Background
Methods
Study locations
Study procedures
Haematological evaluation
Definition of haematological parameters evaluated
Kinetics of the disposition of drug-attributable falls in haematocrit
Statistical analysis
Results
Characteristics of children enrolled in the study and parasite positivity following treatment
Variables | No. with enrolment haematocrit, n (%)a
| Enrolment haematocrit, mean [95% CI] | Anaemia (haematocrit <30%) at presentation, n (%)a
| |||
---|---|---|---|---|---|---|
ALL | Mild | Moderate | Severe | |||
Total | 959 (96.7) | 30.6 [30.3–30.9] | 355 (37) | 323 (33.7) | 30 (3.1) | 2 (0.2) |
Male | 522 (52.6) | 30.5 [30.1–31] | 197 (20.5) | 182 (19) | 14 (1.5) | 1 (0.1) |
Female | 437 (44.1) | 30.7 [30.2–31.2] | 158 (16.5) | 141 (14.7) | 16 (1.6) | 1 (0.1) |
Agedb ≤ 15 months | 121 (12.6) | 29 [28.1–30] | 56 (5.8) | 48 (5) | 8 (0.8) | 0 (0) |
≤ 24 months | 256 (25.8) | 29.7 [29.1–30.3] | 108 (11.3) | 93 (9.7) | 14 (1.5) | 1 (0.1) |
> 24 months | 695 (70.1) | 30.9 [30.6–31.2] | 244 (25.4) | 228 (23.8) | 15 (1.6) | 1 (0.1) |
Asexual parasitaemiac
| ||||||
≤ 25,000 μL−1
| 559 (52.3) | 30.6 [29.6–30.4] | 225 (23.5) | 203 (21.2) | 20 (2.1) | 2 (0.2) |
> 25,000–50,000 μL−1
| 141 (14.7) | 31.2 [30.3–32.2] | 41 (4.3) | 35 (3.6) | 6 (0.6) | 0 (0) |
> 50,000–100,000 μL−1
| 152 (15.8) | 31.3 [30.4–32.1] | 52 (5.4) | 50 (5.2) | 2 (0.2) | 0 (0) |
> 100,000 μL−1
| 101 (10.5) | 31.4 [30.4–32.4] | 35 (3.6) | 33 (3.4) | 2 (0.2) | 0 (0) |
Gametocytaemia | ||||||
Present | 47 (4.7) | 28.8 [27.6–30] | 22 (2.3) | 20 (2.1) | 2 (0.2) | 0 (0) |
Absent | 912 (91.9) | 30.7 [30.3–31] | 333 (34.7) | 303 (31.6) | 28 (2.9) | 2 (0.2) |
Region of enrolment | ||||||
Eastern flankd
| 503 (50.7) | 30.6 [30.1–31.1] | 175 (18.2) | 152 (15.8) | 21 (2.2) | 2 (0.2) |
Western flanke
| 456 (46) | 30.6 [30.1–31] | 180 (18.8) | 171 (17.8) | 9 (0.9) | 0 (0) |
Factors contributing to anaemia at presentation
Variable | Total no. | No. with anaemia at presentation | OR (95% CI) |
P value | AOR (95% CI) |
P value |
---|---|---|---|---|---|---|
Gender | ||||||
Female | 437 | 158 | 1 | |||
Male | 522 | 197 | 1.1 (0.8–1.4) | 0.66 | – | – |
Age (months) | ||||||
> 15 | 837 | 296 | 1 | 1 | ||
≤ 15 | 114 | 56 | 1.8 (1.2–2.6) | 0.01 | 1.5 (0.9–2.5) | 0.09 |
Duration of illness (days) | ||||||
≤ 2 | 295 | 92 | 1 | 1 | ||
> 2 | 330 | 138 | 1.6 (1.1–2.2) | 0.01 | 1.5 (1.1–2.1) | 0.02 |
Enrolment body temperature (°C) | ||||||
≤ 37.4 | 357 | 143 | 1 | |||
> 37.4 | 601 | 211 | 0.8 (0.6–1.1) | 0.14 | – | – |
History of fever | ||||||
Absent | 169 | 70 | 1 | |||
Present | 789 | 284 | 1.2 (0.9–1.8) | 0.22 | – | – |
Asexual parasitaemia (μL−1) | ||||||
> 10,000 | 389 | 160 | 1 | 1 | ||
≤ 10,000 | 564 | 193 | 1.3 (1.1–1.8) | 0.003 | 1.5 (1.1–2.2) | 0.02 |
Gametocyte carriage at presentation | ||||||
Absent | 912 | 333 | 1 | |||
Present | 47 | 22 | 1.5 (0.6–2.8) | 0.2 | – | – |
Season of enrolment | ||||||
Dry (November–March) | 69 | 24 | 1 | |||
Wet (April–October) | 890 | 331 | 1.1 (0.7–1.9) | 0.79 | – | – |
Region of enrolment | ||||||
Eastern flanka
| 456 | 180 | 1 | |||
Western flankb
| 503 | 175 | 0.8 (0.6–1.1) | 0.15 | – | – |
Recovery from pre-treatment anaemia
Factors contributing to progression from normal haematocrit pre-treatment to anaemia within 1 week post –treatment initiation (early-appearing anaemia)
Variable | Total no. | No. with anaemia 1 week post-initiation of ACTs | OR (95% CI) | P value | AOR (95% CI) |
P value |
---|---|---|---|---|---|---|
Gender | ||||||
Female | 278 | 132 | 1 | |||
Male | 325 | 168 | 0.8 (0.6–1.2) | 0.34 | – | – |
Age (month) | ||||||
> 15 | 541 | 255 | 1 | 1 | ||
≤ 15 | 58 | 42 | 2.9 (1.6–5.4) | < 0.0001 | 2.5 (1.4–4.7) | 0.003 |
Duration of illness (day) | ||||||
≤ 2 | 203 | 101 | 1 | |||
> 2 | 192 | 100 | 1.0 (0.7–1.6) | 1.0 | – | – |
Enrolment body temperature (°C) | ||||||
≤ 37.4 | 214 | 104 | 1 | |||
> 37.4 | 390 | 197 | 1.1 (1.0–1.9) | 0.71 | – | – |
History of fever at enrolment | ||||||
Absent | 99 | 39 | 1 | 1 | ||
Present | 505 | 262 | 1.7 (1.1–2.6) | 0.03 | 1.8 (1.1–2.9) | 0.01 |
Fever on day 1 | ||||||
Absent | 501 | 255 | 1 | |||
Present | 70 | 38 | 1.1 (0.7–1.9) | 0.69 | – | – |
Haematocrit (%) | ||||||
> 35 | 140 | 42 | 1 | 1 | ||
≤ 35 | 464 | 259 | 2.9 (2.0–4.4) | < 0.0001 | 2.9 (1.9–4.4) | <0.0001 |
Parasitaemia (μL−1) | ||||||
≤ 50,000 | 434 | 213 | 1 | |||
> 50,000 | 166 | 87 | 1.1 (0.8–1.6) | 0.52 | – | – |
Parasitaemia on day 1 | ||||||
Absent | 244 | 111 | 1 | |||
Present | 360 | 190 | 1.3 (1.0–1.9) | 0.09 | – | – |
Parasitaemia day 1 or 2 | ||||||
Absent | 233 | 104 | 1 | 1 | ||
Present | 371 | 197 | 1.4 (1.0–2.0) | 0.04 | 1.3 (0.9–1.9) | 0.11 |
Gametocytaemia | ||||||
Absent | 579 | 289 | 1 | |||
Present | 25 | 12 | 0.9 (0.4–2.1) | 1.0 | – | – |
Parasite clearance time (day) | ||||||
≤ 2 | 468 | 234 | 1 | |||
> 2 | 136 | 67 | 1.0 (0.7–1.4) | 0.96 | – | – |
Fever clearance time (day) | ||||||
≤ 2 | 367 | 186 | 1 | |||
> 2 | 13 | 9 | 1.9 (0.9–4.3) | 0.13 | – | – |
Season of enrolment | ||||||
Dry (November–March) | 45 | 17 | 1 | |||
Wet (April–October) | 559 | 284 | 1.7 (0.9–3.2) | 0.13 | – | – |
Drug treatment | ||||||
DHP | 226 | 110 | 1 | |||
AL | 191 | 101 | 1.2 (0.8–1.7) | 0.49 | – | – |
AA | 187 | 90 | 1.0 (0.7–1.4) | 1.0 |
Recovery from early-appearing anaemia
Time-course of haematocrit following artemisinin-based combination treatments
Malaria-attributable fall in haematocrit
Variable | Total no. | No. with MAFH >4% | OR (95% CI) |
P value | AOR (95% CI) |
P value |
---|---|---|---|---|---|---|
Gender | ||||||
Female | 314 | 203 | 1 | |||
Male | 380 | 243 | 1.0 (0.7–1.3) | 0.91 | – | – |
Age (month) | ||||||
> 38 | 354 | 213 | 1 | 1 | ||
≤ 38 | 335 | 228 | 1.4 (1.0–1.9) | 0.04 | 2.1 (0.8–1.6) | 0.53 |
Duration of illness (day) | ||||||
≤ 2 | 200 | 120 | 1 | |||
> 2 | 274 | 180 | 1.1 (0.7–1.6) | 0.78 | – | – |
Enrolment body temperature (°C) | ||||||
≤ 37.4 | 264 | 173 | 1 | |||
> 37.4 | 429 | 272 | 0.9 (0.7–1.3) | 0.63 | – | – |
History of fever at enrolment | ||||||
Absent | 123 | 77 | 1 | |||
Present | 571 | 368 | 1.1 (0.7–1.6) | 0.78 | – | – |
Fever on day 1 | ||||||
Absent | 619 | 398 | 1 | |||
Present | 62 | 38 | 0.9 (0.5–1.5) | 0.74 | – | – |
Haematocrit (%) | ||||||
≥ 30 | 379 | 170 | 1 | 1 | ||
< 30 | 315 | 276 | 8.7 (5.9–12.9) | < 0.0001 | 9.4 (6.3–14.1) | <0.0001 |
Parasitaemia (μL−1) | ||||||
> 50,000 | 171 | 91 | 1 | 1 | ||
≤ 50,000 | 521 | 355 | 1.9 (1.3–2.7) | 0.001 | 1.9 (1.3–2.9 | 0.002 |
Parasitaemia on day 1 | ||||||
Absent | 380 | 228 | 1 | 1 | ||
Present | 314 | 218 | 1.5 (1.1–2.1) | 0.01 | 1.6 (1.1–2.3) | 0.01 |
Gametocytaemia (D0–7) | ||||||
Absent | 621 | 390 | 1 | 1 | ||
Present | 73 | 56 | 2.0 (1.1–3.4) | 0.027 | 2.0 (1.0–3.7) | 0.04 |
Parasite clearance time (days) | ||||||
≤ 2 | 551 | 357 | 1 | |||
> 2 | 142 | 89 | 0.9 (0.6–1.3) | 0.71 | – | – |
Fever clearance time (days) | ||||||
≤ 2 | 416 | 261 | 1 | |||
> 2 | 13 | 11 | 3.3 (0.7–14.9) | 0.19 | – | – |
Season of enrolment | ||||||
Dry (November–March) | 41 | 23 | 1 | |||
Wet (April–October) | 653 | 423 | 1.4 (0.8–2.7) | 0.34 | – | – |
Drug treatment | ||||||
DHP | 231 | 137 | 1 | |||
AL | 229 | 154 | 1.4 (1.0–2.1) | 0.1 | – | – |
AA | 234 | 155 | 1.3 (0.9–2.0) | 0.15 |
Drug-attributable falls in haematocrit
Variable | Total no. | No. with DAFH >4% | OR (95% CI) |
P value | AOR (95% CI) |
P value |
---|---|---|---|---|---|---|
Gender | ||||||
Female | 323 | 152 | 1 | |||
Male | 395 | 181 | 0.8 (0.6–1.1) | 0.15 | – | – |
Age (month) | ||||||
> 15 | 627 | 291 | 1 | |||
≤ 15 | 88 | 40 | 1.0 (0.6–1.5) | 0.96 | – | – |
Duration of illness (day) | ||||||
≤ 2 | 235 | 125 | 1 | |||
> 2 | 262 | 122 | 0.8 (0.5–1.1) | 0.17 | – | – |
Enrolment body temperature (°C) | ||||||
< 38 | 389 | 159 | 1 | 1 | ||
≥ 38 | 330 | 175 | 1.6 (1.2–2.2) | 0.001 | 1.3 (1.0–1.8) | 0.09 |
History of fever at enrolment | ||||||
Absent | 109 | 26 | 1 | 1 | ||
Present | 610 | 308 | 3.3 (2.0–5.2) | < 0.0001 | 3.0 (1.8–4.9) | <0.0001 |
Fever on day 1 | ||||||
Absent | 611 | 267 | 1 | 1 | ||
Present | 91 | 58 | 2.3 (1.4–3.6) | 0.001 | 1.8 (1.1–2.9) | 0.02 |
Haematocrit (%) | ||||||
< 37 | 641 | 271 | 1 | 1 | ||
≥ 37 | 78 | 63 | 5.7 (3.2–10.3) | < 0.0001 | 5.5 (3.0–10.2) | <0.0001 |
Parasitaemia (μL−1) | ||||||
≤ 100,000 | 631 | 227 | 1 | 1 | ||
> 100,000 | 85 | 55 | 2.3 (1.5–3.8) | < 0.0001 | 2.1 (1.3–3.5) | 0.004 |
Parasitaemia on day 1 | ||||||
Absent | 288 | 133 | 1 | |||
Present | 431 | 201 | 1.0 (0.8–1.4) | 0.84 | – | – |
Gametocytaemia (D0) | ||||||
Present | 31 | 7 | 1 | 1 | ||
Absent | 688 | 327 | 3.1 (1.3–7.3) | 0.01 | 1.7 (0.5–5.8) | 0.36 |
Gametocyteamia (within D0–7) | ||||||
Present | 61 | 16 | 1 | 1 | ||
Absent | 658 | 318 | 2.6 (1.5–4.7) | 0.001 | 1.4 (0.6–3.3) | 0.44 |
Parasite clearance time (day) | ||||||
≤ 2 | 563 | 259 | 1 | |||
> 2 | 155 | 75 | 1.1 (0.8–1.6) | 0.66 | – | – |
Fever clearance time (day) | ||||||
≤ 2 | 455 | 223 | 1 | |||
> 2 | 19 | 10 | 1.2 (0.5–2.9) | 0.94 | – | – |
Season of enrolment | ||||||
Dry (November–March) | 43 | 16 | 1 | |||
Wet (April–October) | 676 | 318 | 1.5 (0.8–2.8) | 0.27 | – | – |
Drug treatment | ||||||
DHP | 251 | 120 | 1 | |||
AL | 234 | 113 | 1.0 (0.7–1.5) | 0.99 | – | – |
AA | 234 | 101 | 0.8 (0.6–1.2) | 0.35 |
Kinetics of the disposition of drug-attributable falls in haematocrit
Treatment |
P value | ||||
---|---|---|---|---|---|
AA (n = 138) | AL (n = 148) | DHP (n = 146) | ALL (n = 432) | ||
Male/Female | 78/60 | 74/74 | 82/64 | 234/198 | 0.45 |
Age (month) | |||||
Mean (95% CI) | 38.4 (35.6–41.2) | 41 (38.5–43.6) | 36.5 (33.6–39.2) | 38.6 (37.1–40.2) | 0.06 |
Age ≤ 24 [%] | 36 [26] | 27 [18] | 53 [36] | 116 [27] | 0.002 |
Duration of illness (day) | |||||
Mean (95% CI) | 3.6 (3.1–4.1) | 3.6 (3.1–4.1) | 3.4 (2.9–3.9) | 3.5 (3.2–3.8) | 0.79 |
Temperature (°C) | |||||
Mean (95% CI) | 37.9 (37.7–38.1) | 37.9 (37.5–38.2) | 37.8 (37.4–38.2) | 37.9 (37.6–38.1) | 0.76 |
No. with temperature | |||||
> 37.4 °C [%] | 94 [68] | 104 [70] | 95 [65] | 293 [68] | 0.63 |
> 40 °C [%] | 9 [6.5] | 4 [3] | 7 [5] | 20 [5] | 0.29 |
Haematocrit (%) | |||||
Mean (95% CI) | 31.8 (31–32.6) | 31.9 (31.2–32.7) | 32.3 (31.5–33) | 32 (31.6–33.4) | 0.67 |
No. with haematocrit <30% [%] | 44 [32] | 40 [27] | 34 [23] | 114 [26] | 0.54 |
Parasitaemia (μL−1) | |||||
Geometric mean | 17,737 | 22,202 | 20,767 | 20,210 | 0.36 |
Range | 2000–200,000 | 2004–200,000 | 2003–200,000 | 2000–200,000 | |
No with parasitaemia | |||||
> 100,000 [%] | 90 [65] | 102 [69] | 99 [68] | 291 [67] | 0.84 |
Gametocyte carriage [%] | 12 [8.7] | 7 [4.7] | 11 [7.5] | 30 [6.9] | 0.38 |
Fever clearance time (day) | |||||
Mean (95% CI) | 1.1 (1.1–1.2) | 1.3 (1.2–1.4) | 1.2 (1.1–1.3) | 1.2 (1.2–1.3) | 0.07 |
Parasite positivity | |||||
On day 1 [%] | 75 [54] | 98 [66] | 81 [55] | 254 [59] | 0.07 |
On day 3 [%] | 2 [1.4] | 3 [2] | 2 [1.4] | 9 [2.1] | 0.66 |
Parasite clearance time (day) | |||||
Mean (95% CI) | 1.8 (1.6–1.9) | 1.9 (1.8–2) | 1.7 (1.6–1.8) | 1.8 (1.7–1.9) | 0.054 |