Researchers at Case Western Reserve University and Cleveland Clinic Lerner Research Institute have discovered recent genetic mutations in a parasite that causes over 100 million cases of malaria annually-changes that may render tens of millions of Africans who had been considered resistant, susceptible to infection.
Peter A. Zimmerman, professor of international health, biology and genetics at the Case Western Reserve School of Medicine, and David Serre, a scientific staff member of the Genomic Medicine Institute at Lerner and assistant professor of genomics at Case Western Reserve, report their findings at the American Society of Tropical Medicine and Hygiene annual meeting today (11/15).
They and fellow researchers describe the changes in the Plasmodium vivax genome in papers scheduled to be published in the journal PLoS Neglected Tropical Disease on Nov. 21 and Dec. 5.
To learn the functions of the mutations, and whether the parasite is evolving around a natural defense, Zimmerman and Serre have received a $3.5 million grant from the National Institute of Allergy and Infectious Disease at the National Institutes of Health. They will begin their field study in early 2014.
“We’ve found a duplication of a gene known to enable the parasite to infect red blood cells and two possible additional components to a more complex red cell invasion mechanism,” Zimmerman said
Researchers have long thought that P. vivax infects a person one way: a protein on the parasite, called the Duffy binding protein, latches onto a Duffy receptor on the surface of the person’s red blood cell and works itself through the membrane. People who lack the receptor are called Duffy negative and are resistant to infection.
But, during the last decade, reports of cases of Duffy negative patients with P. vivaxinfections have been on the rise in several parts of the world.
P. vivax has been called benign malaria because it is less lethal than malaria caused byPlasmodium falciparum. But unlike its cousin, P. vivax can hide from treatment in a host’s liver and repeatedly emerge to cause relapses of debilitating headaches, nauseaand fever. This chronic malaria often triggers a cycle of poverty for sufferers left unable to work for long periods. By weakening the immune system, the disease contributes to death.
The Malaria Atlas Project estimates 2.5 billion people worldwide are at risk for P. vivaxmalaria.
P. vivax does not grow well in the laboratory, so to try to understand how the parasite lives and operates, the researchers gathered samples from malaria patients and focused on its genome.
They found a duplication of the Duffy binding protein in half of 189 P. vivax infection samples taken in Madagascar. Other researchers’ prior efforts to sequence the P. vivaxgenome missed the duplication but all indications are it’s a recent change, Serre said.
“The way we date duplications is to compare differences between the two parts: the more different they are, the older they are,” he explained. “They accumulate mutations. The two parts of this duplication have, among 8,000 base pairs, only one difference.”
Often a second copy of a gene enables an organism to outmaneuver a defense, Serre continued. “Instead of making a supergene, a duplication is simpler for nature.”
The researchers suspect the mutation is spreading from Madagascar through travelers. They found the duplication in less than 10 percent of samples from Cambodia and Sudan.
The new components found on the P. vivax genome are two proteins that closely resemble binding proteins used by related malaria parasites to enter immature and mature red blood cells. Both were present in samples from Cambodia, Brazil, Mauritania and North Korea.
To continue reading this article please visit the original article in: News Medical
