As the global fight against malaria stalls, malaria vaccine development could be primed for breakout

December 4, 2018 by Dr. Ashley Birkett

During the first 15 years of the 21st century, deaths from malaria fell dramatically. But progress is not inevitable and has recently stalled. New tools, like vaccines, are needed to keep efforts on track.

Dr. John Lusingu checks a young patient in the malaria ward of Korogwe District Hospital in Tanzania. PATH/ John Michael Maas

Dr. John Lusingu checks a young patient in the malaria ward of Korogwe District Hospital in Tanzania. PATH/ John Michael Maas

Malaria has infected humans for a very long time and in more places than many realize. There’s evidence that 3,000 years ago, malaria killed King Tut. It stalked the marshlands and fens of Great Britain and was common in the American South until the middle of the 20th Century.

Yet for this disease that has taken many turns over many millennia, the first 15 years of the 21st century are exceptional. During that time, deaths from malaria—which are primarily concentrated in young, African children—fell dramatically, from 839,000 in 2000 to 438,000 in 2015.

But progress is not inevitable. Over the last two years, malaria deaths and infections have plateaued. In some areas they are rising, and not just in Africa. For example, amidst the deteriorating infrastructure of Venezuela, malaria infections have surged by 69 percent.

Some of the problem involves a failure to invest the resources required to sustain the fight. But there are also other long-term challenges, including growing resistance among malaria-carrying mosquitoes to the insecticides used in bednets and indoor spraying campaigns—control measures that have been very effective at reducing infections.

Malaria parasites are spreading in Southeast Asia that are resistant to the lifesaving malaria medicine artemisinin—and to other malaria drugs as well. There are reports along the Cambodian border of “triple mutant” malaria parasites that are resistant to artemisinin and two other once-reliable malaria drugs. The biggest fear is that these superbugs could spread into India and then into the malaria strongholds of Africa.

Our goal at PATH’s Malaria Vaccine Initiative (MVI) is to help develop vaccines to aid in fighting malaria. If you look at the battle against infectious diseases that once spread death and misery, like smallpox, polio, measles, and whooping cough, vaccines helped turn the tide. Vaccines could do the same for malaria.

However, malaria-causing parasites, like all parasites that cause disease, are biologically complex in ways that have made them notoriously hard to subdue with vaccines. But despite the challenge, and because of substantial investments made over the last couple of decades, we are closer than ever to a world where malaria vaccines can join the battle.

The malaria vaccine closest to deployment is called RTS,S/AS01, and was developed by GSK. No vaccines are currently in use against human parasitic diseases, including against Plasmodium, the mosquito-transmitted parasite responsible for causing malaria. RTS,S will be the first, rolled out next year through a pilot introduction that will make it available to 750,000 young children living in areas of Ghana, Kenya, and Malawi, where malaria is common. This is the first step to possible wider use across Africa, where, alongside currently used interventions like bednets, indoor residual spraying, and drugs, it could help save thousands of lives.

Yet, even as RTS,S is rolled out, which is a huge achievement, we continue to develop the next generation of malaria vaccines. MVI is working with partners on creative ways to optimize the use of RTS,S that could translate to increased public health impact against disease and death in young African children, and potentially support its use in community-wide campaigns to accelerate parasite elimination.

A few years ago, we looked closer at what was originally seen as a fluke finding from more than a decade ago: that delaying and reducing the third dose of RTS,S might boost its protection against malaria. The small trial in 2014 provided intriguing evidence that this approach does indeed improve the quality of the immune response from RTS,S. A series of larger trials are now underway to explore whether different dosing approaches could positively impact efficacy.

“The lesson of the last decades is that a unified, well-funded assault on malaria—one committed to developing a variety of tools and making them widely available—can produce substantial progress.”
— Dr. Ashley Birkett, Director, PATH's Malaria Vaccine Initiative

These studies are being further leveraged, in concert with advances in medicine that enable isolation and testing of individual antibodies with a strong affinity for targeting a disease. These monoclonal antibodies (mAbs) are driving exciting new therapies targeting certain cancers and autoimmune conditions. We are at the cutting-edge of efforts to perform proof-of-concept studies with mAbs to answer critical scientific questions and determine their applicability, as a potential supplemental tool, to preventing infection by malaria-causing parasites.

We’re also excited about the potential to fight malaria with transmission-blocking vaccines (TBVs). A TBV could prevent mosquitoes that feed on malaria-infected humans from passing along their parasites to new victims. While not providing immediate protection from infection, high coverage with a TBV in a community where malaria is common would steadily reduce the risk of getting malaria from a mosquito bite—as the parasite’s survival is pegged to a continuous cycle, moving between humans and mosquito. A successful TBV could prevent malaria from returning to areas where it has been eliminated.

Malaria has been plaguing humans for thousands of years and the parasites that cause the disease are constantly evolving to evade our attempts at control. But while the current fight may have plateaued, the lesson of the last decades is that a unified, well-funded assault on malaria—one committed to developing a variety of tools and making them widely available—can produce substantial progress. If we continue to invest in malaria vaccine development, and fund other promising work now underway to create a new generation of drugs, insecticides, diagnostics, and other tools, while strengthening the programs and systems that deliver them, we can turn the tide. And from there, we can confidently set our sights on eliminating and eradicating the disease forever.

This post originally appeared on the Global Health Technologies Coalition's Breakthroughs Blog.