Minimal Transmission in an Influenza A (H3N2) Human Challenge-Transmission Model with Exposure Events in a Controlled Environment

Autor: Jonathan S. Nguyen-Van-Tam, Ben Killingley, Joanne Enstone, Michael Hewitt, Jovan Pantelic, Michael Grantham, P. Jacob Bueno de Mesquita, Robert Lambkin-Williams, Anthony Gilbert, Alexander Mann, John Forni, Catherine J. Noakes, Min Z. Levine, LaShondra Berman, Stephen Lindstrom, Simon Cauchemez, Werner Bischoff, Raymond Tellier, Donald K. Milton, EMIT Consortium Group
Rok vydání: 2019
Předmět:
Zdroj: SSRN Electronic Journal.
ISSN: 1556-5068
DOI: 10.2139/ssrn.3457429
Popis: Background: Uncertainty about the relative importance of modes of influenza transmission, particularly airborne droplet nuclei (aerosols), fuels controversy concerning recommendations for healthcare worker protection during pandemics. In-depth review by an expert panel, a proof-of-concept study, and an international workshop concluded that human challenge-transmission studies in well-controlled environments would be the most promising approach to fill this critical knowledge gap. Methods: Healthy, seronegative volunteer 'Donors' (N=52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2). Seronegative 'Recipients' randomised to Intervention (IR, N=40) or Control (CR, N=35) groups were exposed to Donors for four days. IRs wore face shields and hand sanitised frequently to limit large droplet and contact transmission. Numbers of Donors and days of Recipient exposure were increased compared to proof-of-concept to increase secondary attack rate (SAR). Symptoms were monitored and viral shedding in nasopharyngeal swabs and exhaled breath viral aerosols were quantified by reverse-transcriptase PCR (qRT-PCR). Serological specimens were analysed for evidence of seroconversion. Findings: Intranasal inoculation produced an infection rate of 81% (42/52); 60% (25/42) of infected Donors had influenza-like illness, 14% (6/42) had fever, and 26% (11/42) had mild or no symptoms. Viral aerosol shedding was observed from 26% (11/42) of the infected Donors. One transmitted infection was confirmed by serology in a CR, yielding a SAR of 2·9% among CR, 0% in IR (p = 0·47 for group difference), and 1·3% overall. Interpretation: The SAR observed was significantly less than 16% (p
Databáze: OpenAIRE