Limits...
Modeling the effects of drug resistant influenza virus in a pandemic.

Brockmann SO, Schwehm M, Duerr HP, Witschi M, Koch D, Vidondo B, Eichner M - Virol. J. (2008)

Bottom Line: If a resistant infection is introduced into the population after three weeks, the outcome dramatically deteriorates.Wide-spread use of NI treatment makes it highly likely that the resistant strain will spread if its fitness is high.This situation is further aggravated if a resistant virus is imported into a country in the early phase of an outbreak.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Epidemiology and Health Reporting, Baden-Württemberg State Health Office, District Government Stuttgart, Germany. stefan.brockmann@rps.bwl.de

ABSTRACT
Neuraminidase inhibitors (NI) play a major role in plans to mitigate future influenza pandemics. Modeling studies suggested that a pandemic may be contained at the source by early treatment and prophylaxis with antiviral drugs. Here, we examine the influence of NI resistant influenza strains on an influenza pandemic. We extend the freely available deterministic simulation program InfluSim to incorporate importations of resistant infections and the emergence of de novo resistance. The epidemic with the fully drug sensitive strain leads to a cumulative number of 19,500 outpatients and 258 hospitalizations, respectively, per 100,000 inhabitants. Development of de novo resistance alone increases the total number of outpatients by about 6% and hospitalizations by about 21%. If a resistant infection is introduced into the population after three weeks, the outcome dramatically deteriorates. Wide-spread use of NI treatment makes it highly likely that the resistant strain will spread if its fitness is high. This situation is further aggravated if a resistant virus is imported into a country in the early phase of an outbreak. As NI-resistant influenza infections with high fitness and pathogenicity have just been observed, the emergence of drug resistance in treated populations and the transmission of drug resistant strains is an important public health concern for seasonal and pandemic influenza.

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The solid curves show the expected total numbers of (a) outpatients, (b) hospitalizations, and (c) deaths, respectively, during a pandemic wave in a population of 100,000 inhabitants where on day 0 a drug-sensitive infection is imported, followed by a drug-resistant one after the time delay given on the horizontal axis. Without introduction of a resistant infection, 20,700 outpatients, 314 hospitalizations and 82 deaths are expected (dashed reference lines). If resistant infection is neither introduced de novo nor imported, 19,500 outpatients, 258 hospitalizations and 66 deaths are expected (dotted reference lines). Parameter values see Figure 1 and text.
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Figure 2: The solid curves show the expected total numbers of (a) outpatients, (b) hospitalizations, and (c) deaths, respectively, during a pandemic wave in a population of 100,000 inhabitants where on day 0 a drug-sensitive infection is imported, followed by a drug-resistant one after the time delay given on the horizontal axis. Without introduction of a resistant infection, 20,700 outpatients, 314 hospitalizations and 82 deaths are expected (dashed reference lines). If resistant infection is neither introduced de novo nor imported, 19,500 outpatients, 258 hospitalizations and 66 deaths are expected (dotted reference lines). Parameter values see Figure 1 and text.

Mentions: If a resistant strain emerges only de novo, its prevalence may remain low, implying little epidemiological consequences (Figure 1a). Importation of resistance, however, increasingly replaces the drug sensitive strain because the latter is continuously eliminated by treatment. The dominance of the resistant strain depends on when its importation starts. E. g. if a drug resistant strain is imported 21 days after seeding the epidemic (with a sensitive strain), the prevalence curve for the resistant strain mimics in a delayed shape the prevalence of the sensitive strain (Figure 1b). If the time point for the importation of the resistant strain is shifted towards the initial phase of the epidemic, the resistant strain increasingly replaces the sensitive strain (Figure 1c). Early importation of resistant infection increases the number of treatment failures and thus, increases the overall number of infections emerging from the epidemic (Figure 1a–c). A sensitivity analysis which addresses the influence of the non-pharmaceutical interventions on these results is presented as an additional file (Additional file 1). Figure 2 illustrates the total numbers of (a) outpatients, (b) hospitalizations, and (c) deaths in dependence of a given time delay between the importation of the drug sensitive and the drug resistant infection (0–30 days).


Modeling the effects of drug resistant influenza virus in a pandemic.

Brockmann SO, Schwehm M, Duerr HP, Witschi M, Koch D, Vidondo B, Eichner M - Virol. J. (2008)

The solid curves show the expected total numbers of (a) outpatients, (b) hospitalizations, and (c) deaths, respectively, during a pandemic wave in a population of 100,000 inhabitants where on day 0 a drug-sensitive infection is imported, followed by a drug-resistant one after the time delay given on the horizontal axis. Without introduction of a resistant infection, 20,700 outpatients, 314 hospitalizations and 82 deaths are expected (dashed reference lines). If resistant infection is neither introduced de novo nor imported, 19,500 outpatients, 258 hospitalizations and 66 deaths are expected (dotted reference lines). Parameter values see Figure 1 and text.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2590604&req=5

Figure 2: The solid curves show the expected total numbers of (a) outpatients, (b) hospitalizations, and (c) deaths, respectively, during a pandemic wave in a population of 100,000 inhabitants where on day 0 a drug-sensitive infection is imported, followed by a drug-resistant one after the time delay given on the horizontal axis. Without introduction of a resistant infection, 20,700 outpatients, 314 hospitalizations and 82 deaths are expected (dashed reference lines). If resistant infection is neither introduced de novo nor imported, 19,500 outpatients, 258 hospitalizations and 66 deaths are expected (dotted reference lines). Parameter values see Figure 1 and text.
Mentions: If a resistant strain emerges only de novo, its prevalence may remain low, implying little epidemiological consequences (Figure 1a). Importation of resistance, however, increasingly replaces the drug sensitive strain because the latter is continuously eliminated by treatment. The dominance of the resistant strain depends on when its importation starts. E. g. if a drug resistant strain is imported 21 days after seeding the epidemic (with a sensitive strain), the prevalence curve for the resistant strain mimics in a delayed shape the prevalence of the sensitive strain (Figure 1b). If the time point for the importation of the resistant strain is shifted towards the initial phase of the epidemic, the resistant strain increasingly replaces the sensitive strain (Figure 1c). Early importation of resistant infection increases the number of treatment failures and thus, increases the overall number of infections emerging from the epidemic (Figure 1a–c). A sensitivity analysis which addresses the influence of the non-pharmaceutical interventions on these results is presented as an additional file (Additional file 1). Figure 2 illustrates the total numbers of (a) outpatients, (b) hospitalizations, and (c) deaths in dependence of a given time delay between the importation of the drug sensitive and the drug resistant infection (0–30 days).

Bottom Line: If a resistant infection is introduced into the population after three weeks, the outcome dramatically deteriorates.Wide-spread use of NI treatment makes it highly likely that the resistant strain will spread if its fitness is high.This situation is further aggravated if a resistant virus is imported into a country in the early phase of an outbreak.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Epidemiology and Health Reporting, Baden-Württemberg State Health Office, District Government Stuttgart, Germany. stefan.brockmann@rps.bwl.de

ABSTRACT
Neuraminidase inhibitors (NI) play a major role in plans to mitigate future influenza pandemics. Modeling studies suggested that a pandemic may be contained at the source by early treatment and prophylaxis with antiviral drugs. Here, we examine the influence of NI resistant influenza strains on an influenza pandemic. We extend the freely available deterministic simulation program InfluSim to incorporate importations of resistant infections and the emergence of de novo resistance. The epidemic with the fully drug sensitive strain leads to a cumulative number of 19,500 outpatients and 258 hospitalizations, respectively, per 100,000 inhabitants. Development of de novo resistance alone increases the total number of outpatients by about 6% and hospitalizations by about 21%. If a resistant infection is introduced into the population after three weeks, the outcome dramatically deteriorates. Wide-spread use of NI treatment makes it highly likely that the resistant strain will spread if its fitness is high. This situation is further aggravated if a resistant virus is imported into a country in the early phase of an outbreak. As NI-resistant influenza infections with high fitness and pathogenicity have just been observed, the emergence of drug resistance in treated populations and the transmission of drug resistant strains is an important public health concern for seasonal and pandemic influenza.

Show MeSH
Related in: MedlinePlus