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Table 2 Summary of characteristics of study participants

From: Association of G6PD status and haemolytic anaemia in patients receiving anti-malarial agents: a systematic review and meta-analysis

No

Author

Country

Number of Subjectsa

Age range

Type of Malaria

Method

Studied drugs, doses (duration)

Duration of Follow Up

Mean difference (SD or 95% CI), G6PD def. vs. normal

Risk ratio anaemia (95% CI)

Other related outcomes

Single dose 0.25 mg/kg PQ

1

Mwaiswelo et al. [24]

Tanzania

88 G6PDn, 21 G6PDd

 ≥ 1 y.o

P.f

RCT

PQ 0.25 mg/kg (SD)

7 days

1.16 (0.67–1.66) vs. 0.81 (0.59–1.02)

N/A

Mean relative Hb reduction (%) (95% CI) G6PD def. vs. normal:

7.9 (4.58–11.18) vs. 7.2 (5.04–9.35)

2

Bastiaens et al. [19]

Burkina Faso, Gambia

20 G6PDn, 42 G6PDd

10–45 y.o

P.f

RCT

1. PQ 0.25 mg/kg (SD)

7, 28 days

Burkina Faso

Day 7, dose 0.25 mg/kg:

− 0.92 (1.43) vs − 0.64 (1.01)

Day 28, dose 0.25 mg/kg:

− 0.29 (1.83) vs 0.04 (1.27)

Gambia

Day 7, dose 0.25 mg/kg:

− 0.99 (0.85) vs − 1.06 (1.55)

Day 28, dose 0.25 mg/kg:

− 0.52 (1.18) vs − 0.4 (2.01)

Changes in Hb conc. > 

− 2.5 g/dL:

Burkina Faso

Dose PQ 0.25 mg/kg

RR = 1.13 [0.46, 2.77]

Gambia

Dose PQ 0.25 mg/kg

RR = 0.60 [0.17, 2.14]

N/A

3

Dysoley et al. [21]

Cambodia

47 G6PDn, 9 G6PDd

4–76 y.o

P.f

RCT

PQ 0.25 mg/kg (SD)

7 days

− 1.46 (− 3.3–0.4) g/dL vs. − 1.24 (− 4.6–2.4) g/dL

Hb reduction ≥ 25% normal, RR: 1.04 [0.14, 7.91]

Mean Hb, G6PD def. vs. normal: 10.9 (8.5–13.2) vs. 12.05 (8.7–14.5)

4

Raman et al. [23]

South Africa

55 G6PDn, 11 G6PDd

 ≥ 2 y.o

P.f

RCT

PQ 0.25 mg/kg (SD)

7, 14, 28, 42 days

N/A

N/A

11 subjects with G6PD deficiency reached the lowest median Hb during day 7, compared to G6PD normal group

Single dose 15 mg

1

Tine et al. [22]

Senegal

105 G6PDn, 30 G6PDd

18–74 y.o

P.f

RCT

PQ 15 mg (SD)

7, 28 days

Day 7, G6PD def. vs normal:

− 1.75 (− 6.1, 2.6) vs − 1.36 (− 4.7, 3.3)

Day 28, G6PD def. vs normal:

− 0.24 (− 3.3, + 3) vs – 0.32 (− 3.7, + 4.8)

Hb reduction > 2 g/dL in day 7, RR = 1.12 [0.78, 1.62]

Mean Hb, Day 28, G6PD def. vs. normal: 12,8 (0.87) vs. 13,2 (1.26)

Single dose 0.25–0.5 mg/kg

1

Bastiaens GJH et al. [19]

Burkina Faso, Gambia

11 G6PDn,

24 G6PDd

10–45 y.o

P.f

RCT

PQ 0.4 mg/kg (SD)

7, 28 days

Burkina Faso

Day 7, dose 0.4 mg/kg:

− 0.93 (1.20) vs − 0.60 (1.70)

Day 28, dose 0.4 mg/kg:

− 0.10 (1.13) vs − 0.12 (2.01)

Changes in Hb conc. > 

− 2.5 g/dL:

Dose PQ 0.4 mg/kg

RR = 0.70 [0.30, 1.66]

N/A

Single dose 0.75 mg/kg

1

Ley et al. [29]

Bangladesh

91 G6PDn,

4 G6PDd

 > 1 y.o

P.f

Cohort

PQ 0.75 mg/kg, SD (P.f)

30 days

N/A

N/A

Mean fractional Hb reduction in day 7, G6PD def. vs normal:

− 9.1% (− 53.2%, + 35.0%) vs. + 2.9% (− 1.14%, + 6.8%), p = 0.739

PQ daily ≤ 0.25 mg/kgb

1

Poirot et al. [25]

Senegal, Bangladesh, Tanzania, Swaziland

107 G6PDn, 16 G6PDd

 > 1 y.o

P.f, P.v, mix

RCT & cohort

PQ ≤ 0.25 mg/kg

7 days

PQ ≤ 0.25 mg/kg:

− 1.38 [− 2.13, − 0.63] vs. − 1.27 [− 1.56, − 0.99]

N/A

N/A

2

Avalos S et al. [28]

Honduras

48 G6PDn, 7 G6PDd

 > 10 y.o

P.f, P.v

Cohort

PQ 0.25 mg/kg, 14d in P. vivax

PQ 0.75/kg, SD in P. falciparum

7 days

All doses:

− 1.63 (1.79) vs. − 0.28 (1.18), p = 0.040

N/A

Mean Hb, G6PD def. vs. G6PD normal: 9.88 (1.63) vs. 12.07 (1.4), p = 0.040

3

Leslie et al. [14]

Pakistan

121 G6PDn, 1 G6PDd

N/A

P.v

RCT

1. PQ 0.25 mg/kg (14 days)

2. PQ 0.75 mg/kg/week (8 weeks)

14 days

N/A

N/A

On day 7, mean Hb fell below mean Hb in G6PD normal: 10.0 g/dL vs 12.6 g/dL), and rise back to normal in day 14: 12.7 g/dL vs. 12.6 g/dL)

PQ daily > 0.25–0.5 mg/kgb

1

Brito− Sousa JD et al. [17]

Brazil

672 G6PDn, 94 G6PDd

4–84 y.o

P.v

Cohort

PQ 0.5 mg/kg, 7 days

7 days

N/A

N/A

Rate of severe anemia in G6PD def. was 55/94 or 58.5% (no comparison to G6PD normal group)

2

Silva et al. [16]

Brazil

8 G6PDn, 3 G6PDd

18–60 y.o

P.v

Cohort

PQ 0.5 mg/kg (7 days)

3 days

N/A

N/A

Mean Hb, G6PD def. vs. normal: 7.8 ± 0.3 vs. 12.73 ± 1.38

3

A. Llanos-Cuentas et al. [15]

Peru, Brazil, Colombia, Vietnam, Thailand

85 G6PDn & G6PDd, 6 G6PDd in all group studies

 > 16 y.o

P.v

RCT

PQ 15 mg (14 days))

14 days

N/A

N/A

Among 5 subjects with protocol-defined Hb decreases, none are G6PD def. patient

4

Khoo KK et al. [26]

Malaysia

23 G6PDd

 > 1 y.o

P.f, P.v, mix

non-RCT

CQ + PQ

– PQ 75 mg (3 days) (P.f)

– PQ 210 mg (14 days) (P.v, mix)

3, 14 days

N/A

N/A

Hemolysis in CQ + PQ group: 7/23 (30.4%)

5

Poirot et al. [25]

Senegal, Bangladesh, Tanzania, Swaziland

125 G6PDn, 15 G6PDd

 > 1 y.o

P.f, P.v, mix

RCT & cohort

1. PQ 0.25–0.5/kg

7 days

PQ > 0.25—≤ 0.5 mg/kg:

− 1.19 [− 1.97, − 0.42] vs. − 0.63 [− 0.90, − 0.37]

N/A

N/A

PQ daily > 0.5 mg/kg

1

Poirot et al. [25]

Senegal, Bangladesh, Tanzania, Swaziland

152 G6PDn,

4 G6PDd

 > 1 y.o

P.f, P.v, mix

RCT & cohort

2. PQ > 0.5 mg/kg

(SD or 14 days)

7 days

PQ > 0.5 mg/kg:

− 2.75 [− 4.22, − 1.28] vs. − 0.86 [− 1.1, − 0.62]

N/A

N/A

PQ 0.75 mg/kg weekly

1

Kheng et al. [27]

Cambodia

57 G6PDn,

18 G6PDd

 > 1 y.o

P.v, mix

non-RCT

PQ 0.75 mg/kg/week (8 weeks)

7, 28 days

D7: − 2.2 (− 4.9, 0.8) vs. − 0.5 (− 2.2, 2.8)

D28: 0.3 (− 2.3, 2.7) vs. 0.2 (− 2, 2.6)

Hb reduction > 25% on day 7, RR: 33.58 [1.95, 579.53]

Mean Hb, G6PD def. vs. normal:

D7: 10.9 (8.9, 13) vs. 13 (9.5, 15.7)

D28: 13.5 (9.5–16.1) vs. 12.8 (10.9–15.4)

CPG-DDS

1

Leslie et al. [18]

Afghanistan, Pakistan

300 G6PDn,2 G6PDd

 > 3 y.o

P.v

RCT

CPG-DDS (3 days)

14

N/A

N/A

1 subject with G6PDd had Hb decreased 1.4 g/dL over 24 h

2

Tiono et al. [20]

Burkina Faso, Ghana, Mali, Nigeria

824 G6PDn, 68 G6PDd

 > 1 y.o

P.f

RCT

1. CDA

2. CPG-DDS

28 days

N/A

Hb reduction ≥ 4 g/dL or ≥ 40% baseline of Hb 5 g/dL or blood transfusion:

– CDA, RR = 33.09 [11.27, 97.15]

– CPG-DDS, RR = 10.74 [3.93, 29.37]

N/A

Tafenoquine

1

A. Llanos- Cuentas et al.)[15]

Peru, Brazil, Colombia, Vietnam, Thailand

166 G6PDn & G6PDd, 6 G6PDd in all group studies

 > 16 y.o

P.v

RCT

Tafenoquine 300 mg (SD)

14 days

N/A

N/A

Among 5 subjects with protocol-defined Hb decreases, none are G6PD def. patient

  1. aNumber of study subjects receiving study drugs
  2. PQ: primaquine; SD: single dose; P.f: Plasmodium falciparum; P.v: Plasmodium vivax; N: number of study participants using the study drug/s; CPG-DDS: chlorproguanil-dapsone; CDA: chlorproguanil-dapsone-artesunate; G6PDd: glucose-6-phosphate dehydrogenase deficiency; G6PDn: glucose-6-phosphate dehydrogenase normal; N/A: data not available; RR: risk ratio; RCT: randomized controlled trial