A pilot meningitis A immunization campaign targeting more than 155,000 people in Benin with a vaccine that does not require constant refrigeration has demonstrated clear benefits, enabling wider reach, more efficient administration and potential cost reduction, researchers say.
Most vaccines must be kept cold, at temperatures between 2 and 8 degrees Celsius, but the meningitis A vaccine known as MenAfriVac can be stored for up to four days at up to 40 degrees Celsius without any loss of potency, efficacy or safety.
MenAfriVac, which was approved for use outside of the cold chain in October 2012, was used to vaccinate 155,596 people, aged 1 to 29, in 150 communities in northern Benin in December 2012. The World Health Organization (WHO) says no cases of meningitis A were reported by the vaccinated population in 2013. The findings were recently published in the journal Vaccine.
“This is really quite revolutionary. This could really change the way mass vaccination campaigns are conducted in remote or low-resources settings,” said Marie-Pierre Preziosi, director of the Meningitis Vaccine Project, a partnership between WHO and global health NGO PATH, which drove the development of MenAfriVac.
Breaking the cold chain
MenAfriVac was first introduced in 2011 in a mass vaccination campaign in Africa’s meningitis belt, which stretches from Senegal to Ethiopia. To date, more than 150 million doses of MenAfriVac have been used to vaccinate people across 12 African countries.
But it was not until the Benin trial that the vaccine was administered outside of the cold chain.
Michel Zaffran, coordinator of WHO’s Expanded Programme on Immunization (EPI), said that it has been known since the early 1970s that a number of vaccines are relatively heat stable.
“Nevertheless, all of these are licensed for storage and use in the very strict temperature range of 2-8 degrees Celsius, which of course is fine for industrialized countries that have electricity and lots of equipment, but it’s actually sometimes quite challenging to achieve for developing countries,” he said.
Much of rural Africa lacks electricity, while power cuts are common in cities and daytime temperatures in most countries exceed 30 degrees. Many villages are too remote to be reached before vaccines spoil.
“The way it normally works is that the vaccines are refrigerated all the way to the district level, and then for that ‘last mile’ - which is often a lot more than a mile - you take those vaccines... and put them into a cold box with ice bags and temperature monitors, so that you can carry the insulated boxes... to the person being vaccinated,” said David Kaslow, the vice president of product development at PATH.
“So getting those freezer bags and ice, and making sure everything is the right temperature, putting them in boxes and all those sorts of things are very labour intensive and quite costly,” he explained.
In the Benin trial, only nine out of 15,000 vials had to be discarded for exceeding the four-day limit, and no vials exceeded the 40 degrees maximum temperature threshold. This represents wastage of a mere 0.06 percent.
Normal wastage during vaccination campaigns can be as high as 5 percent, because as soon as the 2 to 8 degree temperature range is exceeded, the vaccine must be discarded, said Florence Fermon of Médecins Sans Frontières.
Not having to worry about freezer packs or having to return to the district health centres each night to store and replenish vials meant that health staff in Benin could vaccinate more people per day and reach more remote areas.
Researchers estimated that allowing MenAfriVac to work outside the cold chain for a limited time could cut costs by up to 50 percent, to US$0.12 per dose. Most of the savings are due to reduction in transportation and storage during the “last mile”, according to a separate study by WHO.
“So it really seems to be a no-brainer,” Kaslow said. “You have a vaccine that appears to be quite stable... saves money, is less labour intensive… and has been tailored to the needs of people in low-resource settings.”
There were some initial challenges during the study, however, including teaching health workers how to properly use a vaccine outside the cold chain.
“This is a new concept and so after years of working within the constraints of a cold chain, this new delivery approach needed to be accompanied by training and supervision. We didn’t want people to get confused by vaccines in the cold chain and out of cold chain, and how to manage this because it has to be done under proper guidelines and all,” Preziosi said.
The next step will be not only to expand the use of MenAfriVac in controlled temperature chains in other African countries, but also to approve vaccines for diseases such as cholera and yellow fever for use outside of the cold chain.
“It’s a very slow process,” Zaffran said. “However, I think we’ve opened the door, which is likely to create a momentum for more interest in generating the data that could help us use the vaccine in a more suitable manner, in a manner that really takes advantage of its heat stability.”