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Anthrax update
Newsdesk Anthrax update
388
Rights were not granted to include this image in electronic media. Please refer to the printed journal. AP
The perpetrator of the US “anthrax letters” is still at large, and cynics might say that plans to submit employees at two US Army research laboratories to lie-detector tests smack of desperation. But Barbara Rosenberg (State University of New York, NY, USA), who has followed the investigation closely, claims that the Federal Bureau of Investigation (FBI), which will test up to 200 current and former employees at Fort Detrick and Dugway, could have a suspect. “They may be looking for a specific piece of information and are deflecting suspicion by the broad net.” 22 cases of anthrax were reported after the attacks last September and October, and five people (all with inhaled anthrax) died. But the prompt distribution of antibiotics to postal workers and others at risk probably averted many more cases, say US researchers. Glenn Webb (Vanderbilt University, Nashville, TN, USA) and Martin Blaser (New York University, NY, USA), who constructed a mathematical model to simulate the spread of spores, calculate that six anthrax-laden letters (four were recovered) contaminated about 5000 other pieces of mail with between 10 and 10 000 spores each (Proc Natl Acad Sci USA 2002; 99: 7027–32). “A plausible mechanism for release of the spores from inside an envelope is the bellows action of the processing machines, which may draw spores on or into following envelopes”, they say. On May 30 the Pentagon announced that much of the nation’s anthrax vaccine stock (500 000 doses) will be reserved for civilian use in the event of attack. Plans to vaccinate the armed forces have been abandoned, except for those most at risk. Scientists at Merck Research Laboratories (Rahway, NJ, USA) have developed an assay that could lead to the discovery of an inhibitor of Bacillus anthracis lethal factor (LF), one of three components of anthrax toxin. “The pivotal role of LF (a metalloprotease) in the virulence of the toxin suggests that inhibitors of the enzyme may provide protection against cytotoxicity”, the authors explain (Proc
FBI to test US Army over anthrax letters.
Natl Acad Sci USA 2002; 99: 6603–06). “We decided to target the protease activity of LF because mutation in critical residues in the active site of LF abolishes protease activity and cell
toxicity”, says Merck’s Jeff Hermes. The new, simple assay, based on the cleavage of a labelled peptide by LF, “allows rapid screening of large numbers of potential LF inhibitors with nanomolar levels of the enzyme”. Itzhak Brook (US Armed Forces Radiobiology Research Institute) thinks this approach might lead to the development of an adjuvant treatment to be added to antibiotic therapy. “And if it could rid the body of already produced deadly toxin, it could offer a means to reverse the currently irreversible and rapidly deteriorating condition of the victims.” Dorothy Bonn
Modified mosquitoes in malaria research Production of mosquitoes genetically modified to block malaria transmission “is a proof of principle and as such is a milestone in malaria research”, according to Gareth Lycett and Fotis Kafatos (European Molecular Biology Laboratory, Heidelberg, Germany). But experts agree that many further steps are needed before field trials should be considered. “Many of the tools required for the genetic manipulation of mosquito competence have been developed”, notes the team led by Marcelo JacobsLorena (Case Western Reserve University, OH, USA). The hope is that release of transgenic mosquitoes engineered to disrupt the malaria lifecycle might reduce disease prevalence. One crucial stage in plasmodium transmission involves parasites in a mosquito blood meal traversing the midgut epithelium to reach the salivary glands—a process now thought to be receptor-mediated. The researchers screened a library for peptides that bind to salivary and midgut epithelium. SM1 blocks parasite invasion when administered to mosquitoes, so the team transformed mosquitoes with a gene construct that increased expression of the peptide after mosquito feeding. In several trials of feeding on infected mice, transformed
mosquitoes carried on average half the number of malarial oocysts than untransformed mosquitoes. Moreover, most transformed mosquitoes could not transmit the parasite to uninfected mice. The team report that the SM1encoding DNA is stably inherited by offspring (Nature 2002; 417: 452–55). Studies first need to be replicated using wild strains of mosquitoes and human malarial parasites, and Yeya Touré (WHO Molecular Entomology Committee) notes that “it is important to show that transformation is very stable under laboratory conditions and very strong—we need to be able to achieve almost 100% blockage of malaria transmission”. This will reduce the chance of developing resistance but is likely to require multiple antiparasitic genes, the researchers suggest. Later, says Touré, studies need to show stable gene expression in each mosquito under field conditions, while safety and other issues are worked out. “The malaria-research community is strongly against premature field experiments”, note Lycett and Kafatos. Touré anticipates that field trials are at least 8–10 years away, and stresses that any decision to embark on them must be made by the malaria-endemic countries. Kelly Morris
THE LANCET Infectious Diseases Vol 2 July 2002
http://infection.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.
388
Rights were not granted to include this image in electronic media. Please refer to the printed journal. AP
The perpetrator of the US “anthrax letters” is still at large, and cynics might say that plans to submit employees at two US Army research laboratories to lie-detector tests smack of desperation. But Barbara Rosenberg (State University of New York, NY, USA), who has followed the investigation closely, claims that the Federal Bureau of Investigation (FBI), which will test up to 200 current and former employees at Fort Detrick and Dugway, could have a suspect. “They may be looking for a specific piece of information and are deflecting suspicion by the broad net.” 22 cases of anthrax were reported after the attacks last September and October, and five people (all with inhaled anthrax) died. But the prompt distribution of antibiotics to postal workers and others at risk probably averted many more cases, say US researchers. Glenn Webb (Vanderbilt University, Nashville, TN, USA) and Martin Blaser (New York University, NY, USA), who constructed a mathematical model to simulate the spread of spores, calculate that six anthrax-laden letters (four were recovered) contaminated about 5000 other pieces of mail with between 10 and 10 000 spores each (Proc Natl Acad Sci USA 2002; 99: 7027–32). “A plausible mechanism for release of the spores from inside an envelope is the bellows action of the processing machines, which may draw spores on or into following envelopes”, they say. On May 30 the Pentagon announced that much of the nation’s anthrax vaccine stock (500 000 doses) will be reserved for civilian use in the event of attack. Plans to vaccinate the armed forces have been abandoned, except for those most at risk. Scientists at Merck Research Laboratories (Rahway, NJ, USA) have developed an assay that could lead to the discovery of an inhibitor of Bacillus anthracis lethal factor (LF), one of three components of anthrax toxin. “The pivotal role of LF (a metalloprotease) in the virulence of the toxin suggests that inhibitors of the enzyme may provide protection against cytotoxicity”, the authors explain (Proc
FBI to test US Army over anthrax letters.
Natl Acad Sci USA 2002; 99: 6603–06). “We decided to target the protease activity of LF because mutation in critical residues in the active site of LF abolishes protease activity and cell
toxicity”, says Merck’s Jeff Hermes. The new, simple assay, based on the cleavage of a labelled peptide by LF, “allows rapid screening of large numbers of potential LF inhibitors with nanomolar levels of the enzyme”. Itzhak Brook (US Armed Forces Radiobiology Research Institute) thinks this approach might lead to the development of an adjuvant treatment to be added to antibiotic therapy. “And if it could rid the body of already produced deadly toxin, it could offer a means to reverse the currently irreversible and rapidly deteriorating condition of the victims.” Dorothy Bonn
Modified mosquitoes in malaria research Production of mosquitoes genetically modified to block malaria transmission “is a proof of principle and as such is a milestone in malaria research”, according to Gareth Lycett and Fotis Kafatos (European Molecular Biology Laboratory, Heidelberg, Germany). But experts agree that many further steps are needed before field trials should be considered. “Many of the tools required for the genetic manipulation of mosquito competence have been developed”, notes the team led by Marcelo JacobsLorena (Case Western Reserve University, OH, USA). The hope is that release of transgenic mosquitoes engineered to disrupt the malaria lifecycle might reduce disease prevalence. One crucial stage in plasmodium transmission involves parasites in a mosquito blood meal traversing the midgut epithelium to reach the salivary glands—a process now thought to be receptor-mediated. The researchers screened a library for peptides that bind to salivary and midgut epithelium. SM1 blocks parasite invasion when administered to mosquitoes, so the team transformed mosquitoes with a gene construct that increased expression of the peptide after mosquito feeding. In several trials of feeding on infected mice, transformed
mosquitoes carried on average half the number of malarial oocysts than untransformed mosquitoes. Moreover, most transformed mosquitoes could not transmit the parasite to uninfected mice. The team report that the SM1encoding DNA is stably inherited by offspring (Nature 2002; 417: 452–55). Studies first need to be replicated using wild strains of mosquitoes and human malarial parasites, and Yeya Touré (WHO Molecular Entomology Committee) notes that “it is important to show that transformation is very stable under laboratory conditions and very strong—we need to be able to achieve almost 100% blockage of malaria transmission”. This will reduce the chance of developing resistance but is likely to require multiple antiparasitic genes, the researchers suggest. Later, says Touré, studies need to show stable gene expression in each mosquito under field conditions, while safety and other issues are worked out. “The malaria-research community is strongly against premature field experiments”, note Lycett and Kafatos. Touré anticipates that field trials are at least 8–10 years away, and stresses that any decision to embark on them must be made by the malaria-endemic countries. Kelly Morris
THE LANCET Infectious Diseases Vol 2 July 2002
http://infection.thelancet.com
For personal use. Only reproduce with permission from The Lancet Publishing Group.