Article Critical of World Health Organization’s Anti-Malaria Approach

Amir Attaran, who has been highly critical of donor organization’s approach to malaria control, published an opinion article in The Lancet in January arguing that “institutional inadequacies” in the World Health Organization’s anti-malaria efforts impede the organization’s ability to save lives from the disease.

Specifically, Attaran argues that by favoring expensive traditional malaria therapies over newer, more effective — but more expensive –treatments such as artemisinin combination therapies, the WHO is guilty of the equivalent of “medical malpractice.”

Attaran notes that WHO itself concedes that the drugs it using in Africa are growing increasingly ineffective,

WHO now writes of “global malaria control . . . being threatened on an unprecedented scale” by continued use of outdated drugs such as chloroquine, which is ineffective in most parts of Africa, and sulfadoxine-pyrimethamine, which is becoming so. For example, in East Africa, surveillance and clinical trial data show that up to 64% of patients given chloroquine and 45% given sulfadoxine-pyrimethamine will fail treatment, and those figures are climbing.

When treatment failure becomes so frequent, malaria deaths rise greatly, especially in children. In West Africa (Senegal), results of a 12-year community-based study showed that the onset of chloroquine resistance at least doubled childhood malaria death risk, and in some sites, increased it up to 11-fold in the youngest children. In East and southern Africa, the proportion of children dying from malaria doubled as chloroquine and later sulfadoxine-pyrimethamine resistance took hold from the 1980s to the 1990s, even as deaths from other causes declined. Elsewhere in Africa, chloroquine resistance increased the proportion of admissions to hospital and deaths from malaria by two-fold to four-fold.

Moreover, Attaran argues,

The superiority of ACT is now so established that of the five treatments WHO recommends for drug resistant P falciparum malaria, four are ACTs (the other is a “short-term solution” for countries that cannot use ACT immediately).3 ACT is now the preferred policy for WHO and the Roll Back Malaria campaign as a whole:

“Recently WHO has formulated policy that elevates combination drug therapy to preferred first therapy for all malaria infections in areas where P falciparum is the predominant infecting species of malaria. Combination therapy (CT) with formulations containing an artemisinin compound (ACT) is the policy standard . . .”22

However, WHO violates its own policy standard regularly. Most African countries reluctantly cling to chloroquine, sulfadoxine-pyrimethamine, or the insignificantly better combination of chloroquine and sulfadoxine-pyrimethamine, because ACT is ten times more expensive and, therefore, unaffordable to them.2,23 When those same countries seek financial aid from the Global Fund for AIDS, Tuberculosis, and Malaria (GFATM) to purchase ACT, they are forcefully pressured out of it by governments such as the USA, whose aid officials say that ACT is too expensive and “not ready for prime time”.24 WHO acquiesces to this pressure to cut costs, and despite a policy that names ACT as the gold standard of treatment, WHO signs its approval when GFATM funds cheap but ineffective chloroquine or sulfadoxine-pyrimethamine to treat P falciparum malaria.

. . .

These are very obvious errors of scientific and medical judgment; and although WHO might be expected to spearhead a corrective intervention, the evidence suggests that it instead exacerbated the errors. In Kenya, Ethiopia, and Uganda, WHO’s country representatives reviewed the funding proposals in which inappropriate drugs were sought–and signed their approval. Those signatures follow a declaration that WHO “has participated throughout the . . . process” of developing the proposal to GFATM, and that it “reviewed the final proposal and [is] happy to support it”.31-33

These decisions are indefensible. For WHO and GFATM to provide chloroquine and sulfadoxine-pyrimethamine treatments in the countries we cite as examples at least wastes precious international aid money, and at most, kills patients who have malaria. If one takes the measured increase in childhood malaria mortality that follows P falciparum drug resistance (two-fold to 11-fold) and extrapolates it to populations in which GFATM is funding chloroquine or sulfadoxine-pyrimethamine despite resistance (more than 100 million people in the four countries we name), then at least tens of thousands of children die every year as a direct result. Those patients who survive will often become much sicker and require retreatment, at some further expense of time and money. We do not exaggerate to state that, based on the outcomes, there is no ethical or legal difference that separates them from conduct otherwise condemned as medical malpractice (compare the case in which a doctor or pharmacist who, like these institutions, knowingly furnished treatments that failed perhaps 80% of the time, while withholding the alternatives as “too expensive”).

WHO responded with a letter to Lancet saying that it does encourage use of ACT, but that its high cost has hampered efforts to distribute it in Africa,

Although progress is encouraging, there are still major challenges to the adoption of ACTs, especially sustainable financing. Although with growing demand a price decrease can be expected in the coming years, the cost of growing the raw ingredient, Artemisia annua, means that ACTs will remain relatively expensive. Governments need to trust that sustainable funding from the Global Fund and other sources will be available before they can make the commitment–of up to US$2 per head per year–of switching to ACTs. WHO and its partners are developing a new mechanism to facilitate access to quality medicines and other products for malaria control. WHO will continue to work with the public and private sectors, and major institutions such as the Global Fund, to make ACTs more widely available through lowered costs, increased access, and technical cooperation.

The bigger problem is that so little money is devoted worldwide to fighting malaria.

Sources:

WHO, the Global Fund, and medical malpractice in malaria treatment. Amir Attaran, et al, The Lancet 2004; 363: 237-40.

Response to accusations of medical malpractice by WHO and the Global Fund. Fatoumata Nafo-Traoré, The Lancet 2004; 363.

Combination Therapy with Artemisinin Effective at Fighting Malaria

A review of existing studies of anti-malarial compound artemisinin recently concluded that adding the Chinese folk remedy for malaria to existing anti-malarial drugs increased the effectiveness of those drugs in fighting malaria.

The International Artemisinin Study Group looked at 16 clinical trials involving 6,000 patients who were administered artemisinin along with other anti-malarial drugs. Artemisinin is an extract from sweet wormwood has been used for centuries in Asia to treat malaria.

Their review found that adding artemisinin to existing compounds doubled the rate of parasite clearance (the level of parasites removed from the blood) with no additional side effects. Additionally, patients taking artemisinin combination therapies were less likely to suffer a relapse of the disease after ending treatment.

In an article in Lancet describing the results of the survey, the International Artemisinin Study Group wrote,

If used widely, this inexpensive, fixed-dose artemisinin-based combination antimalarial could make important contributions to ‘rolling back malaria’.

Sources:

Drug cocktail ‘may beat malaria’. The BBC, January 2, 2004.

Drug combinations for malaria: time to ACT?. The Lancet, January 3, 2004.

Combination therapy, the best way to tackle malaria: Lancet. January 2, 2004.

Bill Gates Donates $168 Million for Malaria Research

In September, Microsoft Chairman Bill Gates announced a $168 million donation to fund malaria research. Currently only about $100 million is spent annually to research malaria, so Gates’ donation will have a significant impact on efforts to find treatments for the disease.

In announcing the donation, Gates said it was time for the world to get serious about dealing with malaria,

Malaria is robbing Africa of its people and potential. Beyond the extraordinary human toll, malaria is one of the greatest barriers to Africa’s economic growth, draining national health budgets and deepening poverty.

About 90 percent of malaria cases occur in Africa, where the disease kills more than 900,000 people annually — mostly children.

$100 million of Gates’ grant will be devoted to vaccine research, $40 million to develop drugs to combat drug-resistant strains of malaria, and $28 million to research ways to use existing drugs to lower infections in infants.

Sources:

Gates boosts war on malaria. The BBC, September 21, 2003.

Bill Gates Donates $168 Million to Fight Malaria. Wambui Chege, Reuters, September 23, 2003.

Bill Gates donates $168 M for malaria research. Associated Press, September 22, 2003.

Africa’s Malaria Death Toll Still “Outrageously High”. Afshin Molavi, National Geographic News, June 12, 2003.

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.