Stopping prereferral rectal artesunate — a grave error

13 Jul 2022
James A Watson, Marian Warsame, Thomas J Peto, Marie Onyamboko, Caterina Fanello, Arjen M Dondorp, and Nicholas White
  • The WHO recently recommended a moratorium on the implementation of pre-referral rectal artesunate for suspected childhood severe malaria.
  • This was because of the lower referral completion rates and higher case fatality ratios in rectal artesunate recipients reported in a non-randomised, sequential observational study (CARAMAL) conducted in Nigeria, Uganda and the Democratic Republic of Congo.
  • The observational study design, lack of a prespecified statistical analysis plan, strong temporal confounding, likely selection bias and the biological implausibility, all strongly challenge the interpretation of a causal relationship between rectal artesunate roll-out and increased mortality.
  • Early mortality associated with delayed referral following rectal artesunate administration is more likely to have resulted from inadequate treatment of sepsis rather than malaria.

Further delays in rectal artesunate roll-out resulting from inappropriate analysis and interpretation of the CARAMAL study will likely result in preventable childhood mortality.

Stopping prereferral rectal artesunate is a grave error. The WHO should lift its moratorium on rectal artesunate deployment without delay