Seroprevalence and risk factors associated with bovine tuberculosis in cattle in Eastern Bhutan.

Bovine tuberculosis (bTB) is a chronic zoonotic disease affecting cattle of all age groups including wild animals. It poses a significant threat to public health and high economic losses to dairy farmers. While the disease has been eradicated from most of the developed countries through extensive surveillance, testing and culling strategy, it is endemic in Africa, Asia, and the Middle East countries. Currently, there is limited research regarding the prevalence of bTB in cattle in Bhutan. This study aimed to determine the seroprevalence of bTB in cattle in six districts of eastern Bhutan. A two-stage probability proportional to size (PPS) sampling strategy was used to determine the number of animals from which serum samples needed to be collected in each district and sub-district. All farms and cattle for sampling were randomly selected from the data in the annual livestock census of 2020. The samples were tested using bTB ELISA test kit. The seroprevalence and their 95% confidence intervals were calculated. Logistic regression models were constructed to assess the influence of various individual animal and environmental risk factors (breed, age, sex, source of animal, body condition scores of animals, respiratory system status) associated with sero-positivity in animals. The study revealed an apparent seroprevalence of 2.57% (25/971 cattle; 95% CI:1.58-3.57), with an estimated true seroprevalence of 0.91% (95% CI: 0.0-2.81). However, none of the variables were found to be significantly associated with bTB seroprevalence in cattle. We recommend, further sampling and employment of confirmatory testing to fully ascertain the extent of bTB in the cattle herds in eastern Bhutan for prevention and control.

Efforts toward the Elimination of Visceral Leishmaniasis in South Asia: A Review of Progress in Bhutan.

Leishmaniases are a group of diseases under the category of neglected tropical diseases targeted for global elimination. However, they continue to pose major clinical and public health problems, especially among those living in poor socioeconomic conditions. Here, we summarize leishmaniasis elimination efforts in Bhutan. Between 1994 and 2022, Bhutan recorded 54 cases of leishmaniasis across 14 of its 20 districts. There are seven species of Phlebotomus and three species of Sergentomyia sand flies documented in the country. At a subnational level, all endemic districts recorded a visceral leishmaniasis annual incidence <1 per 10,000 population, meeting the regional elimination targets. Serological testing with ELISA and molecular testing with polymerase chain reaction were established at the Royal Center for Disease Control in 2022. A leishmaniasis prevention and management guideline was adopted in 2023 to aid clinicians in diagnosis and management. Active and passive case surveillance was integrated with the national infectious disease early warning and response system. Risk-based entomological surveillance and control have also been prioritized. Climate change may play a major role in rendering districts in the temperate zone favorable for vector proliferation. The country's medical university introduced a diploma course in medical entomology in 2023 to augment the human resources needed for vector surveillance efforts. However, leishmaniasis elimination lacks dedicated programmatic management amid competing priorities for resources against other infectious diseases. Leishmaniasis elimination requires a targeted and programmatic approach in Bhutan, including cross-border collaborative efforts with neighboring Indian states. Bhutan remains highly committed to achieving leishmaniasis elimination targets.

Suspected cutaneous anthrax in a yak herder in a highland community in Bhutan, 2023: A case report.

This case presents cutaneous anthrax in yak herder from a central highland community in Bhutan. We highlight the clinical presentation, diagnosis and management of the case in a resource-limited setting, and the public health response through the One Health approach.

Population-level cancer screening and cancer care in Bhutan, 2020-2023: a review.

Screening of cancers is an important intervention in reducing the incidence and mortality related to cancers. Bhutan is one small country that is witnessing an increasing incidence and mortality related to cancers. The government implemented a time-bound population-level screening for gastric, cervical and breast cancers from 2020 to 2023 with an overall coverage of 91.2% of the eligible population. Among 370,225 individuals screened for H pylori, 32.4% tested positive; among 53,182 who underwent upper gastrointestinal endoscopy and biopsy, 255 (0.07%) had gastric cancer. Among 10,749 tested for HPV DNA, 9.3% were positive; among 9887 evaluated with colposcopy and biopsy, 154 (0.13%) had cervical cancer. For breast cancer screening, 72,283 underwent clinical breast examination, 845 mammography and cancer was detected in 73 (0.10%) individuals. In this article, we review how Bhutan implemented a population-level cancer screening programme with on boarding of multiple stakeholders and the participation of people across all districts.

Delayed Sheehan's syndrome diagnosed during the evaluation of secondary infertility: A case report.

Sheehan's syndrome may present with postpartum lactation failure and amenorrhea or with features of isolated hypopituitarism to panhypopituitarism. A high index of suspicion is required in a relevant clinical setting of postpartum hemorrhage.

Whole genome sequencing of drug-resistant Mycobacterium tuberculosis isolates in Victoria, Australia.

OBJECTIVES: Whole genome sequencing (WGS) can identify clusters, transmission patterns, and drug resistance mutations. This is important in low-burden settings such as Australia, as it can assist in efficient contact tracing and surveillance. METHODS: We conducted a retrospective cohort study using WGS from 155 genomically defined drug-resistant Mycobacterium tuberculosis (DR-TB) isolates collected between 2018-2021 in Victoria, Australia. Bioinformatic analysis was performed to identify resistance-conferring mutations, lineages, clusters and understand how local sequences compared with international context. RESULTS: Of the 155 sequences, 42% were identified as lineage 2 and 35% as lineage 1; 65.8% (102/155) were isoniazid mono-resistant, 8.4% were multi-drug resistant TB and 5.8% were pre-extensively drug-resistant / extensively drug-resistant TB. The most common mutations were observed in katG and fabG1 genes, especially at Ser315Thr and fabG1 -15 C>T for first-line drugs. Ser450Leu was the most frequent mutation in rpoB gene. Phylogenetic analysis confirmed that Victorian DR-TB were associated with importation events. There was little evidence of local transmission with only five isolate pairs. CONCLUSION: Isoniazid-resistant TB is the commonest DR-TB in Victoria, and the mutation profile is similar to global circulating DR-TB. Most cases are diagnosed among migrants with limited transmission. This study highlights the value of WGS in identification of clusters and resistance-conferring mutations. This information is crucial in supporting disease mitigation and treatment strategies.

Challenges in the management of high-altitude illnesses and emergencies in Bhutan and Nepal.

Many popular tourist attractions and trekking routes in Bhutan and Nepal are situated between 3000 and 6000 m in elevation. High-altitude emergencies are becoming more common and medical providers must be aware of the practical and medical issues in managing these disorders. We reflect on the challenges in providing high-altitude emergency medical services in Bhutan and Nepal.

Human rabies encephalomyelitis in the background of rabies outbreak in animals in Gelephu, Bhutan, 2023: a case report.

BACKGROUND: Rabies continues to pose significant public health challenges in many developing countries including Bhutan. A probable case of rabies was admitted to our hospital and its reporting led to the uncovering of an outbreak in domestic and wild animals. We discuss the challenges in the diagnosis and management of rabies in a resource-limited setting. CASE PRESENTATION: A 35-year-old male presented with intermittent fever, bilateral lower limb weakness that was rapidly progressive, urinary incontinence with episodes of palpitations and sweating. He had sustained a Category III bite on the right lower thigh with four bite marks, inflicted by a stray dog. He had received post-exposure prophylaxis with intra-dermal anti-rabies vaccine. On initial examination, the patient was in distress but cooperative for the interview. He had pulse rate ranging from 60 to 100/min with episodes of diaphoresis and palpitations, but with normal capillary blood glucose. In the lower limb, the muscle power was zero with absent tendon reflexes in the lower limb and impaired abdominal reflex below T10 level. He had hyperaesthesia below T8, hydrophobia, aerophobia and photophobia. He had multiple spontaneous fasciculations in both the thighs and right deltoid and these later involved the intercostal muscles, neck and face muscles. He had altered sensorium and desaturation for which he required mechanical ventilation. Polymerase chain reaction for rabies virus was negative in cerebrospinal fluid and saliva. Rabies virus neutralizing antibody was negative in cerebrospinal fluid but had high titres in the serum. He received Human Rabies Immunoglobulin after admission. He was managed in the intensive care unit and died 23 days later. After this case was notified, a rapid response team was deployed in the field, and uncovered rabies outbreak in animals in the locality. CONCLUSIONS: This case called for a serious evaluation of the country's efforts in achieving zero rabies deaths by 2030. The management of this case identified several critical areas of context-specific interventions in Bhutan. There is also an urgent need to improve diagnostic capabilities at the national reference laboratory and enhance the technical competencies of healthcare workers in the management of dog bite cases.

Perspectives on chronic musculoskeletal pain management among healthcare professionals in Bhutan: A qualitative study.

INTRODUCTION: Musculoskeletal pain disorders continue to be one of the leading causes of disability worldwide. Best practice care recommends patient-centred biopsychosocial models of care. Little is known about the chronic musculoskeletal pain management in low- and middle-income countries. OBJECTIVES: To explore the management of chronic musculoskeletal pain by healthcare professionals in Bhutan. METHODS: This study employed a qualitative design involving 19 Bhutanese healthcare professionals managing chronic musculoskeletal pain in Bhutan. We collected data using a semi-structured interview guide. Thematic analysis was done manually. RESULTS: Healthcare professionals reported that patients rely on a combination of home remedies and seek help from local healers and hospitals for chronic musculoskeletal pain management. While healthcare professionals understand chronic musculoskeletal pain as multi-dimensional phenomenon, the primary focus was on identifying and treating structural anomalies. Time constraints, inadequate knowledge and skills, lack of confidence, facilities and expertise were reported as barriers to the effective management of chronic musculoskeletal pain. They proposed a need for clinical guidelines, relevant skills training and creating awareness of chronic musculoskeletal pain. CONCLUSION: The management of chronic musculoskeletal pain in Bhutan is focused on identifying and treating physical abnormalities. Healthcare professionals consider psychosocial dimensions important but lack any form of actionable interventions in this domain.

Clinical description and treatment outcomes of Paederus dermatitis in Phuentsholing, Bhutan in 2021: A cross-sectional study.

An increasing number of beetle population and outbreaks of irritant contact dermatitis are reported from newer geographic locations. Bhutan is one such country that witnessed an outbreak of Paederus dermatitis (PD) in Phuentsholing sub-district in 2021. This study describes the clinical symptoms, skin lesions and treatment outcomes of PD in Bhutan. This was a descriptive cross-sectional study of an outbreak of Paederus-related contact dermatitis in Phuentsholing, Bhutan. Clinical symptoms, skin lesions, duration of illness, recovery time and response to treatment were recorded. Of the 81 patients with PD, the males constituted 54% (44) and the mean age was 22 years (range: 1-51 years). The commonly affected groups were those aged 11-20 years (40.7%) and school or college students (50.6%). The common symptoms were pain, itching, redness, tenderness and blister formation. The lesions were erythematovesicular (70%), linear (54.3%) and kissing lesions (28.4%). All patients received some form of topical or oral steroid therapy and recovery was 100%. The mean duration from the onset till the recovery of the skin rash was 13 days (SD ± 8.3 days). PD outbreak is a self-limiting form of contact dermatitis. This is the first report of PD in the sub-Himalayan region and may be linked to climate change. There is a need for active surveillance and monitoring of such emerging weather/climate-related agents for appropriate health system response in disease prevention and treatment.

Antibiotic use and quality indicators of antibiotic prescription in Bhutan: a point prevalence survey using the Australian National Antimicrobial Prescribing Survey tool.

Background: The National Action Plan on Antimicrobial Resistance in Bhutan promotes the rational use of antibiotics. It is important to establish baseline data on the use of antibiotics and the quality indicators of antibiotic prescriptions to identify where improvement efforts may need to be focused. Objectives: To describe the prevalence and patterns of antibiotic prescription and establish baseline data regarding quality indicators of antibiotic prescriptions in four major hospitals in Bhutan. Methods: This was a point prevalence survey of antibiotic use among inpatients in June 2022 conducted using the Australian National Antibiotic Prescribing Survey (NAPS). Results: There were 314 patients (41.5%) receiving at least one antibiotic on the audit day. Among prescriptions reviewed, 278 (88.5%) had indications for use documented, 102 (32.5%) had a review or stop date documented and 120 (38.2%) had microbiology samples collected prior to antibiotics. Ceftriaxone (68; 21.7%), cefazolin (41; 13.1%) and metronidazole (32; 10.2%), were the common antibiotics prescribed. The most common indications for use were surgical prophylaxis (42; 13.4%), community-acquired pneumonia (39; 12.4%) and sepsis (26; 8.3%). There were 125 prescriptions (39.8%) that were compliant with national/therapeutic antibiotic guidelines and 169 (53.8%) where antibiotic prescriptions were appropriate. Conclusions: This study identified key areas for targeted interventions in antimicrobial stewardship programmes in Bhutan. The prevalence of antibiotic use, indications for use, and drug choices were similar to data from other countries. Documentation plans for durations of use, prolonged surgical prophylaxis and concordance of choices with guideline recommendations present opportunities for improvement.

Nanoplatforms: The future of oral cancer treatment.

Background and Aims: Cytotoxicity is a key disadvantage of using chemotherapeutic drugs to treat cancer. This can be overcome by encapsulating chemotherapeutic drugs in suitable carriers for targeted delivery, allowing them to be released only at the cancerous sites. Herein, we aim to review the recent scientific developments in the utilization of nanotechnology-based drug delivery systems for treating oral malignancies that can lead to further improvements in clinical practice. Methods: A comprehensive literature search was conducted on PubMed, Google Scholar, ScienceDirect, and other notable databases to identify recent peer-reviewed clinical trials, reviews, and research articles related to nanoplatforms and their applications in oral cancer treatment. Results: Nanoplatforms offer a revolutionary strategy to overcome the challenges associated with conventional oral cancer treatments, such as poor drug solubility, non-specific targeting, and systemic toxicity. These nanoscale drug delivery systems encompass various formulations, including liposomes, polymeric nanoparticles, dendrimers, and hydrogels, which facilitate controlled release and targeted delivery of therapeutic agents to oral cancer sites. By exploiting the enhanced permeability and retention effect, Nanoplatforms accumulate preferentially in the tumor microenvironment, increasing drug concentration and minimizing damage to healthy tissues. Additionally, nanoplatforms can be engineered to carry multiple drugs or a combination of drugs and diagnostic agents, enabling personalized and precise treatment approaches. Conclusion: The utilization of nanoplatforms in oral cancer treatment holds significant promise in revolutionizing therapeutic strategies. Despite the promising results in preclinical studies, further research is required to evaluate the safety, efficacy, and long-term effects of nanoformulations in clinical settings. If successfully translated into clinical practice, nanoplatform-based therapies have the potential to improve patient outcomes, reduce side effects, and pave the way for more personalized and effective oral cancer treatments.

Profile and outcome of patients with Warfarin Toxicity admitted in a tertiary care hospital in Bhutan: a cross-sectional study investigators and institutions.

OBJECTIVE: To study the profile, clinical presentation and outcome of hospital stay among patients admitted with warfarin toxicity at the Jigme Dorji Wangchuck National Referral Hospital, Bhutan. This was a cross-sectional study with a review of hospital records of patients admitted between 01 and 2018 and 30 June 2020. RESULTS: There were 22 admissions due to warfarin toxicity. The mean age of patients was 55.9 (± SD 20.2) years, the median duration of warfarin therapy was 30 months (IQR 4.8, 69 months). The indications for warfarin were atrial fibrillation (9, 40.9%), mechanical heart valves (6, 27.3%), deep vein thrombosis (6, 27.3%) and pulmonary thromboembolism (1, 4.5%). The mean of dosage of warfarin was 4.3 (± 2.6) mg and the cumulative dosage in the week prior to admission was 30.9 (± 18.6) mg. The mean of INR at presentation was 7.7 (± 4.3) with the maximum noted at 20. The patients presented with gastrointestinal bleeding, muscle haematomas, epistaxis and oral cavity bleeding. There was no mortality related to warfarin toxicity. The reasons for warfarin toxicity included patient dosing error and drug interactions. Warfarin therapy requires appropriate patient education, adequate facilities for follow-up and avoidance of warfarin wherever possible in clinical settings.

Challenges in epilepsy diagnosis and management in a low-resource setting: An experience from Bhutan.

Epilepsy is an important cause of morbidity and mortality especially in low- and middle-income countries. People with epilepsy (PWE) face difficulties in access to healthcare, appropriate diagnostic tests and anti-seizure medications (ASM). Bhutan is one such country in the Himalayas that has reported doubling of the prevalence of epilepsy from 155.7 per 100,000 population in 2017 to 312.4 in 2021. The country has one centre for electroencephalography and magnetic resonance imaging for a population of 0.7 million and does not have any neurologists as of 2023. There are 16 ASMs registered in the country but only selected medications are available at the primary level hospitals (phenobarbital, phenytoin and diazepam). There are challenges in the availability of these medicines all time round the year in all levels of hospitals. Neurosurgical treatment options are limited by the lack of adequate pre-surgical evaluation facilities and lack of trained human resources. The majority of PWE have reported facing societal stigma with significant impact on the overall quality of life. It is important to screen for psychiatric comorbidities and provide psychological support wherever possible. There is a need for a comprehensive national guideline that will cater to the needs of PWE and their caregivers within the resources available in the country. A special focus on the institutional and human resource capacity development for the study and care of epilepsy is recommended.

Epistaxis, paroxysmal anxiety episodes, and hypertension in a child with SDHB-associated paraganglioma: A case report.

A child presented with anxiety and weight gain which were overlooked until she had epistaxis. She was found to have hypertension secondary to paraganglioma. She was managed with curative surgery involving multidisciplinary care. The tumor removal led to the amelioration of symptoms and marked control of hypertension.

Symptomatic hypoglycemia in a nondiabetic adult female recovering from mild COVID-19 infection: A case report.

A 38-year-old lady, recently recovered from SARS-CoV-2 infection and taking grape seed extract, suffered multiple episodes of severe postprandial hyperinsulinemic hypoglycemia. A careful evaluation ruled out the common etiologies of hypoglycemia and identified grape seed extract consumption as a possible cause. She recovered after stopping the nutritional supplements. In her, hypoglycemia could have resulted from transient beta cell dysfunction associated with SARS-CoV-2 infection or proanthocyanidins in the grape seed extract.

Situation of physical activity in the prevention of non-communicable diseases in Bhutan: challenges and the way forward.

Bhutan is a lower-income-middle-income country in the Himalayas, between India and China. Non-communicable diseases (NCDs) are the leading cause of death and premature mortality in Bhutan, accounting for 69% and 71% of all deaths in 2014 and 2019, respectively. Although the World Health Organisation (WHO) identified physical activity as a key strategy to reduce the burden of NCDs, with rapid urbanisation, motorised transportation, and rural-urban migration, people are adapting to sedentary lifestyles, inflating the incidence of NCDs in the country. The increasing incidence of NCDs exerts a burden on the human and financial resource constraints in the health system in Bhutan. In this view point, we report evidence-based benefits of physical activity for health promotion, primary prevention of NCDs and health benefits for individuals living with NCDs. We also briefly assess the situation of physical activity in Bhutan. Then, shortcomings of existing NCDs prevention programmes are discussed along with opportunities and ways forward to effectively implementing physical activity to harness the benefits of physical activities.

Knowledge and attitude on sexually transmitted infections and contraceptive use among university students in Bhutan.

OBJECTIVES: The unmet needs of contraception can lead to unintended pregnancy and transmission of sexually transmitted infections (STI). Therefore, this study aimed to evaluate the contraception use, knowledge, and attitude on STI among students under Royan University of Bhutan (RUB). METHODS: This was a cross-sectional study using an online questionnaire. The questionnaire was developed in Google forms and the link was shared through the college WeChat groups. The questionnaire consisted of four parts on socio-demographic, sexual behaviour and contraceptive use, knowledge, and attitude on STIs. All the students under RUB were invited to participate voluntarily in this study. The socio-demography was presented in frequency and proportion. RESULT: A total of 1,283 students participated in this survey and 55.0% (701) were females. Of this, 29.4% (377) were sexually active and 94.4% reported using modern contraception. Commonly used contraceptives were: condoms (83.8%, 316) and emergency contraceptives (20.6%, 78), respectively. The mean knowledge and attitude scores on STI were 9.94 (range 2-20) and 12 (range 2-14), respectively. Good knowledge and attitude on STI were reported in 53.2% (683) and 70.1% (899) of participants. CONCLUSION: Students reported average knowledge and a good attitude towards STI. Contraceptive use among university students was low. There is a need to strengthen health education on STIs in schools and universities. All forms of contraceptives especially condoms should be made easily available to sexually active people.