Emergencies preparedness, response

Severe Acute Respiratory Syndrome - Press briefing

Wednesday, 16 April, 13:30 Palais des Nations

World Health Organization
Dr David Heymann, Executive Director, Communicable Diseases Dr Mark Salter, Clinical Management Coordinator
Dr Klaus Stohr, SARS Etiology Coordinator; Project Leader, WHO Global Influenza Programme
Mr Dick Thompson, Communications Officer

SARS laboratory network
Dr Christian Drosten, Institut für Medizinische Virologie im Klinikum der Johann Wolfgang, Goethe-Universität, Frankfurt am Main (in collaboration with the Institute for Tropical Medicine, Hamburg, University of Marburg)
Dr Robin Gopal, Central Public Health Laboratory, United Kingdom
Dr James Le Duc, Centers for Disease Control and Prevention, National Centers for Infectious Diseases, United States
Dr Aiee Ling, Singapore General Hospital, Singapore
Dr Albert Osterhaus, Erasmus Universiteit, National Influenza Centre, the Netherlands
Dr Masato Tashiro, National Institute of Infectious Diseases, Tokyo, Japan
Dr Sylvie van der Werf, Institut Pasteur, National Influenza Centre, France

Mr Dick Thompson: This is a SARS briefing, a science update. We will just get right to it. I will turn this over to Dr David Heymann, Executive Director of the Communicable Diseases section.

Dr David Heymann: Thanks Dick, and thanks to all of you for having come this afternoon. As you know, the World Health Organization (WHO) is only as strong as its partners, because we work through partners and with partners. We do not do work ourselves, but we facilitate the work of others. Certainly nothing is more clearly demonstrating how WHO works – and the comparative advantage of this – with the international partners who are here today attending a meeting, face to face, and with colleagues in Hong Kong and China by videoconference. This meeting is to look at the latest laboratory findings. This network of laboratory directors has been meeting by telephone, sharing on a secure web site for the past four and a half weeks. They are all here today. It is very interesting because these laboratory directors have put aside profit, certainly prestige, and national pride to work together to help put into the public domain the information that is so necessary to learn about this disease. And it has been done in record time. If you think back to when we made the global alert, one of the major reasons it was made was because we did not know what was causing this disease and because it had started to spread internationally. Today, we have made a step closer to that, and I will now turn over to Klaus Stohr who has been orchestrating these collaborations with the laboratory specialists and directors.

Dr Klaus Stohr: Thank you. We have been talking during the past four and half weeks a lot about the contribution of the 11 – now 13 – laboratories in the hunt for the SARS etiological agent. We are very pleased today that we can introduce to you some of the colleagues, others are still missing because they could not get badges made for them in time. These colleagues, jointly with our partners in Hong Kong and in China that have linked in by videoconference, have reviewed this morning what information is available on the SARS etiological agent. All the data have been put on the table, have been reviewed, and the colleagues have come to a consensus agreement. We can now say that the disease called SARS, which was first reported on 12 March, exactly five weeks ago, is being caused by the coronavirus. WHO will call this coronavirus “SARS virus”. The research that has been conducted by this laboratory network has been dedicated to Dr Carlo Urbani, the WHO colleague who detected the disease and died from the disease on 29 March.

I would like to go through our colleagues who are sitting here and briefly introduce them to you, and also quickly mention what they have done to make this statement possible.

On my left here next to David is Dr Masato Tashiro, the director of the Department of Virology in the National Institute of Infectious Diseases, Japan. Dr Tashiro received the first samples from Hanoi. He was instrumental in excluding influenza as the cause of the outbreak in Asia. He has also been key in comparing the performance of various diagnostic tests.

Next to him is Dr Aiee Ling from Singapore. She has been important in understanding the involvement of paramyxovirus in the development of this outbreak and in understanding the involvement of paramyxovirus as a causative agent. She has also done a real-time confirmation of coronavirus findings from patients in Singapore.

Dr Robin Gopal represents the Public Health Laboratory Service in the UK. They have done a number of comparisons of performance of diagnostic tests and have produced reagents for other WHO laboratories.

I would like to continue with Dr Osterhaus. Dr Osterhaus is the one, he and his colleagues, who have been adding the final piece to the puzzle of research that took place during the past five weeks. His team has conducted the trials in monkeys with the coronavirus. He is the one who reported this morning that the Koch's postulates have been fulfilled. We can now with all confidence say that the causative agent of SARS is the coronavirus first detected in Hong Kong on 21 March 2003.

The meeting in which our colleagues participate has two objectives. One I already mentioned: we wanted to look at all the data that are available, to also look at the findings from China as far as chlamydia are concerned, as well as metapneumovirus. The second objective is, this afternoon, we are going to develop a strategy for the development of a diagnostic test, a test that will be reliable and dependable and can be used in developing as well as developed countries. Some new data were put on the table this morning regarding excretion pattern as well as stability of the virus and the usefulness of serological tests for disease diagnosis.

I would like to take the chance also on behalf of WHO to thank these colleagues for having contributed and collaborated so closely. You know very well that scientists are competitors by default, they compete for the fame, they all want to become Nobel prize winners – and some of them might become Nobel prize winners shortly – they all want to have an article in Nature, they want to be first author of an article in Science. All this has been set aside. All this has been overcome by the understanding that we are being faced with a public health emergency. I would like to thank them all.

Just in time we have Dr Sylvie van der Werf from the Pasteur Institute in Paris. She has been mainly working with samples from Viet Nam. They have started, at the first laboratory, with animal testing. They have been contributing to virus sequencing and also understanding the excretion pattern.

Next to her is Dr Jim Le Duc from the Centers for Disease Control and Prevention (CDC) in Atlanta. CDC has conducted certainly the largest number of investigations of samples from many countries. CDC has been key in detecting the genetic material of SARS virus after the first isolation in Hong Kong. They have also posted the complete sequence of the genome on the WHO secure web site. The quality of the sequencing has been confirmed by many other network laboratories.

Next to Dr Jim Le Duc is Dr Christian Drosten, who represents a network of laboratories from Germany. They were the first to detect a paramyxovirus in specimens from the patient from Singapore. They confirmed and expanded the coronavirus findings from other laboratories, and they are now leading in the development as well as the fine-tuning of very sensitive PCR tests. They have also facilitated the development of a test kit, which is now available.

With this I would like to open the floor for questions.

Q. Three questions. The first concerns the PCR test that WHO put on the web site. Can this test detect asymptomatic patients of SARS? The second concerns medication. In Hong Kong, they use ribavirin and steroids. We have seen that they have a lot of side-effects in babies and pregnant women. I wonder what are those medications your countries use and what would be your recommendation. Also, the possibility of a combination of Chinese medicine and western medicine. The third question concerns the situation of Amoy Gardens. Not only is atypical in terms of the means of transmission, also it seems that patients in Amoy Gardens do not respond well to ribavirin and steroids. They have other symptoms such as diarrhoea. Also, unlike in most SARS cases where patients who die and became seriously ill are aged over 40, in Hong Kong we have cases aged 30 or 40 with no chronic diseases in the past, but they also die of SARS and they are all from Amoy Gardens. What are your views on this? Thank you.

A. Dr Stohr: Thank you for the question. I would like to give the floor to Dr Drosten to talk about the PCR test. What I would like to emphasize is that with the identification of the coronavirus as the causative agent, now we can develop more specific diagnostic tests for this pathogen. It is also now possible to fully focus on one pathogen and not be forced perhaps to develop other diagnostic tests for other possible agents. With this I would like to give the floor to Dr Drosten.

Dr Christian Drosten: [speaker off microphone] ... develop molecular diagnostic tests. We were of course not the only laboratory within the network that did this, so for the time being there are some molecular diagnostic tests which in principle all work the same and should in principle all have the same performance characteristics. We have done some evaluation of this. What I can tell is that we can analytically find about 500 viruses per millilitre of respiratory material. But what epidemiology has now to confirm is how useful this will be in clinical terms, for clinicians. There are of course some hints from beforehand that I can tell from now. This is that, most probably, through most of the symptomatic period that the patients show, we can see the virus in these tests, but we cannot for the time being say this will have any consequence to real clinical acting. For this we need more patients and more epidemiology and more evaluating of these tests.

Dr Stohr: This is the reason why these people are going to meet this afternoon. We would like to better understand what the performance criteria are of these tests. With PCR you can only detect genetic material. You cannot detect, you are not sure whether what you are seeing is a live virus or is only an immature virus that cannot cause disease. So from that perspective, even finding of coronavirus traces, in possibly non-clinically ill patients, is not very indicative.

I would briefly like to go with the ribavirin questions. Ribavirin has been tested in Hong Kong for a relatively long period of time. It is no more than two weeks that the Department of Health has been recommending ribavirin treatment in combination with high doses of corticosteroids. They are reporting a significant improvement of the clinical course of the disease. Ribavirin is known for very many years. It has side-effects. They are not unusual, they are not unexpected. On the other hand, in vitro testing, the testing outside the human body, of ribavirin with coronavirus has shown that coronaviruses are resistant. So all this has to be verified. These tests are ongoing.

There is a battery of other antiviral drugs that are currently being tested. This is the reason why we believe the finding of this coronavirus as the causative agent after we have now fulfilled the Koch postulates is so important. Now the research can be focusing on this virus. This virus will help us, or let us say that the research will help us to develop new drugs. Now we can focus on one pathogen, which has now been sequenced, which provides additional information for the development of tests. Now one can also think perhaps about vaccine, if there is a need be. We are still I think optimistic that we can control the disease with the measures that have been implemented and the understanding of the genetic composition of the virus will certainly also help to implement global surveillance.

Dr Heymann: Amoy Gardens. Let me also tell you, Esther, that the PCR test, if it can detect the virus, can detect it in people who do not have symptom as well as those who do. If it is sensitive enough to find the virus, it can find it in all people who might be infected. Amoy Gardens, as you know, as Klaus just said, they have found that the virus particles at least are in faeces and in urine. It is normal that if it is in faeces that it may be causing diarrhoea, and actually 10% of patients do have diarrhoea worldwide. So diarrhoea is a symptom. In fact, I went through Paris airport and on their alert for SARS they do list diarrhoea as one of the symptoms. It is a common symptom. That is some of the intrigue of knowing why people in Amoy Gardnes might be different than other places. It may be the way in which they are getting infected. There are all kinds of theories that you could use in saying why they get diarrhoea. Maybe that they are getting infected by the mouth, that it is only to be determined as time goes on and as the studies are done.

Q. Fuji from Kyoto news Japan. Previously there was some speculation that paramyxovirus and/or chlamydia could have been playing a role in causing SARS. Now today that you have identified the causative agent as coronavirus, can we now safely say that it is caused solely by coronavirus and that paramyxovirus and chlamydia does not play any role in this? Secondly, there has also been some speculation and concern that the SARS virus may still be evolving, could change its composition or shape. Can you comment on this issue as well?

A. Dr Stohr: I think Albert Osterhaus will be the best person to answer your question regarding the involvement of metapneumovirus and other pathogens. Let me quickly talk about possibilities for the evolution of this virus. We have established that this coronavirus is the cause of SARS. We know that it is a coronavirus. All coronaviruses are subject to mutation. All of us, we are subject to evolution. The virus is also, but this virus tends to mutate relatively quickly. It is part of a family of viruses that is just prone to change their genetic material relatively quickly. So it would not be a big surprise if this virus were gradually changing its genetic makeup. How much this change impacts on its pathogenicity, its capacity to cause disease, how much this impacts on immunogenicity, its capacity to develop antibodies, remains to be seen. We will certainly see changes in the genetic makeup of this virus.

Dr Albert Osterhaus: As to the cause of the disease, I think that if you look, what happens is that first of all this paramyxovirus – this human metapnuemovirus – was found. Human metapneumovirus is a virus that we discovered about two years ago as the cause of serious respiratory infections in children, the elderly and also immuno-compromised individuals. But we were quite astonished that this virus as such should be the cause of this new disease; now that would not make sense. Then we were very happy to learn that originally in Mulloch Pierce's work in Hong Kong, identified the virus that we have all followed up. So we ended up with two different viruses: the coronavirus and the HMPV. There is also discussion about this chlamydia agent. This led us to postulate that it would not be impossible that we would perhaps have a double etiology, so one virus coming first and the other one coming later and then aggravating the situation. This is the reason why in discussions with the network, we discussed that in our telephone conferences. Then we decided to do an experiment in monkeys. This experiment was set up in such a way that we infected monkeys either with the coronavirus that was cultured or with the human metapneumovirus. A third group we infected first with coronavirus and then with metapneumovirus. The interesting thing we found, and that goes back to the Koch's postulates that were formulated more than 100 years ago, that the animals infected with the coronavirus alone developed full-blown disease. They developed SARS, they developed clinical symptoms, and they also developed the pathological lesions that are identical to what we have seen in people who have died from SARS. The animals with the human metapneumovirus, the first virus that was found, developed only a very mild rhinitis, they had very mild symptoms, and definitely not the typical SARS pattern. The third group of animals, first infected with the coronavirus and then superinfected with the metapneumovirus, did not develop more serious disease.

The Koch's postulates are firstly that the agent should be present in basically all the individuals that are suffering from the disease. That holds true predominantly for the coronavirus and not for the metapneumovirus because it is less than 50% of the people infected or having SARS that were infected with metapneumovirus. The second postulate is that you should be able to cultivate the virus. That holds true for the two viruses. The third postulate is that you should be able to reproduce the disease in the host or a related host. That is what we have done for the coronavirus, and coronavirus only. The last postulate then is that you should reisolate the virus back from the animals that you have infected with that virus. Those four things have been fulfilled for coronavirus and only three of those for the metapneumovirus.

The conclusion today, the people in the network agreed, that the coronavirus alone is capable of causing the typical symptoms. We cannot formally exclude that other agents, such as the human metapneumovirus, and the chlamydia that has been found in China, or a number of other viruses after you have this primary infection with the coronavirus, would eventually aggravate the situation. We cannot exclude this, but the data especially from Hong Kong, suggest that where we have coronavirus alone, also in humans, those data together with the monkey data I think quite strongly show that the coronavirus is the primary cause of this disease – the new coronavirus that was identified a couple of weeks ago.

Q. It’s been reported that the corona virus is a member of viruses that cause the common cold. If you could comment on that scary thought. Could you come up with the latest information you have the number of cases and deaths - please don’t tell me to go to the web site later because I have to do this report immediately. And then, regarding Beijing, there have been reports saying that the number of cases there is far higher than 37, and also that cases in military hospitals have not been reported. Are you able to go everywhere that you want to go, or is the Chinese government putting restraints upon you in various areas because there has been a lot of reporting regarding that? And then, perhaps this is part of the mutation of the virus that you were discussing earlier, but again reports seem to indicate that the people who are dying now are not really older than 60 with chronic diseases, but that it’s a younger group of people and also a healthier group of people.

A. Dr Stohr: David will answer the question regarding China. I’ll try to answer the question regarding the mutation of the virus in age groups. We have seen actually from the early stage of the outbreak that people of younger age groups were those affected with severe disease, as well as there were deaths also in younger age groups. Now what we are seeing is that the statistics and the epidemiology and the surveillance become better, and what we are now collecting is data on also underlying chronic diseases, pre-existing health conditions as well as age groups - and what we are seeing, I believe, from the data which we have does not indicate that, if there is a shift in age groups …, there is no shift in age groups but what we are seeing is better surveillance.

As far as mutation of the virus is concerned, I would like to come back to what has been said before. First, coronaviruses are subject to mutation anyway. Secondly, this is a new virus in a new environment. It’s subject to intense selective pressure. New substrains will evolve much more rapidly than in a disease which has established itself over a long period of time, with the virus trying to find its ecological niche. What we are seeing is a more rapid change in adaptation now as one would see, let’s say, in measles or mumps or other established viruses. And what is most likely is, if we cannot get rid of the disease, then we might see the whole spectrum of disease or symptoms, as one can see from other infectious diseases; very mild infection, abrupt cause, quicker evolution as well as the full-blown, very severe disease which is leading, particularly in those with chronic and underlying diseases, to more deaths and more sequelae possibly than in the young and those in the prime of their life.

Q. What about the common cold, whether it is a member?

A. Dr Stohr: Common cold – who would like to do that? Rob Gopal, would you like to have a go at this one?

Dr Robin Gopal: Many viruses are part of families which have a spectrum of pathogenicity, and present with a spectrum of diseases - it’s true that the SARS virus is part of the same family of viruses that cause the common cold but it’s also true that, as far as we are able to establish from the genetic work that has been done in a number of laboratories, this virus is quite distinct from the common cold virus, it’s part of a genetically distinct subgroup of the coronaviruses and therefore, it would be unreasonable to extrapolate and expect it to have the same pathogenic properties as a common cold. It might be pathogenically, as we are assuming and are seeing, quite different.

Dr Heymann: Let me answer a little bit about Beijing. Before I do that, on the age issue, it’s always useful to understand that this disease starts out in health workers in most cases, so the first patient infects health workers and they are all of a certain age – they are not young people, they are middle-aged people or in their 20s to 40s or 50s, so it’s natural that that would be the age that’s first infected. Then as it spreads out from those workers into other populations, the ages change, so it’s very important to understand the dynamics of this disease.

As far as Beijing goes, we have spoken with our team just about an hour ago. Last evening, as you know, they visited the military hospital and that’s not easy to do when the Ministry of Health and the Ministry of Defence run hospitals. It’s difficult to get access to the military hospitals from the Health Ministry, which is where we work at WHO. But the team visited last night. They estimated that there are at least 50 patients in this hospital with SARS from what they’ve seen. They also estimate that there are between 100-200 probable cases in Beijing, more than has been reported and they feel that there might even be up to 1000 people who are under observation right now at various stages of infection – some probably are not SARS, in fact many are probably not SARS, but they are taking precautions in observing these. It’s our impression that China needs to get clear on how it reports these diseases and they are working very closely with the Chinese to get better reporting. It’s also the team’s feeling that Beijing has many resources that they can put to work on this disease and that SARS will not be a problem in Beijing if they get these resources working. Their concern is in the provinces, especially in the western provinces and they are afraid that it will not only spread from cities into the communities but into areas where there may not be health facilities that are very closely accessible to people. So, the challenge now is for China to not only report, but to trace infection, to do infection control in the hospitals and do everything that the other countries are doing to stop the spread of this disease.

Q. Are there figures please on how many cases?

A. Mr Dick Thompson. The current cumulative number is 3293 - 159 deaths, 1548 recovered in 22 countries.

Q. Can you tell us about the history of this virus, which environment does it come to human beings, why in Asia, if you have an answer about this? Second, you said about the profits, that laboratories worked without having this in mind, but I would like to know how much it costs so far for the laboratories to come up with this result? And the third question to the network of laboratories in Germany, are you prepared to provide this to developing countries that would not be able to purchase this diagnosis test? Thank you.

Dr Stohr: I would like to ask Dr Masato Tashira to talk about the origin of the virus. Cost, I would like to ask Jim Le Duc to address this, and the third question to Dr Drosten.

A. Dr Masato Tashira: I think that the new coronavirus is one example of emerging viruses. And emerging viruses are not emerging completely from something like [garble] But this virus has long existed in the nature, but we didn’t know the presence of this virus. And probably the new coronavirus we are concerned with is also one of such viruses, that is, present for a long period at least in southern China in some unknown host animals. And the reasoning is not yet known, how this new virus jumped into the humans. But we expect developments of human life into some wildlife or some chains of food [garble] Personally, I think that the people in Guangdong take everything, every creature and they have much chance to get some viruses than other places. So then this is my personal opinion. Anyway, such virus has long existed in nature.

Dr Stohr: I think that’s a clear answer. There might also be clear other answers, other hypotheses. I don’t think that would remain uncontested in the scientific community. As a scientist, these hypotheses have to be put on the table, have to be reviewed in the light of forthcoming scientific information. And with the sequencing and now the fulfilment of the Koch’s postulates, we have done a very important step also towards understanding the evolution of this virus. We now have to see which animals are susceptible. Dr Albert Osterhaus has shown that non-human primates are susceptible. Other network laboratories …, Sylvia van der Werf has tested it in mice, there are tests ongoing in pigs and poultry. And all this evidence will be forthcoming in the next weeks or months. Then we might be able to give a more definite answer.

Dr James Le Duc: If I recall your question correctly it was the cost. I certainly don’t have a good estimate for that. You can read in the financial pages the economic impact that the outbreak has had on the various communities that are directly affected, which has been substantial. And continues. I can speak for our investment at CDC alone. We’ve had over 100 people working on this outbreak since the start. We have 22 people deployed overseas actively investigating the outbreak on site. I suspect that we’re spending close to US$ 2 million a month on it, maybe more.

Dr Drosten: And the last topic was about availability of the test in developing countries. Well, for this we first have to clarify the usefulness of this test for clinical application, and it’s very likely that this test will prove useful. And when we want to transfer the test to developing countries, we have to first clarify what technical prerequisites are there. This will be a problem in many countries but at least at the national level there will be such prerequisites. And the second topic to clarify is funding but there will be means to have this funded for certain developing countries. But first of all, I have to repeat this, we have to clarify the usefulness of this test in day by day clinical application.

Q. Stefan Tile, Newsweek. I’ve got two questions. One is, can you tell us something about the …, give us an update on countries where first cases were recently reported, like Brazil or South Africa, how they’re dealing with the situation, what measures governments there are undertaking. And the second question is, now that the virus has been pin-pointed and the genome has been sequenced, can you tell us something about the fact that the genome has been sequenced, what that means for a) the diagnostics, b) the development of antiviral therapy and c) the search for a vaccine? And to what extent any of this research is either under way or specifically planned. Thank you.

Dr Stohr: David will answer the first question and then Dr Aiee and Sylvie will have a go at the last one, sequencing of the virus, what are the benefits?

A. Dr Aiee Ling: With regard to the sequencing of the virus, it of course gives us tremendous ability to develop more specific primers. Because, as has been stated before, this virus is quite distinct in its grouping. Which means that the previous primers that we were using were not as specific and therefore not as sensitive. So that, of course, the specific primers that we should be able now to develop will go a long way to improving the sensitivity of test. That’s with regard to diagnostics. With regard to vaccines, again of course the sequencing will have a direct ability for us to form clones, to produce the necessary requirements for vaccine.

Dr Sylvie van der Werf: So, about other developments that one can expect from the availability of the sequence. Apart from developing other primer sets for molecular diagnostics, also this should prove extremely useful for serological diagnostics, producing antigens by molecular techniques that can be made readily available. And there are a number of laboratories in the network working on this. Different vaccine strategies can also be explored using recombinant vaccine approaches. Again, based on the possibility to express various proteins through molecular cloning techniques from using the genes from this virus. And finally, this will also allow to set up, probably, maybe some high [garble] tests for testing of antivirals that might be of use against this virus. So, really using molecular techniques based on the sequence information, it will be possible to develop methodologies that will not have to rely anymore on infectious virus, which will also allow to work at a different containment level and make things easier.

Dr Mark Salter: The question I believe was about what’s happening when individual cases are occurring in various countries. Well, the infection control measures for which WHO published guidelines are what most countries are implementing. Obviously they’re using that as a basis in developing their own national guidelines based on what resources they have and what infrastructure they have. But essentially, it’s identifying those individuals clinically, isolating them, and taking the effective control measures which are widely disseminated around the globe at the moment. [interjected question: And that’s happening in places like Brazil and South Africa as well?] It is indeed. Brazil and South Africa have exemplary laboratories and exemplary clinical staff members who are working on that at the moment.

Dr Stohr: Perhaps I could just add two things. You were asking about practical applications of the sequencing of the virus. One practical application is that part of the sequence of the virus, the genetic information, is now being put into insect cells. And these insect cells produce parts of the coronavirus and this part of the coronavirus may not be pathogenic for humans but may be producing an immune response. So that persons who might then be immunized with this partial virus would develop full immunity against the disease. So that’s ongoing.

You heard the word “primer”. What are primers? Primers are very small pieces of genetic material which are very specific for a virus. I mean, you have heard about the large overlap between the mouse gene and the human gene. Well there is a lot of overlap even between these two mammal species. There is also a lot of overlap between coronaviruses themselves. But there are small pieces in their genetic material which is absolutely identical. And if we find these pieces and we develop tests which are specifically detecting those parts, we will have a very, very specific diagnostic test.

And there’s another reason to do the sequencing which is: if we want, for the future, to understand what changes in the genetic make-up of the virus have an impact on immunogeneticity, we need to find out which of these 32,000 base pieces are the ones which are involved in immunity. Or which pieces are involved in pathogenecity, or which pieces could be the target for very specific drugs which would then kill the virus because these drugs would immobolize the certain functions of this virus.

Q. I have two questions. One is, do you have any new findings on the way of transmission? And the second is, how many people do you have right now in China and are you planning to send more people? Thank you.

A. Dr Stohr: This morning the network members presented overviews on the excretion patterns of this coronavirus and the people you are seeing here, and those you unfortunately cannot see because they are linked by video conference, are those who know most about how this virus is being excreted, for how long, by which means. But still the matrix of excretion which we have drawn is still incomplete. We are still not fully aware how much virus is being excreted, by which excretor and secretor, for how long. Is virus excreted before the clinical signs would occur? Would virus continue to be excreted when persons are already discharged? All this has to be looked into. And it’s ongoing.

Was there a second question? That was about number of cases in China and how many people are we going to send there, eh?

Q. How many people is working right now and if you are planning to send more people?

A. Dr Heymann: The China situation is that we have teams that have reported early this week, new reinforcements for our teams. We’ve been asked to send someone who can advise the government on travel issues because the spring holiday is coming up in May and they’re afraid that the disease will spread with internal travel within China. So there will be a travel expert going out very shortly as well. And we’re trying to respond to the requests of the Chinese as they make them. And there have been many requests and much collaboration sought and we are providing all that we can do.

Just let me come back to the transmission. Close personal contact is the major way that we believe this disease is spread, from person to person, sitting next to you or just in front of you, by something that comes from you that lands on them, as you speak or as you cough. There is another way of transmission in Hong Kong that’s carrying the disease from a person, through the environment to another person, and we’ve talked about that before here, it might be an object, it might be a common system linking hotel rooms or apartment building rooms, we don’t know. But those are the studies that are going on now and now that they know where the virus is being secreted, it’s possible that they’ll have more leads as to where they should look. In sewerage for example, in other things where the secreted materials might be ending up. But it’s common for viruses that are in animals to pass their virus on to humans through such things as urine, which then dries out and then becomes airborne and can spread things. Lassa fever, a disease in humans, is transmitted by rats through their urine. And so, it is common that these animal viruses can transmit to humans through something and then, we would assume, from human to human that might also be a mechanism.

Q. I would like to know if this is the beginning of the end for SARS virus? Or if it’s still a long way to have a diagnostic and a treatment? I wanted to know in question of time – is a long way to get a diagnostic and a treatment after the discovery? And because it’s mutant, is going to take a long time, is going to be after tomorrow, we are going to have a diagnostic? How is it going on?

A. Dr Le Duc: With regard to the diagnostic tests, these preliminary tests that have been discussed are being used now in many of the laboratories, where the disease is occurring. And we will be spreading them to other laboratories very soon, so I think we’re talking in terms of weeks, days to weeks for diagnostic tests. For therapeutic interventions, we are much, much further behind and that will take much longer to validate new … [interjected question: months?] months to years. We’re hopeful that it’s less but we don’t have any evidence to suggest so.

Q. Because it’s mutant, you think this is under control? Or this could take a long time to reproduce and to have new forms?

A. Dr Le Duc: This is our first experience with this virus, as you know, it’s what we call a virgin-soil outbreak, it’s never occurred in humans before. How it will progress, nobody really knows. But it’s most difficult to control diseases that are spread by droplets in this person-to-person spread. So I think it would be premature to suggest that we are near the end of this outbreak.

Q. Warren Giles, Bloomberg News: A couple of things. I wonder, is there any evidence that the mortality rate of this virus is increasing just because of the evolution we see in cases and deaths in Hong Kong? And secondly, I wonder at what point a virus that’s not contained becomes an epidemic? Is there any kind of model that suggests there’s a critical point of infections at which point infections become exponential in some way? Thanks.

Dr Stohr: I would like to ask Mark to address the first question and I’ll have a go at the last one.

A. Dr Salter: The first question was: has the case mortality rate increased? No, it hasn’t but what we have seen across the globe is that there are variable case fatalities rates with the different countries. And that probably reflects to some degree the level of facilities available in those countries and the rapidity with which those individual countries have been able to implement their infection control measures.

Dr Stohr: As far as epidemicity is concerned, we are talking about a disease which is causing outbreaks. It causes outbreaks in hospitals from which an infection chain can be followed up into the community, a first transmission perhaps from a health care worker to their family then to their friends and so forth and so on. As long as one can trace back this infection chain and understand how the virus is travelling and spreading from one person to the other, and one can follow this up, as long as this is possible, we are dealing with outbreaks. We can trace back, we can isolate, we can quarantine, there are contacts. When we are beyond that stage, when we would not be able to trace individual cases, when cases are popping up like mushrooms everywhere, then we would be in a situation where the whole control measures would have to be completely rethought, have to be put on a different foundation. So far, it’s identification of first cases, tracing contacts, isolating and quarantining contacts, isolating cases and trying to contain the disease with these measures. There are models which exist for other diseases. There is currently a model being developed for SARS by a group in the UK. We hope that, actually in one minute, by two-thirty, the leader of this group is going to have a presentation by telephone conferencing with our team. So, I also think we may have to go back. But that’s the answer to this question – models are being developed, there’s none yet for this disease. = = =