Questions and Answers

Malaria, a Parasite Laughing at Cheap Drugs

Interview with M. David Alnwick

What is Malaria?
The word comes from the Latin ‘mal aria’ (bad air). In 1880, the scientists discovered the real cause of malaria, a one-cell parasite called plasmodium. Later they discovered that the parasite enters the human bloodstream through the bite of a female Anopheles mosquito, which needs blood to nurture her eggs. The mosquito female bites after dusk and before dawn. Once the parasite is in the bloodand after a period of incubation, the person starts to have fever which is the most typical manifestation of malaria, as well as cough, headache, diarrhoea, muscle pain.

How does malaria cause death?
The parasite multiplies in red blood cells until billions of them spread through thebody causing death from anaemia or by simply clogging the capillaries that carry blood to the brain and other vital organs. There are at least one million deaths a year from malaria. Ninety per cent of these deaths occur in Africa South of the Sahara and most of them occur in children under the age of five.

Where did malaria develop?
Malaria was a global problem even before the Roman times. It was effectively eradicated in Europe and North America around the early sixties thanks to intensive programs based on DDT spraying and additional control measures such as environmental management, treatment of cases and improvement in social and economic conditions. It has been controlled in some countries of the Middle-East and it is relatively less dramatic outside Africa.

Was there a drug to combat malaria at this time? 
The first drug used was Quinine (brought back from Peru in the 16th century). It was then used as an infusion of powder from the “fever bork tree” and in the early 20th century started to be used in a tablet form. So Quinine was the first “antimalarial” treatment.

So why couldn’t malaria be eradicated in Africa? 
Malaria eradication was possible in the temperate zones because malaria transmission rates were lower in these areas and the parasite could be eliminated much more easily compared to the tropical zones in Africa. There were also good resources, investment and human capacity to tackle malaria. During the malaria eradication programme in the sixties, WHO tried to apply the same methods in many tropical areas and in Africa but malaria could not be eradicated in those countries as the mosquitos were extremely strong and able to transmit high levels of parasite inoculations.

Why has the parasite become resistant to drugs and why have the vectors ( the anopheles mosquito ) become resistant to insecticides? 
Through the process of reproduction and its recombination of genes, parasites and vector mosquitoes can mutate to become naturally resistant to drugs and insecticides, respectively. In Africa, the malaria situation is threatening to spiral out of control. Malaria is not just one more tropical disease, it is the single biggest killer of young children. Under –five mortality rates in Africa are enormously high. Nearly 25%of all deaths in children under 5 are due to malaria.

Why are children more prone to develop malaria? 
Babies are born with very little immunity to malaria. If they get infected by malaria either they live or they die. If they recover from infection, they live with some immune protection. The next time, they become infected they get the disease less severely. When they have been infected several times, malaria often tends to be a relatively mild disease.

What are the other major killer diseases in Africa?
Children are dying from malnutrition, pneumonia, diarrhoea and HIV/AIDS. As a direct killer of children, HIV/AIDS con- tributes to a relatively small proportion of childhood deaths. We are pretty sure what to do about diarrhoea, it can be well con- trolled and we are optimistic that treatment of pneumonia will improve. So malaria remains the biggest challenge and if we can do something conclusive about malaria in Africa, we can save nearly 800,000 children a year.

The malaria programme started as soon as WHO was established. What did WHO achieve? 
There was an enormous investment by WHO, by the major international development agencies and by other UN institutions such as UNICEF in the 60s and the 70s to tackle malaria. Unfortunately, that effort was not successful.

Why?
Because of over-reliance on the use of the insecticide DDT, the underestimation of the complexity of the disease, the development of drug resistance and generally because of the neglect of Africa. The global malaria eradication effort believed that malaria in Africa, at that time, was too difficult to tackle. The infrastructure was too poor and transmission too intense. The Global Eradication effort was pretty successful outside Africa although not as successful as some people had hoped. So in 1969, having made an enormous investment and having not seen many results, there followed a period of about fifteen years where malaria in Africa was believed to be just too difficult and people essentially gave up. Renewed international interest in tackling malaria had already started around the time Dr Brundtland was elected as Director General of WHO in 1999. African Heads of State and African Ministries of Healthasked her to take up the mandate to do something very significant about malaria. So, one of the first promises Dr Brundtland made was to put malaria high on the agenda. That was the birth of Roll Back Malaria.

So what is Roll Back Malaria (RBM)?
The concept was very carefully constructed. It conveys the idea of pushing malaria back, not wiping it out or eradicating it. We are not at the stage where we can say that we can eliminate or eradicate malaria. What we want to do is to stop an increase in the spread of malaria and then start to push it back and reduce significantly the numbers of deaths. The Roll Back Malaria cabinet project was launched to call world attention to the problem of malaria; to let people know that there are some things we can do now which are tried and tested, and which work and that there could be better tools which could be developed and which would work even better such as vaccines or even genetically modified mosquitoes.

What can we do now about malaria?
Roll Back Malaria promotes four main activities: ensuring prompt access to effective treatment – preferably within 24 hours; ensuring prevention and control of malaria in pregnant women by encouraging use of insecticide-treated mosquito- nets and preventive doses of anti-malarial drugs; encouraging everyone to use insecticide-treated mosquito-nets; and finally improving the prediction, detection and response to malaria epidemics and developing tools to limit the impact of malaria in complex emergencies. Roll Back Malaria is also working to keep malaria on the political and development agenda and ensure continued focus and funding.

What is the importance of political commitment?
Raising the profile of malaria as a major development issue and galvanising political commitment was the first challenge for the RBM partnership and its founding partners – UNDP, UNICEF, WHO and the World Bank. Securing the political commitment of first world countries and endemic countries was essential if we were all to tackle malaria on a large scale and in a sustainable fashion. The Abuja Summit on malaria two years ago helped secure the support of the Head of State of Nigeria,  H.E. Chief Olusegun Obasanjo, President of the Federal Republic of Nigeria who was convinced that malaria was a political and important problem. Getting one political leader of high reputation such as President Obasanjo to convey this to all the other presidents and leaders in Africa which in turn mobilized their ministers and technicians about malaria, is an example of getting political commitment. The challenge that we have now is maintaining the momentum and reminding people of the promises which were made and following them up.

Can malaria be eradicated?
If we had a very effective vaccine, we could probably eradicate malaria. But if we have a very effective drug which can be given to most people affected by malaria combined with different interventions which can control the infection, this would have a major impact. For example, vector control with either insecticide-treated mosquito-nets, or insecticide spraying, when used together with drugs, may have a synergistic impact on transmission. Theoretically, malaria could be eradicated if we had enough funds to launch a massive effort.

When do you think we will have a vaccine against malaria?
We are not yet certain when we will have a vaccine or if we will ever have a vaccine. Scientists suggest that it is possible to develop a vaccine partly because we know that children develop immunity when they have had repeated attacks of malaria. One of the problems is that immunity does not last very long. If we take a child from Kenya who has repeated attacks of malaria, he will have developed some immunity. When he gets bitten by a mosquito, he will still get sick.. If we bring that child to Geneva for two years and then take him back to Kenya, when he gets bitten by a mosquito, he will get very sick indeed and may die. So you lose immunity if you do not get constantly re-infected.

Why is it taking so long to develop a malaria vaccine? 
Malaria is a disease of poor people and of poor countries and it has largely been ignored. The answer to “will we have a vaccine” depends very much on the volume of research, the number of scientists, the number of trials and the amount of scientific work which is being done. Until recently, there was very little going on indeed, there were a few scientists working very hard but there wasn’t much investment. In the last three or four years, the volume of investment in vac- cine development has increased considerably due to the renewed global interest in malaria, which is partly due to the efforts of Roll Back Malaria.

What is the overall cost of applying the required interventions to prevent malaria? 
The WHO/RBM strategy is not to promote a special single disease control programme which aims at eradication. Our strategy is to tackle malaria within the existing health systems, which are also dealing with other diseases, promoting actions that people can do for themselves. We do not know how much a vaccine will cost, because we don’t have one. What we do have is a way of preventing mosquitoes from biting people through using insecticide-treated mosquito-nets.

Are insecticide-treated mosquito-nets available at low cost so that populations at risk can afford to buy them? 
There are some countries where the cost of mosquito-nets has been brought down from about $10 to about $4 in the last few years. The RBM partnership has helped to do that by increasing the volumes of mosquito-net sales. When you start having a market of millions of nets, international competition comes in and drives the cost down. Secondly, we have worked to reduce the taxes and tariffs to make mosquito- nets more affordable. In some countries, mosquito-nets were treated as a luxury item, like curtains, or wedding dresses, but a mosquito-net is a health item. So we argued with Ministries of Health, Ministries of Finance, the World Bank and the International Monetary Fund to get rid of the import duty so as to reduce the price of insecticide-treated mosquito- nets.

Do people buy them?
It varies from country to country. For example in Tanzania, half of the population have bought a mosquito-net in the last five or six years and they are using it to protect their children.

What strategies does RBM recommend to prevent and treat malaria?
We recommend that all pregnant women and young children sleep under an insecticide-treated mosquito-net. We also recommend that all pregnant women receive intermit- tent treatment doses of effective anti-malarial drugs. Pregnant women and their unborn children are particularly vulnerable to malaria. Roll Back Malaria is also working to ensure that everyone, especially children, get prompt access to antimalarial treatment. Up until ten years ago, there was a very effective and very cheap drug called chloroquine that worked pretty well almost everywhere and it cost about $0.10 cents per treatment. It was a beautiful drug when it worked. The problem is that the parasite has been able to mutate, and develop a mechanism to pump chloroquine out of its body so that it no longer kills the parasite. It is laughing at the drug. So in many parts of the world, the drug with which, ten years ago and for $0.10 cents, you could treat malaria is no longer effective. Now, if you give that drug to a child, the fever may go down for three or four days but then the fever returns. The drug has made the parasite shiver but it hasn’t killed it. In some parts of West Africa chloroquine is still being used because it has retained its efficacy. There is one more new drug called sulfadoxine-pyrimethamine (SP for short) also available at a low price and which is now being used as first-line treatment in Tanzania, Kenya, Uganda and Zambia. Unfortunately, the parasite is laughing at that drug even faster than chloroquine. After five or six years, the parasite has developed resistance to SP. WHO brought scientists together last year and they decided that we could not continue to tackle malaria with just one drug alone. To be successful, we must combine two different drugs, so that the probability of the parasite developing resistance will be minimised. So combination therapy is the big hope for effectively treating malaria. Scientists believe that one of the drugs should be arteminisin, a very effective drug which was discovered through Chinese traditional medicine some time ago.

If Artemisinin was known for years, why didn’t scientists use it earlier against Malaria? 
It was known to Chinese traditional healers and used widely in China. Chinese scientists became aware of it in the seventies and as they were working with Western counterparts, the particular properties of this drug started to be widely known. Further studies produced a scientific consensus that artemisinin combined with another drug is the best way for treating malaria. RBM is looking for ways of making combination drug therapies available to countries where the parasite has developed resistance to chloroquine and/or SP. We are encouraging pharmaceutical companies that can produce these combination treatments to provide them to developing countries at the lowest possible cost.

Why has a well known pharmaceutical company signed an agreement with WHO? 
A Swiss-based company, actually came to WHO and indicated that they had the foresight to buy the licence and manufacture a new combination therapy, which is a mixture of an artemisinin derivative and another effective antimalarial drug. They knew they were not going to make a big profit out of selling this drug in developing countries because it was so expensive. Therefore, they decided to offer WHO the possibility of providing it at cost to developing countries where malaria is resistant.

So, is WHO responsible for its distribution? 
WHO agreed to carry out the international negotiation over the use of the drug. WHO liases with ministries of health or other agencies at the national level and the pharmaceutical company to ensure that the drug will be used and distributed properly.

This is an excellent advertisement for them also 
Yes, but we do hope that this will encourage other companies to do the same thing with similar types of drugs.

Are there other public/private partnerships which support RBM goals? 
One example of a partnership already described is the agreement between the Swiss-based pharmaceutical company and WHO. GlaxoSmithKlinehas taken up the challenge to support communities in endemic countries with information, education and communication (IEC) projects to help roll back malaria. ExxonMobil oil company is working with RBM in a different manner to strengthen malaria control in certain African countries. We are also working closely with the insecticide companies and those producing mosquito nets.

What is the interest of private companies in doing that? 
The interest of the oil companies, like ENI, is buying good-will in countries in which they are working where malaria is a national problem. They have a commitment to reduce the malaria burden within their own staff to obtain higher productivity but again they see it as a relatively inexpensive way to expand those activities and malaria prevention to the surrounding population.

Does malaria increase with natural disasters/wars? 
Malaria transmission is clearly associated with wars and natural disasters because the ecology may change with the production of many breeding places for mosquitoes with excessive rain and flooding. During a war or a major conflict, malaria control measures break down, there is less spraying, health facilities do not work, there is rupture of stocks for drugs and all this brings an increase in malaria transmission and an increase in the number of deaths. This is particular true in Africa where there are increasing numbers of internal conflicts, wars and natural disasters.

I read that insecticide-treated mosquito-nets have reduced malaria by 98% in Vietnam, can you please comment on that? 
A combination of factors. One was the extraordinary political structure in Vietnam, the resources and education level as well as the organization. It was made a political priority and it worked. Also, in essence, the type of malaria was easier to control than in Africa so that the job was easier in Vietnam. In addition, the Vietnamese were able to use the Artemisinin drug very effectively and produce it in country. This combination of factors resulted in a big reduction in malaria cases, which is wonderful. In Africa where there is the worst possible mosquito and parasite, we don’t expect to see the same kind of rapid decrease that we saw in Vietnam but we believe a more gentle reduction in Africa would be possible. 

How can Traditional Medicine help Malaria? 
Quinine is a product of traditional medicine used against malaria first as an infusion and later as tablets and vials. Artemisinin went through the same process. They were first used in infusions and later extracted in a tablet. It is possible that traditional medicine may be able to identify new drugs which may be even more effective than current ones. This is an area where we need to intensify research.

What can now be considered as an efficient antimalarial drug? 
The combination of artemisinin derivative with another effective drug. The scientists hope that this drug will be efficient for ten years or more.

Is such a drug available now? 
A combination drug is available now. However, it is still very expensive, it still would cost perhaps $2 to treat an African child. If you look at the total amount of funds spent on health per person in Tanzania, it is about $7 per year. So, this is an enormous amount of money. Two dollars to treat a child with this combination therapy compared to 10 US cents to treat a child with chloroquine. There is an enormous amount of work to do to bring the price down further. But we cannot rely on drugs alone, we must move forward on insecticide-treated mosquito- nets and prevention, to reduce the total demand for drugs. A combination of different strategies is needed to combat malaria.

When do you think malaria would be more or less under control in Africa? 
We are optimistic that we will be able to reach the RBM target, a very tough target, to halve the burden of malaria by 2010. It still means that Malaria would be terrible problem in 2010 because still a lot of children would be dying from it. It is an ambitious international target. We have the tools, they are not perfect, but they are good enough if we have every government supporting wider access to insecticide-treated mosquito-nets, as in Tanzania. If we have every country ensuring good access to treatment, we will be close to reaching these goals. It would probably require about a billion US dollars a year, half of that money can probably come from governments in Africa themselves and some of the additional money would come from the international community. You mentioned the Global Fund to Fight AIDS, TB and Malaria, and the fact that the amount of money which has been pledged so far is much lower than we need. We hope that as we show success and results, more money will come in. I think we have to remain optimistic, but not naively optimistic. Malaria is certainly a tough challenge, we are not talking about eliminating or eradicating it. Our goal is to reduce the malaria burden particularly in Africa and to increase control in other parts of the world.

The last word
Readers should realize the enormous burden that malaria represents in the world. It contributes to poverty and keeps poor people poor. By tackling malaria, we believe we are making a contribution to reducing poverty. Although malaria is a scientific and technical challenge, we believe that many of the solutions are already at hand. Vaccines or even genetically modified mosquitoes remain potential additional tools for the future but even without them, we believe that we have the tools at hand to make a difference to peoples lives right now.

Thank you to Mr David Alnwick, Dr Andrea Bosman and Ms Prudence Smith who participated in this Q. and A. session.

Website: rbm@who.int

Remember!
Each year, there are more than 300 million cases of malaria. Malaria kills one million people each year mostly African children

Monique Eid, WHO. Photos WHO, P. Virot