Kids are virus factories...

UPDATE #1: 06JUL2016

Ms. Mohinder Sarna and Associate Professor Lambert have just recently published some cool data from a large and very heavily sampled respiratory virus-related study.

The new report comes from a large birth cohort study entitled the Observational Research in Childhood Infectious Diseases (ORChID) study. 

ORChID is a "longitudinal community-based dynamic birth cohort study of ARI [acute respiratory infection] episodes in children from birth to 2 years of age in the subtropical city of Brisbane, Australia". The study followed babies until they were two years old, taking weekly - yes, WEEKLY! - respiratory swabs and dirty nappy swabs and then tested the heck out of them for known viruses and bacteria. 

The testing results are not part of this report so use of the term "infection" is presumptive. For this study I would have preferred ARI=acute respiratory illness; URTI-upper respiratory tract illness; LRTI-lower respiratory tract illness. But infection is being used in the sense of the clinical picture, where a long history of literature and prior knowledge informs a medical doctor's definition of these acute illnesses as most likley due to virus infection. 

The details of the study's intentions were previously spelt out in Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study.[1]

But the topic of this post is the latest publication from this cohort study: The Burden of Community-Managed Acute Respiratory Infections in the First 2-Years of Life.[2; unfortunately it's paywalled but abstract is visible]. 

I'm not reviewing the whole thing today, I just wanted to pick out a couple of bits and a figure because it really exemplifies how often our little darlings become ill. These are generally mild illnesses and usually without any long term problems. Of course, that doesn't make the grown-ups on the receiving of an infant with a very transmissible virus all that much happier!

A couple of interesting things:

• this is a community rather than hospital-based study which gives us a real snapshot of what happens in normal life - interpret that with the knowledge that infants were "from families of more advantaged backgrounds, which is common in longitudinal cohort studies"
• otherwise healthy infants in this cohort had a distinct illness every 2 months on average; fewer during the first 6 or so months but more after that 
• sampling density is phenomenal - weekly samples. Also a good participant retention rate and 78% of expected days were captured
• antibiotics were prescribed in 21.9% of all ARI episodes - usually for acute otitis media (middle ear infection), and more often for a LRTI than an URTI
• when antibiotics were prescribed for upper respiratory tract illnesses (well known to be overwhelmingly viral in nature and thus not targeted by an antibacterial drug), it was most often in family physician visit older male doctors
  Note: Table 4 in the paper should not have had "Antibiotics" indented-personal communication with thanks to A/Prof Lambert for clarifying
• some minor illness may have been missed because symptoms including fever, mood change and poor feeding are hard to measure in this very young age group.
  "I say mother, I'm feeling a tad peaked this morning". Umm, no. More like "Waaah!"

Copyright © 1999-2016 John Wiley & Sons, Inc. All Rights Reserved.
Publication: Pediatric Pulmonology; Content Title: The burden of
community-managed acute respiratory infections in the first 2-years of life;
Content authors: Mohinder Sarna,Robert S. Ware,Theo P. Sloots,
Michael D. Nissen, Keith Grimwood,Stephen B. Lambert.[2]
Reprinted with permission granted by Dr Sarna and RightsLink. License No. 3902730655132. Click on image to enlarge.

It will also be really interesting to see how often these children are infected but without a measurable illness resulting. 

What will the total number of infections look like in a year, in the community, among young children? More than a single infection every 2 months is my (highly biased) bet. That paper is coming, but unlike winter, it is not yet here.

Disclosure...

I have also been a little involved with this study during my previous life, as acknowledged elsewhere.[1]

References...

1. Observational Research in Childhood Infectious Diseases (ORChID): a dynamic birth cohort study.
   http://bmjopen.bmj.com/content/2/6/e002134.long
2. The Burden of Community-Managed Acute Respiratory Infections in the First 2-Years of Life.
   http://onlinelibrary.wiley.com/doi/10.1002/ppul.23480/abstract

Updates...

1. Author title changes

Keep calm and call the lab...without it, you know less than you think you do [UPDATED x2]

This morning there are 2 symptomatic healthcare workers (HCWs) in the United States (of America; I'm just going to use the "US" from from here on) who came into contact with the recently diagnosed MERS-CoV positive 44M (age and sex confirmed yet?) imported case.

The news has driven something of a twitter storm in the #MERS channel. Not unexpected I guess. The implication is that these 2 have acquired MERS-CoV from contact with the imported MERS-CoV-positive person. 

But that link is still far from proven yet. [UPDATE: both HCWs tested negative for MERS-CoV [1]]

This is a slightly revised version of that which I posted 18-March.
Thanks to Dr K Arden for helpful advice.
Click on image to enlarge.
VDU images are free to re-use. I can provide a better quality if needed.
Please just cite Dr Ian M Mackay, and this blog, http://virologydownunder.blogspot.com.au/,
if used elsewhere.

...Something to remember, or become aware of...

There are >200 known human viruses that have at one time or another been linked to patients with signs and symptoms that defined an 'influenza-like illness" (ILI). No-one can predict what these HCWs are infected with, but they have been or currently are infected by something. Lab tests are essential to know this.

I've asked Orlando Health's social media team (@orlandohealth) if these 2 HCWs are also being tested for the more "standard" 8 or 9 endemic human respiratory viruses/virus groups in parallel with MERS-CoV testing. I'll update this post with what I learn.

These standard viruses include influenzaviruses (A and B; red above), respiratory syncytial virus (dark pink), adenoviruses (orange), human metapneumovirus (pale pink) and parainfluenzaviruses 1, 2, 3 (purple). I'd also hope the rhinoviruses (in green above) since they are numerous and a frequent cause of ILI that can confound the very broad ILI tag. This panel of viruses comprise a standard testing menu which may be further extended, or shrunk, depending on the lab and they are included in commercial PCR-based kits. 

Keep in mind too that a positive PCR (if that's what is used) result does not mean the virus found is the cause of the illness. It may be that another virus, that has since dropped below the limit of assay detection was the cause, or a couple of viruses working in series or parallel, or a virus & bacterium working in synergy or a virus that wasn't tested for, or a virus that is not even known yet...pant.

But if these 2 HCWs do test positive for the MERS-CoV, it's not all that unexpected. Respiratory viruses on the scale you see above have not co-evolved with us/been introduced to us recently because they are easy to get rid of or stop from spreading between/to us.

MERS-CoV is just one of a long line of (probable) respiratory viruses that keep taking us to school to teach us just how sneaky and effective they can be at spreading and just how much our preconceptions trip us up, letting them finish with the best grade.

To stop the spread of them in an environment full of sick people, like a hospital, or even a school, a daycare centre, a long term care facility, a cruise ship, a plane, bus, or even a living room, is no mean feat. It's worth remembering that no single virus does only one thing. There is no "pneumonia virus", no "bronchitis virus", there's not a "common cold virus", there's no "droplet-only" spread, there's not "only replicates in nasal cells", there are just respiratory viruses and their very complex multicellular hosts. I'm happy to argue any of these points, but come prepared to show me that every avenue has been exhausted to support your argument beforehand. I'll give you the drum right now, they really haven't.

Respiratory viruses can each do lots of things and the outcome on our health is heavily determined by us; our previous exposures, our age, our general health, our maternal antibody levels, our underlying diseases, our genetic makeup, our environment, our climate, our animal and human contacts, our personal hygiene and our habits.

End of monologue.

Reference...

1. http://www.flutrackers.com/forum/showpost.php?p=534975&postcount=49

Respiratory viruses: the viruses we detect in the human respiratory tract

This post has been moved to the new Virology Down Under platform on Wordpress.

You can get to this specific post by clicking on the link below...
 
https://virologydownunder.com/respiratory-viruses-the-viruses-we-detect-in-the-human-respiratory-tract/

Please adjust your bookmarks.

Apologies for any inconvenience.

RSV retreated, flu fading, parainfluenza picking up: Queensland respiratory virus numbers up to Week 45, 2013

If you like to keep track of influenza cases in Queensland, Australia, then the Queensland Government's Queensland Health (QH) influenza data website is for you.

It's a great place to drop by and check out the comings and goings of influenza viruses and many of the other traditional respiratory viruses including adenoviruses (AdVs), parainfluenzaviruses (PIVs) 1, 2 and 3, human metapneumovirus (MPV) and respiratory syncytial virus (RSV) - the "Big8". Testing is not routinely conducted for the rhinoviruses (RVs).

The snippet below is from data that are publicly reported on the QH website. These images cover to the week beginning 3rd of November (up to Sunday, Nov 10th, 2013).

The charts highlight that the 2013 flu season is winding down in Australia, also reflected by the WHO global updates. This year flu followed on from what seemed to have been a large RSV season. Unfortunately I couldn't find data for this same time period last year to compare RSV prevalence.

In the wake of influenzavirus season, the parainfluenzaviruses are now on the rise in the lead up to summer. I expect the RVs (and enteroviruses) are also climbing, but in greater numbers.

Click to enlarge. 
A snippet from the Queensland Health Statewide Weekly Influenza Surveillance Report for 01.01.2013-10.11.2013

My thanks to the team at the Communicable Diseases Unit, Queensland Health.

The source of these data  can be read in full..

• http://www.health.qld.gov.au/ph/cdb/sru_influenza.asp
• WHO global influenza update http://www.who.int/influenza/surveillance_monitoring/updates/latest_update_GIP_surveillance/en/

Healthcare workers may stay on the job when ill and can be shedding viral RNA...

In a prospective study in the journal Infection Control and Hospital Epidemiology, Esbenshade and colleagues described their analysis of 319 samples from a cohort of ill (119) and asymptomatic (200) healthcare workers (HCW) serving inpatients at Monroe Carell Jr. Children’s Hospital at Vanderbilt (MCJCHV) in Nashville, Tennessee, during Nov 16 2009 - April 16 2012. 

This was a 20-week period when influenza was expected to be circulating. Most HCWs had been vaccinated against influenza A(H1N1)pdm09 virus

Nasal (not nasopharyngeal) swabs were collected by a trained staff member every 2-weeks, with extra swabs taken if a period of illness arose in the meantime. Nasopharyngeal swabs (NPS) do yield higher proportions of viral detections but are not pleasant and may have caused study drop-outs among the volunteers so they were not used. 

Influenza viruses, respiratory syncytial virus, rhinovirus (RV), human metapneumovirus (HMPV), parainfluenzavirus (PIV), endemic coronavirus (HCoV), adenovirus, bocavirus and enterovirus shedding was represented by the presence of viral RNA detected using a commercial PCR assay (MultiCode-PLx-RVP). An internal control target, β-actin, was included to monitor the integrity of the extracted nucleic acids. 

A PCR positive is assumed to represent shedding of an infectious virus.

The findings are relevant to my recent rant on prospective testing (seek and you shall find). Some key findings were:

• HCWs often worked despite being ill
• The strongest and most statistically significant risk of finding a virus in a subject was associated with that subject being symptomatic (I'm going to be writing about asymptomatic infections in the coming weeks)
• Only 42 specimens were positive for a virus - mostly RV (33) followed by PIV (4), CoV (4) and HMPV (1) - lower than expected
• Younger age was positively associated with viral shedding while the subject's role as a nurse or a physician was not
• 15% of RV detections were made from asymptomatic subjects - 25% of PIV or HCoV (OC43 and NL63) detections were from this group.
• 85% of RV detections were from symptomatic (ill) subjects

The authors conclude that HCWs should consider avoiding patient care duties while ill and that institutional policies should be updated to reflect this need to limit hospital-acquired infections.

When you test for things, its amazing what gets found and how this can impact on policy, understanding of infectious disease transmission and improved patient management. 

This is also a timely reminder that issues around infection prevention and control (IPC) are in no way limited to the management of newly emerged viruses like H7N9 or MERS-CoV. IPC is a problem the world over and it requires constant vigilance to stay ahead of. I commend the authors for this study.