Background
Methods
Ethics approval
Study participants
Malariometric indices
Parasite and cell cultures
Assays of IgG to schizont extract, merozoite antigens and measles haemagglutinin
Phagocytosis of infected erythrocytes
Antibody responses during pregnancy
Statistical analysis
Results
Patient characteristics
Characteristic | Single course of CQ and SP treatment (n = 304) | Three courses of SP and AZ treatment (n = 277) |
P-value |
---|---|---|---|
Age, years | 24.0 (21.0–28.0) | 24.0 (21.0–28.0) | 0.2 |
Weight at enrolment, kg | 55.0 (50.0–59.0) | 53.0 (49.0–59.0) | 0.6 |
MUAC at enrolment, cm | 23.0 (22.0–25.0) | 23.0 (22.0–25.0) | 0.5 |
Gravidity | 0.4 | ||
Gravida 1, n (%) | 108 (35.5) | 92 (33.2) | |
Gravida 2, n (%) | 91 (29.9) | 88 (31.8) | |
Gravida 3, n (%) | 105 (34.5) | 97 (35.0) | |
Overall Bed net use | 0.4 | ||
No, n (%) | 2 (0.7) | 0 (0.0) | |
Intermittent, n (%) | 89 (29.3) | 82 (29.6) | |
Regular, n (%) | 213 (70.1) | 195 (70.4) | |
Ethnicity | 0.5 | ||
Madang/Morobe | 194 (63.8) | 193 (69.7) | |
Sepik | 57 (18.8) | 41 (14.8) | |
Highland | 26 (8.6) | 19 (6.9) | |
Others | 27 (8.9) | 24 (8.7) | |
Residence | 0.9 | ||
Urban | 51 (16.8) | 44 (16.0) | |
Peri-urban | 59 (19.5) | 50 (18.1) | |
Rural | 181 (59.7) | 170 (61.8) | |
Migrant | 12 (4.0) | 11 (4.0) | |
Light microscopy (P. falciparum)
| |||
Enrolment (peripheral blood) | 20 (6.6) | 15 (5.4) | 0.5 |
Delivery (peripheral blood) | 7 (2.3) | 5 (1.8) | 0.7 |
Delivery (placental blood) | 7 (2.3) | 4 (1.4) | 0.2 |
qPCR (P. falciparum)
| |||
Enrolment (peripheral blood) | 31 (10.2) | 24 (8.7) | 0.8 |
Delivery (peripheral blood) | 14 (4.6) | 8 (2.9) | 0.1 |
Delivery (placental blood) | 7 (2.3) | 1 (0.3) | 0.1 |
Placental histology | 0.1 | ||
Uninfected | 171 (81.8) | 170 (81.0) | |
Infecteda
| 38 (18.2) | 40 (19.1) |
Antibody to recombinant antigens
Opsonizing antibody to infected erythrocytes
Changes in individual antibody responses by treatment arm between enrolment and delivery
Variable (n) | SP + CQ control arm (n = 304) | SP + AZ intervention arm (n = 277) |
P value |
---|---|---|---|
IgG to schizont extract | 0.7 | ||
Decrease, n (%) | 70 (23.2) | 67 (24.3) | |
No change, n (%) | 198 (65.6) | 184 (66.8) | |
Increase, n (%) | 34 (11.3) | 25 (9.1) | |
IgG to MSP2 | 0.6 | ||
Decrease, n (%) | 63 (20.9) | 49 (17.8) | |
No change, n (%) | 217 (71.9) | 203 (73.6) | |
Increase, n (%) | 22 (7.3) | 24 (8.7) | |
IgG to MSP3 | 0.8 | ||
Decrease, n (%) | 55 (18.2) | 53 (19.1) | |
No change, n (%) | 220 (72.8) | 203 (73.3) | |
Increase, n (%) | 27 (8.9) | 21 (7.6) | |
IgG to PfRh2 |
0.05
| ||
Decrease, n (%) |
34 (11.2)
|
39 (14.1)
| |
No change, n (%) |
244 (80.5)
|
228 (82.3)
| |
Increase, n (%) |
25 (8.3)
|
10 (3.6)
| |
Opsonizing IgG to E8B-ICAM |
0.004
| ||
Decrease, n (%) |
72 (23.9)
|
60 (21.7)
| |
No change, n (%) |
140 (46.5)
|
164 (59.2)
| |
Increase, n (%) |
89 (29.6)
|
53 (19.1)
| |
Opsonizing IgG to CS2 |
0.03
| ||
Decrease, n (%) |
39 (13.0)
|
47 (17.0)
| |
No change, n (%) |
226 (75.1)
|
180 (65.2)
| |
Increase, n (%) |
36 (12.0)
|
49 (17.8)
|
Effect of treatment arm on antibodies at delivery: adjusted analysis
Variables | IgG schizont extract | IgG PfRh2 | IgG MSP2 | IgG MSP3 | Opsonizing IgG E8B-ICAM | Opsonizing IgG CS2 | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Coeff (95 % Cl) |
p
| Coeff (95 % Cl) |
p
| Coeff (95 % Cl) |
p
| Coeff (95 % Cl) |
p
| Coeff (95 % Cl) |
p
| Coeff (95 % Cl) |
p
| |
Intervention arma
| −3.0 (−13.4, 7.4) | 0.6 | −3.6 (−10.9, 3.7) | 0.3 | −7.4 (−17.9, 3.1) | 0.2 | 2.6 (−7.0, 12.2) | 0.6 | 1.0 (−14.2, 16.2) | −7.4 (−19.4, 4.5) | 0.2 | |
Gravidity | ||||||||||||
1 | ||||||||||||
2 | −2.0 (−8.3, 4.3) | 0.5 | −4.6 (−9.1, 0.2) | 0.06 | 1.0 (−5.44, 7.42) | 0.8 | −0.7 (−6.6, 5.1) | 0.8 |
50.3 (42.8, 57.9)
|
<0.0001
|
9.3 (2.5,16.1)
|
0.007
|
3 | 1.6 (−4.5, 7.6) | 0.6 | −0.5 (−4.8, 3.8) | 0.8 | 1.9 (−4.3, 8.1) | 0.6 | 5.72 (−0.04, 11.4) | 0.06 |
32.8 (25.6, 40.1)
|
<0.0001
|
24.3 (17.9, 30.8)
|
<0.0001
|
Overall bed net use | ||||||||||||
No | ||||||||||||
Intermittent | −1.8 (−6.0, 2.4) | 0.4 | −0.5 (−3.4, 2.5) | 0.8 | −1.6 (−5.9, 2.7) | 0.5 | 0.3 (−5.6, 10.5) | 0.9 | 1.2 (−3.8, 6.2) | 0.6 | −2.6 (−7.2, 1.9) | 0.3 |
Regular | −13.0 (−45.2, 19.2) | 0.4 | −5.3 (−28.1, 17.6) | 0.7 | −12.0 (−45.0, 20.9) | 0.5 | −2.5 (−32.7, 27.6) | 0.9 | 25.4 (−13.1, 63.9) | 0.2 | −10.6 (−45.0, 23.8) | 0.6 |
Residence | ||||||||||||
Urban | ||||||||||||
Peri-urban | 0.3 (−8.4, 8.8) | 0.9 | −1.3 (−7.1, 5.9) | 0.7 | 1.5 (−7.2, 10.2) | 0.7 | 2.0 (−5.9, 10.0) | 0.6 | 2.2 (−10.4, 14.9) | 0.4 | −1.9 (−11.8, 7.9) | 0.7 |
Rural |
8.6 (1.2, 15.9)
|
0.02
| 5.0 (−0.2, 10.0) | 0.06 |
8.5 (1.2, 16.0)
|
0.02
|
8.5 (1.7, 15.2)
|
0.01
| −4.1 (−14.8, 6.6) | 0.7 | −0.4 (−8.8, 8.0) | 0.9 |
Migrant | 13.0 (−1.3, 27.3) | 0.07 | −0.1 (−10.1, 10.0) | 0.9 | 13.3 (−1.1, 27.7) | 0.07 | −1.1 (−14.3, 12.1) | 0.9 | 6.4 (−14.4, 27.3) | 0.5 | 2.7 (−13.7, 19.1) | 0.8 |
Ethnicity | ||||||||||||
Madang/Morobe | ||||||||||||
Sepik | −4.7 (−11.0, 11.0) | 0.2 | 0.3 (−4.7, 5.2) | 0.9 | −5.4 (−12.6, 1.7) | 0.1 | 1.7 (−4.8, 8.2) | 0.6 | −1.6 (−11.9, 8.7) | 0.8 | 4.7 (−12.8, 3.4) | 0.2 |
Highlands |
−12.3 (−21.9, −2.6)
|
0.01
| −0.5 (−7.2, 6.2) | 0.9 |
−10.9 (−20.6, −1.2)
|
0.03
| −1.0 (−9.9, 7.7) | 0.82 | −3.7 (−17.7, 10.4) | 0.8 | −6.4 (−17.4, 4.7) | 0.4 |
Others | −4.4 (−13.9, 5.2) | 0.4 | −2.5 (−9.3, 4.2) | 0.5 | −7.5 (−17.0, 2.2) | 0.1 | 1.3 (−7.5, 10.1) | 0.8 | −2.4 (−16.5, 11.7) | 0.9 | −2.6 (13.5, 8.3) | 0.6 |
SP-AZ-graviditya
| ||||||||||||
1 | ||||||||||||
2 | −5.6 (−14.77, 3.56) | 0.2 | 7.1 (0.57, −13.56) | 0.1 | −6.5 (−15.90, 2.87) | 0.2 | −3.5 (−12.10, 5.06) | 0.4 | −6.5 (−17.48, 4.50) | 0.3 | −0.3 (−10.1, 9.5) | 1.0 |
3 | −5.5 (−14.3, 5.6) | 0.3 | 1.2 (−5.1, 7.5) | 0.7 | −7.6 (−16.7, 1.5) | 0.1 | −7.5 (−15.8, 0.8) | 0.08 | −5.6 (−16.2, 5.0) | 0.3 | 0.01 (−9.5, 9.5) | 1.0 |
SP-AZ-residencea
| ||||||||||||
Urban | ||||||||||||
Peri-urban | 5.0 (−7.7, 17.6) | 0.4 | 2.1 (−6.7, 11.0) | 0.6 | 2.9 (−9.9, 15.7) | 0.7 | −1.1 (−12.8, 10.6) | 0.9 | −8.2 (−26.8, 10.3) | 0.4 | 8.4 (−6.1, 23.0) | 0.3 |
Rural | 2.7 (−8.2, 13.6) | 0.6 | 2.7 (−5.0, 10.3) | 0.5 | 7.5 (−3.5, 18.5) | 0.2 | −3.9 (−14.0, 6.1) | 0.4 | −2.8 (−18.7, 13.1) | 0.7 | 7.7 (−4.8, 2.2) | 0.2 |
Migrant | 1.2 (−19.5, 21.9) | 0.9 | 7.2 (−7.3, 21.7) | 0.3 | −5.63 (−26.55, 15.29) | 0.6 | 3.7 (−15.43, 22.78) | 0.7 | −17.6 (−47.8, 12.6) | 0.3 | 0.5 (−23.3, 24.2) | 1.0 |
SP-AZ-ethnicitya
| ||||||||||||
Madang/Morobe | ||||||||||||
Sepik | 0.02 (−11.0, 11.00) | 1.0 | 1.9 (−5.9, 9.6) | 0.6 | 5.1 (−6.0, 16.2) | 0.4 | −4.6 (−14.7, 5.6) | 0.4 | −1.6 (−17.7, 14.4) | 0.8 | 11.5 (−1.1, 24.1) | 0.07 |
Highlands | −1.0 (−16.0, 14.0) | 0.9 | −1.3 (−11.8, 9.2) | 0.8 | 1.6 (−13.6, 16.7) | 0.8 | −5.53 (−19.4, 8.3) | 0.4 | −2.8 (−24.7, 19.1) | 0.8 | 6.7 (−10.6, 23.9) | 0.5 |
Others | 0.5 (−14.2, 13.1) | 0.9 | 3.3 (−6.3, 12.9) | 0.5 | 6.6 (−7.2, 20.5) | 0.4 | −3.6 (−16.2, 9.0) | 0.6 | −1.0 (−21.1, 19.2) | 0.9 | −3.6 (−19.3, 12.1) | 0.7 |