HKU Bulletin November 2021 (Vol. 23 No. 1)

This detection work is made possible by DNA technology Professor Zhang developed to detect antibiotic-resistant genes in water samples, which has been widely adopted by researchers across the world. He has also applied molecular detection work to identify the SARS-CoV-2 virus that causes COVID-19 in local sewage samples. Using an RNA-based technology he developed and working with HKU’s School of Public Health, Professor Zhang and his team began to detect the virus last November, days before cases were confirmed. This led to the government introducing compulsory testing for places with positive signals from sewage samples. The team have since developed a method to identify variants of the virus. “COVID-19 is an example of how we understand One Health from another angle. We see the flow of pathogen from human to environment. We can use information from one compartment to indicate the situation in another. The same thing applies to antibiotic-resistant genes. We survey the environment to not only look at the possible sources of AMR in humans and animals, but also as a reflection of what may be happening in humans and animals,” he said. Our gut contributions One of Professor Zhang’s collaborators has been Dr Hein Tun, a veterinary public health specialist in the School of Public Health who has multiple projects of his own on the non- human sources of human AMR. For instance, an ongoing study is measuring AMR levels and transmission across beaches, healthy people, hospital patients, farms, rivers and creeks in Hong Kong, Mainland China and Thailand. So far, the data shows AMR levels are higher in animal production than in people. Dr Tun is also in the process of studying the levels and sources of AMR in hospital wastewater, which does not require special treatment in Hong Kong before being discharged into the sewage system, and how AMR may be transmitted in the household, such as via countertops or other surfaces. “The One Health concept is very useful not only for COVID-19 but other types of diseases. Whether you look at the community level, the global level or the individual level, this concept can apply. You cannot stay away from the environment,” he said. Dr Tun’s work on a particular type of AMR bacteria, ESBL-E, has been revealing of how environmental and human factors interact. The WHO has prioritised ESBL-E because it can transfer AMR to other bacteria, so if someone with ESBL-E in their gut is exposed to salmonella, it can transfer resistance to the salmonella, making it very difficult to treat it with antibiotics. In a study of 90 Hong Kong travellers that measured their gut microbiota before and after travelling, he found exposure to raw seafood was a factor in those who acquired ESBL-E after their trips (although about 40 per cent tested positive before travelling). People were also more likely to have ESBL-E if their gut lacked bifidobacteria, which are beneficial. “This is why carriage of AMR bacteria is so important. If healthy people carry it in their gut, those bacteria can share the resistant gene to pathogenic bacteria and put their health at risk,” he said. Dr Tun also studied AMR in the wake of COVID-19 among some members of the traveller cohort. There was speculation that AMR would increase as people self-medicated with antibiotics, which the study seemed to support – participants had more AMR bacteria as well as chemicals related to masks in their guts. “We are trying to recall these participants to study the health impacts of this,” he said. “We need to think collectively, across different sectors and expertise, to have more of the multidisciplinary and interdisciplinary collaboration that we’ve seen with COVID-19. It’s also important to have participation from the public,” he said. Dr Tun has been promoting citizen science in less-developed countries to involve residents in collecting data, such as exposure to animals and the environment, through their phones. “This way they can know what their risk is and what the problems are. They can have a sense of ownership of the data and findings.” Stark warning That need for collective purpose is echoed by Professor Zhang and Professor Peiris. The concept of One Health should be an easy sell, Professor Zhang said. “Especially in China because Chinese philosophy tells us that everything is connected, that it’s not separate.” He sees the environmental sector as best placed to lead the way, such as through UNEP. Professor Peiris, however, has seen first- hand the difficulties of having policymakers and businesses monitor and respond to health threats – in the lead-up to the H7N9 outbreak in China, the poultry trade had little incentive to monitor for viruses because any infections meant they would have had to cull their stock. Similarly with MERS, the camel industry in Saudi Arabia has been resistant to evidence that the MERS virus comes from camels. MERS remains a pandemic threat. Recent research by Professor Peiris and international collaborators showed that it is present in camels across North Africa and the Middle East. It is still in a milder form than the Saudi Arabian version, but the worry is that it, too, could evolve to be more pathogenic in humans. “We have to be concerned because MERS is repeatedly jumping to humans. There is no reason why it cannot further adapt to become more efficiently transmissible to humans,” he said. Professor Peiris sees infectious disease threats in the wider context of the great challenges facing the planet and the similar urgent need to collaborate and break down institutional and other barriers in order to find solutions. “It’s not just infectious disease. You can see issues of climate change, environmental pollution, loss of biodiversity – we are really rupturing the limits of sustainability of our planet. I think it’s important for everybody’s education, but particularly for medical education, for us to realise that it’s not just about treating individual humans. We have to take account of animals and the environment, too. We have to be advocates. “If we want human health to be better, we have to look after planetary health, environmental health and animal health,” he said, adding this cautionary note: “Rene Dubos, a French microbiologist, said in 1959 that ‘at some unpredictable time and in some unforeseeable manner, nature will strike back’. COVID-19 is a great illustration of that.” Increased opportunistic pathogens and resistance genes in the gut microbiome during the first wave of COVID-19 in Hong Kong. Professor Zhang Tong (right) giving a presentation to the HKSAR Chief Executive Mrs Carrie Lam, HKU Council Chairman Professor Arthur Li and HKU President Professor Xiang Zhang on the work of the Environmental Microbiome Engineering and Biotechnology Laboratory. Professor Zhang Tong (centre) with Laboratory Manager Ms Vicky Fung (left) and Research Assistant Professor Dr Yu Deng (right). A conceptual model to demonstrate the evolution and emergence of antibiotic- resistant genes accelerated by selective pressure of antibiotics. Extraction of SARS-CoV-2 RNA from sewage using an automatic extraction machine. It is impossible to completely remove antibiotics from wastewater so some inevitably escapes into the environment... Eventually, there will be more and more superbugs. PROFESSOR ZHANG TONG The One Health concept is very useful not only for COVID-19 but other types of diseases. Whether you look at the community level, the global level or the individual level, this concept can apply. You cannot stay away from the environment. DR HEIN TUN 06 The University of Hong Kong Bulletin | November 2021 07 COVER STORY

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