Implementation fidelity of hospital based directly observed therapy for tuberculosis treatment in Bhutan: mixed-method study.

BACKGROUND: Direct observed treatment (DOT) has been implemented in Bhutan since 1997 and currently, it is offered in various model of delivery including a combination of hospital based, home based DOT and ambulatory DOT. Overall, treatment success rate for tuberculosis cases is higher than the global target; however, it is still need to be improved. Evaluation to the implementation fidelity of DOT is important to identify potential rooms for improvement. This study aimed to assess two major components of the program's implementation fidelity: to assess patient's adherence to DOT and explore factors for adherence; to assess provider's compliance with DOT guideline and explore factors for compliance. METHODS: This research used a sequential explanatory mixed method. The conceptual framework of implementation fidelity was adopted to guide this study design. The cross-sectional study of TB patients was enrolled in two hospitals with highest TB load, between September to November 2017 in Bhutan. Interviewer assisted survey was conducted with 139 TB patients who visited the hospital in continuation phase. In-depth interview was then conducted with nine TB patients and four health staffs to explore the barriers and enablers of DOT. RESULTS: Total of 61.9% (86/139) of patients has received DOT at intensive phase. Proportion was higher among MDR-TB cases (100%), and smear sputum positive TB cases (84.7%). In the continuation phase, 5.8% of patients took medicine at hospital, 48.9% at home and the rest 45.3% no longer practiced DOT. More than 90% of patient received correct dosage and standard regimen of anti-TB drugs according to the guideline. The key factors affecting poor adherence to DOT as perceived by patients were; lack of willingness to visit the clinic on daily basis due to long distance, financial implications and family support. However, patient's satisfaction to the quality of TB treatment service delivery was high (98.6%). Providing incentives to the patient was most agreed enabler felt by both health workers and patients. CONCLUSION: In the selected hospital sites, the patient's adherence to DOT and provider's compliance with DOT guideline is partially implemented; the coverage and the duration of DOT is very low, therefore, need to revise and improve DOT model and structure.

Where chloroquine still works: the genetic make-up and susceptibility of Plasmodium vivax to chloroquine plus primaquine in Bhutan.

BACKGROUND: Bhutan has made substantial progress in reducing malaria incidence. The national guidelines recommend chloroquine (CQ) and primaquine (PQ) for radical cure of uncomplicated Plasmodium vivax, but the local efficacy has not been assessed. The impact of cases imported from India on the genetic make-up of the local vivax populations is currently unknown. METHODS: Patients over 4 years of age with uncomplicated P. vivax mono-infection were enrolled into a clinical efficacy study and molecular survey. Study participants received a standard dose of CQ (25 mg/kg over 3 days) followed by weekly review until day 28. On day 28 a 14-day regimen of PQ (0.25 mg/kg/day) was commenced under direct observation. After day 42, patients were followed up monthly for a year. The primary and secondary endpoints were risk of treatment failure at day 28 and at 1 year. Parasite genotyping was undertaken at nine tandem repeat markers, and standard population genetic metrics were applied to examine population diversity and structure in infections thought to be acquired inside or outside of Bhutan. RESULTS: A total of 24 patients were enrolled in the clinical study between April 2013 and October 2015. Eight patients (33.3 %) were lost to follow-up in the first 6 months and another eight patients lost between 6 and 12 months. No (0/24) treatment failures occurred by day 28 and no (0/8) parasitaemia was detected following PQ treatment. Some 95.8 % (23/24) of patients were aparasitaemic by day 2. There were no haemolytic or serious events. Genotyping was undertaken on parasites from 12 autochthonous cases and 16 suspected imported cases. Diversity was high (H E 0.87 and 0.90) in both populations. There was no notable differentiation between the autochthonous and imported populations. CONCLUSIONS: CQ and PQ remains effective for radical cure of P. vivax in Bhutan. The genetic analyses indicate that imported infections are sustaining the local vivax population, with concomitant risk of introducing drug-resistant strains.

Evolution of Influenza A(H3N2) Viruses in Bhutan for Two Consecutive Years, 2022 and 2023.

BACKGROUND: Influenza A viruses pose a significant public health threat globally and are characterized by rapid evolution of the hemagglutinin (HA) gene causing seasonal epidemics. The aim of this study was to investigate the evolutionary dynamics of A(H3N2) circulating in Bhutan during 2022 and 2023. METHODS: We analysed 166 whole-genome sequences of influenza A(H3N2) from Bhutan, obtained from the GISAID database. We employed a Bayesian Markov Chain Monte Carlo (MCMC) framework, with a curated global dataset of HA sequences from regions with significant migration links to Bhutan. Phylogenetic, temporal, and phylogeographic analyses were conducted to elucidate the evolutionary dynamics and spatial dissemination of the viruses. RESULTS: Our phylogenetic analysis identified the circulation of influenza A(H3N2) Clade 3C.2a1b.2a.2 in Bhutan during 2022 and 2023, with viruses further classified into three subclades: 2a.3 (39/166), 2a.3a.1 (58/166) and 2a.3b (69/166). The TMRCA estimates suggest that these viral lineages originated approximately 1.93 years prior to their detection. Phylogeographic analysis indicates introductions from the United States in 2022 and Australia in 2023. The mean evolutionary rate across all gene segments was calculated to be 4.42 × 10-3 substitutions per site per year (95% HPD: 3.19 × 10-3 to 5.84 × 10-3), with evidence of purifying selection and limited genetic diversity. Furthermore, reassortment events were rare, with an estimated rate of 0.045 events per lineage per year. CONCLUSION: Our findings show that primary forces shaping the local evolution of the influenza A(H3N2) in Bhutan are largely stochastic, with only sporadic instances of adaptive change, and thus underscore the importance of continuous surveillance to mitigate the impact of evolving strains.

Respiratory syncytial virus among hospitalized patients of severe acute respiratory infection in Bhutan: Cross-sectional study.

Introduction: Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections worldwide, particularly in young children. In Bhutan, respiratory disease continues to be among the top 10 diseases of morbidity for several years. This study aimed to estimate the prevalence of RSV among hospitalized patients with severe acute respiratory infection (SARI) in Bhutan. Method: Respiratory specimens were collected from SARI patients of all ages in 2016 and 2018 following influenza surveillance guidelines. Specimens were tested for influenza and RSV, human metapneumovirus, adenovirus, and human parainfluenza virus types 1, 2, and 3 using real-time reverse-transcription polymerase chain reaction assay. Descriptive statistics were used to analyze the result in STATA 16.1. Result: Of the 1339 SARI specimens tested, 34.8% were positive for at least one viral pathogen. RSV was detected in 18.5% of SARI cases, followed by influenza in 13.4% and other respiratory viruses in 3%. The median age of SARI cases was 3 (IQR: 0.8-21 years) years. RSV detection was higher among children aged 0-6 (Adj OR: 3.03; 95% CI: 1.7-5.39) and 7-23 months (Adj OR: 3.01; 95% CI: 1.77-5.12) compared with the children aged 5-15 years. RSV was also associated with breathing difficulty (Adj OR: 1.73; 95% CI: 1.17-2.56) and pre-existing lung disease, including asthma (Adj OR: 2.78; 95% CI: 0.99-7.8). Conclusion: Respiratory viruses were detected in a substantial proportion of SARI hospitalizations in Bhutan.

Epidemiology and genetic characterization of influenza viruses circulating in Bhutan in 2022.

INTRODUCTION: Influenza (Flu) causes considerable morbidity and mortality globally, and in Bhutan, Flu viruses are a leading cause of acute respiratory infection and cause outbreaks during Flu seasons. In this study, we aim to analyze the epidemiology and the genetic characterization of Flu viruses circulated in Bhutan in 2022. METHOD: Respiratory specimens were collected from patients who meet the case definition for influenza-like illness (ILI) and severe acute respiratory infection (SARI) from sentinel sites. Specimens were tested for Flu and SARS-CoV-2 viruses by RT-PCR using the Multiplex Assay. Selected positive specimens were utilized for Flu viral genome sequencing by next-generation sequencing. Descriptive analysis was performed on patient demographics to see the proportion of Flu-associated ILI and SARI. All data were analyzed using Epi Info7 and QGIS 3.16 software. RESULT: A weekly average of 16.2 ILI cases per 1000 outpatient visits and 18 SARI cases per 1000 admitted cases were reported in 2022. The median age among ILI was 12 years (IQR: 5-28) and SARI was 6.2 (IQR: 2.5-15) years. Flu A(H3N2) (70.2%) subtype was the most predominant circulating strain. Flu A(H1N1)pdm09 and Flu B viruses belonged to subclades that were mismatched to the vaccine strains recommended for the 2021-2022 season but matched the vaccine strain for the 2022-2023 season with vaccine efficacy 85.14% and 88.07% respectively. Flu A(H3N2) virus belonged to two subclades which differed from the vaccine strains recommended in both the 2021-2022 and 2022-2023 seasons with vaccine efficacy 68.28%. CONCLUSION: Flu virus positivity rates were substantially elevated during the Flu season in 2022 compared to 2021. Flu A(H3N2) subtype was the most predominant circulating strain in the country and globally. Genetic characterization of the Flu viruses in Bhutan showed a close relatedness of high vaccine efficacy with the vaccine strain that WHO recommended for the 2022-23 season.

Genetic diversity and evolutionary patterns of SARS-CoV-2 among the Bhutanese population during the pandemic.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic, caused by a dynamic virus, has had a profound global impact. Despite declining global COVID-19 cases and mortality rates, the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains a major concern. This study provides a comprehensive analysis of the genomic sequences of SARS-CoV-2 within the Bhutanese population during the pandemic. The primary aim was to elucidate the molecular epidemiology and evolutionary patterns of SARS-CoV-2 in Bhutan, with a particular focus on genetic variations and lineage dynamics. METHODS: Whole-genome sequences of SARS-CoV-2 collected from Bhutan between May 2020 and February 2023 (n=135) were retrieved from the Global Initiative on Sharing All Influenza Database. RESULTS: The SARS-CoV-2 variants in Bhutan were predominantly classified within the Nextstrain clade 20A (31.1%), followed by clade 21L (20%) and clade 22D (15.6%). We identified 26 Pangolin lineages with variations in their spatial and temporal distribution. Bayesian time-scaled phylogenetic analysis estimated the time to the most recent common ancestor as February 15, 2020, with a substitution rate of 0.97×10-3 substitutions per site per year. Notably, the spike glycoprotein displayed the highest mutation frequency among major viral proteins, with 116 distinct mutations, including D614G. The Bhutanese isolates also featured mutations such as E484K, K417N, and S477N in the spike protein, which have implications for altered viral properties. CONCLUSION: This is the first study to describe the genetic diversity of SARS-CoV-2 circulating in Bhutan during the pandemic, and this data can inform public health policies and strategies for preventing future outbreaks in Bhutan.

A qualitative study on knowledge, perception, and practice related to non-communicable diseases in relation to happiness among rural and urban residents in Bhutan.

PURPOSE: Bhutan, known as a country of happiness, has experienced rapid social changes and the increasing burden of non-communicable diseases (NCDs) that can impact health and happiness. To inform future NCD prevention programs in Bhutan, this study explores knowledge, perception, and the practices of Bhutanese related to NCDs in the context of the philosophy of happiness. METHODOLOGY: Research was conducted in rural and urban communities of Bhutan in 2017 among 79 inhabitants of both genders, aged ≥18. Participants were recruited through purposive sampling with the data collected by in-depth interviews, participatory observation, and anthropometric measurements. Data were analyzed by thematic analysis. RESULTS/DISCUSSION: Across participants, health was considered as an important element of "happiness". However, lifestyle-related NCD risk factors prevailed due to the lack of effective education programs on NCDs and thus the lack of practical knowledge for NCD prevention across society. We further found that the value of happiness "finding happiness in any situation is virtue" was universal as well as other traditional values and customs, shaping people's health behaviors. From these observations, it is recommended that more practical NCD education/prevention programs should be urgently introduced in Bhutan that involve multiple generations, religion authorities, educational settings, and medical services. ORIGINALITY: This is the first comprehensive qualitative study on the NCD-related lifestyle risks among Bhutanese concerning the concept of happiness.

Malaria elimination in Bhutan: asymptomatic malaria cases in the Bhutanese population living in malaria-risk areas and in migrant workers from India.

In 2018, Bhutan reported 54 cases of malaria, of which six were indigenous, 14 introduced and 34 imported. Considering the continuous reduction in the number of indigenous cases, Bhutan plans to eliminate malaria by 2025 under the Bhutan Malaria Elimination Strategy. The study was conducted to assess the presence of asymptomatic plasmodial infection in both, Bhutanese population living in malaria-risk areas and in migrant workers to guide the elimination strategies. A cross-sectional study was conducted from April to May 2016 in 750 Bhutanese people and 473 migrant workers. Plasmodium falciparum and Plasmodium vivax infections were investigated by using a rapid diagnostic test (RDT) and the polymerase chain reaction (PCR). Prevalence of asymptomatic plasmodial infection based on PCR was 0.27% (95% CI: 0.05-1.07%) among Bhutanese people with a mean age of 43 years old. The proportions of males and females were 45% and 55%, respectively. Among migrant workers, the prevalence of asymptomatic plasmodial infection was 0.42% (95% CI: 0.07-1.69%) with a mean age of 30 years old. The majority of migrant workers were from the neighboring Indian State of West Bengal (57.51%), followed by Assam (12.26%). RDT in both study groups did not detect any plasmodial infection. The presence of a low prevalence of asymptomatic plasmodial infection indicates that the current elimination strategies and interventions are effective.

Temporal Patterns of Influenza A and B in Tropical and Temperate Countries: What Are the Lessons for Influenza Vaccination?

INTRODUCTION: Determining the optimal time to vaccinate is important for influenza vaccination programmes. Here, we assessed the temporal characteristics of influenza epidemics in the Northern and Southern hemispheres and in the tropics, and discuss their implications for vaccination programmes. METHODS: This was a retrospective analysis of surveillance data between 2000 and 2014 from the Global Influenza B Study database. The seasonal peak of influenza was defined as the week with the most reported cases (overall, A, and B) in the season. The duration of seasonal activity was assessed using the maximum proportion of influenza cases during three consecutive months and the minimum number of months with ≥80% of cases in the season. We also assessed whether co-circulation of A and B virus types affected the duration of influenza epidemics. RESULTS: 212 influenza seasons and 571,907 cases were included from 30 countries. In tropical countries, the seasonal influenza activity lasted longer and the peaks of influenza A and B coincided less frequently than in temperate countries. Temporal characteristics of influenza epidemics were heterogeneous in the tropics, with distinct seasonal epidemics observed only in some countries. Seasons with co-circulation of influenza A and B were longer than influenza A seasons, especially in the tropics. DISCUSSION: Our findings show that influenza seasonality is less well defined in the tropics than in temperate regions. This has important implications for vaccination programmes in these countries. High-quality influenza surveillance systems are needed in the tropics to enable decisions about when to vaccinate.