It is the world's deadliest disease, killing more than 900,000 a year in Africa alone. But can Bill Gates's dollars create a vaccine that would save a continent's children?

Shadrack Nuru doesn't know it but he is a soldier on the front line of a global war against the most efficient terrorist the earth has known. The terrorist's name is Plasmodium falciparum, the malaria parasite that invades the organisms of 500m people a year and kills as many every day as al-Qaeda did in New York on 11 September 2001. More than 90 per cent of the disease's 1m annual victims die in Africa, the vast majority of them under the age of five.

Shadrack, nine months old, is one African baby who, with his mother's blessing, will join forces in the first anti-malaria offensive with a fighting chance of victory since the first mosquito spat the first parasite into the human blood system a very long time ago - long before the time even of Hippocrates, the Greek who invented medicine and first recorded malaria's symptoms 2,500 years ago. Among Hippocrates's successors today, the consensus is that - never mind the bubonic plague or TB or Aids - no disease in the history of the human species has caused more sickness or death, and no disease has proved harder to defeat. It decimated armies during the First and Second World Wars and counts among its more illustrious victims Alexander the Great, Dante, the Holy Roman Emperor Charles V, Oliver Cromwell and Lord Byron.

Shadrack is one of 340 babies from the region of Bagamoyo in Tanzania who are part of a newly energised global campaign to defeat nature's most enduringly tenacious killer. They are participating in blind clinical trials under way in Africa to test the efficacy of the most promising malaria vaccine yet devised. Half of the Bagamoyo babies were injected with the prototype vaccine, known as RTS,S and half with a control vaccine.

The doctors at the Bagamoyo heath and research centre, where the trials are being carried out, do not know which child has received which vaccine, but when they saw Shadrack one day recently, they hoped he had not had RTS,S. The child lay on a blanket twitching convulsively; his pupils had rolled back so far into his head all you could see were the whites of his eyes. His mother looked on in horror, aware there was nothing she could do to help her only child. The doctor said it looked like cerebral malaria, the deadliest kind.

The doctor, himself an inhabitant of Bagamoyo, a humid town on Tanzania's Indian Ocean coast, where the malaria parasites and their mosquito carriers run riot, has an urgent personal interest in finding a vaccine for the disease. He and other doctors I spoke to at the health centre, a rickety assembly of low buildings housing world-class malaria researchers, told me malaria attacks here were as routine as the common cold is in Europe. One doctor, in his late thirties, whose wife had recently miscarried after contracting malaria, told me he'd calculated he had succumbed to the disease 70 times.

Shadrack's mother, watching her child's convulsively comatose body on the table, was grateful her child had been among those babies selected for the vaccine trials and would have been grateful if he lived to endure similar recurrences. Those leading the local fight against malaria keep rigorous watch over their infants. The system worked especially effectively this time: a health worker in Shadrack's village radioed the Bagamoyo clinic, who sent an ambulance for him. For rural Tanzania, where the funding for malaria is still 10 times less than that for Aids, this was five-star service. Very few children manage to get access to medical treatment within 24 hours of the symptoms appearing, as Shadrack had done. His chances of surviving now that he was in hospital were much higher than average, in a country where local doctors estimate that more than 100,000 children died from malaria in 2007.

If Shadrack does survive to adulthood, he may look back one day with pride on the small part he played in this battle. He and the other 339 vaccine-testing babies of Bagamoyo are part of a wider effort that will ultimately involve 16,000 children in half a dozen African countries. The objective is to evaluate the efficacy of the RTS,S vaccine. It is a monumental project, one of whose central figures is Pedro Alonso, a Spanish doctor who has conducted remarkably successful initial trials in Mozambique over the past five years and who has spent his career working on malaria all over Africa. The results so far for RTS,S, produced by the pharmaceutical giant GlaxoSmithKline, have shown an efficacy of 65 per cent in the most vulnerable group, children under 12 months old.

Alonso, whose team's findings have been published in The Lancet, is one of the generals in the war. The strategic leadership - and a big chunk of the cash - comes from Bill and Melinda Gates. The $1bn provided by their health foundation has funded a worldwide push that has seen spending to fight malaria quadruple since 2000.

On 17 October last year, the Gateses invited the world's 300 leading malaria experts - scientists, senior UN and government officials, heads of NGOs and of the pharmaceutical industry - to Seattle, to see how best they could combine their efforts to tackle the disease. The high point of the event was a Churchillian keynote speech delivered by Melinda Gates.

Recalling her own Shadrack moment, when she visited the clinic Dr Alonso runs in Manhica, Mozambique, Melinda Gates told the assembly that she was haunted by the memory of a little girl whom doctors had diagnosed with severe malaria.

'No child should die from malaria. No child,' she declared. 'And the only way to end death from malaria is to end malaria.' What she meant, and it provoked gasps from her audience, was 'end' as in 'eradicate' - known as the 'e' word in the malaria community because of its almost taboo status, so improbably, unscientifically dreamy does the task appear.

'Every life,' Melinda Gates continued, 'has equal worth. Sickness and death in Africa are just as awful as sickness and death in America... Any goal short of eradicating malaria is accepting malaria, it's making peace with malaria... That's just unacceptable.'

If it was not peace, then it was war. 'Conquering malaria is one of the most ambitious medical quests of all time,' Melinda acknowledged, yet in the same breath she challenged 'the top scientific minds in the world' to take it on. As did her husband. 'We're not done and we will not stop working,' declared the founder of Microsoft, 'until malaria is eradicated.'

For most of the Seattle 300, the speech was a milestone. 'They are dead right,' reflected Dr Alonso. 'Anything less than the goal of eradication is unacceptable. Before we only talked of "controlling" malaria. That's all past now. The question is no longer whether we will defeat malaria, but how and when.'

This is not to say Bill Gates believes the RTS,S vaccine he is championing represents some sort of holy grail. He agrees with Marcel Tanner, a fluent Swahili speaker who heads the partly Gates-funded Swiss Tropical Institute and divides his life between stately, affluent Basle and sub-Saharan Africa, that, likely as it appears that the first ever malaria vaccine will be registered by 2011, this is not the solution to malaria, no more than the military offensives in Afghanistan and Iraq are the lasting answer to terrorism. 'It will work but it will be an imperfect vaccine,' said Tanner. 'It will take decades before we win, because this is not like the measles or the polio vaccine: there is no one magic bullet. We need lots of magic bullets. You need a complex, multi-pronged approach to fight malaria.'

David Schellenberg, professor of malaria at the London School of Tropical Medicine, makes it his business to untangle those multi-prongs, which means getting down to the nitty-gritty of addressing the disease among communities in deepest, poorest, roadless Africa. Schellenberg, who has just returned to London after 10 years in Tanzania, is excited by the potential of RTS,S, on which he has worked in Bagamoyo, but says that just as important is research on the logistics and economics of delivery: 'We need to find an effective gun to go with the magic bullets, which in and of themselves are of no use to anybody,' he said.

The 'gun' and 'magic bullets' image and the phrase 'multi-pronged approach' recurred like mantras among doctors and scientists I met in Tanzania - in Bagamoyo and its parent health and research centre at Ifakara, 300km and seven hours by bumpy road inland. To travel there from Switzerland, as I did, is to live an experience in time travel that is instructive in the attempt to understand why members of the malaria high command insist on emphasising the logistical aspects of their war.

In chilly, impeccably bourgeois Basle, I visited the vast hi-tech 'campus', as they call it, of the pharmaceutical giant Novartis, leading manufacturer of the best drug available at present to combat malaria. It was 'Big Pharma' central: a space-age town within an ancient European city. Cut from there to the Kilombero valley, the last stretch on the slow road from Bagamoyo to Ifakara, and you are in a world that the technological revolution of the 20th century has barely touched. Yes, one does see a motorised vehicle now and then, as well as a fair number of bicycles, and some men wear football shirts with the names 'Ronaldinho' and 'Beckham' on them. But the women dress in much the same way that Dr Livingstone would have found them.

The villages along the road to Ifakara were like scenes from The Jungle Book: mud huts, big mango trees heaving with fruit, banana trees, coconut trees, lush fields and everywhere fat goats with shiny coats and, in the distance, an elephant or a giraffe. Paradise, were it not for malaria and the sorrow it causes and the desperate burden it puts on the frail economics of subsistence farming.

Ifakara, Tanner had told me, means 'the place of death' in Swahili. Until a decade ago, it was the most lethal malarial area in the world, and it remains so in the town's outlying districts. Here, in the warm, stagnant swamps, mosquitos breed in greater numbers than anywhere else on earth. Ifakara holds the world record for the highest number of mosquitos ever found in one house, in one room - 6,000, in 1988. That the will and the technology existed to count them is down to the existence in town of a health and research centre founded half a century ago by the Swiss pharmaceutical millionaire, Rudolf Geigy. Tanner, his scientific heir, transformed the centre from what he called a Swiss colonial field laboratory into what had become a sort of Oxford University of malaria, a focus of knowledge in the heart of the research zone run today by Tanzanians, and to which the world's leading malaria experts make obligatory pilgrimages.

The questions that had to be asked here were why malaria represented such a vast scientific challenge, and why to defeat the disease it was necessary to fight on so many fronts.

The answer to the first question was provided at the Ifakara centre's laboratory, whose equipment is partly funded by the Gates Foundation and whose exclusively Tanzanian staff are trained, often abroad, to the highest international standards.

'You hate the malaria parasite, but you have to admire it for its complexity, its endless capacity to mutate and develop resistance to the weapons humanity hurls at it,' said Debora Sumari, a molecular biologist. 'Each new drug we come up with in time becomes confused, thrown off balance by the parasite, which radically alters its DNA composition, assumes disguises. It is a very clever parasite, always one step ahead of the cleverest scientific minds.'

Sumari spends her days peering at the tiny organisms through high-powered microscopes. In the war against the disease, she sees herself, she smiled, as a spy infiltrating behind enemy lines, gathering intelligence on the lifestyle and habits of nature's terrorists and trying to anticipate their next move. 'It is like an endless game of chess against a brilliant and cunning adversary,' she said.

The malaria delivery vehicle, the Anopheles mosquito, is brilliant and cunning, too - and almost as inscrutable as the parasite itself. Gerry Killeen, an Irish entomologist who has been in Tanzania for four and a half years and is one of the leading world experts on the mosquito, was speaking only half in whimsy when he told me: 'We know more about the polar bear than we do about the mosquito - we don't even know what the damn thing eats!'

Killeen is working on it, aided by a team of young Tanzanian scientists who are endeavouring to discover, among other things, whether a smell might be found that is more appealing to mosquitos than that of human flesh. 'When it comes to species protection, I have to say that the tiger is higher on my list,' Killeen smiled. 'But you have to hand it to the mosquito: it is a smart and elegant killer.'

Or 'she' is. The males do not need blood to survive; only the females do, in order to lay their eggs. So it is only the females that bite, or rather 'spear', humans, the unintended consequence being that all too often the uninvited parasite they carry then attacks in overwhelming numbers.

The way it works is this: the mosquito, belonging to the malaria-carrying genus Anopheles, stores the parasite in its saliva glands. It alights on human skin, locates a blood vessel, and pierces it with its sharp, serrated proboscis needle. It then spits out saliva in order to stop the blood coagulating and sucks it up into its body. (Small children are particularly appetising prey because they sleep deeply, allowing for long, uninterrupted gorging.) The parasites enter the human bloodstream and make for the liver, where they remain undetected for seven to 10 days. The liver is a sort of orgiastic gymnasium where the parasites not only become big and strong, they reproduce in vast quantities, multiplying the original number that left the mosquito's saliva by a factor of 20,000. They then invade the organism to devastating effect, slaughtering red blood cells, decimating the body's iron content and clogging up the blood vessels that irrigate the vital organs. When the bloodflow to the brain is closed down - cerebral malaria - the parasite's human host dies.

Quinine, a natural product first discovered in the bark of trees in Peru hundreds of years ago, is the oldest weapon used against malaria, though its efficacy has been severely curtailed by the parasite's genius for mutating. It has, however, led to the development of a pharmaceutical byproduct called chloroquine that is still used today. But the latest and best drug is Coartem. This combines a natural product derived from the Artemisin plant, originally found in China, with a chemical compound. Novartis produces 70 per cent of the world's Coartem and, while it is by far the single biggest drug it produces in terms of volume, it sells it at cost. If the pills are taken with the recommended regularity, and in time, they kill off the parasite within three days. 'Yet here we have a perfect example of why we must never drop our guard,' said Jullu Boniphace, Debora Sumari's boss at the Ifakara lab. 'We did the trials on Coartem here in Ifakara and it is working. Yet we know that at any moment we will be surprised, that the parasite will have come up with a defence and that we will have to find a new weapon. If we fall asleep, the enemy will be at our door.'

When Boniphace said 'we' he meant the entire malaria garrison at Ifakara, each with their specialist field. The lab 'spies' must do their part, but propaganda - or 'education', as they more politely call it in Ifakara - is as essential an instrument to combating malaria as the 'top scientific minds' Melinda Gates spoke of.

'One of our greatest enemies is ignorance,' said Angel Dillip, a medical sociologist who helps run a travelling circus of musicians and comedians that arrives in big trucks at remote villages and tries to stress, among other things, the urgency of seeking immediate medical help the moment the first malaria symptoms of fever, exhaustion and muscular aches present. 'One big problem is people's belief in traditional healers, who tell them the illness is a sort of curse created by a djinni, or ghost, that only they are able to address. By the time the convulsions set in, and it is now clear to the parents of a sick child that the traditional cures have not worked, it is often too late,' Dillip said.

Logistics is an even bigger area. It includes, on the one hand, a statistics department at Ifakara that employs more than 60 field workers and keeps records on the health and basic economy of 19,000 households. Without that data it would be impossible for the likes of David Schellenberg to do his research, which in turn leads to the all-important policy question of how much the malaria war costs, or how to judge the efficacy of new drugs. Logistics also means getting the drugs and, critically in recent years, mosquito bednets to outlying areas where roads are practically non-existent. The emergence of increasingly efficient, washable, insecticide-treated bednets - the fruit of extensive research done in part by Pedro Alonso in the Nineties - has had a big impact in reducing malaria deaths in Ifakara.

Ifakara offers 'a vision of success', as one local doctor put it, but the concentration of cutting-edge resources here will not be easily replicated in the rest of Africa. And even so, they are not enough to eradicate the disease locally.

If a country like Italy, where malaria was endemic up to the Thirties, has been able to eliminate malaria it is in large measure because of the giant public works projects it was able to fund to clear out open drains where mosquito larvae breed, and because people have windows in their homes and quick access to medical help.

What African poverty means, as a doctor in Bagamoyo told me, is that parents are often confronted with a desperate choice. 'If you live far from a town and your child falls sick in a season when a subsistence farming family must sow the fields, you are faced with a desperate choice,' Dr Kafuruki Shubis explained. 'Do you take the child on a trip to a health centre that costs you money you barely have, and takes up one or two days there and back, knowing that by so doing you leave the fields unsown and the family hungry? Or do you leave the child to die?'

David Schellenberg has done specific research on this African Sophie's Choice in Ifakara and confirmed Dr Shubis's findings. 'You have a two-week window to plant the seeds, which you've spent a lot of your money to buy,' Dr Schellenberg said. 'That window coincides with the time of heaviest rains, when the mosquitos reproduce in greatest numbers and malaria is at its peak. Yet the peak of malaria admissions to health centres is not highest during this time. This tells us for sure that many people are making the decision to plant instead of taking the children to be treated.'

This brings us back to what Schellenberg calls the 'unsexy but critical' question of the economics of the war on malaria; and to how important money is if the Gateses' dream of final victory is ever to be achieved.

Fortunately, Bill Gates has plenty of it, the main reason why, at the start of the 21st century, money is at last on its way. An effort was made in the Fifties to combat malaria globally, but it was abandoned after Africa proved too intractable for the available science. Thirty years followed during which, apart from a few medical diehards, the world practically gave up on malaria. Until one day Bill Gates looked around and decided in the year 2000 that the most fruitful way to invest his Microsoft billions charitably would be in the attempt to restore the health imbalance between rich and poor countries.

The impetus provided by the Gates Foundation has led in turn to a new phenomenon, a global private-public partnership whereby governments - notably the American and British so far - pool resources with international bodies such as the World Health Organisation, private charities and the pharmaceutical companies to fight malaria together.

This new partnership has been decisive in terms of the development of the RTS,S vaccine. If the chairman of GlaxoSmithKline were to propose developing something as complex, time-consuming and bottomlessly costly as a malaria vaccine at the company's own expense, knowing the only market for such a vaccine is to be found in the world's poorest countries, then, as Dr Alonso pointed out, he would be fired on the spot. 'That is the reality in the capitalist world and it's no use screaming about it,' he said. Some do. 'I have had Latin American colleagues who've argued that it is unethical for us to work with Big Pharma,' said Dr Schellenberg. 'Those are ideologues who get in the way of effective solutions, I'm afraid. Because the truth is that if we don't have Big Pharma, we don't have the products.'

Big Pharma and Big Government, plus Bill Gates. Given that only the likes of GSK have the capacity to develop and manufacture such a drug, the solution has been for the public side of the new malaria partnership to provide funding for pre-clinical, laboratory trials and to offer a guarantee that they will purchase enough of the vaccines, once they are registered, to cover the company's costs.

It is thanks to this co-ordinated effort that places like Bagamoyo and Ifakara have their own well-equipped research centres, increasingly staffed by local scientists. It is thanks to this that free bednets have so far reached 20 per cent of Africa's target population, with more on the way; that Coartem production and delivery has increased 25-fold in the past three years; that research is under way into everything from the study of mosquito larvae-eating fish to electronic devices that fry mosquitos in mid-flight and a complex programme in the US to extract infected saliva from vast numbers of mosquitos and then use it as anti-parasite vaccine; and that the RTS,S vaccine, which is just one more possible magic bullet, was developed.

Salim Abdulla, who now heads the Bagamoyo research centre, is a PhD graduate of the London School of Tropical Medicine and a veteran of Ifakara, where he played a critical role in the development of Coartem. One of the Seattle 300, Abdulla, another man for whom catching malaria is like catching a cold, is more aware than anybody of the difficulties involved, yet he remains cheerful.

'I believe we are the first generation in human history with a serious chance of beating malaria,' he said. 'But I would not have dreamt of saying such a thing 10 years ago, when we were alone, neglected and unfunded. But then six or seven years ago people with big names, like Bill Gates, started making a noise. They said, "You know what? Malaria kills more people - and far, far more kids - than Aids!" And now things have snowballed to the point that there is an energy heading in this direction, towards us in Africa, that we've never felt before. I saw it in Seattle and I was impressed.'

Was he impressed by the rhetoric of the billionaires, too? 'We are painfully aware of the difficulties ahead,' Abdulla said. 'We applaud the scientific work, but the big question is how best to deploy those resources; how they will impact usefully on real people here in the real world. The people who will do it will be people like us, here. The Churchills make the calls for eradication,' he said, 'we carry out and execute. The challenge is tremendous, but that is why we welcome the Churchills - the Bill and Melinda Gates of this world. They inspire us soldiers on the ground to believe that one day we will win.'

(The Observer, 17/02/2008)