The world’s first malaria vaccine is partially effective and could protect small children from the life-threatening disease, according to scientists who have completed the final trials.
The vaccine has been in development for 20 years and has cost more than $500m (£330m) so far. Hopes that it would save the lives of most of the 500,000 children under five who die from malaria each year have long been scaled back, but experts say that even a partially effective vaccine is an important breakthrough.
The latest results, published in the Lancet medical journal, show that the vaccine works better in children from the age of five months than it does in younger babies. This is a blow because it cannot be added to the routine infant vaccination schedule alongside the combined diphtheria, tetanus and whooping cough jab. The protection the vaccination gives wanes over time, which means a later booster shot is needed.
In the trials, children were given three shots of the malaria vaccine plus a booster, which is a formidable schedule for some settings in the developing world. Those given the three shots between the ages of five and 17 months had suffered 36% fewer episodes of clinical malaria by the time they were four years old than those not immunised – this was down from the 50% fewer episodes in the first year after vaccination.
The three shots alone did not protect them against severe malaria, but a booster resulted in 32% fewer severe cases and 35% fewer that required hospital.
Infants given the three shots when they were younger than five months had 26% protection from malaria episodes over the next three years but were not protected from severe cases of the disease.
It was “a classic example of the glass half full and glass half-empty”, said Brian Greenwood, professor of clinical tropical medicine at the London School of Hygiene and Tropical Medicine, who has been involved in the project for two decades.
“It would be very nice if we had a vaccine that gave you 80% protection and lasted for 10 years. We don’t have that although that has to be the long-term aim. It would have been very sad if it had had no effect whatsoever and so we are somewhere in the middle.
“We have to say this is an imperfect vaccine, but it did do something. It protected the older children for four years against uncomplicated malaria and severe malaria, which is a very nasty illness, by about a third. In the younger ones it didn’t do so well. That was one lesson we learned.
“The second lesson from this trial, which is new, is that we knew the effect of the vaccine wanes quite quickly – over a year or two – but if you give a booster dose you can bring it back again. The children who had the booster dose did much better over the four years. But then it began to wane again, so it wasn’t as if giving the booster dose protected you through the rest of your childhood.”
But if you give the vaccine to children older than five months as well as a booster dose, Greenwood said, “you will get an impact that is probably helpful in some parts of Africa, not everywhere”. The vaccine was tested in 11 different African sites.
The vaccine performed as well in Siaya near Lake Victoria in Kenya – an area with some of the most severe malaria anywhere, and where children get three or four attacks a year – as it did in places where the disease was less prevalent. Protection of children in Siaya was about 35-40%.
If you vaccinated 1,000 children in a low-risk area of the Gambia, for instance, said Greenwood, you would prevent about 20 cases. If you did that in a high-risk area, you would prevent almost 2,000 cases. “That may help in guiding where it would be sensible to use this,” he said.
Malaria kills 1,300 children each day in sub-Saharan Africa. As there were 198m malaria cases in 2013, even a partial vaccine could prevent millions of those, said Greenwood.
But another vaccine expert, Prof Adrian Hill, the director of the Jenner institute at the University of Oxford, cautioned that the results might not be good enough to roll out the vaccine. “There was no impact on malaria mortality and no significant effect on severe malaria,” he said. The protection was lower than that afforded by insecticide-impregnated bednets.
Hill said that while the reduction in uncomplicated malaria cases was of interest, he was worried by “new evidence of a rebound in malaria susceptibility”. Vaccinated children who did not get a booster jab after 20 months actually suffered more cases of severe malaria over the next 27 months than those who did not.
“So, overall, this work is a substantial scientific achievement in providing the first vaccine with any efficacy in young children. But its potential public health benefits and utility is not yet clear,” said Hill.
The vaccine – which has been developed by the British drug firm GlaxoSmithKline with additional funding from the international health organisation Path and the Bill and Melinda Gates Foundation – is now being considered for a licence by the European Medicines Agency.
A committee of the World Health Organisation will meet in October to discuss where and how the vaccine might be used. “I think it is extremely unlikely they would say just introduce the vaccine over all the endemic areas of Africa,” said Greenwood.
If the vaccine is approved and recommended for use in those areas where children suffer most from malaria, it will need donor funding because African governments are unlikely to be able to bear the full cost, even though GSK has said it will not seek a profit. GAVI, the global alliance for vaccines and immunisation, is already discussing financial support.
Malaria may have caused an extra 10,900 deaths in the Ebola-hit countries of west Africa in 2014 because of the collapse of their healthcare systems, according to a separate paper in the journal Lancet Infectious Diseases. A further 3,900 deaths may have been caused by the disruption of deliveries of insecticide-impregnated mosquito nets. Hospitals and clinics were effectively closed to everything except Ebola in some places and patients turning up with a malarial fever were liable to be misdiagnosed.
“Our predictions highlight the true magnitude of the humanitarian impact caused by the Ebola epidemic,” said the lead author, Dr Patrick Walker from the MRC centre for outbreak analysis and modelling at Imperial College London.
“In heavily affected Ebola areas the indirect impact of Ebola upon malaria deaths is likely to be of a similar magnitude to the public health burden caused by cases of Ebola directly. Measures to prevent malaria infection, such as the emergency mass drug administration measures currently recommended by the WHO, are urgently needed while these health systems recover.”