Malaria is a disease almost as old as humanity itself, but now science is bringing out the big guns in a bid to destroy it. At stake are nearly half a million lives a year, writes Anne Gulland for The Telegraph.
During his 2015 attempt to be the first person ever to walk the length of Madagascar, the British adventurer Ash Dykes was held up at gunpoint and crossed crocodile-infested rivers – but what almost killed him was a tiny mosquito from which he contracted malaria.
Dykes was just three weeks into his five-month expedition when he fell ill. He and his two Malagasy guides had eaten some eel, prepared by local villagers, which he admitted smelled “a bit funky”.
Over the next two days they all had stomach upsets, but while his guides recovered Dykes got worse, developing a raging fever, hallucinations and extreme fatigue.
“When it took me 45 minutes to summon up the will to sit up and drink a glass of water I realised I was seriously ill,” he says. His friends got him out of the wilderness and to a town where they sought medical help.
“The doctor came and took some blood and then told me that I had contracted the deadliest strain of malaria. My heart sank – I thought that once you got malaria that was it,” he says.
Dykes knows he was lucky. As a phenomenally fit Westerner he was taking anti-malaria pills which reduced the severity of his symptoms. And he could afford a comfortable hotel room, a doctor and the specialist treatment he needed.
“I realised that so many communities are affected by this disease. When you’re in Madagascar you see people lying by the side of the road and you wonder if they’ve got malaria,” he says.
He’s right to wonder. In 2016, the last year for which data is available, there were an estimated 216 million cases of malaria worldwide, the majority of which were in sub-Saharan Africa.
Of those infected, a staggering 445,000 died – 1,219 lives lost every day, or nearly one a minute. And 70 per cent of those deaths are in children under five. For children it is a particularly devastating disease.
The disease is almost as old as humanity itself and at one time affected nearly every region of the world, including much of southern Europe and the southern states of the US where it was only eradicated in the the middle of the last century.
There was a big push to eradicate the disease in the fifties and sixties, but when the global focus shifted malaria returned with a vengeance, gaining a stranglehold on Africa.
A second push in the last decade initially made strong headway, reducing cases by about 20% in just five years. However, once again progress has slowed, with five million more cases in 2016 than the previous year.
Now a major new fightback is planned. The World Health Organization (WHO) believes we are at a “crossroads” and advances in science mean it should be possible – with the right focus, funding and international cooperation – to eradicate the disease by 2030.
In short, humanity may be on the brink of wiping out one of its oldest and deadliest foes.
Six of the 10 countries with the highest incidence of malaria are members of the Commonwealth and leaders at the recent Commonwealth Heads of Government Meeting in London are being urged to make a lasting commitment to fighting the disease.
Global leaders, including UK prime minister Theresa May and philanthropist Bill Gates, have asked countries to pledge enough money and resources over the next five years to prevent 350 million people from catching the disease and save 650,000 lives.
Penny Mordaunt, the UK's international development secretary, said: “A child dies every two minutes from this preventable and treatable disease, yet globally progress has stalled. That is why the UK has pushed for a focus on malaria at the Commonwealth Summit, including co-hosting the Malaria Summit attended by Heads of Government.
“The UK government is the second largest funder globally, with investments in treatment, prevention and research. Our work not only saves lives, it improves people’s health which means they can achieve their full potential and help their countries prosper. A safer, healthier and more prosperous world is in all our interests.”
The new battle plan
Malaria is far more complex than other diseases such as smallpox and polio, which have ceded to scientific advance.
To fight it, experts are waging war on three fronts: the malaria parasite itself, the mosquito that carries it and the human behaviours and living conditions that can feed it and cause it to spread.
Pedro Alonso, director of the global malaria programme at the WHO, believes that the only way malaria will be eradicated once and for all is with a “game-changing” drug, vaccine or a brand new control tool.
One such contender is a mosquito genetic control technique being developed by a global consortium of researchers, led by Imperial College London.
The disease is only transmitted by the female mosquito so researchers are using a state-of-the-art gene editing technique – the newly developed Crispr tool – to interfere with the Anopheles gambiae mosquitoes so that they only carry male eggs. This evolutionary tinkering is called gene drive, in which an entire species is “persuaded” to adopt a gene.
Researchers believe that after 20 mosquito generations – around two years – gene modification will set in and the malaria-carrying culprits will die out.
Delphine Thizy, stakeholder engagement manager of the project, says that the technique holds great promise.
“This has the potential to be a long-term and cost-effective solution, which has always been a big challenge in malaria control tools,” she says.
Researchers are currently looking at how many mosquitos to release, as well as when and where they should be released. They are also looking at what impact a genetically-modified mosquito would have on the local environment.
Like so many in the malaria research world – where false starts and raised hopes are in abundance – Ms Thizy is cautious.
“We think this can help the other tools – drugs, vaccine and bed nets – be more effective. If you have areas where it’s hard to implement these tools, where there is poor infrastructure, the health system is weak or there’s conflict, this could be helpful,” she says.
“It’s going to be another decade before this is ready to use. But in another decade, malaria will still be here,” she adds.
Other genetic tools include sequencing techniques. Researchers at the Wellcome Sanger Institute in Cambridge have mapped 4,500 genes of 500 malaria parasites to create the Malaria Cell Atlas.
The online database is freely available to researchers around the world to help them work out precisely which drugs and vaccines are effective – and those that are not.
It is hoped this will speed up the development of new drugs, as well as saving time on developing targets unlikely to work against the parasite.
Dr Arthur Talman, a researcher from the Wellcome Sanger Institute, said: “We have gained a better understanding of which genes are important for the parasite to transmit between human and mosquito during the spread of a malaria infection.”
He added: “Knowing how the parasite’s lifecycle is controlled by particular genes, we have a stronger chance of interfering with it using drugs.”
Vaccines and treatments
In the fight to eradicate disease, vaccines have always been a key weapon. This September children in Kenya, Ghana and Malawi will get the first doses of the RTS,S vaccine, developed by UK pharmaceutical giant GlaxoSmithKline (GSK).
While the launch of the vaccine is a landmark in the history of the war against malaria, it did not prove to be the game-changer that was so longed for.
Clinical trials only reduced the number of deaths by 40 per cent and the vaccine also needs to be administered in four stages – experts believe the required 18-month interval between the third and fourth doses could prove to be a stumbling block.
Azra Ghani, professor of infectious disease epidemiology at Imperial College London, says: “This will require extra visits to a health clinic and so it needs to be tested to see if this works in practice.”
A single-dose vaccine would be the holy grail for researchers – but alternatives to the RTS,S vaccine are about 10 years away. However, there has been other promising work in prevention: since 2016 children in the Sahel region of Africa have been receiving an anti-malarial drug during the rainy season and researchers have seen a 50 per cent drop in the number of malaria cases.
Researchers at the London School of Hygiene and Tropical Medicine have also been looking at broadening this approach to include older children and have found that this reduces malaria cases in the population as a whole, not just among children.
Malaria is an unpleasant, debilitating illness and those who survive it speak of the toll it takes on the body.
Developing new drugs is crucial in fighting the disease. Timothy Wells, chief scientific officer at the Medicines for Malaria Venture, a public-private partnership, says there is a lot of optimism in terms of the development of new treatments for the disease.
“Not only have people been developing new drugs but old drugs that have got stuck in the pipeline because of lack of funding have been developed. It’s a really exciting time,” he says.
New formulations that are more palatable and easier to administer to children when they are seriously ill have also been introduced.
The standard treatment for malaria is a combination of artemisinin plus one other drug, known as ACT. A combination therapy is important in combating resistance to drugs, a threat hanging over researchers. Resistance has been reported in south-east Asia but it has not yet spread to Africa and the development of new therapies is key to ensuring researchers stay one step ahead of the parasite.
“We now have four and soon to be five potential partner [drugs] which countries will have to choose from when they see resistance,” says Dr Wells.
Researchers are also trialling three-drug combinations in Africa.
Rob Amato, a researcher at the Wellcome Sanger Institute, says it is important that researchers prepare for resistance as avoiding capture is the “parasite’s day job.
“We will never be resistance proof but we can be resistance safe,” he says.
Long-lasting insecticide-treated bed nets and indoor spraying with insecticide have been the bedrock of malaria control for the last few decades. However, they are an imperfect tool.
In many malaria endemic countries it is too hot to sleep under the nets and, in Africa, the mosquito is developing resistance to the insecticide. A prospect described as potentially “catastrophic” by Chris Drakeley, director of the Malaria Centre at the London School of Hygiene and Tropical Medicine (LSHTM).
Researchers at the LSHTM have just announced the results of a new trial which showed that bed nets treated with two chemicals reduced the prevalence of malaria by 44 per cent, compared to a standard bed net treated with the standard insecticide, pyrethroid. The study also showed that indoor spraying using the insecticide pirimiphos reduced the rate of malaria infection by 48%.
Full report in The Telegraph