severe malaria | Africa-Europe team pioneers study response

Severe malaria has the capacity to escalate into a medical emergency, claiming lives within a mere 24 hours if left untreated.
The Africa-Europe joint study will generate evidence on interventions used to buy time for patients to reach a health facility.
In dire situations involving children, the administration of artesunate rectal capsules becomes a crucial intervention, offering millions a lifeline.

A groundbreaking initiative, the SEMA ReACT (SEvere MAlaria treatment with Rectal artesunate and Artemisinin-based Combination Therapy [in remote settings]) consortium, marks a fresh collaboration between Africa and Europe.

This study addresses the knowledge gap surrounding an intervention designed to provide a critical time buffer for seeking additional care in remote settings where transferring to health facilities is difficult.

The challenge of saving severe malaria patients: where systems fall apart

Malaria, a potentially deadly mosquito-borne disease, has the capacity to escalate into a medical emergency, claiming lives within a mere 24 hours if left untreated. The urgency is exacerbated in rural areas where the nearest hospital can be situated more than six hours away.

In dire situations involving severely ill children, the administration of artesunate rectal capsules becomes a crucial intervention, offering a lifeline by buying essential time for the arduous journey to medical facilities. This method becomes a literal capsule of hope, allowing medical professionals to intervene effectively and potentially save lives.

Despite the existence of this intervention, the stark reality persists for those falling ill with malaria in highly isolated settings. The remoteness of these areas poses insurmountable challenges, with health facilities being entirely out of reach.

The lack of transportation infrastructure, compounded by seasonal obstacles such as flooding during the rainy season, further compounds the difficulties.

Moreover, issues such as low availability of services, security concerns, and financial constraints form an intricate web of barriers, making access to healthcare an elusive luxury for many in these regions.

Systemic challenges hampering timely access to healthcare

In addressing the plight of those grappling with malaria in isolated settings, it becomes imperative to not only enhance medical interventions but also to address the systemic challenges that prevent timely access to healthcare.

The multifaceted nature of these barriers underscores the need for comprehensive, community-centred strategies that encompass healthcare accessibility, infrastructure development, and socio-economic support to create a sustainable and effective response to the medical emergencies posed by malaria in remote areas.

In response to recent studies on pre-referral treatment with artesunate rectal capsules, the World Health Organization (WHO) has registered concern that in instances where the recommended follow-up measures, including transfer to a health facility, IV treatment, and proper discharge planning, are not followed, that patients may suffer poor outcomes.

However, there is currently little guidance based on real-world evidence available to inform front-line health workers on what to do when confronted with no timely options to transfer severely ill patients to higher-level health centres.

This Phase IV observational study seeks to optimize pre-referral care of patients with severe malaria in the context of these real-life challenges by implementing and evaluating a novel approach to managing severe malaria—one that may be used if timely transfer to a health facility is not feasible.

Artesunate rectal capsules will be administered at the community level, and clinical outcomes and potential signs of drug resistance will be evaluated. Then, the intervention will be followed up with the administration of oral artemisinin-based combination therapies (ACTs) once patients are well enough to swallow medicine.

Addressing rural patients’ needs

The approach represents an innovative effort to respond to the real challenges faced by those living in highly isolated rural settings, including the inability to reach a health facility in time to receive care.

“The severe form of malaria is the nightmare that every home in Africa dreads,” says Christine Manyando, Head of the Public Health Department at the Tropical Diseases Research Centre in Zambia.

“It can hit without warning and affects children primarily. Homegrown and locally led solutions, such as the one this study is investigating, aim to allow for seamless implementation in the communities most affected by malaria, and long-term sustainability of lifesaving strategies.”

“New tools to combat malaria are only useful if they are integrated in healthcare policies and practices and make a real-life difference for those who need them,” says Jean-Pierre Van Geertruyden, Professor of Global Health at the University of Antwerp in Belgium.

“This implementation project is an indispensable milestone as it will assess—and hopefully help to overcome—barriers to implementing and maintaining severe malaria case management strategies to a high standard.”

More vulnerability in Isolated and less-developed rural settings

“People living in poverty in very isolated rural settings are amongst the most at risk to malaria worldwide,” said George Jagoe, EVP for access at Medicines for Malaria Venture. “By exploring pragmatic ways to use today’s malaria medicines for optimal outcomes when severe malaria occurs in these difficult settings, this study may contribute to better algorithms for rural management of severe malaria in the future.”

The European & Developing Countries Clinical Trials Partnership (EDCTP) and the Swiss State Secretariat for Education, Research and Innovation (SERI) funded the consortium. It is led scientifically by the Tropical Diseases Research Centre in Zambia, and the Global Health Institute at the University of Antwerp in Belgium provides management and coordination.

The social science component of the study is led by The University of Kinshasa in the Democratic Republic of Congo (DRC). The National Institute of Medical Research in Tanzania leads molecular analysis, and Medicines for Malaria Venture leads the communication and dissemination of data generated by the study.

In addition to the consortium partners, the National Malaria Elimination Centre in Zambia and the National Malaria Control Programmes in DRC and Tanzania will play key roles in the study, ensuring the readiness of health workers, training and managing logistics in the local districts where the study will be conducted.

Malaria prevalence in Africa

WHO’s recent data sheds light on the alarming impact of the COVID-19 pandemic on global malaria statistics. Over the peak years of the pandemic from 2020 to 2021, disruptions caused by the response to COVID-19 contributed to a staggering increase of approximately 13 million more malaria cases and an additional 63,000 malaria-related deaths worldwide.

Notably, the burden of malaria falls disproportionately on the WHO African Region, which accounted for a staggering 95 per cent of all malaria cases and 96 per cent of related deaths in 2021.

Disturbingly, children under the age of five bore the brunt of this burden, constituting approximately 80 per cent of all malaria-related deaths in the region, underscoring the urgent need for targeted interventions to protect this vulnerable demographic.

Within the African context, the gravity of the situation is further emphasized by the fact that four countries—Nigeria, the DRC, Tanzania, and Niger—collectively accounted for just over half of all malaria-related deaths globally. Nigeria alone contributed to 31.3 per cent of these fatalities, highlighting the pressing need for intensified efforts and resources to address malaria in these high-burden countries.

The stark statistics underscore the interconnectedness of health crises and the importance of a comprehensive approach that considers the broader health landscape, ensuring that responses to one crisis do not inadvertently exacerbate another.