Background
Methods
Study design, site and population
Study procedures
Laboratory procedures
Statistical methods
Ethical approval
Results
Study profile and characteristics of the malaria episodes
Characteristic
|
Chemoprevention arm
| |||
---|---|---|---|---|
No chemoprevention
|
Monthly
|
Daily
|
Monthly
| |
SP
|
TS
|
DP
| ||
Number of episodes | 992 | 901 | 721 | 444 |
Patient age in months, mean (SD) | 16.0 (5.1) | 16.1 (5.1) | 16.9 (4.8)b
| 17.8 (4.5)b
|
Female gender, n (%) | 428 (43.2%) | 407 (45.2%) | 344 (47.7%) | 211 (47.5%) |
Urban residence, n (%) | 13 (1.3%) | 26 (2.9%) | 14 (1.9%) | 18 (4.1%) |
Household wealth index, n (%) | ||||
Lowest tertile | 319 (32.2%) | 284 (31.5%) | 308 (42.7%)b
| 176 (39.6%)b
|
Middle tertile | 381 (38.4%) | 347 (38.5%) | 236 (32.7%) | 149 (33.6%) |
Highest tertile | 292 (29.4%) | 270 (30.0%) | 177 (24.6%) | 119 (26.8%) |
HIV-exposeda, n (%) | 235 (23.7%) | 179 (19.9%) | 114 (15.8%) | 81 (18.2%) |
Temperature °C, mean (SD) | 38.0 (1.0) | 37.9 (1.0) | 37.9 (1.0) | 37.9 (1.0) |
Parasite density per μL, geometric mean | 16321 | 15257 | 11702b
| 16841 |
Gametocytes present, n (%) | 41 (4.1%) | 34 (3.8%) | 48 (6.7%)b
| 11 (2.5%) |
Haemoglobin g/dL, mean (SD) | 9.7 (1.3) | 9.6 (1.4) | 9.8 (1.3) | 9.9 (1.2) |
Days since last dose of chemopreventive drug assigned, median (IQR) | N/A | 17 (10–24) | 1 (1–1) | 16 (8–23) |
Proportion of prior dose of chemopreventive drug reported taken | N/A | 95.5% | 98.6% | 96.0% |
Efficacy outcomes
Efficacy outcomes
|
Chemoprevention arm
| |||
---|---|---|---|---|
No chemoprevention (n = 992)
|
Monthly SP (n = 901)
|
Daily TS (n = 721)
|
Monthly DP (n = 444)
| |
Fever clearancea, n (%) | ||||
Fever present on day 1 | 497 (50.2%) | 445 (49.5%) | 339 (47.0%) | 203 (46.1%) |
Fever present on day 2 | 73 (7.4%) | 87 (9.7%) | 58 (8.1%) | 32 (7.3%) |
Fever present on day 3 | 37 (3.9%) | 32 (3.7%) | 20 (2.9%) | 16 (3.8%) |
Parasite clearance, n (%) | ||||
Positive blood smear on day 2 | 54 (5.5%) | 51 (5.7%) | 35 (4.9%) | 24 (5.5%) |
Positive blood smear on day 3 | 5 (0.5%) | 4 (0.5%) | 4 (0.6%) | 6 (1.4%) |
WHO treatment outcome, n (%) | ||||
No outcome | 29 (2.9%) | 25 (2.8%) | 24 (3.3%) | 16 (3.6%) |
Early treatment failure | 1 (0.1%) | 8 (0.9%) | 4 (0.6%) | 3 (0.7%) |
Late clinical failure | 172 (17.3%) | 148 (16.4%) | 112 (15.5%) | 71 (16.0%) |
Late parasitological failure | 284 (28.6%) | 240 (26.6%) | 190 (26.4%) | 115 (25.9%) |
Adequate clinical and parasitological response | 506 (51.0%) | 480 (53.3%) | 391 (54.2%) | 239 (53.8%) |
Appearance of gametocytesb, n (%) | 33 (3.5%) | 33 (3.8%) | 24 (3.6%) | 16 (3.7%) |
Haemoglobin recoveryc g/dL, mean (SD) | 0.5 (1.3) | 0.5 (1.2) | 0.6 (1.2) | 0.6 (1.1) |
Risk factor
|
Univariate analysis
|
Multivariate analysis
| |||
---|---|---|---|---|---|
HR
a
(95% CI)
|
p-value
|
HR
a
(95% CI)
|
p-value
| ||
Chemoprevention arm | No chemoprevention | 1.0 (reference) | - | 1.0 (reference) | - |
Monthly SP | 0.95 (0.81-1.11) | 0.51 | 0.95 (0.81-1.12) | 0.52 | |
Daily TS | 0.87 (0.72-1.05) | 0.14 | 0.85 (0.70-1.05) | 0.07 | |
Monthly DP | 0.81 (0.66-0.99) | 0.04 | 0.77 (0.63-0.95) | 0.01 | |
Age (per 6 month increase) | 1.15 (1.09-1.23) | <0.001 | 1.19 (1.12-1.26) | <0.001 | |
Pre-treatment parasite density (per 1og10 increase) | 1.06 (1.01-1.11) | 0.01 | 1.05 (1.00-1.10) | 0.04 | |
HIV-exposure | 0.91 (0.77-1.08) | 0.27 | 0.86 (0.73-1.02) | 0.09 | |
Female gender | 0.94 (0.82-1.07) | 0.33 | 0.94 (0.82-1.07) | 0.34 | |
Urban residence | 0.57 (0.27-1.20) | 0.14 | 0.65 (0.32-1.33) | 0.23 | |
Household wealth index | Lowest tertile | 1.0 (reference) | - | 1.0 (reference) | - |
Middle tertile | 0.92 (0.79-1.07) | 0.27 | 0.91 (0.78-1.06) | 0.24 | |
Highest tertile | 0.77 (0.65-0.91) | 0.002 | 0.78 (0.66-0.92) | 0.003 |
Risk factor
|
Univariate analysis
|
Multivariate analysis
b
| |||
---|---|---|---|---|---|
HR
a
(95% CI)
|
p-value
|
HR
a
(95% CI)
|
p-value
| ||
PQ level (ng/ml) at the time malaria diagnosed | <2.5c (n = 150) | 1.0 (reference) | - | 1.0 (reference) | - |
2.5 - < 10 (n = 67) | 0.80 (0.54-1.17) | 0.25 | 0.83 (0.56-1.24) | 0.37 | |
10 - < 20 (n = 101) | 0.65 (0.47-0.89) | 0.008 | 0.67 (0.49-0.93) | 0.02 | |
20 - < 50 (n = 82) | 0.50 (0.35-0.72) | <0.001 | 0.51 (0.36-0.73) | <0.001 | |
≥50 (n = 25) | 0.27 (0.13-0.54) | <0.001 | 0.30 (0.14-0.63) | 0.001 |
Safety outcomes
Safety outcomes
|
Chemoprevention arm
|
Compliant with monthly DP
a
(n = 107)
| |||
---|---|---|---|---|---|
No chemoprevention (n = 992)
|
Monthly SP (n = 901)
|
Daily TS (n = 721)
|
Monthly DP (n = 444)
| ||
Common adverse events of any severity, n (%) | |||||
Cough | 498 (50.2%) | 403 (44.7%) | 314 (43.6%)b
| 203 (47.7%) | 53 (49.5%) |
Elevated temperature | 320 (32.3%) | 259 (28.8%) | 222 (30.8%) | 129 (29.1%) | 31 (29.0%) |
Diarrhoea | 286 (28.8%) | 192 (21.3%)b
| 163 (22.6%)b
| 95 (21.4%)b
| 26 (24.3%) |
Pallor | 176 (17.7%) | 171 (19.0%) | 125 (17.3%) | 61 (13.7%) | 19 (17.8%) |
Vomiting | 134 (13.5%) | 82 (9.1%)b
| 82 (11.4%) | 45 (10.1%) | 15 (14.0%) |
Anorexia | 64 (6.5%) | 67 (7.4%) | 27 (3.7%)b
| 30 (6.8%) | 13 (12.2%) |
Any grade 3–4 adverse events, n (%) | 87 (8.8%) | 95 (10.5%) | 52 (7.2%) | 38 (8.6%) | 13 (12.2%) |
Any serious adverse events, n (%) | 20 (2.0%) | 26 (2.9%) | 14 (1.9%) | 7 (1.6%) | 2 (1.9%) |