The War Against Malaria: Antimalarial Resistance a Threat

By Alberto Leny

Scientists conducting research in some of Africa’s leading universities have detected that antimalarial resistance to drugs and insecticides is creeping back into the continent.

Malaria Research and Capacity Development in West Africa (MARCAD) Director Oumar Gaye says: “The gains made in the fight against malaria must not be reversed. Despite the significant progress, we’ve seen an increase in indicators marking the resurgence of malaria in some areas, notably the Democratic Republic of Congo (DRC), Nigeria and Rwanda.”

Gaye leads the MARCAD consortium, which includes University of Sciences, Techniques and Technologies of Bamako, Mali, Medical Research Council Unit, The Gambia, University of Yaounde, Cameroon and University of Health and Allied Sciences, Ghana, in collaboration with the London School of Health and Tropical Medicine, the London School of Tropical Medicine and the University Copenhagen, Denmark.

MARCAD, the West African Centre for Cell Biology of Infectious Pathogens (WACCBIP) at the University of Ghana and Developing Excellence in Leadership and Genetic Training for Malaria Elimination (DELGEME) are among the 11 awardees of the $100 million DELTAS Africa programme.

The Deltas Africa Programme is being implemented by The African Academy of Sciences’ Alliance for Accelerating Excellence in Science in Africa (AESA), with the support of Wellcome Trust and the UK Department for International Development (DfID).

Postdoctoral fellows and PhD students are integrated into established research teams with senior scientists in participating institutions within a stimulated research environment.

WACCBIP Director Gordon Awandare says, “We have seen positive developments in malaria treatment. The artemisinin-based combination has proved effective in malaria treatment in Africa and no cases of drug resistance have been reported in the 10-15 years since it was introduced. However, we must keep tracking and monitoring malaria parasites, especially due to the problem of drug resistance.”

At the University of Ghana, WACCBIP has grown from humble beginnings under Awandare’s leadership to gain global recognition and by 2017 had 34 Master’s, 41 PhD candidates and 12 post-doctoral fellows as well as 32 local faculty and more than 40 regional international contributing scientists.

Awandare affirms that scientists are vigorously looking for any evidence of resistance through molecular sampling of parasites and sequencing DNAs for evidence of resistance, acting quickly and sustaining the action.

Despite, malaria medicines working well, there are serious concerns that malaria parasites are once again developing widespread resistance to antimalarial drugs, according to reports from the Worldwide Antimalarial Resistance Network (WWARN).

Protecting the efficacy of existing treatments remains a top priority for malaria endemic countries and the global malaria community. Effective monitoring, supervision and surveillance are needed to respond to the emerging threat of antimalarial resistance, which can arise through multiple mechanisms and multiple genes.

Recent malaria outbreaks have revealed inadequate treatment, coverage of at risk populations and possibly migration in conflict-affected regions, and internally displaced persons (IDPs) located in high-risk areas in most African countries’ general health and surveillance systems.

Vector resistance is not alarming although there have been some cases for drugs and insecticides used on bed nets, calling for development of new categories of insecticides.

In Senegal antimalarial drugs used in treatment and prevention of malaria are one of the main reasons for the current success in controlling malaria. However, this is highly dependent on the continued effectiveness of these drugs, which may be compromised by the spread of drug resistance. Chloroquine (CQ) was the first-line treatment for uncomplicated malaria until 1998.

High rates of CQ treatment failures and an increased risk of childhood malaria deaths prompted health authorities to abandon CQ in 2003. Sulfadoxine-pyrimethamine (SP) plus amodiaquine (AQ) was then introduced despite the fact that low numbers of SP and AQ failures were documented when used alone.

However, because of resistance against widely used antimalarial drugs, most countries were forced to introduce artemisinin combination therapies (ACTs) for malaria treatment. Despite the decrease in the malaria burden in Africa, it is crucial to identify emerging drug resistance in attempt to delay ACT resistance spreading from Southeast Asia where it is evident.

Globally, the level of malaria incidence has decreased due to good progress in science and innovative strategies. In Senegal, only 300 cases of malaria deaths were reported in 2018, down from one million around 2000. But a drop in funding threatens the progress. Gaye says: “There has been a decline in funding for malaria control from the main funders, most external, such as the Global Fund, Malaria Initiative and DfID.”

This decreased amount of funding is also having a negative impact, so it is critical that governments put in more money in the area of malaria prevention and control. The array of actors on the global health stage must leverage their collective strength.

World Health Organisation (WHO) Director-General Dr Tedros Adhanom Ghebreyesus says the first malaria vaccine launched this year in Ghana, Kenya and Malawi as part of a large-scale pilot project has the potential to save tens of thousands of lives. “We have seen tremendous gains from bed nets and other measures to control malaria in the last 15 years, but progress has stalled and even reversed in some areas. We need new solutions to get the malaria response back on track, and this vaccine gives us a promising tool to get there.”

WHO’s Action and Investment to Defeat Malaria (2016-2030), makes a powerful economic and humanitarian case for continued investment in the fights against malaria. Despite the past two decades of great achievements in malaria control, it faces two major challenges – the emergence of resistance to the new generation antimalarial drug resistance, artemisinins and the emergence of malaria vectors to common insecticides in many countries in Africa.

Distribution of resistance to all four classes of insecticides in the major malaria vectors belonging to An. Gambiae complex and An. Funestus group in Africa from 1985 to 2017. The green dots represent full susceptibility, orange is for suspected resistance and red for confirmed resistance. (A) Widespread resistance to pyrethroids. (B) Widespread resistance to DDT (organochlorines) although susceptibility is observed in southern Africa in An. funestus populations. (C) Profile of resistance to carbamate with significant areas of resistance in west and southern Africa. (D) Broad susceptibility to organophosphates across the continent but with pockets of resistance in West Africa and Ethiopia in An. gambiae s.1.