Po Ying Chia

Severe dengue can damage the liver through unestablished mechanisms. We investigated the role of myeloperoxidase (MPO), a neutrophil enzyme, in dengue through patients, fatal liver samples, and mouse infection models. Observations from two independent clinical cohorts revealed elevated plasma MPO levels in dengue and, in one cohort, MPO was further linked to liver injury markers during the critical phase of disease, whereas livers from dengue fatal cases revealed MPO build-up in the vicinity of CD177+ activated neutrophils. In mice, dengue led to MPO overexpression, oxidative damage, and broad activation of innate and systemic inflammatory pathways in livers. Blocking MPO activity alleviated these and improved survival in one model and delayed disease progression without preventing death in another. These findings establish MPO as a functional mediator of severe dengue-associated liver injury and inflammation, which warrants further preclinical investigation into its hepatic pathogenic mechanism and its validity as target for therapeutic intervention.

Dengue-associated liver injury is common, prognostically significant, and associated with high mortality at severe thresholds. Oxidative stress is a key, potentially modifiable mechanism. N-acetylcysteine has strong biological plausibility and supportive preclinical data, but clinical evidence remains limited, underscoring the need for well-designed randomized trials to inform practice and policy.

Dengue remains a public health concern in Singapore, with endemic transmission and recurring outbreaks. This study presents results from a Singapore-focused subgroup of the Growth and Emerging Markets Knowledge, Attitudes, and Practices (GEMKAP) cross-sectional survey, which assessed public Knowledge, Attitudes, and Practices (KAP) levels related to dengue and prevention. A total of 400 adult respondents from Singapore participated in an online survey conducted between September and October 2022. Overall KAP scores were 48% (Knowledge), 61% (Attitudes), and 36% (Practices). Awareness of dengue transmission was widespread (96% identified mosquitoes as the vector and 97% recognised stagnant water breeding), while fewer respondents recognised the availability of a dengue vaccine (23%) or the absence of a medicinal cure (38%). Trust in the government’s dengue control efforts was high, though respondents practised an average of 5.1 out of 10 recommended prevention measures. Of the respondents, 25% had a high willingness to vaccinate against dengue. Multivariate analysis revealed that positive vaccine perceptions, past dengue experience, automatic motivation, and social opportunity were associated with willingness to vaccinate. Respondents supported a multi-pronged dengue management approach combining education, vector control, and vaccination. Future efforts should integrate behaviour change strategies, enhance multi-stakeholder collaboration, and empower communities to ensure sustainable impact.

Reliable prognostic biomarkers remain an unmet need in dengue. We evaluated urinary neutrophil gelatinase-associated lipocalin and soluble urokinase plasminogen activator receptor for severe dengue prediction in the febrile phase. Urinary neutrophil gelatinase-associated lipocalin and soluble urokinase plasminogen activator receptor demonstrated areas under the receiver operating curve of 0.88 and 0.79, respectively, in discriminating against severe dengue. The noninvasive sampling offers practical advantages as risk stratification tools.

SUMMARY: Dengue is an acute mosquito-borne viral disease that is highly prevalent throughout the tropical world. The geographic footprint of the four dengue viruses (DENV-1 to -4) that cause this disease and their Aedes mosquito vector is expanding, extending into North America and Mediterranean Europe. Furthermore, although dengue has historically been a disease that disproportionately affects children, changing population demographics and increasing travel to and from the tropics have contributed to a growing incidence in adults. Dengue in adults, particularly older adults, brings fresh and complex challenges to case management. Although dengue is now a vaccine-preventable disease, the efficacy profiles of licensed vaccines as well as those in late-stage clinical development suggest that vaccination alone would not fully retard the global expansion of dengue. Other countermeasures, including antiviral drugs, will be needed. This paper reviews the molecular interplay underlying dengue pathogenesis, including from virological and immunological perspectives, which are foundational for developing antiviral therapies and new vaccines. It also reviews the hurdles facing antiviral development and discusses new insights on dengue immunity that can guide the deployment of imperfect vaccines to begin reversing the global burden of dengue.

Dengue, caused by any one of four distinct virus serotypes, is the most rapidly spreading mosquito-borne viral disease worldwide. It is a primary arboviral infection with increasing global incidence, driven by climate change, urbanisation, and the expanding range of Aedes mosquito vectors. Despite growing research interest, outcome and measurement instrument heterogeneity in dengue clinical trials remains high, limiting comparability and evidence synthesis. This project aimed to develop a globally relevant Core Outcome Measurement Set (COMS) for use in dengue clinical trials through international consensus.This consensus study followed COMET and COS-STAD guidelines and was conducted in two phases. Phase I focused on developing a core outcome set (COS) through six steps: (1) a systematic literature review; (2) qualitative interviews with people with lived experience of dengue; (3) review by the management group and steering committee; (4) a two-round modified Delphi survey and structured online consensus meetings to finalise the COS for ‘hospitalised’ and ‘early’ stages of dengue. Input from critical care experts informed recommendations for the ‘ICU/HDU’ COS. Phase II involved: (5) targeted review of outcome measurement instruments; and (6) a hybrid international consensus workshop to finalise the COMS.The agreed COMS for ‘hospitalised’ dengue included seven outcomes; the ‘early’ COS includes these plus four more. For critical care trials, use of existing ICU-specific COS was recommended. Unified definitions were developed for nine clinician-reported outcomes.The DEN-CORE COMS provides a consensus-based framework for harmonising outcome selection and measurement in dengue trials, improving comparability and supporting policy and clinical decision-making.

Background In the absence of effective pharmaceutical interventions early in an infectious disease outbreak, non-pharmaceutical measures, especially isolating infected individuals, critically limit its impact. The ongoing COVID-19 pandemic has sparked debates on optimal isolation guidelines. This study proposes a variable isolation period approach (variable-period approach), tailoring isolation durations for distinct population groups with varied viral load dynamics. Methods To compare our variable-period approach with a fixed-period strategy, we developed a simulation model generating synthetic longitudinal SARS-CoV-2 viral load data. The data was generated from the viral dynamics model parameterized using SARS-CoV-2 Delta patient data in Singapore, accounting for age and vaccination status. Results Findings show that age and vaccination status significantly influence viral dynamics, with younger age and vaccination linked to shorter viral shedding durations. The variable-period framework suggests longer isolation lengths for older and unvaccinated individuals. By setting the leaking risk (risk of remaining infectious at the end of isolation) below 10%, the optimal fixed-period isolation is 14 days, with an average excess isolation burden of 7.4 unnecessary days. In contrast, the variable-period guideline reduces the excess isolation burden to 6.0 days, with the optimal isolation periods ranging from 9 to 16 days, depending on the population group. We confirmed similar results when we used the effective reproduction number as an alternative to the leaking risk. Conclusions In this case, study using the SARS-CoV-2 Delta variant, our analysis demonstrates that unnecessary time spent in isolation can be reduced by adopting variable-period guidelines based on patient characteristics.