HKJCDPRI Webinar Series: Emergency Response to Infectious Disease Crisis

HKJCDPRI Webinar Series: Emergency Response to Infectious Disease Crisis


I’m Dr Rex Lam. Sitting next to me is Doctor Thomas Tsang. We are the chairmen of this session. So Dr Tsang, may I ask you to introduce the first speaker of this session? Ok, thank you. So our first speaker for this session is Professor Malik Peiris. He’s currently the Chair Professor, and Director of School of Public Health at the University of Hong Kong. And Professor Malik Peiris was also elected a fellow of the Royal Society of London in 2006, as well as award recipient of the Silver Bauhinia Star from the Hong Kong SAR Government in 2008. Now for those of you who do not come from a microbiology background, let me tell you this. Malik is the pre-eminent microbiologist, particularly virologist in Hong Kong, and he has an extremely high reputation internationally. I have seen a cult of followers following him at international conferences. Professor Peiris is also a key figure and unsung hero when Hong Kong faced our SARS epidemic and also our avian flu epidemic, and the scientific discoveries that Malik made actually changed completely the way that we handle these epidemics. And Malik is an extremely kind and approachable person, and as you’ll find out, his lectures are always clear, stimulating, and gives you a lot of food for thought. So without further ado, let me introduce Malik to you. Thank you. Thank you Thomas for that kind introduction. This particular session is on emergency response to infectious disease crises. One important difference, in terms of crises and disasters associated with infectious disease, to other disasters, whether it be tsunamis or earthquakes, is that infectious disease problems start very insidiously, and then they grow exponentially, whereas most of the other crises, you immediately know you have a problem, and essentially, you are managing it and hopefully things get better over time. So this is infectious disease disaster in Hong Kong, or a crisis in Hong Kong about 120 years ago, which happened not too far from here, and this is in Hollywood Road as you can see, and this is due to the plague outbreak that affected Hong Kong, and clearly, impacted hugely on the population of Hong Kong. Here you can see removal of dead from the affected area. Subsequent to that, in the 1950s and 60s, basically it was believed that problems of infectious diseases were under control and not really a cause for major concern. But in the 90s, there was a gradual awareness, I think, that infectious disease is really, can continue to pose a major threat at every level, but really I think this got crystallized during the SARS outbreak, which as you remember, there was an outbreak in Guangdong, a patient came to Hong Kong, stayed in this Metropole Hotel, and infected people, and they went all over the world and spread the outbreak, an outbreak that Thomas was intimately involved in. So, over 8000 people infected, and about 800 people dead globally. In addition to the numbers, so if you just see the numbers of cases in Hong Kong, about 1700 and close to 300 dead, but beyond the absolute numbers, the impact of SARS was huge, and as you can see here from this newspaper cuttings, these are healthcare workers who died, and the psyche of Hong Kong was scarred during that outbreak, and the economy of Hong Kong was equally damaged, as you can see here. A whole bunch of restaurants were empty, the airport, you never see it like this, Cathay Pacific was affected, the MTRC was affected, etcetera. And here, this just shows the economic impact of a number of infectious disease crises, so SARS is estimated to have cost 40 billion US dollars, avian flu, just in one year, when it spread across Asia, cost about 20 billion US dollars, just for that year. Of course, this includes the cost of poultry culling and the impact on the poultry industry. BSE, or Mad Cow Disease, again in just that one year, about 16, 17 billion US dollars. So these are very costly episodes, and in addition to the economic and health costs of course, there was the social cost and also the political cost, which I’m sure you remember. Now, Hollywood movies are, generally speaking, really far-fetched, but this particular movie actually is fairly realistic. There are some things that are not realistic, if you watch the movie, if you haven’t, I recommend that you do watch it. What is not realistic is, this is partly set in Hong Kong, and the way that the Department of Health or the CHP equilvalent of Hong Kong is depicted I think is completely, completely fictitious. I mean it is said that they kidnapped the WHO official and hold the official hostage until WHO gives them vaccine, and overall, you know, so that part is completely rubbish, but actually, some of the impact of a global pandemic, as is depicted in this film, is not too far from the truth. I mean it does depict the impact of things like Twitter and Facebook and all the social media and how this is important in spreading misinformation and rumors and the impact this might have all across the world. So this is the 2009 influenza pandemic, which fortunately was not very severe, but I think what this shows, and this is data from Hong Kong from serial sero-epidemiology studies in the community, you can see that we knew about this virus in April 2009 and by September 2009, 30% of children were already infected by a virus that emerged half the world away. And within the next two or three months, it went up to 45 and 50 percent. So it just shows how quickly, particularly a respiratory transmitted infection can spread. So some of the lessons from SARS, and I’m sure Thomas can do this better than me, but early recognition, diagnosis, isolation, and infection control clearly is so important, but it’s not just infection control once you know that you have an outbreak because the biggest damage is done before you actually know what the problem is, what the cause is, and really, you need to have robust and sustainable and routine infection control systems that are routinely operating in our health systems. The early, rapid, real-time reporting systems, which have gradually been put into place following SARS. The integration of the hospital sector with the Department of Health and the private sector, the command and control structures, communication, and understanding the perceptions of the population and human behavior in response to such an outbreak, and of course, continued training and drills for such events. So let me first address this issue of early recognition and diagnosis. So why is this so important? Here you have a typical outbreak epidemic curve, and in this particular scenario, you see the first case here, you have gradual increase in number of cases, the detection is delayed up to here, and the confirmation is delayed further up to about here, and the response sets in. So really, the impact you have in containing that outbreak is very limited because most of the damage that has occurred already. On the other hand, if the detection of the outbreak is early and the response is early, you really have a huge opportunity to avoid this huge part of the disease spread and disease burden. Now even if you cannot completely stop an epidemic, for example like in the case of influenza, like influenza pandemic, still, early recognition and measures may be able to spread this epidemic peak and flatten it so that you may have the same number of cases, but then it is spread out over a longer period of time. It helps the logistics and the management of the outbreak overall. So really early detection of novel emerging infectious disease events first and foremost depends on the alert clinician. So of course things did not go too well in mainland China during SARS, but on the other hand, in 2013, it was an alert clinician in Shanghai who actually noticed three people in the same family, three adults in the same family, who had severe pneumonia, and this rang alarm bells, and led to the investigation and identification of a new virus in these people, so clearly, this was a success in terms of early detection. Of course, unfortunately, recognition may take longer than is ideal, as I mentioned, SARS, the MERS outbreak in Korea, just recently, actually this was 2015, not 14, the Ebola outbreak starting in 2014 going on into 2015, and even in places like the Netherlands, a Marburg patient was hospitalized for one week before actually clinical suspicion was raised. So this is very important, but clearly some times causes problems. Now in terms of laboratory diagnosis, I won’t go into this in detail at all because you’re not a primarily laboratory audience. Over the last decade or so, we now have a much more powerful array of tools to recognize and detect pathogens, including molecular methods and also these next gen sequencing methods. However, I think it is important to know that you really have to maintain this whole array of conventional as well as novel diagnostic approaches. It would be a real mistake, I think, to just rely on these new approaches and ignore and shut down some of the traditional approaches. You really need to have the whole panel available to be able to detect these pathogens early. So coming back to SARS, if you look at the global epidemic picture, this is what it looks like. You know that the first cases, in retrospect, started around November, and there are individual cases going on like this, and then the outbreak in Guangzhou and then spilling over to the rest of the world. So clearly, detection and response at this point could potentially have prevented a huge global outbreak. I gather you have heard quite a bit about Ebola, but again this is the epidemic curve of the early part of the Ebola outbreak, and that started also around December of the previous year here, and there were cases grumbling around here, and it was only in March that even the question was raised that this could be Ebola, and specimens were sent for diagnostics, and the diagnosis was confirmed. So that really lost the opportunity to contain this outbreak, just like previous Ebola outbreaks had been contained. So this was the exception, rather than the rule, in that regard. Then , of course, there was also, even after the outbreak was clearly known, there was a delay in the global public health recognition that this was more than the usual Ebola outbreak, and international public health emergency was declared at this point in time, so this clearly has been criticized on a number of levels, so as you know, the total consequence was almost 30,000 human cases and almost 11,000 plus deaths. So as you might know, there was a panel that investigated WHO’s response to the Ebola outbreak, and these are some of the key recommendations they made, the headlines. They made the point that the International Health Regulations, which as you know, all countries in the world signed up to in 2005, member states, and in this particular case in West Africa, have really failed to implement the core capacities that are needed, and actually this was not just in West Africa. More than half the countries of the 190 odd countries that are signed up to this have, up to now, not fulfilled the criteria that are required for surveillance, data collection, laboratory diagnosis due to fulfill the requirements under the International Health Regulations. So I think what is notable is that later in the outbreak, the USA committed 5.6 billion US dollars to combat Ebola outbreak within the United States and abroad, and one cannot help but wonder whether if the developed countries of the world committed this type of money in advance to help the less developed countries to improve their capacity to respond to emerging disease outbreaks, at the epidemiology level and the laboratory level, maybe, you know, these types of issues can be provided in the future. Another important recommendation from the assessment panel was the delay in the declaration of the public health emergency of international concern, which I talked about, and the other important point was that they made was the fact that WHO, perse, does not have the capacity on the ground to respond and intervene. They are usually at a much higher level, at a technical level, they don’t have the grassroots capacity on the ground, so really the need for WHO to have collaborated with the wider NGO and even within the WHO system the humanitarian systems that are on the ground, which are very capable of responding to health crises, like earthquakes, and tsunamis, and such like, that connection really was not made. So we come back to this list of lessons, and I think in the case of Ebola, in addition to all of these things, it was also clear that not understanding the perceptions and behavior of the human population, particularly in Guinea, as you know, some of the healthcare workers were even killed because of people really not understanding and the fact that the communication was not satisfactory. So let me go back to another example of where early recognition and early infection control is so crucial, and that is the MERS outbreak earlier this year. As you remember, there was a man who traveled in the Middle East at the end of April, early May, he came back to Korea on the fourth of May, and he got ill on the eleventh of May, he went to a couple of hospitals, and it took about 10 days or so for him to be diagnosed with MERS. So what happened? So this was the index case, and he first went to one clinic, he was not happy, he went to another clinic, and each of these places, he transmitted the infection to healthcare workers, and then he went into, he was admitted to this Pyeongtaek Hospital, St. Mary’s Hospital, and he was there, and again, he was not happy there as well, so again you might have heard about this hospital shopping tradition that you have in Korea, where people because of their insurance cover can move from hospital to hospital easily, and if they’re not happy in one hospital, they go to another hospital. So this guy then moved to the Samsung Medical Center, and it was at Samsung Medical Center really that the first history, the first travel history of this person was elicited, and the suspicion, his travel to the Middle East led to the suspicion to the possibility of MERS, and MERS was diagnosed. So there was no further transmission from this person at Samsung Hospital. You remember Samsung Hospital had huge problems later, but the initial response for the initial patient was fantastic, then this patient was transferred to the National Isolation Hospital, and that was that. But of course, unfortunately, that was not that because in this Pyeongtaek Hospital, there was a failure of infection control, which led to a number of people on that ward being infected. There was a second failure where once they realized there was an outbreak on the ward, they closed the ward, which is one thing, but then they transferred patients in the ward, who of course in the ward for other healthcare needs, they transferred to another ward, and of course, some of these people were incubating the disease, and then they led to an outbreak in the second ward. The isolation and quarantine of people was not very adequate, so one of the contacts of this particular case, although this guy was identified and had been told to stay at home, in home isolation, this was not really enforced, so he traveled through Hong Kong, as you remember to China, and he caused a lot of problems along the way. Then, another patient from this cluster, of course he was not ill at the time because he was admitted for some other condition, he was discharged, he went home, he got sick, went to a hospital here, he was not happy, then he went to the Samsung Medical Center, and in the Samsung Medical Center, he, again, there was no clear history, and office contact with the, and his admission to the previous hospital, or it was not recognized as important, so he was kept in the Accident and Emergency area for one and a half days, and during this time, he transmitted to a whole lot of people, which led on to a huge outbreak at Samsung Medical Center, with more than 75 or 80 people being infected with MERS. So this just shows now the outbreak at Samsung Medical Center, then going on from this place. So, overall, the outbreak spread, and this, you can see, the waves of the outbreaks St. Mary’s, Pyeongtaek Hospital here, and Samsung Medical Center here. So by the end of the outbreak, it was 186 cases and 36 deaths, and again, the social and economic impact was huge, so this is a recent article which estimates that South Korea lost about 700 to 800 million US dollars purely on the basis of tourism. Now this is not counting the human cost, the social cost, and everything else, but again, pointing out that these outbreaks do have a huge economic cost. Now, in terms of these outbreaks, modern healthcare, we have an added vulnerability, and this is because there are invasive procedures that are done, such as invasive ventilation procedures and others, and some respiratory viruses, and this is true of SARS and MERS survive better and longer in air-conditioned, cool, low humidity environments, and also the fact that these are closed, no windows, and under a normal ward setting, less air changes. These contribute to outbreak. So this actually shows data from the survival of MERS coronavirus and influenza coronavirus compared. If I had influenza, and I’m talking here and i’m coughing, and I contaminate the surface of this podium here, if you come back in about eight or nine hours, essentially, the virus would be dead. If I had MERS, and I do the same thing, and since this is a fairly low humidity, air conditioned environment, you can see that the virus really would be quite alive and well, even one day later. So these viruses survive optimally on surfaces in low humidity, low temperature environments. And this is also true of SARS, as we reported some time ago. Now these outbreaks, of course, they spread from human to human, but at its start, emerging infectious diseases originate from animals to humans, so this is a paper which has mapped high risk areas for emerging infectious disease from zoonotic wildlife, and you can see that we are in a high risk area here, and again from zoonotic non-wildlife, meaning from domestic animals, and again, we are in a high risk area here. So what is happening is some of these pathogens, viruses, are present in domestic livestock, and maybe in wild animals. From time to time, it spills over into humans, most of the time not recognized, but sometimes causing zoonotic disease like H5N1, H7N9, MERS, Nipah, for example. And much more occasionally, they adapt to transmit effectively from humans. So of course you know about influenza pandemics, you know about SARS, but there are two other coronaviruses that have emerged from animals to humans and are present with us everyday. These are the coronaviruses 229E and OC43, the causes of the common cold, and now we know these came from animals. In the case of one from cattle, the other one from bats over the last 200 years. So these viruses have successfully crossed from animals to humans and become endemic, at least these two, in the human population. So these are real threats. So we’re talking about viruses jumping from animals to humans, so this is the time that we see it, when humans start seeking medical care, but then, if you go upstream, ideally, if you can detect it at this stage, maybe at the stage of zoonotic transfer before these viruses get adapted to humans, the cost of containing such an outbreak would be greatly enhanced, but of course this is easier said than done because there are so many viruses out there in animals, and we don’t know which ones to prioritize. So example of that, in the case of SARS, again if you remember going back in time, in November, December 2002, there were outbreaks in a number of cities in Guangdong, and most of these were originating from these game animal markets, so subsequently, my colleague Yiguan showed that in these markets, he could find very closely related viruses to SARS, so these were jumping from these markets to humans, each of them giving rise to short outbreaks, which died down until, of course, there was the big outbreak in Guangzhou, and which then spread globally. Now that of course was a failure, clearly at that point in time, but that is asking quite a lot. But the knowledge that these game animal markets were important for transmission was crucially important because, if you remember, MERS re-emerged in December 2003 and January 2004, so the knowledge that it was coming from these game animal markets, then led to the aggressive containment and control of these game animal markets, and probably prevented the re-emergence of SARS. So these are pandemic viruses, and this is just showing that there are, although you cannot predict which virus might become a pandemic, there’s at least now structured ways in which to risk assess these viruses, and for example, with avian flu H7N9 interventions, such as market closures and other interventions, such as market rest days and banning the holding of poultry overnight, which clearly reduces the risks. So these are preemptive interventions that one can take, once a potential risk is identified. So this also implies a close involvement of the human health sector with the animal health sector. And then, very finally of course, there is also the concern about bioterrorism. These, if you remember, are the letters associated with anthrax outbreak in 2001 after the 9/11 attacks, and these are some of the potential pathogens that have been listed as potential bioterrorist agents, but I think while this is important, you really need to recognize that nature is the most efficient bioterrorist of all, so while we can be worried about this, we really have to be worried about things that nature throws at us. And again, finally, we really have a lack of validated countermeasures. So for example, there are the known knowns. So Ebola was known from the 1970s, and because of the concern of bioterrorism, there were actually vaccines and antivirals tried out and tested in the laboratory and maybe even in animal models, but they were not taken forward. Then we have things like the known unknowns, like MERS, SARS, their re-emergence, and viruses like Nipah, which are crossing from animals to humans. We don’t know whether they will become epidemic and pandemic, but how do you prepare for it? And then of course, there are the complete unknown unknowns, which may come at us from anywhere. And how do we respond to this? How do we make countermeasures for these, without really being able to clearly have a justification for the investment? Clearly big pharma is not going to invest in these types of issues because there is no guarantee, or even a probability, that, of a return on investment, so we really have to think of other ways to prepare for such events. Now when we have life insurance or car insurance, we pay our insurance premiums happily, and we don’t complain that we haven’t had an accident, you know this year or last year. And then we have countries that have these very very expensive machines that are floating around in the sea, and you know a nuclear submarine costs 2.4 billion US dollars, and you know, these we don’t complain that these things do not fire nuclear missiles either. So I think we really have to come to a new approach to develop countermeasures for these in a more proactive way. So just finally, I think just to point out, that early recognition and response to emerging infectious diseases is cost saving as well as life saving. The cost of failure is high. The impact on health, economic impact, social impacts, and political impacts. Epidemics start insidiously but can escalate exponentially. And we live in a global village, so a novel pathogen or infectious disease epidemic anywhere is a threat everywhere. So with that, I will end and thank you very much. Thank you Professor Peiris. Now we have five minutes for Q&A. Are there any questions from the floor? Ok, maybe I’ll fire the first one at you, Malik. Honestly, during the SARS epidemic, your team actually did a very crucial job in finding a pathogen, studying its properties, help evaluate our control measures, a lot of things. Now with the proliferation of all this new diagnostic technology, are we confident that we can easily detect novel pathogens if a similar incident is to happen to Hong Kong? Are you very comfortable, let’s say I give you a specimen, that you can give me an answer in 24 hours time? You’re always a challenging person, Thomas. So I think clearly the technologies have improved quite dramatically. Having said that, I think we would be really being very complacent if you think that, if you have a completely new pathogen causing an outbreak today, that well, I don’t think we can get the result in 24 hours, but even within a few days. I think, I mean many of the technologies really are there, particularly next gen sequencing, in theory should be able to provide the answer. I think if you take it more globally, I mean more, in a wider context outside of Hong Kong, I do have a lot of concerns, and the concerns are, even in a place like the United States, so what is happening now in the laboratory setting is that tests are becoming more and more automated, they are becoming molecular, but targeted to particular pathogens, which of course are known pathogens, and the capacity to detect something unknown, in one respect at the routine level, is shrinking. This is why I made the point that some of these new technologies may be good, but we should not discard the old technologies. I mean if you think about it, it was virus isolation that lead to the discovery of SARS, to the discovery of MERS more recently. So I mean, hopefully, Hong Kong would be able to respond quickly, but I’m not at all sure, even in developed countries, depending on where this happens, which laboratory it goes to, if it doesn’t get recognized as serious enough to be referred up to appropriate laboratories with the capacity, I mean you saw that case in the Netherlands, a patient there for 14 days or something like that, so really, you could have things leaking through the cracks, so I don’t think we can be complacent at all. Yea, excellent answer. I totally agree. So any other questions? Dr. Lo, emergency physician from Kwong Wah Hospital. Professor Peiris, in 2003, when we have the SARS outbreak, there were rumors that it is bioweapon. From your experience, is it possible or is it just rumors? Right, in the case of SARS, I think there is no question that it is a naturally emerging agent because you know, now we know that viruses very close to SARS are present in bats. I mean, very early as I said, it was found in the markets in civet cats and things like that, but the natural reservoir is in bats. So it’s a virus that’s found in nature. So without any absolute doubt, one can say in the case of SARS, it was a naturally emerging virus. Now at another level, now of course I remember very clearly when the Amoy Gardens outbreak was taking place and there was this, dozens of, I remember getting the telephone call in the lab, and they said they were sending 50 specimens of suspected SARS from this one housing complex, and I said what do you mean, 50 specimens from one housing complex? I mean, so at that time, people certainly were wondering whether this is something, some form of terrorism. But I think certainly, once the sequence of the virus was known, it was clear that this was not a patched up job, with genes of one known virus and another known virus put together. It was a completely new agent as far as we knew. And to be honest, technology is nowhere near sophisticated enough to create a life form that is able to spread like this from completely originally, of course we can put together genes of this and that and maybe create something, but not create a completely new virus that will spread maybe we are far away from that. You might have heard people saying that they’ve synthesized life. Yes they have synthesized the polio virus, they have synthesized even a small bacterium, a microplasma-like bacterium, but here, they are just copying a known agent, and they are synthesizing a known sequence, not creating life, which is a different story. So. I have a question for you, Professor. So in public health, we have the concept of one health, that means we are actually not taking care only for humans, we are also taking care of animals, and we know that now that many emerging infections actually come from animals, is it a good idea to build an extensive virus library that cover every virus that you know of from animals as well, in order to facilitate the process of identification in case of a new emerging disease in the region? No, I think that is certainly worthwhile doing, but you have to know the limits because the diversity of viruses out there is almost infinite, right? So you can catalog these, but it’s only a microscopic number of them that really pose any threat to humans, so a big challenge is risk assessing that diversity. But still, it is worth understanding the diversity because we would understand the viral genetic sequences that are out there, so that we are probably better set up with diagnostic tests covering this huge diversity so that if any of these do cross over, we would be better placed to respond. So that is one level. At the diagnostic level, that is important. Then at the second level, I think the real big challenge is to be able to risk assess which of these viruses can jump to humans. So the most advanced, you know group in that regard is with influenza. But even with influenza, we are still quite a long way off from being able to, we of course can’t predict. But I think with influenza, we are getting better and better at risk assessing viruses that are of concern, so I just very quickly went through that slide, but if you look at that paper, that is a whole list of criteria that are now used whenever there is a new virus to try to place it on that graph of emergence risk and severity risk and that allows us to risk assess it.

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