Researchers Discover How Anti-Malaria Drug Works

For centuries people in China have used extracts from a plant called Sweet Wormwood to treat malaria. In August, British researchers published the results of their research outlining exactly how these drugs, known as artemisinins, work.

The prevailing hypothesis had been that artemisinins interfered molecules that the malaria parasite uses to consume haemoglobin. But the British researchers at St. George’s Hospital in London discovered that artemisinins in fact appear to disable part of the parasite that transfers calcium out of cells in order to stabilize calcium levels. With this disabled, calcium levels in the cells of the parasite grow until the cell dies.

Unlike other treatments for malaria, there is no known malarial resistance to artemisinins, raising the possibility that other drugs and vaccines could be developed that also target this calcium transfer mechanism.

Researcher Sanjreev Krishna told the BBC and Reuters,

It’ll take some time to apply our findings, or even to test new artemisinin derivatives which are being developed now. But you can be sure that’s what we’re going to be doing.

. . .

So far there is no evidence at all of any clinical resistance to artemisinins. It’s one of our best hopes for the future and frankly I don’t think we have many other options at the moment.

Sources:

Find could boost malaria fight. The BBC, August 20, 2003.

Scientists find how anti-malaria shrub works. Reuters, August 20, 2003.

Artemisinins target the SERCA of Plasmodium falciparum. U. Eckstein-Ludwig, Nature 424, 957 – 961, 21 August 2003.

Largest Childhood Malaria Vaccine Trial Ever Underway

In July, the Malaria Vaccine Initiative announced that it would begin the largest malaria vaccine trial ever conducted in children. The vaccine trial was to take place in Mozambique.

The vaccine in question — RTS,S — has already gone through initial safety testing with human volunteers and appears safe enough. In addition, testing in adults found that the vaccine was effective in preventing malaria in about 71 percent of adults who received it.

An open question, however, is just how good it is at preventing malaria in young children. To that end, the vaccine will be administered to 2,500 children in Mozambique. Final results for the vaccine will be available in about 18 to 24 months.

If the vaccine proves effective there, research will then move on to see if it could be safely and effectively administered to infants, who face the highest death rate from malaria.

Sources:

Clinical Trial of Advanced Malaria Vaccine Candidate to Begin in Mozambique. Press Release, Malaria Vaccine Initiative, July 8, 2003.

Two thousand kids to get experimental malaria jab. Tom Clark, Nature, July 9, 2003.

Malaria Vaccine Trial To Start In Mozambique. United Nations Wire, July 8, 2003.

Malaria vaccine trial begins. The BBC, July 8, 2003.

Malaria Project Failing Due to Lack of Funds

An article published in the online Malaria Journal argues that the World Health Organization is woefully behind in its 1998 Roll Back Malaria plan that sought to cut malaria deaths in half by 2010 and then in half again by 2015. According to Harvard researchers Vasant Narasimhan and Amir Attaran, the RBM project has attracted barely five percent of the funds it needs to succeed.

Based on surveys of donor countries and external estimates of their spending, Narasimhan and Attaran estimate that RBM receives roughly US$98 million annually. It would need about US$1.5-$2 billion annually to reach its goal of halving malaria deaths.

The odd thing is that this estimate is filled with a bizarre level of uncertainty. Switzerland, for example, told the researchers that not only did they not know how much their country was giving for malaria control, but they did not even know how to go about finding out since malaria control spending was subsumed into larger health spending budgets. Narasimhan and Attaran write that this will pose enormous problems for funding of malaria control efforts,

In short, the Swiss answer, which seems likely to apply to some other donors too, is that the extent of malaria control funding is not just unknown, but actually unknowable. Leaving aside the reasons why this is true (e.g. it is found in integrated health programmes and not easily disaggregated), this poses a huge strategic threat to RBM’s goals: What is the likelihood of increasing malaria control funding, when the donors lack the accounting procedures and ability to know how much they are spending? Without reliable financial surveillance, there is good reason to suspect that aid to malaria control will stagnate, as it has done for decades, without triggering public pressure to demand improvement.

The other interesting thing is that the $98 million spending estimate is significantly smaller than other estimates that put annual malaria control spending at US$130 to $160 million. Part of the reason for the difference is that some organizations, including the World Bank, appear to be exaggerating their malaria control spending (emphasis added),

Although the Bank publicly claims that “at present, World Bank direct financing for malaria control activities is over $200 million in more than 25 countries”, we find on the Bank’s own project list only 10 countries having “active” malaria control projects [22]. In India, where in 1997 the Bank pledged its largest malaria control effort ($164.8 million), the project neared its close in 2003 after disbursing little over a quarter of this amount. In Africa, where 90% of malaria deaths occur, the Bank has only 4 active projects: in the Comoros, Eritrea, Madagascar, and Senegal. Yet not one of these countries suffers particularly intense or sustained malaria transmission – three are hardly malarious at all by African standards – meaning that the Bank’s efforts will contribute little to halving the burden of malaria.

Worst of all, the Bank has practically reneged on the dramatic pledge it made to two dozen African heads of state at Abuja in April 2000 to provide “up to $500 million more…for the fight against malaria in Africa” [23]. Nearly three years after that pledge, Eritrea is the only country to receive a new loan expressly including malaria control (the loan package is $40 million, split among 4 diseases). Assuming that the each disease in the Eritrea loan package receives an equal share, then the Bank’s new lending for malaria control since Abuja amounts to only $10 million; and three years after Abuja, up to $490 million of the $500 million that the Bank promised remains uncommitted and unspent. Furthermore, at this writing (December 2002), the Bank’s own malaria project list shows not one new African malaria control project in the planning pipeline. There seems to be no activity underway at the Bank to keep the promise that was made.

The authors recommend that the World Bank appoint a malaria “czar” to oversee malaria control projects in much the same way it appointed an AIDS “czar” to oversee AIDS control projects.

They also criticize views in Western donor nations that malaria spending is wasted because developing nations do not have the health care infrastructure to meaningfully absorb the aid. Instead, they argue that this is a sort of chicken-or-egg problem — additional spending on malaria would drive the creation of additional health care infrastructure. I suspect donor nations are a bit more skeptical than are Narasimhan and Attaran. As the authors themselves concede, the United States, for example, spent billions on malaria control in the 1960s with very little to show for it.

Source:

Roll Back Malaria? The scarcity of international aid for malaria control. Vasant Narasimhan and Amir Attaran, Malaria Journal, April 15, 2003.

Malaria project in funding crisis. BioMed Central, Press Release, April 25, 2003.

Killing Malaria by Starving It

Researchers at St George’s Hospital Medical School have come up with a novel way to attack the malaria parasite — starve it of the sugar it needs.

The malaria parasite uses large amounts of glucose. The St. George’s researchers were the first to prove that the parasite uses a special transport protein to absorb the glucose. The importance of this finding is that if a way can be found to block that transport protein, the malaria parasite can be effectively starved.

St. George’s researcher Sanjeev Krishna said of the discovery,

This discovery proves for the first time that it is worth going after transport proteins of the malaria parasite and that parasites cannot live without this transporter working properly.

. . .

We are very excited about this research, as this new information gives us the potential to design new drugs against malaria.

The research of Dr. Krishna and his colleagues was published in the Proceedings of the National Academy of Sciences.

Sources:

Scientists starve malaria parasite. The BBC, June 4, 2003.

Parasite’s sweet tooth may provide malaria cure. Ananova, June 3, 2003.

State of The World’s Vaccines and Immunizations

A report by the World Health Organization, UNICEF and the World Bank concluded that 3 out of 4 children around the world now have access to essential vaccines. But, of course, that means that fully 25 percent of the world’s children are not routinely vaccinated against childhood diseases.

According to The State of the World’s Vaccines and Immunization, as many as 37 million children under the age of one are not immunized against the six major vaccine-preventable diseases of childhood: tuberculosis, tetanus, whooping cough, diphtheria, polio and measles.

Moreover, the inability of underdeveloped countries to pay for vaccines combined with ongoing property rights disputes over ownership of drugs and vaccines in such countries acts as disincentive for further research into vaccines for diseases that plague the developing world.

According to the report,

Today, vaccine manufacturers have little commercial incentive to develop vaccines against diseases such as HIV/AIDS, TB and malaria, which kill millions of people in developing countries, but relatively few in the developed world. For example, of the approximately US$600 million a year invested in HIV vaccine research, the majority comes from the US National Institutes of Health (a public sector institution). To put that amount in perspective, in 1999, research spending on drugs to treat HIV/AIDS was about US$3 billion in Europe and the United States alone. Other diseases fare just as badly. In the 1996 report Investing in Health Research and Development, WHO highlighted some of the distortions in global health research funding. At the time of the study, acute respiratory infections, diarrheal disease and TB — which together account for almost 8 million deaths a year, mainly among the poor — attracted an estimated US$99-133 million. . . By contrast, more was spent on research into asthma — an estimated US $127-158 million — which accounts for 218,000 deaths a year worldwide.

Of course the report ignores the possibility that the relatively heavy funding in asthma is what is responsible for such a low worldwide death toll, but even so the amount estimated to be spent on research into diseases that kill 8 million people is staggeringly low.

Source:

Vaccine policy leaves millions at risk. The BBC, November 20, 2002.

State of the World’s Vaccines and Immunization Report (PDF). UNICEF, 2002.

Malaria and Mosquito Genes Decoded

Last week saw the simultaneous publishing of the genomes of both the malaria parasite Plasmodium falciparum and the mosquito that transmits the most cases of the disease, Anopheles gambiae.

The decoding of the genomes for these species will give researchers better insight that might eventually make its way into new treatments and possibly vaccines for malaria. An immediate insight, for example, was that a single genetic mutation in the malaria parasite accounts for the disease’s ability to resist chloroquine drugs.

An estimated million people die each year from malaria-related complications. The disease has been largely eradicated from the developed world but still flourishes in the developed world which cannot afford the expensive public health measures needed to eradicate the disease.

But at least one vaccine researcher was skeptical that the decoding of the genomes would lead to any near-term changes in vaccine research. Dr. Regina Rabinovitch, who heads up the Malaria Vaccine Initiative, told Reuters that the decoding would have little immediate effect on vaccine research,

It’s not as relevant to us. The technology to translate from the genome to a vaccine is still being developed.

The Malaria Vaccine Initiative does have a number of vaccines in various phases of testing, however. Even those potential vaccines, however, are still at best years away from being widely deployed even on a best case scenario.

Sources:

Genes of most deadly malaria form decoded. National Geographic News, October 2, 2002.

Scientists find secret of malaria’s resistance. Maggie Fox, Reuters, October 2, 2002.

Gene maps do little for malaria vaccine-group. Maggie Fox, Reuters, October 3, 2002.