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Africa: Attacking Malaria Before it Sickens

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"We are now witnessing a true renaissance, an awakening, about malaria," Carlos (Kent) Campbell said when he accepted a lifetime achievement award in November at the American Society of Tropical Medicine and Hygiene. Campbell attributed the progress to "a huge global effort". But the award was aimed at recognizing the critical contribution he has made to the development of effective malaria control strategies.

In part two of an AllAfrica interview, he describes the work carried out in Zambia by the Malaria Control and Evaluation Partnership in Africa (Macepa), a program at PATH funded by the Bill & Melinda Gates Foundation. For part one of the interview, view here.

Is the goal to reduce transmission of malaria in Zambia to zero?

That's what's occurring in areas where we have been working. We've been working in areas contiguous to the southern border to drive down transmission, recognizing that the national boundaries have nothing really to do with transmission, except in terms of program implementation. Obviously, there is uncontrolled malaria in Zimbabwe and Mozambique. At the same time, other partners are working intensely on areas in the west and the north that still have a considerable amount of transmission - where coverage has not been sustained because of funding and other issues.

We're a long way from eliminating malaria in Zambia. But there's a strategy, and clearly we've seen that it's possible to build out malaria-free zones using available technology.

Prevention is a big part of what you've been trying to do?

The need for drugs to treat malaria cases is just a marker for the failure of prevention. The higher the coverage with prevention interventions, the less transmission there is, and therefore the less malaria there is to be treated. What has been seen in Zambia - and in Kenya, Tanzania, Senegal and a number of other countries that have made considerable progress - is that need for artemisinin-based combination therapies (ACTs) falls off precipitously as these prevention efforts step up. So the big challenge is to prevent transmission so that there isn't such a demand for the drugs. And then to have a more targeted use of ACTs - only giving ACTs to individuals who have symptomatic parasitic infections.

That has been challenging because it goes against the standard way in which malaria was treated in Africa. Malaria has historically, until recent years, been equal to fever. There is a lot of fever in Africa, and where there is uncontrolled malaria, a lot of that fever in children is caused by the malaria parasite. But increasingly fevers presenting in young children are not malaria, they're something else - pneumonia, for example, and they are hard to diagnose.

The advent of rapid diagnostic tests for malaria to make testing affordable and easily deployed to community health workers - and to be able to quickly determine if a child that is presenting with what might likely be malaria really is malaria - that opens up a great opportunity for two things: decrease in the use of ACTs and a discussion around what illness the child actually has. The latter is a very big issue and is something that a number of communities are trying to work on in a more integrated way.

What role does treatment play in malaria control?

Particularly when the prevalence of parasite infection gets fairly low, one of the strategies used historically is what we call mass drug administration, which was used to get rid of parasites, whether there were symptoms or not. Most of the people who infect mosquitoes are not symptomatic - they're asymptomatic. Because of acquired immunity, they carry low levels of parasite in their blood, but they infect mosquitoes. So the drug is used to eliminate parasites in those individuals. That's not actually treatment of the disease; it's treatment of infection. That is at the heart of what the World Health Organisation (WHO) has proposed - test, treat and track. It's a very solid strategy and something we're working on right now.

Does any of that strategy involve testing in the absence of symptoms?

Yes, it has to do with using rapid diagnostic tests to look for infected people. That's a very cost- and resource-intensive effort, which really only is affordable and makes sense when you have very low levels and you're trying to eliminate parasite carriers. So you've got to have far less than one percent of the population being infected, because otherwise it's not cost effective.

Are you testing whole populations in Zambia now?

Selectively, yes.

What are some of the challenges the malaria fight is up against?

The two issues are insecticide resistance and drug resistance. There is resistance to pyrethroids, which is the insecticide that is impregnated into bed nets in some parts of Africa. That resistance has not translated into making bed nets ineffective, but conceivably, and I think realistically, that's going to evolve.

Resistance to the artemisinins is a fact in pockets in Southeast Asia - not documented to date in Africa, but the drug resistance will spread the more the drug is used. That doesn't argue that we can't eliminate malaria or that we shouldn't try. It says that we should be doing this rapidly so that this doesn't become a long, drawn-out operation. A lot of effort on the part of a lot of researchers is going into finding new insecticides and there is a next generation of anti-malarials, which are at least in the mid-testing stages. We have to believe that solutions will be developed before there's a crisis.

So what is required to eradicate malaria?

Several things. One is optimal utilization of currently available tools, including bed nets, indoor residual spraying, the use of drugs for the treatment of malaria cases, and some innovative uses of malaria drugs and some other currently available interventions to make progress in driving down transmission. We already know from work that has been done by our group and several other groups that, in some areas, malaria transmission has already been extinguished. There has not been great progress made to date in terms of scale up, and not optimal use of malaria interventions. We are still at a point right now where determining what is the 'optimal' utilization of currently available tools is ongoing and has to be tailored to particular settings, so that is the first thing.

There are some other tools that are coming along which hold great promise, including the development of certain types of drugs with characteristics that would be hugely important, not so much for the treatment of illness but for the actual eradication of infection. There is a lot of encouraging work going on right now to find such a drug. So the quest for additional, more effective, or complimentary tools is ongoing. Whether it's a vaccine or whether it's a drug, or whether it's a novel, immunological intervention we have to see.

Do you think that malaria can be eliminated or close to eliminated without a vaccine, just by using this arsenal of approaches?

Yes, but yes in a guarded way. I think that it can be. The question is: are we going to see that happen in the next decade? We're going to see great examples of that occurring in broad geographic areas, but we're also going to continue to see transmission in other, contiguous parts. So it will be a continual battle. The tools that we've got are capable if applied systemically. But the reality is that this is a hard struggle and this depends on a number of things, like financing.

The other reality is that there probably isn't going to be a vaccine in the next five to 10 years that is going to make a big difference in terms of malaria elimination. There's not a vaccine that we have that would turn the tide of malaria elimination in Africa - it just doesn't have that effect. There aren't other vaccines that are coming along after this vaccine called RTS,S that are close to being ready for use. What we've got for the next five to 10 years will be better insecticides, better drugs, but not likely a magic bullet like a vaccine that would make malaria elimination work.

You have said that investment in malaria offers an incredible return, obviously for humanitarian reasons, but what does it mean for development in Africa? Does it reduce the need for other kinds of aid?

There have been various estimates of the cost of malaria to African economies, variably estimated in the U.S.$12 billion GDP range - and those costs go far beyond deaths. Malaria kills the very young, and from a strictly economic standpoint the young don't contribute very much to GDP and so the high infant mortality rates and high childhood mortality rates actually don't constitute, in economic terms, a great economic burden. They do in humanitarian and health care terms. But the ability of the workforce to be predictably strong and able is just a huge issue with malaria. You can see this in terms of reports that have been done by sugar plantations and cotton growers in rural Zambia. So I think that the big thing is that malaria elimination is going to have a tremendous return on investment, and it already does.

In Zambia, the return on investment for getting rid of malaria has just been phenomenal. Reports show that the workforce is basically available. When malaria was not controlled, there would be an average - I forget the exact number - of somewhere around 30 days a year lost to malaria by every worker. That's gone, and so the benefit of that in terms of just how many workers are needed, and even the workers who are on the job in terms of their ability to work effectively has been quite remarkable.

The same things have been seen in other sectors too. The thing about malaria is that it is not transmitted in that many large urban areas of Africa. So the urban workforce is less affected by malaria than is the rural or agricultural workforce. Large agricultural holdings are where this benefit is primarily accrued.

When you have places in conflict, like the Democratic Republic of the Congo, how do you manage to achieve eradication?

With a great deal of effort and a certain amount of patience. A lot of progress has been made in DRC around the deployment of bed nets, using this Scale-Up for Impact (SUFI) model. Now there are parts of DRC that just aren't accessible by the government and that remains a big challenge. But you know, conflict comes and conflict goes. And so the elimination of malaria in Africa is not all going to happen in the next five or 10 years. We may find ourselves in a situation of waiting out DRC.

Can you sum up how you view prospects for making continuing progress.

This is a very exciting time because we are about to see a big push around elimination, moving to eradication. In 2007 Bill and Melinda Gates laid down the gauntlet around malaria eradication, and they didn't do this as a sound byte. They have been pushing very hard on their own organization and on the international community - both science and program - to be on task and to make progress. There is also a push coming from the WHO.

A group at PATH is working with several African countries to understand how a national program structures its interventions, what it needs to do, and how it develops the business model. The campaign for the past five to eight years has been trying to get bed nets out and get a high level of usage of those bed nets - to understand what that single intervention could do in terms of a key health outcome, which is childhood deaths. To our tremendous amazement, the impact has been even greater than we could have imagined.

In Zambia, a 29 percent reduction in all childhood deaths occurred within a couple of years. Now, that is not the backbone of a program for eradication. You can't stay in campaign mode. You have to move to a program where there is a set of inputs and things are occurring, and it has to move to the community level. How that transition occurs and how national governments align themselves around malaria elimination is what is being determined at this point.

Our colleagues in Zambia are doing a tremendous amount of work around this issue. Understanding how much decrease in malaria transmission can occur in defined epidemiological settings is the great frontier. In the next two to three years, we are going to see a great deal of progress. The efforts on malaria are not a one-off!