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Contents

Presentation

Hot topics about microbes, environment and infection (updated July 2003)

A short description of relevant microbes (updated February 2002)

Microbes and cancer

Controversies (updated February 2002)

Some interesting dates relevant to biology

Fads and Fallacies in the Name of Science (updated february 2003)

Your questions

Presentation

Research is financed by public taxes or donations, and most of the time, by governments. It is therefore quite natural that the general public be informed about the outcome of the money used there, either as a voluntary contribution, or through taxes. The aim of this journalist corner is to help journalists, who have the most frequent contact with the general public, to be informed about topics of general interest in biology, and especially about diseases, genes and genomes. It is important that journalists understand their responsability in transmitting information. Exquisite care should be taken to control it. It is also important that what is reported on headlines is accurate. Remember that journalists are excellent accesories to the spread of epidemics... At some point, if this approach appears to be successful, we shall construct restricted connection pages, specifically for the media supporting us.

Summary of the work at the Centre

Three processes make life: metabolism (eating and digesting), compartmentalization (having an inside and an outside) and information transfer (controlling heredity: the genome is at the core of information processing). All three processes are imbedded in small entities named cells. Microbes are usually single cell organisms, while plants and animals are multicellular. Understanding, and hence controlling life means understanding the cell. While general functions such as assimilation, respiration, replication or digestion are common to all forms of life, the objects, and therefore the genes that make them work may be different. This tells everyone that in general knowing a gene is not enough to tell its function...

Understanding how microbes live and multiply has applications in the development of diagnostic tools and of new and powerful antibiotics for use in the treatment of illnesses caused by all pathogens, including bioweapons agents such as the deadly anthrax or plague agents. For this reason, the two model microbes initially chosen to develop genome studies at the HKU-Pasteur Centre were immediate parents of these terrible agents. In addition, foreseeing that mosquitoes would soon become terrible foes in the region, the Centre devoted some of its effort to a microbe which is a powerful insect killer (Photorhabdus luminescens).

Work at the Centre concentrates in particular on the first step of protein synthesis, which is deeply rooted in the assimilation of an atom essential to life, the sulfur atom. Many antibiotic drugs work by distorting the protein synthesizing machinery of disease-causing microorganisms to malfunction, killing the microorganism and curing the disease. Understanding the process will allow investigators to discover new tricks to lure microbe out of their deadly paths.

Our technique, which combines prediction using powerful computers and specialized database construction with experiments can be extended to the study of the functions of antibiotics acting on bacteria that can be used as potential biowarfare agents, such as anthrax, cholera, plague and shigella. They can also be the basis for investigating dangerous fungi, such as Penicillium marneffei, that is a frequent cause of death in AIDS patients.

The insight provided by the new database structure we are creating in collaboration with the Institut Pasteur and Genome Centres in Beijing and Shanghai is proof that unexpected functions of proteins can be predicted on a computer, which opens up the possibility for rapidly modeling metabolism organisation from a variety of organisms.

Organizing microbial sequence and annotation data is a significant challenge given the large number of genes present in the genome and development of both experimental protocols and software applications used for making the predicttions can be extended from the model organisms to other disease-causing microorganisms, also with the goal of giving antibiotic investigators valuable tools in the fight against microbial diseases, particularly diseases caused by bioweapons.

The recent outbreak of Severe Acute Respiratory Syndrome (SARS) prompted the direction of the Centre to focus its activity on viral diseases in the near future.

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Frequently Asked Questions

Some questions are frequently asked, and we endeavour to answer them when they seem to be of broad interest. If you wish to have an idea of the questions and of our answers, please click here.

We provide in this page not only explicit information, some of which is entirely original (and this is why this site and this page are free to use but Copyright-protected to guarantee this freedom), but also links which may help journalists to trace other relevant information, as well as further insight in the topics they are interested in. Note that not all important information is in English! It should be stressed againthat Chinese, mainly as Putonghua, is probably the language spoken by the most people in the world, followed by Latin languages (French, Italian, Portuguese, Romanian, Spanish...), and then by English (or perhaps languages from India). In addition, Greek provides most of the words and concepts used in science. Do not refrain from seeking information in other languages. Do not forget that most of Chinese scientific literature has not been translated into Western languages, and that it conveys information of its own. And note that English is not the sole tongue used at this site (see here, for example).

Of course, it is necessary for understanding biology to be able to write or speak about this science. Some reading may be useful. We shall provide useful links to the World-Wide Web, to help finding out relevant information. In addition, we shall refer to our own publications meant to be used as communicating media. A special page will be devoted to genomics, but broader information can be found in The Delphic Boat (Harvard University Press, Cambridge, USA) which is an updated and reorganized version of the French text, La Barque de Delphes, published by the Editions Odile Jacob in may 1998 (this can be used naturally, by French speaking journalists!).

The information presented here, naturally, does not try to compete with information provided by news agencies such as Agence France Presse or Reuters. It provides selected information (often not uncovered by standard media) related to the topics of interest for the HKU-Pasteur Research Centre. It also provides information in History of Science and in the creation of concepts used by modern biology. An important access to the very nature of Science is discussed in conference given at Zhong Shan University in Guangzhou. Finally, the importance of China is particularly emphasized: the Western world is so dominating in its control of media that this seems of necessity.

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• En français , Nouvelle du Jour au site Arborescience.
• For popularization of science in French (monthly) see La Recherche.
• Monthly short stories about proteins at Expasy.

For the latest data on emerging (and existing) diseases in Hong Kong and its region see the public Health and Disease Surveillance SAR HK site see also the dedicated site on Severe Acute Respiratory Syndrome by the HK government.

For the latest data on bioterrorism see Medline Plus.

Frequently asked questions about flu (in italian)

Facts about influenza, established by the World Healh Organization

The most deadly epidemics spread throughout the world at the end of World War I (1918-1919). The virulent agent was identified by Dujarric de la Rivière, at the Institut Pasteur, and, independently, by Charles Nicolle and Lebally in Tunisia; they demonstrated that it was not the common bacterium Haemophilus influenzae, as supposed earlier by Pfeiffer, but a virus. Recent work unravels significant properties or the virus, and extends information about the pandemic, to the Hong Kong H5N1 virus.

More about the history of influenza by CW. Potter.

Promed: The global electronic reporting system for outbreaks of emerging infectious diseases & toxins, open to all sources

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Hot topics about microbes, environment, infections and related subjects

Facts and hypotheses about SARS

En français: l'histoire de la double épidémie porcine en 1983-1985

Please note that the information provided here is purposedly uncorrected once placed at this site, for being later used for a historical analysis of important events linked to diseases. It is provided "as is" and reflects the perception of the daily events, using available information in real time (using Internet forums in China, in particular, and trying to escape rumors). This explains why there may be contradictions from one day to a later one. In some cases links disappear (and when this happens we unlink the sentence pointing to the obsolete link when we are made aware of that fact): for example, on april 23d an interesting link described in details that existing treatments of SARS were inefficient and probably dangerous. This link was cancelled out a few hours after it was created, for unknown reasons.... Remember that it is the structure of our societies which create our diseases and that epidemics are not separable from our way of life [pdf].

• 10 july 2003. Philippe Desprès, Jean-Louis Virelizier and Fernando Arenzana at the Institut Pasteur have just discovered in vitro the nature of a receptor on the cell surface that allows the dengue virus to enter its host and start this often deadly disease. This has of course to be substantiated by in vivo studies. If the discovery holds it will open the door for medication preventing, or at least controlling the dengue infection after persons are bitten by carrier mosquitoes, Aedes aegypti.
• 8 july 2003. Within the frame of eradication of polyomyelitis a thorough campaign of vaccination was launched in Madagascar. No cases were found since 1997, until, during a survey between october 2001 and april 2002 five new cases were detected. Surprisingly, a study developed at the Institut Pasteur de Madagascar with the Institut Pasteur has demonstrated that these cases are mutants of the vaccine strain (which is a live vaccine). This shows that the campaign of eradication of the disease will be more difficult than expected.
• 7 july 2003. While the WHO removed Taiwan from its list of areas with local transmission of SARS two suspect cases have been found in GuangDong awaiting confirmation. There are no left chain of transmission left, but one should still be extremely cautious, since the diagnostic of the disease is still difficult. Also, its origin is not well understood yet, although a general consensus is that it originated from an animal (presumably feline) host. If this were the case adaptation to man would have required several steps, and it is not unlikely that a parent disease, causing only very mild symptoms, is still present. This might be a reservoir for a resurgence of the disease when the weather cools down in autumn. Meanwhile a team of scientists from the Institut Pasteur is working with authorities in Algeria and the WHO Global Alert and Response Network, to investigate the recent outbreak of plague, that caused 10 infections and one fatality, and control its vectors. In Hong Kong the hot and humid season makes it now important to monitor the possible come back of dengue fever.
• 29 june 2003. The World Health Organisation, as medical authorities world-wide, are investigating the impact of atypical pneumonia on the local health systems and the response they should propose in case the disease (or a similar one) appears again. Extreme variations in the number of fatalities in different places is a remarkable puzzle that is being actively investigated. The disease also triggered reflection at the Pugwash workshop “Science, Ethic and Society” (Paris, 27-29 June 2003). The Pugwash Movement is well-known for the role it has played in promoting recognition of the social responsability of scientists in the domain of arms control and involvement of scientists in violence. At the present time it is of interest to investigate the various reactions of scientific institutions which often, for the pure sake of fashion or short-term considerations, lost the view of what should have been their strategic (i.e. long term) choices. The origin of the SARS virus is not yet certain, and the disease — which is as expected very sensitive to heat because the virus is much less stable at temperatures higher than 30°C — may appear again when the wether cools down in autumn. However its most severe behaviour was due to person-to-person contamination, and we can reasonably hope that, when cooler days will return no human case will still exist. The disease may then have disappeared from the Earth, at least for some time. It is therefore urgent to remember that, among the causes of the havoc were poor hygiene measures (especially in hospitals), and, above all, lack of pre-existing research on the virus. We know some of our future diseases (and flu is one of them: H5N1 in Asia, and H7N7 in Europe, for example, as well as dengue fever in South East Asia), but we do not know most of them. The family of the Human Immunodeficiency Virus was not considered as interesting before the scourge of AIDS appeared, and not many scientists were interested in Coronaviruses. This means that we need urgently basic academic research on all kinds of microbes, on their vectors and on microbial systems that may put them under control, if we wish to be ready for the next epidemic. Will this lesson of SARS be understood?
• 25 june 2003. Beijing's population went to celebrate in the street the end of the WHO warning over travel to the city because of SARS.
• 22 june 2003. On june 18th an even years old child died of plague in Oran (Algeria) where several cases have been diagnosed. He was affected as well as several members of his family since the beginning of the month. This indicates endemy of this disease, in a country that witnessed the large outbreak fifty years ago, made famous by the novel of Albert Camus, The Plague.
• 19 june 2003. 100 days elapsed since the WHO warning on SARS was published. Although SARS is clearly coming under control, the need for continued vigilance is now greater than ever. The chain of person to person transmission everywhere is not yet totally interrupted and, as demonstrated recently in Toronto the disease may suddenly reappear when it was thought to have been. As stated by WHO at a recent conference there is a need for at least a full year of surveillance to determine whether the disease has established endemicity and to ensure that no cases have spread, undetected, to countries with poor surveillance and reporting systems. After a peak of the number of cases at the beginning of May the disease rapidly went under control, most probably because of the efficiency of means that have been implemented in the regions at risk. It is most important that these measures remain in effect.
• 16 june 2003. The World Health Organization advice against travel to Tianjin, Hebei, Shanxi and Inner Mongolia was lifted late Friday while SARS is now rapidly receding in Mainland China. For unknown reasons, the epidemic is still not contained in Canada and in Taiwan, although the situation is improving.
• 12 june 2003. As atypical pneumonia recedes world-wide, and in particular in China (no new case and no new fatality in Hong Kong), the consequences of the disease on human habits begin to be visible. In Mainland China, in particular, this will help the government to implement a strong policy against spitting (a notoriously difficult task, especially in the poor parts of Western China). This will also inevitably have consequences on the dining habits in this country. Chinese use to share dishes, a very friendly social practice, but which may have a significant impact in terms of diseases spreading. The government is starting a reflection in this domain, which will have immense consequences if the western style dining portions is becoming the rule.
• 9 june 2003. The distribution of atypical pneumonia is becoming somewhat erratic. More questions arise about the possible treatments for the disease as the death toll in Canada reaches 32 persons. The Chinese government warns that, because it is not possible to control totally the movements of person in their huge country, some new cases may appear here and there. While the total number of cases, and of deaths is very small as compared to the situation with other diseases such as tuberculosis, malaria, or AIDS (and even typical pneumonia), the particular feature of SARS is its remarkable contagiosity, which forces authorities to implement stringent confinement measures around patients. If no action had been taken it is clear that the level of contamination in the world would have been much higher.
• 5 june 2003. As a sign of hope, for the second time there is no new SARS case in Hong Kong during the past 24 hours. The experience in Toronto, where more than 70 new cases have been reported since 26 May 2003, underscores the risk of a resurgence of cases and reminds us that a single imported case can reignite an outbreak. The WHO reminds us that this is a matter of concern for the future if all cases have not disappeared during the summer.
• 2 june 2003. As the discrepancies between SARS infections at various places in the world increase the disease remains more and more of a puzzle. Some of the data might reflect inaccurate reporting, but that does not seem to explain everything. In fact several reports from the Mainland suggest that many people are immunologically seropositive for the virus but did not show symptoms. Asymptomatic diseases are very frequent, but this would hardly fit with places where up to 50% of the local people got infected (this was the unfortunate situation at the Block E of the Amoy Gardens Estate). One alternative explanation, that we proposed several weeks ago, is that a double epidemic might reconcile these observations: a first outbreak of a mild disease (probably derived from some animal) would have escaped attention (it might have been the gastro-enteritis witnessed since the end of 2002 in Guangdong and in Hong Kong), and a mutant virus, derived from this first one would have acquired a tropism for the respiratory tract. This would have caused SARS. Those people who had been infected with the first disease would have been protected, while the other ones would have the full blown syndrome. This would account for seropositivity in otherwise healthy people. We are in urgent need of a highly sensitive and reproducible test for monitoring the immunological status of the whole population in the regions of interest.
• 31 may 2003. SARS remains a nosocomial infection as there are three new confirmed cases in Hong Kong who are healthcare workers of North District Hospital. Another sad news is that the number of deaths almost reached the 16% figure in the city. Fortunately, if figures can be believed, there was only a single new case in the Mainland. Singapore is removed from the list of areas with recent local transmission of SARS. The change in status comes 20 days after the last locally acquired case was placed in isolation, on 11 May 2003. In Taiwan the disease recedes, but on may 30th Canada was affected again, since the suspected cases recently discovered have been identified as SARS cases.
• 28 may 2003. With less than 8,500 cases as the total number of SARS patients world-wide, one can be confident that the disease is now under control. One should not let one's guard down however because the disease can reappear where it was thought to have been eradicated. In addition we need to prepare for a possible surge when the weather will cool down in autumn. Much will have to be learnt about protective and proper hygiene measures in hospitals since the disease can be classified as a nosocomial infection. In addition handling and eating wild-life animals will have to be severely controlled. The Chinese governement is considering new measures in this domain.
• 27 may 2003. After an alert was sent on may 23d, Toronto is back on the list of places with recent local transmission of SARS, while a new cluster is discovered. Taiwan is now the place where the disease is spreading the fastest.
• 24 may 2003. The SARS epidemic is being under control in Hong Kong, with no new cases and only 9 suspected cases left. The local death toll is unfortunately above the 15% figure. The situation allowed the WHO to remove Hong Kong from the list of places that should be avoided by occasional travellers. The situation in Taiwan is unfortunately growing worse as the number of new patients is steadily on the increase despite severe control measures at the entry of the region. The number of new patients in the Mainland is stable, probably on the decrease. The origin of the virus might be cat since teams investigating the presence of coronaviruses in Guangdong discovered that these viruses were ubiquitously present in animals, cats included, prepared on the local markets for food. Except in Taiwan the disease seems to be receding fairly rapidly. In addition to confinment and control measures implemented, this may be due to the warming up of the climate in this season. It will be extremely important to monitor the situation when the weather will cool down, next autumn.
• 20 may 2003. SARS in the Mainland may have escaped attention for some time, as a WHO expert team returning from Guangxi province found that 2 separate clusters of SARS cases, dating from December 2002 and January 2003, had recently been detected by local health officials following a review of hospital records. Figures seem to be on the decrease everywhere in the Mainland, but the speed of the decrease is probably too fast to reflect reality. On the encouraging side, only four new patients were identified in Hong Kong, where the number of persons still in hospital went below the 250 figure.
• 18 may 2003. While Singapore was about to be declared free of SARS a new case, who became ill on may 11th, was discovered, showing that one should not be confident too early that the fight against SARS is won. For unknown reasons the situation seems to be getting worse in Taiwan, while in Mainland China and in Hong Kong the number of new patients seems to be steadily decreasing. At the first global consultation on SARS epidemiology, held at WHO headquarters in Geneva from 16 to 17 May, experts declared that the overall case fatality ratio is 14% to 15% but with wide variations in case fatality related to age, sex, the presence of other diseases, and treatment protocols.
• 16 may 2003. The cause of SARS as a Coronavirus is proven, as described in "Koch's postulates fulfilled for SARS virus. Ron A. M. Fouchier, Thijs Kuiken, Martin Schutten, Geert Van Amerongen, Gerard J. J. Van Doornum, Bernadette G. Van Den Hoogen, Malik Peiris, Wilina Lim, Klaus Stohr & Albert D. M. E. Osterhaus. Nature 423:240 (2003). It is important to identify as fast as possible patients who carry the virus. At the date of May 8th, on average the time needed for identification was still about 4 days, too long to stop the spread of the disease. If this figure can be lowered to 2 days, the epidemic will rapidly be totally under control. Misdiagnostic, especially of the milder forms of SARS is a matter of much concern, since this might lead to relaxing the confinement of patients who are still contagious. More than 600 deaths have been attributed to SARS world-wide, a high figure for a new disease. In Hong Kong the death toll reached 14%, menacing to be soon the highest recorded death toll for the disease. There is hope that the fight against the disease will succeed as the number of new cases in Beijing and Mainland China seems to be steadily dropping down, suggesting that the methods used to contained the epidemic are effective. It is interesting to have a view of the official position of the Chinese government on the origin, tracing, and management of the epidemic.
• 13 may 2003. The total number of known SARS patients world-wide has passed the 7,500 figure. Sadly, the death toll passed the 13% figure among patients in Hong Kong. In an exemplary move to control the disease, contact tracing has established epidemiological links for the vast majority of Hong Kong’s patients. Around 9% of SARS patients have no identifiable exposure source. Detailed investigation is ongoing to understand the transmission routes. Figures of new SARS cases in the Mainland are much smaller than the day before, but this may be due to the way patients are identified (one witnesses strong oscillations in the daily number of new patients in China). Japan has banned import of poultry from China after it discovered the H5N1 flu virus in an imported duck.
• 11 may 2003. Steady state on the SARS front, with one case in a new country, Finland. The death toll keeps increasing in Hong Kong while the disease recedes (less that 10 suspected cases remain). The Chinese government has formed forums for students abroad, aiming at collecting as much helpful information as possible to fight the disease immediately and in the future. A fruitful students meeting was held in Paris on may 10th. Contradictory reports analyse the sequence of the virus, and suggest that some mutations may have occured during cultivation in laboratories while others are directly due to the selective pressure of the immune system of the hosts. It is very important that sequences are accurate and are obtained totally independently from each other to begin to get a pedigree of the virus and follow its trail. Features specific to the isolate started from the patient that spread the disease from an hotel in Kowloon are now characterized.
• 9 may 2003. The possibility for a success of the fight agains SARS is illustrated in Vietnam where no cases have been detected for several weeks, and where the death toll remained lower than 8%. One likely case in Eastern Russia, after the disease reached Inner Mongolia, then Mongolia, triggers a new concern for expansion of the disease. Awareness, however, allows authorities to stop the creation of an outbreak. The number of confirmed cases in Beijing dropped sharply (48 cases), while in Guangdong it persists oscillating between 5 and 20 per day. The decrease in Hong Kong is confirmed. In order to improve efficiency of treatment it is absolutely essential that governments totally forbid that companies pay medical doctors for enticing them to use the drugs they produce by whatever means they try to use.
• 7 may 2003. An attempt to use serum of recovering SARS patients to lower the viral load and cure patients has apparently meeting success. If this is subtantiated by further studies this is extremely good news, since this suggests that a vaccine will be possible. This also particularly important at a time when the number of deaths passed 12% in Hong Kong, indicating that existing treatments did not work as well as promised. The situation in Mainland China remains stationary. One positive outcome of this epidemic is the reflection triggered in the domain of control of water quality, pollution, and management of both domestic animals and wild life. The suspected cases in France are very unlikely to be SARS, in line with the lack of an outbreak in the Nanjing region.
• 6 may 2003. Two suspected cases of SARS have been detected in France, from persons coming after a stay in Nanjing. Awareness of the existence of SARS may begin to have a positive effect in Mainland China, where the number of new cases in Beijing (more than 16,000 persons are quarantined) experience a significant downturn (70 new cases). 2 cases have been diagnosed in Shanghai, and during the past couple of days the number of new cases rose again in Hong Kong (this is not statistically significant, however), unfortunately with a high death toll. The most surprising observation remains the high number of medical staff infected despite stringent hygiene control measures.
• 4 may 2003. Shanghai, which is still almost rid of SARS has adopted a series of desinfection measures in transportation, and control measures for travellers. While SARS remains constant in China but recedes in Hong Kong, it is time to put the disease in perspective. Many other epidemics are affecting countries in the world at the same time. In particular, as almost every year, meningitis is killing thousands in Burkina Faso. A different type of concern exists in developed countries: a Legionella case in a factory in the centre of France shows that hot water systems, as well as air conditioning are ready to spread dangerous infectious diseases. The particular danger posed by SARS is its contagiosity which forces affected countries to set up extremely tough controls on travels and drastic quarantine measures, resulting in catastrophic negative economic consequences. Any relaxing measure would immediately result in the spread of the disease. This should be a lesson for the future and trigger appropriate support for research on infectious diseases: the cost of research is very small when compared to the huge losses encountered when the diseases spread.
• 3 may 2003. Steady state SARS infection level in Mainland China, 114 new cases in Beijing, and 10 new cases in Hong Kong (where unfortunately the death toll increased by 9 persons). In Taiwan the cumulated number of cases passed 100, while the disease seems to be vanishing in Canada and in Singapore. It is important at this point not only to take this epidemic seriously — and appropriate quarantine measures, coupled to monitoring travellers at many major places in China, are certainly efficient — but to be aware of other diseases that may have similar, or even worse, consequences. This is the case of most diseases affecting our livestocks, and in particular of bird's flu, which has two pending virulent forms, one in Europe (H7N7) and one in China (H5N1). We are at the mercy of reassortments of the genomes coupled to mutations, that would allow transmission of the disease not only from birds to man, but from person to person. Lessons should be learnt from the scientists and veterinarians dealing with the spread of those diseases.
• 2 may 2003. Almost 13,000 people are now quarantined in Beijing. In an un precedented effort the municipality of Beijing put together a work force of 7,000 to build up a 1,000 beds temporary hospital with a number of special facilities for treating SARS patients. The number of new cases was today lower than 100. In Hong Kong 11 new cases were detected while the number of patients dying from SARS has now passed the 10% figure. Shanghai is enforcing strict SARS preventative measures, including a 14-day quarantine period for travellers arriving from affected areas. Traffic checkpoints have been set up where travellers are given temperature checks and asked to fill out health declaration forms. After Viet Nam, the UK and the USA have been removed from the list of areas with recent local SARS transmission. In both countries, the last instance of local transmission occurred more than 20 days ago. Tianjin, China and Ulaanbaatar City, Mongolia, were added to the list. A new country (Poland) is affected by SARS (1 case). The cases in India have been discarded as SARS cases by the WHO.
• 1 may 2003. The number of SARS cases reached today 1,600 in Hong Kong (fortunately with "only" 11 new cases), while more than 180 were diagnosed with the disease in the Mainland (122 in Beijing). 19 cases appeared to have been identified in India, while the South Korean case might be due to a different type of pneumonia. Drastic measures of quarantine are now implemented in Beijing where the authorities organise the local life for quarantined people.

• 30 april 2003. More than 100 new SARS cases identified in Beijing, while Shanghai remains practically immune and a low level of new cases in Guangdong persists. The situation in Shanxi is a matter of concern because the number of new cases seems to be on the rise. In Hong Kong the number of new cases remains constant now for a few days. Also, in Beijing it appears that some cases of mass contamination resembling the Amoy Gardens event is occurring. This might be the case at a dormitory in Northern Jiatong University. In contrast it seems remarkable, as published by a team at the Chinese University in Hong Kong, that children get a much milder form of the disease. It is time to look back at the situation of SARS in the world. The disease seems to be contained outside Eastern Asia, and officials from 12 countries met yesterday in Bangkok to set up rules for controlling health of travellers between their countries. We are facing a situation similar to that faced when the first acts of terrorism affected airplanes: appropriate facilities will probably have to be set up on a stable basis to monitor health parameters of travellers world-wide. The situation of SARS is at a turning point: a number of 5,000 affected people at the end of this month was thought to indicate the turning point where it might go out of control. Since we are just at this border, we still have hope, and the next figure of concern would be 10,000 by the end of may. A feature of great concern is the vast interest shown by companies for the possible royalties that might come out for the disease, triggering a dangerous competition between countries, hospitals and universities, at a time when collaboration is urgently needed (and remarkably well set up by the World Health Organisation).
• 28 april 2003. The news are mixed today: for one week the number of new cases in Hong Kong kept decreasing, raising hope that the measures implemented are effective and that SARS will be contained within one month. Unfortunately deaths of patients previously recruited was still high, rising the local death toll to almost 9%. However the local situation is certainly less serious than what is generally perceived in the absence of explicit information. People should not lower their guard however since a single case started the present world-wide outbreak. In Beijing the number of new patients is of the order of 100 per day, indicating a serious situation in the capital. The World Health Organisation however says that, learning from the situation elsewhere in the world, we still can hope that the disease will be contained. authorities in Beijing are implementing extremely stringent measures and a general cleaning program to prevent further spread of the disease. Patients are discovered throughout the Mainland suggesting that several causes contribute to the outbreak here or there.
• 27 april 2003. Beijing is now severely affected by SARS, and all public places such a cinemas or theaters have been closed for the time being. The People's University has also closed because SARS cases have been reported there. One of the most puzzling feature of SARS is the extreme difference between the situation in Beijing and in Shanghai (where only a few cases have been reported) despite the strong ties between Shanghai and Guangdong or Hong Kong. This is consistent with the double epidemic hypothesis, suggesting that people at some places might have been protected by a previous infection by an innocuous or mildly virulent virus. Another puzzle is the fact that the death toll appeared to increase at some places as compared to others. This may also be linked to the same hypothesis, with a variable virus segregating more virulent mutants. If this were the case, the use of many antivirals may be dangerous because they might enhance the mutation rate of the virus [PDF], as as suggested by the rate of evolution witnessed in bacterial viruses. The Asian health ministers approved a plan to boost screening of possible SARS patients at international departure points, bar travelers with SARS symptoms (fever in particular), and require health declaration forms for visitors from affected countries. "We must use every weapon at our disposal," the regional director of WHO, Shigeru Omi, told the health ministers and senior officials from South East Asia, China, Hong Kong, Japan, and South Korea. A joint symposium on SARS was held in Hong Kong with scientific representatives of the region.
• 26 april 2003. While diagnostic kits for SARS are distributed world-wide, the WHO warns against inaccuracies inherently associated to these kits essentially based on the Polymerase Chain Reaction (PCR). Sensitivity is high but the genetic material of the virus is unstable, leading to false negatives. In contrast, once the assay has been used for some time, the rate of false positives may increase because of contamination of the diagnostic laboratories, unless extreme precautions are taken. After his official visit to Beijing the French Prime Minister stressed that panick is the worse reaction to an epidemic. There were 154 new cases in the Mainland (113 in Beiing) and 17 in Hong Kong. India has identified three new cases (7 in total). No new case in Vietnam for 18 days: it is now likely that the country will be the first one to have contained the disease, setting an example to other countries in the world.
• 25 april 2003. The number of new patients affected by SARS in Hong Kong seems to decrease slowly. Unfortunately the rate of deaths has increased significantly in the past few days, rising the overall death rate to 7.6%. Scientists are collecting isolates from various places and compare them. The first observations demonstrate that the virus is still in a rapidly evolving phase. This is consistent both with the nature of the virus (in general viruses, that are not real living organisms but parasites of life, mutate at a high rate because they do not have the elaborate "proof-reading" system present in most living organisms) and with the hypothesis that it comes from a non human host.
• 24 april 2003. The epidemic has apparently been contained in Vietnam. Figures in Mainland China, although much more accurate than previously are still difficult to evaluate since not all hospitals are able to tell SARS from other diseases with similar symptoms. Some Canadian scientists cast doubt on cause of SARS, because they do not find the suspected coronavirus in 50% of the cases, while they find it in control patients. It seems of the utmost importance that the community reaches a consensus since hundreds of scientists are working round the clock with the hypothesis that the virus is the cause, and are constructing diagnostic tests, and vaccine approaches on this hypothesis while the disease is still progressing. However the experiments with monkeys, showing the very symptoms of SARS, argue strongly in favour of the new coronavirus species as being the cause. For some reason, doubts systematically came from the same place, where some other cause might have altered the symptoms and/or the samples.
• 23 april 2003. Schools will be closed for a fortnight in Beijing. 24 cases and 6 deaths in Hong Kong. Claims about the efficacy of treatments have to be revised because it is extremely dangerous to extrapolate from textbook knowledge to a new type of infection. It seems clear that symptomatic treatment, when delivered early on might be helpful. The difficulty with any urgent situation as the present one is that one should do controlled experiments, ie compared the fate of many patients with, and without treatment, and this is morally difficult, in particular when some believe that this, or that treatment may be efficient. This is the only way out, however.
• 22 april 2003. In Hong Kong a cumulated total of 1,434 cases of SARS have been reported todate. The public perception of the disease worsens in Beijing while the Central government takes an entirely new and open attitude towards the challenges posed by the disease. It is in particular extremely difficult to be careful with a disease that only affects a minute portion of the population, to manage its possible extension (which could be considerable if nothing is done) while controlling the extremely dangerous economic consequences induced by panick. Involving the people in the fight, as done during the past few days in Hong Kong is probably one of the best solutions. There is also an urgent need for totally open collaboration between scientists throughout the world, an attitude that is dramatically illustrating the negative impact of the competition attitude induced by inappropriate management of successful behaviour in science. Part of the problem caused by the virus could be due not to contact through air, but because of an unusual stability on many surfaces. This indicates that excellent hygiene is most important at places where cases have happened.

• 21 april 2003. The situation in Mainland China is somewhat confusing, as authorities in the provinces are trying to provide accurate figures for cases of SARS, at a moment when they often do not have appropriate means to identify cases. In Beijing the population begins to show its concern, after the two political dismissals of the day before, and one observes a large number of masks in train stations. The rumor spreads that the city might be completely closed for travels in and out within two days. The WHO now counts more than 4,000 cases world-wide, while the number of new cases in Hong Kong dropped significantly, unfortunately with still several deaths.
• 20 april 2003. At this date we may reach a turning point for the spread of SARS. Countries are resorting to drastic measures to slow down the spread of the disease. China, using a new method to count patients affected, recognizes that the disease has now severely reached Beijing, with more than 300 patients officially identified. In a political move without equivalent for 25 years, the mayor of the city as well as the Minister of Health were asked to resign from their position in the Communist Party, as a sign that they were not able to cope with the severity of the problem. In addition the Chinese Government has transformed the first week of May, used normally as a nation-wide vacation, into only one day vacation, in an attempt to prevent travels within the country. More than 1400 persons who went to an open market in Singapore where a patient was identified are confined for 10 days quarantine. Toronto has identified new cases that do not appear to be directly connected to previously identified patients, rising fear that the virus might now spread by air. The authorities are considering placing buildings, or even whole blocks, in quarantine. In Hong Kong the disease does not seem to recede. Lessons from the outbreak or Porcine Respiratory CoronaVirus twenty years ago show that the virus may even become airborne. The present virus is a totally new one, from yet unknown origin, but it is of interest to understand how similar viruses evolved in animal communities in the past. Several world-reknown scientists are now involved in the fight against SARS in Hong Kong, in particular David Ho (who devised tritherapy against AIDS), Jeff Copland, Michael Lai and Monto Ho (who solved an enterovirus outbreak in Taiwan several years ago).
• 19 april 2003. This is the worse day in Hong Kong since the beginning of the SARS outbreak, with 12 people passing away, while the number of new cases remains stable. Young people coming from Hong Kong have been placed in quarantine while they arrived from Hong Kong in UK. In a completely different context, the viral epidemic that plagues chicken farms in Netherlands and Belgium has made its first human victim. If this were to give rise to person-to-person transmission of the disease, a major epidemic of another type would be on the verge of starting. All this indicates that we must now be ready to take major measures to control the spread of contagious epidemics, throughout the world.
• 18 april 2003. The first three cases of SARS were reported yesterday from Australia, while the disease appeared to slacken its pace of infection in Hong Kong (1,327 cumulated cases, showing a steady state of infection at around 30 cases per day, similar to the figure before march 27th). India has also reported its first case but the description is not entirely consistent with SARS. At Amoy Gardens in Hong Kong, the cause of the outbreak is identified, suggesting that it would be easy to prevent further incidents of this type. If one takes out this episode, the epidemic in Hong Kong has features similar to that in Guangdong province, suggesting that it is starting to recede. However one must still be extremely cautious because a single patient may start a sudden outbreak, as repeatedly witnessed in the past month. The team at the Faculty of Sciences that sequenced the virus is analyzing its relationships with birds coronaviruses, as well as with similar viruses in other vertebrates. At this time the cause of the disease is consistent with the shift of an enterogastritis virus to a respiratory form, a Human Respiratory CoronaVirus (HCRV).
• 16 april 2003. In a remarkable breakthrough involving world-wide collaboration a Dutch laboratory demonstrates by experiments using monkeys that the new coronavirus recently identified is the cause of SARS. In Hong Kong, the sequence of a local isolate is completed, allowing comparison between three different isolates. While RNA viruses are always highly variable it will be of fundamental importance to link the severity of the disease with variations in the genome sequence. The virus being probably of animal origin it is certainly in a phase of adaptation to its new hosts, human beings, and this may result in particularly virulent mutants. This also may result in attenuation: it is too early to know how the disease will evolve, although extrapolating from the situation in Guangdong should be seen as positive.
• 15 april 2003. The rise of the number of SARS cases world-wide is worrying, since it seems on the verge of beginning a pandemic. The cumulated number of cases in Hong Kong is 1232. Concern comes from the observation that, among the nine deaths recorded in 24 hours, several come from persons under 40 years of age, with no other disease. It is important to monitor the type of treatment used, since antivirals can be extremely toxic. Identification of the virus is still a challenge: a PCR test, developed by the CDC in Atlanta, has been shown to be ten times more sensitive than previous PCR tests for SARS. WHO experts hope that the test will be ready for distribution by the end of this week. The sequence of the isolate of the virus at the CDC has been completed, after a Canadian group sequenced another isolate. The virus differs significantly from previous isolates. Scientists are concentrating on the features of the "spikes" porteins, that are important for penetration into target cells.
• 13 april 2003. The World Health Organisation has raised several caveats about too early and misleading enthusiasm about diagnostic tools and remedies for SARS while a team of Canadian scientists announced that they have completed the sequence of the viral genome. The virus has unique features that make its origin still an enigma. It must be remembered however that the sequence of the AIDS virus is known since 1983 and that we are not yet rid of the disease, and also that antiviral molecules are very dangerous and often have severe secondary effects. Collaboration, without delay, with all relevant partners in the world is essential to try to contain the disease, and limit its extraordinary economic consequences already reaching some 40 billion US$. The team in Canada benefited from an excellent organisation of a team previously working on cancer and of the information provided through the WHO network. A second team at the CDC in Atlanta, with the support of scientists at the Bernhard-Nocht Institute, Hamburg as well as from Rotterdam and San Francisco, is completing the sequence of a second strain, while the Hamburg team is providing information to a company for distribution of free primers meant to help hospitals in the world to identify the virus. It is difficult to know at present whether the disease simply spreads in a linear fashion, or begins an exponential exploration of the available population. Reaching the number of 5,000 patients world-wide by the end of the month would be a sign suggesting that the disease may have become out of control. The transmission pattern still remains ununderstood, with some patients infecting a very large number of persons, while others remain infected while contaminating no other person. Strict quarantine measures are now implemented in Hong Kong, and Mainland China has created an efficient alert system that will be particularly important in the poorest parts of the country. The cumulated number of patients in Hong Kong reached 1,150. One should also note that, because of the lack of essential collaboration between scientists throughout the world, the cause of SARS is still disputed... This is very unfortunate at a time when the disease is spreading. The observation by groups in different continents that the same coronavirus is present in patients however substantiates the idea that it is the cause, rather than an accidental contaminant.

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• 11 april 2003. While it is likely that persons living at Amoy Gardens Estate left before the quarantine measures, the number of new cases increases more or less linearly (1,059 cases at 1 pm) in Hong Kong. Several laboratories of the WHO task force on SARS concentrate on the hypothesis that a new coronavirus, never previously identified from animals or man is the main cause of the disease. The main problem now is to be able to trace the routes of propagation, by identifying contacts of patients. Hong Kong health authorities have announced that all household contacts of confirmed SARS patients will be required to confine themselves at home for up to 10 days with immediate effect. A similar measure will be implemented in the Mainland as soon as a way to identify the disease (remember that pneumonia are very frequent diseases) can be proposed.
• 9 april 2003. Our diseases are strongly linked to the way our society behave. This must be taken into account for analysis of the outbreak in Hong Kong, which reached 970 persons at 3 pm, with a still significant proportion of health care workers. Of course, one expects that scientists involved in the fight against the disease have a very open behaviour, widely sharing their results to increase the probability of finding rapidly a solution to the crisis, but is this what we are witnessing? The future will tell...
• 8 april 2003. At 3 pm, the cumulated number of patients in Hong Kong reached 928. Many hypotheses try to account for the sudden local outbreaks, in particular it is known that coronaviruses are not only involved in respiratory diseases, but also in gut diseases, suggesting that, in some cases they may survive in the gut and be propagated by a faecal-oral route. This hypothesis stresses again the important role of a good hand hygiene. Data are collected to explore this route. The disease, which appeared to have been contained in Hanoi might be reappearing elsewhere at other places in Viet Nam. One of the present difficulties is that diagnostic tests that have been initially proposed have been found to be somewhat problematic. The international collaboration set up by the WHO should however be able soon to provide a reliable test.
• 6 april 2003. The cause of contamination remains elusive, while 42 new persons are infected in Hong Kong. In Singapore the disease appears to be dying out, but there are still new cases, while the quarantine measures are very strictly enforced. In Mainland China, reported cases come from the whole of the country. In Guangdong, the total number of new cases is stable at around 10-15 cases per day. The total number of cases from Hong Kong is higher, in particular because 268 cases have been reported from the Amoy Gardens estate. This large number of cases still remains a puzzle. In the same way, the Singapore government is investigating the situation posed by 29 cases reported on March 29th, in the staff from two wards of the same hospital. It seems highly improbable that a single patient would be the cause of these almost simultaneous cases, suggesting an environmental parameter (which may be of similar nature as that at Amoy Gardens).
• 5 april 2003. In the USA, the cumulated number of patients affected by SARS reached 115, prompting the Federal Government to take action in terms of compulsory quarantine measures. In Hong Kong, the number of new patients rose again, to reach 39. Among those 10 are medical staff, 7 are persons who were residents of Amoy Gardens. The 22 remaining patients correspond to the steady state of the disease that appears to prevail for the last weeks. Two major observations about SARS puzzle observers: the disease is considerably biased towards affecting medical staff, and the outbreak at least at one place, the Amoy Gardens estate, mimicks what happened in hospitals with very high geographically concentrated clusters. In contrast the background of the disease, probably in Hong Kong as in the Guangdong province, stays more or less constant, neither increasing, nor decreasing. This makes the course of the disease highly unpredictable and its propagation route still very enigmatic. Among the many hypotheses that remain to be fully explored is the idea that two viruses, with somewhat different contamination properties, are needed to cause the severe form of the disease. The actual cause of the disease is not yet fully established. Health authorities are currently investigating other cofactors such as propagation through sewage pipes (Block E at Amoy Gardens is a 33 floors high rise building, and a large concentration of patients is in a vertical cluster) as well as airborne through some kind of particles coming from a neighbour construction site... The second patient in France has probably been contaminated while travelling on the plane from Hanoi to Paris.
• 4 april 2003. While the outbreak seems to level off in Hong Kong, new cases are discovered throughout the world. In Hong Kong at 1pm the cumulated number was 761, indicating a constant rate of infection. In the absence of any easily available test for identification of the disease, it is still difficult to count the number of real cases. Most definitions come from epidemiologic investigation and linkage with known cases, as well as clinical signs. This is the more difficult because clinical signs appear to vary from place to place. For example, in the USA, for some reason the clinical signs are milder than at other places. All this suggests that there may be co-factors to the disease, which is still not yet understood, and/or that the virus is still evolving extremely rapidly.

• 3 april 2003. At 1 pm (local time) the cumulated number of cases in HK was 734, representing a sharp drop in the increase of new cases in Hong Kong. While the Mainland authorities have opened their hospitals for WHO investigation and help, many questions arise about the origin of the disease. It has been repeatedly stressed that SARS was originally detected in FoShan and HeYuan county, Guangdong Province. A local newspaper however tells that a medical professor in RenMin hospital of HeYuan county named Xie JinKui does not agree with that assumption. Prof. Xie said the first case in HeYuan was detected in 17th of Dec, last year (2002). The patient is a 35 year old man. He is a cook in ShenZhen, working in a restaurant where he has close contact with wild animals, such as snakes (see more about this story). Although the date does not fit with earlier descriptions of diseases similar to SARS in Guangdong, this raises interesting questions about the origin of the virus. In Hong Kong, if one removes the very special case of the Amoy Gardens Estate, the outbreak is constant since the beginning of march, not exponential. This suggests, as initially proposed, that the disease is propagated by (almost) close contacts only. The situation at Amoy Gardens has to be investigated in details, since it suggests another mode of propagation, specific to that particular place. It will be extremely important to understand what it could be.
• 2 april 2003 (see also the WHO press conference). Once the cluster of patients at Amoy Gardens reaches its maximum, the disease seems to be contained elsewhere in Hong Kong, suggesting that it may begin to become under control (a total of 708 cumulated cases since the begginning of the outbreak). The drastic quarantine measures implemented by the local government seem to have had a significant impact. However the outbreak has some unique features that suggest that an unknown route of contagion may be existing. It is too early to be sure that the situation is stabilising, but the warming up of the weather acts against viability of the virus combined with stringent hygiene measures might have contained the disease. One should not, however, relax a good hygienic behaviour. At this time it becomes important to start reflection on the political, sociological and psychological factors involved in the spreading of the disease. Despite the lack of accurate reports from the Mainland, it appears that, after a peak around mid-february, the outbreak did not come out of control suggesting that some factor(s) have played an important role, whether political, or simply sociological (the structure of cities, buildings etc. is extremely important). The Mainland being now a full partner of WHO, accurate knowledge of the situation will soon be available. Patients at the French Hospital in Hanoi are under strict control measures: on march 14, a group of 12 staffs (specialists of intensive care, nurses, virologists) was sent to Vietnam. Besides taking care of the patients, this staff was involved in a vision of prevention of infection. In Hanoi, the risks of further contamination seem to be under control: since march 25, no new case of chain contamination has been reported. Nine persons from the medical staff of the French Army arrived to replace the orginal staff on march 25. Identification from new cases substantiate the hypothesis of a coronavirus as the cause. One must remember however that until explicit link with the disease has been established one should remain open to other hypotheses.
• 1 april 2003. While SARS does not seem to recede in Hong Kong, a model of the outbreak at Amoy Gardens Estate, constructed by mathematicians at the University of Hong Kong, suggests that contamination follows a route similar to that of flu. This is a matter of great concern, since flu is highly contagious. This also suggests that the outbreak in Mainland China might not be under control yet. If this is the case it is almost inevitable that the disease will spread throughout the world. However it is important to remember that Amoy Gardens Estate is a high rise building and that spread of the disease might be due to this specific situation.
• 31 march 2003. Quarantine measures are implemented in several places in the world while the epidemic does not seem to level off. Eighty more patients have been identified in Hong Kong since yesterday.One block (block E) at Amoy Gardens seems to have been most affected, and investigation is proceeding to try to identify the nature of high contamination there. This would certainly be a lesson for containing the disease elsewhere. The nature of the virus that causes the disease is still under discussion, since there has not been, as yet, an explicit correlation with the immune response of patients who have recovered.

• 30 march 2003. The outbreak might be levelling off in Hong Kong, but at a high level: sixty new cases have been diagnosed there. A thirteenth patient passed away while the Italian doctor who discovered the disease in Hanoi died in Bangkok. A group of French military doctors departed for Hanoi to help their colleagues. Including the recognized Mainland cases, one already counts more than 1600 cases and 58 deaths.
• 29 march 2003. Anxiety rose in Hong Kong while 58 new patients have been affected by SARS. 470 cases have been identified in HK, and 86 in Singapore. The cause of the sudden increase in the past two days is the outbreak that affected 34 new persons at the Amoy Gardens Estate. A twelvth patient, an elderly person, died from the disease in HK. General models describing the progresses of similar outbreaks would predict that, if appropriate prophylactic methods are enforced, the disease should presently level off then go extinct. A favorable circumstance should be the weather that is warming up, provided air conditioning is not creating a situation that would mimick the winter time weather. It must be stressed that identification of the virus, at this point, is mainly useful as it substantiates the hypotheses about its mode of transmission. As in most cases of viral diseases implementation of drastic preventive measures is the only efficient way to stop the outbreak. Vaccination would also be efficient, but creation of a vaccine takes time, and is only rewarding if the disease is supposed to become recurrent. In fact this particular outbreak should become a lesson for political authorities as well as medical staff, since an outbeak of a much more contagious disease like a new form of influenza would certainly have a much more severe impact. Fast reaction, as well as drastic control of hygiene is a necessity.
• 28 march 2003. The number of affected persons in HK jumped with 22 from a single building adding to the steady daily flow (51 more patients enrolled on the evening of 27th). The local governement has finally resorted to measures similar to those implemented in Singapore, restricting the movement of more than 1,000 people. Consistent reports throughout the world suggest that the disease is indeed caused by a coronavirus, making the identification by Pr Peiris an important step in the fight against the disease. Some think that a paramyxovirus could be an aggravating factor: ''The coronavirus is the primary cause of the disease,'' said Pr Peiris, adding that another virus, of the family that causes mumps or measles, may also be involved and increase the severity of the disease. Interestingly, the new strain had characteristics unlike any other he had ever seen. In a parallel statement Pr Bernhard Fleischer, head of Hamburg's Bernhard Nocht Institute for Tropical Medicine, said his institute had probably identified the virus causing Severe Acute Respiratory Syndrome. "I don't assume that there will be a worldwide epidemic which will spread among the population," Fleischer told Reuters in an interview. "We are lucky that this disease is not as contagious and does not spread as easily as first assumed."
• 27 march 2003. While about thirty new cases are discovered in HK, all connected to the initial patients, it appears now clear that the epidemic of SARS in Guangdong affected almost eight hundred people, with thirty deaths. Some indications suggest that the disease is now spreading in Beijing and other parts of China. Clinical symptoms are described at PROMED. The government of Hong Kong is now considering to take measures similar to those in Singapore, asking people who have been in contact with affected patients to stay at home for ten days. The cause of the disease is not yet clear, but the symptoms and propagation makes a pattern that suggest that the world-wide outbreak started from the same origin. At the moment it might be traced back to a patient in Foshan City (Guangdong) who got sick on 16 Nov 2002. Patients of the initial outbreak are now systematically recovering and, if the disease can be contained, this will alleviate some of the extremely tense work load at hospitals. However, in other parts of the world, such as Taiwan and Canada, the outbreak is not yet contained. Scientists world-wide are trying to decide what is the exact cause of the viral disease with no compelling conclusive evidence yet. However the coronavirus hypothesis now seems the most plausible, since tests that had initially been negative appear now to be positive after new types of assays. Also, as said earlier, coronaviruses being highly prone to recombination, they have more potential to create new unknown virulent variants.
• 26 march 2003. 25 new cases were added to the list of HK people affected by SARS. An incident in a plane carrying HK tourists to Beijing from march 15th and march 19th examplifies the way the disease is propagated. In the world the disease continues to spread (see Health Surveillance for airline passengers). It may be affecting Beijing. The puzzle about the nature of the virus continues, while the virus isolated at HKU is better characterized. For journalists interested in the difficulty of identifying viruses, and in the vivid ongoing debate here is a summary provided by scientists at PROMED.
• 25 march 2003. As the number of SARS cases resumed growth in Singapore the local government decided to warn all 700 persons who have been in contact with patients to remain at home for ten days. The CDC in Atlanta has identified another type of virus as the possible cause of the disease. This virus family, the coronaviruses usually causes gastroenteritis in man. It is also the cause of bonchitis in birds as well as many other diseases in all kinds of animals including man. It is also the frequent cause of common cold. The virus that has been isolated at HKU is also a coronavirus. It is difficult to reconcile the data from the previous identification of paramyxoviruses and these new identifications. Several explanations may be proposed, including sample contamination, multiple infection and different outbreaks with similar symptoms. In Hong Kong the Chief Executive of the Hospital authority was found to be affected by the disease and the number of patients reached 260.
• 24 march 2003. The number of Severe Acute Respiratory Syndrome cases kept growing steadily in Hong Kong (about 25 new cases each day, see dedicated government site, 242 cases in the afternoon of march 23d), but the spread of the disease seems to be contained elsewhere in the world. Schools where cases were detected in staff or students are closed for seven days, until the incubation time for possible new cases has elapsed. The World Health Organisation cautions that virus identification is difficult since our respiratory system is commonly infected by many types of more or less innocuous viruses. The easiest to be cultivated might not be the cause of the disease. However all identifications so far concur to the idea that the virus is a paramyxovirus.
• 22 march 2003. The virus identified in the SARS outbreak in Canada is a metapneumovirus (6 identifications out of 8 cases), a virus from the paramyxoviruses family, which has been discovered in 2001 and is usually the cause of common cold-like diseases. This virus may be the common source of the outbreak. In another effort, scientists of the team of Pr Malik Peiris at the University of Hong Kong have cultivated the virus that may have started the outbreak in the city and are testing an efficient diagnostic test that detects the virus [PDF]. This would rapidly tell whether cases of pneumonia, frequent during this period of the year are indeed SARS and prompt appropriate precautions. It is not known however whether this is a metapneumovirus yet. One must also have in mind that pneumonia cases are documented with at least two viruses infecting the same patients.

• 21 march 2003. The number of SARS cases rose to 165 in Hong Kong. The history of the disease in the city is now fairly well understood. At its origin is a medical doctor travelling from Guangdong and staying at a Kowloon hotel, where he infected, either in the elevator or in the elevator lobby several persons who then transmitted the disease. One of those started the outbreak at the Prince of Wales hospital. authorities are actively looking for all the persons who stayed at the time of infection in the hotel. This outbreak is an illuminating illustration of how our travelling habits are spreading diseases throughout the world extremely rapidly. The fact that apparently no staff of the hotel has been affected provides good hope for the disease to be under control rapidly if appropriate hygienic behaviour is followed. Remember that coughing and sneezing, in particular, is an efficient route spreading the virus.
• 20 march 2003. The origin of the SARS in Hong Kong has been traced back to a traveller who stayed in a hotel in Kowloon. Apparently, no personnel at the hotel has been affected, substantiating the reassuring observation that close contact is needed for the disease to spread. A paramyxovirus has further been identified as the cause in Singapore. As yet, no clear connection is made with the epidemic of pneumonia that spread in Guangdong province since november and seems now under control. However, both the symptoms and the spread are so similar that it seems likely that the cause is the same. It will be important to identify the source and political authorities in the Special Administrative Region of Hong Kong and in Mainland China have agreed to tighten their collaboration. This will be particularly important in the future since the risk for an outbreak of a dangerous influenza epidemic is high.
• 19 march 2003. A paramyxovirus has been identified as the probable cause of Severe Acute Respiratory Syndrome (SARS). First indication came from Frankfurt and Marburg, and explicit identification was performed by a team from the Prince of Wales Hospital and Chinese University of Hong Kong. Paramyxoviruses infect vertebrates, and cause often severe outbreaks in communities of birds. They cause outbreaks of encephalitis in South East Asia. The common and highly contagious measles virus belongs to this family. A family of these viruses has a strong tendency to infect lungs.
• 18 march 2003. The origin of the outbreak at the Prince of Wales Hospital has been identified. This permitted local authorities to screen for people who have been in contact and bring them under medical care. The result is that at the present date almost 100 persons are under surveillance most of whom having acquired the severe flu-like disease. The WHO maintains its alert until identification of the virulent pathogenic agent is identified. For ongoing discussion on the subject see PROMED.

• 17 march 2003. The WHO maintains its global alert. Forty two persons have contracted an unknown flu-like disease with frequent pneumonia symptoms at a Hong Kong hospital. One nurse died of a similar disease in Hanoi. Several similar cases have been described, possibly related to South East Asia, in the world. However it must be noted that, until now, no shared infectious agent has yet been identified. What makes the situation complicated is that we are at a period of the year where many flu-like, pneumonia-like diseases prevail. Several important facts must be borne in mind to prevent spreading of a possible new virus or bacterium, taking into consideration the unusual fact that effective contagion seems to occur within hospital premises.

1. Strict personnel hygiene must be enforced: one should never see medical personnel in their work coats outside (in particular at cantines or such public places, as often unfortunately seen); spitting on the ground should be strictly forbidden; after visiting a patient one should wash one's hands carefully; as much as possible, direct contact with patients should be avoided (gloves can be used, and one should not forget, of course, to discard them properly immediately after use).
2. Air conditioning should be monitored: temperature should not be kept too low (most microbes survive much longer at low temperatures), and ventilation should be efficient but indirect (remember that the nose and lungs act as air filters): filters should be cleaned up and as much as possible sterilized.
3. Water quality should be controlled: filters should be cleaned up, and water circuits should be checked as much as possible.

At the present time several possible agents are considered (but none has been identified as a common cause): the influenza virus (which often causes pneumonia-like symptoms and is frequently letal); Legionella pneumophila (a very dangerous bacterium often transmitted trough infection by amoeba that strive in water cooling systems or in the water circuit); Chlamydia pneumoniae (a very fragile bacterium, that may be dangerous in immunocompromized people); Rickettsia psittaci, the cause of psittacosis. Many other causes may exist among which viruses are usually the most difficult to identify readily unless well known previously. Sudden mutation of a rather innocuous virus such as syncytial respiratory virus may even be considered. The present observation that contagion seems highly confined to specific premises suggest either direct physical contact (this is the case with the Ebola virus) or some kind of transmission by water or air fluids.

• 12-14 march 2003.After a concomitant spread of a pneumonia-like flu-like disease in a private hospital in Hanoi (Viet-Nam) and in the Prince of Wales hospital in Hong Kong, the >World Health Organization issued a global alert, waiting for identification of the pathogenic agent involved. A patient diagnosed in Hanoi died in another hospital in Hong Kong. Recommendations are similar to those issued during the previous outbreaks, for which no clear pathogenic agent has been identified. Contagion appears to have remained restricted to the medical personnel who was in contact with the patients. The cause of the disease, presumably a virus, is not known at this date.
• 20 february 2003.It is established that the father of the child treated for H5N1 flu died of the same disease. Although it is not yet established that this was caused by the same avian strain, this is likely. Sporadic cases of bird's flu in Hong Kong, including in wild birds, demonstrated that there are foci of disease in the Mainland. This second identified direct contamination from birds to man in Fujian province demonstrates that the disease must be taken extremely seriously. Fortunately these recent cases do not appear to have been caused by person-to-person contamination. The World Health Organisation is tackling the matter, and considering what types of vaccines should be prepared to be able to react immediately in case of epidemic. It is also important to remember that such disease outbreaks spread from places where birds are in large flocks (poultry farms and markets in particular). The "atypical pneumonia" diagnosed recently in Guangdong does not appear to be related to bird's flu: coincidence of infection with pneumonia-like symptoms, perhaps caused by a variety of pathogens, appears to have triggered the panic after personnel from medical care institutions died. This type of disease is frequent in winter, and the number of people dying from such diseases is always significant.
• 19 february 2003.A nine year old child is treated in Hong Kong for H5N1 influenza. No link has been established with the epidemic that created panic in Guangdong, but it is a matter of extreme concern, since this form of flu, which affected Hong Kong in 1997 is significantly more dangerous than the more common forms. Once again, elementary rules of hygiene should be followed.
• 11 february 2003.An outbreak of "atypical pneumonia" in Southern China led the French General consulate in Guangzhou to close the French School in the city, until more is understood about the disease. The rumor spread that several tens or even hundreds of people have been contaminated, with a high death toll. No reliable information is available at the present time. It seems likely that the cause of the disease is a virus, perhaps a new flu strain (but perhaps "ordinary" flu). This fits the time of the year, and the possibility of hospital contamination. One should also remember that flu is indeed a deadly, albeit ordinary, disease... Usual rules of hygiene should be carefully followed (washing hands frequently in particular) and people should limit contacts with large concentrations of people. One should avoid travelling, to limit the spread of the disease. Also, remember that panic is one of the most efficient way to spread diseases.
• 8 february 2003. An outbreak of Ebola fever is spreading in Congo, at the border with Gabon at a place close where it was declared one year ago.
• 18 january 2003. Work at the Institut Pasteur and de Madagascar results in the creation of a fast test for diagnosing plague. Paper strips are used to detect the presence of the plague agent, Yersinia pestis (discovered by Alexandre Yersin in Hong Kong more than one century ago). The goverment of Madagascar provides a supply to its local health centers to identify the disease, which is still endemic in the island.

• 15 december 2002-21 january 2003. The flu virus H5 reappears in Hong Kong. It is most likely that it is not confined to Hong Kong itself, but is present in the region. This time, it was first identified in waterfowls, before being found in dead chicken at several market places. Open markets are closed for cleaning on New Year's eve.
• 7 october 2002. The Nobel Academy has awarded the Nobel Prize to work on Caenorhabditis elegans. This is an important lesson for those who still do not understand that discovery cannot be planned. Work on the nematode worm C. elegans allowed discovery of programmed cell death (apoptosis). This "suicide" of cells is universal. It is of major importance for the construction of animals, and plays a fundamental role in cancer. This discovery is the result of purely academic research, as are all the processes at the root of genetic engineering...
• 6 october 2002. A new serotype (type 2) of Dengue fever has been identified in Hong Kong. Fortunately, the cooling of the atmosphere, associated to dry conditions will prevent the epidemics to spread.
• 2 october 2002. Dengue fever is spreading in Hong Kong. Several cases of Dengue fever type 1 have been diagnosed since july, raising concern about a possible epidemic.

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A short description of relevant microbes

Microbes Nomenclature

Microbes have a name, which plays the role of an identifier. It is essential, to avoid duplication and erroneous assignments that the names are validated. The process, as in the case of other scientific activities is peer-reviewed.

Validation lists of bacterial species are lists published in the the International Journal of Systematic Bacteriology (IJSB) or in the IJSEM validating bacterial names effectively published elsewhere.
It is important to note that the publication of new names or new combinations in a validation list is the responsibility of the authors who propose the new nomenclatures. authors wishing to have new names and/or combinations included in a validation list should send the pertinent reprint or a photocopy thereof to the IJSEM Editorial Office (IJSEM Editorial Office, Society for General Microbiology, Marlborough House, Basingstoke Road, Spencers Wood, Reading RG7 1AE, UK. - e-mail: ijsem@sgm.ac.uk - Tel: + 44 118 988 1815 - Fax: + 44 118 988 1834).

A list of valid names and identifications is published at the site providing the List of Bacterial Names with Standing in Nomenclature.

Genes nomenclature

Genes nomenclature is not yet standardized, unfortunately. However many bacterial geneticists are endeavoring to implement Demerec's rules as the standard nomenclature. Because E. coli is the reference bacterium gene names will be usually derived from gene names given in E. coli. Some adjustment will be needed however, since many names in E. coli were just given more or less by chance, according to a phenotype that was observed by the first geneticists who came across mutants of this gene. The protein data library, SwissProt, is pioneering in this effort.

Demerec's rules are simple. A gene is written in italics. The name comprises three low case letters (usually a mnemonics of the gene function), followed by a capital. Then an arabic number, indicating a specific allele, follows. In case when there is no capital letter, a dash precedes the allele number. Examples:

argH1, cyaA610, leu-1

when genes are clustered in transcription units (operons) the gene full name is usually not repeated, but only the capital letters are noted, e.g.

hisABCDEFGH

For genes of unknown function the three letters of the gene (temporary) name start with a "y" (Why?), and the following letters are usually indicative of the position of the gene along the chromosome, e.g.

ywhE, ywhFG are located next to each other, and have not (yet) been functionally identified.

When sequences are inserted inside a gene, this is indicated in roman after two colons:

speA::Tn10 means that the speA gene is interrupted by transposon Tn10

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Apart from viruses, many microbes are causing cancer. But the worse toll they take on patients is during cancer treatment. In fact, one of the reason why chemotherapy is often unsuccessful is that, during the treatment, patients become infected with a variety of pathogens, and die from infection. As a consequence, fight against cancer should involve a large effort in fight against microbes, in particular bacteria, and a fungus of the environment Aspergillus fumigatus.

Controversies

The magazine Nature (10 jan 2002) writes an editorial on the use and abuse of citation statistics, pointing at major errors in the assessment of publication records of scientists by the only reference in the domain, the private Institute for Scientific Information.

The magazine Nature (8 sept 2001) writes an editorial on the future of electronic scientific literature, clearly favoring this new medium as the future of scientific exchange. Nature being a "paper" magazine, this triggered reactions at Publishing companies.

An interesting debate centers on the origin of the 1918-1919 influenza epidemic: while it was thought that the negative RNA segments of the virus could only reassort from one virus with another one, sequence data on that letal strain suggest recombination. Mark Gibbs of the Australia National University at Canberra reported findings that support this hypothesis on April 25th at a Royal Society symposium.

The Human Genome Program began in the USA when Charles DeLisi managed to obtain 5.5 million US$ in 1987 to start a feasability study. This mandate derived from its predecessor agency (see A rattling good History) the Atomic Energy commission to study the effects of radiation and chemical by-products of energy production. The start point of this study was triggered by the interest of James Neel in physical anthropology, in particular in the becoming of irradiated persons from Hiroshima and Nagasaki and of their progeny.

			Recently, the work of James Neel has been put into question in a bitter debate because of his keen interest for naive selection processes which might operate in Humans. This debate is strongly linked to ethical issues associated to the Human Genome Program. It is therefore interesting to have some flavour of its content. It is clearly developed in a recent issue of the New York Review of Books, where the role of Neel in the controversial study of a Venezuelian Indian tribe, the Yanomami, is vividly described. As stated by Clifford Geertz Neel's book: Physician to the Gene Pool: genetic Lessons and Other Stories (Wiley, 1994) "is a combination autobiography and homiletical treatise in "genetic medicine." Neel goes on to say; "One of the major disappointments of our fieldwork was that, despite much brainstorming, we could never devise a field test of Yanomama 'smarts' - and if we had devised one, the Yanomama would have no motivation to take it seriously." To Tierney he confessed in a 1997 phone interview, that his failure to isolate the alleles for his index of "Innate Ability", and thus pin down his big man/big smarts/big reproducer theory directly, "was the greatest disappointment of my life.'''' All the controversy is depicted in Patrick Tierney's book: Darkness in El Dorado: How Scientists and Journalists Devastated the Amazon" Norton, 2000. This is an interesting background for the present and future debates about the ethical issues raised by the knowledge of the Human Genome. Mid-january 2002 the controversy is not settled.

The campaign for free Internet access to full text material of published research papers is succeeding (april 2001). The number of publishers agreeing to give free access to the material in their journals six months after publication is steadily increasing. Only the largest commercial publishers (Reed Elsevier and the Nature group) have yet to declare their intentions and there is good reason to believe that even they are actively reconsidering their policies.

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The Origin of Life (preliminary information)

• From minerals to life : an alternative to the prebiotic soup
• Dalle minerali alla vita
• Une Aurore de Pierres
• The tree of life

Fads and Fallacies in the Name of Science

Tip: remember to be critical. This does not mean to ask nasty questions, but to always check the information you get from scientists and doctors! When somebody uses words such as "for the first time", "previouslyundescribed", "unexpected", "dramatic" etc please check. Often, this is indeed unexpected or the first time for the person who informs you (this can be a sheer lie...). This is relative, and has often already been observed elsewhere, or some time (often even a long time) ago. Many simple ways exist to control information. Here is a very fast and efficient one: use the words given by your informer, put them in the "search" field Entrez software at the NCBI, for example in the PubMed database, and read some of the abstracts of the papers you will get to. Often this will tell you about competitors or about related work. Most probably you will be surprised by their sheer number, and by their content. Remember that, at present, there are more than 2.5 million scientists involved in research in biology all over the world. Remember also that scientists of the past (and even of the remote past), were as intelligent, if not more intelligent than those of the present time. In particular, most were aware of the fact that, what they are building is constructed on previous knowledge. They were interested in History. This is an element that journalists should always consider as relevant (and, fortunately, this is deeply rooted in Chinese tradition). Beware of fashion! Fashion has, as a built-in principle, the property to be a non-lasting phenomenon. Fashion must create an ever-changing environment. And this is exactly at the opposite of the main goal of science, which is to provide long-lasting explanations of phenomena. Try to escape the "authority argument" where people who have got coveted honors are thought to know better, even in fields that are different from those where they are specialized, than people with good common sense. Prizes and Medals are deeply rooted in ideology, sociology and human psychology. You have the right to be informed, and not imposed by ready-to-use ideas, from people who think of themselves that they are the best. By construction, a scientist must be modest. And he should have as a motto, that of Montaigne "Que sais-je?" ("What do I know?") or the last sentence said by Jacques Monod when he was dying: "Je cherche à comprendre" ("I try to understand").

Caveat: It is important to note that crooks who construct attractive fallacies in the name of science, use practices (naturally, not all of them) which belong to science, so as to pretend to have a scientific approach. A common way is to use reproducibility as the only landmark of science. Naturally, these crooks ask you to reproduce their experiments. But, of course, systematic errors (are indicated in their name) are reproducible! The way to test for a crooked approach is simple: ask whether an appropriate control has been performed (correctly). For example, some assert that biological molecules can have an effect when they are diluted below Avogadro's number (which means that only their ghost could be active). Well, the control is obvious (but never performed): ask these people to measure the concentration of all components of their mixture, before proceeding further (this is the basic control which would have been asked to a student, and this is easy to do). Now, to correctly perform the required experiment you should monitor the concentration of the atoms and molecules present in the mixture (so that you know what you are doing). You can bet that they will never do it, but, rather, ask you to repeat their experiment! This is the trick... The fashionable magazine Nature thus published a work on the "memory of water" which did not propose or perform any appropriate control for the quality of water used! The study of this paper and related work is an excellent test to investigate someone's gullibility.

• Bad work and Fakes in Biology:

Spring 2002: the magazine Science, publishes another account of "cold fusion", despite very negative advice of the community of physicists. This bad work will certainly increase the Impact Factor of the journal. See for example (the list is unfortunately ever growing, and this is just for the purpose of illustration):

retraction: Metal-insulator transition in chains with correlated disorder
PEDRO CARPENA, PEDRO BERNAOLA-GALVAN, PLAMEN CH. IVANOV & H. EUGENE STANLEY
retraction: A cytosolic catalase is needed to extend adult lifespan in C. elegans daf-C and clk-1 mutants
J. TAUB, J. F. LAU, C. MA, J. H. HAHN, R. HOQUE, J. ROTHBLATT & M. CHALFIE

Another retraction in microbiology (february 2002): the magazine Science had published an "interesting" study on the clonal nature of virulent Staphylococcus aureus isolates in the wild. This work is now retracted: Science (2002) 295: 971. Still another (involuntary) means to increase the Impact Factor of a Journal...

Still another case of (at best) sloppy work published in high profile journals. This time about a very sensitive issue (monitoring Genetically modified Organisms). This demonstrates the dangerous impact of fashion in scientific journals.

"DNA Contamination Feared," declared the Washington Post last fall. Gene-altered DNA may be 'polluting' corn," warned USA Today. Both papers—as well as many other media around the world—were reporting the results of a scientific study published in the prestigious journal Nature. Anti-biotech activists at Greenpeace, Friends of the Earth, and the Union of Concerned Scientists immediately seized on the results to press for a ban on planting and exporting genetically enhanced crops.

Now a comprehensive review published in the February 2002 issue of the journal Transgenic Research, finds that "no credible scientific evidence is presented in the [Chapela and Quist] paper to support claims made by the authors that gene flow between transgenic maize and traditional maize landraces has taken place." The review states, "It is most likely that the report by Quist and Chapela is a testimony to technical failure and artifacts which are common with PCR and IPCR." Typically PCR false positives occur because samples can be easily contaminated with the material being tested for.

A German study on putative cancer vaccines has been invented by its authors (discussed in Nature vol. 412 p. 8: original paper Nature Medicine Kugler et al.). Unfortunately fraudulent articles are rarely retracted and retracted articles are still quoted for a long time....

Why not remember the invention of adenylate cyclase in plants ?

Other fakes...

• The Ig Nobel Prize: see the winners!
• Post-modernism in derision: Sokal's hoax
• Question to test your common sense: growth media for bacteria are made without addition of trace elements such as Zinc, Manganese, Nickel etc. Of course bacterial enzymes contains theses elements. Does that mean that bacteria are able to do what alchemists tried to do, transmute matter?
• Another question for common sense: A huge programme is meant to collect samples from planet Mars and get them back on Earth. Astute marketing gurus have invented the following idea (knowing that it already worked very well on gullible persons, when Orson Welles announced invasion of Earth by Martians): living organisms on Mars might attack us, from the samples we collect there, and this justifies to handle them under high confinement. Why is it a ridiculous idea (scientifically speaking, of course, not stupid if one wants to lure money out of people!)? Hint: Nature and Artifice.

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Hot topics about microbes, environment and infection

A short description of relevant microbes

Controversies

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