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Efforts to make malaria history have had huge success in recent years. Now, there’s hope that the long-awaited RTS,S vaccine can go the last mile
By Jacob Kushner
23 April 2021
Eight-year-old Trizah Makungu sits on the bed she shares with her parents, protected by a mosquito net. These nets, which cost about $5 in the local market, have helped save millions of lives
Update on 6 October 2021: The world’s first malaria vaccine, known as RTS,S, was today recommended by the World Health Organization for general use among children in sub-Saharan Africa and other regions with moderate or high rates of malaria. It was previously used only in large-scale trials.
“We longed for it to come,” Janet Mula told me, recalling her reaction to hearing that scientists were developing a vaccine against malaria. Mula, a nurse I met while travelling in rural Kenya, has seen the devastation caused by this disease first-hand. Each year, it sickens more than 200 million people globally, killing at least 400,000. The vast majority of cases are in sub-Saharan Africa, with the biggest burden falling on younger people. “Malaria causes many complications for children – anaemia, organ failure, jaundice, liver complication,” says Mula.
That could soon change, however. While most of the world is focusing on new vaccines for the coronavirus, thousands of Kenyan children are finally receiving a longed-for malaria vaccine, 37 years after development on it started. Since 2019, Kenya, Ghana and Malawi have been taking part in a pilot programme coordinated by the World Health Organization (WHO). If it is successful, the vaccine will be rolled out to infants across Africa. As this went to press, trial results of another vaccine developed by the University of Oxford suggested it was 77 per cent effective.
Two girls cut grass in a watery field in Kakamega County, Kenya. Malaria is spread by female Anopheles mosquitos, which breed in stagnant water and proliferate during the rainy season
Some hope these vaccines will eventually help to eradicate malaria entirely. Every year on 25 April, World Malaria Day, the WHO assesses the progress made in combating the disease – and it has been considerable. But eradication would be a massive achievement: it has only ever happened with one human disease, smallpox. “Eradicating smallpox – it’s a wonderful story,” says global public health consultant Desmond Chavasse. “But we so nearly failed. The world nearly lost its determination to do it.” When it comes to malaria, even with a new vaccine, if action isn’t fast, we may miss our chance.
The parasites that cause malaria have been around for at least 30 million years. They probably started infecting humans tens of thousands of years ago, in Africa and, by 10,000 years ago, were decimating nomadic societies as far away as Asia. Today, malaria is caused by five species of Plasmodium parasites – Plasmodium falciparum being the most deadly – all of which are spread to humans via mosquitoes. Although malaria is endemic in 87 countries, 95 per cent of cases occur in just 29 countries in Africa. Nigeria seems to be by far the most severely hit, accounting for 27 per cent of known infections and 23 per cent of deaths overall. In 2007, the World Bank estimated that malaria costs Africa $12 billion a year in treatment and lost productivity – that figure is probably higher now.
At Kenya Medical Research Institute, scientists study mosquitoes’ resistance to insecticides
Nevertheless, in the past half-century, we have made big strides against the disease. Between 1955 and 1987, 22 countries were declared malaria free, and five others joined them between 2007 and 2014. Progress has been particularly rapid this century. Malaria cases have dropped from 80 per 100,000 people in at-risk populations in 2000 to 57 per 100,000 in 2019. In the same period, deaths have fallen from 25 to 10 per 100,000. In its World Malaria Report 2020, the WHO describes this as “a period of unprecedented success in malaria control that saw 1.5 billion cases averted and 7.6 million lives saved”.
Mosquito nets sprayed with insecticides have proved the most effective measure for saving lives and reducing sickness, according to the WHO. Bed nets aren’t just effective, they are also cheap, at about $4.50 a pop. But they are no cure-all. “Prevention measures that require daily behaviours – such as the use of a bed net – can be harder to adhere to,” says Eliane Furrer, who works for the WHO on malaria vaccine implementation. Especially in hot climates and in places that bustle after dark, not everyone wants to spend their whole night under a net. And nets won’t stop the species of mosquito that transmit malaria by day.
The second pillar in the fight against malaria is a drug called artemisinin. Discovered in 1972, it is generally given as part of a cocktail of drugs known as artemisinin-based combination therapies (ACTs). ACTs are credited with saving millions of lives, but some people believe they could have an even bigger impact if a novel application is more widely adopted. It entails giving ACTs preventively to an entire community at once, reducing the levels of the malaria parasite in the blood of anyone who might be infected, so that it isn’t passed back to mosquitoes that bite them. Starting in 2007, use of this approach dramatically reduced the spread of malaria in the Comoros islands, a small volcanic archipelago in the Indian Ocean.
Children, like these two girls in Kakamega, are more susceptible to malaria because they lack immunity
Despite such success stories, progress against malaria has stalled. In 2016, the WHO identified 21 countries with the potential to eradicate the disease by 2020. But by 2019, only 10 of them had done so. “We’ve reached this plateau,” says Kate O’Brien, an epidemiologist at the WHO. The challenge is “getting at the hardest to reach children, the hardest to reach communities”. Global health professionals call this the “last mile” problem. They warn that the hardest part of any intervention is to bring it to the most remote places, or to reach every last individual in a dense urban environment.
My own experience suggests the problem is bigger than that. In western Kenya, where Mula works, malaria prevalence can reach 40 per cent, one of the highest incidences in the world. Yet, when I travelled in the region in March 2019, mosquito nets were absent even in inpatient wards inside government healthcare facilities. And the previous year, on a visit to Kenya’s malaria-endemic Indian Ocean coast, people told me they were unable to get ACTs to treat malaria because hospitals that are supposed to administer them for free were out of stock. When it comes to the distribution of bed nets and anti-malarial medication, there seem to be enough “last miles” left to make it a marathon.
So far, the vaccine has taken 37 years and billions of dollars to develop. It is only 40 per cent effective, at best
Even with these challenges, if past interventions are anything to go by, an effective vaccine could be a game changer. “This has been arguably the most successful health intervention programme in history,” says O’Brien of the 21st-century campaign to provide vaccines against a suite of infectious diseases in the developing world. “Every country in the world now has an immunisation programme that’s for every kid in that country.”
That has brought huge health improvements in just two decades. “Close to 10 million children were dying every year due to preventable causes, and 95 per cent were in poor countries,” says Anuradha Gupta, deputy CEO at the GAVI vaccine alliance. Now those deaths have been reduced to about 1.5 million a year.
This helps explain why there is so much hope riding on the malaria vaccine, known as RTS,S. But the road to roll-out has been far from smooth. In development since 1984, it is one of the longest awaited vaccines in history. The challenge lies in the fact that, unlike a virus, such as the one that causes covid-19, the parasites that cause malaria transform themselves through several different stages of life.
Before creating a malaria vaccine, scientists had to work out which stage would be best to target, and how. Following a bite from an infected mosquito, the parasite enters the bloodstream. It then moves to the liver, where it matures into the next phase of its life cycle. RTS,S works by triggering an immune response to fight off the parasite at an early stage, just after infection.
Some critics worry that, although it has already been decades in the making, the vaccine is being rolled out too soon. They argue that it isn’t sufficiently effective, or cost effective. In phase III trials to assess effectiveness, it cut infections by only about 40 per cent – and by less than 30 per cent for severe malaria, the type most likely to kill. To reach even these levels of protection, a child needs four doses. “This has not been a standard vaccine on the level of efficacy,” admits An Vermeersch, head of global health vaccines at GSK, the company that manufactures RTS,S.
Baby Prince Jackson has so far received two of the four doses of malaria vaccine
Then there is the cost. It has been estimated that implementing the vaccine will take an average of $87 per DALY that it averts. DALY stands for disability adjusted life year, typically thought of as one lost year of healthy life. That makes it far cheaper than some medical interventions for infectious diseases: antiretroviral drugs for HIV costs an average of $11,900 per DALY averted, for example. However, distributing more mosquito nets would cost much less, an average of just $27 to achieve the same effect.
Added to that, the cost of implementing the RTS,S vaccine doesn’t include research and development, which may come to billions of dollars. GSK hasn’t disclosed how much it has spent. However, a report published in 2009 revealed the vaccine was costing $200 million a year to develop. And the Bill & Melinda Gates Foundation, which has invested more to stop malaria than any other organisation, has spent hundreds of millions of dollars on the vaccine.
To those who say the cost is too high, Vermeersch counters that the investment signals confidence in the vaccine’s potential. “The fact that everyone is committed to it after more than 30 years shows that there is a willingness to bring this vaccine to market,” she says.
Furrer points out that although the vaccine is more expensive than bed nets, it has some big advantages. “The vaccine is targeted at young African children, who suffer the highest malaria burden,” she says. “Once a child is vaccinated, they carry this protection with them throughout the day and night.”
In the pilot programme currently taking place in Kenya, Ghana and Malawi, all children under 2 years of age are offered the malaria vaccine for free
Besides, RTS,S doesn’t have to be viewed as a replacement for bed nets and artemisinin. It is an addition to the armoury. “[We must] bring new tools to bear in the fight against malaria,” says Scott Filler, at The Global Fund, which aims to end the AIDS, tuberculosis and malaria epidemics. “We will leave no tool on the table.” The reason for that can be summed up in one word: resistance.
Parasites that are resistant to the drug artemisinin have long been observed in Asia, but last year they were found in Africa for the first time. The team that discovered them said the mutation found in P. falciparum in Rwanda could “pose a major public health threat” to people living in Africa. In addition, some scientists fear that drug resistance will rise if ACTs are used preventively in entire communities to try to eradicate malaria, as they were in the Comoros islands. Meanwhile, mosquitoes are becoming increasingly resistant to the insecticides used to spray bed nets. By 2019, 73 countries had reported resistance to at least one of these chemicals, according to the WHO.
Silas Agumba, a research assistant at the Kenya Medical Research Institute, holds a box full of female mosquitoes
But there is some good news. Recently, bed nets sprayed with a chemical called piperonyl butoxide have been found to repel malaria-laden mosquitoes more effectively than those treated with the insecticides currently favoured. Another ray of hope comes from the part of Kenya where the RTS,S vaccine is being rolled out. On the shores of Lake Victoria, mosquitoes carrying a naturally occurring microbe don’t contract the malaria parasite. According to a study published in 2019, of the 5 per cent of mosquitoes that carried this microbe, Microsporidia MB, not one tested positive for the malaria parasite. If we can figure out how to spread the microbe further – or to restrict reproduction among mosquitoes that don’t carry it – it will give us another way to fight malaria.
Unfortunately, as covid-19 spreads across Africa, even existing anti-malarial interventions are being threatened (see “Malaria and covid-19“). And coronavirus-related restrictions have also delayed plans to roll out the vaccine beyond Kenya, Ghana and Malawi, which health officials had hoped to do this year. Nevertheless, some still believe that a healthier future is in sight. Vaccines aside, huge efforts are being made to develop new drugs and insecticides.
Whether we can totally eradicate malaria is another matter. Successes like the vaccine that eventually put an end to smallpox in 1980 may be a thing of the past. In today’s globalised world, we are constantly on the move, carrying parasites and viruses along with us. And with climate change, mosquitoes are moving too, from equatorial regions to northern latitudes where most of the world’s population resides. If we hope to beat this disease, it is crucial that we act fast, before the malaria parasite develops resistance to any new measures employed against it. “If you don’t innovate, resistance goes up, so malaria does too,” says Chavasse.
In Kenya, private clinics such as the Cheldeb Medical Center in Kakamega, administer the majority of anti-malaria treatment
Nets treated with insecticide have been the most effective measure to reduce the incidence of malaria. They are frequently distributed at community gatherings, but because of the spread of covid-19, such gatherings are now often deemed dangerous. A study published in August warned that if routine anti-malarial campaigns such as bed-net distributions continued to be neglected, “the malaria burden in 2020 could be more than double that of 2019”.
By late November, less than half of the 222 million long-lasting insecticidal nets planned for distribution in 2020 had been distributed, according to the World Health Organization. The WHO has also said that 409,000 people died of malaria in 2019. It didn’t yet have a figure for 2020, but said covid-19 would have an impact. “Despite commendable global and national efforts to maintain essential malaria services,” it noted, “it is likely to lead to higher than expected malaria morbidity and mortality.”
Reporting for this story was made possible by a grant from The European Journalism Centre
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