Examining the Acceptability of Helminth Education Packages "Magic Glasses Lower Mekong" and "Magic Glasses Opisthorchiasis" and Their Impact on Knowledge, Attitudes, and Practices Among Schoolchildren in the Lower Mekong Basin: Protocol for a Cluster Randomized Controlled Trial.

BACKGROUND: Helminths are a major global health issue, impacting health, educational, and socioeconomic outcomes. Infections, often starting in childhood, are linked to anemia, malnutrition, cognitive deficit, and in chronic cases of Opisthorchis viverrini (OV), cholangiocarcinoma. The main control strategy for helminth infection is mass drug administration; however, this does not prevent reinfection. As such, prevention strategies are needed. The "Magic Glasses" is a school-based cartoon health education package that has demonstrated success in improving knowledge, attitudes, and practices (KAP) surrounding soil-transmitted helminths (STH) in China and the Philippines. This study is designed to assess the acceptability and impact of the 2 new versions of the Magic Glasses targeting STH and OV designed for the Lower Mekong audience in Cambodia, Lao People's Democratic Republic (PDR), and Thailand. OBJECTIVE: The objective of this study is to evaluate the acceptability of the "Magic Glasses Lower Mekong" and "Magic Glasses Opisthorchiasis" education packages among schoolchildren in the Lower Mekong Basin, and the impact of these education packages on students' KAP surrounding STH and OV, respectively. METHODS: Schoolchildren will be recruited into a cluster randomized controlled trial with intervention and control arms in rural schools in Cambodia, Lao PDR, and Thailand. Schoolchildren's initial acceptability of the intervention will be evaluated using an adapted questionnaire. Sustained acceptability will be assessed at 9-month follow-up through focus group discussions with students and interviews with teachers. Impact will be evaluated by KAP questionnaires on STH and OV. KAP questionnaires will be administered to children at baseline and at follow-up. Indirect impact on parents' KAP of OV and STH will be assessed through focus group discussions at follow-up. RESULTS: The trial is in progress in Lao PDR and Thailand and is expected to commence in Cambodia in January 2024. The results of the study are expected to be available 18 months from the start of recruitment. We hypothesize that participants enrolled in the intervention arm of the study will have higher KAP scores for STH and OV, compared with the participants in the control arm at follow-up. We expect that students will have initial and sustained acceptability of these intervention packages. CONCLUSIONS: This trial will examine the acceptability of the "Magic Glasses Opisthorchiasis" and "Magic Glasses Lower Mekong" interventions and provide evidence on the effectiveness of the "Magic Glasses" on KAP related to OV and STH among schoolchildren in the Lower Mekong Basin. Study results will provide insight on acceptability and impact indicators and inform a scaling up protocol for the "Magic Glasses" education packages in Cambodia, Lao PDR, and Thailand. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12623000271606; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=385315&isReview=true. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/55290.

The effectiveness, feasibility, and acceptability of an education intervention promoting healthy lifestyle to reduce risk factors for metabolic syndrome, among office workers in Ethiopia: A protocol for a randomized control trial study.

BACKGROUND: Nowadays, metabolic syndrome has become a major health threat, and affects over one billion people globally. It also plays a great role in the growth of diseases like type 2 diabetes, coronary diseases, stroke, and other chronicity. It increases the risk of cardiovascular disorder and stroke by three to ten times and diabetic mellitus by ten times. The prevalence of metabolic syndrome is increasing globally as a result of epidemiological shift. Low and middle-income countries are facing an increasing burden of metabolic syndrome. There is a need for concerted efforts to modify behavioral risk factors that significantly contribute to the prevalence of the syndrome. This can be done by developing and implementing appropriate interventions that can bring behavior change after testing for effectiveness, feasibility, and acceptability. Thus, this study aims to develop and test the effectiveness, feasibility and acceptability of an education intervention promoting healthy lifestyle to reduce risk factors for metabolic syndrome, among office workers in Ethiopia. METHODS AND ANALYSIS: This randomized controlled trial will be implemented with 226 bank employees (age ≥18 years) with metabolic syndrome from government and private banks in Bahir Dar City, Ethiopia. Participants will be randomized to intervention (education) and control (general health advice) groups. The intervention group will be given one-on -one base education about healthy diets, physical exercise, stress management, avoidance of harmful alcohol consumption and smoking cessation by experts on health promotion. Text messages will be sent every two weeks and reading materials will also be provided. Additionally, a review meeting will be held at the 3rd and 6th month of the intervention. The primary outcomes of interest will be change in metabolic parameters (obesity levels, blood pressure, fasting blood glucose, total cholesterol, high density lipoprotein, low density lipoprotein, and triglycerides). Secondary outcomes will be knowledge, attitudes and practice of the participants towards lifestyle and cardiovascular risk factors, feasibility, acceptability, implementation fidelity, and cost-effectiveness of the intervention. Data will be collected at three time points: at baseline, at the 6th month of the intervention and at the end of the intervention (9 months). Generalized linear mixed models will be utilized to compare the desired outcome between the trial arms, after accounting for baseline variations. Cost-benefit analysis and a qualitative process evaluation of the intervention will also be conducted. DISCUSSION: This randomized control trial study will provide information on the effectiveness, feasibility, and acceptability of an education intervention promoting healthy lifestyle to reduce risk factors for metabolic syndrome, among office workers in Ethiopia, where the burden of metabolic syndrome is high among office workers. CLINICAL TRIAL REGISTRATION: This trial has been prospectively registered at the Australian New Zealand Clinical Trials Registry: ACTRN12623000409673p.

Application of rational enzyme engineering in a new route to etonogestrel and levonorgestrel: carbonyl reductase bioreduction of ethyl secodione.

Women in developing countries still face enormous challenges when accessing reproductive health care. Access to voluntary family planning empowers women allowing them to complete their education and join the paid workforce. This effectively helps to end poverty, hunger and promotes good health for all. According to the United Nations (UN) organization, in 2022, an estimated 257 million women still lacked access to safe and effective family planning methods globally. One of the main barriers is the associated cost of modern contraceptive methods. Funded by the Bill & Melinda Gates Foundation, Almac Group worked on the development of a novel biocatalytic route to etonogestrel and levonorgestrel, two modern contraceptive APIs, with the goal of substantially decreasing the cost of production and so enabling their use in developing nations. This present work combines the selection and engineering of a carbonyl reductase (CRED) enzyme from Almac's selectAZyme™ panel, with process development, to enable efficient and economically viable bioreduction of ethyl secodione to (13R,17S)-secol, the key chirality introducing intermediate en route to etonogestrel and levonorgestrel API. CRED library screening returned a good hit with an Almac CRED from Bacillus weidmannii, which allowed for highly stereoselective bioreduction at low enzyme loading of less than 1% w/w under screening assay conditions. However, the only co-solvent tolerated was DMSO up to ∼30% v/v, and it was impossible to achieve reaction completion with any enzyme loading at substrate titres of 20 g L-1 and above, due to the insolubility of the secodione. This triggered a rapid enzyme engineering program fully based on computational mutant selection. A small panel of 93 CRED mutants was rationally designed to increase the catalytic activity as well as thermal and solvent stability. The best mutant, Mutant-75, enabled a reaction at 45 °C to go to completion at 90 g L-1 substrate titre in a buffer/DMSO/heptane reaction medium fed over 6 h with substrate DMSO stock solution, with a low enzyme loading of 3.5% w/w wrt substrate. In screening assay conditions, Mutant-75 also showed a 2.2-fold activity increase. Our paper shows which computations and rational decisions enabled this outcome.

Undernutrition increases the risk of unsuccessful treatment outcomes of patients with tuberculosis in Ethiopia: A multicenter retrospective cohort study.

BACKGROUND: While undernutrition has been identified as a common risk factor for tuberculosis (TB), its impact on treatment outcomes has yet to be investigated in high TB burden and low-income countries such as Ethiopia. Therefore, this study aimed to investigate the effect of undernutrition on treatment outcomes among patients with TB in northwest Ethiopia. METHODS: A retrospective cohort study was conducted using data from different hospitals in northwest Ethiopia, for the period from July 2017 to August 2023. A Cox proportional hazard model was performed to determine the effect of undernutrition on TB treatment outcomes, which were defined as a composite of death, treatment failure, or loss to follow-up. RESULTS: A total of 602 patients with TB were included in the analysis. Of these, 367 (60.9%) were male, and 344 (57.1%) were undernourished. Upon completion of the follow-up period, 65 (10.8%) adults with TB had unsuccessful treatment outcomes. After adjusting for potential confounders, patients with undernutrition had a two times higher risk of experiencing unsuccessful treatment outcomes compared to well-nourished patients (AHR: 2.0, 95% CI: 1.2, 3.6). In addition, patients residing in rural areas (AHR: 3.1, 95% CI: 1.7, 5.4), having a history of prior TB treatment (AHR: 2.2, 95%CI: 1.1, 4.1), and the presence of diabetes comorbidity (AHR: 2.4, 95% CI: 1.1, 5.2) were at higher risk of unsuccessful treatment outcomes. CONCLUSIONS: Undernutrition increases the risk of unsuccessful treatment outcomes in Ethiopia. This finding suggests that nutritional support during TB treatment can improve successful treatment outcomes in high TB burden and low-income countries such as Ethiopia.

A review of health education activities targeting schoolchildren for the control of soil-transmitted helminthiasis in Southeast Asia, with emphasis upon the Magic Glasses approach.

Soil-transmitted helminths continue to be a serious problem causing disease and morbidity globally. Children, mostly school-aged, are more at risk of these infections. The main strategy for control remains to be the mass drug administration (MDA) of antihelminthic drugs. With the limitation of MDA to prevent re-infection, the need for additional approaches such as hygiene education and improvements in water, sanitation and hygiene (WASH) infrastructure are required. Although the importance of health education as a crucial component of an integrated approaches to STH control is highlighted, this component has often been disregarded because the other more complex solutions have been the focus of most studies and programmes. We performed literature searches from four bibliographic databases - Scopus, PubMed, Web of Science and Cochrane Library - to determine availability of studies on the impact of health education interventions targeting STH infections on schoolchildren in Southeast Asia. Our review found only three studies that evaluated health education interventions targeting children. The current lack of evidence in this area suggests the need for more studies assessing the impact of health education intervention for STH control. A successful health education programme for STH called "The Magic Glasses" has been developed targeting schoolchildren in China and the Philippines. This public health intervention displayed significant impact in terms of improving knowledge, attitude and practices, reducing prevalence of STH infections in schoolchildren and encouraging compliance to MDA. This article details the successes and benefits of the Magic Glasses programme as a promising control tool for STH in the Southeast Asian region.

Transmission-Blocking Vaccines against Schistosomiasis Japonica.

Control of schistosomiasis japonica, endemic in Asia, including the Philippines, China, and Indonesia, is extremely challenging. Schistosoma japonicum is a highly pathogenic helminth parasite, with disease arising predominantly from an immune reaction to entrapped parasite eggs in tissues. Females of this species can generate 1000-2200 eggs per day, which is about 3- to 15-fold greater than the egg output of other schistosome species. Bovines (water buffalo and cattle) are the predominant definitive hosts and are estimated to generate up to 90% of parasite eggs released into the environment in rural endemic areas where these hosts and humans are present. Here, we highlight the necessity of developing veterinary transmission-blocking vaccines for bovines to better control the disease and review potential vaccine candidates. We also point out that the approach to producing efficacious transmission-blocking animal-based vaccines before moving on to human vaccines is crucial. This will result in effective and feasible public health outcomes in agreement with the One Health concept to achieve optimum health for people, animals, and the environment. Indeed, incorporating a veterinary-based transmission vaccine, coupled with interventions such as human mass drug administration, improved sanitation and hygiene, health education, and snail control, would be invaluable to eliminating zoonotic schistosomiasis.

Serological Comparison of Native Antigen ELISAs with Rapid ICT Test Kits for the Diagnosis of Human Alveolar and Cystic Echinococcosis in China.

BACKGROUND: The aim of this study was to compare the diagnostic performance of native antigen ELISAs and ADAMU-AE/CE commercial ICT test kits in subjects either exposed to Echinococcus infection or with clinically diagnosed alveolar (AE) or cystic (CE) echinococcosis. METHODS: A total of 370 subjects with a previous clinical confirmation of CE or AE from northwestern China were recruited. Serum samples were also obtained from 3923 children/teenagers during a community survey. All sera were tested using native antigen ELISAs. The ADAMU-AE/CE test kits were subsequently used for the serology of the 370 clinically confirmed individuals and of 251 children/teenagers that were ELISA antibody-positive for both Echinococcus species but ultrasound-negative during baseline survey. An analysis of the association between the serological tests and ultrasound classification was carried out amongst 89 AE and 164 CE cases. A Kappa consistency analysis was undertaken to compare the diagnostic performance of the native antigen ELISAs and the ADAMU kits and the ultrasound imaging results. The χ² test was also used for a comparison of the different seropositivity rates between the groups. FINDINGS: There was poor consistency (Kappa = 0.26 and 0.28 for AE and CE respectively) between the native antigen ELISAs and the ADAMU kits for the diagnosis of AE and CE among the cases and the surveyed children/teenagers, but a relatively good consistency (Kappa = 0.63) between the ADAMU-AE kit and ultrasound observations for the AE cases. Additionally, of the 251 teenagers co-positive for both AE and CE antibodies by the native antigen ELISAs, only one was found positive by the ADAMU-AE kit, verified as a new AE case on subsequent ultrasound follow-up. The remainder (N = 250) were negative by serology using the ADAMU-AE/CE kits and by ultrasound examination. The two native antigen ELISAs did not discriminate well between cases of clinically diagnosed AE and CE. In contrast, ADAMU-AE and ADAMU-CE commercial ICT test kits readily differentiated cases of AE from CE with specificities of 99% for AE and 100% for CE. CONCLUSIONS: The ADAMU-AE/CE kits proved reliable, accurate, and amenable diagnostic tools in the clinical setting for confirmation of suspected AE/CE cases. The native antigen ELISAs tests can provide useful information on the level of human exposure to Echinococcus infection.

Protocol for spatial prediction of soil transmitted helminth prevalence in the Western Pacific region using a meta-analytical approach.

BACKGROUND: Soil transmitted helminth (STH) infections are estimated to impact 24% of the world's population and are responsible for chronic and debilitating morbidity. Disadvantaged communities are among the worst affected and are further marginalized as infection prevalence fuels the poverty cycle. Ambitious targets have been set to eliminate STH infections, but accurate epidemiological data will be required to inform appropriate interventions. This paper details the protocol for an analysis that aims to produce spatial prediction mapping of STH prevalence in the Western Pacific Region (WPR). METHODS: The protocol follows the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocol (PRISMA-P) guidelines. The study design will combine the principles of systematic review, meta-analysis, and geospatial analysis. Systematic searches will be undertaken in PubMed, Scopus, ProQuest, Embase, and Web of Science for studies undertaken post 2000, to identify surveys that enable the prevalence of human STH infection within the WPR to be calculated. Covariate data for multivariable analysis will be obtained from publicly accessible sources. Survey data will be geolocated, and STH prevalence and covariates will be linked to produce a spatially referenced dataset for analysis. Bayesian model-based geostatistics will be used to generate spatially continuous estimates of STH prevalence mapped to a resolution of 1 km2. A separate geospatial model will be constructed for each STH species. Predictions of prevalence will be made for unsampled locations and maps will be overlaid for each STH species to obtain co-endemicity maps. DISCUSSION: This protocol facilitates study replication and may be applied to other infectious diseases or alternate geographies. Results of the subsequent analysis will identify geographies with high STH prevalence's and can be used to inform resource allocation in combating this neglected tropical disease. TRIAL REGISTRATION: Open Science Framework: osf.io/qmxcj.

Strongyloidiasis.

Strongyloidiasis is a neglected tropical disease caused primarily by the roundworm Strongyloides stercoralis. Strongyloidiasis is most prevalent in Southeast Asia and the Western Pacific. Although cases have been documented worldwide, global prevalence is largely unknown due to limited surveillance. Infection of the definitive human host occurs via direct skin penetration of the infective filariform larvae. Parasitic females reside in the small intestine and reproduce via parthenogenesis, where eggs hatch inside the host before rhabditiform larvae are excreted in faeces to begin the single generation free-living life cycle. Rhabditiform larvae can also develop directly into infectious filariform larvae in the gut and cause autoinfection. Although many are asymptomatic, infected individuals may report a range of non-specific gastrointestinal, respiratory or skin symptoms. Autoinfection may cause hyperinfection and disseminated strongyloidiasis in immunocompromised individuals, which is often fatal. Diagnosis requires direct examination of larvae in clinical specimens, positive serology or nucleic acid detection. However, there is a lack of standardization of techniques for all diagnostic types. Ivermectin is the treatment of choice. Control and elimination of strongyloidiasis will require a multifaceted, integrated approach, including highly sensitive and standardized diagnostics, active surveillance, health information, education and communication strategies, improved water, sanitation and hygiene, access to efficacious treatment, vaccine development and better integration and acknowledgement in current helminth control programmes.

Perspective: Connecting the dots between domestic livestock ownership and child linear growth in low- and middle-income countries.

Child stunting due to linear growth faltering remains a pervasive issue in low- and middle-income countries. Two schools of thought have existed pertaining to the role of domestic livestock ownership (DLO) in child linear growth. On one hand, it is argued that DLO leads to greater income and financial security, resulting in better child-raising conditions, including greater animal-source food (ASF) consumption, having protective effects towards child stunting. On the other hand, researchers argue that DLO contributes to faecal contamination and transmission of zoonotic enteric infections from animals to children, thus having destructive effects on child growth. Reviews of this association have revealed ambiguous findings. In this perspective, we argue that measuring the association between exposures to domesticated animals and child stunting is difficult and the ambiguous associations revealed are a result of confounding and differences in the management of DLO. We also argue that the increasingly prominent area of research of environmental enteric dysfunction, a sub-clinical condition of the small intestine thought to be due to frequent faecal pathogen exposure and associated with stunting, will be a useful tool to measure the potential destructive effects of DLO on child growth. We present our argument and identify challenges and considerations and directions for future research.

Impacts of body weight change on treatment outcomes in patients with multidrug-resistant tuberculosis in Northwest Ethiopia.

Measuring body weight during therapy has received insufficient attention in poor resource settings like Ethiopia. We aimed to investigate the association between weight change during therapy and treatment outcomes among patients with multidrug-resistant tuberculosis (MDR-TB) in northwest Ethiopia. This retrospective cohort study analysed data from patients with MDR-TB admitted between May 2015 to February 2022 at four treatment facilities in Northwest Ethiopia. We used the joint model (JM) to determine the association between weight change during therapy and treatment outcomes for patients with MDR-TB. A total of 419 patients with MDR-TB were included in the analysis. Of these, 265 (63.3%) were male, and 255 (60.9%) were undernourished. Weight increase over time was associated with a decrease in unsuccessful treatment outcomes (adjusted hazard ratio (AHR): 0.96, 95% CI: 0.94 to 0.98). In addition, patients with undernutrition (AHR: 1.72, 95% CI: 1.10 to 2.97), HIV (AHR:1.79, 95% CI: 1.04 to 3.06), and clinical complications such as pneumothorax (AHR: 1.66, 95% CI: 1.03 to 2.67) were associated with unsuccessful treatment outcomes. The JM showed a significant inverse association between weight gain and unsuccessful MDR-TB treatment outcomes. Therefore, weight gain may be used as a surrogate marker for good TB treatment response in Ethiopia.

Prevalence and determinants of hypertension in South-Asian Urban Communities: findings from Demographic and Health Surveys (DHS) data of South Asian countries.

Hypertension increases risk of stroke and other cardiovascular diseases, however, its prevalence and determinants in South Asian urban communities using country representative community-based datasets is lacking. This study evaluated prevalence of hypertension and it's determinants among urban residents of three South Asian countries. Urban population data from demographic and health surveys in Bangladesh, India, and Nepal were extracted. Hypertension prevalence was defined as systolic/diastolic blood pressure ≥ 140/ 90 mmHg. Age, education, wealth, physical activity, alcohol, BMI were considered as risk factors associated with the increased risk of hypertension. We performed binary logistic regression and calculated adjusted Odds Ratios (AOR) with 95% confidence interval (CI) to assess factors related to hypertension. Hypertension prevalence was 37.4% in India, 25.1% in Bangladesh and 18.4% in Nepal. Prevalence increased with age in all settings. Females had reduced odds of hypertension in Bangladesh (AOR 0.75; CI: 0.69, 0.81) and Nepal (AOR 0.62; CI: 0.54, 0.71), but higher risk in India (AOR 2.54; CI: 2.45, 2.63). Low education, caffeine consumption, obesity was associated with higher prevalence of hypertension in all three countries. Smokers had increased odds of hypertension in India (AOR 1.11; CI: 1.06, 1.15) and Nepal (AOR 1.23; 1.02, 1.47). Overall, hypertension prevalence is high in all three countries. Modifiable socioeconomic and lifestyle factors (education, wealth index, smoking status, caffeine consumption and BMI) associated with hypertension. Comprehensive hypertension pacific and sensitive interventions (including behavioral modification treatments and timely screening and access to health care) are urgently needed to prevent and control hypertension among urban populations in South Asia.

Risk mapping and socio-ecological drivers of soil-transmitted helminth infections in the Philippines: a spatial modelling study.

Background: The Philippines reports a high prevalence of soil-transmitted helminth (STH) infections despite the implementation of nationwide mass drug administration since 2006. The spatial variation of STH infections in the Philippines was last described using the 2005-2007 national STH and schistosomiasis survey. This study aimed to identify sociodemographic and environmental factors that drive STH transmission and predict high-risk areas in the Philippines. Methods: Epidemiological data on STH for students aged 5-16 years were obtained from the 2015 Philippines National Prevalence survey, while environmental data were extracted from satellite images and publicly available sources. Model-based geostatistics, implemented in a Bayesian framework, was used to identify sociodemographic and environmental correlates and predict high-risk areas for STH across the Philippines. The best-fitting model with the lowest deviance information criterion (DIC) was used to interpret the findings of the model and predict STH infection risk for the entire country. Risk maps were developed for each STH infection using the posterior means derived from the model. Findings: The prevalence of Ascaris lumbricoides (20.0%) and Trichuris trichiura (29.3%) was higher in the Visayas Island than in the Luzon and Mindanao Islands. Hookworm prevalence was highest in Mindanao Island (1.3%). Risk of A. lumbricoides was positively associated with males (odds ratio [OR]: 1.197; 97.5% Credible Interval [CrI]: 1.114, 1.286) and temperature (OR: 1.148; 97.5% CrI: 1.033, 1.291), while normalized difference vegetation index (OR: 0.354; 97.5% CrI: 0.138, 0.930) and soil pH (OR: 0.606; 97.5% CrI: 0.338, 0.949) were negatively associated with the transmission. T. trichiura risk was positively associated with males (OR: 1.261; 97.5% CrI: 1.173, 1.341), temperature (OR: 1.153; 97.5% CrI: 1.001, 1.301), and rainfall (OR: 1.004; 97.5% CrI: 1.011, 1.069). Hookworm risk was positively associated with males (OR: 2.142; 97.5% CrI: 1.537, 2.998), while children aged ≤12 years (OR: 0.435; 97.5% CrI: 0.252, 0.753) had a negative association with risk compared to those over 12 years. Focal areas of high risk were identified for A. lumbricoides and T. trichiura in the Visayas Island, and hookworm in the Mindanao Island. Interpretation: The spatial distribution of all three STH infections has considerably decreased since a previous national risk-mapping exercise. The high-risk areas identified in the study can be used to strategically target deworming and health education activities to further reduce the burden of STH and support progress toward elimination. Funding: The Australian Centre for the Control and Elimination of Neglected Tropical Diseases and the Australian National Health and Medical Research Council.

Geospatial Overlap of Undernutrition and Tuberculosis in Ethiopia.

Undernutrition is a key driver of the global tuberculosis (TB) epidemic, yet there is limited understanding regarding the spatial overlap of both diseases. This study aimed to determine the geographical co-distribution and socio-climatic factors of undernutrition and TB in Ethiopia. Data on undernutrition were found from the Ethiopian Demographic and Health Survey (EDHS). Data on TB were obtained from the Ethiopia national TB prevalence survey. We applied a geostatistical model using a Bayesian framework to predict the prevalence of undernutrition and TB. Spatial overlap of undernutrition and TB prevalence was detected in the Afar and Somali regions. Population density was associated with the spatial distribution of TB [ß: 0.008; 95% CrI: 0.001, 0.014], wasting [ß: -0.017; 95% CrI: -0.032, -0.004], underweight [ß: -0.02; 95% CrI: -0.031, -0.011], stunting [ß: -0.012; 95% CrI: -0.017, -0.006], and adult undernutrition [ß: -0.007; 95% CrI: -0.01, -0.005]. Distance to a health facility was associated with the spatial distribution of stunting [ß: 0.269; 95% CrI: 0.08, 0.46] and adult undernutrition [ß: 0.176; 95% CrI: 0.044, 0.308]. Healthcare access and demographic factors were associated with the spatial distribution of TB and undernutrition. Therefore, geographically targeted service integration may be more effective than nationwide service integration.

Community-wide versus school-based targeted deworming for soil-transmitted helminth control in school-aged children in Vietnam: the CoDe-STH cluster-randomised controlled trial.

Background: Soil-transmitted helminth (STH) infection control programs typically consist of school-based preventive chemotherapy (PC) targeted to school-aged children. STH reservoirs in untreated community members contribute to ongoing transmission in children. The CoDe-STH (Community Deworming against STH) trial, conducted in Dak Lak province, Vietnam, between October 2019 and November 2020, aimed to determine whether community-wide mass drug administration (MDA) is more effective than school-based targeted PC in reducing STH prevalence and intensity in children. Methods: In this two-arm cluster randomised controlled trial, 64 primary schools were randomly assigned 1:1 to receive either school-based targeted PC ("school arm") or community-wide MDA ("community arm"). A single dose of albendazole 400 mg was used for deworming. The primary outcome was hookworm prevalence in schoolchildren, measured using quantitative real-time PCR. We also measured infection intensity for Necator americanus only, using qPCR cycle threshold (Ct) values converted into eggs per gram of faeces (EPG). Analysis was by intention to treat. The trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000309189). Findings: The analysis included 4955 children in the school arm and 5093 children in the community arm. N. americanus was the dominant STH species. The relative reduction in hookworm prevalence was not significantly different between the school arm (30.1%, 95% confidence interval [CI] 20.5-36.9) and the community arm (34.6%, 95% CI 19.9-49.4). Due to lower baseline prevalence than expected, the study was underpowered to detect a difference in prevalence reduction between the study arms. The community arm showed significantly greater relative reduction in N. americanus infection intensity (56.0%, 95% CI 39.9-72.1) compared to the school arm (3.4%, 95% CI -24.7 to 31.4). The community arm also showed greater relative reduction in prevalence of moderate-to-heavy intensity (≥2000 EPG) N. americanus infections (81.1%; 95% CI 69.7-92.6) compared to the school arm (39.0%, 95% CI 13.7-64.2). Interpretation: Although no impact was seen on overall prevalence, community-wide MDA was more effective in lowering N. americanus infection intensity in schoolchildren compared to school-based targeted PC, measured 12 months after one round of albendazole deworming with high coverage. Funding: National Health and Medical Research Council, Australia (APP1139561).

Effectiveness of nutritional support to improve treatment adherence in patients with tuberculosis: a systematic review.

CONTEXT: Nutritional interventions substantially improve tuberculosis (TB) treatment outcomes and prevent complications. However, there is limited evidence about the connections between having nutritional support and TB treatment adherence. OBJECTIVE: The aim of this study was to determine the effectiveness of nutritional support in improving treatment adherence among patients with TB. DATA SOURCES: Databases, including PubMed, Embase (Ovid), Web of Science, and Scopus, were comprehensively reviewed to identify relevant studies reporting the impacts of nutritional support on TB treatment adherence. DATA EXTRACTION: Two authors independently screened the title, abstracts, and full article texts to identify eligible studies and assess the risk of bias. Observational and interventional studies were included. DATA ANALYSIS: A narrative synthesis approach was used to summarize the findings qualitatively. RESULTS: From the search, 3059 publications were identified; of these, 8 studies were included in this systematic review. Three types of nutritional interventions were identified: food baskets (eg, energy, micronutrient- or macronutrient-enriched food support), nutritional advice and guidance, and incentives for buying foods. Although 5 studies reported that nutritional support significantly improved treatment adherence in patients with TB, 3 studies showed that nutritional support had no effect on TB treatment adherence. CONCLUSIONS: Providing nutritional support may improve adherence to TB treatment. However, more well-powered, high-quality trials are warranted to demonstrate the effect of nutrition support on cost-effectively improving adherence to TB treatment. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42023392162.

Epidemiology of soil-transmitted helminths using quantitative PCR and risk factors for hookworm and Necator americanus infection in school children in Dak Lak province, Vietnam.

BACKGROUND: Soil-transmitted helminth (STH) infection is driven by a complex interaction of demographic, socioeconomic and behavioural factors, including those related to water, sanitation and hygiene (WASH). Epidemiological studies that measure both infection and potential risk factors associated with infection help to understand the drivers of transmission in a population and therefore can provide information to optimise STH control programmes. METHODS: During October and November 2019, we conducted a cross-sectional survey of the prevalence and intensity of STH infection and associated risk factors among 7710 primary-school-age children from 64 primary schools across 13 districts in Dak Lak province, Vietnam. Quantitative PCR (qPCR) was used to detect and quantify STH infections. RESULTS: The predominant STH species was the hookworm Necator americanus (overall cluster-adjusted prevalence of 13.7%), and its prevalence was heterogeneously distributed across surveyed schools (0% to 56.3%). All other STH species had a prevalence of less than 1%. Using mixed-effects logistic regression, we found that the adjusted odds ratio (aOR) was significantly higher for both infection and moderate-to-heavy-intensity infection with N. americanus among children from multiple ethnic minority groups, compared to children from the majority group (Kinh). Adjusted odds of infection with N. americanus were also higher in children who reported practising open defecation at school (aOR 1.42, 95% CI 1.05, 1.93, P = 0.02) and in those who had an unimproved household water supply (aOR 1.28, 95% CI 1.04, 1.57, P = 0.02). Conversely, children with a flushing household toilet had a reduced risk of infection (aOR 0.58, 95% CI 0.47, 0.70, P < 0.01), as did those whose primary female carer attended secondary (aOR 0.65, 95% CI 0.51, 0.84, P < 0.01) or tertiary education (aOR 0.39, 95% CI 0.24, 0.63, P < 0.01). CONCLUSIONS: This study is the largest reported prevalence survey of STH infections conducted using qPCR as a diagnostic technique. The findings of higher adjusted odds of infection amongst ethnic minority children highlight that STH control programmes may not be reaching certain population groups and that additional culturally appropriate approaches may be required. Additionally, the associations between specific WASH factors and infection indicate potential programmatic targets to complement preventive chemotherapy programmes.

Convergent Biocatalytic Mediated Synthesis of siRNA.

New technologies are required to combat the challenges faced with manufacturing commercial quantities of oligonucleotide drug substances which are required for treating large patient populations. Herein we report a convergent biocatalytic synthesis strategy for an Alnylam model siRNA. The siRNA chemical structure includes several of the unnatural modifications and conjugations typical of siRNA drug substances. Using Almac's 3-2-3-2 hybrid RNA ligase enzyme strategy that sequentially ligates short oligonucleotide fragments (blockmers), the target siRNA was produced to high purity at 1 mM concentration. Additional strategies were investigated including the use of polynucleotide kinase phosphorylation and the use of crude blockmer starting materials without chromatographic purification. These findings highlight a path toward a convergent synthesis of siRNAs for large-scale manufacture marrying both enzymatic liquid and classical solid-phase synthesis.

Impact of COVID-19 on mental health in Bhutan: a way forward for action.

The coronavirus disease 2019 (COVID-19) pandemic continues to impact mental health and wellbeing globally. There is a lack of scientific documentation highlighting the mental health impact of COVID-19 in Bhutan. We present the mental health burdens and control measures taken, and suggest ways to further strengthen mental health services in Bhutan. During the pandemic, a rise in depression and anxiety had been reported in Bhutan. Depression rose from an average prevalence of 9 per 10,000 between 2011 and 2019 to 16 per 10,000 in 2020 and 32 per 10,000 in 2021. Similarly, anxiety rose from an average prevalence of 18 per 10,000, to 29 per 10,000 in 2020, and 55 per 10,000 in 2021. Psychological impacts related to isolation due to lockdowns, economic losses, and poor coping abilities were associated with negative outcomes. Stigma and discrimination towards mental health disorders discouraged mentally distressed people from seeking care. In response to increased demand, Bhutan's government initiated a range of interventions including home delivery of medicines and tele-counselling to people in need of urgent mental health care. Mental health care in Bhutan can be further improved through investment in services and human resources, and decentralization of services to the community.