to her switching positions. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Purpose: Quality-of-care in refractive error services is essential, as it directly affects vision outcomes, wellbeing, educational attainment, and workforce participation. In Cambodia, uncorrected refractive error is a leading cause of mild and moderate vision impairment in adults. We evaluated the quality of refractive error care in Cambodia by estimating the proportion of prescribed and dispensed spectacles appropriate for people's refractive error needs and factors associated with spectacle quality., Methods: A cross-sectional protocol was employed with 18 Khmer-speaking adult participants observing testing procedures in 156 optical services across six provinces in 2022. A total of 496 dispensed spectacles were assessed against spectacle quality indicators., Results: The analysis revealed that 35.1% of dispensed spectacles were of optimal quality. The most common error observed in sub-optimal spectacles was the presence of horizontal prism outside of tolerance limits. The study also found that 44.0% of emmetrope visits involved unnecessary prescription spectacle recommendations, and 18.3% of written prescriptions did not correspond with dispensed spectacles. Sex differences were observed, with men predominantly providing refractive error care and women more likely to be unnecessarily recommended prescription spectacles., Conclusion: The findings highlight the importance of prioritizing quality-of-care in refractive error services. A key recommendation is to consider regulatory mechanisms to ensure optical services employ appropriately qualified staff. Additionally, efforts should be made to eliminate unnecessary prescriptions -- especially for emmetropes and females -- standardize written prescriptions, ensure consistent pupil distance measurements, reduce reliance on autorefraction, and address the gender imbalance in the refractive error workforce.

Background: Severe malaria is associated with impaired nitric oxide (NO) synthase (NOS)-dependent vasodilation, and reversal of this deficit improves survival in murine models. Malaria might have selected for genetic polymorphisms that increase endothelial NO signaling and now contribute to heterogeneity in vascular function among humans. One protein potentially selected for is alpha globin, which, in mouse models, interacts with endothelial NOS (eNOS) to negatively regulate NO signaling. We sought to evaluate the impact of alpha globin gene deletions on NO signaling and unexpectedly found human arteries use not only alpha but also beta globin to regulate eNOS., Methods: The eNOS-hemoglobin complex was characterized by multiphoton imaging, gene expression analysis, and coimmunoprecipitation studies of human resistance arteries. Novel contacts between eNOS and hemoglobin were mapped using molecular modeling and simulation. Pharmacological or genetic disruption of the eNOS-hemoglobin complex was evaluated using pressure myography. The association between alpha globin gene deletion and blood pressure was assessed in a population study., Results: Alpha and beta globin transcripts were detected in the endothelial layer of the artery wall. Imaging colocalized alpha and beta globin proteins with eNOS at myoendothelial junctions. Immunoprecipitation demonstrated that alpha globin and beta globin form a complex with eNOS and cytochrome b5 reductase. Modeling predicted negatively charged glutamic acids at positions 6 and 7 of beta globin to interact with positively charged arginines at positions 97 and 98 of eNOS. Arteries from donors with a glutamic acid-to-valine substitution at beta globin position 6 (sickle trait) exhibited increased NOS-dependent vasodilation. Alpha globin gene deletions were associated with decreased arterial alpha globin expression, increased NOS-dependent vasodilation, and lower blood pressure. Mimetic peptides that targeted the interactions between hemoglobin and eNOS recapitulated the effects of these genetic variants on human arterial vasoreactivity., Conclusions: Alpha and beta globin subunits of hemoglobin interact with eNOS to restrict NO signaling in human resistance arteries. Malaria-protective genetic variants that alter the expression of alpha globin or the structure of beta globin are associated with increased NOS-dependent vasodilation. Targeting the hemoglobin-eNOS interface could potentially improve NO signaling in diseases of endothelial dysfunction such as severe malaria or chronic cardiovascular conditions., Competing Interests: H.C.A., S.B., and P.C. are co-inventors on a patent held by the National Institute of Allergy and Infectious Diseases for structures and uses of beta globin mimetic peptides (PCT/US2023/065432). The other authors report no conflicts.

Dynamic pathogen exposure may impact the immunological response to SARS-CoV-2 (SCV2). One potential explanation for the lack of severe SCV2-related morbidity and mortality in Southeast Asia is prior exposure to related betacoronaviruses. Recent discoveries of SCV2-related betacoronaviruses from horseshoe bats (Rhinolophus sinicus) in Thailand, Laos, and Cambodia suggest the potential for bat-to-human spillover exposures in the region. In this work, serum antibodies to protein constructs from SCV2 and a representative bat coronavirus isolated in Cambodia (RshSTT182) are measured in pre-pandemic Cambodian human sera using ELISA assays. Of 293 Cambodian samples tested (N = 131 with acute malaria, n = 162 with acute undifferentiated febrile illness), 32 (10.9%) are seropositive for SCV2 based on established Spike and receptor-binding domain (RBD) cutoffs. Within SCV2 seropositive samples, 16 (50%) have higher antibody levels to antigens from the representative virus RshSTT182 versus SCV2 antigens; competitive binding ELISA assays demonstrate inhibition of reactivity to SCV2 Spike after pre-incubation with RshSTT182 Spike. Surrogate virus neutralization tests demonstrate that 8/30 (26.7%) SCV2 ELISA positive pre-pandemic Cambodian samples have neutralizing activity against SCV2, while 14/30 (46.7%) have activity against other SCV2-related betacoronaviruses. These data suggest that exposure to related betacoronaviruses may elicit cross-reactive immunity to SCV2 prior to the global pandemic., (Published 2024. This article is a U.S. Government work and is in the public domain in the USA. Advanced Science published by Wiley‐VCH GmbH.)

Avian influenza virus (AIV) in Asia is a complex system with numerous subtypes and a highly porous wild birds-poultry interface. Certain AIV subtypes, such as H14, are underrepresented in current surveillance efforts, leaving gaps in our understanding of their ecology and evolution. The detection of rare subtype H14 in domestic ducks in Southeast Asia comprises a geographic region and domestic bird population previously unassociated with this subtype. These H14 viruses have a complex evolutionary history involving gene reassortment events. They share sequence similarity to AIVs endemic in Cambodian ducks, and Eurasian low pathogenicity and high pathogenicity H5Nx AIVs. The detection of these H14 viruses in Southeast Asian domestic poultry further advances our knowledge of the ecology and evolution of this subtype and reinforces the need for continued, longitudinal, active surveillance in domestic and wild birds. Additionally, in vivo and in vitro risk assessment should encompass rare AIV subtypes, as they have the potential to establish in poultry systems.

Precise and rapid methods are needed to improve monitoring approaches of L. pneumophila (Lp) in cooling towers (CTs) to allow timely operational adjustments and prevent outbreaks. The performance of liquid culture (ASTM D8429-21) and an online qPCR device were first compared to conventional filter plate culture (ISO 11731-2017), qPCR and semi-automated qPCR at three spiked concentrations of Lp (serogroup 1) validated by flow cytometry (total/viable cell count). The most accurate was qPCR, followed by liquid culture, online and semi-automated qPCR, and lastly, by a significant margin, filter plate culture. An industrial CT system was monitored using liquid and direct plate culture by the facility, qPCR and online qPCR. Direct plate and liquid culture results agreed at regulatory sampling point, supporting the use of the faster liquid culture for monitoring culturable Lp. During initial operation, qPCR and online qPCR results were within one log of culture at the primary pump before deviating after first cleaning. Other points revealed high spatial variability of Lp. The secondary pumps and chiller had the most positivity and highest concentrations by both qPCR and liquid culture compared to the basin and infeed tank. Altogether, this suggests that results from monthly compliance sampling at a single location with plate culture are not representative of Lp risks in this CT due to the high temporal and spatial variability. The primary pump, rather than the CT basin, should be designated for sampling, as it is representative of the health risk. An annual multi point survey of the system should be conducted to identify and target Lp hot spots. Generally, a combination of liquid culture for compliance and frequent qPCR for process control provides a more agile and robust monitoring scheme than plate culture alone, enabling early treatment adjustments, due to lower limit of detection (LOD) and turnover time., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cambodia strives to eliminate all species of human malaria by 2025, requiring that foci among forest-exposed populations in remote settings be addressed. This study explores malaria risk factors amongst forest-exposed groups in Mondulkiri and Kampong Speu Provinces, Cambodia as part of a multi-stage study on novel bite prevention tools (Project BITE)., Methods: A serial cross-sectional survey explored the demographics, housing structure openness, mosquito bite prevention habits, and gaps in protection amongst three target groups: forest goers who work in the forest, forest dwellers who live in the forest, and forest rangers who patrol forested regions. Malaria prevalence data was collected at three time points using rapid diagnostic tests (RDTs) for febrile individuals and qPCR for all participants. Infection locations and travel patterns of P. falciparum-infected individuals were analyzed for clustering and the potential movement of infections., Results: 2,935 participants were enrolled between October 2022 and February 2023, consisting of 1,093 (37%) forest goers and 1,787 (61%) forest dwellers across both provinces, and 55 (5%) forest rangers in Mondulkiri province. Most worked outdoors as farmers, day laborers, and forest collectors, and reported going to the forest five to seven days a week. For housing, 29% and 39% of participants reported living in partially open primary and secondary structures, respectively. The main methods of mosquito bite protection used were insecticide-treated nets, wearing long sleeves, and burning mosquito coils, with gaps in protection during the daytime and outside at night. All febrile individuals had negative RDT test results. For qPCR, 24 P. falciparum infections (<1%) were detected among forest goers and dwellers, clustered in Pu Trom and Pu Nhav villages in Mondulkiri Province, and Banteay Roka and Banteay Roka Kirisenchey (M) villages in Kampong Speu Province. P. vivax cases were detected (216 cases, 5%) across all enrolled villages. Only two infections were found in forest rangers., Conclusion: Malaria elimination strategies for forest-exposed populations in Cambodia should focus on vector intervention strategies that offer protection during the day and outside at night, and the use of drug-based strategies to clear subpatent infections, targeting forest goers and dwellers in villages where cases are detected., Competing Interests: Additional Declarations: No competing interests reported. Competing interests: Study authors declare that they have no competing interests.

The incidence of dengue virus disease has increased globally across the past half-century, with highest number of cases ever reported in 2019 and again in 2023. We analyzed climatological, epidemiological, and phylogenomic data to investigate drivers of two decades of dengue in Cambodia, an understudied endemic setting. Using epidemiological models fit to a 19-y dataset, we first demonstrate that climate-driven transmission alone is insufficient to explain three epidemics across the time series. We then use wavelet decomposition to highlight enhanced annual and multiannual synchronicity in dengue cycles between provinces in epidemic years, suggesting a role for climate in homogenizing dynamics across space and time. Assuming reported cases correspond to symptomatic secondary infections, we next use an age-structured catalytic model to estimate a declining force of infection for dengue through time, which elevates the mean age of reported cases in Cambodia. Reported cases in >70-y-old individuals in the 2019 epidemic are best explained when also allowing for waning multitypic immunity and repeat symptomatic infections in older patients. We support this work with phylogenetic analysis of 192 dengue virus (DENV) genomes that we sequenced between 2019 and 2022, which document emergence of DENV-2 Cosmopolitan Genotype-II into Cambodia. This lineage demonstrates phylogenetic homogeneity across wide geographic areas, consistent with invasion behavior and in contrast to high phylogenetic diversity exhibited by endemic DENV-1. Finally, we simulate an age-structured, mechanistic model of dengue dynamics to demonstrate how expansion of an antigenically distinct lineage that evades preexisting multitypic immunity effectively reproduces the older-age infections witnessed in our data., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Antimicrobial resistance (AMR) surveillance in low- and middle-income countries (LMICs) often relies on poorly resourced laboratory processes. Centralized sequencing was combined with cloud-based, open-source bioinformatics solutions for national AMR surveillance in Cambodia., Methods: Blood cultures growing gram-negative bacteria were collected at six Cambodian hospitals (January 2021 - October 2022). Isolates were obtained from pure plate growth and shotgun DNA sequencing performed in-country. Using public nucleotide and protein databases, reads were aligned for pathogen identification and AMR gene characterization. Multilocus sequence typing was performed on whole genome assemblies and haplotype clusters compared against published genomes., Findings: Genes associated with acquired resistance to fluoroquinolones were identified in 59%, TMP/SMX in 45%, and aminoglycosides in 52% of 715 isolates. Extended-spectrum beta-lactamase encoding genes were identified in 34% isolates, most commonly blaCTX-M-15, blaCTX-M-27, and blaCTX-M-55 in E. coli sequence types 131 and 1193. Carbapenemase genes were identified in 12% isolates, most commonly blaOXA-23, blaNDM-1, blaOXA-58 and blaOXA-66 in Acinetobacter species. Phylogenetic analysis revealed clonal strains of A. baumannii, representing suspected nosocomial outbreaks, and genetic clusters of quinolone-resistant typhoidal Salmonella and ESBL E. coli cases suggesting community transmission., Interpretation: With accessible sequencing platforms and bioinformatics solutions, bacterial genomics can supplement AMR surveillance in LMICs., Funding: Research was supported by the National Institute of Allergy and Infectious Diseases and the Bill and Melinda Gates Foundation [OPP1211806]., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2024.)

Plastics in aquatic ecosystems rapidly undergo biofouling, giving rise to a new ecosystem on their surface, the 'plastisphere.' Few studies quantify the impact of plastics and their associated community on ecosystem traits from biodiversity and functional traits to metabolic function. It has been suspected that impacts on ecosystems may depend on its state but comparative studies of ecosystem responses are rare in the published literature. We quantified algal biomass, bacterial and algal biodiversity (16S and 18S rRNA), and metabolic traits of the community growing on the surface of different plastic polymers incubated within rivers of the Lower Mekong Basin. The rivers selected have different ecological characteristics but are similar regarding their high degree of plastic pollution. We examined the effects of plastics colonized with biofilms on ecosystem production, community dark respiration, and the epiplastic community's capability to influence nitrogen, phosphorus, organic carbon, and oxygen in water. Finally, we present conceptual models to guide our understanding of plastic pollution within freshwaters. Our findings showed limited microalgal biomass and bacterial dominance, with potential pathogens present. The location significantly influenced community composition, highlighting the role of environmental conditions in shaping community development. When assessing the effects on ecosystem productivity, our experiments showed that biofouled plastics led to a significant drop in oxygen concentration within river water, leading to hypoxic/anoxic conditions with subsequent profound impacts on system metabolism and the capability of influencing biogeochemical cycles. Scaling our findings revealed that plastic pollution may exert a more substantial and ecosystem-altering impact than initially assumed, particularly in areas with poorly managed plastic waste. These results highlighted that the plastisphere functions as a habitat for biologically active organisms which play a pivotal role in essential ecosystem processes. This warrants dedicated attention and investigation, particularly in sensitive ecosystems like the Mekong River, which supports a rich biodiversity and the livelihoods of 65 million people., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

In resource-scarce settings, melioidosis is associated with up to 80% mortality. Studies of melioidosis in Cambodia report primarily on pediatric populations with localized infection; however, literature describing Cambodian adults with severe melioidosis is lacking. We present a case series of 35 adults with sequence-confirmed Burkholderia pseudomallei bacteremia presenting to a provincial referral hospital in rural Cambodia. More than 90% of the patients had diabetes, an important risk factor for developing melioidosis. Inappropriate antimicrobial therapy was significantly associated with lower odds of survival. Improved diagnostic testing and greater access to first-line antibiotics for acute melioidosis treatment present potential targets for intervention to reduce mortality associated with this disease in resource-limited settings.