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.

Evolutionary druggability: leveraging low-dimensional fitness landscapes towards new metrics for antimicrobial applications.

The term "druggability" describes the molecular properties of drugs or targets in pharmacological interventions and is commonly used in work involving drug development for clinical applications. There are no current analogues for this notion that quantify the drug-target interaction with respect to a given target variant's sensitivity across a breadth of drugs in a panel, or a given drug's range of effectiveness across alleles of a target protein. Using data from low-dimensional empirical fitness landscapes composed of 16 ß-lactamase alleles and seven ß-lactam drugs, we introduce two metrics that capture (i) the average susceptibility of an allelic variant of a drug target to any available drug in a given panel ("variant vulnerability"), and (ii) the average applicability of a drug (or mixture) across allelic variants of a drug target ("drug applicability"). Finally, we (iii) disentangle the quality and magnitude of interactions between loci in the drug target and the seven drug environments in terms of their mutation by mutation by environment (G × G × E) interactions, offering mechanistic insight into the variant variability and drug applicability metrics. Summarizing, we propose that our framework can be applied to other datasets and pathogen-drug systems to understand which pathogen variants in a clinical setting are the most concerning (low variant vulnerability), and which drugs in a panel are most likely to be effective in an infection defined by standing genetic variation in the pathogen drug target (high drug applicability).

Association of COVID-19 Vaccination With Symptomatic SARS-CoV-2 Infection by Time Since Vaccination and Delta Variant Predominance.

IMPORTANCE: Monitoring COVID-19 vaccine performance over time since vaccination and against emerging variants informs control measures and vaccine policies. OBJECTIVE: To estimate the associations between symptomatic SARS-CoV-2 infection and receipt of BNT162b2, mRNA-1273, and Ad26.COV2.S by day since vaccination before and during Delta variant predominance (pre-Delta period: March 13-May 29, 2021; Delta period: July 18-October 17, 2021). DESIGN, SETTING, AND PARTICIPANTS: Test-negative, case-control design with data from 6884 US COVID-19 testing sites in the pharmacy-based Increasing Community Access to Testing platform. This study included 1 634 271 laboratory-based SARS-CoV-2 nucleic acid amplification tests (NAATs) from adults 20 years and older and 180 112 NAATs from adolescents 12 to 19 years old with COVID-19-like illness from March 13 to October 17, 2021. EXPOSURES: COVID-19 vaccination (1 Ad26.COV2.S dose or 2 mRNA doses) 14 or more days prior. MAIN OUTCOMES AND MEASURES: Association between symptomatic infection and prior vaccination measured using the odds ratio (OR) from spline-based multivariable logistic regression. RESULTS: The analysis included 390 762 test-positive cases (21.5%) and 1 423 621 test-negative controls (78.5%) (59.9% were 20-44 years old; 9.9% were 12-19 years old; 58.9% were female; 71.8% were White). Among adults 20 years and older, the BNT162b2 mean OR for days 14 to 60 after a second dose (initial OR) was lower during the pre-Delta period (0.10 [95% CI, 0.09-0.11]) than during the Delta period (0.16 [95% CI, 0.16-0.17]) and increased with time since vaccination (per-month change in OR, pre-Delta: 0.04 [95% CI, 0.02-0.05]; Delta: 0.03 [95% CI, 0.02-0.03]). The initial mRNA-1273 OR was 0.05 (95% CI, 0.04-0.05) during the pre-Delta period, 0.10 (95% CI, 0.10-0.11) during the Delta period, and increased with time (per-month change in OR, pre-Delta: 0.02 [95% CI, 0.005-0.03]; Delta: 0.03 [95% CI, 0.03-0.04]). The Ad26.COV2.S initial OR was 0.42 (95% CI, 0.37-0.47) during the pre-Delta period and 0.62 (95% CI, 0.58-0.65) during the Delta period and did not significantly increase with time since vaccination. Among adolescents, the BNT162b2 initial OR during the Delta period was 0.06 (95% CI, 0.05-0.06) among 12- to 15-year-olds, increasing by 0.02 (95% CI, 0.01-0.03) per month, and 0.10 (95% CI, 0.09-0.11) among 16- to 19-year-olds, increasing by 0.04 (95% CI, 0.03-0.06) per month. CONCLUSIONS AND RELEVANCE: Among adults, the OR for the association between symptomatic SARS-CoV-2 infection and COVID-19 vaccination (as an estimate of vaccine effectiveness) was higher during Delta variant predominance, suggesting lower protection. For mRNA vaccination, the steady increase in OR by month since vaccination was consistent with attenuation of estimated effectiveness over time; attenuation related to time was greater than that related to variant.

Correlates of Sedentary Behavior among Bhutanese Adults: Findings from the 2014 Bhutan STEPS Survey Data.

BACKGROUND: Sedentary behavior is associated with several adverse health outcomes. Data on factors that influence sedentary behavior are lacking in Bhutan. This study examined factors associated with increased sedentary behavior in Bhutan, with a focus on exploring sex differences. METHODS: Data of 2,796 adults from the nationally representative 2014 Bhutan STEP-wise surveillance (STEPS) survey were analyzed. Factors associated with sedentary behavior were identified using backward elimination multiple logistic regression analysis, disaggregated by sex. The analysis accounted for the complex survey design used in the primary survey. RESULTS: The overall prevalence of sedentary behavior was 8.2%, with a higher proportion among women than men (10.3% vs. 4.9%). In the full sample, female sex, being single, high education and income, urban residence, inadequate physical activity, and high blood sugar were associated with increased odds of sedentary behavior. Among females, those who had high education and income, were single, physically less active, and urban residents were more likely to be sedentary. Self-employment was related to reduced odds of sedentary behavior among women and in the overall sample population. In males, being single, higher education level, and urban residence were associated with sedentariness. CONCLUSION: The findings suggest that interventions targeting females, especially those who are physically less active and from higher socioeconomic groups, urban residents, and those with hyperglycemia can potentially help reduce sedentary behavior and avert the associated detrimental impacts.

Limited Secondary Transmission of the Novel Coronavirus (SARS-CoV-2) by Asymptomatic and Mild COVID-19 Patients in Bhutan.

As the COVID-19 pandemic continues, there is growing concordance and persisting conflicts on the virus and the disease process. We discuss limited transmissibility of the virus by asymptomatic and mild cases of COVID-19 patients in Bhutan. We followed up the secondary transmission of SARS-CoV-2 in the contacts of asymptomatic and mild COVID-19 patients in Bhutan. Bhutan had 33 confirmed COVID-19 cases in the country as of May 29, 2020. Of these, 22 (67%) were females. Except the first two cases (American tourists), the rest were Bhutanese living outside the country. The mean age of the Bhutanese patients was 26.3 (range 16-33) years. Close contacts of 27 of the 33 cases were followed up for signs and symptoms and COVID-19 positivity. The first two cases had 73 and 97 primary contacts, respectively, and equal number of secondary contacts (224). From the third case, a mandatory 21-day facility quarantine was instituted, all primary contacts were facility quarantined, and there were no secondary contacts. In total, the 27 cases had 1,095 primary contacts and 448 secondary contacts. Of these, 75 individuals were categorized as definite high-risk contacts. Secondary transmission occurred in seven high-risk contacts. Therefore, the overall secondary transmission was 9.0% (7/75) and 0.6% (7/1,095) among the high-risk and primary contacts, respectively. No transmission occurred in the secondary contacts. In contrast to several reports indicating high transmissibility of SARS-CoV-2 in contacts of confirmed cases, the mostly young, asymptomatic, and mild cases of COVID-19 in Bhutan showed limited secondary transmission.

Factors associated with different forms of alcohol use behaviors among college students in Bhutan: a cross-sectional study.

BACKGROUND: Alcohol use has impacts on several dimensions of health, including physical health and mental health, particularly in college-age populations. Therefore, this study aimed to estimate the prevalence and to determine factors associated with alcohol use behaviors among college students in Bhutan. METHODS: A cross-sectional design was applied to collect data from the participants. A simple random method was used to select the participants from the lists of students who were attending the four selected colleges in Bhutan in the academic year of 2019. A questionnaire was developed, and validity and reliability were verified before use. Descriptive statistics were applied to describe the general characteristics of participants, while logistic regression was used to detect the associations between variables at the significance level of α = 0.05. RESULTS: A total of 432 college students were recruited into the study, of whom 62.0% were females. The average age was 20.0 years, 40.7% were the third-year students, and 79.9% lived in college dormitories. The prevalence of current drinking was 51.6% and that of binge drinking was 19.4%. After controlling for all potential confounder factors, three variables were found to be associated with current drinking: students who had low income were more likely to be current drinkers than those who had high income (AOR = 2.59, 95% CI = 1.29-5.21); students who did not use tobacco were more likely to be current drinkers than those students who used tobacco (AOR = 6.99, 95% CI = 2.90-16.81); and students who had close friends who did not use alcohol were more likely to be current drinkers than those who had close friends who used alcohol (AOR = 5.14, 95% CI = 3.04-8.69). Four factors were found to be associated with binge drinking after controlling for all possible confounder factors: students who had high income were more likely to be binge drinkers than those who had low income (AOR = 3.03, 95% CI = 1.72-5.31); students who used tobacco were more likely to be binge drinkers than those students who did not use tobacco (AOR = 2.28, 95% CI = 1.35-3.87); students whose parents used alcohol were more likely to be binge drinkers than those students whose parents did not use alcohol (AOR = 1.75, 95% CI = 1.02-3.01); and students whose close friends used alcohol were more likely to be binge drinkers than those who had close friends who did not use alcohol (AOR = 2.26, 95% CI = 1.05-4.87). CONCLUSIONS: There is a high prevalence in alcohol use among the college students in Bhutan. Effective health promotion programs should be implemented by focusing on reducing the alcohol consumption among college students.

Visual impairment and refractive error in school children in Bhutan: The findings from the Bhutan School Sight Survey (BSSS 2019).

PURPOSE: To estimate the nationwide prevalence of visual impairment and associated refractive error in school children in Bhutan. METHODS: The sample of this prospective cross-sectional national survey comprised of randomly selected classes in levels IV-IX (age 10 to 15 years) from schools throughout Bhutan. The examination included measurement of visual acuity (VA), evaluation of ocular motility, refraction under cycloplegia, examination of the external eye, media and fundus. The principal cause of impairment was determined for eyes with uncorrected VA ≤6/12. The main outcome measures were distance VA and cycloplegic refractive error. RESULTS: With a sampling frame of 1967 class-based clusters from 190 schools, 160 classes in 103 schools were randomly selected; 4985 (98.5%) of 5060 enumerated children were examined. The prevalence of uncorrected, presenting, and best-corrected visual impairment (VA≤6/12) in the better eye was 14.5%, 12.8%, and 0.34%, respectively. Refractive error was the principal cause (94.2%) of impaired vision and 88% of children who could achieve VA ≥6/9 with best correction were without necessary spectacles. The prevalence of myopia (≤ -0.5 D) was 6.64% and was associated with female gender (P = 0.004), urban schooling (P = 0.002), and greater parental education (P<0.001). The prevalence of hyperopia (≥ +2.0 D) was 2.17% and was significantly associated with lower class-level (P = 0.033), and female gender (P = 0.025). The overall prevalence of astigmatism (≥ 0.75 D) was 9.75%. CONCLUSIONS: Reduced vision because of uncorrected refractive error is a public health problem among school-age children in Bhutan. Effective school eye health strategies are needed to eliminate this easily treatable cause of visual impairment.

Utility of MALDI-TOF MS for differentiation of Neisseria gonorrhoeae isolates with dissimilar azithromycin susceptibility profiles.

BACKGROUND: Antibiotic-resistant gonorrhoea has been a chronic public health burden since the mid-1930s. Recent emergence of isolates resistant to the current recommended antibiotics for gonorrhoea further magnifies the threat of untreatable gonorrhoea. The lack of new, effective antibiotics highlights the need for better understanding of the population structure of Neisseria gonorrhoeae in order to provide greater insight on how to curtail the spread of antimicrobial-resistant N. gonorrhoeae. OBJECTIVES: To explore a potential application of MALDI-TOF MS to differentiate N. gonorrhoeae displaying different levels of susceptibility to the antibiotic azithromycin. METHODS: We conducted MALDI-TOF MS using the Bruker Biotyper on 392 N. gonorrhoeae isolates collected through the Gonococcal Isolate Surveillance Project (GISP) and/or the Strengthening the United States Response to Resistant Gonorrhea (SURRG) project. The MALDI-TOF MS spectra were visually analysed to assess the presence of distinctive peak(s). Statistical analysis was performed to assess the relationship between gonococcal isolates with the distinct protein peak and antibiotic susceptibility. RESULTS: In this study, we were able to differentiate N. gonorrhoeae isolates into two distinct subpopulations using MALDI-TOF MS. Isolates were distinguished by the presence or absence of a spectral peak at 11 300 Da. Notably, these two groups exhibited different levels of susceptibility to azithromycin. CONCLUSIONS: We have shown that in addition to its ability to identify N. gonorrhoeae, MALDI-TOF MS could also be used to differentiate gonococcal isolates with different levels of susceptibility to azithromycin.

Factors associated with multidrug-resistant tuberculosis (MDR-TB) in Bhutan: A nationwide case-control study.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a growing public health concern globally. In Bhutan, the rates of MDR-TB are high. Data on the risk factors of MDR-TB that can help inform policies are limited in Bhutan. This study aimed to determine the risk factors associated with MDR-TB. METHODS: A nationwide unmatched case-control study was conducted that included 79 MDR-TB cases and 118 controls. Data was collected by trained health workers through interviews using a structured questionnaire. Logistic regression analysis was performed to identify the risk factors associated with MDR-TB. RESULTS: The mean age of the participants was 32.4 and 33.7 years among the cases and the controls, respectively. In the multivariate analysis, the odds of having MDR-TB was higher among those who slept for less than 9 hours a day (AOR: 2.77, 95%CI: 1.11-6.92), frequently travelled in public transport (AOR: 2.96, 95% CI: 1.36-6.48), and had previous TB treatment (AOR: 5.90, 95%CI: 2.55-13.64). A greater number of rooms was also marginally associated with odds of having MDR-TB. CONCLUSIONS: The findings suggest previous TB treatment, inadequate sleep duration, and travelling by public transport to be the risk factors associated with having MDR-TB in Bhutan. Intensification of early case detection, strengthening directly observed treatment strategy, improving treatment adherence, and increasing awareness can help control the rising MDR-TB epidemic.

Identification of US Counties at Elevated Risk for Congenital Syphilis Using Predictive Modeling and a Risk Scoring System.

BACKGROUND: Although preventable through timely screening and treatment, congenital syphilis (CS) rates are increasing in the United States, occurring in 5% of counties in 2015. Although individual-level factors are important predictors of CS, given the geographic focus of CS, it is also imperative to understand what county-level factors are associated with CS. METHODS: This is a secondary analysis of reported county CS cases to the National Notifiable Diseases Surveillance System during the periods 2014-2015 and 2016-2017. We developed a predictive model to identify county-level factors associated with CS and use these to predict counties at elevated risk for future CS. RESULTS: Our final model identified 973 (31.0% of all US counties) counties at elevated risk for CS (sensitivity, 88.1%; specificity, 74.0%). County factors that were predictive of CS included metropolitan area, income inequality, primary and secondary syphilis rates among women and men who have sex with men, and population proportions of those who are non-Hispanic black, Hispanic, living in urban areas, and uninsured. The predictive model using 2014-2015 CS outcome data was predictive of 2016-2017 CS cases (area under the curve value, 89.2%) CONCLUSIONS: Given the dire consequences of CS, increasing prevention efforts remains important. The ability to predict counties at most elevated risk for CS based on county factors may help target CS resources where they are needed most.

Risk factors associated with suicidal ideation and suicide attempts in Bhutan: An analysis of the 2014 Bhutan STEPS Survey data.

Suicide is a major public health problem globally. Data on the factors influencing suicidal behaviours that can inform prevention policies are limited in Bhutan. This study used the dataset of the nationally-representative Bhutan STEPS Survey conducted in 2014 that assessed the non-communicable disease risk factors. Using a backward elimination approach, multiple logistic regression analysis accounting for the complex survey design was performed to identify the factors associated with suicidal ideation and suicide attempts in adults separately. The prevalence of suicidal ideation and suicide attempt was 3.1% and 0.7%, respectively. We found female gender, being unemployed, low and middle household income than high household income, and having a family history of suicide were associated with higher odds of having suicidal ideation. Younger age and alcohol consumption were associated with both suicidal ideation and suicide attempts. While those from the middle-income group compared to those in the high-income group had reduced odds of attempting suicide. The findings can help inform policy investments for suicide prevention. Prevention programs that target young people, females, and low socioeconomic groups, and aimed to reduce harmful alcohol use can help prevent suicidal behaviours.

Association between trends in county-level opioid prescribing and reported rates of gonorrhea cases in the United States.

PURPOSE: We investigated the association between county-level trends in opioid prescribing rates, a proxy for opioid misuse, and rates of reported gonorrhea (GC) among males in the United States. METHODS: We used linear mixed-model regression analyses to evaluate the association between county-level trends in opioid prescribing rates and rates of reported GC among males during 2010-2015. RESULTS: There was a positive association between trends in county-level opioid prescribing rates and rates of GC among males (ß = 0.068, 95% confidence interval [CI] = 0.030, 0.105) during 2010-2015. However, the magnitude of this association decreased significantly over time in counties where opioid prescribing rates decreased (ß = -0.018, 95% CI = -0.030, -0.006) and remained stable (ß = -0.020, 95% CI = -0.038, -0.002) but was unchanged in counties where opioid prescribing rates increased (ß = -0.029, 95% CI = -0.058, 0.001). CONCLUSIONS: During 2010-2015, we found a positive association between increases in county-level opioid prescribing rates, a proxy for opioid misuse, and rates of reported GC among males especially in counties most affected by the opioid crisis. Integrating sexual health with opioid misuse interventions might be beneficial in addressing the GC burden in the United States.

Laboratory Evaluation of a Commercially Available Rapid Syphilis Test.

Serological diagnosis of syphilis depends on assays that detect treponemal and nontreponemal antibodies. Laboratory certification and trained personnel are needed to perform most of these tests, while high costs and long turnaround time can hinder treatment initiation or linkage to care. A rapid treponemal syphilis test (RST) that is simple to perform, accessible, and inexpensive would be ideal. The Syphilis Health Check (SHC) assay is the only Food and Drug Administration (FDA)-cleared and Clinical Laboratory Improvement Amendments (CLIA)-waived RST in the United States. In this study, 1,406 archived human serum samples were tested using SHC and traditional treponemal and nontreponemal assays. Rapid test results were compared with treponemal data alone and with a laboratory test panel consensus defined as being reactive by both treponemal and nontreponemal assays for a given specimen, or nonreactive by both types of assays. The sensitivity and specificity of the SHC assay compared with treponemal tests alone were 88.7% (95% confidence interval [CI], 86.2 to 90.0%) and 93.1% (95% CI, 90.0 to 94.9%), respectively, while comparison with the laboratory test panel consensus showed 95.7% (95% CI, 93.6 to 97.2%) sensitivity and 93.2% (95% CI, 91.0 to 95.1%) specificity. The data were further stratified based on age, sex, pregnancy, and HIV status. The sensitivity and specificity of the SHC assay ranged from 66.7% (95% CI, 46.0 to 83.5%) to 91.7% (95% CI, 87.7 to 94.7%) and 88% (95% CI, 68.8 to 97.5%) to 100% (95% CI, 47.8 to 100%), respectively, across groups compared to traditional treponemal assays, generally increasing for all groups except the HIV-positive (HIV+) population when factoring in the laboratory test panel consensus. These data contribute to current knowledge of the SHC assay performance for distinct populations and may guide use in various settings.

Current tobacco use and its associated factors among adults in a country with comprehensive ban on tobacco: findings from the nationally representative STEPS survey, Bhutan, 2014.

BACKGROUND: Despite a comprehensive ban on cultivation, manufacture, distribution, and sale of tobacco products since 2004, two nationwide surveys conducted in 2012 and 2013 reported high tobacco use in Bhutan. National Health Survey 2012 reported that 4 % of the population aged 15-75 years used smoked tobacco and about 48 % used smokeless tobacco. Similarly, Global Youth Tobacco Survey (GYTS) of Bhutan reported tobacco use prevalence of 30.3 % in 2013. However, factors associated with this high tobacco use were not systematically studied. Hence, we assessed the prevalence of tobacco use and its associated sociodemographic, behavioral, and environmental factors. METHODS: This cross-sectional analytical study used secondary data collected in a nationally representative Non-communicable Disease Risk Factors Surveillance STEPS Survey 2014 conducted among Bhutanese adults (18-69 years). The survey included a total of 2820 adults; selected using multistage stratified cluster sampling. Weighted analysis was done to calculate the prevalence of tobacco use. Unadjusted and adjusted prevalence ratios were calculated using log binomial regression. RESULTS: The prevalence of current overall tobacco use was 24.8 % (95 % CI: 21.4-28.3) and that of smoked, smokeless, and dual forms (smoked and smokeless forms) were 7.4 % (95 % CI: 5.8-9.0), 19.7 % (95 % CI: 16.5-22.9), and 2.3 % (95 % CI: 1.8-2.9), respectively. Significantly higher prevalence of tobacco use in all forms was found among males, younger age groups, and alcohol users. The prevalence of smoked form was higher in urban areas compared to rural areas (11 % vs 6 %; aPR 1.8, 95 % CI: 1.5-2.0). Among individuals who reported having a non-communicable disease, the prevalence of smoked tobacco use was significantly lower than those who did not have disease (3.5 % vs. 8.3 %; aPR 0.5, 95 % CI: 0.3-0.9). Exposure to health warnings was protective for current tobacco use and smokeless tobacco use, while exposure to tobacco warnings through the media was helpful among smokers and overall tobacco users. CONCLUSIONS: Despite a comprehensive ban on tobacco, tobacco use was high in Bhutan, especially the smokeless form. Males, younger age groups, and alcohol users should be targeted with behavioral interventions along the stricter implementation of tobacco control measures.

An approach to diabetes prevention and management: The Bhutan experience.

Bhutan has been witnessing a trend of increasing diabetes in recent years. The increase is attributed to a rise in risk factors such as overweight, high blood pressure, unhealthy diet and sedentary lifestyle among the population. To address the rising burden, the health-services response has been to establish diabetes clinics in all hospitals and grade one basic health units. People visiting the health centres who have high risk factors and symptoms for diabetes are screened using the World Health Organization cut-off level for blood glucose. They are then classified into prediabetes and diabetes. Accordingly, diet, medicine and physical activity are recommended as per their body mass index. To improve prevention and control of noncommunicable diseases, which include diabetes, the country piloted the WHO Package of Essential Noncommunicable (PEN) disease interventions for primary health care in low-resource settings in 2009, to promote early screening, treatment and follow-up, and adopted it in 2013. The WHO PEN has now been successfully integrated into the primary health-care system nationwide. It is planned that diabetes clinics will be upgraded to NCD clinics.

A first country-wide review of Diabetes Mellitus care in Bhutan: time to do better.

BACKGROUND: There is an increasing trend of non-communicable diseases in Bhutan including Diabetes Mellitus (DM). To address this problem, a National Diabetes Control Programme was launched in 1996. There is anecdotal evidence that many patients do not visit the DM clinics regularly, but owing to lack of cohort monitoring, the magnitude of such attrition from care is unknown. Knowledge of the extent of this problem will provide a realistic assessment of the situation on the ground and would be helpful to initiate corrective actions. In this first country-wide audit, we thus aimed to determine among type 2 DM patients registered for care the i) pre-treatment attrition ii) one-year programme outcomes including retention in care, died and Lost-to-follow-up (LTFU, defined as not having visited the clinic at least once within a year of registration) iii) factors associated with attrition from care (death + LTFU) and iv) quality of follow-up care, measured by adherence to recommended patient-monitoring protocols including glycaemic control. METHODS: A retrospective cohort study involving a review of records routinely maintained under the National Diabetes Control Programme. All type 2 DM patients registered between 1st January and 31st December 2012 in 18 district hospitals of Bhutan were included. Glycaemic control was defined as glycosylated haemoglobin of <7% or [Fasting Blood Sugar of <130 mg/dl and, Post-prandial Blood Sugar of <180 mg/dl]. RESULTS: Of 350 registered DM patients (52% female, median age 55 years), 63(18%) were LTFU before treatment initiation (pre-treatment attrition). Of the remaining 287 individuals who started treatment, 226(79%) were retained in care while 61(21%) either died or were LTFU. Glycaemic control was achieved in 85(38%) patients retained in care. Between 7 and 98% of monitoring parameters had missing data. CONCLUSION: Nearly one-third of DM patients were LTFU and there were short comings in monitoring. Qualitative research is urgently needed to find out the reasons for high attrition. Given the high political commitment by the Royal Government of Bhutan, the findings provide ample grounds for instituting corrective measures and propelling DM care further. It is time to do better!

Introduction of a National HPV vaccination program into Bhutan.

BACKGROUND: Cervical cancer is the most common cancer in Bhutanese women. To help prevent the disease, the Ministry of Health (MoH) developed a national human papillomavirus (HPV) vaccine program. METHODS: MoH considerations included disease incidence, the limited reach of cervical screening, poor outcomes associated with late diagnosis of the disease, and Bhutan's ability to conduct the program. For national introduction, it was decided to implement routine immunization for 12 year-old girls with the quadrivalent HPV6/11/16/18 (QHPV) vaccine and a one-time catch-up campaign for 13-18 year-old girls in the first year of the program (2010). Health workers would administer the vaccine in schools, with out-of-school girls to receive the vaccine at health facilities. From 2011, HPV vaccination would enter into the routine immunization schedule using health-center delivery. RESULTS: During the initial campaign in 2010, over 130,000 doses of QHPV were administered and QHPV 3-dose vaccination coverage was estimated to be around 99% among 12 year-olds and 89% among 13-18 year-olds. QHPV vaccine was well tolerated and no severe adverse events were reported. In the three following years, QHPV vaccine was administered routinely to 12 year-olds primarily through health centers instead of schools, during which time the population-level 3-dose coverage decreased to 67-69%, an estimate which was confirmed by individual-level survey data in 2012 (73%). In 2014, when HPV delivery was switched back to schools, 3-dose coverage rose again above 90%. DISCUSSION: The rapid implementation and high coverage of the national HPV vaccine program in Bhutan were largely attributable to the strength of political commitment, primary healthcare and support from the education system. School-based delivery appeared clearly superior to health centers in achieving high-coverage among 12 year-olds. CONCLUSIONS: Bhutan's lessons for other low/middle-income countries include the superiority of school-based vaccination and the feasibility of a broad catch-up campaign in the first year.

A Prospective Hospital-based Surveillance to Estimate Rotavirus Disease Burden in Bhutanese Children under 5 Years of Age.

As part of efforts to develop an informed policy for rotavirus vaccination, this prospective study was conducted to estimate the burden of rotavirus diarrhea among children less than 5 years old attended to the Department of Pediatrics, Jigme Dorji Wangchuk National Referral Hospital (JDWNRH), Thimphu, Bhutan. The duration of the study was three years, extending from February 2010 through December 2012. We estimated the frequency of hospitalization in the pediatric ward and dehydration treatment unit (DTU) for diarrhea and the number of events attributable to rotavirus infection among children under 5 years of age. During the study period, a total of 284 children (1 in 45) were hospitalized in the pediatric ward, and 2,220 (1 in 6) in the DTU with diarrhea among children residing in the Thimphu district. Group A rotavirus was detected in 32.5% and 18.8% of the stool samples from children hospitalized in the pediatric ward, respectively. Overall, 22.3% of the stool samples were rotavirus-positive, and the majority (90.8%) of them was detected in children under 2 years of age. From this study, we estimated that the annual incidence of hospitalization in the pediatric ward and DTU due to rotavirus diarrhea was 2.4/1000 (95% CI 1.7-3.4) and 10.8/1000 (95% CI 9.1-12.7) children, respectively. This study revealed that rotavirus is a major cause of diarrhea in Bhutanese children in Thimphu district and since no study has been performed previously, represents an important finding for policy discussions regarding the adoption of a rotavirus vaccine in Bhutan.

Is diabetes and hypertension screening worthwhile in resource-limited settings? An economic evaluation based on a pilot of a Package of Essential Non-communicable disease interventions in Bhutan.

In response to a lack of cost-effective data on screening and early treatment of diabetes and hypertension in resource-limited settings, a model-based economic evaluation was performed on the World Health Organization (WHO)'s Package of Essential Non-communicable (PEN) disease interventions for primary health care in Bhutan. Both local and international data were applied in the model in order to derive lifetime costs and outcomes resulting from the early treatment of diabetes and hypertension. The results indicate that the current screening option (where people who are overweight, obese or aged 40 years or older who visit primary care facilities are screened for diabetes and hypertension) represents good value for money compared to 'no screening'. The study findings also indicate that expanding opportunistic screening (70% coverage of the target population) to universal screening (where 100% of the target population are screened), is likely to be even more cost-effective. From the sensitivity analysis, the value of the screening options remains the same when disease prevalence varies. Therefore, applying this model to other healthcare settings is warranted, since disease prevalence is one of the major factors in affecting the cost-effectiveness results of screening programs.

Chikungunya fever outbreak, Bhutan, 2012.

In 2012, chikungunya virus (CHIKV) was reported for the first time in Bhutan. IgM ELISA results were positive for 36/210 patient samples; PCR was positive for 32/81. Phylogenetic analyses confirmed that Bhutan CHIKV belongs to the East/Central/South African genotype. Appropriate responses to future outbreaks require a system of surveillance and improved laboratory capacity.