Antimicrobial resistance in Asia. An interview with Prof. Honda


Antimicrobial resistance (AMR) is an arms race that must be addressed locally and globally. In this regard, fieldwork is crucial to understand the dynamics of antibiotic resistance and to identify sources of pollution and the lack of sufficient infrastructure to prevent the leakage of contaminated water into the environment.


Recently, we interviewed Prof. Ryo Honda, from Kanazawa University in Japan, who recently joined our scientific board. His work has been focusing on environmental monitoring of antibiotic resistance in various countries, in Asia and India. He shares insights into his research with us:



AMR TDT: Hello Prof. Honda. You have published about how urbanization can impact the prevalence of antibiotic-resistant E Coli - for example with a case study in Thailand - can you talk about this work?

R.H. Our work has indeed studied the prevalence of resistant genes, mainly, in E. coli, in Thailand, and other Asian countries. We have been sampling E. coli isolates and analyzing their antibiotic resistance against 6 antibiotic classes. Our work revealed that the presence of AMR in Asian countries, Thailand, Sri Lanka, India is highly dependent on local urbanization, and land usage rather than the upstream conditions. Meaning that the land usage upstream impacted less than the urbanization (Kumar et al. 2020).



What about the wastewater infrastructures over there?

R.H. A few Thailand areas have infrastructures, but population coverage is low (50%). Wastewater is not connected to houses, it’s a common thing. This highlights that urban infrastructure for wastewater and mitigating environmental pollution are insufficient. In other countries such as Sri Lanka, the coverage is awfully bad.

In Sri Lanka, the Kelani River is one of the most important rivers as the Kelani River remains a vital resource for about 25 percent of the Sri Lankan population who reside in its catchment area.

The river gets pollutants from liquid waste discharged by the rapidly expanding industries that operate alongside the river and agricultural runoff and domestic and municipal waste. Various industries are located along the banks of this river and known as EPZ, consisting of 180 acres of beverage processing, latex, apparel, chemical manufacturing, and food processing industrial area. Yet it is also the drinking source for over 4 million people living in Colombo City. (Honda et al. 2016, Kumar et al. 2020).



In France, a previous national survey conducted in 2013 by the government found that 92 % of the 2950 sampling sites along the rivers were polluted (source 1). In Japan, do cities and urban-waste-water management plants have strict regulations regarding AMR?

R.H. Despite the excellent level of Japanese infrastructures, wastewater treated effluent contains a few antimicrobial AMR resistance genes. But all water sources are not connected to the wastewater infrastructure. If we try to quantify the total of effluents, we find that 25% of water is untreated because of sewer overflows when it rains heavily.

In our research, we highlighted in several countries such as Thailand and Sri Lanka that a ratio of antibiotic-resistant bacteria is likely to increase when urban land use nearby exceeds a certain ratio. Especially, a resistance ratio to fluoroquinolones tends to be high in a highly-populated area.



How about the methods and processes to clean waste efficiently?

R.H. I observe that conventional sedimentation has been used in many wastewater plants worldwide. Yet, extracellular AMR cannot be removed by those methods. Hence, membrane filtration could enable targeting extracellular antibiotic-resistant genes, thus efficiently reducing the presence of AMR.

Our research has also highlighted that the monitoring extension towards sediments is also required. This means that urban areas need to design and implement a tertiary treatment with effective disinfection and management of sludge.



At AMR TDT we believe that climate change is a facilitating factor in AMR spread. Your work points out seasonal effects?

R.H. Yes indeed, many Asian countries have an intense rainy season, which is a significant difference from European or American countries. Rainy seasons cause a huge discharge of antimicrobial-resistant genes in the environment, which is a huge issue. Typically, field studies show high AMR abundance during rainy seasons. However, the concentration of AMR, tends to be lower because the AMR is diluted in the rainy season. In dry seasons, however, concentrations are higher.



How about the evolution of the prevalence of gene resistance across several years?

R.H. Long-term evolution? We have unfortunately not this much visibility. We recently obtained research for 3 years to monitor AMR on sites using metagenomics. International databases, however, limited in number, are available.



I see. We observed among the scientific community that the research funds shifted to short-term programs over the past decade. We believe it is getting difficult to conduct long-term studies, such as environmental surveys. So, how about the methods and their relative costs in your field?

R.H. Many researchers believe that several key indicators exist. Recently, metagenomics has gained tremendous interest as it is a powerful tool, but it is also too expensive for standard monitoring. This is also a limitation if we are to consider long-term studies. Quantitative PCR and standard cultivation methods, which are cheaper, are still useful in this regard. A number of our studies have been focusing on antibiotic resistance in E. coli for example, which is a useful indicator because prevalent in the environment and urban areas.



In Japan, has AMR monitoring been put into practice for AMR?

R.H. Surveillance programs in the medical and agricultural sectors have been put in place. However, we definitely need now to put in motion environmental monitoring programs. Some groups found resistance genes, not in wastewater but rather directly observed in the environment.

Such a program would not only increase our knowledge and detect clusters of AMR, but it would also benefit the medical service too.


In fact, if a particular resistance is found locally, then doctors can get the right drug to use, at the local scale. That would surely reduce the death and comorbidities due to antibiotic resistance.



Great point indeed. Would you think a smaller city size enables more easily manageable water treatment?

R.H. Depending on the country you consider, in Japan, 80% of houses are connected to water treatment plants. Big cities have combined sewage with combined untreated and treated water. That makes a heavy load of water to process, which is costly, and certainly not the best efficient way. Perhaps, smaller communities could be better if they had wastewater treatment plants, but now, they don’t. National or prefecture-dependent funds will only build such expensive infrastructures if a given number of criteria are met.



Agriculture in Japan has changed tremendously in the past 70 years. Livestock farming has gone from 50 000 farms in 1950, to 5000 farms in 2020. Livestock animals are the main antibiotic drug consumers. Your thought about that?

R.H. There is a need for an increase of people to raise awareness. Perhaps we could have more compulsory labels regarding the presence of antibiotics in meat-based food, such as meat, or in dairy products such as milk or egg. I am not aware of project aiming toward such regulations in Japan.

Japan also imports a lot of products from countries where there is no regulation regarding the use of antibiotic drugs (or food additives). People also need to be aware of such uses outside our country. There are many efforts to do in these regards.



Did Japan invest to monitor SARS-COV2 in urban wastewater?

R.H. No, not to my knowledge. I am aware of research programs and feasibility studies, either by public or private institutions. One city has assessed the presence of COVID near hospital and warehouse facilities. Nothing yet comparable to cities like Ottawa which applied for intensive monitoring programs at the city scale.



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Note: As a member of the Trans-Pacific-Network on AMR, AMR TDT has been advocating for solutions, starting with

1) Environmental monitoring of AMR in countries

2) Building novel waste-water infrastructures and optimize current systems, ensure that houses and factories are connected to the waste-water treatment plant.

3) Drive finance to support these efforts

4) Address pollution globally by stringent regulations on polluters.


A recent study points out the cities with the largest contaminations events. It reveals a great disparity among cities worldwide. We believe that these locations should be the priority targets to receive financial help, and improve ASAP sanitary systems, sewage and wastewater systems, in addition to other actions.



Sources:

Source 1: https://www.notre-planete.info/actualites/4383-pesticides-cours-eau-France

Source 2: Honda et al. - 2016 - Impacts of urbanization on the prevalence of antibiotic-resistant Escherichia coli in the Chaophraya River and its tributaries https://pubmed.ncbi.nlm.nih.gov/26819392/

Source 3: Kumar et al. - 2020 - Prevalence of antibiotic resistance in the tropical rivers of Sri Lanka and India https://doi.org/10.1016/j.envres.2020.109765

Source 4: Kumar, Chaminda, Honda - 2020 - Seasonality impels the antibiotic resistance in Kelani River of the emerging economy of Sri Lanka https://www.nature.com/articles/s41545-020-0058-6



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