Friday, 29 November 2013

Rhinovirus (RV) transmission by aerosol: does it happen or is transmission solely by hand-contact and self-inoculation?

I'll be writing a few posts over the coming weeks based in the papers I've found on this topic of RV transmission. How applicable these study results are to transmission of other respiratory viruses is unknown.

The focus will be on answering the question of "Do rhinoviruses transmit by an aerosol route?" The endpoint is usually the development of a clinical upper respiratory tract infection (URTI) or "common cold". 

A lot of volunteer human infection experiments have been conducted using RVs since their identification 60-years ago. This is likely because RVs were seen to cause only mild illness, reducing the health risk for human volunteers. Less common were influenza studies of this sort (correct me if I'm wrong though). It's also worth noting that adults rather than children were included, so the true spectrum of RV disease was not observed. 
From Elliot Dick et al, the Journal of
Infectious Diseases
 

Author: Elliot Dick et al
Journal:  J Infect Dis 156(3):442-448
Year: 1987
RV type used: RV-A16
RV receptor type: major group; ICAM-I

This study set out to see whether RV was transmitted by aerosol, indirect contact, or both.

Key features of the study layout..

  • 27-34 males >18-years of age were inoculated intranasally with 56-2,500 TCID50 of safety tested1 RV-A16 on 2 successive days.
  • 8-days after inoculation, the 8 cases with the most severe URTIs played cards with 12 RV-B16 neutralizing antibody-free males for ~12-hours in a room containing 4 tables spaced 1.4m apart.
  • Each table seated 2 "donors" and 3 "recipients" and the recipients moved locations each hour. Donors were replaced with fresh donors if their URTIs waned
  • Coughs, sneezes, nose blows and hand-to-face movements were monitored
  • Acquisition of a separate infection during meal times was eliminated by staggering their egress and entry into the card-playing room and by seating recipients 50ft (15m) apart in a well-ventilated room
  • 4 experiments, A-D, were performed.
    • Experiment A-C tested aerosol transmission.
      • 6/12 males used cloth handkerchiefs; the remaining 6 were restrained from any hand-to-head movements
      • In experiment A, a 3ft (1m) plastic collar was worn around the neck
      • In experiment B and C, arm restraints were used
    • Experiment D utilised Experiment C's contaminated furniture and card playing equipment, moving it all into a 2nd card playing room. 
      • 12 new recipients were immediately introduced to the room for 12-hours of poker with exaggerated hand-to-face movements
      • Card-playing equipment was exchanged between rooms each hour to keep the contaminant levels high
      • All meals were eaten in the experiment room to avoid contact with any donors
  • After the 12-hour game, recipients returned to the laboratory each day for 2-weeks to provide nasal washings and record symptoms. If they were symptomatic they were taken to a separate laboratory for sampling.
  • Exaggerated exposures of "sentinel" recipients consisted of recipients present during the donor's nasal wash collections or undertaking nasal washing alongside symptomatic recipients
  • Nasal washing were collected into Hanks balanced sslt solution (HBSS) medium with 0.5% gelatin and inoculated onto WI-38, Hep-2 and primary rhesus monkey kidney cells within 4-hours after collection
Key results included...
  • Experiment A: 11/2 recipients were infected, 5 by aerosol alone
  • Experiment B: 6/12 infected, 1 by aerosol alone
  • Experiment C: 5/12 infected, 4/5 in the restrained recipients
  • 12/18 (67%) control recipients (could be infected by any route) were infected versus 10/18 (56%) restrained recipients
    • infected recipients were symptomatic and shed virus for ≥1-day 
  • Experiment D: no infections but 5/8 donor hands yielded culturable RV-A16 virus while none of the recipient's hands did
  • No sentinel recipients became symptomatic
The authors concluded...
  • Aerosol transmission was the most important  mechanism of natural spread of RV in adults in this study
  • Aerosol transmission was nearly as efficient as transmission by combined aerosol/direct contact/indirect contact
  • RV-A16 load declined rapidly to near zero on the journey between donor and the nose of the recipient.
  • Virus shedding in a recipient was usually first detected 3-days after proximity to the donor

The authors raised some interesting points...
  • Some previous studies to defining that RV transmission was primarily due to fomite and droplet contact may have failed to detect a small and large aerosol modality because recipient exposure was too short or to too small a viral inoculum
  • In a previous study by these authors, the donor had to have a mild to moderate URTI, in which they shed ≥103 TCID50/ml, before transmission reached the desired endpoint
  • Brief, casual exposures to an infected RV case infrequently results in adequate transmission as measured by occurrence of a symptomatic episode
  •  Exposure by direct inoculation with fresh nasal secretions is practically unlikely
Further reading and references...
  1. Safety testing of RV preparations.
    D'Alessio et al. J Infect Dis. 1976;133:28-36.