10 January 2013

Africa: Working Toward Malaria Eradication the 'Only Viable Long-Term Strategy'

interview

Dr. David Brandling-Bennett, deputy director of the malaria programme at the Bill & Melinda Gates Foundation, says that recent success in Zambia is proof that real progress can be made in the fight against malaria. AllAfrica recently spoke with him about current tools being used to fight the disease, the prospect for a vaccine and the hope of new drugs to accelerate progress.

Carlos (Kent) Campbell says the world is essentially on the brink of something great when it comes to malaria - do you agree?

I certainly agree that the situation today is very different from what it was 10 years ago and probably even five years ago. Everywhere, in Africa and outside Africa, the malaria burden cases and deaths are down and that is palpable. And certainly in Africa it's very different from anything we have seen previously. Even outside of Africa, in Asia and the Americas, we have seen significant declines for the past decade. We're almost back to levels we last saw during the previous eradication effort (in the 1960s) where malaria cases were reduced with intensive effort, quite significantly. It's great to see this progress.

To what extent is the malaria fight a race against time?

We need to get this done as quickly as we can. Malaria fights back, and recent gains can be lost if we don't keep up the momentum. The longer it takes, the more we will have to deal with issues of the parasite's resistance and the ability of the human population to sustain a long-term effort. Hopefully, we will be able to contain drug resistance before it goes to Africa.

Insecticide resistance is a much wider problem. At this point, it's not clear that it has that much of an impact but we have to assume that level of resistance will rise and at some point will impact our programs. It has the ability to seriously compromise what we are doing, so the sooner we do it the better and by doing it sooner we are also going to be saving more lives.

What do you think about the prospect for a successful malaria vaccine?

We had hoped that the RTS,S vaccine would have had a higher level of efficacy and effectiveness than we have seen with the most recent results. We still need more data from these trials that are still underway now will continue through 2014. We will have more evidence, for example, on the duration of immunity and whether a booster dose is needed and produces a more effective result from the vaccine. But we also realise that we do need a vaccine that will interrupt transmission to assist in elimination.

The RTS,S is certainly not the elimination vaccine; it is not the eradication vaccine. We are working on producing what we hope will be a more effective vaccine, but that is going to take time.

Is it fair to say that we can achieve eradication without a vaccine?

That is fair to say, but a vaccine that produces solid, what we call sterilized immunity, so it prevents infection and has a durable effect, would be tremendously beneficial. We are also looking at vaccines that would block the infection in the mosquito, so when you give a person a vaccine against the forms that are transmitted by a mosquito - we call those transmission-blocking vaccines - that would be advantageous. It would help at a population level by reducing the amount of transmission.

Ideally we would like to combine those because that would then both protect the individual and protect the population but we don't have to have that. That would be a tremendous asset for accomplishing eradication but we believe that eradication is achievable even if we can't develop a vaccine. And I do think a vaccine is feasible but it may take a long time and we might achieve eradication before we get the vaccine - that's okay.

We do have effective tools but we need to improve upon those. What we are very interested in now is not just preserving and improving the effectiveness of treatment, but using drugs for preventive measures. That is already in place, to a limited extent. We use drugs, for example, to prevent the adverse effects of malaria during pregnancy. We use drugs for preventing serious infections in infants and children.

But large-scale use of drugs for actually reducing transmission and preventing further infection and reducing the total burden of malaria, the total number of parasites in a population, is not something we have done on a large scale or very consistently. It is certainly something we need to explore and probably exploit in order to be able to accomplish our goal of eradication.

What if you could make an anti-malarial such as Malarone cheaper and distribute it to malaria-endemic areas during the rainy season, what kind of effect would that have?

You are on to the right idea. If you could give drugs that are safe and highly effective to a population where over a period of time you are actually reducing the total number of people who are affected and therefore transmitting the infection - that would be an asset.

A drug like Malarone, which needs to be given frequently, is probably not the one you want. You want a drug that is long acting, so you only have to give it occasionally, because you can't get to the population all that often. But the challenge with any drug like that is safety. So if you are giving - particularly healthy people - a drug that has a long duration of action, you want a drug that is highly safe, and actually those are the most difficult drugs to develop, ones that have long duration of action and are highly safe.

Here's an analogy: we have a drug that we use for treating and preventing Onchocerciasis, river blindness, and lymphatic filariasis, elephantiasis, called ivermectin. It's an old veterinary drug, you give it once a year and its very, very safe. It would be great to have something like that for malaria - very challenging to develop, but if we can that would be a tremendous tool.

Can you talk a little bit about the success in Zambia of the Malaria Control and Evaluation Partnership in Africa (Macepa) program at Path?

Macepa's success is in demonstrating that we can drive down transmission. Back in 2003 when we first came up with the idea of working with some countries to show that they could scale up what were then at that point accepted interventions - bed nets, indoor residual spraying where that's appropriate, intermittent preventive treatment in pregnancy and good case management with diagnosis. Those were understood and accepted, and African heads of state committed to doing this at the Abuja meeting in April 2000 in Nigeria, but that didn't happen.

So we wanted to show that it could be done and it would have impact. We worked with Zambia - I think that was very successful. We have worked with other countries and I think the Roll Back Malaria partnership with funding from the Global Fund, The U.S. President's Malaria Initiative, and the World Bank has actually led to significant areas of decline across Africa.

Many partners have helped in Zambia, so I don't know that we would want Macepa to get all of the credit for what has happened, but they have been in the lead. And now we want them to lead in the next stage because we still have a lot to do with scaling up to get better control, to take full advantage of what we have. But now we need to drive transmission down further, so where it is feasible to interrupt transmission or where that is still not feasible, how do we get transmission down further where that is not happening?

We want to understand what it will require to get countries ready for elimination. Now in southern Africa, looking particularly at the south of Zambia where transmission has been reduced in parts of areas, how can one build on that, really interrupt transmission in those areas? Northern Senegal is a similar situation. In parts of Ethiopia where transmission is lower, what can one do to further reduce and eventually interrupt transmission in those areas?

So Macepa has a list of countries where this approach could yield similar results but Nigeria is not one of them?

Nigeria is very challenging. It is a quite complex country for various reasons. The governmental structure is part of it. There is a very heavy reliance on the private sector for treatment - 60 to 80 percent of people get their drugs through the private sector rather than the government. This is fine, we have to work with it, but there are very challenging settings which we need to work with partners to succeed in reducing malaria comparably in those areas. Scale up is happening, if you look at what is happening with net distribution in Nigeria, in the DRC, good progress is being made, although there is much more to be done.

One of the emerging interventions in Nigeria is work with the small patent medical vendors.

Certainly some of the work that has come out of the Affordable Medicines Facility for Malaria (AMFM) has shown that if you can get the cost of drugs down, then people will purchase the drugs. You can improve what we call access. So the drugs become available and people can afford to buy them and if they recognise them as quality drugs, they will buy them and that's a critical thing. Whether a subsidy or a co-payment scheme with the AMFM is something that can be sustained, can be extended, we will have to wait to see.

We are also working with the pharmaceutical industry in various countries to see how the actual cost of producing artemisinin-combination treatments (ACTs) can be reduced. It is challenging but we believe there are ways to get the actual cost of these drugs down, and therefore the prices down.

Certainly making these drugs available to people in Nigeria, where the private sector, even informal drug sellers, are the major source of drugs, that is critical in order for us to be able to ensure that people have adequate treatment which does impact the amount of malaria that is going to happen.

What will it take to tackle malaria in Nigeria?

It is going to be a multi-pronged effort. Certainly to further scale up the use of bed nets and indoor residual spraying, which is not that widely used in Nigeria at this point in time, to ensure access to quality treatment and introduce more rapid diagnostic tests.

Eventually we would like to have universal diagnosis so that people are treated based on a diagnostic. That is very challenging to achieve in the private sector. We still don't understand adequately what will drive a shopkeeper, for example, to use a diagnostic test.

So those measures will hopefully serve to reduce the burden of malaria across Nigeria significantly. In northern Nigeria we are beginning to do some work with the Malaria Consortium, to look at this approach called Seasonal Malaria Chemoprevention. It entails giving three or four doses of a drug just before and during the high transmission season, where there is a three- to four-month transmission season to children under five years of age or potentially under 10 years of age, which significantly reduces the amount of malaria. It is almost like it is epidemic when it's highly seasonal. So that certainly is effective in reducing the burden of malaria.

So many people still buy chloroquine but there is widespread resistance to the malaria drug. Why are these drugs still on the market?

Actually, it is interesting. Chloroquine had two good properties when parasites were sensitive. One, it killed the parasites, and two, chloroquine is a pretty strong anti-inflammatory so it is like aspirin or Tylenol and people will feel better if they take it and their fever will go down in addition to the effect on the parasite. That still happens, especially in people who have some immunity, even if the chloroquine doesn't cure their infection.

The problem that was very evident when I was working in Africa when chloroquine resistance was increasing, was that children might get a little better but their infection wasn't cured, and then they get re-infected anyway. So these children would develop severe anaemia from multiple episodes of malaria. Malaria sort of became a chronic disease in western Kenya, for example. Children would come into the hospital and they would get treated and go home, and then they would die a month later, whether from that malaria episode, another malaria episode or some other illness that just took them over. That was the serious problem with chloroquine resistance in the 1980s and 90s. It wasn't until the introduction of ACTs that we really started to see things improve, and that has been very evident in terms of mortality declines in Africa.

There is probably not much point in trying to get rid of chloroquine. It's more important to make the other drugs more available and to help people understand that these are better drugs. It's a positive, approach rather than a negative one. In the public sector there is less of a problem. So where people access drugs, if the drugs are available, they are generally the appropriate drugs. A problem in the public sector is often stock-outs - drugs are not where they should be.

The problem in the private sector is the wrong drugs are there, primarily because they are much cheaper. So if we can make the quality of drugs more affordable and have people understand that those drugs are indeed better, than they'll seek those out and probably will pay a little bit more if they can afford them.

We realized in the early 2000s in working with a group of investigators that we needed to do two things. One, we needed to improve access to these very effective drugs which are relatively expensive, but we also wanted to be sure that these drugs were reaching those who needed them. So we formed the ACT Consortium with the idea that we want to bring these two circles -- those who are treated and those who have malaria -- together, to overlap, to improve access and to improve targeting.

Is there anything else you would like to tell us?

It is tremendously exciting what has been happening. I find it very rewarding that the malaria community really seems to come around the idea of elimination and eradication, whereas five years ago many people would have expected people to say, 'What is this idea? Are you nuts?' This has really galvanized the malaria community but it is a challenge.

There is a lot of work to be done to extend the gains we have got but also to build upon those so that we actually do achieve interruption of transmission in more and more places and eventually eradication. Working toward eradication is the only viable long-term strategy to fight malaria.

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