How Ebola paralyses the immune system

                                    

  

Deaths in Africa from Ebola reached 1013 earlier this week, with 1848 cases reported. The World Health Organization, which had declared the outbreak a global health emergency, gave ethical clearance to treat patients with the untested drug ZMapp. With all the activity on the ground in Africa – not to mention the amount of media coverage – it was something of a surprise to find that the specific way Ebola kills has only just been discovered.

In essence, the virus blocks what would usually be an instant response to infection, paralysing the body's entire immune system. Gaya Amarasinghe of the Washington University School of Medicine in St Louis, Missouri, and colleagues say the breakthrough could guide the development of new treatments.

There are no vaccines for Ebola, and until recently ZMapp had only been tested in monkeys. Normally, the body responds to infections by producing a substance called interferon, which acts as a fast-track message to white blood cells, telling them to mobilise genes and proteins. Amarasinghe's team found that the Ebola virus produces a substance called VP24, which blocks the channel through which interferon usually travels, crippling the immune system.

With its usual protective mechanisms knocked out, a cell is then defenceless against the virus. Amarasinghe says that drugs which target VP24 might provide alternative ways to combat the virus. Other virologists say that neutralising VP24 alone might not be enough because, like many other viruses, Ebola has other methods to thwart interferon's distress signals. "The rest of the parts of the virus can still work and replicate without VP24," says Ben Neuman of the University of Reading, 

Neuman says it might be difficult to find drugs that target VP24 exclusively without causing side effects. But he says that there are already drugs that target a similar molecule in the hepatitis C virus, called NS5A, without damaging healthy cells. "They're astoundingly effective," he says. "So in theory it could be done for VP24, but it won't be cheap or easy."

Options for treatments are now urgently needed. Liberia this week received a small amount of ZMapp, a mixture of three monoclonal antibodies, but only enough to treat two people. The company that makes the drug, Mapp Biopharmaceutical in San Diego, California, says only very limited supplies of ZMapp are available. So far it has been used on two infected US aid workers, who both showed signs of improvement. But yesterday it emerged that it had failed to save the life of a Spanish priest, Miguel Pajares, who was infected in Liberia.

The WHO declares a Public Health Emergency of International Concern when an outbreak crosses borders and poses an unusual threat. It has made such a declaration only twice before: for swine flu in 2009 and the polio resurgence in Pakistan earlier this year. The Ebola declaration asserts that "a coordinated international response" is required to stop further spread, because of "weak health systems in the most at-risk countries".

                                                                        

Faerie World

                                                               

1757, Wales: a well-known cleric, when a young child, was playing in a field with several other children. There at football-field distance away, were several dwarf/gnome-sized creatures, apparently in couples, all dressed in red and flourishing white kerchiefs. One of the males spotted the children and rushed at them, nearly catching them. The child described the gnome as having an "ancient, swarthy, and grim complexion". The other gnomes were shouting at the chaser the whole time in a language which none of the children could understand. Dr. Edward Williams, the cleric, summarized his encounter in a charming way: "I am forced to class it among my unknowables". One suspects that we will have to do the same as to this whole menagerie of beings.

 Mid-19th century, UK: The famous historian, Reverend Sabine Baring-Gould, had an experience when he was very young in which he saw "legions of dwarves" two feet tall keeping pace beside the carriage in which he was riding and trying to climb up on the horses, laughing all the way. His parents saw nothing at all.

  

 Mid-19th century, Yorkshire: If that youth experience might be waved off as some oddity of the very young, S B-G's wife had an encounter when she was 15. She was walking down a lane when she came across "a little green man, perfectly made, who looked at her with beady black eyes". [I am almost certain that the phrase "little green man" refers to him being dressed in green in such stories]. This frightened her badly and she ran home.

 Late-19th century, UK. And S B-G had a further encounter in his family. One of his sons was fetching peas in their garden when he came across a member of the Good People wearing a green jacket, brown knee britches, and a red cap [just about our ideal garden gnome]. He had a weathered old face, gray beard and stark black eyes. His stare unnerved the son and he ran inside. Doubtless, Sabine Baring-Gould had little reason to disbelieve him.

Probably late 1800s, Wicklow Mountains, Ireland: This one will stretch you on how far you want to go. A farmer and his wife worked their farm just after their marriage and along came a winter's snow season. The man saw a Wee Folk outside and "brought him in and sat him on the dresser". [peculiar to say the least, but I'm not of the times....] . The farmer was telling this story to some folklore luminaries visiting him [including Lady Gregory and William Butler Yeats]. He said that the being stayed with them for about a week. His wife promptly interrupted him to remind him that it was two to three weeks. [!!!].The being was described as 15" high and very friendly. He was dressed almost entirely in red: cap to checked coat to skirt to stockings. The being had to be fed by spoon by the farmer himself. His meals consisted of bread in milk, it seems. His appearance was young and fresh at first, but rapidly he began to appear old and wrinkled [yep, I remember the Changeling legends]. He was no secret locally, and tipsy knuckleheads from the town pub would come over and they would laugh at him there on his dresser.One day the farmer saw another like being outside. That being was dressed in a grayish theme and looked more feminine. When the farmer remarked upon this to his wife, the Little Man who had never spoken, cried out: "That's Geoffrey-a-Wee that's coming for me!!". At that, he leapt down from his dresser and bounded out the door. If this story is true [two interviewed witnesses and several well-known interviewers], then just about anything goes as far as the typical historic folkloric fairy stories go. Encounters passing in the lane are one thing; stay-around family house gnomes are another. And the changeling-similar thing.... it is almost a line-in-the -sand over which the mind resists crossing.

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