A WHO advisory committee has given green light to limited manipulation of the smallpox virus. If the recommendation is accepted by the director of the WHO and the World Health Assembly next year, it would mark the first time since smallpox was erradicated (1979) that scientists would be allowed to genetically modify the virus. According to the committee the following experiments would be allowed: a) insertion of a single marker gene into the virus, b) transfer of one smallpox gene into a related virus and c) free distribution of very short (<500 bp) fragments of smallpox DNA to labs and companies working on diagnostic tests. Scientists of the US army want to insert a gene coding for green fluorescent protein into the virus to make it easier to screen for new antiviral drugs. A visual assay would make it possible to automate some of the screening tests, making them both faster and safer. (Science , Vol. 306, p 1270-71)

Zoo workers who come into close contact with nonhuman primates, such as apes and monkeys, may be at increased risk for exposure to simian virus 40 (SV40). SV40 causes cancer in laboratory animals, and SV40 DNA has been observed in some human tumors, although possible routes of infection are unknown. In an american study 254 zoo workers were tested for antibodies to SV40. 25 of 109 of the workers who had direct contact with primates (23 percent) tested positive for SV40, as compared with 15 of 145 workers (10 percent) who had no direct contact with primates. The author of a related article also points out that, while humans who come into contact with primates may become infected with SV40, there is currently no evidence to suggest that SV40 has spread outside of zoo environments or that it plays a role in the development of cancer in humans. In the 1950's, early batches of poliovirus vaccine were grown in monkey kidney cells that harbored a simian vacuolating virus, now known as simian virus 40 (SV40). It has been estimated that between 10 and 30 million people received one or more doses of live SV40 in contaminated vaccine. Many developed antibodies to SV40 proteins, but there have been no documented negative consequences to this exposure. (The Journal of Infectious Diseases, 15 Dec 2004).

Staying in intensive care units 55 000 people die in Germany every year from blood poisoning, i.e. 150 deaths every day. This statement is the the result of a study, which was presented at a medical conference in Hamburg. Thus, the mortality rate is as high as with acute heart attacks and higher as breast or intestine cancer. A septicemia can emerge, when the microorganisms of a local infection spread through the blood to other organs of the body. The most prominent cause for a septicemia is a pneumonia while the immune system is impaired. The data has been collected by the scientists from 3800 hospital patients. Eleven percent of the patients suffered at the day of the investigation from a heavy blood poisoning or had a so-called septic shock. Of these patients 52 percent died.

A new set of regulations will prohibit Chinese lab directors from allowing experiments on risky pathogenic microbes without approval. China will grade its pathogenic microbe labs by four levels. The first and second grades are labs forbidden to conduct experiments on risky pathogenic microbes, which can cause severe diseases in human and animals and easily spread. The third and fourth grade of labs are off limits for experiments without special certificates from the health and veterinary medicine administrations. These labs also must get approval from the administration when they plan to take up the experiments on risky pathogenic microbe and report the result when the research ends. Early this year, a chines laboratory did experiments with the SARS virus without proper qualification and facilities to prevent the virus from spreading. The administration found that the lab researchers used an untested method to kill the SARS virus and did not test the result of the process. The director and deputy director of the centre resigned. The head and deputy head of the centre's Institute of Virus Diseases as well as director of the lab were dismissed in July. Now, according to the regulations, the head of the institution that owns a lab and head of the lab will be dismissed if a mistake like this happens again.

Inhalation of salty water may have effects to decrease the spreading of diseases like influenza or tuberculosis. Already six minutes of inhalation with salty water reduced germ-containing aerosol droplets by more than half. This effect can be observed for up to six hours. In a study with 11 men, researchers observed that at normal breathing some individuals exhausted more germ-loaded aerosol droplets than others. The number of germ-loaded aerosol-droplets varied dramatic between individuals and also during time. It started at one particle/liter of air to more than 10 000 particles. The described salt water treatment reduced the number of exhausted germs by 72%. (Preprint Proc.Natl.Acad.Sci.).

Researchers have used an ELISA to determine the prevalence of IgG antibodies specific for the Zaire subtype of Ebola virus in 790 nonhuman primates, belonging to 20 species, studied between 1985 and 2000 in Cameroon, Gabon, and the Republic of Congo. The seroprevalence rate of Ebola antibody in wild-born chimpanzees was 12.9%, indicating that (1) Ebola virus circulates in the forests of a large region of central Africa, including countries such as Cameroon, where no human cases of Ebola infections have been reported; (2) Ebola virus was present in the area before recent outbreaks in humans; (3) chimpanzees are continuously in contact with the virus; and (4) nonlethal Ebola infection can occur in chimpanzees. These results, together with the unexpected detection of Ebola-specific IgG in other species (5 drills, 1 baboon, 1 mandrill, and 1 Cercopithecus), may help to narrow the search for the reservoir of Ebola virus. They also suggest that future Ebola outbreaks may occur anywhere in the central African forest region. (Leroy et al., The Journal of Infectious Diseases, 2004;190:1895-1899).

The WHO has warned of a worldwide spreading of avian influenza. The head of the WHO section for infectious diseases, David Heymann, said at a conference in Miami that the incomplete knowledge of the rsik factors could lead to a pandemic of avian influenza. He said that the risk is ,high", however, the experts do not know how high. "The world is not prepared to deal with this disease" Heymann warned. The presently existing 300 million doses of the vacine would by far not be enough to cover the entire need, the expert added - and the vaccine can not be stored. The fear of a worldwide spreading of avian influenza was stirred up by the outbreaks of the disease in Thailand and in Vietnam. In these countries 32 people died this year after infection with avian influenza.

Recent cases of severe acute respiratory syndrome (SARS) linked to exposures in research laboratories have prompted concerns about the role of laboratories as a reservoir for the reintroduction of SARS into the community. Since the containment of the global SARS outbreak in July 2003, most of the reported cases have been associated with exposures occurring in laboratories working with live SARS-associated coronavirus (SARS-CoV). These cases underscore the need for strict adherence to appropriate biosafety protocols and precautions when working with live SARS-CoV and other Biosafety Level 3 (BSL-3) pathogens.

Through a natural process known as antigenic drift, a new strain of influenza that can diminish the effectiveness of today's vaccine is already emerging in New Zealand. Like weather forecasters watching tropical storms, epidemiologists for the World Health Organization track the ever-evolving strains of influenza. Tests suggest that 43 percent of recent New Zealand flu cases spring from the new strain, or variants of it. One reason for concern is that laboratory animal tests suggest that the current vaccine is about 2/3rds less effective in stirring antibodies against the New Zealand strain than it is against the targeted strain. When flu vaccines are well-matched to the prevailing flu strains, the shots can prevent flu in 70 to 90 percent of vaccinated adults, according to the CDC. Although well matched shots may prevent flu in only 30 to 40 percent of nursing home residents, they can reduce the death rate from influenza and pneumonia in that population by 80 percent. Vaccine manufacturers need a 9-month lead to produce a new flu vaccine.

The 1918 flu virus spread across the world in three months and killed at least 40 million people. If it escaped from a lab today, the death toll could be far higher. Yet despite the danger, researchers in the US are working with reconstructed versions of the virus at less than the maximum level of containment. The researchers working on the 1918 virus say their work is vital to understand what changes make flu viruses dangerous. So far five of the 1918 flu virus's eight genes have been sequenced, using fragments retrieved from victims of the pandemic. Several teams have added one or more of these genes to modern flu viruses, or plan to - in effect partially recreating the long-vanished pandemic virus. One team showed that adding the 1918 gene for the surface protein haemagglutinin to modern viruses made them far deadlier to mice. The team started the work at the highest level of containment, BSL-4, then they decided the viruses were safe enough to handle at the next level down. The researchers said that the decision to move down to a lower security level was taken only after experiments showed that giving mice the antiviral drug oseltamivir (Tamiflu) in advance prevented them getting sick, meaning, that if all lab workers take oseltamivir, they cannot become infected. Yet this assumes that the mouse results apply to humans. In similar experiments other researchers got quite different results: they found that mice given oseltamivir still got sick and 1 in 10 died. (ProMed)

Indonesia's agriculture ministry said on Wed 6 Oct 2004 that tests showed [the avian influenza virus] strain that had killed millions of chickens in the country could not be transmitted to humans. Tests conducted at a laboratory in Hong Kong, to which Jakarta was referred by the World Health Organization, found that the H5N1 avian influenza virus strain in Indonesia was different from that [circulating] in Thailand and Viet Nam. The genetics analysis showed that the [RNA] chain of our virus is similar to the kind in the Yunan province on mainland China, and distinct from that in Viet Nam and Thailand. The officials have always questioned why there are no human cases in Indonesia. The possibility lay open for the virus to mutate into a deadlier form that could be transmitted to humans. Around 16 million fowl, have died in Indonesia since the end of last year [2003] due to avian influenza and Newcastle disease. The disease hit a chicken farm in Central Java last week [final week of Sep 2004], killing 350 birds. The carcasses were cremated to prevent the virus from spreading to other areas. Overall, avian influenza was under control, but sporadic outbreaks might occur during the rainy season that usually runs from October to February. Asked whether the government could take firmer action by killing healthy chickens in affected areas, The officials responded that they simply don't have the money for compensation. Although sequence analysis may suggest that the Indonesian isolate of H5N1 influenza virus resembles Chinese isolates more than avian influenza viruses circulating in Thailand and Viet Nam, it is premature to relate this to the potential transmissibility of the Indonesian strain. Nonetheless it is likely, in due course, that phylogenetic data of this type will lead ultimately to the understanding of the genetic determination of transmissibility of avian H5N1 virus to humans.

Polio-viruses have escaped from two indian labs and have infected humans according to the indian newspaper Times of India. Laboratory strains have been confirmed in seven patients as the newspaper anounced last week. As a consequence all laboratories that store polio-viruses should be added to a list. However, this process could take up to two years, as the officials leading the investigation mentioned. Such incidents could hamper the effort to eradicate polio in India and even worldwide. The disease is still endemic in some asian and african countries. The United Nations have decided to eradicate polio worldwide until 2005. In India there still were 300 cases of polio detected in 2004 and according to UNICEF there were 667 cases worldwide. By the end of last week the World Health Organisation startet the largest vaccination campaign in Africa.

China has required all localities to strengthen preventive efforts against the possible outbreak of the highly pathogenic avian influenza virus, or bird flu, during autumn 2004 and winter 2005, according to a circular recently issued by the Ministry of Agriculture. According to the circular, poultry should be immunized more strongly in key areas and quarantined before and after butchering. "Sterilization work should also be carefully done to remove all potential build-ups. Farms, slaughterhouses, markets, cool-houses and transport tools should be disinfected," it says. "Since the autumn and winter period is a key period for birds to migrate, the bird flu is quite likely to break at any time," warns the circular, which cites the ongoing highly pathogenic bird flu in some Asian countries as a threat to China. "Various localities of the country must understand the current situation and increase their sense of responsibility in preventing the highly pathogenic bird flu," it says. It also requires all related authorities to substantively enhance coordination to form a united power. "Authorities should also prepare and improve their emergency plans and make ready vaccine and sterilizing drugs," says the circular.

Thailand on Thursday added three deceased patients to the list of suspected cases of bird flu infection. The three patients, including a pair of mother and daughter and a separate boy, passed away with pneumonia symptoms in the northeastern province of Kamphaengphet in past 15 days, said the officials of Communicable Diseases Department of the Public Health Ministry. It was stated that the lab test of the three cases would come out in a few days. Since the avian influenza rebounded in the kingdom in July, an 18-year-old man has died last month in central Thailand, pushing the kingdom's bird flu casualty to 9. In the first wave of bird flu outbreak at the beginning of this year, eight people in Thailand were killed by the epidemic. Another 19 people have died in Vietnam, bringing the Asian death toll to 28. Besides, there have been 128 patients in Thailand under observation for possible infection of the disease since early July. Now, 114 of the cases have been cleared and the rest are still waiting for the test result. (http://www.xinhuanet.com/english/)

A paper published by dutch scientists confirms that the virus can infect cats and that felines can transmit the virus to other cats as well – and perhaps to humans. Although there is no evidence yet that cats have helped spread the disease anywhere, their vulnerability to the virus increases the concern that it may evolve into a more dangerous strain that could setoff an influenza pandemic. The virus was first reported in cats in January, when a leopard at a zoo near Bangkok died from an infection. A month later, a sick white tiger at the same zoo tested positive for avian flu. Three domestic cats that died near a Thai farm were also found to harbour the virus. In each case, eating raw, infected poultry was the likely infection route. The study underscores the virus' ability to infect multiple mammal species, which is unusual for strains that circulate in birds. The experts note that there is no reason for the chinese public at large to worry about their pet cats, but some precautions would be wise. For example, the practice of feeding dead carcasses to carnivores in zoos and on farms is not a good idea. And cats with access to poultry should be watched for signs of illness. (Science Vol. 305, No. 5689, page 1385)

Many infectious diseases in humans can be acquired through contact with pets. Dogs and cats may be the most frequent household pets around the world, but there are also many other vertebrates that share our household environment. Lizards, snakes and ferrets are less common pets. At least 55% of all households in the United States have a dog or a cat, and 15 to 20% have pet birds, but the pet population is also composed of millions of rodents, reptiles or aquarium fish, not to mention less common species such as wild carnivores, monkeys or more recently the miniature pig. If one excludes gastrointestinal infections such as salmonellosis or yersiniosis, most zoonoses are rare events associated with pet ownership. Among the pets, the domestic or European rabbit is certainly an excellent pet for children. Although many rodents can potentially transmit many infectious organisms, lagomorphs (which include rabbits) are rather safe pets, most of the health problems encountered being allergies. Because of the diversity and the large size of the pet population, exposure to animals should be systematically ascertained when examining a patient. (Bruno B. Chomel, DVM PhD. Pediatric Infectious Diseases Journal, 1992, 11:479-487)

The kick-off-meeting of the CTI(Commission for Technology and Innovation)-project „Development of a national biosafety-network“ was held on September 3, after the start of the project in July 2004. During the next two years, both the technical colleges of the Swiss BioteCHnet (FHBB, HEVS, HSW, ZHW, FHBurg) and b-safe Ltd will develop a network bringing the national biosafety competence together. As product there will be high leveled biosafety training courses, which will serve as model systems for a unified, effective and optimal safety and training concept. B-safe Ltd has already got into contact with cantonal authorities as well as with industry, in order to make their information accessible for the project. (Newsletter September 2004 on the b-safe homepage)

Chinese health officials confirmed this week that H5N1 avian influenza had been found in pigs there in 2003 but says no such findings have occurred in 2004. The Chinese ministry of agriculture stated that they have tested 1.1 million samples from poultry and some samples from pigs and that no H5N1 has been found in pigs. Confusion began when a prominent Chinese avian influenza expert said in a presentation at an international meeting late last week that the H5N1 virus had been found in pigs in China in both 2003 and 2004, to the surprise of WHO and FAO officials, who were not aware of this. A press official of the Chinese health ministry was likewise surprised when told later of the expert's comments and that he said his office had no information on the subject. In other developments, the state-run Thai News Agency reported the death of a dozen pigs in a northern province in August 2004 . The animals reportedly had symptoms of coughing, breathing difficulty, and swelling eyes. Chickens on the same farm had died earlier of avian flu, the story says. However, this report has not been confirmed yet.

Bird flu has been discovered in more than 10 provinces and cities in China's southern neighbour since June, while a total of 15 people have been killed by the virus and more than 60,000 chicken were slaughtered. People entering China from Viet Nam would be required to report their health condition to the entry-exit inspection and quarantine bodies once they have the symptoms resembling those of bird flu, such as fever, coughing and muscle ache. Also, the inspection and quarantine bodies across China will offer the travellers the latest information on situation of the spreading of bird flu in Viet Nam as well as necessary tips on preventing the virus. The administration advises people to stay away from contaminated poultry and the infected individuals. The public is also advised to treat the excrement of the contaminated creatures with caution. According to the administration, raw or undercooked poultry should be not eaten and masks should be worn when raising and butchering poultry. Washing of hands is recommended as an efficient way to counter the infection. The World Health Organization announced recently that no pig imported from the mainland to Hong Kong was found to have contracted bird flu. Strict measures have been adopted to prevent the spread of bird flu in areas bordering Viet Nam. In another development, markets on the Sino-Vietnamese border are being closely monitored to prevent the sale of poultry from Viet Nam. Vehicles crossing the border have also been carefully examined and sterilized. (http://www.chinadaily.com.cn/english/doc/2004-08/25/content_368452.htm)

Outbreaks of diseases like SARS are expected to recur, and they may rapidly spread across the globe. In an unaffected country like the Netherlands, true risk may have been low, but SARS still received broad media attention, which may have increased perception of risk. Researchers explored SARS-related risk perceptions, knowledge, actions, and use of information sources in an area where no cases occurred during the 2003 SARS outbreak. Respondents were 373 persons ages 19-78 years; 48% were male. All but two of the respondents had heard of SARS. Most respondents knew that it is a severe type of pneumonia (91.2%) and caused by a virus (88.7%). The correct estimate of 15% for the death rate for SARS-infected patients was reported by 9%, while 34.1% made estimates close to that number (10%-20%). While 38.9% were worried about SARS as a health problem, few respondents were worried about getting SARS themselves (4.9%) or about SARS in the Netherlands (4.9%). Only 2.6% rated their risk of getting SARS as high or very high. This first study on public perceptions of SARS outside an affected area indicates that the Dutch population was well aware of the SARS outbreak, knew what SARS was, was not overly concerned about their risk, and obtained their information primarily from television and newspapers, which were also rated as trustworthy sources of information. Many respondents reported that they took precautionary actions to reduce their risk for SARS, but very few took possible diagnostic actions. (http://www.cdc.gov/ncidod/EID/vol10no8/04-0283.htm)

Done by american researchers, a bold set of prion experiments in mice may have proven that the misshapen proteins are, by themselves, infectious. In their tests the researchers used transgenic mice, making 16 times the normal amount of the prion protein (PrP). These mice express a truncated PrP that may more readily make up prion clumps. This might sensitize the animals to introduced PrP. To obtain pure, brain free Prp the researchers genetically altered Escherichia coli bacteria into producing PrP fragments that they misfolded to form amyloid fibrils, which have been implicated in various brain diseases. Then they injected those prion fibrils into the brains of the mice. After more than a year one of the mice showed sympptoms of a prionlike disease. Eventually all seven inoculated mice showed neurological diesase, the last one 660 days after infection. Then normal mice were infected with brain tissue from one of the sick ones. These rodents took about 150 days to sicken. (Science Vol 305 p589)

Most virologists believed the question was not wether the bird virus H5N1 would return, but when. In the past month China, Vietnam and Thailand have all reported new outbreaks of the strain that scientists fear could evolve into a global catastrophe when unchecked. A massive epidemic of avian influenza swept through eight Asian countries early this year, killing at least 23 people and leading authorities to kill more than 100 million fowl. In May, the virus appeared to be conquered, but given its vast geographical range and its ability to infect wild birds, it was not thought to be stamped out. Experts worry that this virus may evolve or recombine to produce a virus that humans can easily transmit, setting the stage for a potential flu pandemic. The seriousness of this fear has been confirmed by two published research articles that show that the virus has become more lethal to mice and that it can spread more easily among poultry. (Science, Vol. 305, p321)

The director and a deputy director of the Chinese Center for Disease Control and Prevention, have resigned for "mismanagement of the Severe Acute Respiratory Syndrome (SARS) virus," at the nation's most important infectious disease laboratory. Poor management of the virus triggered the SARS outbreak. The SARS reccurence has been determined as a case of major incident due to negligence. Three of the directors colleagues at the center were disciplined. The outbreak was contained in May, when the last patient was released from hospital, but only after hundreds of people who had contact with the infected people were isolated. Lab workers may have triggered the infection during experiments inside the institute's laboratory. The institute and its laboratory likely became contaminated, which explained why the intern and another laboratory worker were infected even though their work did not involve handling of the virus. No other infections have occurred so far this year. (http://news.yahoo.com/news)

The World Health Organisation called on all member states to review biosafety standards and the way viral material is handled after the recent SARS outbreak in China. The use of inactivated SARS coronavirus, which was not tested to determine the effectiveness of the inactivation, in a general laboratory at the Institute appears the most likely cause of the outbreak. The WHO said that the outbreak of Severe Acute Respiratory Syndrome at the National Institute of Virology in Beijing raised concerns about biosafety in general, and the way in which inactivated viral material is handled. WHO believes that member states should carefully review biosafety standards and strengthen them to avoid further incidents. The WHO statement also emphasized that scientists working with highly pathogenic viruses such as SARS need to handle inactivated material with the utmost caution. In particular the WHO has recommended that researchers use internationally accepted methods for validating the inactivation of live viruses. It also said that inactivated material should be handled only in laboratories at biosafety level (BSL) 2 or above. (http://news.yahoo.com/news)

Although not all detailed information has been made available to WHO, the following conclusions have been made about the source of the outbreak: i) the National Institute of Virology in Beijing was the most likely source of the outbreak, ii) at least 4 individuals have been infected with SARS at the Institute (these include the 2 laboratory workers reported in April, and 2 additional laboratory workers that were found positive for SARS antibodies) and iii) the use of inactivated SARS coronavirus, which was not tested to determine the effectiveness of the inactivation. At the same time, other possible explanations of the cause of the outbreak cannot be fully excluded. Core components of new biosafety programmes at country level are likely to include: i) a containment policy to reduce the number of laboratories storing and working on SARS coronavirus, ii) a legislative framework and independent advisory body to assist in the development, implementation and evaluation of a national biosafety programme and in the investigation of biohazard incidents, iii) the dissemination of lessons learned to the global scientific community, iv) a laboratory accreditation system based on standardized biosafety criteria, v) an occupational health service to monitor the well being of laboratory workers and vi) comprehensive biosafety and training programmes in all diagnostic and research institutes. (ProMED-mail)

According to a survey made in Italy (with 994 participants), 84% of the italians are in favour to continuing research in medical biotechnology, whereas only 57% think that research on food biotechnology should be continued. That antiscience attitudes are not the key to these answers is also confirmed by scientist being indicated as the most truthworthy source of informatgion on biotechnologies (39%). To the question who should decide wether to continu research on biotechnology, the answer was the following: 29.9% the European Union, 20.9% all citizens, 14.4% no one is in the position to decide, 11.9% scientists, 9% the italian government, 5.1% the potential beneficiaries of applications,, 4.5% don't know, 2.2% the catholic church and 2% entrepreneurs funding research. The researchers of the study conclude that neither the elitist approach („leave it to the experts“) nor the utopian approach (which assumes that all citizens can be transformed into scientific experts) is visible. (Science, 2004, Vol. 304, page 1749)

DNA wise, humans and chimps are virtually identical. Now researchers have found key differences among the close cousins in the location of DNA recombination hotspots: places where matching chromosomes exchange DNA much more frequently than normal. These sequences are typically less than 2000 Basepairs long. Preliminary results show, that at least in some cases, chimps do not have the hotspots at the same places as humans. And also it is unclear wether chimps have as many hotspots as people. Recombination, in or out of hotspots, introduces variety into a genome and can eliminate bad genes - or, possibly, introduce deleterious mutations. (Science Vol. 304, p 190)

At least five workers developing an anthrax vaccine at a children's hospital research lab in Oakland were accidentally exposed to the deadly bacterium because of a shipping mistake. Officials with the Children's Hospital Oakland Research Institute said none of the researchers has shown symptoms of infection since the first exposure about two weeks ago, but each is being treated with precautionary antibiotics. The researchers believed they were working with syringes full of a dead version of anthrax. Instead, they were shipped live anthrax by a lab of the Southern Research Institute. Anthrax produces severe flu-like symptoms in most of its victims. If inhaled, ingested or otherwise introduced into the body, it can kill. Other workers may also have been exposed while the researchers handled the live anthrax. Though the five workers were exposed, state health officials and the hospital don't believe anyone was infected because researchers took proper safety precautions. The researchers used the sample on lab mice which died soon after. The researchers started their own investigation, and on Wednesday night, California state health officials confirmed that live anthrax was in the syringes. The case is being investigated now. (http://news.yahoo.com/)

Mounting evidence suggests that ecological and climatic conditions influence the emergence, spread, and recurrence of infectious diseases. Global climate change is likely to aggravate climate-sensitive diseases in unpredictable ways. Researchers have addressed the influence of ecological factors on the biological diversity and distribution of parasitic and infectious diseases. After compiling epidemiological data on 332 different human pathogens across 224 countries, the researchers used sophisticated statistical modeling methods to identify and characterize the influence of a number of potential contributing factors on species richness. They found that climatic factors are the most important determinant of the global distribution of human pathogens. The finding has important implications for predicting and managing future infectious disease outbreaks, indicating that global climate change could have far more significant effects on global patterns of disease, with diseases once relegated to the tropics migrating to temperate zones, for example. (Guernier et al., 2004, PLoS Biol 2(6):e141. DOI: 10.1371/journal.pbio.0020141).

One year of SARS-research has brought big insights into the disease. There are hints that civets are not the elusive, natural hosts: the virus has been detected in lungs of 3 out of 6 rats in the building, where one of the 4 recent patients lived. Furthermore, animal models have shown that vaccines rather worsen the disease, instead of being protective. Only four mini-outbreaks have occurred worldwide during the last year. However, three of these cases were the result of labs failing to contain the virus. Unfortunately, a clear source of the lab-infections could not be found. For this reason, health experts fear that the next SARS epidemic may be more likely to emerge from a research lab than from the presumed animal reservoir. According to WHO experts, the reported lab infections are believed to have occurred outside the biosafety level 3 area, which raises questions about the managment structure and the training of the staff. (Science, Vol 304, pages 1097 and 1223-1224)

Prions have been found in sheep muscle. It is the 1st time they have been discovered in animal flesh that many humans normally eat. However, the scientists emphasized that the finding does not mean that this fact poses a danger to humans. The prions were found at 1/5000 the concentrations that are found in sheep brains, and therefore likely to be much less infectious. Also, the animals were infected with scrapie, a prion disease that is not the same as bovine spongiform encephalopathy, or mad cow disease. Although the symptoms of scrapie have been described in sheep for centuries, and scientists believe that mutated scrapie prions may have caused the British epidemic of mad cow disease of the 1980's, no case of scrapie transmitted to humans has ever been found.

The ties of 50 percent of the doctors in the hospitals are contaminated with pathogens. This is the result of a survey of medical researchers in the New York Hospital Queens. The researchers examined the old ties of doctors, housemen and medical students and compared the results to the contamination of the ties of the hospital's safety personel. Pathogens were detected on 47.8 percent of the ties of the doctors. The number of dangerous pathogens was eight times as high as with other tie carriers.

A russian virologist has accidentally infected herself with an Ebola virus and has died a few days later. A commission investigates the circumstances of her death at the Center for Virology and Biotechnology at Novosibirsk. Probably the 46 year old scientist pricked herself with a needle that was contaminated with Ebola and died two weeks later.

Exactly one year ago the Biosafety Institute b-safe Ltd was founded. This March we could move into our new office at the Seftaustrasse 37a in Bremgarten b. Bern. For this reason b-safe has arranged an "Apéro" on Thursday, May 27, starting at 4:00 pm. Several successful conferences and workshops were hold by b-safe during the last year. In the near future b-safe will develop new training modules and consolidate its training program.

The latest of three different lab incidents within a year (and the most serious), originated from a failure in laboratory containment. One death is tentatively attributed to it, eight people are confirmed or suspected of contracting the disease and hundreds have been quarantined. This case is especially troubling, because it occurred in Chinas leading SARS lab. Although two people were exposed both in the same lab, the onset of the symptoms indicates two different exposure events. The prospect of two separate exposure events suggests some part of systemic or procedural failures in the lab. Experts of the WHO investigate the case at the moment. (Science, Vol. 304, pages 659-660)

An automatic mini-Laboratory is under development in an EU research project (BIOMIC = Bioanalytical System Based on an Optical Biochip). All central functions with nine sensors are located on a silicium-based chip with 6 millimeter square size. Already today, the prototype of the chip is able to detect eight different substances in a short time interval. Mostly, these substances are proteins or DNA fragments. Thus the chip may be a good means for biochemical analyses, especially for surveillance of pocesses in the pharma or food industry or for monitoring relevant substances in the environment. (BioWorld, 2004, 02, page 10).

An international team of experts is coming to examine a sealed-off SARS research lab in Beijing where two workers became sick. In what could be the world's first SARS death this year, the mother of one of the workers died this week. Several hundred lab employees and people with whom the ill people came into contact were reported in quarantine. A WHO team of two or three experts in lab biosafety will work with a group from China's Health Ministry in the next few days. They will interview lab workers, take samples and study equipment at the virus control institute at China's Centers for Disease Control. From all of that, they will hopefully be able to draw conclusions on whether those cases were contracted in the lab and, if there is a link, what happened and what sort of breach of biosafety occurred. The WHO team, assembled at the request of the Chinese ministry, may also travel to eastern Anhui province, where one of the lab workers and her mother are from. The mother died Monday, although Chinese officials said SARS had not been confirmed in her case. They said she had a heart condition, but it was not immediately clear if it was related to her death. A statement on WHO's Web site said the woman had "clinical symptoms ... compatible with SARS." If her case is confirmed as SARS, it would be the first death from the disease this year. After arising in southern China in November 2002, SARS killed 774 people around the world and infected more than 8,000 last year. The dead woman's daughter, a 26-year-old medical student working at the institute, was confirmed to have SARS and may have infected her mother. The daughter was treated last month at a Beijing hospital, where she came into contact with a 20-year-old nurse who is now a confirmed SARS case. The ministry said the institute would remain sealed until at least May 7. More than 180 of its workers were quarantined in a hotel on Beijing's outskirts. An additional 300 people in Beijing and Anhui who had been in contact with the sick workers and the dead woman also are in isolation. (http://news.yahoo.com/)

In march, the standard-setting organization US Pharmacopeia (USP) has published a document providing advice to companies on the steps needed to demonstrate the safety of ancillary reagents, which are used ex vivo in the preparation of cell, gene and tissues therapies. The USP document, though not legally binding, provides recommendations on how to use ancillary reagents (e.g. serum, cytokines, culture media and growth factors) in clinical work and addresses a lack of specific guidance from the US and European authorities, FDA and EMEA respectively. Although the report’s clarifications are welcome, the regulators de facto requirement for reagents produced under good manufacturing practice (GMP) standards means firms must anticipate a potential shortage of GMP reagents. Although ancillary reagents used ex vivo are not intended to end up in the final product, reagent residues can have undesirable effect on patients if they are toxic of functionally active. Published evidence shows that reagents like fetal calf serum used as cell culture medium is difficult to remove during washing and can trigger an immunologic reaction in patients who receive cell infusions. In addition, following the discovery of the first case of mad cow disease in the US at the end of 2003, bovine-derived products are expected to come under regulatory scrutiny. The USP document gives user-friendly advice how to handle ancillary reagents to ensure the highest level of safety and quality during clinical trials. Although the document does not define mandatory practices , it could be the closest thing to a guideline that companies will get. (Nature Biotechnology, Vol. 22, 3, pages 253-254)

A newly developed rapid test for can show within a few hours if the cause of an infection is based on antibiotic-resistant bacteria or not. Traditional tests, based on the cultivation of suspicious bacteria in cultures, can last for some days. The new test does not work with cultivation of bacteria, but with the detection of a protein that emits light. The light can be detected even when only a low number of organisms is present. Up to now resistant bacteria are tested in media which contain antibiotics along with the substances necessary for normal growth. If the bacteria grow after some days in such a antibiotic-supplemented medium, they are resistant against the tested antibiotic. In contrast to the traditional test, the result of the new test (developed by Acolyte Biomedica in Porton Down) is obtained after a few hours: the suspicious bacteria are submersed in a media that contains small magnetic balls. The balls are covered with antibodies, capable of fixing the bacteria to their surface. The balls including the bacteria are collected with a magnet. Subsequently the balls are transferred to a medium containing the antibiotic “methicillin”. After a few hours, when the antibiotic has killed all sensitive bacteria, a specific enzyme is added to the solution. This protein starts to emit light, when living (i.e. resistant) microorganisms are present. Starting in may, the company plans to evaluate the new test in a few hospitals,. More and more bacteria, e.g. Staphylococcus aureus can no longer be killed by traditional antibiotics. Even the most recent drug used for antibiotic therapy , „methicillin“, is not working. This is a big problem in hospitals, where infection with these “superbugs” cannot be controlled and thus pose a hazard to human health. Therefore, the identification of resistant bacteria is crucial for the fight against infections. (Nature, online)

By end of march microbiologist Thomas Butler was sentenced to 2 years in prison for mishandling plaque samples that he mailed to Africa. Deviating from government sentencing guidelines that called for up to 9 years, the judge cited Butler’s “great service to society” and his lack of “evil” motives. Prosecutors called the sentence fair, since it sent the appropriate message to the academic and scientific community. The US government is not going to tolerate a cavalier attitude in sending deadly agents. The government ultimately charged Butler with 69 counts of lying to investigators, moving the bacteria without proper permission, tax fraud, and stealing from his university by diverting clinical trial payments to his own use. At the end Butler was convicted on 47 of the 69 charges. He was acquitted of the central lying charge, however, and found guilty of just three plague-related offenses, all linked to a mismarked Federal Express package containing plague samples that Butler sent back to Tanzania. Since the verdict, Butler has repaid the university $250,000, resigned from his post at the Texas Tech University Health Sciences Center, and given up his medical license. At the end of the trial Butler read a short statement, saying that he was very sorry, that the export of bacteria to Tanzania was done for humanitarian reasons….so that the Tanzanians could continue their research in this area and that the specimens arrived safely and no one was harmed. Prosecutors said the sentence should remind scientists not to ship dangerous bacteria without the proper paperwork and packaging. (Science Vol. 303, No. 5665, pages 1743-1744)

Dutch scientists have announced they had identified a previously unknown corona virus that causes respiratory disease and is likely to have spread around the world. The virus is only the 4th corona virus to be found in nearly 4 decades. The virus causes symptoms similar to a bad cold and does not unleash the pneumonia characterised by severe acute respiratory syndrome (SARS) corona virus. Young children and people whose immune system has been compromised by HIV or other diseases are more at risk although not apparently fatally so. In a recently published study a research team reports on their detective work, launched after a 7-month-old girl was admitted to a hospital in April 2003 with an inflammation of the lower airways. Tests for common cold viruses, influenza virus, and other well-known viruses all proved negative. After molecular analysis, closer examination of its genetic code showed that it shares about 2/3 of its nucleotides with the 3 established human corona viruses. In other words, it was an independent member of the corona virus family that had never been spotted before. The team then tested stored samples taken from other admissions and found that another 7 patients with respiratory problems had been infected by the same virus. These findings suggested that this novel corona virus is already widespread in the population and is causing perhaps the symptoms of common colds, but in the younger individuals it is causing more severe respiratory problems. The researchers admitted it was surprising that this virus had never been found before, but part of the problem was the lack of tools to detect new agents easily. In general, corona viruses are usually transmitted by airborne droplets breathed in from someone in proximity who, for instance, sneezes or coughs.

In a recent publication, researchers from the Netherlands report the first animal evidence that a well-known antiviral drug called interferon-alpha may work against SARS – if given in time. Interferon-alpha is already registered as a drug for the treatment of hepatitis C and several cancers. Interferon-alpha, which comes in more than a dozen different varieties with different potencies, not only blocks the replication of several viruses but also activates the immune system. In the study published in February 2004, macaques that were given a special form of interferon-alpha (which lasts longer in the bloodstream) 3 days before infection with SARS virus, excreted far less virus from their throats and their lung damage was reduced by some 80%. When interferon was given 1 and 3 days after exposure, lung damage was also reduced, although not as much. That would probably make the compound most effective as a prophylactic for e.g. patients’ family members or health care workers, who were exposed to the virus. Meanwhile, other approaches are emerging as well: a study from the US showed that human monoclonal antibodies against the so-called spike protein, can inhibit virus replication in cell cultures and another not-yet published study provides evidence, that the antibodies block viral replication in a mouse model of SARS. (Science Vol. 303, No.5662, pages 1273-1275)

Ever since bovine spongiform encephalopathy (BSE) was first identified in the United Kingdom in the mid-1980s, scientists have blamed one unique strain of the infectious agent for the disease. What was later shown to be a misfolded protein, called a prion, seemed to maintain its molecular characteristics and produce the same brainwasting symptoms even when it infected humans and mice. This consistency helped track the worldwide spread of the disease among cattle back to feed made from slaugtherhouse waste. But this consistency in what is also known as mad cow disease was somewhat puzzling. Other brainwasting diseases, such as sporadic Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have been linked to a variety of slightly different prions, each causing slightly different disease manifestations. Now research groups in France, Japan and Italy claim to have identified atypical BSE cases and the prion in Italy shows molecular similarity to the one implicated in a form of human sporadic CJD. These findings may indicate that either the prions sometimes change after infecting a new host or that more than one strain of the BSE prion is circulating. At this stage the researchers do not know whether this new agent is transmissible. (Science Vol. 303, No.5662, page 1285)

A highly lethal group of viruses has struck again. More than 40 people in central Bangladesh appear to have fallen ill with encephalitis, and 14 have died. Tests (the presence of specific antibodies) point to the Nipah virus, which debuted during a devastating outbreak in Malaysia in 1999. The disease has occurred in several clusters and many of the patients are children. The Nipah virus and an Australian cousin, Hendra, both naturally infect fruit bats. Hendra using horses as intermediate host first jumped to humans in 1994, killing two. Nipah made its way to humans in Malaysia after causing a massive outbreak in pigs, killing 105 of its 276 victims. Due to their high mortality and the ability to jump species barriers, they have attracted high research interest. Bangladesh had similar, smaller outbreaks in 2001 and 2003, but epidemiologically the disease is very different than that in Malaysia. Most victims in Malaysia were pig farmers, whereas in Bangladesh there has been no pig outbreak and many of the patients are young boys. Tests in Bangladesh with fruit bats have shown that they carry a Nipah-like virus. There is no cure for Nipah at the moment, but a vaccine is in development. Recently, researchers reported that vaccinia viruses, engineered to express either one of two Nipah’s surface glycoproteins , protected golden hamsters from a lethal challenge of Nipah. (Science Vol. 303, No. 5661, page 1121)

SARS (for severe acute respiratory syndrome) swept through Asia last year and jumped to Canada before it came to a halt in July after imposing strict controls and isolating of the sick. 774 people died and the fear of a pandemic is still around – especially because researchers were not able yet to identify the animal reservoir of the virus. Several countries and independent labs have taken efforts to develop new drugs and SARS vaccines. Less than a year after SARS appeared, about half a dozen of candidate vaccines are now at hand. However, all of them face some uncertainties because there is no good animal model available in which to test them. And without a good animal test, human trials could be dangerous. In particular, vaccine developers are worried that a faulty design might “enhance“ SARS or make it more aggressive, as occurred with a test vaccine used to inoculate cats against a related feline virus. Such a scenario in a major human trial could end in a disaster. However, WHO experts eventually accepted in a meeting in February in Rotterdam that China can start phase I trials ahead of the rest of the world. A chinese company – at greater risk of a repeat outbreak and under political pressure to push ahead - will start testing their vaccine (an inactivated form of SARS virus, which is already tested in macaques, in rabbits and in mice) by end of march with 30 volunteers (15 men and 15 women). (Science Vol. 303, No. 5660, pages 944-946)

The former Texas Tech University professor Dr. Thomas C. Butler, 62, was sentenced to two years in prison. He also was fined $15,000 and ordered to pay restitution of $38,000. He earlier had agreed to retire from the school and surrender his medical license. He remains free on bond, but must report to federal authorities on April 14. The father of four had faced up to 240 years in prison and millions in fines for convictions that stemmed from an investigation after his report that 30 vials of the bacteria were missing from his lab in January 2003. He later said he accidentally destroyed the samples, but during his trial he testified he had no clear memory of destroying the vials and that they could have been destroyed during his cleanup of an accident. In January, after his conviction, Butler agreed to pay $250,000 to the school and retire. Last month, Butler voluntarily surrendered his medical license to the Texas State Board of Medical Examiners. In December, a jury found Butler guilty of mislabeling a Fed Ex package that contained plague samples he sent to Tanzania and their unauthorized export to the African country. He was acquitted of the most serious charges of smuggling and illegally transporting the potentially deadly germ and charges of lying to federal agents about the missing vial. (CNN)

A civilian Army researcher at Fort Detrick, Maryland, is in isolation after possibly being exposed to the Ebola virus. The researcher accidentally pricked herself with a needle that contained a weakened form of the Ebola virus last week while she was injecting mice with the virus as part of a research effort. The woman has shown no signs of the fatal illness, but will be for up to 30 days in isolation. Local government officials have been notified, but no one else is believed to have been exposed. The Ebola virus, named for the river in Africa where it first struck nearly 30 years ago, causes high fever, a rash, and bleeding from the internal organs. According to the Centers for Disease Control and Prevention, the incubation period is between two and 21 days, but a small number of people who have been exposed have been found not susceptible to serious effects. In addition to exposure through a cut, scrape, or injection, it can be passed person-to-person through body secretions. (CNN)

In Mid-January 2002 Dr. Thomas Butler, a well-known plague expert of the Texas Tech University Health Sciences Center in Lubbock, was charged of mishandling plague samples: 30 vials with plague cultures had disappeared from the refrigerator in his laboratory. He reported the incident to the biosafety officer of the University and to his superiors. This information lead to a dramatic development: The Police and the FBI were informed, finally leading to a half year long court trial that was just closed recently. In due course he was also accused of having imported from Tanzania plague samples (obtained in a clinical trial) in plastic petri dishes without having an official permission. The jury found him guilty in 22 of 47 accusations. Although there is no official verdict yet, already the violation of the import regulations could cost him 10 years in prison. (Science, Vol. 302, No. 5653, 2003, pages 2054-2063)