The animal that kills humans worldwide most are not the shark, lion or grizzly bear: He is the mosquito. In 2012, about 0 million people have developed malaria after being bitten by the insect; about 0,000 deaths, 0% of them in Africa and most of the children under 5 slippery parasite that causes the disease has long defied the efforts to develop a vaccine. But a study of the children of resistant malaria in Tanzania has turned to an antibody that will stop the infection in its tracks. Based on the action of this antibody, scientists have developed a preliminary vaccine shows promise in mice.
The parasite that causes malaria is a single-celled organism called Plasmodium . He might as well have been designed by an evil mad scientist, said Jonathan Kurtis, an immunologist at Brown University and lead author of the new study. When an infected mosquito bites a human female, the microbe enters the blood of the victim and made to the liver, where it multiplies by tens of thousands. By the liver, it rises in the blood, to infect and multiply within red blood cells. Finally, he broke again in a form called schizont - infect more blood cells and re-enter the bloodstream to infect the next hungry mosquitoes, in whose body it requires a more complex cycle. Step bursting-out, which occurs about every 24 hours, produces fever, chills and pain that make the patient miserable. "It's like the worst flu you've ever had," said Kurtis.
Because different proteins are produced at each stage of the microbe cycle Plasmodium presents a moving target potential vaccines. So far, the most promising candidate is dubbed RTS, S. in a clinical trial phase III reported at the end of 2012, this vaccine, which works by reducing the amount of infected liver cells, has led to a 50% decrease in the number of severe symptoms and parasite blood levels in children aged 5 months to 17 months.
But even in areas where malaria is hit, some people symptoms or not mild at all, and they can show only minimal levels of parasite in blood samples. to see why, Kurtis and his colleagues compared the blood of people who are resistant to those that are not. with National Institutes of Health colleagues, Harvard Medical School and the University of Washington, the team examined a group of children in Tanzania who had been studied since shortly before birth. First researchers collected blood samples from 23 2-year-old children (the age at which resistance to malaria usually develops); 12 were resistant to the disease, as evidenced by the small number of parasites in their blood. To see if these 12 had unique antibody protection, the team checked the-plasma, the liquid containing the antibodies clear the blood of all the children against a set of Plasmodium genes known to be activated when the parasite infects the blood.
Among the proteins produced by about 3 million possible genes, antibodies in the blood of children locked without symptoms only three, the team announced today online science . A gene produces a protein known to assist the parasite infects red blood cells and is already being investigated as a target for a vaccine. When another gene, previously unknown to investigators worked on the structure of its proteins and studied in tissue culture has proved to be just the opposite. The protein helped the schizont leave cell infected blood
"At first it did not make sense. We checked the results three times, "says Kurtis. Apparently, the antibodies against this protein protected against malaria by trapping inside the schizont erythrocyte - and not preventing it from infecting new. The researchers checked the largest group of participants in the study. From about 450 infants from about 6% had antibodies against the protein; none of these children developed severe malaria (defined as difficulty breathing, convulsions, high fever, blood sugar, or severe anemia). When the researchers checked blood samples from a group of teenagers in an unrelated study in Kenya, they found that the blood containing the antibody were only about half as many parasites as have samples made without it.
Finally, Kurtis and his colleagues used antibodies to develop a vaccine candidate that gave mice infected with a particularly deadly form of malaria. Vaccinated animals lived almost twice as long, and in one case, had about a quarter as many parasites untreated mice. Kurtis said a vaccine that exploits the ability of the antibody to imprison Plasmodium in the blood cells would have more time to work with than trying to block re-infection. "The parasite infects a new cell in about 15 seconds, so a vaccine to prevent this action would have to work immediately," he said. Infected blood cells are eliminated by the immune system, he said.
" it is a very elegant approach, "said David Lanar, parasitology at Walter Reed Army Institute of research in Silver Spring, Maryland. After the few seconds Plasmodium takes to invade a red blood cell infected earlier, it is hidden from antibodies, he said. When the new cell is infected, however, the membrane becomes leaky for several hours before schizonts erupt again, giving larger molecules, such as an antibody or vaccine a chance to get. A vaccine that keeps them trapped schizonts shift the chronology in favor of the patient, he said.
A vaccine based on this approach would need to work in tandem with others to different parts of the cycle Kurtis warns. The strategy would not eliminate the parasite, only reduce to levels that can relieve the symptoms, he says.
"At this stage of the game, which is a good thing," said Lanar. No treatment breaks the cycle of infection between humans and mosquitoes, he said. The best thing is to reduce the number of clinical symptoms. "The number of parasites in the blood determines sick, you will be."
A vaccine would be particularly effective in people who have never been exposed to the disease before, or who have lost their immunity from childhood, leaving malaria affected areas, Lanar said, because these groups are more vulnerable to very serious forms of the disease than those who are partially immunized. As a next step, the group of Kurtis conducting a study of the vaccine in non-human primates. If it is successful, the team will start clinical trials in humans
* Update, May 23, 12:12 :. This article has been updated to clarify that the red blood cell membrane leaky push to allow Schizonts escape, it provides an opportunity for treatments to enter
* Correction, May 27, 4:57 p.m. :. An earlier version of the caption of this article incorrectly described the image. The malaria parasite takes most of the red blood cell; dark, rod-shaped forms are bits of hemoglobin that has digested.
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