By Kelly A. Reynolds, MSPH, Ph.D.

A new study has been published on the use of mathematical models to estimate the impact of influenza medications on treatment plant efficacies. This theoretical approach enables researchers to readily change model parameters and forecast potential pandemic events in order to evaluate the range of environmental impacts resulting from a sudden influx of pharmaceuticals into the environment.

Trade-offs and opportunity costs

Life is a constant balance of choices and consequences. There are many examples in science were an intended benefit to the public or environment resulted in unforeseen consequences or side effects. The same is likely true for each of us as we make individual, family or career decisions. The Environmental Literacy Council puts it plainly:

“As we make everyday choices – how much time to spend working or studying, what to spend our money on – we are experiencing what economists call trade-offs and opportunity costs. A trade-off is when we choose one option in favor of another and the opportunity cost is what is sacrificed in order to get something. Whether we realize it or not, we are constantly evaluating the costs and benefits of each decision we make; therefore, it can also be said that we are performing our own cost-benefit analysis each time we make a choice. As decisions are made – either individually or as a society – we constantly make trade-offs in order to get more of one thing by giving up another.”¹

Consider the example of medications. We know that trade-offs for effective treatment will likely involve some mild side effects. There is another trade-off, however, that is less apparent but in need of consideration: the impact of medications on the environment- i.e., their ecotoxicity.

What is ecotoxicity?

Ecotoxicity simply means the adverse effect of a stressor (chemical, biological or physical) on an ecosystem. The ecosystem is a delicate balance of microscopic and macroscopic organisms. A disruption at any level can have a trickling effect to many other related or dependent systems. While concern has been mounting for decades over the steady increase of pharmaceuticals in use that make their way into water, few have queried: What happens when a sudden increase in a particular medication occurs in response to a massive outbreak or global pandemic? Parameters associated with past and future influenza pandemics serve as an experimental field to evaluate the ecotoxicity of increased antiviral and antibiotic agent use. Much effort was expended tracking H1N1 disease trends during the 2009 pandemic. These data can be used to predict medical responses – by region – in pandemics of increasing severity. This information can be combined with clinical data on excretion rates of medications and studies on how medications impact essential environmental microbes (including those used for wastewater treatment processes) to estimate ecotoxic effects.

Sensitive wastewater microbes

Typically, the growth of microbes is encouraged in the secondary treatment step of wastewater (following primary settling of large matter and particulates) where dissolved organic matter is broken down or degraded. This biodegradation process reduces the organic load discharged to the environment via treated wastewater effluent. Therefore, microbes play a pivotal role in the wastewater treatment process. If an imbalance occurs in the microbial population of the treatment plant, the system can experience a build-up of organic matter, reducing treatment efficacy. Excess use, and subsequent excretion, of antibiotics could disrupt the balance of the microbial population in wastewater treatment plants as well as in natural waters. This effect can be seen following heavy rainfall events but little is known about how vulnerable this balance is to a sudden increase in the use of antimicrobial medications as would be expected in a severe pandemic.

Predicting the unpredictable

An international team of researchers from The Centre for Ecology and Hydrology and The University of Sheffield in the United Kingdom, The Institute for Scientific Interchange in Italy, Utrechet University in the Netherlands and Indiana University recently posed the question: “When a disease spreads globally, what is the impact of the medical response to that pandemic?”²

We know that increased use of antiviral and antibiotic treatments for the treatment of influenza and related secondary infections, such as pneumonia, can potentially effect the ecosystem and wastewater treatment plant operations – but to what degree is currently unknown. As with many drugs and hormone therapies, following use, most antibiotics and antiviral medications are largely unchanged when excreted into wastewater via urine and feces. Conventional wastewater treatment methodologies do not remove all of the contaminants, particularly when treatment processes may also be compromised by the contaminants. Given that real-time monitoring of pandemic disease rates and medical responses is not practical – or even possible for events that have not yet occurred – computer models provide a means to mock up (or model) such scenarios. In this case, models were used to simulate quantities of antiviral medications and antibiotics that would be used in an influenza pandemic. Researchers utilized a range of model inputs based on varying severities of the predicted outbreak correlating with varying use levels of medical treatments. Drug usage patterns are used to estimate release concentrations and forecast levels expected to occur in receiving rivers that might lead to microbial ecotoxicity.

The model results are interesting. During mild pandemics, it is assumed that antibiotic use increases only slightly (an estimated one percent) compared to moderate to severe outbreaks where antibiotic use is projected to increase between 13 and 252 percent, respectively. Likewise, during mild pandemics, the slight increase in antibiotic and antiviral use had negligible effects on the wastewater treatment plant ecosystem. System effects were determined by the percent of microbial species susceptible to growth-inhibition following exposure to the contaminants. The model indicates, however, that with increasing outbreak severity, and increasing use of antivirals and antibiotics, nearly all (80-100 percent) wastewater treatment plants are predicted to experience inhibition of microbial growth in the plant operations.

Extended effects- drinking water sources and antibiotic resistance

Other adverse endpoints evaluated in the model included measurement of oxygen levels in natural surface waters – a determining factor for water quality and ecosystem balance. Contaminants were predicted to adversely affect about half of the drinking water supplies in the Thames basin, the targeted model catchment site in the UK.

In addition to the possibility of deficient wastewater treatment and contaminated drinking water supplies, the potential of antibiotic resistance developing in existing bacterial populations is an issue. Antibiotic resistance in bacteria can develop naturally but is enhanced by exposure to sub-lethal levels of antibiotics. Bacteria that survive in the presence of antibiotics have resistance genes that can be passed to other bacteria in the microbial community. Although the authors of this study recognized the concern over antibiotic resistance relative to the increased use of antibiotics during an influenza pandemic, they provided only qualitative risk information on this topic.

Empirical data

More empirical data is needed to validate the predictive pandemic response model and determine if a mitigation strategy is needed. Another group of researchers supplied some encouraging data where concentrations of 28 antibiotics in three hospital effluents and five wastewater treatment plants were monitored. The upper range of antibiotics in hospital effluents was 14.5 µg/L compared to 64 µg/L of wastewater treatment plant influent. The wastewater treatment process removed 80% of the antibiotics with maximum concentrations in the effluent of 3.4 µg/L. Concentrations in surface waters ranged up to 2 µg/L but none of the targeted antibiotics were detected in the drinking water samples.³ This study suggests antibiotics from concentrated sources could be kept at low levels in drinking water. Similarly, several studies support that use of certain types of antivirals, including Tamiflu, Zanamivir and peramivir, at high levels would not negatively impact typical fresh and marine water microbial ecosystems. However, evidence still points toward the potential disturbance of microbial biofilms that are critical to wastewater treatment processes.⁴ Overall, the type of treatment at the plant may play a major role in the efficacy of medication removal.

Prevention benefits

The pandemic influenza response study may have another unintentional benefit – that of vaccine promotion. If more of the global population were vaccinated as a preventative approach to pandemic influenza, there would be no need for the use of ecotoxic antibiotics and antivirals. Thus, vaccines provide the known benefit of decreased illness and death without the trade-off of ecotoxicity. The H1N1 pandemic did not help to validate the influenza medical response model predictions, as widespread wastewater treatment failures were not reported. This outcome is contrary to model indications. Nonetheless, the development and continued improvement of the model will aid in analysis of varying environmental conditions and clinical response parameters to improve our understanding of complex ecosystem relationships and ecotoxicological hazards.

References

¹The Environmental Literacy Council. Updated by Dawn Anderson.

http://www.enviroliteracy.org/article.php/1331.html. Accessed April 8, 2011.

²Singer, A. C., Colizza, V., Schmitt, H., Andrews, J., Balcan, D., et al. 2011 Assessing the ecotoxicologic hazards of a pandemic influenza medical response. Environmental Health Perspectives doi:10.1289/ehp.1002757

³Watkinson, A. J., Murby, E. J., Kolpin, D. W. and Costanzo, S. D. 2008. The occurrence of antibiotics in an urban watershed: from wastewater to drinking water. Science of the Total Environment. 407 (8): 2711-2723

⁴Slater, F. R., Singer, A. C., Turner, S., Barr, J. J., Bond, P. L. 2011. Pandemic pharmaceutical dosing effects on wastewater treatment: no adaptation of activated sludge bacteria to degrade the antiviral drug Oseltamivir (Tamiflu®) and loss of nutrient removal performance. FEMS Microbiology Letters. 315(1): 17-22.