Speedy ID

Ian Lipkin's team at Columbia University hit the headlines again this April with another rapid identification of a new pathogen. Lipkin became involved after three transplant recipients in Australia died in quick succession in January of this year. The fact that all three had received organs from the same donor indicated that an infectious agent could be involved, and when all the standard diagnostic tests came up negative the Australian team from the Victorian Infectious Disease Reference Laboratory in Melbourne contacted Lipkin. Using 454 rapid sequencing technology, Lipkin's group identified a previously unknown virus, which is related to lymphocytic choreomeningitis virus (LCMV) and which may be a new member of the Arenaviridae. The findings have yet to be published. news@nature.com

H5N1 vaccine news

At a meeting of vaccine manufacturers from industrialized and developing countries and representatives from more than 30 member countries held at WHO headquarters at the end of April, a consensus was reached that creating a global stockpile of a vaccine for use in an H5N1 'flu pandemic was 'feasible'. As a next step, WHO will establish expert working groups to discuss the many details involved. Many countries have already begun to stockpile the antiviral oseltamivir but, because of the difficulties associated with vaccine development, agreement on whether to stockpile a vaccine has been slower. In a related development, WHO also announced that it will help six developing countries to develop their own vaccine manufacturing facilities. The countries — Brazil, India, Indonesia, Mexico, Thailand and Vietnam — will receive funds provided by the US and Japanese governments. WHO/ScienceNOW

Successful combination

Using combinations of antibiotics is becoming an increasingly important strategy in the battle against antibiotic resistance. Intriguing results from Roy Kishony's group, recently reported in Nature, indicate that a suppressive combination — that is, a combination of two antibiotics that is less effective than either drug alone — can select against the emergence of resistance. To investigate this, the authors analysed the effects of synergistic and suppressive antibiotic combinations on a wild-type (doxycycline-sensitive) and doxycycline-resistant Escherichia coli strain. The bacteria were exposed to increasing concentrations of doxycycline plus erythromycin (a synergistic combination) or doxycycline plus ciprofloxacin (a suppressive combination). Comparison of the responses revealed that treatment with the synergistic combination appeared to select against the sensitive strain, as expected, but the suppressive combination appeared to select against the resistant strain and this unexpected result was confirmed by a direct competition assay between the sensitive and resistant strains. As yet, these experiments have only been carried out in vitro, but eventually they could have implications for treatment strategies. Nature

New entry inhibitor for HIV-1?

There was widespread media coverage this month of the Cell paper describing the discovery and optimization of a new HIV-1 entry inhibitor. A variety of natural anti-HIV compounds are present in blood and tissues but these compounds have proven difficult to purify and characterize. Münch et al. set out to tackle this problem by creating a peptide library from 10,000 litres of filtered human blood that essentially contained all of the compounds in the bloodstream that have a molecular weight of <30 kDa. The library was then screened to identify factors that block HIV-1 replication. The peptide present in the most potent fraction was identified as a 20-residue peptide that was named virus-inhibitory peptide, or VIRIP. VIRIP corresponds to residues 353–372 in the C terminus of the serine protease inhibitor α1-AT and was shown to specifically block infection by all of the HIV-1 variants tested. More detailed analysis of the effects of VIRIP revealed that this peptide is an entry inhibitor that has a distinct target — the highly conserved gp41 fusion peptide — from that of the entry inhibitors that are already under investigation. As a few amino-acid alterations increased the anti-HIV-1 activity of VIRIP by two orders of magnitude, this peptide could be a new drug candidate for the future. Cell

Casting a NET over sepsis

It has long been known that platelets and neutrophils are involved in sepsis, but the precise nature of this involvement has remained unclear, Now, reporting in Nature Medicine, researchers have found that platelets can sense intracellular bacteria and stimulate neutrophils to release neutrophil extracellular traps (NETs) to trap the bacteria. Clark et al. demonstrated that platelet Toll-like receptor 4 (TLR4) detects bacterial lipopolysaccharide (LPS) and, using a mouse model of endotoxemia, they found that the LPS–platelet TLR4 interaction induced neutrophil activation, including significant degranulation. On closer inspection using phase-bright contrast microscopy, the authors found that the neutrophils had produced NETs. In vitro and in vivo experiments then confirmed that the formation of NETs enhanced bacterial trapping. Sepsis almost always involves the liver, and in this study the production of NETs occurred primarily in the liver sinusoids and pulmonary capillaries. Nature Med.

One-stop online shop for drug targets

There are hopes that a new drug target prioritization database, which is available online at http://tdrtargets.org, will help researchers to identify and prioritise drug targets against tropical diseases such as leishmaniasis, lymphatic filariasis and Chagas disease, which predominantly affect developing countries. The database is one output from the Drug Target Prioritization Network, a consortium which was established by WHO in 2005 and based in the TDR and which includes researchers from TDR, the University of Washington, the University of Pennsylvania, the Wellcome Trust Sanger Institute, the University of Melbourne and the Universidad Nacional de General San Martín in Argentina. Currently, the website brings together the available diverse genomic and bioinformatics datasets from Mycobacterium tuberculosis, Plasmodium falciparum, Leishmania major, Trypanosoma brucei and Trypanosoma cruzi, and plans are afoot to include the data for five more parasites (Plasmodium vivax, Brugia malayi, Schistosoma mansoni, Onchocerca volvulus and Mycobacterium leprae) in the near future. TDR

Keep Chikungunya in mind

New figures in the CDC Morbidity and Mortality Weekly Report reveal that 37 cases of Chikungunya fever were imported into the USA in 2006 by returning US travellers. This is in contrast to only 3 cases in the preceding 15 years. This large increase was caused by the 2005–2006 epidemic of Chikungunya fever on Reunion Island and the surrounding islands in the Indian Ocean, which spread eventually to India, and emphasizes the need for clinicians to be aware of the disease and its symptoms. The first clinical report from Reunion Island, where an estimated 266,000 people from a population of 770,000 were affected, was published in a recent issue of Clinical Infectious Diseases, and detailed the clinical features and laboratory findings for a group of adults with acute Chikungunya fever. MMWR/CID

Turtles pose infection risk

The US Food and Drug Administration (FDA) issued an alert in April warning parents not to keep pet turtles in households with young children, after a 4-week old baby in Florida died from a Salmonella enterica serotype Pomona infection that has been traced to the family's pet turtle. The bacteria can be found on the outer skin and shell of turtles, and the FDA emphasized the importance of hand-washing after turtles have been handled. More than 20 years ago the sale of turtles with shells measuring less than four inches in length was banned in order to discourage people from buying small turtles as pets for their children. An estimated 74,000 people in the USA develop turtle-related Salmonella infections each year. CID

Bovine TB goes human to human

The UK Health Protection Agency (HPA) published the results of their investigation into a cluster of human cases of bovine tuberculosis in The Lancet in April. Human cases of the bovine form of the disease are rare and are usually associated with individuals who drink unpasteurized dairy products. In this instance, the HPA began investigating after two linked cases of human Mycobacterium bovis infection were identified through routine surveillance. Further investigation found a cluster of six linked cases in the Birmingham area, all in young people. Five of the patients had pulmonary disease, and there was one fatal case of M. bovis meningitis. Evidence of consumption of unpasteurized dairy products was only present in the first case but all six individuals were known to have had contact in two different bars in Birmingham, which indicates human-to-human transmission. Lancet

Simple but effective

WHO and UNICEF issued a joint policy statement on the role of vaccine vial monitors in improving access to immunization at the beginning of May. A vaccine vial monitor is an extremely simple device — a circular indicator with an inner square made of heat-sensitive material. The indicator can be printed directly onto the vial label or stuck to the top of the vial. The inner square is initially light in colour but becomes darker over time when exposed to heat. This simple system allows health workers to determine whether the vaccine has been spoiled by heat exposure by comparing the colour of the square to the surrounding reference ring. The policy statement called for countries, donor agencies and non-governmental organizations to require these monitors as a minimum standard in every vaccine donation. Michel Zaffran, Deputy Executive Secretary of the GAVI Alliance, commented that 'vaccine vial monitors have played a crucial role in overcoming challenges related to safe delivery of vaccines, especially in hot climates where vaccine refrigeration is weak or inexistent'. WHO

Does H. pylori protect against asthma?

Helicobacter pylori infection might protect children from developing asthma, according to a new paper recently published in the Archives of Internal Medicine. The presence of H. pylori protects against gastro-esophageal reflux disease (GERD) and as some asthma cases are related to GERD, Martin Blaser and Yu Chen from New York University School of Medicine wondered if H. pylori also protected against asthma. They used data from a health survey known as the Third National Health Nutrition Examination Survey (NHANES III), which involved ∼40,000 people and was conducted between 1988 and 1994. The questions in the survey included history of asthma and allergy symptoms, and in addition just over 7,500 survey participants had been tested for the presence of H. pylori and H. pylori CagA antibodies. The presence of cagA+ H. pylori was inversely correlated with ever having had asthma, and there was a strong inverse correlation for childhood (≤15 years)-onset asthma. An inverse correlation was also found between cagA+ H. pylori and allergy symptoms. The authors say that one explanation could be that the immune response to H. pylori as it is acquired during childhood drives the immune counter-regulation necessary to prevent asthma and allergy. Arch. Intern. Med.

In the News was compiled with the assistance of David Ojcius, University of California, Merced, USA. David's links to infectious disease news stories can be accessed on Connotea (http://www.connotea.org), under the username ojcius.