First controlled trial shows how focal drug administration and vector control can be used to accelerate malaria elimination

This year’s World Malaria Day, April 25th, occurs as countries around the world continue to battle the spread of COVID-19. The occasion is an important reminder that while good progress has been made against malaria, it remains an important infectious disease that still causes an estimated 230 million cases and over 400,000 deaths each year. A new study, published on the eve of this day, demonstrates how mass drug administration and vector control can be used in the fight to eliminate malaria. Conducted by researchers at the University of California, San Francisco (UCSF), the University of Namibia (UNAM), and in collaboration with Namibia Ministry of Health and Social Services, University of Texas, Southwestern, London School of Hygiene and Tropical Medicine, and University of the Witwatersrand, the study found that two approaches – reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) – significantly reduced malaria transmission in low endemic settings. The study is the first-ever controlled trial of its kind.

New approaches needed to bring malaria transmission to zero
Dramatic success fighting malaria over the last two decades has inspired many countries to commit to the goal of eliminating transmission of the disease altogether. As reported by the World Health Organization, more countries than ever are eliminating malaria, with 38 countries and territories certified malaria-free to date.

In recent years, progress in some regions has slowed, highlighting the need for new approaches. Where malaria cases have been reduced to low levels, transmission still occurs due a reservoir of chronic, low density infections in people without symptoms. This means these infections are largely undetectable through standard surveillance approaches. Because the mosquitoes that carry the malaria parasite are still present, these infections may seed further infections in their immediate neighborhood, potentially leading to outbreaks of malaria cases. To prevent such outbreaks from leading to wider epidemics, effective focal responses, such as those assessed in this study, need to be mobilized.

In this study, researchers conducted a trial to evaluate the effectiveness and safety of two interventions: reactive focal mass drug administration, rfMDA, and reactive focal vector control, RAVC, and their combination. The study took place in Zambezi Region, northern Namibia, and targeted people that were at highest risk of malaria infection based on their proximity within 500 meters of malaria index cases that emerged during the transmission season. The study, published in The Lancet, is the first randomized controlled trial of rfMDA and/or RAVC.

Targeting and tailoring existing approaches for elimination
Mass drug administration (MDA) refers to the administration of antimalarial drugs without malaria testing to target the parasite reservoir in humans. MDA is recommended by WHO for elimination of Plasmodium falciparum malaria. However, as the effort and cost required to implement MDA on a large scale can be challenging, this study sought to target MDA to the small ring of people around recent index cases – the people at highest risk of malaria.

Malaria vector control using long lasting insecticidal nets or preseason indoor residual spraying (IRS) to target large populations has been the primary driver of reduced malaria cases and deaths in sub-Saharan Africa since 2000. These interventions are normally administered in a ‘blanket’ style before the malaria season. This study targeted IRS using a new, highly effective - but expensive - organophosphorus insecticide formulation, pirimiphos-methyl, among households within the small ring of people around recent index cases.

Study findings
Researchers found that rfMDA and RAVC, when implemented alone and in combination, significantly reduced malaria transmission among targeted populations in the Zambezi region of Namibia. The two interventions, when used in combination, had an additive effect – reducing rates of new malaria cases by 75%. Both interventions were found to be safe, and saw high levels of participation. While additional studies will help determine the optimal scenarios in which these approaches could be implemented, the authors suggest that rfMDA and/or RAVC can be applied in other countries or subnational areas that have Plasmodium falciparum malaria, are close to elimination, and have good case reporting systems. The cost effectiveness of these interventions will be reported separately.

Published on the eve of World Malaria Day, the study shows how tailoring and targeting of existing tools and strategies can help improve their effectiveness – accelerating progress towards the ultimate goal of ending malaria transmission once and for all.