TABLE 7 Effect of SP During Treatment Period, Rebound Period, and Time from Randomization to End of Follow-Up

 

Incidence of First Case of Clinical Malaria

 

Randomization Through End of Treatment Period

Potential Rebound Period: End of Treatment Period Through End of Follow-Up Period

Randomization Through End of Follow-Up

Study

% PE

95% CI

% PE

95% CI

% PE

95% CI

Ifakara

59

(41, 72)

36

(11, 53)

42

NR

Kumasi

18

(4, 31)

−1.5

(−22, 15)

5

NR

Lambaréné

13

(−32, 43)

−12

NR

28

(−22, 58)

Manhiça

22

(4, 37)

NR

NR

NR

NR

Navrongo

25

(14, 34)

−5

(−21, 9)

16

(7, 25)

Tamale

30a

(20, 40)a

1.8b

(−9, 11)b

8b

(−5, 19)b

NOTE: CI: confidence interval; NR: not reported; Pbo: placebo; PE: protective efficacy. Values in italics were not reported in the papers and represent the Committee’s rough calculation of protective efficacy given the published data.

a Data for the first 12 months of life, which does not include the last three months of treatment.

b Data for all cases of malaria.

SOURCE: Compiled from published manuscripts of the six efficacy trials.

Analysis of All Clinical Events in the Period During 35 Days After an IPTi Dose at Varying Ages

In this report, we have alluded several times to the long period between the dose of IPTi administered at 3 or 4 months and the next dose given at 9 months of age and has raised questions about what occurs during that long period. In its unpublished report, the SWG estimated protective efficacies during several specific follow-up intervals to shed light on this issue. First, they assessed the level of efficacy of IPTi against all episodes of malaria in the 35-day period after a dose of SP or of placebo was given to infants 3 months of age (“prophylactic effect 1”). In infants who received SP, one would expect the levels of drug present in most infants to be protective against sensitive and moderately sensitive parasites during this 35-day period. The results are shown in the Table 8 below.

Every trial showed that a moderate or high level of protection was observed at every trial site during this 35-day period. In five of the six trials, the difference in incidence between SP and placebo groups was significant—sometimes highly significant—and the lower limit of the 95 percent CI was well above zero. Very similar results were observed in the 35 days after an IPTi dose administered at 9 months of age (“prophylactic effect 2”), as shown below in Table 9.

Of the four sites that administered IPTi doses in the second year of life, the point estimates of efficacy in the 35 days after the dose (“prophylactic effect 3”) were 92 percent (95 percent CI, 80, 95) for Tamale; 72 percent (95 percent CI, 57, 82) for Navrongo; 31 percent (95 percent CI, −3.6, 54) for Kumasi; and 29 percent (95 percent CI, −210, 84) for Lambaréné.



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