Limits...
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.

Show MeSH

Related in: MedlinePlus

Prevalence of infection. Prevalence of people infected with the drug sensitive virus (solid lines), the drug resistant one (dashed lines) and the sum of both (dotted lines). All cases who seek medical help receive antiviral treatment; additionally, a fraction of (a) 0%, (b) 10% and (c) 20% of all adults between 20 and 60 years of age are given prophylaxis. The grey curves and the right hand scales indicate the fractions of resistant infections among all infections. Assumptions: (1) A single drug-sensitive infection is introduced on day 0 into a Swiss population of 100,000 individuals. (2) Resistance develops de novo in 4.1% of children and 0.32% of adults who receive medication. (3) Social distancing reduces the number of contacts by 10% for all individuals; isolation additionally prevents 10%, 20% and 30% of contacts of moderately sick cases, severely sick cases at home, and hospitalized cases, respectively. (4) Antiviral treatment reduces the contagiousness of patients by 80%, their duration of sickness by 25% and their need of hospitalization by 50% if they are infected with the drug sensitive virus. (5) Prophylaxis furthermore reduces susceptibility by 50%. Upon infection, it doubles the fraction of individuals who stay asymptomatic from one third to two thirds, but only one of the two thirds becomes immune. (6) R0 = 2.5 for the drug sensitive and the drug resistant virus (fitness = 100%).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2654456&req=5

Figure 2: Prevalence of infection. Prevalence of people infected with the drug sensitive virus (solid lines), the drug resistant one (dashed lines) and the sum of both (dotted lines). All cases who seek medical help receive antiviral treatment; additionally, a fraction of (a) 0%, (b) 10% and (c) 20% of all adults between 20 and 60 years of age are given prophylaxis. The grey curves and the right hand scales indicate the fractions of resistant infections among all infections. Assumptions: (1) A single drug-sensitive infection is introduced on day 0 into a Swiss population of 100,000 individuals. (2) Resistance develops de novo in 4.1% of children and 0.32% of adults who receive medication. (3) Social distancing reduces the number of contacts by 10% for all individuals; isolation additionally prevents 10%, 20% and 30% of contacts of moderately sick cases, severely sick cases at home, and hospitalized cases, respectively. (4) Antiviral treatment reduces the contagiousness of patients by 80%, their duration of sickness by 25% and their need of hospitalization by 50% if they are infected with the drug sensitive virus. (5) Prophylaxis furthermore reduces susceptibility by 50%. Upon infection, it doubles the fraction of individuals who stay asymptomatic from one third to two thirds, but only one of the two thirds becomes immune. (6) R0 = 2.5 for the drug sensitive and the drug resistant virus (fitness = 100%).

Mentions: Figures 2a–c show how the prevalence of infection with the drug sensitive and the resistant virus change during the pandemic wave if all severe cases are treated with NI and if additionally 0%, 10% or 20% of the people between 20 and 60 years of age receive prophylaxis (assuming that the fitness of the NI resistant strain is as high as that of the drug-sensitive one, i.e. 100%). The simulations start with one drug-sensitive infection in a susceptible population of 100,000 individuals. NI resistance develops de novo and gradually builds up during the epidemic wave. If no prophylaxis is given, the drug-sensitive strain dominates most of the epidemic wave (full curve) and the resistant strain (dashed curve) only becomes prevalent in the end (Fig. 2a).


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)

Prevalence of infection. Prevalence of people infected with the drug sensitive virus (solid lines), the drug resistant one (dashed lines) and the sum of both (dotted lines). All cases who seek medical help receive antiviral treatment; additionally, a fraction of (a) 0%, (b) 10% and (c) 20% of all adults between 20 and 60 years of age are given prophylaxis. The grey curves and the right hand scales indicate the fractions of resistant infections among all infections. Assumptions: (1) A single drug-sensitive infection is introduced on day 0 into a Swiss population of 100,000 individuals. (2) Resistance develops de novo in 4.1% of children and 0.32% of adults who receive medication. (3) Social distancing reduces the number of contacts by 10% for all individuals; isolation additionally prevents 10%, 20% and 30% of contacts of moderately sick cases, severely sick cases at home, and hospitalized cases, respectively. (4) Antiviral treatment reduces the contagiousness of patients by 80%, their duration of sickness by 25% and their need of hospitalization by 50% if they are infected with the drug sensitive virus. (5) Prophylaxis furthermore reduces susceptibility by 50%. Upon infection, it doubles the fraction of individuals who stay asymptomatic from one third to two thirds, but only one of the two thirds becomes immune. (6) R0 = 2.5 for the drug sensitive and the drug resistant virus (fitness = 100%).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Prevalence of infection. Prevalence of people infected with the drug sensitive virus (solid lines), the drug resistant one (dashed lines) and the sum of both (dotted lines). All cases who seek medical help receive antiviral treatment; additionally, a fraction of (a) 0%, (b) 10% and (c) 20% of all adults between 20 and 60 years of age are given prophylaxis. The grey curves and the right hand scales indicate the fractions of resistant infections among all infections. Assumptions: (1) A single drug-sensitive infection is introduced on day 0 into a Swiss population of 100,000 individuals. (2) Resistance develops de novo in 4.1% of children and 0.32% of adults who receive medication. (3) Social distancing reduces the number of contacts by 10% for all individuals; isolation additionally prevents 10%, 20% and 30% of contacts of moderately sick cases, severely sick cases at home, and hospitalized cases, respectively. (4) Antiviral treatment reduces the contagiousness of patients by 80%, their duration of sickness by 25% and their need of hospitalization by 50% if they are infected with the drug sensitive virus. (5) Prophylaxis furthermore reduces susceptibility by 50%. Upon infection, it doubles the fraction of individuals who stay asymptomatic from one third to two thirds, but only one of the two thirds becomes immune. (6) R0 = 2.5 for the drug sensitive and the drug resistant virus (fitness = 100%).
Mentions: Figures 2a–c show how the prevalence of infection with the drug sensitive and the resistant virus change during the pandemic wave if all severe cases are treated with NI and if additionally 0%, 10% or 20% of the people between 20 and 60 years of age receive prophylaxis (assuming that the fitness of the NI resistant strain is as high as that of the drug-sensitive one, i.e. 100%). The simulations start with one drug-sensitive infection in a susceptible population of 100,000 individuals. NI resistance develops de novo and gradually builds up during the epidemic wave. If no prophylaxis is given, the drug-sensitive strain dominates most of the epidemic wave (full curve) and the resistant strain (dashed curve) only becomes prevalent in the end (Fig. 2a).

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