Severe Dengue Epidemics in Sri Lanka, 2003–2006

One-sentence summary for table of contents: Changes in transmission dynamics and virus genes are likely increasing emergence of severe epidemics in this country

Development of standard clinical endpoints for use in dengue interventional trials: introduction and methodology

Background: As increasing numbers of dengue vaccines and therapeutics are in clinical development, standardized consensus clinical endpoint definitions are urgently needed to assess the efficacy of different interventions with respect to disease severity. We aimed to convene dengue experts representing various sectors and dengue endemic areas to review the literature and propose clinical endpoint definitions for moderate and severe disease based on the framework provided by the WHO 2009 classification. Methods: The endpoints were first proposed and discussed in a structured expert consultation. After that, the Delphi method was carried out to assess the usefulness, validity and feasibility of the standardized clinical disease endpoints for interventional dengue research. Results: Most respondents (> 80%) agreed there is a need for both standardized clinical endpoints and operationalization of severe endpoints. Most respondents (67%) felt there is utility for moderate severity endpoints, but cited challenges in their development. Hospitalization as a moderate endpoint of disease severity or measure of public health impact was deemed to be useful by only 47% of respondents, but 89% felt it could bring about supplemental information if carefully contextualized according to data collection setting. Over half of the respondents favored alignment of the standard endpoints with the WHO guidelines (58%), but cautioned that the endpoints could have ramifications for public health practice. In terms of data granularity of the endpoints, there was a slight preference for a categorical vs numeric system (e.g. 1–10) (47% vs 34%), and 74% of respondents suggested validating the endpoints using large prospective data sets. Conclusion: The structured consensus-building process was successful taking into account the history of the debate around potential endpoints for severe dengue. There is clear support for the development of standardized endpoints for interventional clinical research and the need for subsequent validation with prospective data sets. Challenges include the complexity of developing moderate disease research endpoints for dengue

Spatial repellents: The current roadmap to global recommendation of spatial repellents for public health use.

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

Phylogenetic relationships of Pakistan DENV-1.

<p>Phylogenetic relationships of Dengue viruses type 1 isolated from severe cases in 2011 in Lahore, Pakistan. Numbers at branch nodes indicate maximum likelihood bootstrap values. Underlined virus names represent newly generated sequences. Analyses were based on 505 nts of the envelope gene region. Trees are midpoint rooted. Scale bars indicate nucleotide substitutions per site.</p

New Dengue Virus Type 1 Genotype in Colombo, 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

Emergence and Diversification of Dengue 2 Cosmopolitan Genotype in Pakistan, 2011

10.1371/journal.pone.0056391PLoS ONE83

Phylogenetic relationships of Pakistan DENV-2.

<p>Phylogenetic relationships of Dengue viruses type 2 isolated from severe cases in 2011 in Lahore, Pakistan. Numbers at branch nodes indicate maximum likelihood bootstrap values. Underlined virus names represent newly generated sequences. Analyses were based on 2373 nts of the capsid, pre-membrane, and envelope gene region. Trees are midpoint rooted. Scale bars indicate nucleotide substitutions per site.</p

Serologic and virologic confirmation of dengue virus infection in Pakistan patients by age group.

1<p>IgM and IgG specific dengue antibody detected using an in-house Luminex platform based microsphere-bead immunoassay. ²Virus isolation was done by intra-thoracic circulation of mosquitoes. ³Combined IgM, PCR and virus isolation results</p