Table S1 Summary of the characteristics of the included trials in our meta-analyses evaluating antischistosomal drugs (PZQ, AM and AS), used alone or in combination, for
human schistosomiasis treatment or prevention
Author, Year
Test sites
Time
Participants
Species
Interventions
Follow-up
Treated
Controlled
Relative Risk
Design
time
(n/ N△)
(n/ N)
(95%CI)▲
Type
8 weeks
12/44
40/44
0.30 (0.18, 0.49)
RCT†
T
1-2 years
47/763
980/1644
0.10 (0.08, 0.14)
nRCT‡
T
1 year
546/1436
1230/1624
0.50 (0.47, 0.54)
nRCT
T
53 weeks
237/825
754/1109
0.42 (0.38, 0.47)
nRCT
T
8 months
14/354
247/354
0.06 (0.03, 0.10)
nRCT
T
Diagnostic approach
Usage
Adim village in Biase
Local Government
Form August
Treated: a single oral dose of
Inyang-Etoh
Urine filtration (10 ml ×
schoolchildren,
Area of Cross River
2005 to June
Sh
PC, 2009*
PZQ at 40 mg/kg, Control:
aged 4-20 yr,
State in southeastern
2 specimens)
2006
placebo 40 mg/kg
Nigeria
Burkina Faso, western
Touré S, 2008*
schoolchildren,
Sh & S.
aged 6-14 yr
mansoni
2004-2006
Africa
Tohon ZB,
Niger
Schoolchildren,
Sh & S.
aged 7, 8 and 11 yr
mansoni
2004
2008*
Primary
Saathoff E,
KwaZulu/Natal, South
Africa
Urine filtration (10 ml; 1
PZQ at 60 mg/kg; Control: no
specimen); Kato–Katz (2
drug given
slides × 1 specimen)
Treated: a single oral dose of
Urine filtration (10 ml ×
PZQ at 40 mg/kg; Control: no
1 specimen); Kato–Katz
drug given
(2 slides × 1 specimen)
Treated: a single oral dose of
Urine filtration (10 ml ×
From March 1998
schoolchildren (age
2004*
Treated: a single oral dose of
Sh
PZQ at 40 mg/kg; Control: no
to 1999
1 specimen)
not specified)
the village of Taabo, in
Lasted
south-central Côte
months
for
8
drug given
primary
Treated: two doses of PZQ at 40
Urine filtration (10 ml ×
N'Goran EK,
from
schoolchildren,
Sh
mg/kg by 4-week interval;
2003*
2 specimens)
d’Ivoire
November 2000
aged 5–15 yr
Control: no drug given
Bindo, Tsouke´, and
Nombake´le´, in the
From October
Borrmann S,
Treated: a single oral dose of
Urine filtration (10 ml ×
Children, aged
province
2000 to February
2001*
Sh
PZQ at 40 mg/kg; Control: one
5-13 yr
Moyen-Ogooue´,
8 weeks
24/89
24/30
0.34 (0.23, 0.50)
RCT
T
54/114
85/114
0.64 (0.51, 0.79)
nRCT
T
63 days
22/253
194/253
0.11 (0.08, 0.17)
nRCT
T
7 months
1/11
11/11
0.13 (0.03, 0.59)
nRCT
T
12 months
27/116
43/43
0.24 (0.17, 0.33)
RCT
T
RCT
T
2 specimens)
2001
dose of PZQ placebo 40mg/kg
Gabon
Campagne G,
From 1995 to
Schoolchildren,
Niger
2001*
Treated: a single oral dose of
Urine filtration (10 ml ×
over 34
PZQ at 40 mg/kg
10 specimens)
months
Sh
1997
aged 7–15 yr
Treated: two oral doses of PZQ
primary
Utzinger J,
Fagnampleu, western
From November
schoolchildren,
2000*
Côte d’Ivoire
at 30 mg/kg, administered 3h
Kato–Katz (2 slides × 4
apart, and another dose at 40
specimens)
S. mansoni
1998 to1999
aged 6 -14 yr
mg/kg
Nash TE,
Patients, aged 4-47
Bethesda, Maryland
Sj &
Treated: dosage of PZQ at 60
Kato–Katz (2 slides × 2
mg/kg in three divided doses
specimens)
Not reported
1982*
yr
S. mekongi
Treated: a single oral dose of
PZQ at 50 mg/kg, or 3×20
Santos AT,
Palo, Leyte,
Patients, aged
Not reported
1979*
Philippines
Kato–Katz (2 slides × 3
Sj
mg/kg given by 4-hour
above 6 yr
specimens)
intervals; Control: placebo
given similarly
Treated: PZQ at 30 mg/kg, 40
(a) 6/28
McMahon JE,
Tanga, Tanzania,
1979*
Africa
Schoolchildren,
Not reported
mg/kg, 40 mg/kg in two divided
Urine filtration (10 ml ×
doses by 4-hour apart; Control:
3 specimens)
Sh
aged 7-15 yr
6 months
(b) 8/28
(c) 6/31
placebo given similarly
0.23 (0.12, 0.45)
30/30
0.30 (0.17, 0.53)
0.21 (0.10, 0.41)
Treated: PZQ: (a) 1×20 mg/kg,
military police of
Katz N, 1979*
Male patients, aged
Not reported
Minas Gerais, Brazil
(b) 2×20 mg/kg, and (c) 3×20
Kato–Katz (2 slides × 3
mg/kg; Control: placebo given
specimens)
S. mansoni
20-48 yr
(a) 3/4
2/2
0.84 (0.39, 1.81)
(b) 1/5
5/5
0.27 (0.07, 1.11)
(c) 2/7
7/8
0.33 (0.10, 1.08)
0/2250
45/60
0.00 (0.00, 0.00)
6 -12
RCT
T
nRCT
P
RCT
P
RCT
P
months
similarly
Treated: a single oral dose of
Huang YX,
Jiangsu province,
1998*║
China
PZQ at 40 mg/kg at the 5th week
People fighting
1995
Sj
against flood
No
Half a year
after contact; Control: no drug
given
Treated: (a) first dose of PZQ at
40 mg/kg 7 days after the first
exposure and once every 14
Xiachong village,
Kato–Katz (? slides × ?
Liu ZG,
Villagers patients
Yangxin County,
August in 1995
days until 7 days after the last
Sj
(age not specified)
1997*║
(a) 0/85
specimens) and miracidia
28 days
exposure; (b) PZQ at 40 mg/kg
Hubei province, China
0.01 (0.00, 0.10)
59/61
(b) 3/70
0.04 (0.01, 0.13)
hatching test
at 7th, 25th, 35th day after first
exposure; Control: no drug
given
Treated:(a) AM at 6 mg/kg×13
doses by 15-day intervals; (b)
Song Y,
Jiangxi province,
From May to
Villagers, aged
AM at 6 mg/kg×7 doses by
Kato–Katz (4 slides × 1
Sj
2006**
China
November 2004
6-65 yr
(a) 14/413
40~60 days
1-month interval + placebo 6
mg/kg×6 doses by 15-day
intervals; Control: placebo
specimen)
0.25 (0.14, 0.44)
79/587
(b) 42/402
0.78 (0.55, 1.10)
given similarly
Poyang Lake region,
Treated: AM at 6 mg/kg×9~11
From May to
Li YS, 2005**
Villagers, aged
Jiangxi province,
Kato–Katz (3 slides × 2
Sj
October in 2004
doses by 15-day intervals;
6-60 yr
5 months
3/373
56/361
0.05 (0.02, 0.16)
RCT
P
7 months
76/156
97/150
0.75 (0.62, 0.92)
RCT
P
3 weeks
31/128
68/140
0.50 (0.35, 0.71)
RCT
P
1 month
3/131
60/141
0.05 (0.02, 0.17)
RCT
P
2 weeks
2/41
3/24
0.39 (0.07, 2.17)
RCT
P
40-50 days
4/202
48/212
0.09 (0.03, 0.24)
RCT
P
4 weeks
0/433
40/452
0.01 (0.00, 0.21)
RCT
P
specimens)
China
Control: placebo given similarly
Treated: AM at 6 mg/kg×6
N’Goran EK,
Taabo, the district of
From November
Urine filtration (10 ml ×
schoolchildren,
Sh
2003**
Tiassalé, Côte d’Ivoire
2000 to July 2001
doses once every 4 weeks;
aged 6-15 yr
4 specimens)
Control: placebo given similarly
Treated: AM at 6 mg/kg×6
Utzinger J,
Fagnampleu, western
From November
schoolchildren,
Kato–Katz (1 slides × 4
S. mansoni
2000**
Côte d’Ivoire
1998 to July 1999
doses once every 3 weeks;
aged 6-15 yr
specimens)
Control: placebo given similarly
From May to
Tian ZY,
Treated: AM at 6 mg/kg×8
Fishermen, aged
Muping lake, China
September in
1999**
Kato–Katz (3 slides × 1
Sj
15-60 yr
specimen)
1996
Huang AS,
1999**
Control: placebo given similarly
From August to
People working
November in
with water (age not
Treated: AM at 6 mg/kg×7
The Yangtze River,
Kato–Katz (? slides × ?
Sj
Poyang Lake, Jiangxi
1998**
Province, China
specimen)
1996
specified)
Control: placebo given similarly
From mid-July to
People fighting
Treated: AM at 6 mg/kg once
Kato–Katz thick stool
mid-August in
against floods (age
every 15 days×2~3 doses
smears (? slides × ?
1996
not specified)
Control: placebo given similarly
specimen)
Sj
From April to
Guichi, Anhui
Treated: AM at 6 mg/kg×10
Villagers, aged
November in
1997**
doses once every 2 weeks;
China
Song Y,
Xu MS,
doses once every 15 days;
province, China
Kato–Katz (? slides × ?
Sj
doses once every 15days;
6-65 yr
1996
specimen)
Control: placebo given similarly
Hanshou county,
Tian ZY,
From June to
Villagers, aged
October in 1996
5-60 yr
Hunan province,
1997**
Sj
China
Wang JL,
Yongsheng, Yunnan
1997**
province, China
Dali, Yunnan province,
1996**
China
Kato–Katz (3 slides × 1
doses once every 15 days;
specimen) and miracidia
Control: placebo given similarly
hatching test
Treated: AM at 6 mg/kg×10 doses
Kato–Katz (3 slides × 1
once every half month; Control:
specimen) and miracidia
placebo given similarly
hatching test
1 month
5/290
82/305
0.06 (0.03, 0.16)
RCT
P
1 month
23/789
87/717
0.24 (0.15, 0.38)
RCT
P
25-32 days
13/307
46/306
0.28 (0.16, 0.51)
RCT
P
25-32 days
20/365
51/376
0.40 (0.25, 0.66)
RCT
P
8 weeks
13/44
40/44
0.33 (0.20, 0.52)
RCT
T
8 weeks
65/89
24/30
0.91 (0.73, 1.14)
RCT
T
Villagers, aged
1996
Xiao SH,
Treated: AM at 6 mg/kg×9
Sj
3-60yr
Treated: AM at 6 mg/kg×4
Kato–Katz (3 slides × 1
doses once every half month;
specimen) and miracidia
Control: placebo given similarly
hatching test
Treated: AM at 6 mg/kg×4
Kato–Katz (3 slides × 1
doses once every half month;
specimen) and miracidia
Control: placebo given similarly
hatching test
Villagers, aged
1995
Sj
4-60 yr
Xiao SH,
Yiyang, Hunan
From August to
Villagers, aged
1995**
province, China
October in 1994
4-60 yr
Sj
Adim village in Biase
Local Government
From August
Inyang-Etoh
Treated: AS at 4 mg/kg daily for
Urine filtration (10 ml ×
schoolchildren,
Area of Cross River
2005 to June
PC, 2009§
Sh
3 consecutive days, Control:
aged 4-20 yr,
State in southeastern
2 specimens)
2006
placebo given similarly
Nigeria
Bindo, Tsouke´, and
Nombake´le´, in the
Treated: PZQ placebo and AS at
From October
Borrmann S,
4 mg/kg/day, once per day over
Urine filtration (10 ml ×
Children, aged
province
2000 to February
2001§
Sh
3 days, rounded to the nearest
5-13 yr
Moyen-Ogooue´,
Gabon
2001
2 specimens)
half; Control: AS placebo over 3
days and PZQ placebo once
People fighting
From April to
Tangtian, Yanghe,
Treated: AS at 6 mg/kg once
against floods,
October in 1996,
Yinhui, and Shahe
Xu MS, 2001§
every 2 weeks since 7-10 days
Kato–Katz (? slides × ?
after exposure to 1 week later
specimen) and miracidia
away from infected water;
hatching test
fishermen, people
and from July to
county, Anhui
Sj
4 weeks
9/2438
189/2660
0.05 (0.03, 0.10)
RCT
P
4 weeks
0/305
16/305
0.03 (0.00, 0.50)
RCT
P
4 weeks
1/208
18/207
0.06 (0.01, 0.41)
RCT
P
(a1) 0/185
7/166
0.06 (0.00, 1.04)
(a2) 0/56
8/52
0.05 (0.00, 0.92)
(b1) 1/132
7/148
0.16 (0.02, 1.28)
RCT
P
(b1) 4/151
13/156
0.32 (0.11, 0.95)
(c) 6/51
12/64
0.63 (0.25, 1.56)
2/168
22/200
0.11 (0.03, 0.45)
RCT
P
living in boats,
September in
province, China
villagers, aged 6-65
1997 to 1998
Control: placebo given similarly
yr
Treated: AS at 6 mg/kg ×14
Taiyang village, Huihe
From April 1998
Kato–Katz (? slides × ?
Villagers, aged
Cui JF, 2001§
County, Tongling City,
to November
doses by 2-week interval since 7
Sj
3-65 yr
Anhui province
specimen) and miracidia
days after exposure; Control:
1999
hatching test
placebo given similarly
From April 1998
Sun MX,
Kato–Katz (? slides × ?
to November
2000§
Treated: AS at 6 mg/kg×14
Tongling, Anhui
High risk villagers
Sj
doses by 2-week intervals;
province, China
specimen)
1999
Control: placebo given similarly
Poyang lake, Jiangxi
Treated: (a) AS at 6 mg/kg×8
province; Guichi and
Zhang SJ,
Wangjiang county,
From 1993 to
Villagers, aged
2000§
Anhui province; Jiayu
1998
6-65yr
Sj
doses by 7-day intervals; AS at
Kato–Katz (? slides × ?
6 mg/kg by 15-day intervals:
specimen) and miracidia
(b): 5 doses, (c): 3 doses;
hatching test
30 days
county, Hubei
Control: placebo given similarly
province
From July to
Both farmers, aged
August of both in
18-38 yr and
1997 and 1998
soldiers fighting
Treated: AS at 6 mg/kg×3 doses
Jiangling county,
Yi ZH, 2000§
Sj
at the 7th, 14th and 15th day after
Hubei province, China
exposure; Control: placebo
Miracidia hatching test
4 weeks
against flood aged
given similarly
18-32 yr
Xinjian county,
From June to
Treated: AS at 6 mg/kg×13
Kato–Katz (? slides × ?
doses by 15-day intervals;
specimen) and miracidia
Control: placebo given similarly
hatching test
Treated: AS at 6 mg/kg×4 doses
Kato–Katz (? slides × ?
by 2-week intervals; Control:
specimen) and miracidia
placebo given similarly
hatching test
Treated: AS at 6 mg/kg×8 doses
Kato–Katz (? slides × ?
by 1-week interval; Control:
specimen) and miracidia
placebo given similarly
hatching method
Villagers, aged
Liu HY, 1999§
Jiangxi province,
November in
Sj
30 days
0/43
4/58
0.15 (0.01, 2.70)
RCT
P
4 weeks
2/380
18/400
0.12 (0.03, 0.50)
RCT
P
4 weeks
0/226
26/179
0.01 (0.00, 0.24)
RCT
P
4 weeks
1/323
31/323
0.03 (0.00, 0.23)
RCT
P
4 weeks
0/346
15/323
0.03 (0.00, 0.50)
RCT
P
45 days
2/95
4/101
0.54 (0.05, 5.77)
RCT
T
6-65 yr
China
1997
From July to
Wangjiang county,
Xu MS, 1998§
Villagers, aged
September in
Anhui province, China
Sj
6-65 yr
1997
Poyang Lake, Jiangxi
Liu ZD, 1996§
Villagers (age not
Summer in 1994
Sj
specified)
province, China
Treated: AS at 6 mg/kg×10
Tangtian county,
From April to
Kato–Katz (? slides × ?
Villagers, aged
Xu MS, 1996§
Guichi, Anhui
November in
doses by half a month interval;
Sj
6-65 yr
province, China
specimen) and miracidia
Control: placebo given
1996
hatching test
similarly
Xinjian county and
Treated: AS at 6 mg/kg×8 doses
Kato–Katz (3 slides × 1
by 1-week interval; Control:
specimen) and miracidia
placebo given similarly
hatching test
Treated: 60 mg/kg PZQ+6
Kato–Katz (? slides × ?
mg/kg AM once; Control: 60
specimen) and miracidia
mg/kg PZQ+AM placebo once
hatching test
Villagers, aged
Wu LJ, 1995§
Jinxian county, Jiangxi
Autumn in 1993
Sj
10-70 yr
province, China
Patients (farmer,
Dongting Lake region,
From May 2003
Hou XY,
fisherman,
Hunan province,
to December
2008††
Sj
businessman,
China
2005
student), aged
10–60 yr
Treated: PZQ at 40 mg/kg once
Adim village in Biase
and AS at 4 mg/kg daily for 3
Local Government
From August
Area of Cross River
2005 to June
Inyang-Etoh
schoolchildren,
PC, 2009‡‡
aged 4-20 yr
State in southeastern
consecutive days; Control: AS
Urine filtration (10 ml ×
placebo at 4 mg/kg for 3
2 specimens)
Sh
8 weeks
5/44
12/44
0.42 (0.16, 1.08)
RCT
T
8 weeks
17/88
24/89
0.72 (0.41, 1.24)
RCT
T
30-40 days
2/1362
4/112
0.04 (0.01, 0.22)
nRCT
P
2006
consecutive days and PZQ at
Nigeria
40mg/kg once
Bindo, Tsouke´, and
Nombake´le´, in the
Treated: PZQ at 40 mg/kg once
From October
Borrmann S,
and AS at 4 mg/kg/day×3;
Urine filtration (10 ml ×
children aged 5-13
province
2000 to February
2001‡‡
Sh
Control: PZQ at 40 mg/kg once,
yr
Moyen-Ogooue´,
2 specimens)
2001
rounded to the nearest half and
Gabon
AS placebo at 4 mg/kg/day×3
Treated: 300mg AS by 1-week
From July to
Xia CS,
Yangtze River region,
2000‡‡
China
Soldiers fighting
Immunological test for
interval and 1200mg PZQ
September in
against floods (age
Sj
schistosomal antigen and
divided into two doses; Control:
1998
not specified)
antibody
no drugs received
* Studies of PZQ efficacy for schistosomiasis control
† RCT denotes randomized controlled trial.
‡ nRCT denotes non-randomized controlled trial.
§Studies of AS efficacy for schistosomiasis control.
║ The two studies were separately included in this meta-analysis because of their different purpose from other studies of PZQ.
** Studies of AM efficacy for preventing schistosomiasis
†† Study of PZQ and AM in combination for treating schistosomiasis
‡‡ Studies of PZQ with AS in combination for schistosomiasis control
△ n/N=number diagnosed as positive over number of participants diagnosed
▲95% CI=95 percent confidence interval. Sh=Schistosoma haematobium, Sj=Schistosoma japonicum, P=Prevention, T=Treatment, yr=years old