Traditional Treatments for Malaria

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QUESTION

What are some traditional treatments for malaria?

ANSWER

Many different cultures have had their own traditional ways of treating malaria. Perhaps the two best known come from the native tribes in the Western Amazon basin and the ancient Chinese.

Tribes in the Amazon used the bark of a shrub called Cinchona to treat fevers and shivering; Spanish priests in this region observed traditional Quechua healers using this bark and started using it themselves to treat the fevers associated with malaria. Many centuries later, the active ingredient from this bark was isolated and called quinine, which is still used in the treatment of malaria today.

In ancient China, traditional healers would use the plant sweet wormwood (Artemisia annua, to give it its full Latin name), also to treat fevers and the symptoms of malaria. For many hundreds of years, this traditional cure was forgotten about, until the 1970s when a concerted effort led by Mao Tse-Tung began to search for new anti-malarial compounds as part of their Vietnam war effort. Their scientists, led by Dr Youyou, re-discovered sweet wormwood and extracted a potent anti-malarial compound from it, called artemisinin. This compound and and its many derivatives, in the form of artemisinin-based combination therapies (ACTs), are now the mainstay of the World Health Organization’s first-line recommended treatment against uncomplicated malaria.

World Health Organization Seeks Funding for Emergency Response to Drug-resistant Malaria

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BANGKOK — The World Health Organization is warning that about $450 million is needed over the next three years to stop a strain of drug-resistant malaria from spreading beyond Southeast Asia to the rest of the world.

Researchers say the artemisinin-resistant strain has spread to Burma and Vietnam since it was first detected along the Cambodian-Thai border in 2008. In addition to sounding the alarm about drug-resistant malaria, the World Health Organization is rolling out an emergency response to what it terms a potentially serious global health threat. [Read more…]

Scientists Describe Breakthrough in Anti-Malarial Precurser

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Scientists from Amyris published in the journal Nature the details of a major breakthrough in the field of synthetic biology that allows for the production of a key precursor to Artemisinin, the key ingredient in the world’s most effective and preferred drug in combating malaria. Earlier today, pharmaceutical company Sanofi announced the launch of large-scale industrial production of Artemisinin utilizing Amyris designed strains.

“Yesterday, a group of scientists led by Amyris detailed how we engineered simple baker’s yeast strains to produce unprecedented concentrations of the precursor to the anti-malarial drug ingredient. Today, Amyris scientists celebrate Sanofi’s successful launch of the industrial production of the world’s first semi-synthetic Artemisinin utilizing Amyris designed strains,” said John Melo, President & Chief Executive Officer of Amyris.

“Sanofi’s commercial launch of this key precursor to life-saving drugs produced with our technology underscores not only the success of Amyris’s synthetic biology platform at scale but also the positive impact this technology can have on our planet,” Melo concluded.

Malaria is a preventable disease that affects over a quarter of a billion people and claims the lives of 650,000 people annually, mostly children under the age of five in Africa. Artemisinin, sourced from the wormwood plant, Artemisia annua, has been used for centuries in treating malaria but its availability, cost and quality have been highly volatile.

Working with a number of partners, and with generous support from the Bill & Melinda Gates Foundation via OneWorld Health (now PATH’s Drug Development Program), Amyris developed technology to convert plant-sugars into Artemisinic Acid, a late stage precursor to the anti-malarial drug ingredient, Artemisinin. The details of this breakthrough process, as well as an alternative process for converting Artemisinic Acid into Artemisinin, can be found in the online publication of the scientific journal Nature.

In 2008, as part of this non-profit project, Amyris made available its Artemisinic Acid-producing yeast strains to Sanofi, via OneWorld Health, on a royalty-free basis. As separately announced by Sanofi earlier today, this technology is now being used at large-scale to produce Artemisinin, which will be combined in pill form with another anti-malarial in what is called Artemisinin-based Combination Therapy (ACT). Sanofi has indicated it plans to produce enough semi-synthetic Artemisinin for up to 150 million ACT treatments by 2014 and will ensure its distribution under the “no profit, no loss” principle.

“Amyris technology will alleviate drug manufacturers’ dependency on erratic supply of plant-derived Artemisinin and reduce costs to malaria patients. This non-profit project is at the core of Amyris’s values and culture, born from a passion to make a positive impact in the world through science,” said Jack Newman, Amyris co-founder and Chief Scientific Officer.

Source: Amyris

Medicine for Malaria

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QUESTION

is rotam and maladar malaria medicine?

ANSWER

I have never heard of Rotam, but Maladar is the brand name of a combination sulfadoxine-pyrimethamine, and is used to treat malaria. However, it should be noted that it is not recommended by the World Health Organization as a first-line treatment option, due to concerns about drug resistance, and also lack of efficacy against certain types of malaria.

Instead, first-line recommended treatment is of an artemisinin-based combination therapy, or ACTs, which combine an artemisinin derivative (such as artesunate, artemether or dihyrdoartemisinin) with another anti-malarial drug, such as lumefantrine, piperaquine or mefloquine. Common brand names include Coartem, Lonart and Duo-Cotecxin.

Chemists Develop New Synthesis for Antimalarial Drug, Artemisinin

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Chemists at Indiana University have developed a new synthesis for the world’s most useful antimalarial drug, artemisinin, giving hope that fully synthetic artemisinin might help reduce the cost of the live-saving drug in the future.

Effective deployment of ACT, or artemisinin-based combination therapy, has been slow due to high production costs of artemisinin. The World Health Organization has set a target “per gram” cost for artemisinin of 25 cents or less, but the current cost is about $2.40 per gram, and production of low-cost semi-synthetic artemisinin has yet to materialize.

“In 2005, the WHO claimed that the structure of artemisinin was too complex for cost-effective synthesis,” said IU Bloomington College of Arts and Sciences chemistry professor Silas Cook. “We saw this as a natural challenge to the creativity and tenacity of organic chemists.”

Published recently in the Journal of the American Chemical Society as “A Concise Synthesis of Artemisinin,” Cook and postdoctoral co-author Chunyin Zhu report a succinct five-part process beginning with inexpensive cyclohexenone, an ideal feedstock available on metric-ton scale. Subsequent chemistry highlights several new reactions developed in the Cook group to enable this short, low-cost synthesis.

The result was the production of fully synthetic artemisinin on gram scale, greater than all previous total syntheses combined.

“The key to the ultimate success of synthetic artemisinin will be the large-scale production of the drug,” Cook said. “As such, we had to completely rethink what qualified as suitable starting materials for this synthesis and invent new chemistry.” The result was the use of readily available commodity chemicals in a process that was shorter than any other artemisinin total synthesis ever conducted.

The next challenge will be to move from gram-scale to kilogram-scale production, a process Cook may or may not be involved with.

“There is still work to be done. And we’d love to do it here, but the project has yet to attract outside funding,” he said. “This is still in an experimental phase until you can scale up. We patented it, so the intellectual property rights are in place.”

Source: Indiana University; Journal of the American Chemical Society

Malaria in Pakistan

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QUESTION

4 years ago I traveled to FATA Pakistan and in every year in the month of August I caught malaria. Last few days I feel much Headache and fever in the evening and go to doctor. He diagnosed malarial parasites in blood and has advised me take tab artem ds 2 BD for three days after complete the course I feel same headache fever with shivering. Please recommend something.

ANSWER

I am not sure which malaria treatment you have taken—was it just artemisinin, or a combination drug which also included another anti-malarial? The latter type is what is recommended by the World Health Organization (WHO); treatments only containing artemisinin are very effective short term, but can sometimes leave a few parasites alive at the end of the course, which not only may result in a recurrence of symptoms (known as recrudescence) but is very bad in terms of leading to drug resistance in the malaria parasite. However, it is also possible that you are merely experiencing some slight side effects to the medication you took; often these mild side effects are very similar to the symptoms of malaria! If you don’t feel better in a few days, it might be worth visiting the doctor again to check that you don’t still have malaria parasites in your blood.

First in Malaria: U.S. or China?

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QUESTION

Who discovered the world’s first malaria vaccine? Is it the US marines in Washington DC or the People’s Republic of China?

ANSWER

Unfortunately there is still no effective malaria vaccine.  You might be referring to the race between the US and China to find an effective malarial treatment during the Vietnam War years.  Currently, artemisinins, from the wormwood plant, discovered in China is the recommended treatment for malaria caused by Plasmodium falciparam.

New Treatment for Malaria

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QUESTION

New treatment for malaria?

ANSWER

The most recently developed type of treatment for malaria actually has very ancient origins. The herb wormwood (Artemisia annua) has been used in ancient Chinese medicine for hundreds, even thousands, of years to cure certain fevers.

In the 1970s, a Chinese research program intensively sought new medications against malaria, as part of their Vietnam war effort. They re-discovered wormwood, and from it isolated the compound artemisinin, which is highly effective against malaria parasites in the blood, and kills them very quickly. Due to its quick action against malaria, there was concern that use of artemisinin alone would lead to resistance developing rapidly in the malaria parasite, as was seen with chloroquine in many parts of the world. As such, the World Health Organisation recommended that artemisinin should only be used in combination with another anti-malarial drug with a longer lasting action, to prevent resistance.

A number of such compounds, containing artemisinin derivatives and a second anti-malarial, have now been developed. These are collectively called “artemisinin-based combination therapies,” or ACTs. Some of the main artemisinin compounds used in these drugs are artemether, artesunate and dihydroartemisinin, and the brand names of the drugs as they are marketed (in combination with other compounds, such as lumefantrine, piperaquine and pyronaridine) include Coartem, Pyramax and Duo-Cotecxin.

Herbal Treatment for Malaria

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QUESTION

Can any form of malaria be treated by herbs or plants, and how long does it take to recover from malaria?

ANSWER

Actually, two of the most important kinds of anti-malarial medication are derived by substances found naturally in plants, though they need to be processed in certain ways before the full pharmaceutical effect is felt.

Quinine, administered intravenously, is currently the first-line treatment for complicated malaria (i.e. when the patient has a history of high fever, plus additional severe symptoms such as impaired consciousness). It is derived from the bark of trees of the genus Cinchona, which are native to the tropical rainforests of western South America. Long known to native populations for its medicinal properties, it became known to Europeans in the early 17th century when the Countess of Chinchón, the wife of the viceroy of Peru at the time, was cured by it, having been suffering from what was likely malaria.

Similarly, artemisinin, currently used in combination with other anti-malarial compounds as the first-line treatment against non-complicated malaria (these combinations are known as artemisinin-based combination therapies, or ACTs), is derived from wormwood, a shrub native to Asia but now found throughout the world. As with the Cinchona trees, traditional healers in China had used wormwood to treat fever for thousands of years, but its use had been forgotten in modern times, until its rediscovery in the 1970s. Nowadays, artemisinin is not recommended for treatment alone, as it is feared this will lead to resistance developing, and so it is only used in the combination therapies described above.

If treated promptly, and with the correct form of medication, recovery from malaria can take only a few days. If not, recovery can take much longer (even up to weeks), and in the case of P. falciparum malaria, the most deadly kind, the infection can become life threatening in only a day or two. P. knowlesi (found in parts of south-east Asia), though less fatal than P. falciparum, can also become severe rapidly, and so prompt treatment is especially necessary for these two kinds of malaria.

Malaria Drug Binding Site

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QUESTION

What is malaria, and drug binding site?

ANSWER

Malaria is caused by a single-celled protozoan parasite of the genus Plasmodium. Five kinds of Plasmodium are known to infect people: P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi.

There is no one drug binding site with respect to malaria: different anti-malarial drugs have different modes of action, and not all are well described. I will briefly outline the proposed mechanism of action of two of the most common types of anti-malarials: artemisinin (and derivatives) and chloroquine (quinine is thought to act similarly to chloroquine).

Artemisinin is thought to have anti-malarial properties by virtue of possessing an endoperoxide moiety, or double oxygen bridge (-Carbon-Oxygen-Oxygen-Carbon). In the presence of intracellular free ion, this moiety is converted by a chemical reaction to “free radicals”, atoms with unpaired electrons which are highly reactive. The free radicals act as alkylating agents and induce cell death, but only those that are already pathologically crippled, for example due to malaria infection. Another hypothesis is that the free radicals directly damage the malaria parasite.

Chloroquine is thought to act by causing buildup of the toxic by-product of hemoglobin metabolism, heme – the malaria parasite usually converts heme to hemozoin, a non-toxic crystal, and stores it in the digestive vacuole. When chloroquine diffuses into an infected red blood cell, it reacts with heme to “cap” it, preventing further conversion into hemozoin. Moreover, chloroquine also converts hemozoin into a highly toxic substance called the FP-Chloroquine complex. This build-up of toxicity leads to breakdown of the cell membrane, and eventual cell death and autodigestion.