Comparison of shedding characteristics of seasonal influenza virus (sub)types and influenza A(H1N1)pdm09; Germany, 2007-2011

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Figure 1. Study flow diagram.

Figure 2. Viral shedding in laboratory confirmed symptomatic index and secondary cases.

Median and interquartile range of log Copies/ml in index patients (green line) and secondary symptomatic cases (orange line) as well as individual values for participants with presymptomatic shedding (blue dots). For negative tests a value of 0 was used. By definition, symptom onset started on day 1.

Figure 3. Viral shedding and symptom scores in patients with influenza-like illness symptoms.

Viral shedding (expressed as median of log Copies/ml) and symptom scores (expressed as median) for all cases with influenza-like illness symptoms. Top left: viral shedding, top middle: symptom scores; top right: seasonal/prepandemic influenza A(H1N1), bottom left: influenza A(H1N1)pdm09, bottom middle: influenza A(H3N2), bottom right: influenza B. For negative tests a value of 0 was used.

Figure 4. Symptomatic and asymptomatic shedding in influenza patients.

Median and interquartile range of log Copies/ml in 6 asymptomatic influenza patients (green; 2 A(H1N1)pdm09, 2 A(H3N2), 2 B) as well as in influenza patients with influenza-like illness of any type or subtype (red).

Figure 5. Viral shedding and symptom scores in patients with influenza-like illness stratified by age.

Viral shedding (expressed as median and interquartile range of log Copies/ml) and symptom scores (expressed as median and interquartile range) for adult and child patients with influenza-like illness symptoms. adults - continuous line, children - dashed line) starting on the day of symptom onset. For negative tests a value of 0 was used.

Figure 6. Influence of antiviral therapy and vaccination on viral shedding and symptoms in influenza patients.

Viral shedding expressed as median and interquartile range of log Copies/ml and influenza symptoms expressed as median and interquartile range. Top: patients with influenza-like illness, by antiviral treatment, bottom: not vaccinated patients (all with influenza-like illness) in green, vaccinated patients (with any symptoms) in orange. For negative tests a value of 0 was used.

Figure 7. Viral load in specimens measured by qRT-PCR or viral culture, by (sub)type.

Viral load in specimens of patients with influenza-like illness measured by qRT-PCR (expressed as median of log Copies/ml) as well as in patients with any symptoms measured by viral culture expressed as median of log Plaque forming units (PFU), stratified by (sub)type. No data available for influenza A(H1N1)pdm09. For negative tests a value of 0 was used.