Wednesday, December 12, 2012

PLoS One: Influenza Viral Shedding & Asymptomatic Infections


Photo Credit PHIL (Public Health Image Library)


# 6776



Despite major advances in the study of influenza viruses, there remain significant gaps in our understanding of just how they work once they infect a human (or any other animal) host. 


Basic questions, such as `How long are we infectious?, or `How common are asymptomatic infections?  remain only partially answered.


Complicating matters, variations in individual host’s immune responses, and different strains of flu may produce varying results. Meaning that most studies can only add incrementally to our knowledge, rather than completely answering these questions.


Previously, we’ve seen evidence of asymptomatic and `presymptomatic’ shedding of influenza viruses.


In 2011, in EID Journal: Pre-Symptomatic Influenza Transmission we looked at three clusters of suspected pre-symptomatic transmission of the 2009 H1N1 virus in Japan.


And in Pre-Symptomatic Transmission Of H1N1 Influenza In the Ferret Model, researchers inoculated ferrets with the 2009 H1N1 flu, and then placed them near uninfected ferrets (some in direct contact, others in adjacent cages) at different stages after infection.


They then tested the exposed ferrets to see when, and under what circumstances, they became infected. They found that ferrets became infectious just 24 hours after becoming infected, and nearly 24 hours before showing the earliest outward signs of infection (fever).



The importance of all of this is, if presymptomatic and asymptomatic carriers of a flu virus are able to efficiently transmit the illness on to others, then strategies that seek to identify and isolate flu cases would have only limited success in containing a pandemic.


Similarly, understanding how long a person sheds the virus after becoming infected is crucial, so we can know when it is (relatively) safe for flu victims to return to work or school without endangering others.


The CDC’s general take on this topic is:


The Flu Is Contagious

Most healthy adults may be able to infect others beginning 1 day before symptoms develop and up to 5 to 7 days after becoming sick. Children may pass the virus for longer than 7 days. Symptoms start 1 to 4 days after the virus enters the body. That means that you may be able to pass on the flu to someone else before you know you are sick, as well as while you are sick. Some persons can be infected with the flu virus but have no symptoms. During this time, those persons may still spread the virus to others.



Yesterday, a new study appeared in PloS One, conducted in Germany over 4 flu seasons (2007-2011) and involving 4 flu strains - seasonal (A(H3N2), A(H1N1), influenza B, and pandemic (A(H1N1)pdm09 - that looks at many of these transmission issues. 


Comparison of Shedding Characteristics of Seasonal Influenza Virus (Sub)Types and Influenza A(H1N1)pdm09; Germany, 2007–2011

Thorsten Suess, Cornelius Remschmidt, Susanne B. Schink, Brunhilde Schweiger, Alla Heider, Jeanette Milde, Andreas Nitsche, Kati Schroeder, Joerg Doellinger, Christian Braun, Walter Haas, Gérard Krause, Udo Buchholz


Influenza viral shedding studies provide fundamental information for preventive strategies and modelling exercises. We conducted a prospective household study to investigate viral shedding in seasonal and pandemic influenza between 2007 and 2011 in Berlin and Munich, Germany.


Study physicians recruited index patients and their household members. Serial nasal specimens were obtained from all household members over at least eight days and tested quantitatively by qRT-PCR for the influenza virus (sub)type of the index patient. A subset of samples was also tested by viral culture. Symptoms were recorded daily.


We recruited 122 index patients and 320 household contacts, of which 67 became secondary household cases. Among all 189 influenza cases, 12 were infected with seasonal/prepandemic influenza A(H1N1), 19 with A(H3N2), 60 with influenza B, and 98 with A(H1N1)pdm09. Nine (14%) of 65 non-vaccinated secondary cases were asymptomatic/subclinical (0 (0%) of 21 children, 9 (21%) of 44 adults; p = 0.03).


Viral load among patients with influenza-like illness (ILI) peaked on illness days 1, 2 or 3 for all (sub)types and declined steadily until days 7–9. Clinical symptom scores roughly paralleled viral shedding dynamics.


On the first day prior to symptom onset 30% (12/40) of specimens were positive. Viral load in 6 asymptomatic/subclinical patients was similar to that in ILI-patients. Duration of infectiousness as measured by viral culture lasted approximately until illness days 4–6. Viral load did not seem to be influenced by antiviral therapy, age or vaccination status.


Asymptomatic/subclinical infections occur infrequently, but may be associated with substantial amounts of viral shedding. Presymptomatic shedding may arise in one third of cases, and shedding characteristics appear to be independent of (seasonal or pandemic) (sub)type, age, antiviral therapy or vaccination; however the power to find moderate differences was limited.



While this was a relatively small study, and their findings don’t always align perfectly with others we’ve seen (for instance, children didn’t appear contagious any longer than adults), it does provide us with some interesting data.


  • First, nearly 1/3rd of cases began shedding virus while pre-symptomatic
  • Second, viral loads in (six studied) asymptomatic cases were similar to that to patients exhibiting ILI (influenza-like-illness) symptoms.
  • Third, viral load among symptomatic patients peaked on illness days 1, 2 or 3 and declined steadily until days 7–9


Some other gems (bolding mine) excerpted from this open access article include:


  • Overall 63% of non-vaccinated secondary household cases had an ILI-syndrome and the proportion of asymptomatic/subclinical secondary cases was 14%.
  • Frequency distribution of clinical symptoms did not differ between A(H1N1)pdm09 cases and non-pandemic influenza cases.
  • Interestingly, 21% of adult secondary cases were asymptomatic/subclinical, while all children that contracted influenza were symptomatic.
  • Based on the population of ambulatory patients investigated we found no evidence that the amount of shedding is particularly higher in children, nor that duration of viral shedding is significantly longer in children compared to adults.



The authors conclude by saying:


In summary, our study addresses several important questions on clinical manifestation, duration of infectiousness, viral shedding patterns, including shedding before symptom onset and in asymptomatic/subclinical patients, as well as the effect of vaccination and antiviral therapy on viral shedding.


Important single results include the finding that children do not seem to be infected asymptomatically, that shedding one day before symptom onset may occur in one third of influenza patients, that asymptomatic/subclinical influenza patients occur rarely, but viral load (and probably infectiousness) may be substantial, and vaccinated influenza patients do not show different shedding patterns compared to non-vaccinated cases with ILI.


Overall results do not show marked differences between seasonal influenza (sub)types and influenza A(H1N1)pdm09.

No comments: