Editorial

Malaria in 2018: A glass half full

Malaria has been one of the most important infectious diseases of humans for millennia. Our understanding of malaria has progressed steadily, from the discovery of the parasite by Laveran and the elaboration of its life cycle by Ross, both in the late 19th century, to progress in characterizing malaria clinical features and epidemiology through the 20th century, to an explosion in our understanding of parasite biology, vector mechanisms and host responses in recent years. But has all this progress in our understanding of malaria gotten us closer to eradication of this deadly disease?

Philip J. Rosenthal

Malaria has been eliminated from dozens of countries around the world. Much of this progress took place decades ago (eg, most of North America and Europe), but there are also recent success stories (eg, Sri Lanka was declared malaria free in 2016). Some past ambitious efforts to eradicate malaria, notably a plan put forth by WHO in 1955, demonstrated some successes but eventual failure. In particular, progress was not seen in most of Africa, where the large majority of episodes of malaria, mostly from the potentially lethal Plasmodium falciparum parasite, occur. More recently, the conversation has moved from control back to the more ambitious agenda of elimination (getting rid of the disease in a defined place) and eradication (getting rid of the disease from the whole planet). This conversation has been accompanied by dramatic increases in funding for malaria research and control in recent years. In particular, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and the President’s Malaria Initiative have spent billions on malaria control interventions. In parallel, spending on malaria research by numerous government and private agencies has been generous. So, how are we doing?

In fact, progress in malaria control has been mixed. Our ability to measure malaria has improved, with more widespread surveillance, more standardized metrics and improved modeling techniques to make sense of data that remain sparse in much of the malaria-endemic world. Although it is difficult to compare numbers generated by different approaches, we have seen a steady decrease in malaria mortality since the beginning of this century, with worldwide estimates decreasing from 1 to 2 million to roughly half a million deaths per year. But the numbers remain uncertain. Two estimates for deaths from malaria in 2015 were 446,000 from WHO and 631,000 from an academic group.

Very recently, we have been seeing a bit of a change in mood in the malaria control community. We have gone through about a decade of optimism, with key players celebrating our advances and exhorting us to keep up our efforts as we move, country by country, from control to elimination. Then came the latest World Malaria Report, published in late 2017 by WHO. The cover of this report shows a signpost, emphasizing that we are at a crossroads. After years of improvement, the numbers did not get better in 2017. Estimated cases of malaria rose from 211 million in 2015 to 216 million in 2016. Estimated death rates were basically flat — from 446,000 to 445,000. And there has been debate about which estimates to report; other methods show considerably higher estimates for morbidity and mortality.

So we appear to be stalled in our move toward malaria eradication. This is not surprising. As often happens in public health, initial enthusiasm for malaria elimination has waned somewhat, and overall funding has plateaued. Besides the political and economic realities, there are biological challenges. Malaria parasites are increasingly resistant to malaria drugs. Mosquito vectors are increasingly resistant to available insecticides. We continue to learn of complex means by which malaria parasites and anopheline mosquitoes defy simple solutions. As an example, Plasmodium vivax, the second most important human malaria parasite, is a particular challenge because the dormant liver stage is not eliminated by most available therapies, leading to relapses after dormant parasites progress to bloodstream infection. As another example, mosquitoes under attack from indoor insecticides may evolve to bite outdoors or to bite early in the evening, before individuals are under their bednets.

What can we predict for the future? There are reasons for continued optimism. Despite the recent identification of resistance to leading new antimalarials — notably the artemisinins and some of their partner drugs in Southeast Asia — the efficacy of these drugs to treat malaria generally remains excellent in Africa. Further, there is a robust pipeline of new drugs in development. Insecticide resistance threatens key vector control tools, but new insecticides and new insecticide strategies are under development. After decades of research, the first effective malaria vaccine, albeit with modest efficacy for the prevention of malaria in African children, may soon be available. Looking forward, improved genetic engineering techniques may enable the introduction of mosquitoes that are refractory to malaria. Financial and logistical constraints remain challenging, but the tools are in place to markedly decrease the burden of malaria.

But there are also reasons for caution. Malaria is so deeply entrenched in parts of Africa and other high-endemicity areas that even marked cuts in transmission may have small impacts on the incidence of disease. Further, control measures may allow persistence of parasites in a subset of the population, often without clinical symptoms, enabling continued transmission, especially if use of control measures declines. Despite advances, we still have a long way to go in Africa and some other highly endemic regions. In other areas, where we are moving toward elimination, we are encouraged by drops in morbidity and mortality, but it is very difficult to finish the deal and fully eliminate transmission of malaria.

So the malaria glass is half full. Much-improved tools are available, and the last couple of decades have seen unprecedented progress in the control of malaria. But progress appears to have stalled, and elimination and eventual eradication will be very challenging. We should celebrate our successes and redouble our efforts to control and eradicate this deadly disease.

Disclosure: Rosenthal reports no relevant financial disclosures.

Malaria has been one of the most important infectious diseases of humans for millennia. Our understanding of malaria has progressed steadily, from the discovery of the parasite by Laveran and the elaboration of its life cycle by Ross, both in the late 19th century, to progress in characterizing malaria clinical features and epidemiology through the 20th century, to an explosion in our understanding of parasite biology, vector mechanisms and host responses in recent years. But has all this progress in our understanding of malaria gotten us closer to eradication of this deadly disease?

Philip J. Rosenthal

Malaria has been eliminated from dozens of countries around the world. Much of this progress took place decades ago (eg, most of North America and Europe), but there are also recent success stories (eg, Sri Lanka was declared malaria free in 2016). Some past ambitious efforts to eradicate malaria, notably a plan put forth by WHO in 1955, demonstrated some successes but eventual failure. In particular, progress was not seen in most of Africa, where the large majority of episodes of malaria, mostly from the potentially lethal Plasmodium falciparum parasite, occur. More recently, the conversation has moved from control back to the more ambitious agenda of elimination (getting rid of the disease in a defined place) and eradication (getting rid of the disease from the whole planet). This conversation has been accompanied by dramatic increases in funding for malaria research and control in recent years. In particular, the Global Fund to Fight AIDS, Tuberculosis and Malaria, and the President’s Malaria Initiative have spent billions on malaria control interventions. In parallel, spending on malaria research by numerous government and private agencies has been generous. So, how are we doing?

In fact, progress in malaria control has been mixed. Our ability to measure malaria has improved, with more widespread surveillance, more standardized metrics and improved modeling techniques to make sense of data that remain sparse in much of the malaria-endemic world. Although it is difficult to compare numbers generated by different approaches, we have seen a steady decrease in malaria mortality since the beginning of this century, with worldwide estimates decreasing from 1 to 2 million to roughly half a million deaths per year. But the numbers remain uncertain. Two estimates for deaths from malaria in 2015 were 446,000 from WHO and 631,000 from an academic group.

Very recently, we have been seeing a bit of a change in mood in the malaria control community. We have gone through about a decade of optimism, with key players celebrating our advances and exhorting us to keep up our efforts as we move, country by country, from control to elimination. Then came the latest World Malaria Report, published in late 2017 by WHO. The cover of this report shows a signpost, emphasizing that we are at a crossroads. After years of improvement, the numbers did not get better in 2017. Estimated cases of malaria rose from 211 million in 2015 to 216 million in 2016. Estimated death rates were basically flat — from 446,000 to 445,000. And there has been debate about which estimates to report; other methods show considerably higher estimates for morbidity and mortality.

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So we appear to be stalled in our move toward malaria eradication. This is not surprising. As often happens in public health, initial enthusiasm for malaria elimination has waned somewhat, and overall funding has plateaued. Besides the political and economic realities, there are biological challenges. Malaria parasites are increasingly resistant to malaria drugs. Mosquito vectors are increasingly resistant to available insecticides. We continue to learn of complex means by which malaria parasites and anopheline mosquitoes defy simple solutions. As an example, Plasmodium vivax, the second most important human malaria parasite, is a particular challenge because the dormant liver stage is not eliminated by most available therapies, leading to relapses after dormant parasites progress to bloodstream infection. As another example, mosquitoes under attack from indoor insecticides may evolve to bite outdoors or to bite early in the evening, before individuals are under their bednets.

What can we predict for the future? There are reasons for continued optimism. Despite the recent identification of resistance to leading new antimalarials — notably the artemisinins and some of their partner drugs in Southeast Asia — the efficacy of these drugs to treat malaria generally remains excellent in Africa. Further, there is a robust pipeline of new drugs in development. Insecticide resistance threatens key vector control tools, but new insecticides and new insecticide strategies are under development. After decades of research, the first effective malaria vaccine, albeit with modest efficacy for the prevention of malaria in African children, may soon be available. Looking forward, improved genetic engineering techniques may enable the introduction of mosquitoes that are refractory to malaria. Financial and logistical constraints remain challenging, but the tools are in place to markedly decrease the burden of malaria.

But there are also reasons for caution. Malaria is so deeply entrenched in parts of Africa and other high-endemicity areas that even marked cuts in transmission may have small impacts on the incidence of disease. Further, control measures may allow persistence of parasites in a subset of the population, often without clinical symptoms, enabling continued transmission, especially if use of control measures declines. Despite advances, we still have a long way to go in Africa and some other highly endemic regions. In other areas, where we are moving toward elimination, we are encouraged by drops in morbidity and mortality, but it is very difficult to finish the deal and fully eliminate transmission of malaria.

So the malaria glass is half full. Much-improved tools are available, and the last couple of decades have seen unprecedented progress in the control of malaria. But progress appears to have stalled, and elimination and eventual eradication will be very challenging. We should celebrate our successes and redouble our efforts to control and eradicate this deadly disease.

Disclosure: Rosenthal reports no relevant financial disclosures.