Epidemiology of dengue in Bhutan

Abstract

Dengue has been rapidly spreading worldwide, resulting in higher morbidity than other vector-borne viral diseases. The majority of this burden is borne by the South-East Asia Region of the World Health Organization (WHO-SEAR). Bhutan is a lower-middle-income country located in the WHO-SEAR. After the first documented outbreak in 2004, dengue has gradually expanded its geographical range with a concomitant increase in incidence and severity. The aim of my research was to describe the epidemiological characteristics of dengue in Bhutan. Member countries in the WHO-SEAR have become hyper-endemic with the co-circulation of multiple dengue virus (DENV) serotypes. Although case fatalities have decreased steadily, dengue incidence has increased dramatically over the past decade in the region. As 0.5%-5% of the infection progresses to severe dengue including deaths, a meta-analysis was conducted to identify the risk factors of the disease. Children (odds ratio [OR]: 1.96; 95% CI: 1.22, 3.13), patients with secondary infection (OR: 3.23; 95% CI: 2.28, 4.57), and patients with pre-existing co-morbidities such as diabetes (OR: 2.88; 95% CI: 1.72, 4.81) and renal disease (OR: 4.54; 95% CI: 1.55, 13.31) were shown to have an increased risk for severe dengue. The study also corroborated the WHO's recommendation to monitor seven warning signs of severe dengue. However, the current surveillance system in Bhutan and other countries in the WHO-SEAR does not provide adequate information for early case detection and for effective management of dengue due to inadequate reporting. Additionally, vector surveillance was predominantly carried out using larval indices without routinely employing adult mosquito sampling. To explore the spatio-temporal pattern of dengue incidence, an ecological study was conducted in a Bayesian framework. Individuals aged >14 years (relative risk [RR]: 0.471, 95% confidence interval [CI]: 0.378-0.582) and temperature (RR: 1.625, 95% CI: 1.493-1.772) were positively associated with dengue incidence, while normalised difference vegetation index [NDVI] (RR: 0.515, 95% CI: 0.353-0.748) was negatively associated with dengue incidence. Bhutan experienced the worst dengue epidemic in 2019, which resulted in cases greater than the combined total cases in all the previous years. Dengue expanded from six to 44 sub-districts across 19 districts. The effective reproduction number was <3 for most of the epidemic period, except for ~1 month period of explosive growth, coinciding with a period of monsoon season, where the effective reproduction number peaked >30. A multicriteria decision-making analysis (MCDA) was used to develop a vulnerability map of dengue at a fine spatial resolution. Interestingly, this study pointed out new geographical locations including the nation's capital, as being at risk of dengue. An online survey revealed critical gaps in the clinical management of dengue amongst medical practitioners (MPs). Major gaps included limited knowledge about the peak activity of feeding time of the dengue vector, the use of clinical warning signs of severe dengue for monitoring dengue patients, the use of NS1 antigen for early diagnosis, and the clinical significance of hematological parameters. This thesis illustrates the contemporary epidemiology of dengue in Bhutan and identified ecological, clinical, and demographic risk factors of dengue transmission. This information will be crucial for forward planning of dengue prevention and control by the public health authorities in the country. Show more