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Pathway Discovery May Lead to Malarial Drugs and Vaccines

September 4, 1991

PHILADELPHIA (AP) _ Antibodies can attack the malaria parasite through a newly discovered pathway inside infected cells, a finding that scientists say could lead to drugs specially designed to prevent the critical stage of the disease.

One immunologist working to develop vaccines for the U.S. Army called the work ″elegant and the first direct demonstration of the open channels″ through which antibodies could assault the parasite, stopping the disease early in its course.

″This work should be a real boost for scientists working on vaccines to protect people against″ the disease, said Dr. J. David Haynes of the Walter Reed Army Institute of Research.

According to the scientists at Thomas Jefferson University, drugs attached to antibodies could slip through the pathway, called the parasitophorus duct, into the parasite and kill it. The researchers’ report appears in Thursday’s issue of the journal Nature.

Malaria, which strikes about 300 million people in the world annually, can cause chills, fever, headache, anemia and, in severe cases, death. When an infected Anopheles mosquito sucks blood from a victim, it introduces into the bloodstream a parasite called the malaria sporozoite.

The parasite multiplies in the liver and then erupts back into the bloodstream with millions of new parasites.

Researchers had thought that the parasite was completely embedded within the red blood cell and was sealed inside the cell, said lead author Theodore Taraschi.

According to that view, antibodies would only be able to act when the red blood cell membrane was dissolved by the parasite, exposing it for a short period of time before the parasite invaded another cell.

″Because the parasite was considered to be in a protected environment, researchers did not think it possible to selectively attack malaria-infected red blood cells during this developmental stage,″ Taraschi said.

But based on recent research, that view is now doubtful, scientists said.

With the knowledge that the pathway provides direct access to the parasite developing within the red blood cell, Taraschi said scientists could have the whole 48-hour life cycle of the infected cell to try to kill the parasite.

Taraschi said he believes that the duct normally is small enough to prevent the immune system from sending in components to kill the parasite, but the researchers are not sure how some people survive several bouts of malaria and develop limited immunity to the disease.

Malaria occurs mostly in tropical areas, where the mosquito is most common. The disease, which kills about 1 percent of its victims, can be treated by a number of drugs, but some forms of the disease are resistant to treatment.

Taraschi said it would be premature to discontinue the current line of potential vaccines trying to attack the outside of the red blood cell to get at the parasite, as it’s too early to tell where the Jefferson work will lead.

One parasitologist, John Barnwell of New York University, said the finding of the pathway was ″an important observation,″ but said it was questionable how well it could be manipulated to treat malaria.

″How effective that will be will take a lot more experimentation,″ Barnwell said, ″but it opens up a new way of looking at the parasite.″

But Haynes was more optimistic about the future development of drugs targeted to attack the parasite through the duct.

″We can now confidently develop drugs, antibodies and vaccines to attack many (targets) present on the malaria parasite while it is still developing inside the red blood cell,″ he said.

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