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

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 Cure

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QUESTION

What medicine is good for curing malaria?

ANSWER

There are lots of different types of medication which are effective against malaria. However, for uncomplicated, unsevere cases, the World Health Organization (WHO) recommends using a type of medication called artemisinin-based combination therapy, or ACT. Again, there are many types of ACTs, so the name may vary depending on what is most common in your area, but some widespread brands include Coartem, Lonart, Duo-Cotecxin, etc. In some countries, they are known by an abbreviation of the drug name – for example, in Tanzania, the most common ACT is a combination of artemether and lumefantrine, and the different brands are collectively known as Alu.

For severe or complicated malaria (there is no hard and fast definition, but the clinical diagnosis may include cerebral involvement, seizure, coma, inability to take oral medication, severe anaemia, etc), the WHO recommends intravenous  (IV) artesunate, with quinine as a second choice.

There are also additional forms of treatment which may be used in certain settings, depending on the geographical region and the type of malaria, or if one of the above treatments is not successful. Likewise, pregnant women should not take ACTs, so they need to seek alternative forms of treatment, such as chloroquine (if the local malaria is known to be sensitive), mefloquine or sulfadoxine-pyremethamine.

Malaria Fever

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QUESTION

My Father aged 65 years was diagnosed with 2 types of malaria almost a week back. he has been given medicines but temperature is fluctuating and not coming down. all other organs are functionining properly except platelet count which is little less.

Now he has been suggested new medicines for a duration of 14 days.
How fast can he recover from this malaria and when will the fever come down?

ANSWER

When patients are given the appropriate treatment against malaria, the fever is usually reduced very quickly and the patient will start to recover after a few days. The right kind of treatment depends on the severity of the infection and the type (or, in your father’s case, types) of malaria the patient is infected with.

If your father was infected with P. falciparum alongside another type of malaria (probably P. vivax, P. malariae or P. ovale), then he should have first received an artemisinin-based combination therapy (ACT) drug first. These drugs combine artemisinin or a derivative (such as artemether, artesunate or dihydroartemisinin) with another anti-malarial, such as lumefantrine. Common brand names of these ACTs include Coartem, Alu and Duo-Cotecxin.

There are no reported cases of resistance to these combination therapies at present, so if your father continued to feel sick after completing this treatment, he should be re-tested for malaria; it is possible that the malaria parasites were killed, and his continuing fever was an after effect either of the medication or just an indication that the body was recovering from the infection.

If he was re-tested and found positive, then other second-line drugs can be prescribed. However, it is important to note that malaria is resistant to chloroquine in many areas, and so this drug is not suitable for treatment in these places. Similarly, resistance is widespread to sulfadoxine-pyrimethamines, such as Fansidar, and in south-east Asia, P. falciparum is also resistant to mefloquine (Lariam) in some cases. As such, your father’s doctor should be careful to prescribe him an appropriate treatment for the area in which he is living.

In addition, if your father was found to be co-infected with either P. vivax or P. ovale, then there is a chance of later relapse into malaria again, weeks or even months after the initial infection has been treated. This is because the parasites in these types of malaria can form dormant stages in the liver, where they escape being killed by the normal forms of treatment. In this case, your father should ask about the possibility of being treated with primaquine; the course is normally 14 days, so it may be that this is what his doctors have currently given him. If so, this will kill the dormant liver stages and prevent relapse. Prior to taking primaquine, patients should be tested for G6DP deficiency, as patients with this condition may become dangerously anaemic when they take primaquine.

Cure for Malaria

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QUESTION

Is there a cure for Malaria?

ANSWER

Yes. Several different medications exist which are used for the treatment of malaria. The exact drug and method of treatment depends somewhat on the type of malaria the patient is infected with. In most cases of non-complicated (i.e. when the patient is stable and conscious) malaria, the World Health Organisation recommends an orally-administered (in the form of solid pills) artemisinin-based combination therapy (ACT), such as Coartem (a combination of artemether and lumefantrine). Other types of medication include atovaquone-proguanil (Malarone) and sulfadoxine-pyrimethamine (Fansidar). In some locations, where chloroquine-resistance is not a problem, chloroquine can also be used as a treatment. For complicated malaria, where the patient is in a more severe state, intravenously administered quinine is usually the first-line treatment.

If diagnosed early and the patient is given appropriate medication, virtually all cases of uncomplicated malaria can be effectively treated.

ACT Therapy, Missed Doses

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QUESTION

I had recently encountered with malaria and started artemether and lumefantrine . Out of 6 tab of 80mg 4  I had taken 2 missed. Please suggest.

ANSWER

When a dose of ACT is missed, do not take an extra dose to compensate. Instead, take the next dose as soon as you remember, and continue until you have taken all of the tablets. Keep a close watch on any symptoms of illness that might suggest recrudescence (which occurs when all the parasites in the blood have not been killed, and so can begin to multiply again after treatment finishes).

If you suspect recrudescence, go back to your doctor for another diagnosis, and another dose of ACT. Please comply to the treatment and do not miss doses! This can lead to resistance against the drugs developing in the malaria parasites.