Shedding the h1n1 virus

A further limitation of the review is that there was little insight into pre-symptomatic and asymptomatic shedding; only one study examined these but given its setting in isolated communal farming communities in Canada is unlikely to be representative. This review has provided insights into viral shedding duration of influenza A H1N1 pdm09 and the relative effects of age, clinical severity and oseltamivir treatment.

Additional reviews examining viral loads and correlation of symptoms over time may provide further insights into the relative infectivity and transmissibility of influenza A H1N1 pdm09 and are warranted now that influenza A H1N1 pdm09 has become established as the seasonal H1N1 influenza virus and that there is a large body of literature examining its properties.

We thank Associate Professor Ben Cowling for critical review of the manuscript and corresponding authors of reviewed papers who provided additional data and clarification of viral shedding definitions. Additional Supporting Information may be found in the online version of this article:. National Center for Biotechnology Information , U.

Influenza Other Respir Viruses. Published online Dec 2. Author information Article notes Copyright and License information Disclaimer. James E. E-mail: ua. Accepted Oct This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. This article has been cited by other articles in PMC.

Associated Data Supplementary Materials Figure S1 Proportion of community setting study cases positive for influenza A H1N1 pdm09 by day of virus shedding and oseltamivir treatment. Abstract Duration of viral shedding following infection is an important determinant of disease transmission, informing both control policies and disease modelling.

Keywords: adult, antiviral agents, child, influenza A virus, H1N1 subtype, influenza, human, virus shedding. Introduction Prior to , pandemic plans assumed that all influenza pandemics arise from the emergence of a different antigenic subtype, as was observed for the three pandemics of the 20th Century. Data analysis Meta-analyses using a random-effects model were conducted in Stata, version Results A total of citations were returned from the search, of which were excluded following title and abstract review.

Table 1 Identified studies and reasons for exclusion. Open in a separate window. Table 2 Participant profiles and methodologies of studies included in the review.

Figure 1. Age Given the small number of studies among hospitalised and intensive care patients, age stratification was restricted to studies of community-based cases.

Figure 2. Asymptomatic shedding One study by Loeb et al. Antiviral treatment Summary measures of viral shedding duration stratified by treatment modality were available from 11 studies of community-based cases, of which four further differentiated by whether or not oseltamivir was administered within 48 hours of illness onset. Figure 3. Discussion Several studies have reported that duration of pre seasonal influenza virus shedding is longer in children 20 — 22 and has become a widely accepted assumption in text books 23 and pandemic planning documents.

Box 1 Proposed standard parameters for measurement and reporting of influenza viral shedding duration Unless measuring pre-symptomatic or asymptomatic shedding, the duration of viral shedding should be defined as from the day of symptom s onset to the day on which the last positive specimen was collected.

The age threshold for classification as a child or adult should be clearly defined. Acknowledgments We thank Associate Professor Ben Cowling for critical review of the manuscript and corresponding authors of reviewed papers who provided additional data and clarification of viral shedding definitions.

Supporting Information Additional Supporting Information may be found in the online version of this article: Figure S1 Proportion of community setting study cases positive for influenza A H1N1 pdm09 by day of virus shedding and oseltamivir treatment. Click here to view. References 1. The signature features of influenza pandemics—implications for policy.

N Engl J Med. Kilbourne ED. Influenza pandemics of the 20th century. Emerg Infect Dis. Australian Government Department of Health and Ageing. Origins and evolutionary genomics of the swine-origin H1N1 influenza A epidemic. Comparison of the pandemic H1N1 experience in the southern hemisphere with pandemic expectations. World Health Organization. Pandemic influenza preparedness and response: a WHO guidance document.

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Epidemiol Infect. Longitudinal study of influenza molecular viral shedding in Hutterite communities. J Infect Dis. Duration of viral shedding in hospitalized patients infected with pandemic H1N1. BMC Infect Dis. Virus shedding and environmental deposition of novel A H1N1 pandemic influenza virus: interim findings.

Health Technol Assess. Viral shedding duration of pandemic influenza A H1N1 virus during an elementary school outbreak—Pennsylvania, May-June Patterns of shedding of myxoviruses and paramyxoviruses in children.

Viral shedding patterns of children with influenza B infection. Viral shedding in children with influenza virus infections treated with neuraminidase inhibitors. Pediatr Infect Dis J. Treanor JJ. Influenza viruses, including avian influenza and swine influenza. Participants not available for sampling on the first day of collection were entered into the study on the subsequent sampling day.

In this method, 0. After incubation, the coverslip was stained with influenza A monoclonal antibody by using immunofluorescence 6.

Nasal wash samples were not quantified by culture. Questionnaire responses, employee health record data, symptom log, and laboratory data were entered into a spreadsheet and analyzed by using SAS version 9. Frequencies were calculated for categorical variables, and Fisher exact tests were used to examine associations between categorical variables.

Medians were calculated for continuous variables. An accelerated failure time model with a Weibull survival function was used to assess the effect of test type i.

This model accounts for interval censoring present in data and uses a range for shedding duration. This range is based on the fact that initiation of shedding was considered to be the day of symptom onset, and cessation of shedding was considered to range from the collection date of the last positive test result to collection date of the first of 2 consecutive negative test results. Shedding duration was calculated as the number of days between initiation and cessation of shedding 7.

For participants who showed negative results on the first day of nasal wash sampling, cessation was considered to range from symptom onset to obtaining the first of 2 consecutive negative test results.

To evaluate whether fever was a predictor of viral load, a linear regression model was fit by using viral load as the dependent variable. The retreat occurred from am to pm daily for 5 days, with optional evening social activities. Forty-six persons participated in retreat activities. The remaining 32 core participants attended all 5 days of the retreat and participated in evening activities. Most core participants also stayed overnight in 1 cabin on Thursday, September On Friday, September 25, the last day of the retreat, the first retreat participant with documented illness experienced a cough.

The following day, this person had fever and was DFA positive for influenza A. By Monday, September 28, active surveillance of the 46 retreat attendees by Hospital A staff identified 20 persons with respiratory symptoms; 19 were core participants and 1 was a facilitator.

The other 3 participants with respiratory symptoms were virus negative; all were afebrile. Sixteen infected HCP provided serial nasal wash samples and completed a symptom log for the duration of their illness. One virus-infected participant did not complete a questionnaire but did provide serial nasal wash specimens. Another participant who was virus positive completed a questionnaire but did not provide serial nasal wash specimens. HCP infected with pandemic H1N1 virus ranged in age from 26 to 33 years median All HCP reported completing antiviral treatment as prescribed, and no deaths or hospitalizations occurred.

From the onset of symptoms, the duration of viral shedding determined by real-time RT-PCR results ranged from 3 to 13 days compared with 3—10 days by rapid culture results.

Figure 1. Survival curves were modeled on data for 16 persons who became infected In our initial model using data from all 16 participants, which included test type real-time RT-PCR vs. Our final model, which included only test type as a predictor of shedding duration, indicated that shedding duration was significantly different between rapid culture and real-time RT-PCR Figure 1.

Shedding duration measured by rapid culture was 0. Eight of 16 HCP remained positive by rapid culture 4. Figure 2. Each colored line represents a virus RNA concentration for an infected person tested The person with the highest concentration of viral RNA on the first day of serial sampling also had one of the longest shedding durations by real-time RT-PCR.

However, viral load was not a significant predictor of shedding duration in our analysis. We describe a pandemic H1N1 outbreak with a high attack rate that involved relatively young, healthy HCP after a hospital-associated retreat. Because of the single source of infection in an enclosed environment, we were able to prospectively monitor study participants to document duration of clinical symptoms and laboratory parameters.

Infected HCP often did not report a fever during their illness. Virus infection was documented by real-time RT-PCR and rapid culture for prolonged periods, even though all infected HCP were treated with oseltamivir within 24—48 hours of illness onset.

The shedding duration measured by real-time RT-PCR was significantly longer than that measured by rapid culture. The high attack rate we observed might be explained by a susceptible population without immunity to pandemic H1N1 virus, active surveillance for infection, or by prolonged close contact among participants, including sharing a cabin. Although viral load of the index case on day 1 of illness was not quantified, the initial viral load 5. These findings highlight the potential for rapid spread of influenza among populations with ongoing close contact.

In the absence of an available vaccine, handwashing and respiratory hygiene practices e. This study had several limitations.

Although all persons received standardized instructions to minimize variation in collection methods, nasal washes were self-collected and had the potential for variability in collection technique. Self-collection of nasal washes might have led to underestimation of presence or quantity of influenza virus.

Other studies have demonstrated increased sensitivity with nasal washes, compared with nasal swabs, in respiratory virus detection 4 , 13 , and we believe that self-collection of nasal washes likely increased compliance with study procedures. For logistical reasons, persons were not tested daily, which affected our ability to more precisely define duration of shedding.

We chose to use an accelerated failure time model with a Weibull survival function in our analysis because this method accounts for interval censoring. However, our model did not account for the paired nature of the data, in that each sample was tested by rapid culture and real-time RT-PCR. Our unpaired analysis likely led to an overly conservative p value, indicating that a statistically significant p value in our analysis also might have been detected by an analytic technique that accounts for pairing.

The small sample size of this study might have decreased the power to detect associations observed in previous studies even if they existed, such as an association between fever and shedding duration or fever and viral load In addition, viral load was not measured on the day of symptom onset in our study but began on the first day that the participant provided serial nasal wash specimens. This delayed measurement might have affected the ability to detect associations between viral load and shedding duration and between fever and viral load.

Furthermore, our findings should be considered in light of the fact that all participants were treated with antiviral medication, which might have affected relationships between symptoms, shedding duration, and viral load. These general themes apply to seasonal flu, too," Schaffner said. Grant support for ASP provided by. Become an underwriter». All rights reserved. The University of Minnesota is an equal opportunity educator and employer. Skip to main content. University of Minnesota.

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