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Prophylaxis after exposure to Coxiella burnetii.

Moodie CE, Thompson HA, Meltzer MI, Swerdlow DL - Emerging Infect. Dis. (2008)

Bottom Line: We calculated the threshold points at which the number of PEP-related adverse events was equal to the cases averted.PEP was defined as doxycycline (100 mg 2x/day for 5 days), except for pregnant women, where we assumed a PEP of trimethoprim-sulfamethoxazole (160 mg/800 mg 2x/day) for the duration of the pregnancy.PEP would begin 8-12 days postexposure.

View Article: PubMed Central - PubMed

Affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA. claire_moodie@hotmail.com

ABSTRACT
Coxiella burnetii is a category B bioterrorism agent. We numerically evaluated the risks and benefits from postexposure prophylaxis (PEP) after an intentional release of C. burnetii to the general population, pregnant women, and other high-risk populations. For each group, we constructed a decision tree to estimate illness and deaths averted by use of PEP/100,000 population. We calculated the threshold points at which the number of PEP-related adverse events was equal to the cases averted. PEP was defined as doxycycline (100 mg 2x/day for 5 days), except for pregnant women, where we assumed a PEP of trimethoprim-sulfamethoxazole (160 mg/800 mg 2x/day) for the duration of the pregnancy. PEP would begin 8-12 days postexposure. On the basis of upper-bound probability estimates of PEP-related adverse events for doxycycline, we concluded that the risk for Q fever illness outweighs the risk for antimicrobial drug-related adverse events when the probability of C. burnetii exposure is >or=7% (pregnant women using trimethoprim-sulfamethoxazole = 16%).

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Cases of illness averted in the general population after Coxiella burnetii exposure with the use of postexposure prophylaxis while accounting for a 1.0% probability of adverse events, broken down by virulence scenario and drug efficacy. The “best estimate” scenario (primary analysis, A) uses best estimate input values, the “less virulent” scenario (B) uses input values that result in the least harmful outcome, the “more virulent” scenario (C) applies input values that result in the most harmful outcome or worst-case scenario. Drug efficacy refers to the efficacy of doxycycline as a post-exposure prophylaxis against C. burnetii infection. Analyses for doxycycline (used by the general and high-risk populations) were run at 2 potential drug efficacies: 96.5% and 82%. The threshold points, the probability of exposure where the risk of adverse events equals the risk of illness, are noted on the graphs.
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Figure 4: Cases of illness averted in the general population after Coxiella burnetii exposure with the use of postexposure prophylaxis while accounting for a 1.0% probability of adverse events, broken down by virulence scenario and drug efficacy. The “best estimate” scenario (primary analysis, A) uses best estimate input values, the “less virulent” scenario (B) uses input values that result in the least harmful outcome, the “more virulent” scenario (C) applies input values that result in the most harmful outcome or worst-case scenario. Drug efficacy refers to the efficacy of doxycycline as a post-exposure prophylaxis against C. burnetii infection. Analyses for doxycycline (used by the general and high-risk populations) were run at 2 potential drug efficacies: 96.5% and 82%. The threshold points, the probability of exposure where the risk of adverse events equals the risk of illness, are noted on the graphs.

Mentions: The threshold point is defined as the probability of exposure to C. burnetii where the risk for adverse events equals the benefit of PEP use. Figure 4 illustrates the general population threshold points (run at 2 different drug efficacy values) for total cases of illness averted for the primary, less, and more virulent scenarios. The x-intercept on these graphs is the probability of exposure to C. burnetii at which the total number of cases of illness averted because of PEP use is equal to the number of moderate PEP-related adverse events. Therefore, for any probability of exposure greater than the stated threshold value, PEP would prevent more cases of illness than the number of adverse events PEP would cause. As Figure 4 illustrates, the less virulent or more virulent scenarios affect the estimated number of cases but do not greatly affect the threshold probabilities of exposure. For further analyses, refer to Appendix Tables 2, 3, and 4 to review univariate sensitivity analyses on various variables used in the risk/benefit scenarios. These tables show which variables have the greatest independent influence on the respective outcomes and how modifications to the input values impacts the estimated number of cases averted.


Prophylaxis after exposure to Coxiella burnetii.

Moodie CE, Thompson HA, Meltzer MI, Swerdlow DL - Emerging Infect. Dis. (2008)

Cases of illness averted in the general population after Coxiella burnetii exposure with the use of postexposure prophylaxis while accounting for a 1.0% probability of adverse events, broken down by virulence scenario and drug efficacy. The “best estimate” scenario (primary analysis, A) uses best estimate input values, the “less virulent” scenario (B) uses input values that result in the least harmful outcome, the “more virulent” scenario (C) applies input values that result in the most harmful outcome or worst-case scenario. Drug efficacy refers to the efficacy of doxycycline as a post-exposure prophylaxis against C. burnetii infection. Analyses for doxycycline (used by the general and high-risk populations) were run at 2 potential drug efficacies: 96.5% and 82%. The threshold points, the probability of exposure where the risk of adverse events equals the risk of illness, are noted on the graphs.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2609859&req=5

Figure 4: Cases of illness averted in the general population after Coxiella burnetii exposure with the use of postexposure prophylaxis while accounting for a 1.0% probability of adverse events, broken down by virulence scenario and drug efficacy. The “best estimate” scenario (primary analysis, A) uses best estimate input values, the “less virulent” scenario (B) uses input values that result in the least harmful outcome, the “more virulent” scenario (C) applies input values that result in the most harmful outcome or worst-case scenario. Drug efficacy refers to the efficacy of doxycycline as a post-exposure prophylaxis against C. burnetii infection. Analyses for doxycycline (used by the general and high-risk populations) were run at 2 potential drug efficacies: 96.5% and 82%. The threshold points, the probability of exposure where the risk of adverse events equals the risk of illness, are noted on the graphs.
Mentions: The threshold point is defined as the probability of exposure to C. burnetii where the risk for adverse events equals the benefit of PEP use. Figure 4 illustrates the general population threshold points (run at 2 different drug efficacy values) for total cases of illness averted for the primary, less, and more virulent scenarios. The x-intercept on these graphs is the probability of exposure to C. burnetii at which the total number of cases of illness averted because of PEP use is equal to the number of moderate PEP-related adverse events. Therefore, for any probability of exposure greater than the stated threshold value, PEP would prevent more cases of illness than the number of adverse events PEP would cause. As Figure 4 illustrates, the less virulent or more virulent scenarios affect the estimated number of cases but do not greatly affect the threshold probabilities of exposure. For further analyses, refer to Appendix Tables 2, 3, and 4 to review univariate sensitivity analyses on various variables used in the risk/benefit scenarios. These tables show which variables have the greatest independent influence on the respective outcomes and how modifications to the input values impacts the estimated number of cases averted.

Bottom Line: We calculated the threshold points at which the number of PEP-related adverse events was equal to the cases averted.PEP was defined as doxycycline (100 mg 2x/day for 5 days), except for pregnant women, where we assumed a PEP of trimethoprim-sulfamethoxazole (160 mg/800 mg 2x/day) for the duration of the pregnancy.PEP would begin 8-12 days postexposure.

View Article: PubMed Central - PubMed

Affiliation: Centers for Disease Control and Prevention, Atlanta, Georgia, USA. claire_moodie@hotmail.com

ABSTRACT
Coxiella burnetii is a category B bioterrorism agent. We numerically evaluated the risks and benefits from postexposure prophylaxis (PEP) after an intentional release of C. burnetii to the general population, pregnant women, and other high-risk populations. For each group, we constructed a decision tree to estimate illness and deaths averted by use of PEP/100,000 population. We calculated the threshold points at which the number of PEP-related adverse events was equal to the cases averted. PEP was defined as doxycycline (100 mg 2x/day for 5 days), except for pregnant women, where we assumed a PEP of trimethoprim-sulfamethoxazole (160 mg/800 mg 2x/day) for the duration of the pregnancy. PEP would begin 8-12 days postexposure. On the basis of upper-bound probability estimates of PEP-related adverse events for doxycycline, we concluded that the risk for Q fever illness outweighs the risk for antimicrobial drug-related adverse events when the probability of C. burnetii exposure is >or=7% (pregnant women using trimethoprim-sulfamethoxazole = 16%).

Show MeSH
Related in: MedlinePlus