Characteristics of included studies [ordered by study ID]
Krudsood 2003
|
| Methods | Generation of allocation sequence: not described; randomization in ratio 2:1
Allocation concealment: not described
Blinding: none
Inclusion of all randomized participants in final analysis: 88% (114/130) |
|
| | Participants | Number: 130 adults
Inclusion criteria: acute uncomplicated falciparum malaria; positive blood slide; weight > 40 kg; age > 14 years; oral intake; agree to hospital admission
Exclusion criteria: severe malaria; oral intake not possible; pregnancy or lactation; concomitant disease; taken other antimalarials within past 14 days; urine sulphonamides or 4-aminoquinolones |
|
| | Interventions | 1. Artemether-lumefantrine: 6 doses over 72 h; artemether 80 mg/dose, lumefantrine 480 mg/dose
2. Dihydroartemisinin-napthoquine-trimethoprim (DNP): 2 tablets over 24 h |
|
| | Outcomes | 1. 28-day cure
2. Parasite clearance time
3. Fever clearance time
4. Adverse events |
|
| | Notes | Location: Bangkok, Thailand
16 participants withdrew from trial (9 artemether-lumefantrine, 7 DNP)
Local antimalarial drug resistance: multiple-drug resistance
Malaria transmission: not specified |
|
|
Lefevre 2001
|
| Methods | Generation of allocation sequence: not described; randomization 3:1
Allocation concealment: not described
Blinding: none
Inclusion of all randomized participants in the analysis: 95% (208/219) |
|
| | Participants | Number: 219 participants aged 12 to 71
Inclusion criteria: microscopically confirmed Plasmodium falciparum
Excluded: severe, complicated malaria |
|
| | Interventions | 1. Artemether-lumefantrine: 6 doses over 48 h; artemether 80 mg/dose, lumefantrine 480 mg/dose)
2. Mefloquine plus artesunate: mefloquine 2 doses over 48 h (day 2 = 15 mg/kg, day 3 = 10 mg/kg); artesunate 3 doses over 48 h (4 mg/kg/dose) |
|
| | Outcomes | 1. 28-day cure
2. Parasite clearance time
3. Fever clearance time
4. Gametocyte carriage within first 72 h
5. Gametocyte clearance time
6. Parasite reduction at 24 h
7. Adverse effects
8. Polymerase chain reaction (PCR) analysis |
|
| | Notes | Location: Bangkok, Thailand
Trial designed to compare artemether-lumefantrine with historical controls in which artesunate-mefloquine was used
11 not evaluated on day 28: 9 (artemether-lumefantrine); 2 (artesunate-mefloquine)
Local antimalarial drug resistance: not specified
Malaria transmission: low |
|
|
Mayxay 2004
|
| Methods | Generation of allocation sequence: not described; block randomization
Allocation concealment: sealed, opaque envelopes
Blinding: none
Inclusion of all randomized participants: 98% (324/330) |
|
| | Participants | Number: 330 participants
Inclusion criteria: Plasmodium falciparum of 5000 to 20,000/µL; age > 1 year; fever; no signs of severe malaria |
|
| | Interventions | 1. Artemether-lumefantrine: 6 doses over 72 h; artemether 1.3 to 2.6 mg/kg/dose, lumefantrine 8 to 16 mg/kg/dose
2. Chloroquine plus sulfadoxine-pyrimethamine: chloroquine 25 mg base/kg; sulfadoxine 25 mg/kg, pyrimethamine 1.25 mg/kg
3. Mefloquine plus artesunate: mefloquine 12.5 mg/kg; artesunate 3 mg/kg/dose |
|
| | Outcomes | 1. 42-day cure
2. Parasite clearance time
3. Fever clearance time
4. Gametocyte carriage
5. Polymerase chain reaction (PCR) analysis
6. Adverse events |
|
| | Notes | Location: Savannakhet Province, Lao People's Democratic Republic
Local antimalarial drug resistance: chloroquine, sulfadoxine-pyrimethamine
Malaria transmission: not specified |
|
|
Mutabingwa 2005
|
| Methods | Generation of allocation sequence: computer; block randomization
Allocation concealment: sealed opaque numbered envelopes
Blinding: none
Inclusion of all randomized participants: 97% (1659/1811) |
|
| | Participants | Number: 1811 children aged 4 to 59 months
Inclusion criteria: microscopically confirmed Plasmodium falciparum parasitaemia > 2000/µL; oral intake; can attend clinic for follow up
Exclusion criteria: severe malaria; mixed plasmodium infection; taken other antimalarial (apart from chloroquine) within past 7 days; known hypersensitivity to trial drugs; presence of disease masking assessment of response to antimalarial treatment |
|
| | Interventions | 1. Artemether-lumefantrine: 6 doses over 72 h; artemether 1 to 2 mg/kg/dose, lumefantrine 8 to 14 mg/kg/dose
2. Amodiaquine: 3 doses over 72 h; total dose 25 mg/kg
3. Amodiaquine plus sulfadoxine-pyrimethamine: amodiaquine total dose 25 mg/kg (as 3 doses over 72 h); sulfadoxine 25 mg/kg, pyrimethamine 1.25 mg/kg (as single dose)
4. Amodiaquine plus artesunate: amodiaquine total dose 25 mg/kg as (3 doses over 72 h); artesunate 4 mg/kg over 72 h |
|
| | Outcomes | 1. 28-day cure
2. 14-day cure
3. Gametocyte carriage on day 14
4. Polymerase chain reaction (PCR) genotype
5. Haemoglobin
6. Adverse events |
|
| | Notes | Location: Muheza, Tanzania
Local antimalarial drug resistance: chloroquine, sulfadoxine-pyrimethamine
Malaria transmission: perennial |
|
|
Ndayiragije 2004
|
| Methods | Generation of allocation sequence: not described; block randomization
Allocation concealment: not described
Blinding: none
Inclusion of all randomized participants: 98% (290/295) |
|
| | Participants | Number: 295 children aged 6 to 59 months
Inclusion criteria: weight > 7 kg; microscopically confirmed Plasmodium falciparum parasitaemia > 2000/µL; fever
Excluded: severe malaria; severe malnutrition; other infectious febrile illness |
|
| | Interventions | 1. Artemether-lumefantrine: 6 doses over 60 h; artemether 1.3 to 2.6 mg/kg/dose, lumefantrine 8 to 16 mg/kg/dose
2. Artesunate: 3 doses over 48 h (4 mg/kg/dose); amodiaquine 3 doses over 48 h (10 mg/kg/dose) |
|
| | Outcomes | 1. 14-day cure
2. Gametocyte carriage on days 0, 3, 7, and 14
3. Adverse effects |
|
| | Notes | Location: Buhiga and Kigobe, Burundi
Local antimalarial drug resistance: chloroquine, sulfadoxine-pyrimethamine
Malaria transmission: not specified |
|
|
Piola 2005
|
| Methods | Generation of allocation sequence: computer; block randomization
Allocation concealment: sealed envelopes
Blinding: none
Inclusion of all randomized participants: 96% (918/957) |
|
| | Participants | Number: 957 children and adults
Inclusion criteria: fever; weight > 10 kg; monoinfection with Plasmodium falciparum; parasitaemia of 500 to 100,000 trophozoites/µL; no signs of severe malaria |
|
| | Interventions | 1. Supervised artemether-lumefantrine: 6 doses over 3 d (for each dose 1 tablet 10 to 14.9 kg; 2 tablets 15 to 24.9 kg; 3 tablets 25 to 34.9 kg; 4 tablets >35 kg)
2. Unsupervised artemether-lumefantrine: 6 doses over 3 days |
|
| | Outcomes | 1. 28-day cure
2. Proportion of afebrile patients on days 1, 2, and 3
3. Gametocyte carriage
4. Polymerase chain reaction (PCR) analysis
5. Haematological recovery
6. Adverse events |
|
| | Notes | Location: Mbarara, Uganda
Local antimalarial drug resistance: chloroquine, sulfadoxine-pyrimethamine
Malaria transmission: perennial |
|
|
Stohrer 2004
|
| Methods | Generation of allocation sequence: not described; block randomization
Allocation concealment: sealed envelopes
Blinding: none
Inclusion of all randomized participants: 93% (101/108) |
|
| | Participants | Number: 108 participants aged 2 to 66 years
Inclusion criteria: fever; microscopically confirmed Plasmodium falciparum 1000 to 100,000 parasites/µL
Exclusion criteria: severe or complicated malaria; severe malnutrition; weight < 10 kg |
|
| | Interventions | 1. Artemether-lumefantrine: 6 doses over 72 h; artemether 1.4 to 2 mg/kg/dose, lumefantrine 8.5 to 16 mg/kg/dose
2. Mefloquine plus artesunate: mefloquine total dose over 48 h (25 mg/kg); artesunate 3 doses over 72 h (4 mg/kg/dose) |
|
| | Outcomes | 1. 42-day cure
2. Gametocyte carriage
3. Gametocyte clearance time
4. Polymerase chain reaction (PCR) analysis |
|
| | Notes | Location: Luang Namtha Province, Lao People's Democratic Republic
Hospital- and community-based study
Local antimalarial drug resistance: chloroquine, sulfadoxine-pyrimethamine
Malaria transmission: perennial |
|
|
Sutherland 2005
|
| Methods | Generation of allocation sequence: not described; block randomization
Allocation concealment: numbered envelopes
Blinding: single, all personnel apart from field assistants and recruiting clinic
Inclusion of all randomized participants: 88% (368/419) |
|
| | Participants | Number: 497 children
Inclusion criteria: fever; microscopically confirmed Plasmodium falciparum > 500/µL
Exclusion criteria: severe malaria; no oral intake; gametocyte carriage at presentation |
|
| | Interventions | 1. Artemether-lumefantrine: 6 doses over 72 h (for each dose, half-tablet per 5 kg up to 2 tablets; children > 25 kg 3 tablets per dose)
2. Chloroquine plus sulfadoxine-pyrimethamine: 30 mg/kg/base chloroquine; 250 mg sulfadoxine, 12.5 mg pyrimethamine; plus additional 12.5 mg sulfadoxine and 6.25 mg pyrimethamine for each 5 kg over 10 kg body weight |
|
| | Outcomes | 1. Infectiousness of patients to Anopheles mosquitoes from day 7
2. 7, 14, and 28-day cure
3. Gametocyte carriage
4. Polymerase chain reaction (PCR) analysis
5. Adverse events |
|
| | Notes | Location: Farafenni, The Gambia
Local antimalarial drug resistance: chloroquine and sulfadoxine-pyrimethamine
Malaria transmission: high seasonal |
|
|
Van Vugt 2000
|
| Methods | Generation of allocation sequence: not described; block randomization (3)
Allocation concealment: sealed envelopes
Blinding: none
Inclusion of all randomized participants: 90% (181/200) |
|
| | Participants | Number: 200 participants aged 2 to 63
Inclusion criteria: parasitaemia > 500/µL
Excluded: severe malaria |
|
| | Interventions | 1. Artemether-lumefantrine: 6 doses over 48 h; artemether 1.3 to 2.6 mg/kg/dose, lumefantrine 7.8 to 15 mg/kg/dose
2. Mefloquine plus artesunate: mefloquine 2 doses over 48 h (day 2, 15 mg/kg; day 3, 10 mg/kg); artesunate 3 doses over 48 h (4 mg/kg/dose) |
|
| | Outcomes | 1. 28-day cure
2. Proportion of patients with fever on days 0 to 3
3. Proportion of patients with parasitaemia on days 0 to 3
4. Gametocyte carriage within first 72 h
5. Adverse events
6. Electrocardiogram (ECG) findings |
|
| | Notes | Location: Bangkok and Karen, Thailand
2 trial centres: Bangkok - inpatients for 28 days; Karen - outpatients
19 not evaluated on day 28: 16 (artemether-lumefantrine), 3 (artemether plus mefloquine)
Local antimalarial drug resistance: multiple-drug resistance
Malaria transmission: low |
|
|
Characteristics of excluded studies [ordered by study ID]
|
| Study | Reason for exclusion |
|---|
| | Espino 2002 | Four-dose regimen of artemether-lumefantrine used |
| | Falade 2005 | Not a randomized controlled trial |
| | Hatz 1998 | Four-dose regimen of artemether-lumefantrine used |
| | Jiao 1997 | Compared artemether-lumefantrine with lumefantrine, which is not a recommended standard therapy for uncomplicated malaria |
| | Karbwang 2002 | Artemether-lumefantrine not compared with another antimalarial |
| | Kshirsagar 2000 | Four-dose regimen of artemether-lumefantrine used |
| | Lefevre 2002 | Parallel 3-group trial where participants received sequential artemether-lumefantrine and quinine |
| | Looareesuwan 1999 | Four-dose regimen of artemether-lumefantrine used |
| | Popov 2002 | Not a randomized controlled trial |
| | Sun 2000 | Compared artemether-lumefantrine with lumefantrine, which is not a recommended standard therapy for uncomplicated malaria |
| | Van Agtmael 1999 | Four-dose regimen of artemether-lumefantrine used |
| | Van Vugt 1998b | Four-dose regimen of artemether-lumefantrine used |
| | Van Vugt 1999a | Compared four-dose and six-dose regimens of artemether-lumefantrine |
| | Von Seidlein 1997 | Not a randomized controlled trial (safety trial) |
| | Von Seidlein 1998 | Four-dose regimen of artemether-lumefantrine used |
| | Zhiwei 1999 | Compared artemether-lumefantrine with lumefantrine, which is not recommended standard therapy for uncomplicated malaria |
|
|
Comparison 1. Artemether-lumefantrine vs amodiaquine
Comparison 2. Artemether-lumefantrine vs chloroquine plus sulfadoxine-pyrimethamine
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Total failure by day 28 | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected |
| | 2 Total failure by days 42, 14, and 7 | 2 | | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected |
| | | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| | | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| | | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| | 3 Gametocyte carriage on days 28, 14, and 7 | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected |
| | | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| | | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| | | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
|
|
Comparison 3. Artemether-lumefantrine vs amodiaquine plus sulfadoxine-pyrimethamine
Comparison 4. Artemether-lumefantrine vs amodiaquine plus artesunate
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Total failure by day 28 | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected |
| | 2 Total failure by day 14 | 2 | 1283 | Risk Ratio (M-H, Fixed, 95% CI) | 0.11 [0.05, 0.23] |
| | 3 Gametocyte carriage on days 14 and 7 | 2 | | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only |
| | | 2 | 941 | Risk Ratio (M-H, Fixed, 95% CI) | 0.56 [0.35, 0.91] |
| | | 1 | 290 | Risk Ratio (M-H, Fixed, 95% CI) | 0.68 [0.33, 1.41] |
|
|
Comparison 5. Artemether-lumefantrine vs mefloquine plus artesunate
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Total failure by day 28 | 2 | 389 | Risk Ratio (M-H, Fixed, 95% CI) | 4.20 [0.55, 31.93] |
| | 2 Total failure by day 28: PCR adjusted | 2 | | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only |
| | | 2 | 389 | Risk Ratio (M-H, Fixed, 95% CI) | 3.50 [0.45, 27.03] |
| | | 2 | 389 | Risk Ratio (M-H, Fixed, 95% CI) | 4.20 [0.55, 31.93] |
| | 3 Total failure by day 42 | 2 | 315 | Risk Ratio (M-H, Fixed, 95% CI) | 2.93 [1.48, 5.80] |
| | 4 Total failure by day 42: PCR adjusted | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected |
| | | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| | | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | 0.0 [0.0, 0.0] |
| | 5 Gametocyte carriage on day 7 and in first 72 h | 3 | | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only |
| | | 1 | 100 | Risk Ratio (M-H, Fixed, 95% CI) | 1.35 [0.44, 4.15] |
| | | 2 | 240 | Risk Ratio (M-H, Fixed, 95% CI) | 1.09 [0.58, 2.06] |
|
|
Comparison 6. Artemether-lumefantrine vs dihydroartemisinin-napthoquine-trimethoprim (DNP)
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Total failure by day 28 | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Subtotals only |
|
|
Comparison 7. Artemether-lumefantrine: supervised vs unsupervised treatment
|
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
|---|
| | 1 Total failure by day 28 | 1 | | Risk Ratio (M-H, Fixed, 95% CI) | Totals not selected |
|
|
Table 1. Risk of bias of each included studya
|
| |
|
aInclusion of all randomized participants in the analysis; see the 'Methods of the review' for the assessment methods, and the '' for the methods used in each trial.
|
