Respiratory syncytial virus (RSV) in Australia – worth not(ify)ing

Once upon a time, we grew viruses from sick patients’ samples. This took an age, failed often, had low throughput and was not a good diagnostic tool. Then we developed PCR and could find RSV cases more quickly, among more people, more sensitively and very accurately. We’ve been doing that in Australia since the 1990s. Reporting of these detections only became notifiable in 2021, which means RSV-positive results now have to be reported, and better data can be (confidentially) collected about the cases. Let’s dig into the 2023 RSV buzz.

Notifiable diseases in Australia

Notifiable diseases (often this is about reporting detection of the pathogens that cause the disease) get reported and captured by official lists as soon as identified. There are State (e.g. Queensland) and Territory (e.g. the Northern Territory) lists and the National list. We diagnose a notifiable disease based on a case definition. A confirmed case relies heavily on definitive laboratory-based evidence of the presence of the causative agent, whereas a Probable case may only require clinical and epidemiological evidence, e.g. Pertussis (whooping cough; Ver 1.0. 2004). A confirmed Measles case (Ver 1.1. 15 MAY 2019), for example, can be defined using either laboratory evidence or clinical plus epidemiological evidence.

A newly notifiable disease – RSV

Some media coverage about Australia’s many RSV cases in 2023 was a bit loud and off the mark. It could easily have been perceived as worrying by some. It has made it seem like we don’t know anything about RSV; we weren’t tracking it, and this year is the worst ever before it became a notifiable disease In July 2021.[1]

The surveillance case definition for respiratory syncytial virus (RSV) infection, which is a nationally notifiable infection within Australia.
The surveillance case definition for respiratory syncytial virus (RSV) infection, which is a nationally notifiable infection within Australia[1]

When budgets allow, making a disease notifiable may also trigger increased testing capacity or changes in ‘promoting’ existing testing to increase the identification of cases of the pathogen causing the notifiable disease. The aim is usually to understand better the pathogen’s transmission, season, and impacts. In this case, we’ll be seeing vaccination of the elderly and children in the not-too-distant future, so it will be essential to know more about RSV before this and once vaccination begins.

I completely understand that you may never have heard of this virus, but just so we’re on the same page, we haven’t just discovered RSV.

RSV was identified in the 1950s but caused disease long before then

Human RSV and bovine RSV are estimated to have broken away from a common viral ancestor about 450 (based on an F gene analysis [9]) to 921 (based on a G gene analysis [10]) years ago. We don’t have any sequences from back then, so modelling and estimation are based on the genome sequences we have now. The two RSV subgroups or ‘types’ that exist today, RSV-A and RSV-B, are thought to have split 250 [9] to 338 [10] years ago. Further splits within each type started about 80 years ago [10], and these keep occurring.

We first identified the virus in humans in 1957. Each year at a given location, genotypes change [11] but are not entirely replaced as we often see with influenza.[12] Data from the United States showed that 2.9 in 1,000 (0.29%) children under five years of age may require hospitalisation due to RSV infection. [15] This rate increases to 14.7 per 1,000 (1.5%) among children under six months of age and 25 per 1,000 (2.5%) among those aged one month or less. Most of these hospitalisations were among otherwise healthy children.[15]

We’ve been tracking RSV for a long time.

Granted, lots of the data we have and conclusions we’ve drawn come from research studies rather than ongoing collections of nationwide data, so making RSV a notifiable disease will improve the recording of better data. If you want to see how far back records of other notifiable diseases in Australia go, take a look at this trove of reports!

Graphs of data from RSV in Queensland, 2013.
A 2013 Virology Down Under blog post about RSV in Queensland (from the old blog site).

We have weekly or fortnightly statewide RSV data. I’ll dip into some of my past blog posts to provide evidence that we have even been discussing RSV in social media, not to mention recording the circulation of cases, for over a decade.

In November 2013, I wrote about Queensland’s data and RSV using their report. That report link still works to get you to data that stretches all the way back to 2010! Excellent work, Queensland Health!

Graphs of data from RSV in Queensland, 2014.
A 2014 Virology Down Under blog post about RSV.

Here’s a post from 2014 discussing a big RSV season.

Not to be outdone, New South Wales Health has influenza virus epidemiology report archives from 2009! These reports also include other respiratory virus data.

A table of data from RSV in New South Wales, 2009.

The patterns and impacts of RSV and its big and little seasons are unsurprising to professionals, experts and interested virus watchers. This is all to say the media may be breathless about a big season, but this is not a new virus on the block. And guess what? RSV is a respiratory virus that can be spread through an airborne route, so the same ways you can reduce your risk of SARS-CoV-2 infection work here.

RSV transmits via surfaces and aerosols.

In 1975, leading RSV clinician-researchers were still uncertain of precisely how RSV was transmitted, highlighting the lack of evidence to support useful interventions to block the spread within hospitals.[16]

An illustration of a  spherical RSV virion.

Most of what is written about reducing RSV transmission prioritises surfaces, droplets and handwashing over aerosols. In one description, good infection control was described as being “convenient, consistent, pragmatic, and
publicized”…but not effective?[17]

Sometimes, there is no mention of aerosols, although larger droplets do get a mention in the context of rare and the reason for infection that appears to occur without direct contact and only across short distances. With what we now know, I find it hard to believe this old and limited research. I’m not advocating that aerosols are the main route because no research supports that (or discounts it, by the way). But aerosols must be considered in any serious messaging about preventing RSV cases because, as we’ll see below, RSV-laden aerosols absolutely can be a route of infection for cells and animals. That means wearing N95 respirators and cleaning the air should also be listed as necessary for reducing the likelihood of a significant viral dose.

Text from the CDC Website highlighting its ways to reducetransmission.
How to prevent RSV – from the US CDC. No serious consideration of aerosols. https://www.cdc.gov/rsv/high-risk/infants-young-children.html#

A few RSV transmission studies

One example is a paper from 1978.[2] A study of hospital-acquired (nosocomial) RSV infections in which the isolation of infected babies, strict use of handwashing and the wearing of gowns were lauded by the authors as significant (in a mathematical sense) in reducing the rate of nosocomial infections among the babies from 45% to 19%, while among staff, the rate went up from 42% to 56%. The authors suggested this was due to more time spent with the infected babies. Staff may also have acquired RSV from the community during RSV season. But did masks help in reducing the proposed nosocomial spread? Well, they didn’t use masks, as seen below.

Also, since the use of masks routinely is particularly disliked by staff and patients, control of spread of infection without the use of masks was attempted.

Control of Nosocomial Respiratory Syncytial Viral Infections [2]

What’s missing from this and other RSV transmission studies is an explanation of the air exchanges – how often all the air in a room is changed out for a fresh volume. How might that impact the findings and perhaps lead people towards thinking contact is more critical than aerosols at a distance when aerosols may have been more diluted in well-ventilated, often hospital rooms?

Further, the authors decided that aerosols were an unlikely route because this route would cause ‘explosive’ outbreaks. In a later review, the authors refer to this thinking but say that it is more likely a non-touch route would involve larger droplets because of the need for close person-to-person contact in their past research with RSV.[6]

I think we understand now that during a surge of a novel virus/virus variant, not everyone gets infected. Some remain uninfected (which can be shown by measuring antibodies) or at least asymptomatic or too mildly ill to be bothered getting tested.

We also know that aerosols work well up close – it’s a concentration thing, not just a size thing. There are many more aerosol particles close to the source than there are droplets, and overall, both decrease with distance unless the latter are allowed to build up through poor ventilation.

A graphical representation of aerosol density with distance from the emitting source. Too often, people make a massive assumption that up close, the infection source must be virus-laden droplets, when in fact, it’s much more likely to be virus-laden aerosolised particles because they are in higher concentration -there are more of them per volume of air – than droplets, near the source (see the red versus the black dots in the image above. Also, the virus is in higher concentration within the aerosol particles, and they travel further, building up in concentration if the air is not refreshed or filtered.

The other thing to consider here is that RSV is estimated to have been circulating among humans for 900 years, and in that time, becoming an endemic virus, we have all been infected. Usually, our first infection is soon after birth, but we’re re-exposed throughout life. So, remember that any adults in a research study you might read will have years of infections that provide some form of immunity to RSV.

There have been many studies, including this next one from 1981 by two of the same authors, building on their earlier work.[13] It concluded that only volunteers who cuddled (‘cuddlers’) RSV-infected infants (while wearing gowns) and volunteers who touched surfaces exposed to now-removed infected infants, then rubbed their own eyes/nose (‘touchers’) became infected (70% of cuddlers, 40% of touchers). None of the ‘sitters’ who wore a gown and gloves and sat >1.8m from an infected infant and read became infected. Infection was defined here by successful viral culture and antibody testing (serology). Infectious virus was also recovered from at least one surface in each infected infant’s room. Cuddlers became sick quicker and had more severe illnesses than touchers, suggesting a viral dose-related phenomenon. This study concluded that aerosol played a less critical role in RSV transmission and that large droplets and surfaces were possible avenues. The authors noted the focus should be on handwashing, and through studies like this, surfaces and fomites have become the focus of strategies to limit RSV transmission, sometimes with surgical masks thrown in to prevent large droplet contact (i.e. droplets with the apparent precision of a guided missile!). The findings of this study were also leaned on early in a review on RSV transmission in the home, which was, in turn, referred to by at least one textbook.[18] And so it goes. This study did not exclude aerosols, though. Aerosols could have played some role for the cuddlers, and aerosols, moreso than droplets, may also have played a role for the touchers who visited the airspaces where the infants were located before their removal. The study setup showed that distance prevented RSV transmission from these stationary ill infants in this setup. At the end of the day, this study shouldn’t be taken as evidence that a more mobile infected human, or several of them in a poorly ventilated room or household, can’t spread RSV via aerosols. But is there any evidence that infectious RSV remains in aerosols?

RSV and aerosols (the small floaty particles)

Despite a focus on surfaces and handwashing, human RSV most definitely can infect cells via aerosolised particles (exact sizes weren’t described), as was seen when infant Rhesus macaque non-human primates developed the disease after exposure to aerosolised preparations of RSV.[3,4] There is clear evidence that such infection is possible. Nebulised human RSV can also infect newborn lambs, and nebulised bovine RSV was used to infect calves to develop an RSV infection model.[5,7]

RSV aerosol and humans

In support of this route, a study in 2010 captured RSV RNA-laden aerosol particles from the air near infected patients.[14]

A study from 2016 identified infectious RSV from aerosol-sized particles (<10uM) emitted into the air 1m from the head of 10 RSV-infected infants.[8] At 5m from the head of the index case, infectious virus could still be recovered, but at much lower viral loads. This study showed human aerosols are infectious and that distance from the source helps to dilute their impact. The study also showed the virus captured could infect laboratory cells and ciliated nasal cells from healthy volunteers and those with chronic obstructive pulmonary disease.

What have we learned?

RSV has been among humans for a lot of years. We have public testing data from over a decade. It shows RSV can surge into big numbers some years, especially ahead of a flu season (around autumn – usually). We also know (because you’ve been reading this blog, right?) that SARS-CoV-2 and our response to it disturbed the usual RSV season pattern. Now that RSV is a notifiable disease, these data will get better ahead of the widespread use of an RSV vaccine for older adults and soon for children. It will be essential to watch the change in RSV epidemiology. And while we’re told droplets and surfaces are key factors in the transmission of RSV infections, it’s clear – at least to me – that we should be considering removing aerosols instead of droplets when discussing reducing RSV transmission. It might be an inconvenient fact, but it’s a fact nonetheless.

References

  1. Respiratory Syncytial Virus. Australian national notifiable diseases case definition
    https://www.health.gov.au/resources/publications/respiratory-syncytial-virus-surveillance-case-definition?language=en
  2. Control of Nosocomial Respiratory Syncytial Viral Infections
    https://publications.aap.org/pediatrics/article/62/5/728/49183/Control-of-Nosocomial-Respiratory-Syncytial-Viral
  3. A rhesus monkey model of respiratory syncytial virus infection.
    https://pubmed.ncbi.nlm.nih.gov/12110049/
  4. DNA immunization against respiratory syncytial virus (RSV) in infant rhesus monkeys
    https://www.sciencedirect.com/science/article/pii/S0264410X04009120?
  5. Kinetics of Respiratory Syncytial Virus (RSV) Memphis Strain 37 (M37) Infection in the Respiratory Tract of Newborn Lambs as an RSV Infection Model for Human Infants.
    https://pubmed.ncbi.nlm.nih.gov/26641081/
  6. Nosocomial Respiratory Syncytial Virus Infections: The “Cold War” Has Not Ended
    https://pubmed.ncbi.nlm.nih.gov/10987726/
  7. A MODEL FOR RESPIRATORY SYNCYTIAL VIRUS (RSV) INFECTION BASED ON EXPERIMENTAL AEROSOL EXPOSURE WITH BOVINE RSV IN CALVES.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7133857/
  8. Evidence of Respiratory Syncytial Virus Spread by Aerosol. Time to Revisit Infection Control Strategies?
    https://pubmed.ncbi.nlm.nih.gov/26890617/
  9. Detailed Evolutionary Analyses of the F Gene in the Respiratory Syncytial Virus Subgroup A
    https://pubmed.ncbi.nlm.nih.gov/34960794/
  10. Genetic diversity and molecular evolution of human respiratory syncytial virus A and B
    https://pubmed.ncbi.nlm.nih.gov/34155268/
  11. Genetic diversity and molecular epidemiology of respiratory syncytial virus over four consecutive seasons in South Africa: identification of new subgroup A and B genotypes.
    https://www.microbiologyresearch.org/content/journal/jgv/10.1099/0022-1317-82-9-2117
  12. Phylogeny and population dynamics of respiratory syncytial virus (Rsv) A and B
    https://pubmed.ncbi.nlm.nih.gov/24954788/
  13. Modes of transmission of respiratory syncytial virus.
    https://pubmed.ncbi.nlm.nih.gov/7252646/
  14. Distribution of Airborne Influenza Virus and Respiratory Syncytial Virus in an Urgent Care Medical Clinic.
    https://pubmed.ncbi.nlm.nih.gov/20100093/
  15. Respiratory Syncytial Virus-Associated Hospitalizations Among Young Children: 2015-2016.
    https://pubmed.ncbi.nlm.nih.gov/32546583/
  16. Nosocomial Respiratory Syncytial Virus Infections
    https://www.nejm.org/doi/full/10.1056/NEJM197512252932604
  17. The Spread of Influenza and Other Respiratory Viruses: Complexities and Conjectures.
    https://pubmed.ncbi.nlm.nih.gov/17599315/
  18. Transmission of viral respiratory infections in the home.
    https://pubmed.ncbi.nlm.nih.gov/11052396/

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