Table 4. Risk factors for PCR-confirmed recrudescence at day 28.
| Total N (n)* |
Univariable analyses
|
Multivariable analyses
†
|
PAR calculations
‡
|
||||
|---|---|---|---|---|---|---|---|
| Crude HR (95% CI) | p value | Adjusted HR (95% CI) | p value | Frequency§ | PAR | ||
| Age, every 1-year increase | 14 139 (304) | 0·96 (0·94–0·99) | 0·001 | · · | · · | · · | · · |
| Bodyweight, every 1 kg increase | 14 139 (304) | 0·98 (0·97–0·99) | 0·001 | · · | · · | · · | · · |
| Lumefantrine dose, every 5 mg/kg increase |
14 139 (304) | 0·98 (0·95–1·02) | 0·380 | 0·98 (0·94–1·02) | 0·380 | 27·46% | 6·30% |
| Enrolment clinical variables | |||||||
| Parasitaemia, parasites per μL every ten-times increase |
14 139 (304) | 1·47 (1·2–1·81) | 0·0002 | 1·41 (1·15–1·74) | 0·0012 | 9·51% | 4·01% |
| Fever, temperature >37·5°C | 13 024 (290) | 1·09 (0·85–1·41) | 0·500 | · · | · · | · · | · · |
| Haemoglobin, every 10 g/L increase | 10 303 (221) | 0·95 (0·88–1·01) | 0·100 | · · | · · | · · | · · |
| Anaemia, haemoglobin <100 g/L | 10 303 (221) | 1·24 (0·93–1·65) | 0·150 | · · | · · | · · | · · |
| Gametocytes present | 9008 (198) | 1·01 (0·62–1·65) | 0·970 | · · | · · | · · | · · |
| Sex | |||||||
| Female | 6448 (143) | Reference | · · | · · | · · | · · | · · |
| Male | 7393 (156) | 0·95 (0·76–1·20) | 0·690 | · · | · · | · · | · · |
| Age category, years | |||||||
| ≥12 | 3160 (34) | Reference | · · | · · | · · | · · | · · |
| <1 | 809 (21) | 1·73 (0·92–3·29) | 0·091 | 1·78 (0·89–3·55) | 0·100 | 5·72% | 4·76% |
| 1 to <5 | 7231 (204) | 2·17 (1·35–3·47) | 0·001 | 2·00 (1·23–3·23) | 0·005 | 51·14% | 37·92% |
| 5 to <12 | 2939 (45) | 1·33 (0·81–2·18) | 0·260 | 1·27 (0·76–2·12) | 0·360 | 20·79% | 7·96% |
| Transmission setting | |||||||
| Low | 3432 (60) | Reference | · · | · · | · · | · · | · · |
| High | 5336 (160) | 1·75 (0·92–3·33) | 0·086 | · · | · · | · · | · · |
| Moderate | 5371 (84) | 1·13 (0·58–2·23) | 0·720 | · · | · · | · · | · · |
| Region | |||||||
| Africa | 11 674 (260) | Reference | · · | · · | · · | · · | · · |
| Asia | 2306 (43) | 0·81 (0·34–1·90) | 0·630 | · · | · · | · · | · · |
| South America | 159 (1) | 0·25 (0·02–4·16) | 0·330 | · · | · · | · · | · · |
| Treatment supervision | |||||||
| Full | 10 929 (232) | Reference | · · | · · | · · | · · | · · |
| Partial | 1909 (51) | 1·40 (0·76–2·59) | 0·280 | · · | · · | · · | · · |
| Unsupervised | 1301 (21) | 1·31 (0·52–3·28) | 0·570 | · · | · · | · · | · · |
| Coadministration with fat | |||||||
| With fatty meal | 6346 (142) | Reference | · · | · · | · · | · · | · · |
| Without fatty meal | 1181 (23) | 0·95 (0·34–2·67) | 0·920 | · · | · · | · · | · · |
| Advised with fatty meal | 2120 (39) | 0·98 (0·40–2·41) | 0·960 | · · | · · | · · | · · |
| Dose calculation method | |||||||
| Per protocol | 9473 (231) | Reference | · · | · · | · · | · · | · · |
| Tablet counts | 4666 (73) | 0·73 (0·43–1·24) | 0·250 | · · | · · | · · | · · |
| Drug tradename | |||||||
| Coartem | 13 891 (296) | Reference | · · | · · | · · | · · | · · |
| Generic artemether–lumefantrine | 248 (8) | 1·12 (0·42–2·99) | 0·820 | · · | · · | · · | · · |
HR=hazard ratio. PAR=population-attributable risk.
Number of patients (number with recrudescence by day 28).
The assumption of proportional hazard held for the model (p=0·47 for global test) and for all the individual covariates in the multivariable model (p>0·05). The variance of random eff ect was 0·95. The likelihood ratio test was not significant for bodyweight (p=0·19), haemoglobin (p=0·29), and transmission (p=0·53) in the presence of mg/kg dose, parasitaemia, and age category; thus, these were dropped from the multivariable analysis.
Overall PAR for model: 51·1%. Cumulative PAR for parasitaemia >100 000 parasites per μL and age 1 to <5 years: 40·4%.
The proportion of patients with the risk factor. Continuous covariates were categorised as follows: baseline parasitaemia at 100 000 parasites per μL and mg/kg lumefantrine dose at 60 mg/kg (lower bound of WHO therapeutic range). The adjusted HR used for estimating the PARs (obtained from the categorised model) were 1·44 for baseline parasitaemia, 1·24 for lumefantrine dose <60 mg/kg, 1·87 for age <1 year, 2·19 for age 1–5 years, and 1·42 for age 5–12 years.