Antimalarial Drug Proves Ineffective at Saving Children’s Lives

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A drug used for the initial treatment of malaria failed to improve child survivaA drug used for the initial treatment of malaria failed to improve child survival in in real world circumstances.

Rectal artesunate, a promising antimalarial drug, has no beneficial effect on the survival of young children with severe malaria when used as an emergency treatment in resource-constrained settings. These are the results of a large-scale study conducted by the Swiss Tropical and Public Health Institute and local partners in three African countries.

Rectal artesunate (RAS) proves ineffective at saving the lives of young children suffering from severe malaria, according to the results of a new study. A viewpoint about these findings was published in Lancet Infectious Diseases.

The study, which investigated a large-scale roll-out of RAS in the Democratic Republic of the Congo, Nigeria and Uganda, found that when used as an emergency treatment under real-world conditions, RAS did not improve the odds of survival for young children with severe malaria.

"Our findings point to a very inconvenient but important issue," said Manuel Hetzel, Research Group Leader at the Swiss Tropical and Public Health Institute and Professor at the University of Basel.

"We found that the overall management of severe malaria cases is so poor, that adding a single product does not seem to make a positive difference. Our focus must be on investment in improving existing health systems instead of relying on individual interventions."

The observational study, which included 6,200 severely ill children under the age of 5 years, found that in some instances, the children who received RAS were more likely to die than those who did not.

Inadequate follow-up care

"RAS was previously shown to have a beneficial effect if it is followed by adequate post-referral care at a hospital, which raised hopes in the malaria community," added Hetzel. "But more often than not, children do not finish the entire treatment due to lack of transportation to hospitals, cost of transport and treatment, or poor quality of care at hospitals."

Pre-referral treatment with RAS is the administration of a single suppository by a community health worker or in a remote health facility as an emergency treatment, in order to bridge the time until a child is admitted to a hospital where comprehensive post-referral care is available.

Post-referral care for severe malaria includes treatment with an injectable antimalarial, followed by a full oral course of artemisinin-based combination therapy, plus antibiotics and measures to manage potential complications.

Recommendation by the WHO

Based on the results of this new study, the WHO recommends that countries either delay scale-up until further guidance on the safe implementation of RAS is made available, or urgently review the conditions under which it is currently being used.

"The real-world evidence generated in our study should be taken into consideration before pushing for a large-scale roll-out of pre-referral RAS in systems that do not have a functioning continuum of care," said Hetzel.

"Without a comprehensive approach that acknowledges the complex realities faced by caregivers and health workers in remote, underserved areas, children will continue to die from malaria, and promising interventions such as RAS will fail to meet their full potential."

Original publication

Manuel W. Hetzel et al.
Pre-referral rectal artesunate - no cure for un-healthy systems
The Lancet Infectious Diseases (2022), doi: S1473-3099(22)00762-9

This text is based on a press release by the Swiss TPH.