Antiflu drug flows into rivers during flu season.

Jan 04, 2010

Ghosh, GC, N Nakada, N Yamashita and H Tanaka. Oseltamivir carboxylate – the active metabolite of oseltamivir phosphate (Tamiflu), detected in sewage discharge and river water in Japan. Environmental Health Perspectives doi: 10.1289/ehp.0900930.



Synopsis by Heather Hamlin and Wendy Hessler

2009-1203tamiflucapsules
  rom ahisgett/Flickr

Scientists report they found the anti-viral medication Tamiflu in  rivers in Japanese cities during last year's flu season. Tamiflu is an antiviral drug used to slow the spread of the influenza, or flu, virus by both treating and preventing influenza, including H1N1 and avian flu (H5N1). The contamination raises serious public health safety concerns about the overuse of antiviral drugs that may lead to development of Tamiflu-resistant flu strains. The results highlight a need for enhanced treatment of wastewater, especially during periods of elevated flu risk.

 

Context

In the United States, approximately 36,000 people die and more than 200,000 are hospitalized every year after they get sick from influenza, also called the flu. Certain viral strains – such as H1N1 (swine flu) – may cause more illness or more severe illness than other strains (CDC 2009).

The H1N1 virus is unique in that it is responsible for the first flu pandemic (global outbreak of disease) in more than 40 years (World Health Organization 2009a). Pandemics are thought to occur when a new strain of flu virus is transmitted from animals to people. Birds, chickens and pigs can transmit flu strains to humans, and health experts consider these animals to be the biggest concern.

Antiviral drugs, such as Tamiflu, can decrease the severity of symptoms and the duration of the flu. The drugs can also prevent other serious health complications associated with the flu and are considered a critical line of defense in the battle against flu viruses.

The active ingredient in Tamiflu is a drug called oseltamivir phosphate (OP). OP can be converted in the body and discharged in the urine as another compound called oseltamivir carboxylate (OC). More than 80 percent of the oral dose of OC is excreted unchanged.

Most sewage treatment plants do not remove antiviral medications from the wastewater. The drugs end up in rivers, streams and other water bodies where the effluent is released. Anti-flu medications in the environment can interact with flu viral strains that are also in the water, promoting strains that are not affected by Tamiflu and increasing the likelihood that new, drug-resistent strains will develop in the areas near where sewage dumps into surface waters.

Health officials worry that the widespread use of OP to fight seasonal influenza in humans could lead to the development of OC-resistant strains of the viruses in wild birds.

Many subtypes of the flu virus are transmitted through waterfowl. The microbes incubate in the birds and are then excreted in the bird droppings.

Waterfowl often remain close to sewage treatment discharges, since the water temperature is warmer and food is more plentiful. These habits can put them in direct contact with resistant strains of the flu virus, where they can infect waterfowl and be passed to other wildlife and possibly people.

Health experts have already noted an increase in resistance of the H1N1 virus to Tamiflu – a finding that has raised concern about the widespread use of Tamiflu in treating seasonal flu outbreaks (World Health Organization 2009b).
 

What did they do?

Researchers from Kyoto University in Japan sampled water from several rivers and treated sewage effluent that was released into the rivers prior to and during the 2008-09 flu season. The samples were analyzed for levels of the popular antiviral medicine OC.

Samples taken between June and October of 2008 represent the non-flu season. The flu season samples were collected during three outings – one in December 2008 and two in February 2009 – from 11 locations along the Katsura River and several of its tributaries. The Katsura River system receives more than 80 percent of the wastewater from Kyoto City – a city of more than 1.3 million people.

The water samples were analyzed for the drug using a new method developed by the research team. Amounts in the river water and effluents were then calculated and compared. 

What did they find?

OC was not detected in samples taken prior to the start of the flu season.

It was found in all of the sewage treatment plant discharges that were examined during the three sampling campaigns taken during flu season. Concentrations of up to 293.3 nanograms/liter (ng/L) were measured in water collected from sewage outflows.

It was also detected in river water downstream of the sewage treatment outflows. Levels ranged from 6.6 to 190 ng/L in river water samples.

The OC concentrations varied with the level and type of sewage treatment used. Sewage treated with a more stringent process called ozonation had lower concentrations of OC. With higher treatment, levels were reduced up to 85 percent and measured at 37.9 ng/L when compared with a less efficient type of sewage treatment called activated-sludge.

What does it mean?

OC was found in all sewage treatment plant discharges for all sampling times during the flu season in this study. In some cases, OC was found in appreciable quantities. OC is the active metabolite of the anti-flu medicine Tamiflu.

This is the first study to identify OC in sewage treatment plant discharge during flu season. The results suggest that standard sewage treatment is not effective at removing the OC residue from sewage. 

Wildlife – including waterfowl that can transmit the flu – are exposed to the low and continuous doses of OC during the flu season. This exposure increases the likelihood that an OC-resistant virus strain could develop and be picked up by the waterfowl that congregate at sites of sewage effluent discharge. Waterfowl and other birds are identified as animals of high concern in the transmission of new strains of flu virus to humans.

H1N1 has reached pandemic status and is becoming resistant to Tamiflu – which is a critical first line of defense in flu treatment.

A serious question raised by the study's findings is whether Tamiflu should be dispensed so widely during flu season. Its widespread use could increase the risk of drug resistant flu strains that are currently untreatable. If the drug is doled out sparingly, many people will be at increased risk for dangerous complications from the flu.

The scientists reported a bright side, however.

Sewage treatment plants that incorporate ozone into their treatment processes had much lower concentrations of OC than those without ozone. Although ozone increases the cost of sewage treatment, this study highlights an important reason to mandate the use of ozone in sewage treatment processes, at least during flu season.


Resources

Influenza A(H1N1) virus resistance to oseltamivir - 2008/2009 influenza season,
northern hemisphere. World Health Organization. March 18, 2009. PDF.

Pandemic (H1N1) 2009. World Health Organization.

Seasonal Influenza: The Disease. US Centers for Disease Control and Prevention. November 2009.

 

 

 

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