Hormones and drugs that control blood pressure also control malaria infection

September 18, 2003

CHICAGO --- Hormones that regulate cardiovascular function have been discovered to influence malaria infection. As a consequence, beta-blockers, which are safe, inexpensive and commonly prescribed drugs used worldwide to treat high blood pressure, are effective against the deadliest and most drug-resistant strain of malaria parasites.

These findings, by Kasturi Haldar, Jon Lomasney, Travis Harrison and colleagues at the Feinberg School of Medicine at Northwestern University, were reported in an article in the Sept. 19 issue of the journal Science.

Rather than targeting the parasite that causes malaria, an approach that has resulted in mounting resistance to a variety of antimalarial drugs, Haldar and co-researchers focused instead on identifying and blocking the process by which red blood cells allow parasite entry.

Haldar is Charles E. and Emma H. Morrison Professor in Pathology and professor of microbiology-immunology at the Feinberg School.

Malaria is a blood-borne illness transmitted by mosquitoes. Forty percent of the world's population lives at risk for infection and between 200 and 300 million people are afflicted each year, particularly in underdeveloped and impoverished tropical and sub-Saharan countries.

The most virulent form of the four human malaria parasite species, Plasmodium falciparum, kills over 1 million children each year and is responsible for 25 percent of the infant mortality in Africa, according to latest estimates by the World Health Organization. Recently, however, P. falciparum also has been confirmed as the cause of over 50 cases of malaria among the 625 U.S. troops sent into Liberia. Another strain of malaria, P. vivax, has been confirmed in seven cases in Florida.

World wide there has been a resurgence of malaria in recent years, due mainly to the parasite's growing resistance to drugs and the mosquito's acquired resistance to insecticides developed to control the spread of the disease.

Athough malaria infects both liver and blood cells, it is during the "blood stage" of malaria -- when infected red blood cells that are "incubating" thousands of parasites literally explode and release more parasites into the blood stream -- that the symptoms of malaria occur. These symptoms include fever and flu-like symptoms such as chills, headache, muscle aches and fatigue. Immunity is slow to develop, and left untreated, malaria may be fatal, taking its greatest toll in children.

Blocking blood-stage infection by preventing the entry of the P. falciparum parasite into red blood cells provides the most direct way to control infection and quell the symptoms of malaria. But how red blood cells allow the entry of malaria parasites was unknown.

Travis Harrison, who is first author on the article and a research assistant in Haldar's laboratory, found that G proteins in the red blood cell may be used by the parasite.

G proteins are essentially "go-betweens," or transducers, that translate signals from hormones, neurotransmitters and other substances and in turn activate such cell processes as gene transcription, motility, secretion and contractility. G proteins have been intensively studied in a wide range of cells, but their functions in oxygen-carrying red blood cells are only beginning to be understood, Haldar said.

Research by Haldar and co-investigators showed that a G protein subunit, called Gs, concentrates around the malaria parasite during infection of the red blood cell.

Using special peptides, compounds similar to proteins, that inhibited the interaction of Gs protein, the researchers were able to show in several laboratory models of malaria that blocking the Gs signal resulted in decreased malaria infection.

Two major Gs-associated receptors, the beta-adrenergic and the adenosine receptors, are known to be present in red blood cells. Stimulating these receptors with a drug called an agonist increased infection of P. falciparum, while beta-blockers, which are antagonists, prevented the P. falciparum parasite from entering red blood cells.

"The use of beta-receptor antagonists, such as those already used to treat high blood pressure, may provide new approaches for treating malaria. Since beta-blockers are directed against a host target, there is low chance of rapid emergence of resistance to these drugs. Moreover, they may be used in combination therapy with existing drugs against parasite targets," Lomasney and Haldar said.

"This finding offers the opportunity to use well-characterized, inexpensive drugs for a new, much-need application and the impetus for the development of new beta-blockers and other drugs to be tested for effectiveness against malaria," they said.

Haldar's co-authors on this study were Travis Harrison, Benjamin U. Samuel, and Thomas Akompong, departments of pathology and of microbiology-immunology, Feinberg School of Medicine; Heidi Hamm, Vanderbilt University, Nashville; Narla Mohandas, New York Blood Center, New York; and Jon W. Lomasney professor of pathology, Feinberg School of Medicine.
-end-
Grants from the National Institutes of Health supported this study.

KEYWORDS: malaria, Plasmodium falciparum, G protein, beta-blockers

CONTACT: Elizabeth Crown at (312) 503-8928 or at e-crown@northwestern.edu
Broadcast Media: Tamara Kerrill at (847) 491-4888 or tlk@northwestern.edu

Northwestern University

Related Malaria Articles from Brightsurf:

Clocking in with malaria parasites
Discovery of a malaria parasite's internal clock could lead to new treatment strategies.

Breakthrough in malaria research
An international scientific consortium led by the cell biologists Volker Heussler from the University of Bern and Oliver Billker from the UmeƄ University in Sweden has for the first time systematically investigated the genome of the malaria parasite Plasmodium throughout its life cycle in a large-scale experiment.

Scientists close in on malaria vaccine
Scientists have taken another big step forward towards developing a vaccine that's effective against the most severe forms of malaria.

New tool in fight against malaria
Modifying a class of molecules originally developed to treat the skin disease psoriasis could lead to a new malaria drug that is effective against malaria parasites resistant to currently available drugs.

Malaria expert warns of need for malaria drug to treat severe cases in US
The US each year sees more than 1,500 cases of malaria, and currently there is limited access to an intravenously administered (IV) drug needed for the more serious cases.

Monkey malaria breakthrough offers cure for relapsing malaria
A breakthrough in monkey malaria research by two University of Otago scientists could help scientists diagnose and treat a relapsing form of human malaria.

Getting to zero malaria cases in zanzibar
New research led by the Johns Hopkins Center for Communication Programs, Ifakara Health Institute and the Zanzibar Malaria Elimination Program suggests that a better understanding of human behavior at night -- when malaria mosquitoes are biting -- could be key to preventing lingering cases.

Widely used malaria treatment to prevent malaria in pregnant women
A global team of researchers, led by a research team at the Liverpool School of Tropical Medicine (LSTM), are calling for a review of drug-based strategies used to prevent malaria infections in pregnant women, in areas where there is widespread resistance to existing antimalarial medicines.

Protection against Malaria: A matter of balance
A balanced production of pro and anti-inflammatory cytokines at two years of age protects against clinical malaria in early childhood, according to a study led by ISGlobal, an institution supported by ''la Caixa'' Foundation.

The math of malaria
A new mathematical model for malaria shows how competition between parasite strains within a human host reduces the odds of drug resistance developing in a high-transmission setting.

Read More: Malaria News and Malaria Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.