Diagnostic performance of the WHO definition of probable dengue within the first 5 days of symptoms on Reunion Island.

The relevance of the World Health Organization (WHO) criteria for defining probable dengue had not yet been evaluated in the context of dengue endemicity on Reunion Island. The objective of this retrospective diagnostic study was to evaluate the diagnostic performance of the 2009 WHO definition of probable dengue and to propose an improvement thereof. From the medical database, we retrieved the data of subjects admitted to the emergency department of the University Hospital of Reunion Island in 2019 with suspected dengue fever (DF) within a maximum of 5 days post symptom onset, and whose diagnosis was confirmed by a Reverse Transcriptase Polymerase Chain Reaction (RT-PCR). The intrinsic characteristics of probable dengue definitions were reported in terms of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-), using RT-PCR as the gold standard. Of the 1,181 subjects who exhibited a positive RT-PCR, 652 (55%) were classified as probable dengue. The WHO definition of probable dengue yielded a sensitivity of 64% (95%CI 60-67%), a specificity of 57% (95%CI 52-61%), a LR+ of 1.49 (95%CI 1.33-1.67), and a LR- of 0.63 (95%CI 0.56-0.72). The sensitivity and LR- for diagnosing and ruling out probable dengue could be improved by the addition of lymphopenia on admission (74% [95%CI: 71-78%] and 0.54 [95%CI: 0.46-0.63] respectively), at the cost of slight reductions of specificity and LR+ (48% [95%CI: 44-53%] and 1.42 [95%CI: 1.29-1.57], respectively). In the absence of, or when rapid diagnostic testing is unreliable, the use of the improved 2009 WHO definition of probable dengue could facilitate the identification of subjects who require further RT-PCR testing, which should encourage the development of patient management, while also optimizing the count and quarantine of cases, and guiding disease control

Harness risk stratification of diabetic patients with dengue in a cohort study

Background: Identifying predictors of severe dengue (SD) is key for triage and management of patients as well as for advising travellers to countries where dengue is endemic. In this, meta-analyses have raised diabetes mellitus as a risk factor for SD and a prognostic factor for dengue-related mortality. The purpose of this study was to assess whether diabetic patients (DPs) are at increased risk for SD in comparison to non-diabetic patients (NDPs) in a setting of high prevalence of type 2 diabetes mellitus and increasing endemicity for dengue. Methods: In a cohort study conducted during the 2019 dengue epidemic on Reunion Island, we estimated the risk ratios (RR) of DPs for SD (WHO 2009 definition), hospitalisation, intensive care unit (ICU) admission, critical care need or death in the ICU, and scales rating severity or multiple organ dysfunction syndrome (MODS), among confirmed cases of dengue (positive RT-PCR or NS1 antigen). Results: In a Poisson regression model adjusted for age, gender and comorbidity, DPs were more likely to develop SD (adjusted RR: 1.46, 95%CI 1.10–1.95), to be hospitalised, admitted to the ICU, and need critical care or die in the ICU. Subgroup analyses identified female DPs, non-elderly DPs (< 65 years) and DPs with low Charlson score (< 3) to be at higher risk for SD, the two first subgroups trough more severe presentation (higher Simplified Acute Physiology Score-2 values; higher MODS scores, respectively). Male gender, age less than 65 years and mixed comorbidity were identified as prognostic factors for critical care need or death in the ICU, male and non-elderly DPs being more likely to develop MODS than their non-diabetic counterparts. Conclusions: Together, these data highlight the role of diabetes mellitus in the progression from dengue to SD through higher severity per se or the event of MODS

STARD flow diagram 2009 WHO probable dengue definition.

WHO, World Health Organization; RT-PCR, Reverse Transcriptase Polymerase Chain Reaction.</p

Independent predictive factors for RT-PCR (Reverse Transcriptase Polymerase Chain Reaction) positivity.

Independent predictive factors for RT-PCR (Reverse Transcriptase Polymerase Chain Reaction) positivity.</p

Description of the study population on the variables retained by the optimal classification tree.

Description of the study population on the variables retained by the optimal classification tree.</p

Diagnostic performance of probable dengue definitions.

Diagnostic performance of probable dengue definitions.</p

STARD flow diagram Improved 2009 WHO probable dengue definition.

WHO, World Health Organization; RT-PCR, Reverse Transcriptase Polymerase Chain Reaction.</p

Description of the study population on variables associated with RT-PCR (Reverse Transcriptase Polymerase Chain Reaction).

Description of the study population on variables associated with RT-PCR (Reverse Transcriptase Polymerase Chain Reaction).</p

Partnership for Research on Ebola VACcination (PREVAC): protocol of a randomized, double-blind, placebo-controlled phase 2 clinical trial evaluating three vaccine strategies against Ebola in healthy volunteers in four West African countries

International audienceAbstract Introduction The Ebola virus disease (EVD) outbreak in 2014–2016 in West Africa was the largest on record and provided an opportunity for large clinical trials and accelerated efforts to develop an effective and safe preventative vaccine. Multiple questions regarding the safety, immunogenicity, and efficacy of EVD vaccines remain unanswered. To address these gaps in the evidence base, the Partnership for Research on Ebola Vaccines (PREVAC) trial was designed. This paper describes the design, methods, and baseline results of the PREVAC trial and discusses challenges that led to different protocol amendments. Methods This is a randomized, double-blind, placebo-controlled phase 2 clinical trial of three vaccine strategies against the Ebola virus in healthy volunteers 1 year of age and above. The three vaccine strategies being studied are the rVSVΔG-ZEBOV-GP vaccine, with and without a booster dose at 56 days, and the Ad26.ZEBOV,MVA-FN-Filo vaccine regimen with Ad26.ZEBOV given as the first dose and the MVA-FN-Filo vaccination given 56 days later. There have been 4 versions of the protocol with those enrolled in Version 4.0 comprising the primary analysis cohort. The primary endpoint is based on the antibody titer against the Ebola virus surface glycoprotein measured 12 months following the final injection. Results From April 2017 to December 2018, a total of 5002 volunteers were screened and 4789 enrolled. Participants were enrolled at 6 sites in four countries (Guinea, Liberia, Sierra Leone, and Mali). Of the 4789 participants, 2560 (53%) were adults and 2229 (47%) were children. Those < 18 years of age included 549 (12%) aged 1 to 4 years, 750 (16%) 5 to 11 years, and 930 (19%) aged 12–17 years. At baseline, the median (25th, 75th percentile) antibody titer to Ebola virus glycoprotein for 1090 participants was 72 (50, 116) EU/mL. Discussion The PREVAC trial is evaluating—placebo-controlled—two promising Ebola candidate vaccines in advanced stages of development. The results will address unanswered questions related to short- and long-term safety and immunogenicity for three vaccine strategies in adults and children. Trial registration ClinicalTrials.gov NCT02876328 . Registered on 23 August 2016