Discovering new drug candidates against malaria

Fabrice Fekam Boyom is a Cameroonian biochemist and Professor at the Department of Biochemistry, Faculty of Science at the University of Yaounde 1. Prof. Boyom is the Founder of the “Antimicrobial and Biocontrol Agents Unit (AmBcAU)” whose mission is to contribute to reducing the burden of malaria and selected neglected tropical diseases (NTDs) in Africa through the discovery of novel lead compounds. Prof. Boyom is also a grantee of Grand Challenges Africa programme (GC Africa), and his work consists of discovering novel lead compounds to support new drug development against the target diseases. GC Africa promotes Africa-led scientific innovations to help countries achieve the UN’s Sustainable Development Goals (SDGs) by awarding seed and full grants to develop innovative solutions. GC Africa is implemented through the Alliance for Accelerating Excellence in Science in Africa (AESA), a funding, agenda-setting, programme management initiative of the African Academy of Sciences (AAS), the African Union Development Agency (AUDA-NEPAD), founding and funding global partners, and through a resolution of the summit of African Union Heads of Governments. GC Africa is supported by the Bill & Melinda Gates Foundation, Swedish International Development Cooperation Agency (Sida), and the German Federal Ministry of Education and Research (BMBF).

Summary

Genomic studies have revealed the features of Plasmodium falciparum parasites that confer resistance to anti-malarial drugs across Africa, putting previous success in controlling malaria at risk unless new and effective treatments are developed. To this end, African scientists have benefited from partnerships between research organizations from the ‘global north’ and south to build critical effort in evidence-based sustainable research, the prime example being a collaborative effort between the University of Cape Town’s holistic drug discovery and development (H3D) and the Swiss-based non-profit organization Medicines for Malaria Venture (MMV). Following this example, Prof. Boyom’s team is partnering with pharmaceutical companies (Johnson&Johnson, GlaxoSmithKline, Eisai Co., Ltd.) to identify new drug candidates for the treatment of malaria, leishmaniasis and Human African trypanosomiasis.

In spite of great efforts to control and eliminate malaria, it is still one of the major causes of death and poverty in Africa. It disproportionately affects vulnerable groups, including women and children, particularly from the poorest households. Endemic countries are facing the double challenge of protecting their citizens from existing threats to public health, like malaria, and emerging ones, like COVID-19.

Malaria is caused by Plasmodium parasites through the bites of infected female Anopheles mosquitoes, acting as "malaria vectors." The World Health Organization (WHO) estimates that in 2018, P. falciparum, the most virulent and drug resistant human malaria parasite, accounted for 99.7% of malaria cases in the African Region. The burden is heaviest in sub-Saharan Africa, where an estimated 90% of all malaria deaths occur, and in children under five, who account for 78% of all malaria deaths.

In addition to loss of life, malaria is an economic burden on African nations. In the absence of an effective vaccine, the management of malaria relies mainly on vector control and chemotherapy. These efforts are frustrated by a lack of treatment compliance, and vector and parasite drug resistance. Researchers at AmBcAU are seeking new drugs to treat uncomplicated Plasmodium falciparum malaria that are cost-effective, safe and able to evade parasite resistance.

Existing malaria treatment in Africa targets potentially drug-resistant organisms using Artemisinin-based Combination Therapies (ACTs). But reduction of the efficacy of treatment of severe malaria with one of these drugs (intravenous artesunate) has been recently reported among Ugandan children and throughout East Africa. These are serious indications that people may be developing resistance to current first-line ACTs. Novel antimalarial drug candidates must therefore be developed urgently.

The WHO Global Technical Strategy for Malaria 2016–2030 (GTS) includes a technical framework for all malaria-endemic countries with the “High Burden to High Impact” approach to be supported by WHO, the Roll Back Malaria Partnership to End Malaria and other partners, and is implemented at the country level. Goals for 2020 include to reach at least 40% reduction in malaria incidence and death rates and the elimination of malaria in at least 10 countries. However, progress toward these milestones has been poor, particularly in Africa.

One of the most serious threats to malaria control has been resistance to ACTs in the Greater Mekong Subregion in Southeast Asia. If artemisinin-resistant strains of P. falciparum arise in or are imported to Africa, it would be catastrophic for malaria control on the African continent. Further driving drug resistance is the wide availability of substandard and counterfeit malaria treatments in affected countries. Emphasis must therefore be on the search for alternative active agents which can replace ACTs in the event of widespread resistance.

Moreover, COVID-19 appears to have had a significantly negative impact on control of malaria and other major killers as major resources are currently diverted to the new threat, and also the fear of being contaminated or diagnosed positive for Coronavirus has led malaria patients to be reluctant to attend health centres during and after lock-downs.

All sectors of society, including governments, donors, the private sector and civil society organisations, have crucial roles to play to prevent malaria resurgence. Sparse resources must be allocated efficiently to ensure integrated health care systems that can sustain control activities against malaria while also fighting COVID-19. Importantly, science, technology and innovation must be used as drivers of novel drug discovery, development and delivery. Such efforts will promote basic, clinical and implementation research, which can be lifesaving for vulnerable populations.

The scarcest resources for full-scale drug discovery are technological, infrastructural, human resources and economic. Despite this, African scientists – led by African academics -- and international scientists working on African health problems, have made remarkable progress in drug discovery.  For example, H3D, at the University of Cape Town, Africa’s only fully integrated drug discovery centre, was the first university to start an “African anti-malarial drug” in Phase II clinical trials, in 2017. 

AmBcAU working in collaboration with pharmaceutical companies (Johnson & Johnson, Eisai Co., Ltd.) and Medicines for Malaria Venture, have identified new products that have good properties and that kill the agent of malaria (Plasmodium falciparum). Fabrice and his team plan to better the properties of these new products to the level where they will be used with success against the incidence of malaria in Africa.