Assessing the ecotoxicologic hazards of a pandemic influenza medical response

Abstract

Background: The global public health community has closely monitored the unfolding of the 2009 H1N1 influenza pandemic to best mitigate its impact on society. However, little attention has been given to the impact of this response on the environment. Antivirals and antibiotics prescribed to treat influenza are excreted into wastewater in a biologically active form, which presents a new and potentially significant ecotoxicologic challenge to microorganisms responsible for wastewater nutrient removal in wastewater treatment plants (WWTPs) and receiving rivers.

Objectives: We assessed the ecotoxicologic risks of a pandemic influenza medical response.

Methods: To evaluate this risk, we coupled a global spatially structured epidemic model that simulates the quantities of antivirals and antibiotics used during an influenza pandemic of varying severity and a water quality model applied to the Thames catchment to determine predicted environmental concentrations. An additional model was then used to assess the effects of antibiotics on microorganisms in WWTPs and rivers.

Results: Consistent with expectations, our model projected a mild pandemic to exhibit a negligible ecotoxicologic hazard. In a moderate and severe pandemic, we projected WWTP toxicity to vary between 0-14% and 5-32% potentially affected fraction (PAF), respectively, and river toxicity to vary between 0-14% and 0-30% PAF, respectively, where PAF is the fraction of microbial species predicted to be growth inhibited (lower and upper 95% reference range).

Conclusions: The current medical response to pandemic influenza might result in the discharge of insufficiently treated wastewater into receiving rivers, thereby increasing the risk of eutrophication and contamination of drinking water abstraction points. Widespread drugs in the environment could hasten the generation of drug resistance. Our results highlight the need for empirical data on the effects of antibiotics and antiviral medications on WWTPs and freshwater ecotoxicity.

Figure 1

Illustration of the Thames River Basin boundary. Dark blue represents river stretches receiving WWTP effluent within the LF2000‑WQX; light blue represents river stretches upstream of the first WWTP found within the LF2000‑WQX. A river stretch is defined by the length of river bounded at both ends by an input to or abstraction from the river (e.g., another river, WWTP, drainage canal, abstraction point).

Figure 2

Predicted toxicity to microorganisms in WWTPs and river stretches resulting from exposure to antibiotics during influenza pandemics. Scenarios: s1, AVP = 0, rate of AVT = 30%, limited supply of Tamiflu; s2, 2 week AVP, AVP = 0.1%, rate of AVT = 30%, limited supply of Tamiflu; s3, 4 week AVP, AVP = 0.1%, rate of AVT = 30%, limited supply of Tamiflu; s4, 2 week AVP, AVP = 1%, rate of AVT = 30%, limited supply of Tamiflu; s5, 4 week AVP, AVP = 1%, rate of AVT = 30%, limited supply of Tamiflu; s6, AVP = 0, rate of AVT = 30%, unlimited supply of Tamiflu. (A,C,D) Percentage of WWTPs (A), river stretches (C), and river length (total length of the river stretches in the Thames River Basin; D) predicted to exceed the toxicity threshold of 5% PAF by transmission scenario (mild, moderate, and severe). Values shown are median and 95% RRs obtained from the drug use pattern predicted by the 1,000 stochastic runs of the GLEaM model. No bar is visible when the median value equals zero; this is the case, for example, for the mild and moderate scenarios. Note that antiviral treatment is assumed in the moderate and severe pandemic scenarios only, with 30% case detection and drug administration. Intervention with antivirals is modeled by assuming that each country has limited stockpiles of the drug [s1–s5; see Supplemental Material, Figure 4 (doi:10.1289/ehp.1002757)] (Colizza et al. 2007; Singer et al. 2008) or that each country can count on a hypothetical unlimited supply of drugs (s6). PAF calculations are based on the antibiotic sensitivity distributions of human pathogens and a combination of two mixture toxicity models. (B and E) Absolute toxicity, shown as a percentage of microbial species predicted to be growth inhibited (PAF) per each WWTP (B) and river stretch (E) according to the pharmaceutical mitigating conditions explored, in the mild, moderate, and severe transmission scenarios.

Figure 3

Maps showing the predicted toxicity of wastewater in WWTPs (A–C) and river stretches (D–F) corresponding to the drug use patterns shown in Figure 1C,D and Supplemental Material, Figure 3 (doi:10.1289/ehp.1002757), respectively, assuming no AVP. Toxicity values are binned and color coded as in Figure 2B and E. In A, individual WWTPs are indicated by circles that are scaled to indicate the size of the population served by each plant.