Updated research agenda for water, sanitation and antimicrobial resistance

The emergence and spread of antimicrobial resistance (AMR), including clinically relevant antimicrobial-resistant bacteria, genetic resistance elements, and antibiotic residues, presents a significant threat to human health. Reducing the incidence of infection by improving water, sanitation, and hygiene (WASH) is one of five objectives in the World Health Organization’s (WHO) Global Action Plan on AMR. In September 2019, WHO and the Health-Related Water Microbiology specialist group (HRWM-SG) of the International Water Association (IWA) organized its third workshop on AMR, focusing on the following three main issues: environmental pathways of AMR transmission, environmental surveillance, and removal from human waste. The workshop concluded that despite an increase in scientific evidence that the environment may play a significant role, especially in low-resource settings, the exact relative role of the environment is still unclear. Given many antibiotic-resistant bacteria (ARB) can be part of the normal gut flora, it can be assumed that for environmental transmission, the burden of fecaloral transmission of AMR in a geographical area follows that of WASH-related infections. There are some uncertainties as to the potential for the propagation of particular resistance genes within wastewater treatment plants (WWTPs), but there is no doubt that the reduction in viable microbes (with or without resistance genes) available for transmission via the environment is one of the goals of human waste management. Although progress has been made in the past years with respect to quantifying environmental AMR transmission potential, still more data on the spread of environmental AMR within human communities is needed. Even though evidence on AMR in WWTPs has increased, the reduction in the emergence and spread of AMR by basic sanitation methods is yet unresolved. In order to contribute to the generation of harmonized One Health surveillance data, WHO has initiated an integrated One Health surveillance strategy that includes the environment. The main challenge lies in rolling it out globally including to the poorest regions.


INTRODUCTION
Antimicrobial resistance (AMR) has been raised as an important issue on the international agenda for over a decade. AMR is not only a major threat to global health but also to our   The second question discussed in this breakout group was: What kind of sample metadata are needed to make better use of the data? Suggestions from the participants were climate information (wet vs. dry season, precipitation, river flow, water/air temperature, tidal influence), water quality (pH, dissolved oxygen, biochemical oxygen demand, conductivity, total suspended solids, total coliforms, 16S sequence counts for normalization, antibiotics, toxicity), geographical information (land use, population density, antibiotics use/sales), operational information from wastewater treatment plants (WWTPs; number of people serviced, animals serviced, discharge volume), watershed information (source tracking), and sampling strategy (taking multiple samples to account for variability, high flow situation sampling, comparison with low flow sampling, sediments/biofilms, good documentation on sampling location (GPS location), type of water body (river/lake)).
These can be classified as variables to assure that the sample was taken correctly and research would be repeatable, as well as to identify underlying causative factors.  Peracetic acid seems to be effective against ARB (Kitis ).
Systems, such as algae ponds with high pH, may be useful for the elimination of ARB in LEDCs. However, operation and maintenance of waste stabilization ponds in LEDCs with high population growth is a major concern.
According to the global database on country progress in if ARBs and susceptible bacteria behave similarly in wastewater treatment; (5) to consider AMR in wastewater guidelines and its cost-effectiveness; (6) to establish standardized detection methodologies for AMR in wastewater; (7) to clarify AMR terminology across One Health domains; (8) to involve engineers in NAPs on AMR; (9) to establish the impact of AMR release into the environment; and (10) to raise public awareness of AMR. The coordinator raised another concern about the control of AMR in food, in which livestock have been focused as one of the possible drivers of AMR, but the infection from produce items are often overlooked.
There were several suggestions from the participants as follows: Risks are location-specific (e.g. due to varying irrigation water quality), and washing of vegetables is not always effective (e.g. due to root uptake, variable treatment performance in production facilities, e.g. due to inconsistent chlorine levels). Therefore, it is important to focus on the release of pathogens rather than treatment efficiency.
Also, several important points for discussion were raised by the participants. One of them is the disconnection between the research in clinical and environmental settings.

The importance of better communication and coordination
between clinical researchers and water engineers was emphasized. It was also highlighted that the knowledge of Another point was that sustainability interventions could also carry risks; for example, green buildings and water conservation can increase the stagnation potential and dead-ends in distribution systems (also major issues in older hospitals where water distribution systems may be poorly mapped).
The other main knowledge gap/action point raised by the participants was the importance of distinguishing between home and hospital to consider how AMR spreads within communities. It was suggested that future research should link dissemination of AMR to specific behavioral factors (e.g. swimming in surface water vs. fountain mist exposure).
Another point was the measurement of antibiotic residues levels in water used for different purposes.

OVERALL DISCUSSION
Following the group discussion, the coordinators presented the discussion summary of each group followed by a general discussion time with all the workshop participants ( Table 2).
The latter was focused on the issues including the definition of AMR, the health risk of ARGs/ARB from human exposure to aquatic environments, and the need for standardized methods for the analysis of AMR in aquatic environments to compare results. The workshop concluded that fundamental questions are not new, but the unity of language is very important and the reduction of the spread Which kind of wastewater treatment systems should be developed/implemented to remove antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB)?
• For low-and middle-income countries (LMICs), basic sanitation systems such as pit latrines are better than open defecation in terms of the reduction of ARB/ARGs emission to environments • It is important to understand the extent to which systems applicable in LMICs would reduce ARB/ARGs with the potential use of high pH lime • Importance in developing standardized protocols for quantification of ARGs • Importance of having a balance between improving sanitation and removal/transformation of micropollutants • Evaluating the contribution of decentralized systems in the removal and release of ARB/ARGs in the aquatic environments • The necessity for data sharing and collaboration Group 3: Environmental pathways for AMRdecision tree for country prioritizing WASH and environment actions Are there potentially important transmission routes other than commonly recognized ones?
• Indoor airborne transmission, and fecal sludge • The potential transmission routes of antimicrobial fungi including agricultural settings, ice machines, and shower water • Livestock have been focused as one of the possible drivers of AMR, but the infection from produce items are often overlooked How to prioritize WASH and environmental interventions?
• Importance of better communication and coordination between clinical researchers and water engineers • Linking dissemination of AMR to specific behavioral factors (e.g. swimming in surface water vs. fountain mist exposure • Quantitative microbial risk assessment (QMRA) can aid in prioritization