Scientists Near Effective Malaria Vaccine, Solve 20-Year-Old Mystery

Ahead of the World Malaria Day (WMD), April 25, scientists across the globe have recorded major breakthroughs in efforts to eradicate and eliminate the female anopheles mosquito-borne disease.

The human piece of a malaria infection puzzle has been revealed for the first time, solving a long-standing mystery. A protein displayed on the surface of malaria parasites called “TRAP” is a high-priority vaccine target, but how it interacts with human host cells has remained a puzzle. Scientists from the Wellcome Sanger Institute have discovered a receptor protein on the surface of human cells that the TRAP protein interacts with as it navigates through the body.

The results, published April 9 in journal PNAS could help improve the development of an effective malaria vaccine.

Also, thousands of scientists from across the African continent and around the world (representing 70 countries) are gathering next week in Senegal for the 7th Multilateral Initiative on Malaria (MIM) Pan African Malaria Conference. They will share the latest research in the fight against malaria and discuss ways to end the epidemic for good.

This year’s meeting falls four months after the release of the World Health Organization’s (WHO) 2017 World Malaria Report, which found there is a dire need for new malaria interventions, particularly in sub-Saharan Africa. The report found that despite recent advances, overall progress against global malaria control has stalled. In 2016, there were an estimated 216 million cases of malaria, about five million cases more than in 2015. Ninety percent of these cases occurred in sub-Saharan Africa.

A consultant pharmacist and immediate past President of Pharmaceutical Society of Nigeria (PSN), Olumide Akintayo, told The Guardian: “Our nation is reputed to record about 65 per cent of clinical visitation directly traceable to malaria. Over time, the approach had always been to embrace a curative mechanism.

“This comes as Intermittent Preventive Therapy (IPT) especially for pregnant women or direct treatments with ACTs as prescribed in the National Malaria Policy.

“As we celebrate yet another World Malaria Day, the National Council on Health must consider and approve a preventive control of malaria through the use of safe chemicals to treat the environment.

“Other adjunct methodologies to this include the active involvement of Environmental Health Officers who should be actively engaged at Primary Healthcare level to carry out oversight responsibilities in our various communities. Government should dedicate more budget to preventive healthcare as this has tendencies to combat other new generation infectious diseases including Lassa Fever, Ebola and soon.”

Meanwhile, recent reports indicate that nearly half of the world’s population is at risk of malaria and more than 200 million people are infected each year. The disease caused the deaths of almost half a million people globally in 2015.

Malaria is caused by Plasmodium parasites that are transmitted to people through the bites of infected mosquitoes. Once the parasites have migrated from the mosquito bite site in the human skin, they must then navigate their way to a blood vessel and through the blood stream before finally infecting the liver for the next stage of the lifecycle. However, the molecular cues between the parasites and human host cells, which direct this migration, have remained unclear, making it challenging to intervene and stop the parasites in their tracks.

In this study, scientists from the Wellcome Sanger Institute have shown for the first time that the malaria parasite surface protein, TRAP, interacts directly with proteins called integrins on the surface of human cells.

Dr. Kirsten Dundas, first author from the Wellcome Sanger Institute, said: “For the first time, we’ve found a human receptor for the high-priority malaria vaccine target, TRAP. The TRAP protein on the surface of malaria parasites has been studied for the last 20 years, but a major unanswered question was how it interacted with human cells. Disrupting this interaction could be a key strategy for blocking malaria parasites’ journey through human tissues to prevent infection.”

The team dissected infected mosquitoes and extracted malaria parasites in the transmission stage of the lifecycle, known as sporozoites. It is the sporozoites that are transmitted to a person after being bitten by an infected mosquito. They then navigate through the skin to a blood vessel, where they travel in the bloodstream to the liver, invade liver cells and develop to the next stage of the lifecycle.

To investigate which receptors on the surface of human cells the sporozoites interact with as they travel through the body, the team tested the TRAP protein against a panel of human proteins known to be expressed on liver cells. The scientists used a technique developed at the Sanger Institute called AVEXIS, which is designed to detect the typically fleeting interactions between proteins displayed at the surface of cells. This approach revealed that the parasite TRAP protein interacted with human alpha-v-beta-3 integrins. It is possible the integrins act as signposts along the parasites’ journey to the liver.

Dr. Gavin Wright, lead author from the Wellcome Sanger Institute, said: “We have discovered a human receptor for the malaria parasite TRAP protein, and have provided an example which demonstrates that sporozoite surface proteins can directly interact with human cell surface receptors. This provides an important first clue in mapping the guidance cues that the malaria parasite must use to locate and invade the human liver.”

Meanwhile, highlights from some of the research being presented at the Senegal conference include:

1: Rethinking the Fight as Surge of Malaria Deaths in Conflict Zones Threatens to Upend Progress

Countries experiencing armed conflict—including Nigeria, Ivory Coast, South Sudan and the Democratic Republic of Congo—saw an increase in malaria infections and deaths in the past ten years, despite the progress that has been made globally in the fight against malaria in the same time period.

New studies presented at the MIM Conference will explore strategies to prevent and treat malaria in conflict zones. Some of the new studies that will be presented include outfitting community health workers in Central African Republic with mini-malaria clinics in a backpack and launching trials with new types of bednets in South Sudan.

2: Nearly one out of every four blood transfusions in Sub Saharan Africa contains malaria parasites

New research has found that almost one quarter of blood bank supplies in Sub Saharan Africa contains the parasites that cause malaria. Half of all children receiving blood transfusions need the procedure to address malaria-induced anemia, so these blood transfusions risk exposing them to more malaria-causing parasites. A second study examined the blood supply in Equatorials Guinea’s capital of Malabo, and found that screening technology commonly used in the region is unable to detect malaria parasites in most of the contaminated supplies.

4: Against background of increasing mosquito resistance to existing insecticides, a new class of insecticide shows promise for us in bednets and indoor spraying

Malaria control is being threatened by the spread of mosquitoes resistant to pyrethroids, the class of insecticide that is widely used for indoor residual spraying (IRS). Several studies being presented at the MIM Conference examine the IRS products being used and devise frameworks that will help African malaria control programmes choose the most cost-effective IRS product according to local endemicity, seasonality of transmission, level of resistance, bednet use and alternative malaria control interventions. The Liverpool School of Tropical Medicine will also announce the launch of the online Malaria Atlas Project, an insecticide resistance database.

This database includes over 14,000 georeferenced, time-stamped malaria vector samples, which provide data on susceptibility to resistance to pyrethroids. This is a progressive step in the process of global data sharing and demonstrates progress in tackling the public health problem of insecticide resistance.