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Old Stain in a New Combination
May 21, 2009Methylene blue can curb the spread of malaria parasites when administered together with new malaria medication / Heidelberg researchers publish in PLoS One
New combinations of agents based on the oldest synthetic malaria drug, the methylene blue stain, can curb the spread of malaria parasites and make a significant contribution to the long-term eradication called for by the international "Roll Back Malaria Initiative." In a study on 160 children with malaria in Burkina Faso, specialists in tropical medicine from the Heidelberg University Hospital have shown that in combination with newer malaria drugs, methylene blue prevents the malaria pathogen in infected persons from being re-ingested by mosquitoes and then transmitted to others and is thus twice as effective as the standard therapy. The results of the study were published in May 2009 in the online journal PLoS One.
Malaria is still one of the deadliest tropical diseases. Every year, 300 million people are infected with malaria and more than one million of them die or suffer severe brain damage. Children under five years are particularly susceptible.
Malaria pathogens need humans and mosquitoes
When the Anopheles mosquito bites, the malaria parasites (plasmodia) in the saliva of the mosquito enter the human body, reproduce in liver cells and then attack the red blood cells. This causes severe symptoms such as high fever or anemia; children in particular can even fall into a coma. During reproduction in the human body, some parasites develop into special reproductive cells, gametocytes. If they are ingested by an Anopheles mosquito, they continue to reproduce in the mosquito. The cycle is complete.
The gametocytes are the key for the spread of malaria by the Anopheles mosquito. Common malaria drugs known as artemisinins block reproduction of the parasites in the human body and reduce the number of gametocytes in blood by half. This makes the transmission of the parasite to the mosquito more difficult but does not completely prevent it. "We urgently need alternative therapies that are effective against the gametocytes and thus improve the control of malaria," states Professor Dr. Olaf Müller, Project Head in the Department of Tropical Medicine and Public Health of the Hygiene Institute at the University of Heidelberg.
Methylene blue prevents transmission to mosquitoes
The appropriate component for such an alternative is a proven agent - the methylene blue stain which has been given to malaria patients since the end of the 19th century has proven to be safe, well tolerated, and effective in combination with various malaria medications.
In the current study in Burkina Faso with 160 malaria patients between the ages of six and ten the Heidelberg scientists tested the effect of combination therapies with artemisinins and methylene blue on gametocytes in the blood. One group of the children received the standard treatment, consisting of a combination of artesunate and amodiaquine. Two other groups received methylene blue combined with one of the two drugs respectively. The physicians checked the number of gametocytes in blood samples three, seven, and fourteen days after the start of therapy.
Combination therapy is twice as effective as standard therapy
It was shown that both combination therapies are twice as effective against gametocytes as the standard therapy - these parasites had almost completely disappeared in the first few days. "Methylene blue not only inhibits the formation of the reproductive forms, but also destroys already existing cells," explains Professor Müller. "In this way, the profiles of methylene blue and artemisinins, which quickly and effectively eliminate the parasites in the red blood cells, complement each other." Since the study group from Heidelberg has used methylene blue in Western Africa for years, it has already been adequately clinically tested - severe or frequent side effects did not occur. Especially important is that the combination makes it more difficult for resistance to artemisinins to develop.
The study is a project in the special research area SFB 544 "Control of Tropical Infectious Diseases" of the German Research Association, to which scientists and physicians from the university hospital and other Heidelberg research centers belong.
Heidelberg University Hospital
Malaria pathogens need humans and mosquitoes
When the Anopheles mosquito bites, the malaria parasites (plasmodia) in the saliva of the mosquito enter the human body, reproduce in liver cells and then attack the red blood cells. This causes severe symptoms such as high fever or anemia; children in particular can even fall into a coma. During reproduction in the human body, some parasites develop into special reproductive cells, gametocytes. If they are ingested by an Anopheles mosquito, they continue to reproduce in the mosquito. The cycle is complete.
The gametocytes are the key for the spread of malaria by the Anopheles mosquito. Common malaria drugs known as artemisinins block reproduction of the parasites in the human body and reduce the number of gametocytes in blood by half. This makes the transmission of the parasite to the mosquito more difficult but does not completely prevent it. "We urgently need alternative therapies that are effective against the gametocytes and thus improve the control of malaria," states Professor Dr. Olaf Müller, Project Head in the Department of Tropical Medicine and Public Health of the Hygiene Institute at the University of Heidelberg.
Methylene blue prevents transmission to mosquitoes
The appropriate component for such an alternative is a proven agent - the methylene blue stain which has been given to malaria patients since the end of the 19th century has proven to be safe, well tolerated, and effective in combination with various malaria medications.
In the current study in Burkina Faso with 160 malaria patients between the ages of six and ten the Heidelberg scientists tested the effect of combination therapies with artemisinins and methylene blue on gametocytes in the blood. One group of the children received the standard treatment, consisting of a combination of artesunate and amodiaquine. Two other groups received methylene blue combined with one of the two drugs respectively. The physicians checked the number of gametocytes in blood samples three, seven, and fourteen days after the start of therapy.
Combination therapy is twice as effective as standard therapy
It was shown that both combination therapies are twice as effective against gametocytes as the standard therapy - these parasites had almost completely disappeared in the first few days. "Methylene blue not only inhibits the formation of the reproductive forms, but also destroys already existing cells," explains Professor Müller. "In this way, the profiles of methylene blue and artemisinins, which quickly and effectively eliminate the parasites in the red blood cells, complement each other." Since the study group from Heidelberg has used methylene blue in Western Africa for years, it has already been adequately clinically tested - severe or frequent side effects did not occur. Especially important is that the combination makes it more difficult for resistance to artemisinins to develop.
The study is a project in the special research area SFB 544 "Control of Tropical Infectious Diseases" of the German Research Association, to which scientists and physicians from the university hospital and other Heidelberg research centers belong.
Heidelberg University Hospital
Malaria Current Events and Malaria News RSSPATH Malaria Vaccine Initiative shares strategy for developing 'next-generation' malaria vaccines
Marking its tenth anniversary year, the PATH Malaria Vaccine Initiative (MVI) today unveiled a new strategy that sets the stage for an aggressive push targeting the long-term goal of eliminating and eradicating malaria. Malaria is one of the world's deadliest infectious diseases, killing nearly 900,000 people a year, most of them children in sub-Saharan Africa.
Global challenges and opportunities in fighting HIV/AIDS and neglected diseases
Responding to the HIV/AIDS pandemic and tackling so-called neglected tropical diseases are the focus of the November/December 2009 edition of Health Affairs.
Media availability: The role of biomedical research in malaria eradication
Although malaria has been controlled in many local and regional populations, the permanent elimination of malaria parasites throughout the world remains an elusive goal, and the disease continues to claim nearly one million lives each year.
Ineffective monotherapies common in high-burden malarious countries
ACTwatch, a research project led by PSI, in collaboration with the London School of Hygiene and Tropical Medicine, released evidence today that indicates that artemisinin combination therapy, the most effective medicines for treating malaria, continue to have a significantly low presence on the market among populations considered to be most at risk.
New tool promises more accurate antimalarial drug dosing
Scientists at LSTM have developed a tool to support the development of appropriate age-based dosing regimens for malaria drugs.
Cell phones become handheld tools for global development
Mobile phones are on the verge of becoming powerful tools to collect data on many issues, ranging from global health to the environment.
Exon-skipping drug prevents muscle wasting, maintains muscle function in dystrophin deficient mice
An exon skipping PPMO has demonstrated dramatic effects in the prevention and treatment of severely affected, dystrophin and utrophin-deficient mice, preventing severe deterioration of the treated animals and extending their lifespan.
UM School of Medicine researchers find extreme genetic variability in malaria parasite
Researchers at the University of Maryland School of Medicine Center for Vaccine Development (CVD) have charted the extreme genetic differences that occur over time in the most dangerous malaria parasite in the world.
Outfoxing pox: Developing a new class of vaccine candidates
In the annals of medicine, Edward Jenner's 1796 vaccination of a young boy against smallpox, using fluid from cowpox blisters, remains a landmark case. In a new study, Kathryn Sykes, a researcher at Arizona State University's Biodesign Institute and her colleagues have taken a fresh look at cowpox.
Ironing out the genetic cause of hemoglobin problems
A gene with a significant effect on regulating hemoglobin in the body has been identified as part of a genome-wide association study, which looked at the link between genes and hemoglobin level in 16,000 people.
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