World Health Organisation right to be wary about first malaria vaccine.

Mosquirix is one of the most widely anticipated vaccines to have been developed. It is the first vaccine for malaria – a disease that kills more than 1,200 childrenevery day– and has been clinically proven to provide protection against the disease. So, given that it has passed the toughest regulatory hurdles required of it, why is it only being made available in a handful of countries?

Demand for the vaccine is likely to be high. With more than 200m cases a year, malaria is endemic in almost every country in sub-Saharan Africa, as well as large parts of Asia and Latin America. Last week, two advisory bodies to the World Health Organisation, the strategic advisory group of experts on immunisation and the malaria policy advisory committee, recommended against its immediate widespread use, and many people may have been left wondering why.

But it was a smart call. While there is a potential to save many lives with this vaccine, we have reason to tread carefully. Rather than being a simple solution, Mosquirix comes with complex caveats and some outstanding questions that the clinical studies were not able to address. While some may argue that any delay in getting the vaccine out to people could end up costing lives, experts first want certainty that, in a real-life setting, it indeed brings the benefits we expect, based on what was shown in the trials.

Clinical trials found Mosquirix to be both safe and effective, providing 39% efficacy at preventing clinical cases of malaria over the course of a four-year trial. While this is low for a vaccine, it is worth remembering that given the large number of people at risk, providing protection in just four out of 10 cases could still go a very long way. Moreover, since there can be more than one episode per child, the trials found that the vaccine prevented on average 1,774 cases of malaria per 1,000 children.

However, what happens during the controlled setting of a clinical trial does not necessarily translate into a real-world situation, and here lies the concern.

To begin with, Mosquirix requires four doses. That’s a lot for a vaccine. What’s more, trials suggest that its already low efficacy is further reduced if the fourth dose is not administered, down to about 28% protection against clinical malaria and reducing its impact on severe cases of malaria to nearly zero. That is worrying because, typically, the more doses required of a vaccine the higher the dropout rate.

It then becomes a question of how reliably the vaccine can be administered – and, again, Mosquirix presents challenges. To achieve maximum effect, it should be given to children from five months, with the fourth dose given around the age of two. This is out of sync with the typical immunisation schedule for children in poorer countries, who are brought in for routine vaccination when they are six to 14 weeks old.

That doesn’t mean it can’t be done. In light of how big a priority malaria is for these countries they may well indeed make it work. After all, we have seen this happen with the human papillomavirus (HPV) vaccine, another much sought after vaccine for developing countries, which is given to school-age girls to prevent cervical cancer.Delivering the vaccine will require unprecedented efforts to inform and mobilise people to bring their children to health clinics at the prescribed time to complete all four doses. But, with many of the countries in question already struggling to improve routine immunisation rates, it remains to be seen how reliably four doses of Mosquirix can be deployed.

But even if high coverage can be achieved, there is still a danger that news of the vaccine will give people a false sense of security and lead to a reduction in the use of other malaria interventions, which would be tragic. Insecticide treated bednets and anti-malarial medicine have already led to a 37% global decrease in malaria cases since 2000, and a 60% decline in the malaria mortality rate.

Mosquirix is no magic bullet and at best may prove to be a useful complementary tool in reducing malaria, but only one of many already being used.

All this combined is why the WHO has been so cautious, recommending that we proceed with just a few demonstration projects in three to five settings, and involving around 1 million children. This is a sensible approach; it is due diligence. With so many lives at stake, it is critical that we shed more light on these unknowns, so that we fully understand the impact of this vaccine before, or even if, we should make it more widely available.

• Dr Seth Berkley is CEO of Gavi, the vaccine alliance. Dr Mark Dybul is executive director of the Global Fund to Fight Aids, Tuberculosis and Malaria