“Synergistic Plants Could Be A Source Of Combination Therapy For Malaria”-Researcher

Africa bears the burden of malaria with children under five accounting for 80 percent of Malaria deaths. WHO announced a global technical strategy aimed at reducing the global burden of malaria with research and innovation as one of the focus areas. Africa has joined the race with the African Academy of Sciences, the European Union, and the African Union supporting research through a 25 million euro project, African Research for Scientific Excellence-ARISE. In an interview with Cameroon Factfinder, ahead of World Malaria Day, Dr. Protus Arrey Tarkang a grantee of the African Research Initiative for Scientific Excellence (ARISE) program talked about his research, drug resistance, and policy around the implementation of research results. Read the excerpt:

Cameroon Factfinder: Is there enough investment in terms of research for malaria drugs in Africa?

Dr. Protus Tarkang: Investment in terms of research for malaria drugs is substantial but we cannot say it’s enough in the present circumstances. First, Africa bears the greatest burden of malaria. According to the WHO World malaria report 2021, it accounted for 96% (241 million) of global malaria cases in 2020 and 98% of global malaria deaths, with the poor and vulnerable populations experiencing the highest burden. Children under five accounted for about 80% of all malaria deaths in the same year. Secondly, over the past two decades, research for malaria drugs has taken up approximately 25% of the total funding dedicated to malaria control in Africa. In 2015, WHO announced a new global technical strategy (GTS) for malaria 2016-2030, aimed at reducing the global malaria burden by 90% by 2030. One of the three major pillars of that strategy is Innovation and research, which includes research on drugs for malaria. WHO estimates that additional funding of $673 million annually is needed for malaria research, which includes drugs, thereby justifying the fact that the available funding is not enough. Finally, despite the significant efforts to tackle malaria in Africa over the last 20 years, progress stalled during the COVID-19 pandemic, in addition to the emergence of resistance and poor health systems. Consequently, the envisaged goals in the GTS were not met and the funding gap between calculated needs and funds available has widened in recent years. This indicates that the total funding is inadequate to achieve the WHO global targets to reduce the malaria burden by 2030. Evidence for this is that the rate of withdrawal of malaria drugs from the list of essential drugs is higher than the rate of approval of new drugs. There is therefore a huge need for an increase in funding for malaria control, including research for malaria drugs.

What is the innovation in research around drug resistance?

Drug resistance is the reduction in the effectiveness of a medication in treating a disease or condition. In the context of malaria treatment, Artemisinin-based Combination Therapies (ACT) are the WHO-recommended treatment of choice for uncomplicated malaria. This consists of an artemisinin derivative and a partner drug that work together to reduce and eliminate the parasites. Therefore, we can talk about Artemisinin partial resistance, which is delayed parasite clearance after treatment with a drug containing an artemisinin derivative. Although a significant reduction of treatment efficacy has not been observed in association with delayed parasite clearance after treatment with a drug containing an artemisinin derivative, increases in the proportion of parasites carrying the malaria parasite mutation marker (PfKelch13) indicate that parasites with this mutation have an advantage under current treatment strategies and transmission dynamics. This could be due to higher transmissibility or improved fitness. Therefore innovation in research around malaria drug resistance is aimed at mitigating the risks and responding to the emergence and spread of antimalarial drug resistance, in accordance with the recommendations of the WHO strategy to respond to antimalarial drug resistance in Africa. Its objectives are to: i) improve the detection of resistance to ensure a timely response; ii) delay the emergence of resistance to artemisinin and artemisinin-based combination therapy (ACT) partner drugs; and iii) limit the selection and spread of resistant parasites where resistance has been confirmed. This strategy for attaining these objectives is centered around four pillars: strengthen surveillance of antimalarial drug efficacy and resistance, optimize and better regulate the use of diagnostics and therapeutics to limit drug pressure through pre-emptive measures, react to resistance by limiting the spread of antimalarial drug-resistant parasites, stimulate research and innovation to better leverage existing tools and develop new tools against resistance.

Can Africa attain zero malaria in terms of treatment?

Saying that Africa can attain zero malaria in terms of treatment will be an overstatement for the following reasons: First, zero malaria is a status that cannot be attained through treatment alone but through the implementation of many interlinked strategies, which include the product area (diagnostics, vaccines, and therapeutics), other areas of science (clinical trials, interventions, and product development, public health and cross-disciplinary), functional health systems and relevant policy implementation. All these areas contribute to their quota and require huge funding. Secondly, not all African countries possess the same level of national and international funding for malaria control or the same level of health delivery systems. Furthermore, extending malaria control measures to universal health coverage targets is a key challenge to many African countries. Insufficient investment contributes to the current intervention coverage gaps and the malaria burden. Finally, interlinkages between progress towards malaria elimination and economic wealth also imply that as countries get wealthier, they face graduation from donors’ funding while successful malaria elimination requires predictable sustained funding to reach and sustain malaria-free status, which is not the case for many African countries. Therefore, for Africa to attain zero malaria, it will need to do more.

What is your search on drugs about and how can this help Africa?

My current research is an African Research Initiative for Scientific Excellence (ARISE) project. Our focus is on the application of innovative mass spectrometry technologies for profiling bioactive molecules of selected synergistic antimalarial plants, combined with the development of high and medium-throughput screening methods, for the discovery of new therapeutic leads for malaria drug discovery. We are aware that plants have played a vital role in the therapeutics of malaria, by providing the main drugs such as quinine (and its derivative chloroquine), atovaquone, and artemisinin (and its derivatives). Furthermore, the rapid emergence of resistance in the malaria parasite to synthetic drugs compared to drugs sourced from natural sources indicate the relevance of plants. Therefore, in the context of combination therapies, synergistic plants could be a source of combination therapy for malaria. Hence, we can term this project “ looking back into the future” of malaria drug discovery.

The expected outcomes that will be useful for Africa include the: Implementation of a drug discovery platform with MTS and high throughput screening (HTS) liquid handling systems. Development of an advanced technological platform by direct combination of High-Resolution Mass Spectrometry (HRMS) and malaria parasite asexual blood stage-specific susceptibility, generating data to improve knowledge on malaria combination therapy, the discovery of synergistic plant secondary metabolites, as leads with established modes of action, to enable further development, promotion of national and international collaboration, development of Leadership skills and capacity building in Pharmaceutical medicine, training of graduate students, knowledge transfer, and dissemination of scientific knowledge, strengthening capacities for science in Africa by developing the human capital through training of students and scientists. Provision of scientific evidence for policy. ARISE fellowships are aimed at building the capacity of African researchers, particularly early-career scientists, to deliver cutting-edge research in contribution to efforts being made towards the transformation of Africa into a knowledge-based and innovation-led continent. Specifically, ARISE seeks to: enhance the capabilities of emerging African early career research leaders committed to a research and teaching career in Africa, strengthen institutional research management and support systems to enable pan-African research to thrive, and support the generation of cutting-edge research in contribution to the transformation of Africa into a knowledge-based and innovation-led continent. ARISE is a Euro 25 million program implemented by the African Academy of Sciences (AAS) in partnership with the European Union (EU) and the African Union (AU).

What advice to malaria-endemic countries like Cameroon and other African countries?

My advice to malaria-endemic countries like Cameroon and other African countries would directly fall in line with the “Rethinking Malaria” global consultation forum of health experts, which through its discussions along governance, integrated service delivery, and training and capacity building, made the following recommendations on defined themes: Perception of the malaria problem: Malaria needs to be viewed as a societal problem of development, and not as a medical problem alone, the leadership of the malaria problem: Efforts must be led by endemic countries in partnership with multiple stakeholders within each country., investment in the health workforce: Health workers at all levels should be empowered through readiness, training, and education, visibility and use of reliable and real-time data, knowledge, and information: Malaria data needs to be valued and visible and used by the public and policy-makers, as it has been for COVID-19 decision-making, innovation: Globally, greater attention should be given to innovation and problem-solving and to support endemic countries in entrepreneurship, R&D, and manufacturing, strengthening health systems: Health for all means solving the problem of malaria as a pillar of universal health coverage.

What are some of the challenges around Malaria research in Africa?

Some of the challenges around malaria research in Africa include institutions with inadequate research support structures to attract relevant funding for research and promote fruitful collaborations, inadequate technological platforms to promote innovation, poorly developed health systems that hinder relevant health delivery, inadequate national and international funding to enable good science and relevant data generation poor remunerations for researchers, thereby encouraging researchers’ mobility to greener pastures, lack of strategies for the promotion of research results., inadequate exploitation of research results for policy.

Do African governments implement research results?

Implementation of research results brings about development in various domains. In this regard, the various indices of development of the various African countries would be evidence of their level of economic development and would reflect the government’s effort at the implementation of research results.

What advice in terms of policy around Malaria research?

When it comes to global strategies towards attaining certain policy objectives, it is advisable not to reinvent the wheel but to endeavor to explore the strategies at the disposal of policymakers before trying to propose new ones, because there is a lot to learn from their implementation. My advice in terms of policy around malaria will be to explore available documents such as the various annual world malaria reports, available scientific data, and especially the Global Technical Strategy for Malaria 2016-2030 and keenly consider the new information therein, which includes the following; under the Global Technical Strategy for Malaria 2016–2030, annual investment targets per person at risk of malaria have been estimated and are expected to increase by 2030. The total investment needed for malaria control and elimination is not expected to decrease before 2030, reflecting in part population growth in currently high-burden countries and the costs of surveillance in countries near elimination. Therefore, considering the urgent need to increase domestic and international funding for malaria and health more generally, the priority of policymakers should be to ensure the efficient use of currently available resources to maximize value for money by investing in the health workforce, implementing technological innovation surveillance, and strengthening health systems.

Do you have any message to pass across concerning malaria?

Malaria control and elimination strategy is not a myth but a reality and the meaningful participation of everyone living in endemic areas is essential. Therefore, all stakeholders should endeavor to understand what is needed in order to know their role.

Interviewed by Leocadia Bongben