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A new, souped-up version of the BCG vaccine may offer new hope in the global fight against tuberculosis

TB is one of the planet’s biggest killers. One third of the world’s population is infected with the microbe, Mycobacterium tuberculosis, and about 10% of these people go on to develop the devastating illness. In some parts of sub-Saharan Africa, a lethal combination of TB and HIV infection is accelerating deaths from both diseases. The BCG – or Bacillus Calmette-Guérin – vaccine has given reasonable protection against TB since it was created in the 1920s. The vaccine consists of live, weakened Mycobacterium bovis microbes and invokes an immune response without causing illness when given to newborn babies and young children. But its effectiveness is limited in adults and against newly emerging drug-resistant strains. BCG’s usefulness also varies with region – in areas with a lot of natural exposure to Mycobacterium strains in soil, it is less effective.

Now, Stefan Kaufmann, director of the Max Planck Institute for Infection Biology in Berlin, Germany, and colleagues have devised a way of boosting BCG’s power. Their souped-up vaccine was 10 times more effective than conventional BCG in protecting mice from infection. And it slashed the presence of “drug-resistant” TB bacteria to about 1% of its initial level in mice infected with this strain – the standard BCG had no effect. “We think it’s a very promising vaccine,” says Kaufmann. He envisions the new vaccine working in tandem with another. “We shouldn’t have competing vaccines, but should combine them,” he told New Scientist.

The improved BCG could “prime” the immune system if given early in life. And this immune response could be boosted in adults by a “subunit” vaccine. The latter type of vaccine uses just a component of the organism, such as its DNA, to trigger the previously established immune response. The traditional BCG vaccine protects against TB infection by enlisting immune cells called CD4 helper T-cells. These cells activate other immune cells called macrophages, which eat up invading organisms, alongside other defence mechanisms.

But BCG does not invoke killer T cells, or CD8 T-cells, which provide another strong immune response. Inducing this response would be especially beneficial as the TB bacterium hijacks macrophages for its own use. Macrophages gobble up most invaders in a pouch called a phagosome. This is a “dead-end street” for most bacteria, explains Kaufmann, but the TB bacterium actually makes use of the phagosome. Kaufmann’s team engineered a new BCG strain which secretes a protein that punches holes in the membranes of the phagosome, spilling the invader’s proteins out into the macrophage cell’s cytoplasm. This also lets out degrading enzymes into the cell – leading to the cell’s death.

It is the broken down vesicles of the dying macrophage that are ultimately what attracts CD4 and CD8 cells. It is this powerful “cross-priming” immune response which makes the new version of the BCG vaccine very effective. However, Douglas Lowrie at the National Institute for Medical Research in London, UK, whose group researches TB vaccines, cautions that developing another live vaccine based on BCG may not address some of the problems associated with the conventional vaccine. “There is a tendency to move away from live vaccines,” he notes, since immuno-deficiencies caused by the growing HIV problem mean that the BCG itself could cause disease. “A change in the nature of the immune response is needed, not merely an intensification,” he told New Scientist. Other candidate vaccines have been shown to alter the response, he adds.

Kaufmann says he is aware of the issue, and that at this stage there is no question of the vaccine being used in immuno-compromised patients. But he also notes that their souped-up BCG was safe in immuno-compromised mice. Lowrie also suggests that the new BCG vaccine does not tackle the problem of BCG’s effectiveness being diluted by environmental exposure to Mycobacterium. But Kaufmann points out environmental exposure is only a problem when BCG is given in adulthood. “We want to focus on a replacement for BCG early in life.” He hopes to move the new vaccine to clinical safety trials in humans in 2006.

Journal reference: Journal of Clinical Investigation

New Scientist
September 13, 2005

Original web page at New Scientist

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Millions of bacterial species revealed underfoot

The soil beneath our feet may be teeming with a hundred times more species of bacteria than previously thought, according to biologists in New Mexico, US. Their calculations reveal that one gram of dirt can harbour a million microbial species – and that metal pollution kills 99% of these as-yet unknown germs. Measuring the bacterial biodiversity of soil is difficult because only a few species can be cultured in the lab, according to Jason Gans of Los Alamos National Laboratory, New Mexico, US. Fortunately, biologists can also estimate biodiversity using a technique called DNA reassociation. This involves chemically unzipping the two strands of all the bacterial DNA in a sample, mixing them up and seeing how long they take to join up again with matching partners.

If all the DNA strands were the same, they would find matching partners very quickly. But the more diverse the DNA strands, the longer this match-making takes, allowing researchers to estimate how many different species there are in the sample. When this technique was applied to soils in the late 1990s, it suggested that a gram of dirt contained about 16,000 species. But this estimate contained a simplification that the populations of all the different species in the soil were roughly equal in size. So Gans and his colleagues have developed new equations to reanalyse the same DNA reassociation data but without this size assumption.

Their results reveal that there are a few very common species in soil but lots of rare species. “There is a very large number of low abundance species,” says Gans. So many rare species, in fact, that the estimate of bacterial biodiversity rises to one million species per gram of soil.
These rare species appear to be absent in soil contaminated with heavy metals, however. The team also reanalysed the DNA reassociation pattern of soil experimentally polluted with metal-rich sewage sludge. Gans suggests that the contamination may have killed 99% of the bacterial species. But the consequences of losing so much bacterial biodiversity in polluted plots of land are unknown. “Now that we have a way to measure it, the next thing is to correlate species diversity with how well plants grow,” he says.

As the new calculations reveal far more bacterial species in soil than anyone realised, the next challenge is to identify those species and the roles that they play in ecosystems. “They might have some key functions that are known, or even unknown,” says Ruth-Anne Sandaa of the University of Bergen in Norway, who measured the original DNA reassociation patterns used in Gans’ analysis.

Journal reference: Science (vol 309 p 1387)

New Scientist
September 13, 2005

Original web page at New Scientist

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Bacteria recognize antimicrobials, respond with counter-defenses

Many living things, from fruit flies to people, naturally produce disease-fighting chemicals, called antimicrobial peptides, to kill harmful bacteria. In a counter move, some disease-causing bacteria have evolved microbial detectors. The bacteria sense the presence of antimicrobial peptides as a warning signal. The alarm sets off a reaction inside the bacteria to avoid destruction. Salmonella typhimurium can contaminate meats such as beef, pork, and chicken, as well as cereals and other foods, and cause severe intestinal illness. Certain strains of the bacteria are difficult to treat, and are behind the increase of salmonellosis in people. Some food science institutes anticipate that virulent strains of salmonella will become more common throughout the food chain. Learning how this sometimes deadly organism fights back against the immune system may lead to treatments that get around bacterial resistance.

Work in this area may also suggest ways other disease-causing Gram-negative bacteria maintain a stronghold in the midst of the body’s attempts to get rid of them. Strangely enough, the same molecules that the body sends out to help destroy salmonella inadvertently launch bacterial defenses.
It is as if missles armed, rather than demolished, the target. The body’s antimicrobial peptides bind to an enzyme, PhoQ, which acts as a watchtower and interceptor near the surface of bacterial cell membranes. The peptide binding activates PhoQ, which sets off a cascade of signals. The signals turn on a large set of bacterial genes. Some of the genes are responsible for products that fortify the bacterial cell surface and protect the bacteria from being killed.

Science Daily
September 13, 2005

Original web page at Science Daily

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One bacteria stops another on contact: findings have implications for urinary tract infections

Scientists have discovered a new phenomenon in which one bacterial cell can stop the growth of another on physical contact. The bacteria that stop growing may go into a dormant state, rather than dying. The findings have implications for management of chronic diseases, such as urinary tract infections.

The discovery by a team of scientists working in the laboratory of David Low, professor of biology at the University of California, Santa Barbara, is reported in the August 19 issue of the journal Science. The findings indicate that Escherichia coli, one culprit in urinary tract infections, contains genes that when turned on block the growth of other E. coli bacteria that they touch. The finding was a complete surprise to the scientists, said Low. The discovery may eventually lead to new antimicrobial agents to halt bacterial growth which would be an entirely new system to shut bacteria down, according to the scientists. “This has potential implications for new antibiotics,” said Low. “If bacteria can do this, then maybe we can do it.”

Doctoral student and first author Stephanie Aoki, and a team of scientists working in the Low lab, made the discovery while studying other aspects of E. coli. After working for two years, the team identified two genes required for this “stop on contact” phenomenon. “We don’t know if these ‘stopped’ cells are dead or alive,” said Low. “They don’t grow after they’ve been touched. They don’t grow on plates, but laboratory stains show they may be alive. You might call them dead, but they don’t break apart the way dead cells do. These cells appear to stay intact, perhaps in a quiescent mode, or dormant state.”

Aoki explained, “We are currently exploring how contact between bacteria can inhibit cell growth and determining what this contact-dependent inhibition of growth (CDI) system is used for. These genes are present in E. coli, including uropathogenic E. coli that cause urinary tract infections, and similar genes may be present in other pathogens such as the plague bacillus, Yersinia pestis.” Low said that one possible interpretation is that bacteria use this system to eliminate competition in the environments they grow in. “Another possibility is that the bacteria use the CDI system to shut themselves off inside a host, going into a dormant state where they may go undetected by the immune system,” he said. Thousands of women in this country have chronic urinary tract infections, noted the scientists. The disease seems to go away for awhile, then something triggers recurrence of the disease.

Work by Scott Hultrgen at Washington University has indicated that E. coli cells may hide in the walls of the bladder and urinary tract in a dormant state, explained Low. It is possible that the newly discovered CDI system contributes to this process. “By studying the CDI system, we hope to understand more about how bacteria interact with each other and with their hosts, and how these interactions contribute to disease,” said Aoki.

The findings may have repercussions outside of better understanding of urinary tract infections. Other diseases may have similar mechanisms, according to the scientists. “This research is in its infancy, but opens the door for exploration of the roles of contact-dependent growth inhibition in urinary tract infections and possibly other diseases,” said Low. “Aoki has discovered an entirely new phenomenon,” explained Low, who has studied E. coli for over 20 years. “It is fascinating that bacteria have developed a system by which one cell can contact another and inhibit its growth.”

Science Daily
September 13, 2005

Original web page at Science Daily

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Pig disease may be spreading between humans

Vaccines to combat a deadly pig-borne disease were flown to south-western China on Sunday, where the spread of the rare illness has already killed 36 people and infected 198. The unusually high numbers of people infected by the swine disease has led scientists to speculate that it may be being spread from human-to-human – or that another disease entirely is to blame. Streptococcus suis type II, although relatively common in swine, spreads to humans extremely rarely, and the size and virulence of this current outbreak, in the province of Sichuan, has taken the World Health Organization by surprise.

The Chinese government responded on Sunday by airlifting the first batch of a vaccine for the infection – enough to treat 360,000 pigs – from the southern city of Guangzhou to the affected towns. The vaccine’s manufacturers say they will be producing enough vaccine to treat 10 million pigs in the coming days – but vaccines take three weeks to produce immunity in the pigs. Health authorities in the province have distributed two million notices to educate poor, often illiterate farmers and their children not to slaughter pigs or eat their meat. Thirty-nine temporary roadside quarantine stations have been set up to prevent dead pigs reaching markets – they will be burned instead.

China’s state-controlled media says the government has brought the disease under control, and that no human-to-human transmission of infection has been found. But there has been widespread criticism of the way the situation has been handled – with parallels being drawn to China’s handling of the SARS – severe acute respiratory syndrome – and bird flu outbreaks. The authorities knew of the first human cases on 24 June, but it only allowed the news out on 25 July. And China has banned local and foreign reporters from entering the region.

The secrecy has bred suspicion elsewhere. The WHO has said that it was baffled because S. suis has never affected so many people in an outbreak before – it usually just infected one or two people at a time. And where people have been infected previously, mortality rates have been below 10% and different symptoms have been exhibited. “It could be another disease altogether, it need not be Streptococcus suis because the presentation is so atypical,” Samson Wong, a microbiologist at the University of Hong Kong, told Reuters. “In past literature, there have been one or two cases when people died within 36 hours, but those were exceptions rather than the rule. The deaths in China are very unusual.”

Wong also says many patients in Sichuan were bleeding under the skin, a symptom that has been cited in only two or three cases in medical literature on the infection – and that deafness, which is commonly found with the disease has been little mentioned in the outbreak. Experts quoted in other news reports have also said that the swine bacterium is an unlikely cause, with the symptoms, widespread geography of those affected and the speed of infection pointing to a viral infection. Other experts question China’s denial of human-to-human spread. “The organism is carried on the pig’s tonsils and is spread pig-to-pig through nose rubbing or coughing. But it’s only found in small concentration on the pigs’ tonsils, so it’s difficult for a human to catch it that way,” says Jill Thompson from the UK’s Veterinary Investigation Centre in Edinburgh.

“When the infection spreads to the brain, causing meningitis, it’s in far greater concentration and so it can be transmitted to humans who eat raw infected pork or handle the dead animal with open cuts,” she told New Scientist. “It is so rare for humans to become infected; most farm workers develop some immunity from the endemic disease. What might have happened is that the bacteria have acquired virulence factors from another organism – a bacterium or virus that might be harmless – and the combined virulence factors have turned it into a superbug, which could be transmitted human-to-human through coughing,” she suggests.

Andrew Rycroft, a microbiologist from the Royal Veterinary College in Hertfordshire, UK, agrees. “The likelihood is that once it gets established in the human respiratory tract, it can be transmitted by the respiratory tract between humans very much more quickly,” he says, citing an analogy between the bubonic plague, which soon became the far more virulent pneumonic plague when it was transmitted by the human respiratory system.

New Scientist
August 16, 2005

Original web page at New Scientist

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New test detects pathogens in minutes

A new technique for detecting dangerous pathogens could lead to faster and cheaper diagnosis of disease and prevent food poisoning, say US researchers. The team claims their biosensor is accurate enough to identify different strains of disease-causing organisms in a blood sample in just 30 minutes, and at a fraction of the current cost. The researchers hope the test could soon be incorporated into an inexpensive hand-held device for use in the field and in the developing world.

Current biosensors rely on a costly and time-consuming technique called gene amplification, which involves taking a piece of DNA from the sample and adding enzymes to make enough copies to allow the pathogen to be detected. It can take up to 48 hours for a positive result. By contrast, the new process exploits a natural matching technique. A sample of the pathogen-containing material to be tested – blood or food, for example – is placed in a test tube and heated in the presence of an enzyme to break down the cells and release their genetic material. Then a dipstick is placed into the mixture and left for a few minutes. Like in a pregnancy test, if a red line appears, the particular pathogen is present. The process takes just half an hour from start to finish.

“Instead of taking many hours and costing several hundred dollars to be carried out in a specialist lab, the new test should be fully portable – the size of a cellphone – and cost just a couple of dollars for a fast result,” says team member Antje Baeumner, associate professor of biological and environmental engineering at Cornell University. “The idea is that it could be used directly in the field to sample meats and food products, or to test for diseases quickly and cheaply in cost-limited countries.” It works because the dipstick is impregnated with artificial cells containing sections of complementary DNA sequences which exactly match particular sections of RNA on the pathogen being tested for, along with a dye. So, if the RNA is present, it sticks to the dipstick DNA and the red dye is activated.

Lead researcher Sam Nugen designed computer software that selects sequences of complementary DNA to match the RNA from a range of pathogen bacteria, viruses and fungi, including E. coli, Streptococcus and the virus responsible for dengue fever. Biotech companies can then produce the required DNA sections in volume at low cost. Anything that speeds up the testing process will be welcomed, says Andrew Brabban, who carries out lab tests of beef for the deadly E. coli 0157:H7 at Evergreen State College in Washington, US. “Currently we have a ‘test and hold’ procedure, whereby meat is tested for E. coli and then the whole batch must be held back for about 24 hours until the test results come back. It costs time and money, so anything that’s faster, easier and costs less would be great,” he says.

The researchers hope to be able to multi-test samples for several pathogens soon. At the moment, they can detect the four different strains of the mosquito-borne dengue fever virus using several red bands on the testing dipstick. “And we’re working towards sequences for a full range of pathogens and detecting them at even lower concentrations. It would be great if this became a standard,” Baeumner told New Scientist. The study was presented on Monday at the Institute of Food Technologists Annual Meeting and Food Expo in New Orleans, US.

New Scientist
August 2, 2005

Original web page at New Scientist

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Pet rodents linked to multidrug-resistant salmonellosis outbreak

Handling pet rodents is a potential health risk, according to a report published in the May 6 issue of the Morbidity and Mortality Weekly Report. Public health practitioners are urged to consider pet rodents as a potential source of salmonellosis. During 2004, the Minnesota Department of Health’s Public Health Laboratory notified the CDC, which publishes the MMWR, about the isolation of multidrug-resistant Salmonella Typhimurium from ill hamsters from a Minnesota pet distributor. The report describes two of the first identified human cases associated with the outbreak, summarizes the multistate investigation of human Salmonella Typhimurium infections associated with exposure to rodents purchased at pet stores, and highlights methods for reducing Salmonella transmission from pet rodents to their owners. This is the first documented salmonellosis outbreak associated with pet rodents.

Veterinarians, breeders, and distributors are advised to consider submitting specimens to clinical laboratories for Salmonella isolation if substantial diarrhea-associated morbidity or mortality occurs among pet rodents intended for sale. Heightened infection-control practices by pet stores and distributors, including routine sanitizing of animal transport containers and cages, may reduce transmission. These strategies could reduce the need for antimicrobials to prevent disease in rodents.

JAVMA
July 5, 2005

Original web page at JAVMA

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Bacterial IQ, extroverts and introverts

Analysis of complete microbial genomes showed that intracellular parasites and other microorganisms that inhabit stable ecological niches encode relatively primitive signaling systems, whereas environmental microorganisms typically have sophisticated systems of environmental sensing and signal transduction.

The complexity of signaling systems differs even among closely related organisms. Still, it usually can be correlated with the phylogenetic position of the organism, its lifestyle, and typical environmental challenges it encounters. The number of encoded signal transducers (or their fraction in the total protein set) can be used as a measure of the organism’s ability to adapt to diverse conditions, the ‘bacterial IQ’, while the ratio of transmembrane receptors to intracellular sensors can be used to define whether the organism is an ‘extrovert’, actively sensing the environmental parameters, or an ‘introvert’, more concerned about its internal homeostasis. Some of the microorganisms with the highest IQ, including the current leader Wolinella succinogenes, are found among the poorly studied beta-, delta- and epsilon-proteobacteria. Among all bacterial phyla, only cyanobacteria appear to be true introverts, probably due to their capacity to conduct oxygenic photosynthesis, using a complex system of intracellular membranes. The census data, available at http://www.ncbi.nlm.nih.gov/Complete_Genomes/SignalCensus.html, can be used to get an insight into metabolic and behavioral propensities of each given organism and improve prediction of the organism’s properties based solely on its genome sequence.

BioMed Central
July 5, 2005

Original web page at BioMed Central

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Dog, cat treats recalled after humans infected with Salmonella

TW Enterprises of Ferndale, Washington today alerted consumers that it is recalling certain dog and cat treats it markets because they may be contaminated with Salmonella Thompson. People handling these treats can become infected with the organism, especially if they have not thoroughly washed their hands after having contact with any the treats or any surfaces exposed to these products.

Salmonellosis is an infection that can cause serious infections in small children, frail or elderly people, and others with weakened immune systems. Healthy people may only suffer short-term symptoms, such as high fever, severe headache, vomiting, nausea, abdominal pain, and diarrhea. Long-term complications can include arthritis.

S. enterica_ serotype Thompson, when associated with an animal source, appears to be primarily associated with beef. An example is the report of an outbreak of 52 infections with this organism associated with improperly handled roast beef, published in 1999. Contaminated produce may also be a vehicle for human acquisition, as noted in the posting below linked to lettuce, as well as 76 cases associated with fresh cilantro .

In 2001, the irradiation of pet food (including pet treats) was approved for use in the USA. The posts do not state whether these products were irradiated. Likewise, since the products were salmon-, shrimp-, or beef-based, the mechanism of contamination is not yet clear.

It is interesting that there are no reports of dogs or cats suffering from the infection. [- Mod.JW]

ProMed Mail
June 21, 2005

Original web page at ProMed Mail

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Contagious equine metritis in horses

A stallion, that was diagnosed as having Contagious Equine Metritis Organism (CEMO), has now been successfully treated. Horses that were ‘at risk’ or that had come into contact with the stallion have also been traced and tested. Those tests were negative. Defra has now lifted restrictions on the Somerset premises where the stallion is kept, and the investigation has been concluded.

CEMO is a treatable venereal disease of horses, which poses no risks to human health. This case was detected in March this year through routine testing. Previous cases of CEMO have occurred in a stallion and a mare in 2002, and a mare in 2003. The Horserace Betting Levy Board’s Code of Practice is aimed at preventing and controlling CEMO. Defra advises those intending to use horses for breeding to follow the guidelines for disease prevention that are contained in the code.

CEM was first described as a disease in 1978. It is not prevalent worldwide, and outbreaks are sporadic. Since 1980 there have been no reported cases except in Europe and Japan. Numbers of reported cases annually are generally in single figures. The usual measures of control are surveillance, monitoring, screening and movement controls. The disease in the UK is notifiable. There are no EU rules on the control of CEMO. However some third countries require disease free status for CEMO for trade purposes. There were 14 UK cases in 1996, two in 1997, 2 cases in 2002, 1 case in 2003. After the last outbreak, the UK had regained disease free status.

The severity of disease caused by the CEMO organism varies. The main outward clinical sign in a mare is a mild to heavy discharge from the vulva, resulting from an inflammation of the uterus (endometritis). Occasionally mares will show no clinical signs. Whilst infected most mares will fail to conceive. There have been cases of abortion associated with CEMO. The incubation period is 2-12 days and the period of clinical infection lasts on average 2 weeks. Infected stallions do not usually show clinical signs of infection, but merely harbour the organism on their external genitalia.

E-mail address Boglet
June 7, 2005

Original web page at WVA

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An emptying quiver: antimicrobial drugs and resistance

Since the dawn of the antibiotic era, resistance has shadowed the success of infectious disease therapy. In his 1945 Nobel Prize acceptance speech, Alexander Fleming noted the danger of resistance: “It is not difficult to make microbes resistant to penicillin in the laboratory by exposing them to concentrations not sufficient to kill them, and the same thing has occasionally happened in the body…. Moral: If you use penicillin, use enough”. Sixty years later, our understanding of resistance has grown vastly more sophisticated and the proliferation of new antimicrobial drugs has engendered an equally varied collection of resistance mechanisms. Resistance is now an important problem in virtually all areas of infectious diseases, including viral, bacterial, fungal, and parasitic diseases.

In a 2003 Institute of Medicine report, Microbial Threats to Health, antimicrobial resistance was noted as a paramount microbial threat of the twenty-first century. Some strains of pathogenic bacteria are now resistant to essentially all available antimicrobial drugs, and some remain susceptible to only one. At the same time, what once was an apparent deluge of antimicrobial drug development is now barely a trickle. The lack of new drug classes is a consequence of difficulties in discovery of new compounds that has persisted for many years. In addition, pharmaceutical companies are finding in industrialized nations more potent markets for other disease treatments and lower profit in nonindustrialized countries. This trend is reflected in the absence of any novel class of antibacterial drug approved for use in the United States between 1968 and 2000. Indeed, most of the new drugs approved since 1968 have been chemical modifications of existing drugs. However, since 2000, two new drug classes have been approved by the U.S. Food and Drug Administration. Whether this trend will continue is unclear and does not obviate the need for more new classes.

Barring the arrival in the near future of new antimicrobial drugs that are effective against disparate organisms, we are left with imperfect tools to control drug resistance.
With a notable exception, vaccines have not been produced that address the problem of resistance. Infection control in healthcare settings, which is essential for preventing transmission of susceptible and resistant microorganisms alike, remains imperfect. Reducing the discretionary use of antimicrobial drugs when possible is helpful, but even if we use these drugs with exquisite precision, resistance will continue to evolve and spread.
Ensuring adherence to multidrug regimens to prevent emergence of resistance requires uninterrupted drug supplies and is vulnerable to human inconstancy. Finally, efforts to modify behavior (sexual and otherwise), will always have limitations in a free society. All of these shortcomings emphasize the critical role of research and dissemination of information. For that reason, this issue of Emerging Infectious Diseases (volume 11, number 6-June 2005) is devoted to antimicrobial resistance and highlights both burgeoning and neglected areas.

Articles address antimicrobial resistance in pathogens from the community, healthcare settings, and agriculture, among children and adults, and in several countries. In the case of community-associated methicillin-resistant Staphylococcus aureus (MRSA), articles cover outbreaks in Uruguay and in a US hospital nursery and maternity unit, emergence of a particular clone in Canada, prevalence in US emergency department patients, characteristics of patients admitted to a Swiss hospital, and the severity of this infection in pediatric patients. One article estimates hospitalizations associated with MRSA infection. These articles show some of the changing spectrum of disease and populations affected by this pathogen. The success of a relatively new vaccine against resistant Streptococcus pneumoniae and its impact on resistant infections is described. Resistance towards macrolides and structurally related drugs is the subject of several articles.
Antimicrobial-resistant foodborne infections are addressed in articles on Salmonella spp. and Campylobacter jejuni.
Several articles discuss resistant organisms that are largely problems in healthcare settings or among persons with underlying illness, such as extended-spectrum ß-lactamase (ESBL) producing Escherichia coli, vancomycin-resistant Enterococcus faecium, and gram-negative bacilli. Multidrug-resistant tuberculosis, perennially transmitted inside and outside healthcare and other institutional settings, is also discussed in 2 articles. An article on Trypanosoma brucei gambiense describes the importance and difficulty in determining resistance in parasitic infections, which can have countrywide implications for treatment, control, and use of resources.

This issue does not cover resistance in malaria, gonorrhea, and HIV infection. An estimated 300–500 million clinical cases of malaria occur each year, and resistance exists to some extent to nearly all available antimalarial drugs.
Efforts are under way to produce new drugs, but one of the most efficacious candidates has run into economic and manufacturing obstacles. Gonorrhea treatment and control are becoming increasingly difficult because of increases in resistance to multiple classes of drugs and the discontinued production of a preferred oral medication.
Antiretroviral drug resistance has been well demonstrated in countries in which the standard of care mandates treatment of HIV-infected persons. The imminent widespread use of antiretroviral drugs in countries with large populations infected with HIV, but for whom treatment has not been provided, will carry with it the specter of global resistance, thereby threatening the intended benefits.
Finally, in the absence of vaccine, the long-anticipated arrival of a global influenza pandemic, caused by H5N1 or another strain, would have potentially devastating consequences with respect to resistance. The potential for antiviral drug resistance to develop during treatment is manifest. The likely increased use of oral antibacterial drugs for patients with possible influenza and for prophylaxis and treatment of secondary bacterial pneumonia would enhance the existing evolutionary pressure toward resistance. The predictably large numbers of secondary bacterial pneumonias may be caused by established resistant pathogens (e.g., pneumococcus) and emerging ones (e.g., community-associated MRSA).

Fleming’s warning about inappropriate use has resonance today. Several articles describe the importance of the appropriate use of antimicrobial drugs as well as the difficultly of enforcement. The hope of preserving the effectiveness of existing drugs through appropriate use as well as the urgent need for the development of new drugs are both represented by the artwork featured on the cover of this issue. We hope to promote greater awareness among our readers of the strong link between antimicrobial drug use and the development of resistance and to make clear that improving use in community, healthcare, and agriculture settings, combined with other strategies, is imperative if we are to confront effectively the further development and spread of antimicrobial resistance.

Emerging Infectious Diseases
June 7, 2005

Original web page at Emerging Infectious Diseases

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Outbreaks of salmonella associated with Roma tomatoes

Three outbreaks of Salmonella infections associated with eating Roma tomatoes were detected in the USA and Canada in the summer of 2004.In one multistate USA outbreak during 25 Jun -18 Jul 2004, multiple Salmonella serotypes were isolated, and cases were associated with exposure to Roma tomatoes from multiple locations of a chain delicatessen. Each of the other two outbreaks was characterized by a single Salmonella serotype: Braenderup in one multistate outbreak and Javiana in an outbreak in Canada. In the three outbreaks, 561 outbreak-related illnesses from 18 states and a province in Canada were identified.

This report describes the subsequent investigations by public health and food safety agencies. Although a single tomato-packing house in Florida was common to all three outbreaks, other growers or packers also might have supplied contaminated Roma tomatoes that resulted in some of the illnesses. Environmental investigations are continuing. Because current knowledge of mechanisms of tomato contamination and methods of eradication of Salmonella in fruit is inadequate to ensure produce safety, further research should be a priority for the agricultural industry, food safety agencies, and the public health community.

In July 2004, a total of 429 culture-confirmed, outbreak-associated salmonellosis cases were identified in nine states (Maryland, Michigan, Missouri, North Carolina, New Hampshire, Ohio, Pennsylvania, Virginia, and West Virginia); these cases occurred among persons eating at delicatessen chain A sites, with symptom onset during Jul 2004 The median age of patients was 35 years (range: 1-81 years); 52 percent were male. No deaths occurred, but 30 percent of patients were hospitalized. These cases yielded Salmonella enteric serotypes Javiana, Typhimurium, Anatu, Thompson, Muenchen, and Group D untypable.

Roma tomatoes were removed from all delicatessen chain A sites on 14 Jul 2004. A total of 22 (5 percent) patients reported illness onset after 19 Jul 2004, outside the incubation period for salmonellosis. These illnesses might be explained by factors such as continued Roma tomato use, poor recall, low infectious dose, food saved and eaten later, or secondary transmission.

ProMed Mail
April 26, 2005

Original web page at ProMed Mail

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Statements BSAVA and WVA following information on MRSA in dogs and cats (ref. Veterinary Sciences Tomorrow, News March 29, 2005)

Current BSAVA statement on MRSA.
Current scientific evidence supports the opinion that the risk of pet-transmitted MRSA is small and that pet owners that undertake hygienic precautions are at minimal risk. MRSA, furthermore, does not normally harm healthy people including pregnant women, babies and children. The BSAVA, however, recommends that all reported infections with MRSA are investigated and that medical and veterinary staff co-ordinate in eliminating infection. The BSAVA strongly advocates the responsible use of anti-bacterial agents to minimise the development of resistant species and strains of all bacterial pathogens particularly those with zoonotic potential. High-risk individuals (long-term sick, elderly or patients with a poor immune system for example) may need to take extra care and seek advice from their veterinary surgeon and doctor.

Source: BSAVA Policy on MRSA, Created on 31 March 2005

BSAVA
April 12, 2005

Original web page at BSAVA

Statement WVA: Plea to pet owners MRSA panic unnecessary Commenting on fears being generated over MRSA (Methicillin Resistant Staphylococcus Aureus) in pets, the President-Elect of the BVA (British Veterinary Association) Dr Freda Scott-Park begged pet owners not to panic. The alarm being generated is completely unnecessary, she said. While MRSA has been isolated from a variety of domestic animals it is important for people to realise that the incidence is still very, very low. Dr Scott-Park stressed that any loss of a much-loved pet, whatever the cause, is tragic, but the circumstances surrounding the death of the dog that has triggered the latest concerns were, to say the least, extremely unusual as well as deeply regrettable. Clearly awareness of the potential dangers of MRSA is vital but detailed information was provided to the veterinary profession at the beginning of the year (via the Journal of Small Animal Practice, the journal of the British Small Animal Veterinary Association (BSAVA)). Practical advice and guidelines to the profession will also continue to be issued as and when relevant information becomes available. Dr Scott-Park continued: Current scientific evidence supports the opinion that the risk of pet-transmitted MRSA is small and that pet owners who undertake hygienic precautions are at minimal risk. MRSA does not normally harm healthy people including pregnant women, babies and children. Furthermore, there are no proven recorded cases of MRSA jumping from animal to human. High-risk individuals (long-term sick, elderly or patients with a poor immune system for example) may need to take extra care while vets need to remain aware of the need for extra precautions when treating similarly potentially vulnerable animals. In emphasising that there was already widespread awareness within the veterinary profession of MRSA and the problems that could occur Dr Scott-Park noted that the BVAs major concern at present relates to MRSA passing from humans to animals, the more likely path,” which was why she said we are urging vets to adopt best practice and take precautions – use sterile gloves, masks and scrub suits during operations – to prevent animals getting the organism.

E-mail address: Boglet.com
April 12, 2005

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Probable psittacosis outbreak linked to wild birds

In autumn 2002, an outbreak of probable psittacosis occurred among residents of the Blue Mountains district, Australia. We conducted a case-control study to determine independent risk factors for psittacosis by comparing exposures between hospitalized patients and other residents selected randomly from the telephone directory. Of the 59 case-patients with laboratory results supportive of psittacosis, 48 participated in a case-control study with 310 controls. Independent risk factors were residence in the upper Blue Mountains (odds ratio [OR] 15.2, 95% confidence interval [CI] 5.6–41.7), age of 50–64 years (OR 3.9, 95% CI 1.5–10.5), direct contact with wild birds (OR 7.4, 95% CI 2.5–22), and mowing lawns without a grass catcher (OR 3.2, 95% CI 1.3–8.0). Protective equipment is recommended for residents in areas frequented by free-ranging birds if contact with birds and their droppings is likely when performing outdoor activities such as lawn mowing.

Psittacosis is a human disease caused by infection with the bacterium Chlamydophila psittaci. The bacterium also causes avian chlamydiosis, a disease reported in psittacine birds such as parrots, cockatiels, and parakeets. Chlamydophila psittaci can be present in large numbers in the droppings of sick birds and in dust contaminated by infected droppings. The organism can remain infectious in the environment for months. Human infection usually occurs when a person inhales the bacterium shed in feces and secretions of infected birds. Sheep, goats, cattle, and reptiles can also be infected, but these animals have rarely been linked to human cases.

Psittacosis has an incubation period of 1 to 4 weeks, and manifestations of disease can range from asymptomatic infection to systemic illness with severe pneumonia. Untreated psittacosis has a reported case-fatality rate of 15% to 20%. Psittacosis is most commonly reported among people in close contact with domestic birds, such as bird owners, poultry farmers, veterinarians, and workers within pet shops and poultry-processing plants. Sporadic cases and an outbreak in Australia linked to contact with free-ranging (wild) birds have been reported; however, little information is available on the role of wild birds in the transmission of Chlamydophila psittaci to humans.

Psittacosis became a notifiable disease in New South Wales (NSW), Australia, in 2001, and 38 laboratory notifications were received by the state health department that year, an incidence of 5.7 cases per 1,000,000 population for NSW. In May 2002, clinicians at the Blue Mountains Hospital (BMH), in the Wentworth Area Health Service, NSW, a 1-hour drive west of Sydney’s central business district, reported an increase in adult admissions for severe community-acquired pneumonia. From March to May 2002, a total of 160 persons with pneumonia were seen at the BMH emergency department, compared with 82 from March to May 2001. The population of the Blue Mountains is ˜80,000 persons, and the area includes a large national park. The lower Blue Mountains (altitude ˜160 m) is on the western outskirts of Sydney, and residences tend to have suburban-style yards. The upper Blue Mountains district (altitude ˜1,044 m) lies further west, receives more rain, and has more bush land; its residential areas have larger yards and are closer to bush land. Reports that patients had found increased numbers of dead free-ranging birds in their yards, handled dead birds, and occasionally mowed over dead bird carcasses prompted clinicians to suspect psittacosis, although no case had been confirmed by laboratory testing. We report on our investigation into the extent and most likely cause of this outbreak.

Emerging Infectious Diseases
March 29, 2005

Original web page at Emerging Infectious Diseases

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Effect of regulation and education on reptile-associated salmonellosis

Reptiles have become increasingly common as domestic pets, and with them reptile-associated Salmonella infections in humans. From 1990 to 2000, a total of 339 reptile-associated Salmonella cases were reported in Sweden. In 1996, as part of its efforts to adapt its import regulations to those of the European Union, Sweden no longer required certificates stating that imported animals were free of Salmonella. A subsequent increase was noted in the incidence of reptile-associated cases from 0.15/100,000 in the period 1990–1994 to 0.79/100,000 in 1996 and 1997. After a public education campaign was begun through the news media, the incidence dropped to 0.46/100,000. Children were the most affected age group among patients (incidence 1.3/100,000). Salmonella enterica serotype Enteritidis was the most frequent serotype (24% of isolates), followed by S. Typhimurium (9% of isolates). Import restrictions and public information campaigns are effective public health measures against reptile-associated salmonellosis.

Salmonellosis is an important worldwide health problem, affecting both humans and animals. In the United States, Salmonella causes an estimated 1.4 million episodes of infection and 400 deaths annually in humans. Salmonella usually causes a moderate gastrointestinal disorder, but it may result in more severe disease, such as bacteremia or meningitis, sometimes with fatal outcome. For decades, reptiles have been recognized as a source of human salmonellosis. Salmonella species were first isolated from snakes, turtles, and lizards in the 1940s, and more recent studies have shown that at least 50%–90% of these animals are carriers of Salmonella. The bacteria are excreted intermittently in the feces but can also be isolated from the cloacae, skin, and throat of water-living reptiles.

Reptiles have become increasingly common as domestic pets. In Canada, pet turtle–associated salmonellosis was recognized as a serious health problem in the 1960s and 1970s, and the country banned imported turtles in 1975.
Sweden has a long tradition of combating and controlling Salmonella in feed, animals, and humans, dating back to a large outbreak of salmonellosis in 1953 that affected >9,000 persons and caused 90 deaths. From 1970 to 1994, these control measures also included import restrictions on reptiles; anyone who wanted to import reptiles or turtles needed a certificate stating that the animals were free of Salmonella, and importing of turtles with shells <10 cm was not allowed. In 1995, Sweden dropped its requirement for a Salmonella certificate and instead required an import permit issued by the Swedish Board of Agriculture. When Sweden became a member of the European Union (EU) in January 1995, a number of new rules were adopted. As a result of these changes, Sweden no longer required import permits for reptiles and turtles, and it also lifted the import ban on small turtles. The adaptation of import regulations for reptiles took effect on March 1, 1996. Emerging Infectious Diseases
March 29, 2005

Original web page at Emerging Infectious Diseases

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Research into an evidenced-based review of the information available on MRSA in dogs and cats.

Recent press headlines such as ‘Hospital superbug MRSA spreads to animals’ (Revill 2003) and ‘MRSA on the rise in UK veterinary clinics’ (Veterinary Times, October 2004) have focused attention on the potential risk of MRSA to companion animal health and also on the role of dogs and cats in the epidemiology of human MRSA infection. During the first half of 2004, the BSAVA Scientific Committee asked one of its members, Dr Tim Nuttall, of the University of Liverpool, to spearhead the preparation of an evidence-based review of current literature on MRSA in dogs and cats.

The review, ‘Methicillin-resistant Staphylococcus aureus in dogs and cats: an emerging problem?’, by Dr Robert Duquette and Dr Nuttall, was published in the December issue of the Journal of Small Animal Practice and provides both historical and current information on the epidemiology of MRSA in dogs and cats and the risk of zoonotic spread. It also provides a scientific basis on which to identify those animals that may be at higher risk of contracting infection, and to underpin any future recommendations on control of MRSA in companion animals. In particular, references are given for barrier nursing methods. Using a treatment strategy relatively novel for dogs, an absorbable gentamicin-impregnated sponge was surgically implanted into the affected joint.

This had the benefit of achieving prolonged high intra-articular concentrations of gentamicin while limiting the requirement for systemic administration to that appropriate for elimination of S. aureus in other sites. This also minimised both the risk of nephrotoxicity and the potential risks of MRSA contact by humans. The treatment was successful. In retrospect, it would have been interesting to know if this dog was indeed carrying MRSA in its nasopharynx and if the owners had previous hospital contact.

BSAVA
March 29, 2005

Original web page at BSAVA

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Ice age bacteria brought back to life

A bacterium that sat dormant in a frozen pond in Alaska for 32,000 years has been revived by NASA scientists. Once scientists thawed the ice, the previously undiscovered bacteria started swimming around on the microscope slide. The researchers say it is the first new species of microbe found alive in ancient ice. Now named Carnobacterium pleistocenium, it is thought to have lived in the Pleistocene epoch, a time when woolly mammoths still roamed the Earth.

NASA astrobiologist Richard Hoover, who led the team, said the find bolsters the case for finding life elsewhere in the universe, particularly given this week’s news, broken by New Scientist, of frozen lakes just beneath the surface of equatorial Mars. The team initially set out to find bacteria that thrived at extremely low temperatures, so it was a surprise to find organisms that tolerated the cold, but preferred room temperature. “I think the most important thing from this observation is that microorganisms can be preserved in ice for long periods of time,” Hoover told New Scientist.

He retrieved the bacteria from a tunnel in the Alaskan permafrost, carved by the US Army’s Cold Regions Research and Engineering Laboratory. Walking through the tunnel, Hoover saw a fossilised mammoth tusk protruding from one side and an ancient jawbone on the other. The bacteria came from a cross-section of a preserved pond. The bottom of the pond was a brownish hue, which Hoover thought might be caused by diatoms – single-celled algae. “Frankly, I was disappointed that there weren’t any diatoms at all,” he says. Instead, he saw a host of pigmented bacteria that started swimming as soon as the ice melted. He took the samples back to Marshall Space Flight Center in Alabama, US, and cultured the samples. Initially, the team thought it might be an existing bacterium, but gene sequencing revealed it as a new species.

Another group of researchers from West Chester University in Pennsylvania, US, claimed in 2000 that they had isolated a 250-million-year-old bacterium. But other scientists disputed that the microbes could so very old. For example, those particular microbes like salty environments. And salt deposits tend to have water moving through them, potentially bringing contamination, says Robert Hazen, a geophysicist with the Carnegie Institution of Washington and president of the Mineralogical Society of America. “The fact you have extracted microbes from the salt doesn’t really tell you the microbes are as old as the salt,” he says. While Hazen says that 250-million-year-old microbes seemed unlikely, “I wouldn’t be surprised at microbes that are a few tens of thousands of years old”.

Journal reference: International Journal of Systematic and Evolutionary Microbiology (vol 55, p 473)

New Scientist
March 15, 2005

Original web page at New Scientist