Threatwatch: Disease may run amok while the CDC sleeps

 

Threatwatch is your early warning system for global dangers, from nuclear peril to deadly viral outbreaks. Debora MacKenzie highlights the threats to civilisation – and suggests solutions

“We are less safe.” So Tom Frieden, head of the US Centers for Disease Control and Prevention in Atlanta, Georgia, announced on Twitter last week, as he prepared to send 8754 of his staff – two-thirds of the world’s biggest body of disease-watchers – home on furlough due to lack of government funding. It was part of the massive shutdown of US federal agencies in the wake of political intransigence in Congress over a budget.

“They protected you yesterday, can’t tomorrow. Microbes [and] other threats didn’t shut down,” Frieden added. But are we really less safe? And if so, how, exactly?

Obviously, this makes less difference if you live outside the US, but the uniquely global reach of the CDC affects us all in some ways. Even in the US, the effect may be subtle, because state governments have primary responsibility for public health. But they have always needed the CDC to marshal them in the face of any threat that crosses state lines – and sometimes even those that don’t.

Salmonella outbreak

That became clear earlier this week when CDC had to call back 10 of the people who run PulseNet, a computerised system for genetically tracking germs carried on food. US agriculture inspectors – deemed too important to furlough – had announced that chicken producers in California were the probable source of an outbreak of Salmonella that the CDC had been tracking since March, which has sickened 278 people in 18 states.

The affected states were tracking their own strains. But the PulseNet platform allowed the CDC to put the data together, and find that four of the seven strains of bacteria in the outbreak are novel, many have multiple resistance to antibiotics, and all came from chicken plants in California that have spread some of these bacteria before.

Nearly half the people infected have been hospitalised, twice the usual rate, suggesting these are nastier bugs than normal. Thankfully no one has died in the outbreak, though Salmonella can leave lifelong, debilitating after-effects.

Tuberculosis cluster

James Wilson of Ascel Bio, an epidemiological consulting firm in Denver, Colorado, believes the CDC should focus its limited resource on the tuberculosis cluster left by a Nevada woman who died, along with her twin babies, of the infection in July.

Of 200 people who had contact with the woman and have been tested, 26 were infected. Nevada state officials had asked the CDC for help testing 140 babies who shared intensive care with the twins, says Wilson. But because of the shutdown, that is now on hold.

So is an investigation of evidence, published this week, that the mosquito-borne virus dengue fever has been spreading unrecognised in Houston, Texas, since 2002. Dengue kills 25,000 people a year across the tropics. It had been absent from the US since the 1950s – but sporadic cases recently have crept back into the south.

It is especially dangerous when people encounter one strain, then another, as this can trigger a deadly immune reaction. Worryingly, the Houston strain is different from one seen in Florida in 2010, meaning encountering both might now be a possibility if they have spread along the Gulf coast. Finding out if they have will require intensive surveillance of people and mosquitoes across the southern US, says Peter Hotez, head of tropical medicine at Baylor College of Medicine in Houston. Only the CDC can do that.

Global network

Outside the US, the CDC runs a network of 10 global disease-detection centres, of which eight are now closed. They are often the only modern epidemiology available in tropical countries where novel outbreaks could be brewing, such as the next flu pandemic, or something completely unexpected like MERS, the coronavirus that emerged in Saudi Arabia last year. The annual Hajj pilgrimage to Mecca is now under way, and the CDC would normally be first to help investigate any suspicious disease outbreaks in returning pilgrims across the world. But as long as the shutdown persists, it cannot.

The worst problem for the CDC, however, might turn out to be that nothing really severe happens while most of its staff are forbidden from coming to work.

Political ideologues committed to “small government” could claim that this shows that the world does not need a publicly funded agency like the CDC and its comprehensive disease monitoring and rapid-response capabilities. Yet as New Scientist has reported many times, rapid forms of travel, booming populations of humans and animals, ecological disruption and changing global climate add up to a myriad new disease threats waiting to happen. Electing to stop watching for them because of a political spat does not change that fact.

 

http://www.newscientist.com/article/dn24387-threatwatch-disease-may-run-amok-while-the-cdc-sleeps.html#.Uln-ycHn_Vg

Frog-in-bucket-of-milk folklore leads to potential new antibiotics

Contact: Michael Bernstein m_bernstein@acs.org 202-872-6042 American Chemical Society

Following up on an ancient Russian way of keeping milk from going sour — by putting a frog in the bucket of milk — scientists have identified a wealth of new antibiotic substances in the skin of the Russian Brown frog. The study appears in ACS’ Journal of Proteome Research.

A. T. Lebedev and colleagues explain that amphibians secrete antimicrobial substances called peptides through their skin. These compounds make up the majority of their skin secretions and act as a first line of defense against bacteria and other microorganisms that thrive in the wet places frogs, toads, salamanders and other amphibians live. A previous study identified on the skin of the Russian Brown frog 21 substances with antibiotic and other potential medical activity. Lebedev’s team set out to find more of these potential medical treasures.

They used a sensitive laboratory technique to expand the list of such substances on the frogs’ skin, identifying 76 additional substances of this kind. They describe lab tests in which some of the substances performed as well against Salmonella and Staphylococcus bacteria as some prescription antibiotic medicines. “These peptides could be potentially useful for the prevention of both pathogenic and antibiotic resistant bacterial strains while their action may also explain the traditional experience of rural populations,” the scientists concluded.

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New pathogen epidemic identified in sub-Saharan Africa : non-Typhoidal Salmonella up to 45% mortality rate

Public release date: 30-Sep-2012

Contact: Aileen Sheehy press.office@sanger.ac.uk 0044-012-234-96928 Wellcome Trust Sanger Institute

Researchers track the spread of human invasive non-Typhoidal Salmonella in sub-Saharan Africa

A new study out today (Sunday 30 September) reveals that the emergence and spread of a rapidly evolving invasive intestinal disease, that has a significant mortality rate (up to 45%) in infected people in sub-Saharan Africa, seems to have been potentiated by the HIV epidemic in Africa.

The team found that invasive non-Typhoidal Salmonella  (iNTS) disease is caused by a new form of the bacteria Salmonella Typhimurium that has spread from two different focal hubs in Southern and Central Africa beginning 52 and 35 years ago, respectively. They also found that one of the major contributing factors for the successful spread of iNTS was the acquisition of genes that afford resistance to several front line drugs used to treat blood-borne infection such as iNTS.

iNTS is a blood-borne infection that kills approximately one of four people in sub-Saharan Africa who catch it. Yet, in the rest of the world, NTS is a leading cause of acute inflammatory diarrhoea that is self-limiting and tends to be fatal in less than 1 per cent of people infected. The disease is more severe in sub-Saharan Africa than the rest of the world because of factors such as malnutrition, co-infection with malaria or HIV and potentially the novel genotype of the Salmonella bacteria.

“The immune system susceptibility provided by HIV, malaria and malnutrition at a young age, may provide a population in sub-Saharan Africa that is large enough for this detrimental pathogen to enter, adapt, circulate and thrive,” says Chinyere Okoro, joint first author from the Wellcome Trust Sanger Institute. “We used whole genome sequencing to define a novel lineage of Salmonella Typhimurium that is causing a previously unrecognised epidemic across the region. Its genetic makeup is evolving  into a more typhoid like bacteria, able to efficiently spread around the human body”

From sequenced samples, the team created a phylogenetic or ‘family tree’, depicting the pathogen’s evolution, dating when each sample first emerged and overlaying this with geographical information about where these samples came from. They found that this invasive disease comprises of two very closely related waves; the first wave originated from a possible south-eastern hub, about 52 years ago and the second originated about 35 years ago, possibly from the Congo Basin.

“The HIV epidemic in sub-Saharan Africa is thought to have begun in a central region and underwent expansion eastwards, a strikingly similar dynamic to that observed for second iNTS wave,” says Dr Robert Kingsley, joint first author from the Wellcome Trust Sanger Institute. “Our findings suggest the current epidemic of iNTS and its transmission across sub-Saharan Africa may have been potentiated by an increase in the critical population of susceptible, immune-compromised people.”

The team identified that the vast majority of samples from the second wave of iNTS contains a gene that makes them resistant to chloramphenicol, a frontline antibiotic in the treatment of Salmonella. This gene was not present in the samples from the first wave of iNTS. This observation suggests that iNTS acquired this gene early on in the evolution of the second wave, probably around the time of its spread from the Congo basin.

“Because it acquired resistance to chloramphenicol, this pathogen has much greater opportunity to survive and spread across the region,” says Professor Gordon Dougan, lead author from the Wellcome Trust Sanger Institute. “This is the first time that the power of whole-genome sequencing has been used to track the spread of iNTS. Our research highlights the power this approach has to monitor the emergence and spread of dangerous pathogens both locally and globally over time.”

“There has been some evidence that this disease can be passed from human to human. Now the race is on to discover how NTS is actually transmitted in sub-Saharan Africa so that effective intervention strategies can be implemented.”

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Notes to Editors

Publication Details

Chinyere K. Okoro, Robert A. Kingsley, Thomas R. Connor et al. ‘Intra-continental spread of human invasive Salmonella Typhimurium pathovariants in sub-Saharan Africa’

Published in Nature Genetics 30 September 2012. DOI: 10.1038/ng.2423

Funding

This work was funded by the Wellcome Trust and Tropical Research Fellowship from the Wellcome Trust and Clinical Research Fellowship from GlaxoSmithKline.

Participating Centres

Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton Cambridge, UK. CB10 1SA

Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand

Department of Clinical Infection, Microbiology and Immunology, Institute for Infection and Global Health, University of Liverpool, Liverpool, UK

Centre for Microbiology Research, Kenya Medical Research Institute, Nairobi, Kenya

Malawi-Liverpool-Wellcome Trust Clinical Research Program, University of Malawi College of Medicine, Blantyre, Malawi

Department of Microbiology, College of Medicine, University of Malawi, Blantyre, Malawi

Department of Gastroenterology, Institute of Translational Medicine, Liverpool University, Liverpool, UK. L69 3GE

Health Protection Agency, Laboratory for Gastrointestinal Infections, Centre for Infections, London, United Kingdom

Norwich Medical School, University of East Anglia, Norwich, United Kingdom

Cellular and Molecular Medicine, School of Medical Sciences, University of Bristol, Bristol, United Kingdom

Division of Paediatric Infectious Diseases, Department of Paediatrics and Human Development, Michigan State University, East Lansing, MI 48824, USA

National Hospital Abuja, Plot 132 Central District (Phase II), Garki Abuja, Nigeria

Barcelona Centre for International Health Research (CRESIB, Hospital Clínic-Universitat de Barcelona), Barcelona, Spain

Centro de Investigação em Saúde de Manhiça (CISM), Manhiça, Mozambique

Instituto Nacional de Saúde, Ministerio de Saúde, Maputo, Mozambique

Novartis Vaccines Institute for Global Health S.r.l. (NVGH), Via Fiorentina 1, 53100 Siena, Italy

MRC Centre for Immune Regulation, School of Immunity and Infection, College of Medicine and Dental Sciences, University of Birmingham, Birmingham, B15 2TT, UK.

Center for Vaccine Development, University of Maryland, Baltimore, HSFI 480, 685 West Baltimore St., Baltimore, MD 21201, USA

Department of Medicine, University of Maryland, Baltimore, HSFI 480, 685 West Baltimore St., Baltimore, MD 21201, USA

Selected Websites

The Wellcome Trust Sanger Institute is one of the world’s leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.

http://www.sanger.ac.uk

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.

http://www.wellcome.ac.uk

Contact details

Don Powell Media Manager Wellcome Trust Sanger Institute Hinxton, Cambridge, CB10 1SA, UK Tel +44 (0)1223 496 928 Mobile +44 (0)7753 7753 97 Email press.office@sanger.ac.uk

End of Notes to Editors

Cinnamon is lethal weapon against E. coli O157:H7

Contact: Angela Dansby aldansby@ift.org 312-782-8424 x127 Institute of Food Technologists

When cinnamon is in, Escherichia coli O157:H7 is out.  That’s what researchers at Kansas State University discovered in laboratory tests with cinnamon and apple juice heavily tainted with the bacteria.  Presented at the Institute of Food Technologists’ 1999 Annual Meeting in Chicago on July 27, the study findings revealed that cinnamon is a lethal weapon against  E. coli O157:H7 and may be able to help control it in unpasteurized juices.

Lead researcher Erdogan Ceylan, M.S., reported that in apple juice samples inoculated with about one million E. coli O157:H7 bacteria, about one teaspoon (0.3 percent) of cinnamon killed 99.5 percent of the bacteria in three days at room temperature (25 C).  When the same amount of cinnamon was combined with either 0.1 percent sodium benzoate or potassium sorbate, preservatives approved by the Food and Drug Administration, the E. coli were knocked out to an undetectable level.  The number of bacteria added to the test samples was 100 times the number typically found in contaminated food.

“This research indicates that the use of cinnamon alone and in combination with preservatives in apple juice, besides its flavoring effect, might reduce and control the number of E. coli O157:H7,” concluded Ceylan, a Ph.D. graduate assistant at K-State. “Cinna-mon may help protect consumers against foodborne bacteria that may be in unpasteurized juices and may partially or completely replace preservatives in foods to maintain their safety,” he said.

“If cinnamon can knock out E. coli O157:H7, one of the most virulent foodborne microorganisms that exists today, it will certainly have antimicrobial effects on other common foodborne bacteria, such as Salmonella and Campylobacter,” noted Daniel Y.C. Fung, Ph.D., professor of Food Science in the Department of Animal Sciences and Industry at K-State, who oversaw the research.

Last year, Fung and Ceylan researched the antimicrobial effects of various spices on  E. coli O157:H7 in raw ground beef and sausage and found that cinnamon, clove, and garlic were the most powerful.  This research led to their recent studies on cinnamon in apple juice, which proved to be a more effective medium than meat for the spice to kill the bacteria.

“In liquid, the E. coli have nowhere to hide,” Fung noted, “whereas in a solid structure, such as ground meat, the bacteria can get trapped in the fat or other cells and avoid contact with the cinnamon.  But this cannot happen in a free-moving environment.”

Regardless of the K-State findings, people who are at greater than normal risk for foodborne diseases– namely the elderly, young children, or immune-compromised– would be urged to avoid drinking unpasteurized juices or unthoroughly cooked hamburgers, which may contain harmful microorganisms.

For a copy of the study presented at IFT’s Annual Meeting, contact Angela Dansby at 312-82-8424 x127 or via e-mail at aldansby@ift.org .

###Founded in 1939, IFT is a non-profit scientific society with 28,000 members working in food science, technology and related professions in industry, academia and government.  As the society for food science and technology, IFT brings sound science to the public discussion of food issues

Reposted for Filing 1999 Data

New salmonella-based ‘clean vaccines’ aid the fight against infectious disease:To accomplish this, a recombinant strain of Salmonella was constructed using genes from another pathogen, Francisella tularensis

* They are using genes from tularensis ” inhaling as few as 10 bacteria could be potentially deadly ” I feel uncomfortable with the Gates foundation funding support utilizing a Bioweapon strain of  Rabbit Fever?

 

New salmonella-based ‘clean vaccines’ aid the fight against infectious disease

A powerful new class of therapeutics, known as recombinant attenuated Salmonella vaccines (RASV), holds great potential in the fight against fatal diseases including hepatitis B, tuberculosis, cholera, typhoid fever, AIDS and pneumonia.

Now, Qingke Kong and his colleagues at the Biodesign Institute at Arizona State University, have developed a technique to make such vaccines safer and more effective. The group, under the direction of Dr. Roy Curtiss, chief scientist at Biodesign’s Center for Infectious Diseases and Vaccinology, demonstrated that a modified strain of Salmonella showed a five-fold reduction in virulence in mice, while preserving strong immunogenic properties.

Their findings appear in the cover story of the current issue of the Journal of Immunology.

Streptococcus pneumoniae, an aerobic bacterium, is the causative agent of diseases including community-acquired pneumonia, otitis media, meningitis, and bacteremia. It remains a leading killer—childhood pneumonia alone causing some 3 million fatalities annually, mostly in poorer countries.

Existing vaccines are inadequate for protecting vulnerable populations for several reasons. Heat stabilization and needle injection are required, which are often impractical for mass inoculation efforts in the developing world. Repeated doses are also needed to induce full immunity. Finally, the prohibitively high costs of existing vaccines often deprive those who need them most.  The problem is exacerbated by the recent emergence of antibiotic-resistant strains of pneumococcus causing the disease, highlighting the urgency of developing safe, effective, and lower-cost antipneumococcal vaccines.

One of the most promising strategies for new vaccine development is to use a given pathogen as a cargo ship to deliver key antigens from the pathogen researchers wish to vaccinate against. Salmonella, the bacterium responsible for food poisoning, has proven particularly attractive for this purpose, as Curtiss explains: “Orally-administered RASVs stimulate all three branches of the immune system stimulating mucosal, humoral, and cellular immunity that will be protective, in this case, against a majority of pneumococcal strains causing disease.”

Recombinant Salmonella is a highly versatile vector—capable of delivering disease-causing antigens originating from viruses, bacteria and parasites.  An attenuated Salmonella vaccine against pneumonia, developed in the Curtiss lab, is currently in FDA phase 1 clinical trials.

In the current research, the team describe a method aimed at retaining the immunogenicity of an anti-pneumonia RASV while reducing or eliminating unwanted side effects sometimes associated with such vaccines, including  fever and intestinal distress. “Many of the symptoms associated with reactogenic Salmonella vaccines are consistent with known reactions to lipid A, the endotoxin component of the Salmonella lipopolysaccharide (LPS),” the the major surface membrane component , Kong explained.   “In this paper, we describe a method for detoxifying the lipid A component of LPS in living cells without compromising the ability of the vaccine to stimulate a desirable immune response.”

To achieve detoxification, Salmonella was induced to produce dephosphoylated lipid A, rendering the vaccine safer, while leaving its ability to generate a profound, system-wide immune response, intact.

To accomplish this, a recombinant strain of Salmonella was constructed using genes from another pathogen, Francisella tularensis, a bacterium associated with tularemia or rabbit fever. Salmonella expressing lipid A 1-phosphatase from tularensis (lpxE) showed less virulence in mice, yet acted to inoculate the mice against subsequent infection by wild-type Salmonella.

In further experiments, the group showed that Salmonella strains could also be constructed to additionally synthesize pneumococcal surface protein A (PspA)—a key antigen responsible for generating antibodies to pneumonia. Again, the candidate RASV displayed nearly complete dephosphorylation of lipid A, thereby reducing toxicity.

Following inoculation with the new Salmonella strain, mice produced a strong antibody response to PspA and showed greatly improved immunity to wild-type Streptococcus pneumoniae, compared with those inoculated with Salmonella lacking  the PspA antigen. Tissue culture studies showing reduction of inflammatory cytokines following application of modified lipid A further buttressed the results.

Francisella LpxE was shown to effectively strip the 1-phosphate group from Salmonella‘s lipid A, without loss of the bacterium’s capacity for colonization. The research holds promise for constructing modified live attenuated Salmonella vaccine strains for humans, with dephosphoylated lipid A providing additional safety benefits.

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The research was supported by grants from the Bill and Melinda Gates Foundation and the National Institute of Health

* Reposted on Request