Saturday, 5 November 2016

During the first 4 weeks of life "common cold" viruses occur frequently and can make your little one sick....

UPDATE #1 08NOV2016
Not much is known about the number of, and burden due to, virus infections that happen during the very first four weeks of life - called the "neonatal period".

I've talked previously about the Observational Research in Childhood Infectious Diseases (ORChID) study.[1]

In this post I'm talking about the latest publication it has produced - Respiratory Viruses in Neonates: A Prospective, Community-Based Birth Cohort Study
.[2]

The enrolled cohort and the samples...

From this study, 157/164 enrolled neonates (74 males, 47.1%) provided 574 nasal swab specimens (1-5 per neonate).


These swabs represented 552-weeks of data and represented 88% of the number of parent-collected samples that were expected to be returned by mail-which is good. 

A big thankyou to the parents who took part in this really big study.[3] Weekly sampling is no easy job!

Testing of samples for viruses...

Respiratory viruses were sought in the nucleic acids purified from these swabs using sensitive real-time polymerase chain reaction (rtPCR) techniques. 

Since most respiratory viruses have an RNA genome, we often added a reverse-transcription step (RT-rtPCR). 

The viral targets were:
  • rhinoviruses (RVs)
    • we also sought out the species and genotype of each RV using a nested, conventional RT-PCR
  • respiratory syncytial virus (RSV)
  • influenza virus (IFV) A and B
  • parainfluenza virus (HPIV) 1, 2, 3 and 4
  • adenoviruses (AdVs)
  • human metapneumovirus (HMPV)
  • human coronaviruses (HCoV) 229E, OC43, NL63 and HUK1
  • human bocavirus (HBoV) type 1
  • human polyomavirus WU and KI 

Viruses were found from early on...

You can see from the paper's [2] reprinted supplementary figure below, that there is a lot of respiratory virus activity during those first four weeks of new life. 

The first detection of a virus occurred at two days of age and the first infections linked to symptoms occurred during the first week - both infections by distinct viruses belonging to the species Rhinovirus A.

Of 157 neonates, 29 yielded a virus-positive swab. There were 13 ill neonates among the 29 (45% of infected neonates), 3 others who did not return symptom diaries and 13 neonates (45%) who remained asymptomatic, despite the finding of a virus up their nose.

Rhinovirus detection: with and without illness...

Among the 29 neonates shown, 21 had at least 1 RV infection during the first four weeks of life. This resulted in 31 RV(+) specimens. 

Unfortunately there were a fair number of completely untypeable RVs (white boxes). There were also some genotypes that did not match up with a previously described type at the time of the analysis (black boxes). These will require further study to sequence the viral protein 1 (VP1) region - or their entire genome - to get a better of idea of what they are and whether they are previously unknown RVs.

Among the 21 RV positive neonates (72% of all neonates)...

  • 8 had symptoms (38% of RV positive neonates)
  • 3 did not return symptom diaries (14%)
  • 10 did not have symptoms.
    These 10 RV infections represent 48% of the 21 positive neonates, or 56% of those who returned diaries. 

An RV(+) sample was considered linked to a symptomatic episode if it was collected 7-days before or after the episode.

Figure reprinted on Virology Down Under blog with
permission
from Wolters Kluwer. Source is Supplementary Digital
Content Fig 1 from “Respiratory Viruses in Neonates: A Prospective,Community-Based Birth Cohort Study.”
Pediatric Infectious Disease Journal, 2016. [1]

http://journals.lww.com/pidj/Abstract/publishahead/Respiratory_Viruses_in_Neonates___A_Prospective,.97285.aspx




While RVs are often burdened by tales of glorious wimpiness, that does not usually hold up to close scrutiny. 

It also turned out that in our study, RVs were not the only viruses to be detected in the absence of any symptoms. The only detections of RSV, IFV B and HCoV-NL63 were also made in the absence of any symptoms. 

Summary...

Most of the neonates had at least one virus detected during the first four weeks of life, but only 40% showed any obvious signs of illness. 

Rhinoviruses were the most frequently detected viruses and 38% of infected neonates were linked to an illness. Other viruses - like RSV and an IFV - sometimes attributed to much more severe disease, were found less frequently than RVs and when detected, did not seem to have caused symptoms. 

Respiratory virus infections start from birth and most do not cause symptoms in the neonatal period. But you can be sure these infections are teaching the newly developing immune systems all about the tiny invaders they will face for the rest of their 'lives'. These encounters create the immunological tools we all need to defend against a world shared by many challenges.

References...
  1. Kids are virus factories...
    http://virologydownunder.blogspot.com.au/2016/07/kids-are-virus-factories.html
  2. Respiratory Viruses in Neonates: A Prospective, Community-Based Birth Cohort Study.
    Sarna, M,  Alsaleh, A, Lambert SB, Ware, RS, Mhango, LP, Mackay, IM, Whiley DM, Sloots TP, Grimwood K. Published ahead of print. Pediatric Infectious Disease Journal, 2016.
    http://journals.lww.com/pidj/Abstract/publishahead/Respiratory_Viruses_in_Neonates___A_Prospective,.97285.aspx
  3. The nose knows – even newborns get viruses
    https://www.uq.edu.au/news/article/2016/10/nose-knows-%E2%80%93-even-newborns-get-viruses
Updates...
  1. Text altered to clarify RV symptomatic vs asymptomatic episode numbers

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