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.

Identifying socio-ecological drivers of common cold in Bhutan: a national surveillance data analysis.

The common cold is a leading cause of morbidity and contributes significantly to the health costs in Bhutan. The study utilized multivariate Zero-inflated Poisson regression in a Bayesian framework to identify climatic variability and spatial and temporal patterns of the common cold in Bhutan. There were 2,480,509 notifications of common cold between 2010 and 2018. Children aged < 15 years were twice (95% credible interval [CrI] 2.2, 2.5) as likely to get common cold than adults, and males were 12.4% (95 CrI 5.5%, 18.7%) less likely to get common cold than females. A 10 mm increase in rainfall lagged one month, and each 1 °C increase of maximum temperature was associated with a 5.1% (95% CrI 4.2%, 6.1%) and 2.6% (95% CrI 2.3%, 2.8%) increase in the risk of cold respectively. An increase in elevation of 100 m and 1% increase in relative humidity lagged three months were associated with a decrease in risk of common cold by 0.1% (95% CrI 0.1%, 0.2%) and 0.3% (95% CrI 0.2%, 0.3%) respectively. Seasonality and spatial heterogeneity can partly be explained by the association of common cold to climatic variables. There was statistically significant residual clustering after accounting for covariates. The finding highlights the influence of climatic variables on common cold and suggests that prioritizing control strategies for acute respiratory infection program to subdistricts and times of the year when climatic variables are associated with common cold may be an effective strategy.

Sustaining progress towards malaria elimination by 2025: Lessons from Bhutan & Timor-Leste.

In Asia Pacific, several nations that were part of the World Health Organization's initiative to eliminate malaria by 2020 or the E2020 Initiative reported being off-track. The COVID-19 pandemic further strained health systems and has the potential to stall the efforts and reverse earlier progress made towards the fight against malaria. These nations have since recommitted to eliminating malaria by 2025, in a renewed E2025 Initiative. This viewpoint presents efforts of the national malaria programs in Bhutan and Timor-Leste as they prepare for this new commitment. It includes insights on the approaches adapted by both countries that have helped them keep the spotlight on malaria whilst preventing large COVID-19 outbreaks. This viewpoint proposes key strategies that near-elimination countries can consider to sustain malaria interventions and realize their elimination goal. Of note, it calls for national strategic plans to consider a whole-of-government approach to ensure progress - which includes sustaining political commitment, systematically collaborating across borders, empowering communities and strengthening health systems particularly through surveillance and data management - that will benefit all existing and future infectious threats and pave the way for integrated response mechanisms across diseases.

Spatio-temporal patterns of childhood pneumonia in Bhutan: a Bayesian analysis.

Pneumonia is one of the top 10 diseases by morbidity in Bhutan. This study aimed to investigate the spatial and temporal trends and risk factors of childhood pneumonia in Bhutan. A multivariable Zero-inflated Poisson regression model using a Bayesian Markov chain Monte Carlo simulation was undertaken to quantify associations of age, sex, altitude, rainfall, maximum temperature and relative humidity with monthly pneumonia incidence and to identify the underlying spatial structure of the data. Overall childhood pneumonia incidence was 143.57 and 10.01 per 1000 persons over 108 months of observation in children aged < 5 years and 5-14 years, respectively. Children < 5 years or male sex were more likely to develop pneumonia than those 5-14 years and females. Each 1 °C increase in maximum temperature was associated with a 1.3% (95% (credible interval [CrI] 1.27%, 1.4%) increase in pneumonia cases. Each 10% increase in relative humidity was associated with a 1.2% (95% CrI 1.1%, 1.4%) reduction in the incidence of pneumonia. Pneumonia decreased by 0.3% (CrI 0.26%, 0.34%) every month. There was no statistical spatial clustering after accounting for the covariates. Seasonality and spatial heterogeneity can partly be explained by the association of pneumonia risk to climatic factors including maximum temperature and relative humidity.

Space-Time Clustering Characteristics of Malaria in Bhutan at the End Stages of Elimination.

Malaria in Bhutan has fallen significantly over the last decade. As Bhutan attempts to eliminate malaria in 2022, this study aimed to characterize the space-time clustering of malaria from 2010 to 2019. Malaria data were obtained from the Bhutan Vector-Borne Disease Control Program data repository. Spatial and space-time cluster analyses of Plasmodium falciparum and Plasmodium vivax cases were conducted at the sub-district level from 2010 to 2019 using Kulldorff's space-time scan statistic. A total of 768 confirmed malaria cases, including 454 (59%) P. vivax cases, were reported in Bhutan during the study period. Significant temporal clusters of cases caused by both species were identified between April and September. The most likely spatial clusters were detected in the central part of Bhutan throughout the study period. The most likely space-time cluster was in Sarpang District and neighboring districts between January 2010 to June 2012 for cases of infection with both species. The most likely cluster for P. falciparum infection had a radius of 50.4 km and included 26 sub-districts with a relative risk (RR) of 32.7. The most likely cluster for P. vivax infection had a radius of 33.6 km with 11 sub-districts and RR of 27.7. Three secondary space-time clusters were detected in other parts of Bhutan. Spatial and space-time cluster analysis identified high-risk areas and periods for both P. vivax and P. falciparum malaria. Both malaria types showed significant spatial and spatiotemporal variations. Operational research to understand the drivers of residual transmission in hotspot sub-districts will help to overcome the final challenges of malaria elimination in Bhutan.

The trend of tuberculosis case notification and predictors of unsuccessful treatment outcomes in Samdrup Jongkhar district, Bhutan: A fourteen-year retrospective study.

Tuberculosis (TB) continues to be an important public health issue in Bhutan. This study aims to describe the trend of tuberculosis and investigate factors associated with a unsuccessful treatment outcome in Samdrup Jongkhar District in Bhutan. A fourteen-year (2004-2017) case records in two TB centres of Dewathang and Samdrup Jongkhar Hospitals were reviewed and analyzed to examine trends in case notification and treatment outcomes. Univariable and multivariable logistic regression analysis was undertaken to identify covariates of unsuccessful TB treatment. Of the total of 820 TB cases registered in surveillance record, 729 cases were analysed. Males made up 53.8% (397) of total cases and the median age was 29 years (range: 2-87 years). A gradual downward trend in TB case notification was noticed in the district with overall case notification rate of 139/100,000 during the study period. The annual treatment success rate was over 90% except for years 2013-2015 with overall treatment success rate for the study period at 93%. A re-treatment TB patient, sputum-positive at the second month of treatment and being of Indian nationality were significant correlates of unsuccessful treatment outcomes. The overall TB inclidence has declined and TB treatment success rate was above WHO recommended 90% in Samdrup Jongkhar District during the study period. A special attention should be paid to the poor treatment outcome predictors including re-treatment cases and failed sputum conversion at the second month of treatment.

Has COVID19 derailed Bhutan's national malaria elimination goal? A commentary.

The COVID-19 pandemic has resulted in massive global disruptions with considerable impact on the delivery of health services and national health programmes. Since the detection of the first COVID-19 case on 5th March 2020, the Royal Government of Bhutan implemented a number of containment measures including border closure and national lockdowns. Against the backdrop of this global COVID-19 pandemic response, there was a sudden surge of locally-transmitted malaria cases between June to August 2020. There were 20 indigenous cases (zero Plasmodium falciparum and 20 Plasmodium vivax) from a total of 49 cases (seven P. falciparum and 42 P. vivax) in 2020 compared to just two from a total of 42 in 2019. Over 80% of the cases were clustered in malaria endemic district of Sarpang. This spike of malaria cases was attributed to the delay in the delivery of routine malaria preventive interventions due to the COVID-19 pandemic. As a result, Bhutan is unlikely to achieve the national goal of malaria elimination by 2020.

An assessment on potential risk pathways for the incursion of highly pathogenic avian influenza virus in backyard poultry farm in Bangladesh.

BACKGROUND AND AIM: Highly pathogenic avian influenza (HPAI) is a deadly virus of zoonotic potential. The study mainly aims to determine the risk pathways (RPs) for the probable incursion of HPAI virus (HPAIV) in backyard poultry in Bangladesh. MATERIALS AND METHODS: The study involves expert elicitation technique. The concept map determines the possible RPs. The map consists of 16 concepts, each with nodes from which probabilities of an event originates. These probabilities are described by qualitative descriptors ranging from negligible to high. Risk assessment has been performed using the subjective risk assessment tool. RESULTS: The tool demonstrates positive correlation among groups of experts in the level of agreement by scoring RP; however, the level of agreement varies from 71% to 93% among group of experts. The median risk score of viral incursion through the "Exposure of backyard poultry with farm poultry in the trading market" was 11 and ranked as top, followed by "Contaminated live bird market environment" and "Sharing common scavenging space with migratory birds" (median risk score, 10.5; rank, 2), and "Scavenging of infected slaughtered poultry remnants by backyard poultry" (median risk score, 5.3; rank, 3) when no control options were applied along with the RPs. After applying or considering control option along with contaminated live bird market environment, the median risk score was reduced to 5.0. Applying a specific control option along with each RP reduced estimated median risk scores for HPAIV incursions. CONCLUSION: This study provides an insight into the incursion risks of HPAIV through various RPs in backyard poultry in Bangladesh.

Evaluation of post-exposure prophylaxis practices to improve the cost-effectiveness of rabies control in human cases potentially exposed to rabies in southern Bhutan.

BACKGROUND: Rabies is endemic in southern Bhutan, associated with 1-2 human deaths and high post exposure prophylaxis (PEP) costs annually. Evaluation of clinicians' management of human cases potentially exposed to rabies could contribute to improving PEP prescribing practices to both reduce unnecessary costs associated with PEP and reach the target of zero human deaths due to rabies by 2023. METHODS: A cross-sectional survey of 50 clinicians' management of human cases potentially exposed to rabies was conducted in 13 health centers in high-rabies-risk areas of Bhutan during February-March 2016. RESULTS: Data were collected on clinicians' management of 273 human cases potentially exposed to rabies. The 50 clinicians comprised health assistants or clinical officers (55%) and medical doctors (45%) with a respective median of 19, 21 and 2 years' experience. There was poor agreement between clinicians' rabies risk assessment compared with an independent assessment for each case based on criteria in the National Rabies Management Guidelines (NRMG). Of the 194 cases for which clinicians recorded a rabies risk category, only 53% were correctly classified when compared with the NRMG. Clinicians were more likely to underestimate the risk of exposure to rabies and appeared to prescribe PEP independently of their risk classification.. Male health assistants performed the most accurate risk assessments while female health assistants performed the least accurate. Clinicians in Basic Health Units performed less accurate risk assessments compared with those in hospitals. CONCLUSIONS: This study highlights important discrepancies between clinicians' management of human cases potentially exposed to rabies and recommendations in the NRMG. In particular, clinicians were not accurately assessing rabies risk in potentially exposed cases and were not basing their PEP treatment on the basis of their risk assessment. This has significant implications for achieving the national goal of eliminating dog-mediated human rabies by 2030 and may result in unnecessary costs associated with PEP. Recommendations to improve clinician's management of human cases potentially exposed to rabies include: reviewing and updating the NRMG, providing clinicians with regular and appropriately targeted training about rabies risk assessment and PEP prescription, and regularly reviewing clinicians' practices.

Determinants of health seeking behavior of animal bite victims in rabies endemic South Bhutan: a community-based contact-tracing survey.

BACKGROUND: Dog bites are the main source of rabies infection and death in humans, contributing up to 99% of all cases. We conducted a contact-tracing study to evaluate the health seeking and treatment compliance behaviors of people following potential exposure to rabies in rabies endemic south Bhutan. METHODS: Using information from the rabies post exposure prophylaxis (PEP) register, animal-exposed victims who had visited five hospitals in south Bhutan between January and March 2017 were traced and further data were collected from them using a structured questionnaire. A snowballing technique was used to identify victims who did not seek PEP.The survey was conducted between April and June 2017. Logistic regression was performed to assess factors associated with PEP-seeking and compliance behavior by the victims. RESULTS: Amongst 630 who reported to hospitals, 70% (444) of people could be traced and additional 8% (39) who did not seek PEP was identified through contact tracing. Therefore, a total of 483 people were interviewed. Seventy one percent (344/483) of exposure were due to animal bites of which 80% (365/455) were considered to be provoked incidents. Common reasons for not seeking health care included assumptions that risks of infection were minor if bitten by an owned or vaccinated dog. The victims who are male (OR: 0.36; 95% CI: 0.16-0.77) and educated (OR: 0.41; 95% CI: 0.17-0.96) were less likely to seek PEP, while those that experienced unprovoked bite (OR: 5.10; 95% CI: 1.20-21.77) were more likely to seek PEP in the hospitals. Overall, 82% of the victims sought PEP from the hospitals within 24 h after exposure. Eighty three percent completed the PEP course prescribed by the physician. The respondents living in urban areas (OR: 2.67; 95% CI: 1.34-5.30) were more likely to complete the prescribed PEP course than rural dwellers. CONCLUSIONS: There is high risk of rabies infection in southern Bhutan. It is critical to bridge knowledge gaps and dispel existing myths which will help to improve PEP seeking and compliance behavior of people exposed to rabies infection from animals. A risk-based advocacy program is necessary to prevent dog-mediated human rabies deaths.

Descriptive assessment of rabies post-exposure prophylaxis procurement, distribution, monitoring, and reporting in four Asian countries: Bangladesh, Bhutan, Cambodia, and Sri Lanka, 2017-2018.

BACKGROUND: There are approximately 35,000 human deaths from rabies in Asia annually. Rabies can be prevented through timely post-exposure prophylaxis (PEP) consisting of wound washing, rabies vaccine, and in some cases, rabies immunoglobulin (RIG). However, access to rabies PEP often remains limited to urban areas and is cost-prohibitive. There is little information on procurement, distribution, monitoring, and reporting of rabies PEP. METHODS: We interviewed key informants in the public sector from various levels in Bangladesh, Bhutan, Cambodia, and Sri Lanka between March 2017 and May 2018 using a descriptive assessment tool to obtain information on procurement, distribution, monitoring, and reporting of rabies PEP. These four countries in Asia were chosen to showcase a range of rabies PEP systems. National rabies focal points were interviewed in each country and focal points helped identify additional key informants at lower levels. RESULTS: A total of 22 key informants were interviewed at various levels (central level to health facility level) including national rabies focal points in each country. Each country has a unique system for managing rabies PEP procurement, distribution, monitoring, and reporting. There are varying levels of PEP access for those with potential rabies exposures. Rabies PEP is available in select health facilities throughout the country in Bangladesh, Bhutan, and Sri Lanka. In Cambodia, rabies PEP is limited to two urban centers. The availability of RIG in all four countries is limited. In these four countries, most aspects of the rabies PEP distribution system operate independently of systems for other vaccines. However, in Bhutan, rabies PEP and Expanded Programme on Immunization (EPI) vaccines share cold chain space in some locations at the lowest level. All countries have a monitoring system in place, but there is limited reporting of data, particularly to the central level. CONCLUSION: Systems to procure, deliver, monitor, and report on rabies PEP are variable across countries. Sharing information on practices more widely among countries can help programs to increase access to this life-saving treatment.

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.