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Spatial repellent (SR) products are envisioned to complement existing vector control methods through the continual release of volatile active ingredients (AI) providing: (i) protection against day-time and early-evening biting; (ii) protection in enclosed/semi-enclosed and peri-domestic spaces; (iii) various formulations to fit context-specific applications; and (iv) increased coverage over traditional control methods. SR product AIs also have demonstrated effect against insecticide-resistant vectors linked to malaria and Aedes-borne virus (ABV) transmission. Over the past two decades, key stakeholders, including World Health Organization (WHO) representatives, have met to discuss the role of SRs in reducing arthropod-borne diseases based on existing evidence. A key focus has been to establish a critical development path for SRs, including scientific, regulatory and social parameters that would constitute an outline for a SR target product profile, i.e. optimum product characteristics. The principal gap is the lack of epidemiological data demonstrating SR public health impact across a range of different ecological and epidemiological settings, to inform a WHO policy recommendation. Here we describe in brief trials that are designed to fulfill evidence needs for WHO assessment and initial projections of SR cost-effectiveness against malaria and dengue.

In 2017, a dengue epidemic of unexpected magnitude occurred in Sri Lanka. A total of 186,101 suspected cases and 440 dengue-related deaths occurred. We conducted a comprehensive analysis of this epidemic by comparing national surveillance data for 2017 with data from the preceding 5 years. In all Sri Lanka districts, dengue incidence in 2017 increased significantly over incidence during the previous 5 years. Older schoolchildren and young adults were more clinically symptomatic than those at extremes of age. Limited virologic surveillance showed the dominant circulating variant was dengue virus type 2 cosmopolitan genotype in the most affected district. One quarter of total annual cases were reported 5 weeks after the southwest monsoon started. Changes in vector abundance were not predictive of the increased incidence. Direct government expenditures on dengue control activities in 2017 were US $12.7 million. The lessons learned from this outbreak are useful for other tropical nations facing increasing dengue incidence.

Abstract Background A major challenge in dengue management in resource limited settings is the confirmation of diagnosis. Clinical features of dengue often overlap with other infections and molecular diagnostic tools are not readily accessible to clinicians at hospitals. In addition, the prediction of plasma leakage in dengue is also difficult. Hematocrit level and ultrasound scans (combined with clinical parameters) are helpful to detect plasma leakage once it has happened, not before. Methods Colombo Dengue Study (CDS) is a prospective cohort study of clinically suspected adult dengue patients recruited from the National hospital of Sri Lanka (within the first 3 days of fever) that aimed to a) identify clinical and basic laboratory test parameters to differentiate dengue from non-dengue fever, b) evaluate the comparative efficacy of loop-mediated isothermal amplification (LAMP) for dengue diagnosis (vs. NS1 antigen test and RT-qPCR) and c) identify early associations that are predictive of plasma leakage or severe dengue. The basic laboratory tests considered here included hematological parameters, serum biochemistry and inflammatory markers. Results Only 70% of clinically suspected patients were confirmed as having dengue by either the NS1 antigen test or RT-qPCR. On a Bayesian latent class model which assumes no “gold standard”, LAMP performed equally or better than RT-qPCR and NS1 antigen test respectively. When confirmed dengue patients were compared with others, the earlier group had significantly lower lymphocyte counts and higher aspartate aminotransferase levels (AST) within the first 3 days of fever. Confirmed dengue patients with plasma leakage had a lower mean age and a higher median baseline AST level compared to those without plasma leakage (p

Recent emergence of dengue hemorrhagic fever in the Indian subcontinent has been well documented in Sri Lanka. We compare recent (2003–2006) and past (1980–1997) dengue surveillance data for Sri Lanka. The 4 dengue virus (DENV) serotypes have been cocirculating in Sri Lanka for >30 years. Over this period, a new genotype of DENV-1 has replaced an old genotype. Moreover, new clades of DENV-3 genotype III viruses have replaced older clades. Emergence of new clades of DENV-3 in 1989 and 2000 coincided with abrupt increases in the number of reported dengue cases, implicating this serotype in severe epidemics. In 1980–1997, most reported dengue cases were in children. Recent epidemics have been characterized by many cases in children and adults. Changes in local transmission dynamics and genetic changes in DENV-3 are likely increasing emergence of severe dengue epidemics in Sri Lanka.

The number of cases and severity of disease associated with dengue infection in Sri Lanka has been increasing since 1989, when the first epidemic of dengue hemorrhagic fever was recorded. We identified a new dengue virus 1 strain circulating in Sri Lanka that coincided with the 2009 dengue epidemic.

Abstract Background Dengue is a major public health problem in Sri Lanka. Aedes vector surveillance and monitoring of larval indices are routine, long-established public health practices in the country. However, the association between Aedes larval indices and dengue incidence is poorly understood. It is crucial to evaluate lagged effects and threshold values of Aedes larval indices to set pragmatic targets for sustainable vector control interventions. Methods Monthly Aedes larval indices and dengue cases in all 10 Medical Officer of Health (MOH) divisions in Kalutara district were obtained from 2010 to 2019. Using a novel statistical approach, a distributed lag non-linear model and a two-staged hierarchical meta-analysis, we estimated the overall non-linear and delayed effects of the Premise Index (PI), Breteau Index (BI) and Container Index (CI) on dengue incidence in Kalutara district. A set of MOH division-specific variables were evaluated within the same meta-analytical framework to determine their moderator effects on dengue risk. Using generalized additive models, we assessed the utility of Aedes larval indices in predicting dengue incidence. Results We found that all three larval indices were associated with dengue risk at a lag of 1 to 2 months. The relationship between PI and dengue was homogeneous across MOH divisions, whereas that with BI and CI was heterogeneous. The threshold values of BI, PI and CI associated with dengue risk were 2, 15 and 45, respectively. All three indices showed a low to moderate accuracy in predicting dengue risk in Kalutara district. Conclusions This study showed the potential of vector surveillance information in Kalutara district in developing a threshold-based, location-specific early warning system with a lead time of 2 months. The estimated thresholds are nonetheless time-bound and may not be universally applicable. Whenever longitudinal vector surveillance data areavailable, the methodological framework we propose here can be used to estimate location-specific Aedes larval index thresholds in any other dengue-endemic setting. Graphical Abstract

Background Dengue is one of the major public health problems in Sri Lanka. Its outbreak pattern depends on a multitude of drivers, including human mobility. Here we evaluate the impact of COVID–19 related mobility restriction (lockdown) on the risk of dengue in Sri Lanka. Methodology Two-stage hierarchical models were fitted using an interrupted time-series design based on the notified dengue cases, January 2015 to July 2020. In the first stage model, the district level impact was estimated using quasi-Poisson regression models while accounting for temporal trends. Estimates were pooled at zonal and national levels in the second stage model using meta-analysis. The influence of the extended period of school closure on dengue in children in the western province was compared to adults. Findings Statistically significant and homogeneous reduction of dengue risk was observed at all levels during the lockdown. Overall an 88% reduction in risk (RR 0.12; 95% CI from 0.08 to 0.17) was observed at the national level. The highest impact was observed among children aged less than 19 years showing a 92% reduction (RR 0.8; 95% CI from 0.03 to 0.25). We observed higher impact in the dry zone having 91% reduction (RR 0.09; 95% CI from 0.05 to 0.15) compared to wet zone showing 83% reduction (RR 0.17; 95% CI from 0.09 to 0.30). There was no indication that the overall health-seeking behaviour for dengue had a substantial influence on these estimates. Significance This study offers a broad understanding of the change in risk of dengue during the COVID–19 pandemic and associated mobility restrictions in Sri Lanka. The analysis using the mobility restrictions as a natural experiment suggests mobility patterns to be a very important driver of dengue transmission. Author summary Every year about 100 million symptomatic dengue cases occur with the highest-burden reported in Southeast Asia followed by Latin America. The burden is increasing and considered driven by population densities, human mobility, vector proliferation, and climate variability. Evaluation of the impact of human mobility on dengue transmission is methodologically challenging, but an important aspect in public health research. The ongoing COVID-19 pandemic has resulted in dramatic reductions in human mobility due to social distancing measures. These population-level interventions in most countries have changed the exposure patterns to Aedes vectors and the spread of the dengue virus. The mobility restrictions due to the COVID-19 response in Sri Lanka provided a natural experiment to understand the importance of human mobility on dengue in an endemic setting. Using interrupted time series design, we evaluated the impact of mobility restriction on dengue transmission in all 25 administrative districts, climate zones, and age groups in Sri Lanka. The results of this empirical study provided evidence of an overall statistically significant reduction of dengue during the period of mobility restriction in the country, which appears not to be related to changes in health seeking behaviour. Our study provides a methodological framework to quantify the impact of lockdown interventions on dengue transmission and its heterogeneous nature at different geographical, climatic, and socio-demographic levels within and between countries.

BackgroundDengue is one of the major public health problems in Sri Lanka. Its outbreak pattern depends on a multitude of drivers, including human mobility. Here we evaluate the impact of COVID-19 related mobility restriction (lockdown) on the risk of dengue in Sri Lanka.MethodologyTwo-stage hierarchical models were fitted using an interrupted time-series design based on the notified dengue cases, January 2015 to July 2020. In the first stage model, the district level impact was estimated using quasi-Poisson regression models while accounting for temporal trends. Estimates were pooled at zonal and national levels in the second stage model using meta-analysis. The influence of the extended period of school closure on dengue in children in the western province was compared to adults.FindingsStatistically significant and homogeneous reduction of dengue risk was observed at all levels during the lockdown. Overall an 88% reduction in risk (RR 0.12; 95% CI from 0.08 to 0.17) was observed at the national level. The highest impact was observed among children aged less than 19 years showing a 92% reduction (RR 0.8; 95% CI from 0.03 to 0.25). We observed higher impact in the dry zone having 91% reduction (RR 0.09; 95% CI from 0.05 to 0.15) compared to wet zone showing 83% reduction (RR 0.17; 95% CI from 0.09 to 0.30). There was no indication that the overall health-seeking behaviour for dengue had a substantial influence on these estimates.SignificanceThis study offers a broad understanding of the change in risk of dengue during the COVID-19 pandemic and associated mobility restrictions in Sri Lanka. The analysis using the mobility restrictions as a natural experiment suggests mobility patterns to be a very important driver of dengue transmission.

Major dengue epidemics have been observed in the Indian subcontinent since the 1980s and have occurred with increased hospitalizations and mortality. In 2011, the first major epidemic of dengue occurred in Lahore, the second largest city in Pakistan, and resulted in 21,685 confirmed cases and 350 deaths. To investigate the possible viral causes for the increased epidemic activity, we determined the predominant serotype and characterized the viruses genetically. Of 50 patients carefully selected as probable dengue fever or dengue hemorrhagic fever, 34 were positive by virologic testing (i.e. PCR and/or virus isolation). DENV-2 was detected in 32 patients and DENV-1 in two. A total of 24 partial and three full DENV genomes were sequenced. Phylogenetic analyses of the capsid (C), pre-membrane (prM), and envelope genes comprising 2500 nucleotides in length indicated that all DENV-2 isolates in Pakistan since 2007 form a monophyletic lineage that is endemic in the country. These viruses were all of the cosmopolitan genotype (IV) and most closely related to viruses isolated in India and Sri Lanka in the past two decades. Phylogenetic analyses of data currently available in GenBank suggest that the Cosmopolitan genotype has diverged into two geographically distinct sub-lineages: sub-lineage IV-a has only been observed in Southeast Asia, China and Oceania, while IV-b is prevalent in the Indian subcontinent. These results highlight the increased diversity of dengue viruses as they spread geographically within the region.