Development of Ebola virus disease prediction scores: Screening tools for Ebola suspects at the triage-point during an outbreak.

BACKGROUND: The control of Ebola virus disease (EVD) outbreaks relies on rapid diagnosis and prompt action, a daunting task in limited-resource contexts. This study develops prediction scores that can help healthcare workers improve their decision-making at the triage-point of EVD suspect-cases during EVD outbreaks. METHODS: We computed accuracy measurements of EVD predictors to assess their diagnosing ability compared with the reference standard GeneXpert® results, during the eastern DRC EVD outbreak. We developed predictive scores using the Spiegelhalter-Knill-Jones approach and constructed a clinical prediction score (CPS) and an extended clinical prediction score (ECPS). We plotted the receiver operating characteristic curves (ROCs), estimated the area under the ROC (AUROC) to assess the performance of scores, and computed net benefits (NB) to assess the clinical utility (decision-making ability) of the scores at a given cut-off. We performed decision curve analysis (DCA) to compare, at a range of threshold probabilities, prediction scores' decision-making ability and to quantify the number of unnecessary isolation. RESULTS: The analysis was done on data from 10432 subjects, including 651 EVD cases. The EVD prevalence was 6.2% in the whole dataset, 14.8% in the subgroup of suspects who fitted the WHO Ebola case definition, and 3.2% for the set of suspects who did not fit this case definition. The WHO clinical definition yielded 61.6% sensitivity and 76.4% specificity. Fatigue, difficulty in swallowing, red eyes, gingival bleeding, hematemesis, confusion, hemoptysis, and a history of contact with an EVD case were predictors of EVD. The AUROC for ECPS was 0.88 (95%CI: 0.86-0.89), significantly greater than this for CPS, 0.71 (95%CI: 0.69-0.73) (p < 0.0001). At -1 point of score, the CPS yielded a sensitivity of 85.4% and specificity of 42.3%, and the ECPS yielded sensitivity of 78.8% and specificity of 81.4%. The diagnostic performance of the scores varied in the three disease contexts (the whole, fitting or not fitting the WHO case definition data sets). At 10% of threshold probability, e.g. in disease-adverse context, ECPS gave an NB of 0.033 and a net reduction of unnecessary isolation of 67.1%. Using ECPS as a joint approach to isolate EVD suspects reduces the number of unnecessary isolations by 65.7%. CONCLUSION: The scores developed in our study showed a good performance as EVD case predictors since their use improved the net benefit, i.e., their clinical utility. These rapid and low-cost tools can help in decision-making to isolate EVD-suspicious cases at the triage point during an outbreak. However, these tools still require external validation and cost-effectiveness evaluation before being used on a large scale.

Antibacterial mouthwash to prevent sexually transmitted infections in men who have sex with men taking HIV pre-exposure prophylaxis (PReGo): a randomised, placebo-controlled, crossover trial.

BACKGROUND: Bacterial sexually transmitted infections (STIs) are highly prevalent among men who have sex with men who use HIV pre-exposure prophylaxis (PrEP), which leads to antimicrobial consumption linked to the emergence of antimicrobial resistance. We aimed to assess use of an antiseptic mouthwash as an antibiotic sparing approach to prevent STIs. METHODS: We invited people using PrEP who had an STI in the past 24 months to participate in this single-centre, randomised, double-blind, placebo-controlled, AB/BA crossover superiority trial at the Institute of Tropical Medicine in Antwerp, Belgium. Using block randomisation (block size eight), participants were assigned (1:1) to first receive Listerine Cool Mint or a placebo mouthwash. They were required to use the study mouthwashes daily and before and after sex for 3 months each and to ask their sexual partners to use the mouthwash before and after sex. Participants were screened every 3 months for syphilis, chlamydia, and gonorrhoea at the oropharynx, anorectum, and urethra. The primary outcome was combined incidence of these STIs during each 3-month period, assessed in the intention-to-treat population, which included all participants who completed at least the first 3-month period. Safety was assessed as a secondary outcome. This trial is registered with Clinicaltrials.gov, NCT03881007. FINDINGS: Between April 2, 2019, and March 13, 2020, 343 participants were enrolled: 172 in the Listerine followed by placebo (Listerine-placebo) group and 171 in the placebo followed by Listerine (placebo-Listerine) group. The trial was terminated prematurely because of the COVID-19 pandemic. 151 participants completed the entire study, and 89 completed only the first 3-month period. 31 participants withdrew consent, ten were lost to follow-up, and one acquired HIV. In the Listerine-placebo group, the STI incidence rate was 140·4 per 100 person-years during the Listerine period, and 102·6 per 100 person-years during the placebo period. In the placebo-Listerine arm, the STI incidence rate was 133·9 per 100 person-years during the placebo period, and 147·5 per 100 person-years during the Listerine period. We did not find that Listerine significantly reduced STI incidence (IRR 1·17, 95% CI 0·84-1·64). Numbers of adverse events were not significantly higher than at baseline and were similar while using Listerine and placebo. Four serious adverse events (one HIV-infection, one severe depression, one Ludwig's angina, and one testicular carcinoma) were not considered to be related to use of mouthwash. INTERPRETATION: Our findings do not support the use of Listerine Cool Mint as a way to prevent STI acquisition among high-risk populations. FUNDING: Belgian Research Foundation - Flanders (FWO 121·00).