A global village to address malaria

Malaria is a parasitic infectious disease that is prevalent in many tropical regions of the world where the mosquito vector thrives. At least 3 billion people are at risk globally, nearly half the world’s population.

In 2017, there were nearly 220 million new cases, most of which were successfully treated with antimalarial drugs. Even though the mortality rate has declined substantially since 2000, the infection still kills more than 400,000 each year with more than 90% of deaths occurring in sub-Saharan Africa.

What illustrates the true tragedy of malaria is that it is preventable and curable when diagnosed and treated promptly and correctly at an early stage.

Professor Susan Charman leads a team of 25 research scientists and postdoctoral fellows who undertake physicochemical, metabolism and pharmacokinetic investigations to inform drug candidate design and progression. In partnership with international collaborators, her work has contributed to one new antimalarial drug, five new antimalarials currently in clinical development, and numerous preclinical drug development candidates.

The Director of the Centre for Drug Candidate Optimisation at the Monash Institute of Pharmaceutical Sciences, Monash University was the latest speaker at the Sir John Monash Lecture where she presented on “The Power of Partnerships in Antimalarial Drug Discovery”.

In 2015, new targets were set by the WHO Global Technical Strategy for Malaria 2016-2030. The target for 2030 is for more than 90% reduction in incidence and mortality relative to 2015 and elimination in more than 35 countries that were actively transmitting in 2015. According to the WHO 2020 Initiative of 21 Malaria-Eliminating Countries: 2019 Progress Report, Malaysia is on track for the elimination of human malaria by the target date of 2020. Over the period of 2000-2015, Malaysia has accomplished a 75% decrease in human malaria case incidence. This success is contributed to increased government funding and commitment as well as the improved diagnosis, treatment, prevention and surveillance in hard-to-reach regions where malaria is prevalent.

The road to the elimination of malaria is complex as there are many factors that lead to this disease. Elimination will require a multifaceted approach including vector control with insecticide-treated bed nets and indoor spraying, rapid and accurate diagnostic tests, new drugs and vaccines for prevention and treatment, the commitment of governments, communities and health systems and funding.

One of the most important historical discoveries occurred in the early ‘70s when a Chinese pharmaceutical chemist, Tu Youyou, isolated and identified the active component from an extract of a plant known as artemisia annua or sweet wormwood, which later became known as artemisinin. Tu received the 2015 Nobel Prize in Physiology or Medicine for her discoveries.

Artemisinin and its derivatives were found to be very effective drugs to treat malaria and a combination containing the derivative artemether and another Chinese drug, lumefantrine, was registered in China in the early 90s. This same artemisinin-based combination therapy was later registered in Europe in 1999 by Novartis as Coartem and this combination is still used today. Artemisinin Combination Therapies or ACTs have had a major impact on reducing malaria mortality over the past 15-20 years, however, there is now evidence of emerging resistance to these drugs in the Greater Mekong Subregion highlighting the need for new drugs with different mechanisms of action.

Looking forward, new medicines have a somewhat different role to fill for the goals of eradication. “We need to clear all forms of parasite from the human host and in doing so, disrupt the transmission cycle. New drugs will also be needed to protect the malaria-free population such that disease is not reintroduced back into these groups. We also need new medicines that focus on improved patient compliance, ideally with a single dose administration, and medicines that are suitable for vulnerable populations including children and pregnant women,” she said.

To address these challenges, global partnerships that combine the expertise and skillsets that exist within academia, the pharmaceutical industry and endemic countries have shown the greatest promise for success.

One of the best-known partnerships is a product development partnership (PDP) known as the Medicines for Malaria Venture (MMV). As a PDP, MMV brings together academic groups, government and non-government organisations, philanthropic groups and private industry with the goal to discover, develop and develop new, effective and affordable antimalarial drugs.

“One area where MMV has been instrumental is to establish centres of excellence and expertise around the world to study the complex lifecycle stages of the parasite. This enables the effectiveness of drugs against the different stages to be tested and it would be almost impossible to find all of these skills within a single institution.

“These centres ensure that we have the tools available to address the challenges of antimalarial drug discovery. MMV also provides access to the wide-ranging skills and expertise needed to take a new molecule from the early hit stage through lead optimisation and into preclinical and clinical development in accordance with industry best-practice standards,” Professor Charman said.

So, what does it take to eliminate malaria? First, it takes a vision – a world where there is no malaria.

“It also requires goals and targets that set the agenda for eradication, and a plan to deliver the objectives of those goals. It takes multiple strategies and approaches to fulfilling the goals of the plan. And finally, it takes committed people working around the world in different areas with different skill sets to discover and develop new drugs; collectively working as a global village to address the many challenges associated with malaria eradication.” Professor Charman said.