By Hannah Zhihan Jiang

South Africa is edging closer to eradicating malaria but experts warn that drug resistance now poses a significant challenge to progress made in the last twenty years. 

The World Malaria Report 2022 confirms South Africa recorded 5,812 cases in 2021. But it’s expected to miss its target to eliminate the disease by 2023. 

“Yes, we have very low numbers of cases, but that doesn’t mean that you can move our resources and move it to another disease that seems to have a high number of cases. Because if we can’t do the follow-up, and if we can’t do the water tracking, the cases will go up again,” says Dr Jaishree Raman, Principal Medical Scientist at the National Institute for Communicable Diseases.

The best available treatment against Malaria is the artemisinin-based combination therapy (ACT) regimen recommended by the WHO since 2001. The treatment is a combination of an artemisinin derivative and a partner drug. The short-lived artemisinin derivative rapidly reduces the parasite biomass. And the long-acting partner drug eliminates the remaining parasites. 

Resistance to treatment will increase malaria cases

But there are signs of parasite partial resistance to the treatment, particularly in areas such as Eritrea, Rwanda and Uganda. This partial resistance could delay parasite clearance after treatment, potentially leading to larger parasite biomass remaining after three days of treatment. However, even in areas with parasite mutations, a seven-day treatment has shown over 90% efficacy, according to Strategy to Respond to antimalarial drug resistance in Africa by the WHO.

“It can be very problematic if you have resistance to both components, which is not the case yet in Africa, but which could happen anytime,” says Dr Pascal Ringwald, lead author of the Strategy and a former coordinator in the WHO Global Malaria Programme.

If the malaria parasite becomes resistant to both artemisinin and the most common partner drugs, researchers at Imperial College London estimated 16 million additional malaria cases per year in Africa. This would be a 7% increase in cases compared to a scenario with no resistance. 

“If there’s much stronger resistance, we are going to really have no treatment. And that’s going to basically roll back any efforts moving towards elimination because we just won’t have any drugs to effectively treat patients,” says Raman.

Efforts to get ahead of full resistance

While Medicines for Malaria Venture, a not-for-profit foundation developing antimalarial drugs, manages a portfolio of over 65 antimalarial medicines, Raman says it will take about another 5 to 10 years before any antimalarial medicine with a different mechanism comes to market. 

The most promising non-artemisinin-based combination, ganaplacide-lumefantrine, is in the patient exploratory phase (Phase IIb), according to the WHO.

The process of discovering new medicines can be a lengthy and expensive process as a new antimalarial drug has to be developed through a mechanism that the parasite has never seen before, says Dr Kelly Chibale, founder and director at the Holistic Drug Discovery and Development Centre (H3D) at the University of Cape Town. 

An additional hurdle is posed by the low volume of clinical trials conducted in Africa, which is a critical step in determining whether a new drug is efficacious and safe in the African region where most malaria cases are found. Researchers also need clinical trials to determine the best combination of drugs to treat malaria.

The paucity of clinical trials has been an issue: a recent assessment of clinical trials on clinicaltrials.gov suggest that of over 2.74 million studies, barely 7000 were conducted in Africa. Reasons include a lack of a well-structured regulatory environment, a scarcity of research funding and the reluctance of trial participation due to colonial history.

“We need to look at doing more clinical trials in more regions of Africa because Africa is arguably the most genetically diverse continent,” says Chibale. “It’s a constant war, and we have to be ahead of the parasite every time.”

Prevention and surveillance remain critical

Experts say the development of new drugs needs to be partnered with extending the lifespan of the current ART treatment as well as continued malaria prevention and surveillance. 

“We need to buy time by making sure that we have good stewardship, people finish their treatment and we fight fake medicines that really compromise the standards and the quality of our medicines,” says Chibale.

If a drug is used at a concentration too low to produce a medical effect, it will allow resistant infections to be maintained and transmitted, according to the WHO.

The WHO recommends the deployment of either insecticide-treated nets or indoor residual spraying for malaria vector control, a highly effective way to reduce malaria transmission and prevent infection. 

The first malaria vaccine RTS.S was approved by the WHO in 2021. As of April 2022, the vaccine was given to one million children living in areas with moderate-to-high malaria transmission. It reduces hospital admissions of severe malaria by 30%.

A second vaccine has recently been approved in Ghana and Nigeria in April, though the WHO has yet to issue approval. It shows a 77% efficacy rate in trials by the University of Oxford.

“It is very encouraging to have two vaccines come to market. We need more tools to control malaria effectively,” says Raman. – Health-e News