Leo Braack has spent most of his life in Africa working on vectors of malaria, arboviruses and also stints on ebola and marburg viruses. He is now responsible for vector control aspects with the Bangkok-based Malaria Consortium where he is also the Technical Lead for the Vector Control Working Group of the Asia-Pacific Malaria Elimination Network
In the early years of the new millennium, the headlines were heady and euphoric: Malaria cases were plummeting globally, a strong decline across all continents, with the successes backed by a trio of seemingly invincible tools.
These were a combination of long-lasting insecticide impregnated bednets, indoor residual spraying of insecticides to kill mosquitoes inside, and a new anti-malarial drug artemisinin to which no resistance was in sight. In addition to this was the ever-prevailing hope of a malaria vaccine in the offing.
Back in 1998, already several major global institutions – led by the World Health Organization – optimistically linked hands and announced an alliance called Roll Back Malaria, with the stated aim to eliminate malaria as a public health problem, as captured in the Abuja Declaration in 2000.
Gone was the gloom lingering from a previous global attempt at malaria eradication during the 1950s, when a combination of DDT as an all-powerful insecticide and the highly effective and inexpensive drug chloroquine seemingly boded an imminent farewell to a scourge that has devastated humanity over thousands of years.
But it all came crashing down – mosquitoes developed resistance to the DDT and the malaria parasites to the chloroquine, so that the global eradication campaign was abandoned in the 1960s.
With a new generation taking over global agendas, and an appetite spurred by successes in eradicating smallpox and close to doing so with polio, enthusiasm resurged for taking on malaria. In the new millennium donors lined up, willing to commit hundreds of millions of dollars to the fight, global health networks were strong and committed, and country national institutions had developed internal capacity to combat this most persistent of historic foes.
In 2005, the World Health Assembly set as a target the reduction of malaria cases and deaths by 75% by 2015. And then in October 2007 at a Gates Malaria Forum the call went out that, well, what the heck, maybe eradication should be back on the agenda.
Enthusiasm swelled to adopt this most ambitious of goals. You could almost imagine John F. Kennedy up there, proclaiming a new moon landing, except this time it was a planet void of malaria. A few sage voices tried to taper expectations – that we didn’t have the right tools as yet, we needed a new set of armaments – but the genie was out the bottle, subconsciously now eradication was the objective.
In 2011 the RBM partnership updated the objectives set out in the Global Malaria Action Plan in 2008, aiming to reduce malaria cases by 75% from 2000 levels by 2015, but also the more ambitious target of the reduction of malaria deaths to near zero by 2015.
In the decade or so after the year 2000 a minor miracle did indeed take place. From 2000-2017, malaria mortality rates were reduced by about 60% globally, and malaria cases declined by 36%.
This was undeniably a remarkable achievement. But then things went sour. Mosquitoes were once again becoming resistant to insecticides, international funding levels never matched what was really needed, and, alarmingly, malaria parasites were starting to show resistance to the main drug of choice, artemisinin-based combination therapies.
Each year the rate of success declined, a plateau had been reached, and malaria case numbers even started going up again in many places. Our most recent global figures show a total of 228 million cases worldwide in 2018, and, most tellingly, an associated 405,000 deaths – a far cry from the “near zero” target set for 2015.
Acknowledging this reality, a special Lancet Commission on malaria eradication provided recommendations which were summarised as “Malaria eradication within a generation: ambitious, achievable, and necessary. The feasibility of eradication by 2050 is an assertion, based on the balance of evidence and on the probability that particular challenges will be overcome.”
This is no longer the unbridled euphoric call to arms of a decade ago for malaria eradication by 2030, but it retains the word “eradication” as the desired endpoint, and puts the target at a more modest 2050.
Where does Southeast Asia fit into this picture, and how does it compare with the rest of the malaria world?
Africa has always been the hardest hit and shoulders by far the major burden. According to the latest available statistics, taken from the World Health Organization Malaria Report 2019, there were around 228 million cases globally in 2018, of which 213 million, that means 93%, were from Africa.
Southeast Asia accounted for a mere 3.4% of global cases, which translates to about 5 malaria cases per 1,000 people in 2018, down from 17 per 1,000 in 2010 – a dramatic drop of 70% over 8 years. Through sheer dint of hard work and dedication, the nations comprising Southeast Asia have managed to achieve a consistent year-on-year decrease across the region.
Of the entire Asia-Pacific region, India is possibly the only nation where some doubt exists, but for the other countries, there is high confidence that regional malaria elimination will in fact be achieved by 2030, not 2050 – which is a target actually aimed at Africa.
In fact, some Asian nations have already achieved that target: Sri Lanka, once a nation with millions of malaria case each year, was certified malaria-free by the World Health Organization in 2016 after three consecutive years of zero local transmission in that country. China, too, from having 30 million cases per annum at one point, has had several years of zero local transmission.
So what are the humps and bottle-necks that face malaria elimination in Asia?
Two things make Asia unique, in particular Southeast Asia. This region has managed to strongly drive down the incidence of plasmodium falciparum, the most deadly of the five parasites that cause the disease we know as malaria.
Falciparum is by far the single largest cause of deaths associated with malaria, all the other varieties causing very unpleasant illness but not the high level of mortality. But falciparum has the one major advantage that when you are treated with an effective drug, you kill all the parasites in the body, without leaving a residual population of parasites in the liver.
This unfortunate trait is a key challenge associated with plasmodium vivax, which accounts for about 72% of malaria cases in Southeast Asia today. This means when a patient gets treated, the parasites in the blood-stream that cause you to feel ill are killed, and you go home feeling happy and recovered, only to fall ill again some days, weeks or even months later when the hibernating parasites move from the liver into your blood.
Each year the noose tightens, the case numbers decline, and that means the reservoir for infecting mosquitoes also gets less. We are going to win this battle in Southeast Asia, it just requires the sustained commitment of national governments
While great successes have been achieved in reducing the deadly falciparum malaria, the complications of recurring vivax malaria and its treatment mean that it is a much more complicated challenge to fight.
But even for this pernicious Vivax malaria, its prime areas of distribution have been squeezed into pockets mostly along border areas, or low residual transmission in specific rural regions. Each year the noose tightens, the case numbers decline, and that means the reservoir for infecting mosquitoes also gets less. We are going to win this battle in Southeast Asia, it just requires the sustained commitment of national governments.
The other issue that thus far has been unique to Asia is the development and spread of drug resistance. As far back as the glory days in the 1950s when chloroquine formed one half of the heavy artillery in the fight against malaria, Southeast Asia was the region where malaria parasites first breached the defensive walls by developing resistance against the drug, and from there it spread across the planet so that by the mid-1990s chloroquine was abandoned as the drug of choice against our most deadly form of malaria, falciparum.
A series of other drugs were then thrown at malaria, but like cascading dominoes these drugs too soon showed reduced efficacy as the parasites evolved. Soon only one drug remained, artemisinin, which interestingly was first used by the Chinese as a herbal cure for malaria some thousands of years ago and “re-discovered” by the Chinese scientist Tu You You, earning her a Nobel Prize in Medicine in 2015.
More highly effective derivatives of the rapid-acting artemisinin were combined with other anti-malarial compounds to slow down the likelihood of resistance developing, and by the early 2000s became the frontline preferred product globally for use against the deadly falciparum malaria. It saved literally millions of lives, mostly among small children.
Then, in 2002, came the dreaded news, parasite resistance to the artemisinin-based drugs had been detected in the eastern region of Cambodia, the same general area where chloroquine resistance had first emerged.
From here it jumped into Thailand, and soon it was present in Myanmar, Vietnam, Laos, and the threat now existed that it would jump to Africa, where there was no alternative drug available for the most lethal form of malaria. Thankfully, the drug-resistant strains of the malaria parasites have remained confined to Southeast Asia, but it is only a matter of time before the jump occurs, and that will spell disaster.
The race is now on to find a new drug to take over from artemisinin, but that takes years and millions of dollars.
Fighting malaria is largely based on providing people with insecticide-impregnated bednets, or spraying walls of households with insecticides, and also testing people to find those with malaria parasites and treating them so that they do not infect mosquitoes and ultimately other people.
This relatively simple combination is what resulted in the dramatic reductions of malaria cases between 2000 and 2010, before the limits of their efficiency were reached. Now outdoor biting and insecticide resistance are among the most serious challenges confronting the malaria war.
Most difficult to deal with is malaria transmission that takes place among mobile or migrant peoples and forest-workers, groups which have lifestyles that take them beyond the reach of malaria protection. This is our current frontier, where malaria continues to smoulder and jump to new foci, and where we have to find new ways to stop transmission.
Scientists are advocating for integrated approaches, to find these core areas of transmission, get the understanding and cooperation of these people who often are engaged in illegal activities and therefore avoid contact. Moreover, to provide them with a combination of preventive drugs that kill parasites before they can enter the liver to reproduce, and transmission-stopping drugs that kill a particular stage of the parasite that infects mosquitoes.
We have shown in multiple countries that malaria elimination can be achieved with existing tools, and that we need not wait for a vaccine and improved tools to throttle this deadly disease into local extinction, we already have the means.
If China can do it, and so too Sri Lanka, the rest of Asia can also do it. And in truth, they are already well down the path of doing so, as annual statistics prove.
