Sweet incentives

Incentives to develop treatments for "neglected diseases including malaria, tuberculosis and leishmanaisis" may encourage drug companies to focus more on potentially life-saving research and development, declares a U.S. business professor. The suggested incentive comes in the form of a "priority review voucher", which "would give a company accelerated regulatory review of one of its other drugs as a reward for developing a treatment for neglected disease".

Although these diseases affect more than 1 billion people, they occur most frequently in developing nations, providing little financial incentive for pharmaceutical companies to create and test new treatments.

Writing in the Sept. 11 issue of The Lancet, professor David Ridley of Duke University's Fuqua School of Business and Alfonso Calles-Sánchez, a patent expert with the Spanish Patent Office and former pharmaceutical policy maker at the European Commission, propose a European Union version of the priority review voucher system instituted in the United States in 2007.

Bill Gates explained an example of such incentives at the 2008 World Economic Forum in Davos. "If you develop a new drug for malaria, your profitable cholesterol-lowering drug could go on the market a year earlier...This priority review could be worth hundreds of millions of dollars [to the company]," Gates said.


In the U.S., the vouchers and other incentives are working. Firms and drug companies are motivated to begin clinical testing; although, these drugs may take several years to reach patients in need. Still, any forward movement in these fields is improvement. With continued encouragement, drug companies may enact the demise of malaria and other currently neglected diseases.

Do you have ideas or suggestions for other incentives that may encourage the eradication of malaria?


Sources:
David B Ridley, Alfonso Calles Sánchez. Introduction of European priority review vouchers to encourage development of new medicines for neglected diseases. The Lancet, 2010; 376 (9744): 922-927 DOI: 10.1016/S0140-6736(10)60669-1

Duke University (2010, September 9). European Union could create incentive for new drug treatments, experts propose. ScienceDaily. Retrieved September 19, 2010, from http://www.sciencedaily.com­ /releases/2010/09/100909193359.htm

Image by Petar Marjanovic

A new treatment

A new anti-malarial drug may soon progress to clinical trials. This new treatment "is made from simple organic molecules and will be cheaper to mass produce compared to existing therapies."

Malaria is widespread and deadly. Many of the nearly 250 million people who contract the malaria parasite each year do not have access or cannot afford adequate treatment. Drugs that are easy and cheap to produce and distribute may save many of the nearly one million lives that are lost each year due to malaria infection.

With the goal of easing the cost of malaria eradication on poor countries and individuals, the research "team at Liverpool" has "created a synthetic drug based on the chemical structure of artemisinin, an extract of a Chinese herb commonly used in malaria treatment. The new drug, which can be taken orally, is more potent than naturally derived artemisinin."

"Malaria affects the world's poorest countries and hospitals are unable to afford expensive treatments. The problem with current artemisinin-based therapies is their limited availability, poor oral absorption and high cost. We have created a new drug that is easily absorbed by the body, chemically stable and highly potent. It is made from very simple organic materials and therefore will be more cost-effective to mass produce than current therapies," says Professor Paul O'Neill.

Artemisinin is known to interact with a substance inside parasite-infected red blood cells, causing a chain of events that destroys malaria. The treatment, however, is difficult to mass produce and can be chemically unstable in the body. Scientists have now found a way of creating the most reactive part of artemisinin synthetically and fusing it with a cage-like structure made of organic molecules to make the drug more chemically stable. The stability of the chemical structure in the body makes the drug last longer, reducing the chance of the parasite reappearing.

Source:
University of Liverpool (2010, August 16). New drug treatment for malaria?. ScienceDaily. Retrieved August 31, 2010, from http://www.sciencedaily.com­ /releases/2010/08/100816095715.htm

Safer anti-malarials

In the arms race against malaria, humans wield the biggest weapons, but their cost is great. In recent years, malaria has mutated and adapted to resist the drugs used to combat it. Caused by a parasite and transmitted by mosquitoes, malaria is an infectious disease that kills nearly one million people each year. Humans struggle to prevent malaria transmission and to treat those infected with the deadly disease.

Unfortunately, some of the malaria treatments are potentially deadly as well. "Amodiaquine was introduced as an antimalarial drug, but. . . withdrawn from the market when it became clear that the drug caused serious adverse effects in the form of liver damage and impaired immune system." The drug is still used in the most severe cases of drug-resistant malaria. It saves lives, but endangers them as well.

Endeavoring to create safer drugs, scientists at the University of Gothenburg, Sweden, studied the byproducts of drugs, looking for toxins. "A pharmaceutical in the body is, in the optimal case, broken down into harmless products (metabolites) that leave the body, for example via the urine. Some pharmaceuticals, however, can be converted into toxic products, which may result in serious adverse effects." Proposed by Tove Johansson Mali'n, the scientists uncovered a process that can "simulate the metabolism of pharmaceuticals in the body". In this way they can identify and characterize several potentially toxic products that arise as the metabolites of drugs". With the aid of this methond, Mali'n "has now managed to identify. . . previously unknown metabolites that may have caused, or contributed to, the adverse effects of amodiaquine."

"We hope that the method can simplify the work of identifying potentially toxic metabolites at an early stage, and thus facilitate the development of safe drugs," says Tove Johansson Mali'n.

Tove Johansson Mali'n, Lars Weidolf, Neal Castagnoli, Ulrik Jurva. P450-catalyzed vs. electrochemical oxidation of haloperidol studied by ultra-performance liquid chromatography/electrospray ionization mass spectrometry. Rapid Communications in Mass Spectrometry, 2010; 24 (9): 1231 DOI: 10.1002/rcm.4505
University of Gothenburg (2010, May 9). New method for developing safer drugs. ScienceDaily. Retrieved May 10, 2010, from http://www.sciencedaily.com¬ /releases/2010/05/100509202645.htm

Malaria and antibiotics

Malaria is a parasite that is transmitted by mosquitoes and infects a million people a year. Since this disease is not caused by a bacterium, how is it that antibiotics affect malaria and improve the health of sickened individuals?

From 1920 to 1950, antibiotics were a widely used treatment for malaria, although medical practitioners were not entirely sure why this treatment was so effective (Butcher). In the early 1980s, it was "discovered that antibiotics ... are active as antimalarial agents" (Oronsky). More recently, azithromycin [also called Zithromax] has been used to treat malaria in Ethiopia after it was shown "to have efficacy in the prevention and treatment of malaria due to both Plasmodium falciparum and Plasmodium vivax," (Travis).

After research, scientists have hypothesized that antibiotics treat malaria because they attack the plasmodia (a protozoa) within the parasites; therefore the antibiotics diminish the malaria" (Flam). Furthermore, antibiotics alleviate the immune system of other infections that may coexist with malaria.

"The treatment may also have unintended consequences...including the inducement of antibiotic resistance" (Travis). However, the situation is further complicated by the development of drug-resistant bacteria in malaria-infested areas that have had no exposure to antibiotics.

As mysterious as the seemingly unfounded effectiveness of antibiotics on malaria in the 20th century, the unexplained drug-resistant bacteria in "remote rainforest communities in Guyana" confounded scientists (Juncosa). New studies revealed "that overuse of a drug used to prevent and treat malaria may be contributing to growing antibiotic resistance...Drug-resistant bacteria are known to arise from the overuse of antibiotics, which is why researchers were surprised to discover that they can develop in areas that do not have access to" that particular antibiotic [ciprofloxacin]. Michael Silverman, "an infectious disease specialist at Lakeridge Health Network in Ontario" says that antibiotic-resistant E. coli were more widespread in these remote Guyanese villages than in U.S. hospitals "where every second person is on antibiotics." Silverman's study showed that the patients infected with drug-resistant E.coli had been "given the drug chloroquine to prevent and treat malaria" (Juncosa).

According to Silverman, "It is very possible that the antimalarial drugs may be inducing a large amount of the antibiotic resistance that occurs in the tropics." Unfortunately, "plasmodia, the causative organisms of malaria, have developed resistance to antibiotics" as well and "at the same time, the mosquitoes that carry plasmodia have become resistant to the insecticides that were once used to control them. Consequently, although malaria had been almost entirely eliminated, it is now again rampant in Africa, the Middle East, Southeast Asia, and parts of Latin America" (MSN).

The increasing number of drug-resistant strains of malaria parasite, plasmodia, and other bacteria is another reason why an effective malaria vaccine is so important. We cannot continue treating malaria in the ways that we have in the past, for very soon, these old methods will be rendered ineffective.

Sources:
Butcher, Geoff. “Million Murdering Death.” History Today April 1998: 24-28.

Flam, Fray. “Scientists Find Weak Spot in Defense of Tenacious Malaria Parasite.” Tribune News Service November 1997: 26-28.

Juncosa, Barbara. "Antibiotic Resistance: Blame it on Lifesaving Malaria Drug?" Scientific American 21 July 2008.

MSN Encarta."Antibiotics"

Oronsky, Arnold L. Treatment of malaria with antibiotics. "United States Patent 4496549" 29 Jan 1985.

Science News. "Distribution Of Antibiotic For Eye Disease Linked To Low Death Risk Among Ethiopian Children." 1 Sept 2009.

Travis C. Porco; Teshome Gebre; Berhan Ayele; Jenafir House; Jeremy Keenan; Zhaoxia Zhou; Kevin Cyrus Hong; Nicole Stoller; Kathryn J. Ray; Paul Emerson; Bruce D. Gaynor; Thomas M. Lietman. Effect of Mass Distribution of Azithromycin for Trachoma Control on Overall Mortality in Ethiopian Children: A Randomized Trial. JAMA, 2009; 302 (9): 962-968

The Threat of Drug Resistant Malaria

Recent tests indicate that the most common malaria strains are becoming resistant to combination treatments in vulnerable areas. "Selected trials" showed "high failure rates for some combinations" of medicines. Anti-malarial treatments must be questioned, particularly in susceptible regions (Wiley).

The most common type of malaria parasite causes uncomplicated malaria, which is a mild form of the disease. However, if this strain remains untreated, it can develop into a life-threatening condition. "Resistance" of this strain "to the older antimalarials has led the WHO to recommend treatments combining" a fast-acting drug with a "longer-lasting drug to combat resistance."

Malaria can be a difficult disease to cure and is most often treated with a combination of medicines. During the recent tests, "there were examples of treatment failure rates above 10% for all evaluated combinations." According to the WHO, this exceeds the "maximum allowable failure rate for a first line antimalarial" treatment.

A recently introduced drug, dihydroartemisinin-piperaquine, performed well when compared to the standard treatment of artemisinin-based combination therapies (ACTs). This new treatment "offers another potential first-line therapy for the disease".

"Patterns of resistance change from place to place and over time," so continued testing of infected individuals and monitoring of progress is necessary to ensure successful treatment. These research and medical programs are costly, and severely underfunded. If you would like to contribute money to malaria research, please visit the following sites.

Anti-malaria agencies:

• Roll Back Malaria Partnership: Index of non-profit organizations that fight malaria (and need donations)
• United Nations Foundation: With your donation you are helping us expand the worldwide fight against disease, poverty, climate change, and conflict

(Infectious bite is not currently accepting donations. Please see the appropriate agencies for information on donations)

Source:
Wiley-Blackwell. "Continued Vigilance Against Drug-resistance Malaria Is Needed." ScienceDaily 7 July 2009. 9 July 2009 < http://www.sciencedaily.com­ /releases/2009/07/090707201209.htm >.

Advances Against Malaria | Combination Treatment

New studies conducted with children in Burkino Faso 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" (University).

Methylene blue is one of the oldest synthetic treatments of malaria. In 1891, Paul Ehrlich identified its success at treating the disease (Schirmer). The chemical fell out of favor because of its cosmetic side-effects: whites of the eyes acquire a blue tint (image) and urine turns green.

Methylene blue is relatively cheap to produce and may see a resurgence in use since "combination therapies are twice as effective against gametocytes as the standard therapy" (University).

Sources:
Schirmer H, Coulibaly B, Stich A, et al. (2003). "Methylene blue as an antimalarial agent--past and future". Redox Rep 8: 272–276. doi:10.1179/135100003225002899

University Hospital Heidelberg. "Spread Of Malaria Parasites Curbed With Combination Of Methylene Blue And New Malaria Drugs." ScienceDaily 26 May 2009. 24 June 2009