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Antiviral prophylaxis during pandemic influenza may increase drug resistance.

Eichner M, Schwehm M, Duerr HP, Witschi M, Koch D, Brockmann SO, Vidondo B - BMC Infect. Dis. (2009)

Bottom Line: Neuraminidase inhibitors (NI) and social distancing play a major role in plans to mitigate future influenza pandemics.Although NI drug resistance may emerge in treated patients in such a late state of their disease that passing on the newly developed resistant viruses is unlikely, resistant strains quickly become highly prevalent in the population if their fitness is high.The authors show scenarios where pre-exposure antiviral prophylaxis even increases the number of influenza cases and deaths.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Biometry, University of Tübingen, Tübingen, Germany. martin.eichner@uni-tuebingen.de

ABSTRACT

Background: Neuraminidase inhibitors (NI) and social distancing play a major role in plans to mitigate future influenza pandemics.

Methods: Using the freely available program InfluSim, the authors examine to what extent NI-treatment and prophylaxis promote the occurrence and transmission of a NI resistant strain.

Results: Under a basic reproduction number of R0 = 2.5, a NI resistant strain can only spread if its transmissibility (fitness) is at least 40% of the fitness of the drug-sensitive strain. Although NI drug resistance may emerge in treated patients in such a late state of their disease that passing on the newly developed resistant viruses is unlikely, resistant strains quickly become highly prevalent in the population if their fitness is high. Antiviral prophylaxis further increases the pressure on the drug-sensitive strain and favors the spread of resistant infections. The authors show scenarios where pre-exposure antiviral prophylaxis even increases the number of influenza cases and deaths.

Conclusion: If the fitness of a NI resistant pandemic strain is high, any use of prophylaxis may increase the number of hospitalizations and deaths in the population. The use of neuraminidase inhibitors should be restricted to the treatment of cases whereas prophylaxis should be reduced to an absolute minimum in that case.

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Related in: MedlinePlus

Course of disease. Model assumptions on the course of disease of cases with and without prophylaxis if people are infected with the drug sensitive virus. Without prophylaxis, one third of infected individuals remains asymptomatic, one third becomes moderately sick and one third becomes severely sick and needs medical help. Prophylaxis halves the fractions of moderately and severely sick individuals and doubles the fraction of infected individuals who remain asymptomatic, but only half of the asymptomatic infections lead to protective immunity.
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Figure 1: Course of disease. Model assumptions on the course of disease of cases with and without prophylaxis if people are infected with the drug sensitive virus. Without prophylaxis, one third of infected individuals remains asymptomatic, one third becomes moderately sick and one third becomes severely sick and needs medical help. Prophylaxis halves the fractions of moderately and severely sick individuals and doubles the fraction of infected individuals who remain asymptomatic, but only half of the asymptomatic infections lead to protective immunity.

Mentions: We employ a basic reproduction number of R0 = 2.5 [14], and assume that one third of all infected individuals remain asymptomatic, that another third becomes moderately sick and that the remaining third becomes severely sick and seeks medical help (Fig. 1). A proportion of severely sick cases needs hospitalization and may die from the disease, depending on the age and on the risk group of the patient (see Additional file 1, Table A1). Adults who develop severe disease are sick and contagious for 7 days on average and need 5 more days to recover before they can resume work. Treatment reduces their remaining duration of the disease by 25%, their contagiousness by 80% [2] and their need of hospitalization (and concurrently their risk of death) by 50% [15]. A fraction of the population between 20 and 60 years of age is offered antiviral prophylaxis. We assume that people who take prophylaxis are less susceptible to the infection with the drug sensitive strain (the standard value of 50% is varied in an uncertainty analysis). If they are infected, twice as many of them remain asymptomatic than without prophylaxis; their contagiousness, their duration of being sick and their need for hospitalization are reduced in the same way as described above for therapeutic treatment. We furthermore assume that only half of the individuals who take prophylaxis become immune after asymptomatic infection whereas the other half is left susceptible (Fig. 1).


Antiviral prophylaxis during pandemic influenza may increase drug resistance.

Eichner M, Schwehm M, Duerr HP, Witschi M, Koch D, Brockmann SO, Vidondo B - BMC Infect. Dis. (2009)

Course of disease. Model assumptions on the course of disease of cases with and without prophylaxis if people are infected with the drug sensitive virus. Without prophylaxis, one third of infected individuals remains asymptomatic, one third becomes moderately sick and one third becomes severely sick and needs medical help. Prophylaxis halves the fractions of moderately and severely sick individuals and doubles the fraction of infected individuals who remain asymptomatic, but only half of the asymptomatic infections lead to protective immunity.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2654456&req=5

Figure 1: Course of disease. Model assumptions on the course of disease of cases with and without prophylaxis if people are infected with the drug sensitive virus. Without prophylaxis, one third of infected individuals remains asymptomatic, one third becomes moderately sick and one third becomes severely sick and needs medical help. Prophylaxis halves the fractions of moderately and severely sick individuals and doubles the fraction of infected individuals who remain asymptomatic, but only half of the asymptomatic infections lead to protective immunity.
Mentions: We employ a basic reproduction number of R0 = 2.5 [14], and assume that one third of all infected individuals remain asymptomatic, that another third becomes moderately sick and that the remaining third becomes severely sick and seeks medical help (Fig. 1). A proportion of severely sick cases needs hospitalization and may die from the disease, depending on the age and on the risk group of the patient (see Additional file 1, Table A1). Adults who develop severe disease are sick and contagious for 7 days on average and need 5 more days to recover before they can resume work. Treatment reduces their remaining duration of the disease by 25%, their contagiousness by 80% [2] and their need of hospitalization (and concurrently their risk of death) by 50% [15]. A fraction of the population between 20 and 60 years of age is offered antiviral prophylaxis. We assume that people who take prophylaxis are less susceptible to the infection with the drug sensitive strain (the standard value of 50% is varied in an uncertainty analysis). If they are infected, twice as many of them remain asymptomatic than without prophylaxis; their contagiousness, their duration of being sick and their need for hospitalization are reduced in the same way as described above for therapeutic treatment. We furthermore assume that only half of the individuals who take prophylaxis become immune after asymptomatic infection whereas the other half is left susceptible (Fig. 1).

Bottom Line: Neuraminidase inhibitors (NI) and social distancing play a major role in plans to mitigate future influenza pandemics.Although NI drug resistance may emerge in treated patients in such a late state of their disease that passing on the newly developed resistant viruses is unlikely, resistant strains quickly become highly prevalent in the population if their fitness is high.The authors show scenarios where pre-exposure antiviral prophylaxis even increases the number of influenza cases and deaths.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Medical Biometry, University of Tübingen, Tübingen, Germany. martin.eichner@uni-tuebingen.de

ABSTRACT

Background: Neuraminidase inhibitors (NI) and social distancing play a major role in plans to mitigate future influenza pandemics.

Methods: Using the freely available program InfluSim, the authors examine to what extent NI-treatment and prophylaxis promote the occurrence and transmission of a NI resistant strain.

Results: Under a basic reproduction number of R0 = 2.5, a NI resistant strain can only spread if its transmissibility (fitness) is at least 40% of the fitness of the drug-sensitive strain. Although NI drug resistance may emerge in treated patients in such a late state of their disease that passing on the newly developed resistant viruses is unlikely, resistant strains quickly become highly prevalent in the population if their fitness is high. Antiviral prophylaxis further increases the pressure on the drug-sensitive strain and favors the spread of resistant infections. The authors show scenarios where pre-exposure antiviral prophylaxis even increases the number of influenza cases and deaths.

Conclusion: If the fitness of a NI resistant pandemic strain is high, any use of prophylaxis may increase the number of hospitalizations and deaths in the population. The use of neuraminidase inhibitors should be restricted to the treatment of cases whereas prophylaxis should be reduced to an absolute minimum in that case.

Show MeSH
Related in: MedlinePlus