Malaria is a serious infectious disease caused by a parasite called Plasmodium, which is transmitted to humans through the bites of infected mosquitoes. The most common symptoms of malaria include fever, chills, sweating, headache, muscle pain, and fatigue. In severe cases, it can lead to complications such as anemia, kidney failure, and brain damage. Malaria is most common in tropical and subtropical regions of the world, particularly in sub-Saharan Africa, where it is a leading cause of death and illness. Malaria
According to a study conducted by the Swiss Tropical and Public Health Institute (Swiss TPH) and partners, results show that the promising antimalarial drug, rectal artesunate (RAS), is ineffective at saving the lives of young children who are suffering from severe malaria. The viewpoint about the study’s findings was recently published in The Lancet Infectious Diseases.
The study, conducted in the DR Congo, Nigeria, and Uganda, which aimed to investigate the large-scale roll-out of the antimalarial drug RAS, has found that when used as an emergency treatment in real-world conditions, RAS was not effective in improving the survival rate of young children suffering from severe malaria.
“Our findings point to a very inconvenient but important issue,” said Manuel Hetzel, Professor of Epidemiology at Swiss TPH and first author of the publication. “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. “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 (ACT), plus antibiotics and measures to manage potential complications.
The current recommendation by the WHO
The current WHO guidance on using RAS as pre-referral treatment is based on a randomized controlled trial that took place between 2000 and 2006 in Ghana, Tanzania, and Bangladesh. The trial offered limited guidance on introducing RAS at scale. “Under real-life conditions, many factors influence whether an individual is appropriately treated and cured, which is why interventions that work well in a controlled trial may not always fulfill their potential in real life,” said Phyllis Awor, co-investigator of the study at the Makerere University School of Public Health in Uganda.
Based on the results of this new study, the WHO issued an Information Note in October 2021 recommending 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. At present, the current WHO guidelines on RAS are under review by a team of WHO-appointed experts.
“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.”
Reference: “Pre-referral rectal artesunate: no cure for unhealthy systems” by Manuel W Hetzel, Phyllis Awor, Antoinette Tshefu, Elizabeth Omoluabi, Christian Burri, Aita Signorell, Mark J Lambiris, Theodoor Visser, Justin M Cohen, Valentina Buj, and Christian Lengeler, 19 December 2022, The Lancet Infectious Diseases.
DOI: 10.1016/S1473-3099(22)00762-9