Protective efficacy is defined as [1 − (Incidence in the IPTi-SP group/Incidence in the control group)] × 100, which is analogous to the standard definition for vaccine efficacy. To compare results across the six trials, the committee used the estimates of 12-month protective efficacy whenever the data were available in the publications. As Table 4 shows, all the studies except the Lambaréné trial demonstrate a statistically significant reduction in the probability of contracting clinical malaria; for two of those five trials (Ifakara and Tamale), the lower limit of the 95 percent CI around the point estimate of efficacy is above 20 percent. The trials that report the effect of IPTi-SP on severe malaria all show a statistically significant benefit of IPTi; similarly, in three trials (Ifakara, Kumasi, and Navrongo), the lower limit of the 95 percent CI around the point estimate of efficacy is above 10 percent. For all trials, the estimated protective efficacy for anemia and all-cause hospitalization was in the direction of benefit, but only four trials showed a statistically significant benefit for anemia (Ifakara, Navrongo, Lambaréné, and Kisumu). Only three trials showed statistically significant benefit for all-cause hospitalizations (Ifakara, Manhiça, and Tamale). Because malaria is an episodic disease in the countries where IPTi-SP would be used, as mentioned above, the committee was most interested in assessing the effect of IPTi on the total burden of disease, not only in decreasing the probability of having one or more episodes. The next section of this letter report describes the data relevant to assessing the effect of IPTi-SP on the total burden of malaria in the first year of life.

TABLE 4 Summary of Outcomes of the Six IPTi-SP Studies and the Kisumu Trial During the First Year of Life

 

At Least One Episode of Malaria

At Least One Episode of Anemiab

Episodes of All-Cause Hospitalizations

 

Clinical Malaria

Severe Malariaa

Study

% PE

(95% CI)

P

% PE

(95% CI)

P

% PE

(95% CI)

P

% PE

(95% CI)

P

Ifakara

59

(41, 72)

<0.0001

68

(49, 80)

<0.0001

50

(8, 73)

0.023

30

(8, 47)

0.01

Kumasi

18

(4, 31)

0.01

20c

(11, 29)

<0.001

13

(−5, 28)

0.16

8.7

(−23, 32)

0.6

Lambaréné

13

(−32, 43)

0.50

NR

NR

26

(0, 45)

0.05

NR

NR

Manhiça

22

(4, 37)

0.020

24

(5, 39)

0.017

13

(−17, 35)

0.37

19

(4, 31)

0.014

Navrongo

25c

(14, 34)

<0.001

24c

(11, 34)

NR

36c

(11, 53)

NR

13c

(−5, 27)

NR

Tamale

33c

(21, 44)

<0.0001

28c

(6, 45)

<0.05

21

(−10, 43)

Not significant

38

(7, 59)

<0.05

Kisumud

26

(6, 41)

0.01

42

(4, 65)

0.04

32

(−0.1, 53)

0.05

7.2

(−20, 28)

0.6

NOTES: NR = not reported; P = p-value; PCV = packed cell volume; PE = protective efficacy. Where available, table shows protective efficacy through 12 months of age even for studies where the primary outcome was after 12 months. The data for the outcomes of the Navrongo study, which come from the publication, are for 15 months. The columns labeled P give p-values where available. For the Kisumu study, the data come from unpublished information provided by the IPTi Consortium.

a Kumasi and Manhiça: >500 parasites/μL; Ifakara, Kisumu, Navrongo, and Tamale: >5,000 parasites/μL.

b Ifakara (PCV<25%): Kisumu (Hb<8.0 g/dL); Kumasi (Hb<7.5 g/dL); Lambaréné (Hb<9.0 g/dL); Manhiça (PCV<25%); Navrongo (PCV<24%); Tamale (Hb<7 g/dL).

c All episodes are in the first year of life.

d Results for sulfadoxine-pyrimethamine once plus artesunate 3 days (SP-AS3) vs. placebo.

SOURCE: Compiled from published articles of the trials and from documents provided by the IPTi Consortium for the Kisumu trial.



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement