Table 1 Comparison of outcome classifications in therapeutic efficacy study protocols for malaria

Classifications for treatment efficacy

Sensitivity: clearance of asexual parasitaemia within 7 days of the first day of treatment, without subsequent recrudescence

Adequate clinical response (ACR): Absence of parasitaemia on Day 14 irrespective of axillary temperature, without previously meeting any of the criteria of ETF or LTF or Axillary temperature < 37.5 °C irrespective of the presence of parasitaemia, without previously meeting any of the criteria of ETF or LTF

Adequate clinical and parasitological response (ACPR): For low to moderate transmission area: Absence of parasitaemia on day 28 irrespective of axillary temperature without previously meeting any of the criteria of early treatment failure or late clinical failure or late parasitological failure

For intense transmission area: Absence of parasitaemia on day 14 irrespective of axillary temperature without previously meeting any of the criteria of early treatment failure or late clinical failure or late parasitological failure

Adequate clinical and parasitological response (ACPR): Absence of parasitaemia on day 28 (or day 42), irrespective of axillary temperature, in patients who did not previously meet any of the criteria of ETF, LCF or LPF

Classifications for treatment failure

Resistance RI: Clearance of asexual parasitaemia as above, but followed by recrudescence before or after day 7

Early treatment failure (ETF): If the patient develops one of the following during the first 3 day of follow-up:

Development of danger signs or severe malaria on day 1, 2 or 3, in the presence of parasitaemia;

Axillary Temperature ≥ 37.5 °C on day 2 with parasitaemia higher than the day 0 parasite count;

Axillary Temperature ≥ 37.5 °C on day 3 in the presence of parasitaemia;

Parasitaemia on day 3 ≥ 25% of the parasite count on day 0

Early treatment failure (ETF): For all transmission area: development of danger signs or sever malaria on day 1, day 2, day 3 in the presence of parasitaemia; Parasitaemia on day 2 higher than on day 0 irrespective of axillary temperature; Parasitaemia on day 3 with axillary temperature ≥ 37.5 °C; parasitaemia on day ≥ 25% of count on day 0

Early treatment failure (ETF): Danger signs or severe malaria on day 1, 2 or 3, in the presence of parasitaemia; Parasitaemia on day 2 higher than on day 0, irrespective of axillary temperature; Parasitaemia on day 3 with axillary temperature ≥ 37.5 °C; and parasitaemia on day 3 ≥ 25% of count on day 0

Resistance RII: Marked reduction of asexual parasitaemia within the first 7 days of follow-up, but no clearance

Late treatment failure (LTF): Development of danger signs or severe malaria in the presence of parasitaemia on any day from day 4 to 14, without previously meeting any of the criteria of ETF;

Axillary temperature ≥ 37.5 °C in the presence of parasitaemia on any day from day 4 to 14, without previously meeting any of the criteria of ETF

Late clinical failure (LCF): For low to moderate transmission area: Development of danger signs or severe malaria after day 3 in the presence of parasitaemia without previously meeting any of the criteria of early treatment failure; presence of parasitaemia and axillary temperature ≥ 37.5 °C (or history of fever) on any day from day 4 to day 28 without previously meeting any of the criteria of early treatment failure

For intense transmission area: Development of danger signs or severe malaria after day 3 in the presence of parasitaemia without previously meeting any of the criteria of early treatment failure; presence of parasitaemia and axillary temperature ≥ 37.5 °C (or history of fever) on any day from day 4 to day 14 without previously meeting any of the criteria of early treatment failure

Late clinical failure (LCF): Danger signs or severe malaria in the presence of parasitaemia on any day between day 4 and day 28 (or day 42) in patients who did not previously meet any of the criteria of ETF; and presence of parasitaemia on any day between day 4 and day 28 (or day 42) with axillary temperature ≥ 37.5 °C in patients who did not previously meet any of the criteria of ETF

Resistance RIII: No marked reduction of asexual parasitaemia within the first 7 days of follow-up

Late parasitological failure (LPF): For low to moderate transmission area: Presence of parasitaemia on any day from day 7 to day 28 irrespective of axillary temperature and without previously meeting any of the criteria of early treatment failure or late clinical failure

For intense transmission area: Presence of parasitaemia on day 14 and axillary temperature < 37.5 °C without previously meeting any of the criteria of early treatment failure or late clinical failure

Late parasitological failure (LPF): Presence of parasitaemia on any day between day 7 and day 28 (or day 42) with axillary temperature < 37.5 °C in patients who did not previously meet any of the criteria of ETF or LCF