‘You get goosebumps from the data’: hopes rise for new malaria vaccine
When Annah Kadhenghi had her first child last year, she named him Brighton Ushindi Baraka: baraka meaning “blessing” in Swahili, ushindi meaning victory. Last month, at the age of seven months, Brighton fought his first battle against an enemy that plagues millions of the world’s poorest: malaria.
“His temperature was very high; he was vomiting. I took him to the hospital,” says Kadhenghi, a schoolteacher in Kilifi, eastern Kenya. Brighton defeated the mosquito-borne disease, and now sits contentedly at the weigh-in clinic at Kilifi county hospital.
More than 600,000 in Africa in 2020 and about 12,500 in Kenya alone, according to the World Health Organization (WHO), were not as lucky. Across vast swathes of the continent, malaria remains a leading killer of under fives. So Kadhenghi was relieved to hear there could soon be an effective vaccine.
“A lot of people are suffering in this area from malaria,” she says. “So I think it’s a very good thing.”
Scientists at the Jenner Institute at Oxford University – birthplace of the AstraZeneca Covid vaccine – are hoping Kadhenghi, and others like her, won’t have to wait long. WHO has already endorsed one malaria jab for widespread use, and there should soon be a second, which those who have been working on it say is worth the wait.
The RTS,S vaccine, given the green light last year, has a modest level of efficacy, preventing 39% of all malaria cases and 29% of severe cases; however, the new R21 jab is the first to exceed the WHO target of 75%. In a 2019 trial in Burkina Faso it demonstrated high-level efficacy of 77%, results expected to be echoed at the end of a larger trial in four African countries.
The Serum Institute of India, the world’s largest vaccine manufacturer, stands ready to deliver at least 200m doses annually – a scale necessary to beat malaria. In 2020, Africa saw an estimated 228m cases of the disease, about 95% of the world’s total.
Mainga Hamaluba, head of clinical research at the Kemri-Wellcome Trust in Kilifi and principal investigator on the phase III trial, says watching R21’s progression has been astonishing. In 2017, when she returned to Kenya after training in the UK, it was just one of several promising vaccine candidates. It looked like “a bit of a leap of faith – until we saw the data from the Phase II trial”.
When the results were shown to her and her colleagues, she recalls: “The data was being presented. And … you get goosebumps. It was absolutely extraordinary. It still is.” At that point, before the world had seen the speed at which Covid vaccines were developed and manufactured, the idea that R21 would be approved by 2023 had seemed ambitious. “Then you see that,” Hamaluba says, “and you think: gosh, this might be possible.”
If backed up with adequate funding, the jab could save “exponentially more lives”, says Hamaluba. It can’t be looked at as the sole weapon in the armoury: it will not mean the end any time soon of insecticide-treated bed nets, or of antimalarial drugs. “But it is pretty amazing.”
Adrian Hill, director of the Jenner Institute, who has long championed the vaccine believes that R21 could reduce deaths substantially from next year, and by as much as 75% by 2030. “With a fair wind, the 2030s could see the reduction of malaria from a major killer … to a more localised minor cause of mortality,” he says. He believes the world could be on course for the ultimate goal of eradicating malaria by 2040.
The vaccine hunt has been a century in the making. Plasmodium falciparum, the deadliest malaria parasite, is complex, with more than 5,000 genes, evading human immune systems with skill. “Pinning down what is the Achilles heel is tougher [than a virus],” says George Warimwe, a vaccinologist at Kemri-Wellcome. “That’s one of the reasons why it has taken so long.”
Warimwe suspects there are other reasons, aside from biological complexity, behind the long wait for a jab. “We know a lot more about the epidemiology of malaria than we do of some of these newly emerging [diseases] – I can’t help but think about Covid,” he says. “But malaria continues to kill very many people, very many children, in Africa. It should be at the same scale as Covid in terms of prioritisation, but unfortunately that doesn’t happen.”
He says a vaccine demonstrating high protective efficacy, should be considered for the same WHO emergency authorisation as the Covid vaccines. “This is something that fits that bill, so why is it not happening?” he asks.
The response to the pandemic has puzzled the community in Kilifi, a sleepy coastal town, which – in partnership between the Kenya Medical Research Institute (Kemri), the Wellcome Trust and Oxford university – gained a world-class health research unit in 1989. When staff returned to work after Kenya’s lockdown, the unit’s community liaison group faced awkward questions, recalls Mary Mwangoma, community facilitator at Kemri-Wellcome Trust.
“The community members would ask … how come you got this [Covid] vaccine so fast when there are other diseases like HIV and malaria you’ve done studies on for quite some time and you haven’t got a vaccine?” she says. While locals appreciate the work the researchers do, “they would really wish that there was a permanent solution” to malaria, a far bigger threat here than Covid.
Deep in the lush countryside inland, the village of Junju has seen more than 5,000 cases of malaria so far this year. The tally is kepton a blackboard outside the dispensary: 1,708 for January, 655 for February, 1,283 for March. “Malaria is the commonest illness we encounter here – you can see here the number of cases,” says Stephen Chakaya, a medical officer who says numbers will peak at the end of the rainy season in July. “We can see more than 50 cases in a day.”
Outside the dispensary, mothers wait with children to be seen. A baby cries. A chicken stalks in the dust. In the chipped paint on the walls is written: “Vision: a nation free from preventable diseases and ill health.”
Junju, home to nearly 8,000 people, including more than 1,000 under-fives, is a high-transmission area for malaria, as is much of the undulating, tropical land on Kenya’s coast.
Things have improved significantly in the past two decades: most children sleep under insecticide-treated bed nets, and most cases Chakaya sees are mild or moderate. At the dispensary, medics use rapid diagnostic tests that detect malaria in less than 20 minutes.
But anyone over 30 here can remember what it used to be like and they take nothing for granted. Peter Chitsao, who was a child in Junju in the 1980s, says death from malaria was common. “You might see a child taken to the medicine man [a traditional healer] – that was what people called him. And then the child would die.”
Mwangoma recalls the itchy skin, bitter taste and bad dreams that came from a childhood taking chloroquine: “We would call it malariaquine.”
The experience of Junju is mirrored in the statistics: globally, malaria deaths reduced steadily from 2000-2019, from 896,000 in 2000 to 558 000 in 2019. By 2015, the mortality rate was half what it had been in 2000. Better targeted health education and greater investment in the science meant that more and more children avoided the worse.
But, as of 2018, that progress has stalled, and in 2020, with services disrupted by the Covid pandemic, malaria deaths rose for the first time in decades, revealing how easily fragile gains could be squandered. There are fears over growing resistance – in the parasite to drugs and in the mosquito to insecticides.
So a vaccine could be coming in the nick of time. Scientists believe R21 has the potential to be a game-changer, if funded. The stalling of progress on malaria has been accompanied, says the WHO, by a widening gap in what is needed and what wealthy donor countries like the UK are investing. By 2020, the gap had reached $3.5bn.
Will Boris Johnson’s government commit to ensuring the research is translated into action? A crucial sign will come this autumn when Britain makes its pledge to the Global Fund, the body providing more than half of all international financing for malaria programmes. The Fund has said that to get back on track after the pandemic it needs funding to rise by 30%, which would require the UK raising its contribution from £1.46bn to £1.8bn, according to Malaria No More UK. Given Liz Truss’s plan to almost halve the aid budget for multilateral bodies, the mood music is not encouraging.
For now Kemri-Wellcome scientists remain focused on the phase III trial, which in Kenya saw 600 babies and toddlers – half of them from Junju – take three doses of the vaccine four weeks apart. In the autumn, a year after the first jab, they will have a booster. Across Tanzania, Burkina Faso, Mali and Kenya, a total of 4,800 children are participating.
There was little trouble finding participants for the trial says Chakaya, “Everyone is optimistic [about] having a malaria vaccine … [Malaria] is a high cause of morbidity for under fives and pregnant women, so for the community [the possibility of the vaccine coming] is motivation enough,” he says.
The enthusiasm is at least partly down to Mwangoma and her community liaison team, who try to work, tactfully and respectfully, towards engaging people in what researchers are doing and explain the science. Johnson Masha, a community facilitator working with Mwangoma, says, when discussing a trial, “we talk of altruism. That you aim to do good for the benefit of society.”
Hill, who has dedicated his career to malaria research, with a brief detour into Covid, for which he was given an honorary knighthood, says the Kemri unit in Kilifi has played a major role in R21’s development – from being the first site in Africa to test the vaccine, finding “it showed excellent safety and strong immune responses in adults and children”, to building on that in phase III.
For Hamaluba the importance of an African-led team embedded in an African community cannot be understated. “It has to be African-led scientists [working on] diseases of importance in the areas they live and they work. It has to be,” she says. “Because otherwise things are lost.” Kemri workers are in “a continuous conversation,” she says, with the community.
In Junju, Khadija Mcharo Kapitao, 32, sits with her toddler Rumeisa waiting to see a nurse. She remembers the malaria she suffered as a child, reoccurring two or three times a year with “chills, abdominal pain, back pain, vomiting”. She doesn’t have the same worries for her three children, who sleep under bed nets. She has heard a lot about the jab. “When the vaccine comes I will get my daughter vaccinated,” she says.
Related: WHO endorses use of world’s first malaria vaccine in Africa
On the dispensary blackboard, the left-hand column lists all the regular immunisations that children in the village can expect, against diseases such as diphtheria and hepatitis A. The right-hand column has the numbers diagnosed with the three big childhood killers: malaria, pneumonia, and diarrhoea. Perhaps in the not-too-distant future, at least one will also feature in the left-hand column. “We hope,” says Juliana Wambua, a Kemri-Wellcome field studies manager. “And we hope very soon.”
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