Malaria drugs failure rate high among malnourished children

Malaria is among the leading causes of disease-related suffering and death in Kenya.

It affects 19.4 percent of the population based on the 2019 Economic Survey.

The most affected are usually and children below the age of five and pregnant women due to their low immunity.

For those diagnosed with the disease, treatment with recommended drugs — known as artemisinin-based combination therapies (ACTs) — are paramount to effectively manage the disease and prevent adverse outcomes including death.

Though the drugs are effective at tackling the disease, research now shows that they may be underperforming in severely malnourished children.

Yet, malnutrition is common among children in Kenya’s malaria hotspots due to high poverty levels afflicting most families.

A new study published in the Clinical Pharmacology and Therapeutics Journal has found that severe malnutrition is associated with lower exposure to a type of ACT malaria drug know as artemether-lumefantrine (coartem) among children.

This is the most common treatment for uncomplicated malaria caused by parasites known as Plasmodium Falciparum that is predominant in Kenya. The World Health Organisation (WHO) recommends the therapy.

The study, which is the first to specifically address this treatment challenge, calls urgently for further research into optimised drug doses for undernourished children.

According to the researchers, the altered physiology in malnourished children may change the uptake and distribution of antimalarial drugs into the body. For example, the absorption and elimination of the medicines might be reduced in those affected.

Despite this knowledge, the study notes that there has been little research into how well treatments work in this particular group of young patients.

This is because malnourished children and other vulnerable patients such as pregnant women and very young children are often excluded from malaria drugs clinical studies, as they are difficult to recruit in large numbers.

Besides, their participation also raises specific ethical concerns as they may suffer from adverse health effects when subjected to such studies.

The institutions that conducted the new study include the University of Cape Town, Malaria Research and Training Centre in Mali, Ministry of Health in Niger, Mahidol-Oxford Tropical Medicine Research Unit (MORU), the Médecins Sans Frontières (Doctors Without Borders) and Epicentre Organisation.

They compared the effect of the Artemether Lumefantrine drug in the treatment of malaria in two hospitals in Mali and Niger among 131 children with severe malnutrition compared to 226 children without malnutrition.

Key measures of malnutrition collected include weight-for-height, mid-upper arm circumference or presence of nutritional oedema (a condition characterised by an excess of watery fluid collecting in the feet and extending upwards to other parts of the body).

According to the researchers, these malnutrition indicators are not usually routinely collected in clinical malaria trials.

Yet, they need to be analysed to provide deeper insights into the systematic underexposure of antimalarial drugs in malnourished children.

The results of the study showed that severely malnourished children had an average of 19 percent less exposure to the anti-malaria drug compared to other children.

This resulted in an increased risk of drug failure leading to the acquisition of new malaria infections during the follow-up period.

Overall, all children were found to have significantly lower drug exposure compared to adults.

Yet, children are currently prescribed the same dosing regimen as adults — having the artemether-lumefantrine drug twice daily for three days.

“There are serious knowledge gaps in associations between malnutrition and antimalarial drug efficacy,” said Prof Joel Tarning, the head of the Worldwide Antimalarial Resistance Network Pharmacometrics group who led the study.

“Malnourished children are more severely affected by malaria and they have lower levels of antimalarial drug in their bodies after standard treatment. This needs further study so that we can treat these patients better. “Dr Rebecca Grais, a Research Director at Médecins Sans Frontières said the study is critical to improving treatment protocols among this highly vulnerable group of children. “Those suffering from both severe acute malnutrition and malaria need care the most,” she said.

Dr Palang Chotsiri, a researcher at MORU says this is because drug absorption, distribution, metabolism, or elimination might be affected by the nutritional status in children.

Nevertheless, the researchers note that further studies are still required to investigate optimised dosing regimens to improve antimalarial treatments in malnourished children.