Preliminary findings from a randomized controlled trial of the effect of fever suppression by antipyretics on medically attended influenza virus infections

Abstract

BACKGROUND: Being one of the commonest conditions encountered in modern clinical practice, fever is commonly regarded as an illness that has to be treated although objective evidence about it harm is lacking. Evidence is growing to suggest that fever is an important component in the host defense mechanism against viral infections, and suppressing fever might cause more harm than good. Many earlier studies have demonstrated that antipyretic therapy can prolong the duration of illness, suppress humoral antibody responses, and increase the level and duration of viral shedding potentially implying increased onwards transmission of the infection. METHOD: A double-blinded randomized placebo-controlled trial was conducted to investigate the potential benefits and risks of antipyretic use in naturallyoccurring medically-attended influenza virus infections. Healthy adults aged 18-30 years who presented with acute respiratory symptoms within 48 hours of illness onset were recruited from university health clinics in Hong Kong. Recruited patients with positive rapid influenza test result were randomized to receive either paracetamol (paracetamol 500mg QID) or placebo. Back-up NSAID (ibuprofen 200mg TDS) was provided to all subjects for intolerable fever when required. Nasal and throat swabs were collected from participants on days 1 (baseline), 4, 7 and 10 for quantitative RT-PCR analysis. Participants recorded their temperature and symptoms in daily diaries from day 1 to 10. The primary outcomes were the time from recruitment to (1) cessation of detectable viral shedding and (2) clinical illness resolution. RESULTS: As of 30 April 2015, 140 participants were enrolled into the trial and 6 were lost to follow up. Seventy-eight participants were PCR-positive for influenza on their day 1 swab sample including 40 and 38 participants randomized into the treatment and placebo group respectively. The mean duration of viral shedding in the treatment group was 7.8 days compared to 6.1 days in the placebo group (p=0.02). No significant difference was detected between the groups in the time to clinical illness resolution. Recruitment is currently ongoing to achieve our target sample size of 150 patients in each group. CONCLUSION: Our preliminary findings indicate that antipyretic treatment of medically-attended influenza virus infection could prolong the duration of virus shedding, while not reducing the duration of illness. Findings from this study will have important contribution to evidence-based clinical management of medically-attended influenza, and public health strategies to control transmission in the community.