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Table 3 Risk factors for the change in haemoglobin concentration on day 7 following ACT first dose administration

From: Safety of single-dose primaquine as a Plasmodium falciparum gametocytocide: a systematic review and meta-analysis of individual patient data

Parameter Absolute change in haemoglobin concentration Fractional drop > 25% compared to baseline levels
Na change (g/dL) 95% CI P-value na AOR 95% CI P-value
Age/sex category
 < 5 years 733 − 0.82 − 0.99, − 0.66 < 0.001 27 6.20 2.73, 14.12 < 0.001
 5–11 years 1561 − 0.57 − 0.70, − 0.45 < 0.001 35 2.70 1.32, 5.50 0.006
 12+ years females 612 − 0.60 − 0.72, − 0.47 < 0.001 28 3.20 1.67, 6.13 < 0.001
 12+ males 969 0.00    22 1.00   
Transmission intensityb
 Low 2444 − 0.40 − 0.90, 0.10 0.117 96 4.20 1.41, 12.51 0.010
 Moderate 769 − 0.38 − 0.62, − 0.14 0.003 11 1.64 0.47, 5.78 0.438
 High 662 0.00    5 1.00   
Pf malaria status
 Yes 2462 − 0.72 − 1.20, − 0.24 0.003     
 No or unknownc 1413 0.00       
Log 10 parasitaemia 3875 Nonlineard < 0.001     
Haemoglobin (g/dL) 3875 Nonlineare < 0.001 112   Nonlineare < 0.001
G6PD status
 Normal 3170 0.00    78 1.00   
 Deficient 194 − 0.03 − 0.30, 0.24 0.834 20 1.45 0.51, 4.16 0.486
 Unknown 511 − 0.14 − 0.40, 0.13 0.312 14 0.24 0.04, 1.59 0.140
Primaquine dose (0.1 mg/kg)f
 Normal G6PD status 2265 − 0.01 − 0.03, 0.01 0.334 55 1.06 0.98, 1.15 0.162
 G6PD deficient 127 − 0.27g − 0.34, − 0.19 < 0.001 18 1.63h 1.32, 2.01 < 0.001
 G6PD status unknown 389 − 0.01 − 0.05, 0.03 0.732 14 1.36 1.04, 1.78 0.026
  Moderate/severe anaemia (Hb < 10 g/dL) Severe anaemia (Hb < 7 g/dL)i
na AOR 95% CI P-value na AOR 95% CI P-value
Age/sex category
 < 5 years 294 3.52 2.18, 5.68 < 0.001     
 -11 years 234 1.89 1.23, 2.92 0.004     
 2+ years: females 68 1.35 0.85, 2.16 0.209     
 12+ years: males 43 1.00       
Log 10 parasitaemia (/μL) 639 Nonlineard < 0.001     
Haemoglobin (g/dL) 639 Nonlineare < 0.001 35 Nonlineare < 0.001
G6PD status
 Normal 533 Reference       
 Deficient 44 0.99 0.43, 2.24 0.974     
 Unknown 62 0.66 0.27, 1.62 0.368     
Primaquine dose (per 0.1 mg/kg increase)f
 Normal G6PD status 403 1.04 1.00, 1.09 0.079 9 1.19 0.99, 1.42 0.059
 G6PD deficient 33 1.60k 1.28, 1.99 < 0.001 6 1.89l 1.49, 2.40 < 0.001
 G6PD status unknown 47 1.07 0.94, 1.23 0.291 7 1.34 1.09, 1.65 0.005
  1. Multivariable regression models (logistic or normal, as appropriate) with a random intercept for the study site were fitted. Random coefficient models (for primaquine dose) could not be reliably evaluated for binary outcomes and for the absolute change in Hb concentration in patients with G6PD deficiency due to small numbers. For the absolute change in Hb concentration in patients without G6PD deficiency, a random coefficient model has not improved the fit significantly and provided similar population estimates, with a population mean = 0.03 (95% CI − 0.03, 0.10) and standard deviation = 0.103 (95% CI 0.056, 0.190) for the random slope for primaquine dose (0.1mg/kg)
  2. aN = number of observations in that category and n = number of patients in that category with FC < − 25% or moderate or severe anaemia, respectively
  3. bTransmission intensity defined based on estimates of P. falciparum prevalence rate (PfPR), assuming low transmission for study sites with a PfPR < 0.15, moderate transmission if PfPR 0.15 to < 0.40, and high transmission if PfPR ≥ 0.40
  4. cIncludes individuals with no malaria (n = 224), malaria-positive or gametocytaemic at screening (n = 564), and symptomatic individuals from the community who were not tested (n = 625)
  5. dFor nonlinear relationship, see Additional file 3: Fig. S5
  6. eFor nonlinear relationship, see Fig. 2
  7. fN and n, defined as before but refer to individuals who received primaquine in that category
  8. gChange in Hb = − 0.528, (95% CI − 0.887, − 0.168), P = 0.004, for comparison of 0.25 mg/kg primaquine (83) and no primaquine arms (67) in patients with G6PD deficiency
  9. hAOR = 3.98, (95% CI 0.77, 20.59), P = 0.099, for comparison of 0.25 mg/kg primaquine (8/83) and no primaquine arms (2/67) in patients with G6PD deficiency, only adjusted for haemoglobin due to small numbers
  10. iAdjusted only for baseline haemoglobin levels due to small numbers
  11. kAOR = 3.25, (95% CI 0.96, 10.95), P = 0.057, for comparison of 0.25 mg/kg primaquine (17/83) and no primaquine arms (11/67) in patients with G6PD deficiency
  12. lAOR = 10.36, (95% CI 0.28, 389.51), P = 0.206 for comparison of 0.25 mg/kg primaquine (2/83) and no primaquine (1/67) arms in patients with G6PD deficiency, not adjusted for the site due to small number of events observed