Background
Methods
Study location and participants
Plasma samples preparation
Culturing and maintaining parasites
Measuring IgG to malaria merozoite antigens and schizont extract
Measurement of total IgG levels against VSA
Data analysis
Results
Study population characteristics
Characteristics | IFAa n (%) | MMNb n (%) | LNSc n (%) | P valued |
---|---|---|---|---|
Number of children | 145 (33.6) | 140 (32.4) | 147 (34.0) | 0.87 |
Male | 69 (47.6) | 61 (43.6) | 77 (52.4) | 0.32 |
Parasitaemia by microscopy at 6 months | 12 (8.3) | 5 (3.6) | 5 (3.4) | 0.10 |
Parasitaemia by RDTe at 6 months | 11 (7.6) | 10 (7.1) | 10 (6.8) | 0.97 |
Haemoglobin level at 6 months, mean ± SD, g/l | 102.7 ± 16.7 | 103.6 ± 16.0 | 103.7 ± 14.7 | 0.74 |
Anaemiaf at 6 months | 86 (59.3) | 81 (57.9) | 84 (57.1) | 0.93 |
Low socioeconomic status | 95 (65.5) | 75 (53.6) | 81 (55.1) | 0.08 |
Mother’s education below median | 79 (54.5) | 66 (47.1) | 80 (54.4) | 0.34 |
Characteristics | Included (432) | Excluded (349) | P valuea |
---|---|---|---|
Parasitaemia by microscopy | 22 (5.1) | 6 (1.7) | 0.01 |
Parasitaemia by RDTb | 31 (7.17) | 35 (10.0) | 0.15 |
Haemoglobin level, mean ± SD, g/l | 103.4 ± 15.8 | 101.4 ± 15.9 | 0.09 |
Anaemiac | 251 (58.1) | 250 (71.7) | < 0.0001 |
Low socioeconomic status | 251 (58.1) | 215 (61.6) | 0.32 |
Mother’s education below median | 225 (52.1) | 193 (55.3) | 0.37 |
The magnitude and prevalence of antibodies in different age groups
Antigen tested/Pfa isolate | Antibody levelb | P valued | Antibody seropositivityc (%) | P valuee | ||
---|---|---|---|---|---|---|
6 months | 18 months | 6 months | 18 months | |||
MSP1f | 0.97 [0.38, 2.89] | 2.80 [0.83, 6.35] | < 0.0001 | 128 (29.6) | 236 (54.6) | < 0.0001 |
MSP2g | 2.14 [1.31, 3.59] | 2.95 [0.92, 9.12] | < 0.0001 | 114 (26.3) | 117 (27.0) | 0.1004 |
EBA175h | 2.50 [1.44, 4.13] | 3.73 [2.19, 18.73] | < 0.0001 | 48 (11.1) | 51 (11.8) | 0.5764 |
Rh2A9i | 5.49 [2.01, 33.78] | 8.5 [4.68, 14.29] | 0.2829 | 14 (3.2) | 122 (28.2) | < 0.0001 |
Schizont | 1.92 [0.84, 6.99] | 3.32 [1.44, 6.89] | 0.2522 | 202 (46.7) | 233 (53.9) |
0.0314
|
E8B | 0.20 [0.03, 0.45] | 0 [0, 0.21] | < 0.0001 | 105 (25.2) | 34 (7.8) | < 0.0001 |
R29 | 0.18 [0, 0.63] | 0 [0, 0.11] | < 0.0001 | 37 (9.1) | 16 (3.7) |
0.0016
|
3D7 | 0.23 [0.01, 0.53] | 0 [0, 0.29] | < 0.0001 | 94 (22.2) | 36 (8.3) | < 0.0001 |
Association between nutrient supplementation and antibody seroprevalence in 6 months old children
Outcome | Number of children seropositive/total number of children | Comparison between LNS and IFA group | Comparison between LNS and MMN group | Comparison between MMN and IFA group | ||||||
---|---|---|---|---|---|---|---|---|---|---|
IFAa | MMNb | LNSc | P valued | OR (95% CI) | P valuee | OR (95% CI) | P valuee | OR (95% CI) | P valuee | |
MSP-1f 19kD | 43/145 (29.7%) | 44/140 (31.4%) | 41/147 (27.9%) | 0.806 | 0.96 (0.74, 1.23) | 0.739 | 0.84 (0.51, 1.40) | 0.512 | 1.07 (0.64, 1.77) | 0.804 |
Adjusted modelg | 0.97 (0.73, 1.28) | 0.808 | 0.86 (0.49, 1.49) | 0.583 | 1.01 (0.57, 1.76) | 0.981 | ||||
MSP-2h | 38/145 (26.2%) | 40/140 (28.6%) | 36/147 (24.5%) | 0.734 | 0.96 (0.73, 1.24) | 0.736 | 0.81 (0.48, 1.37) | 0.434 | 1.07 (0.63, 1.80) | 0.807 |
Adjusted modelg | 0.98 (0.74, 1.31) | 0.893 | 0.80 (0.45, 1.42) | 0.447 | 1.09 (0.62, 1.94) | 0.764 | ||||
EBA-175i | 15/145 (10.3%) | 20/140 (14.3%) | 13/147 (8.9%) | 0.320 | 0.92 (0.62, 1.35) | 0.663 | 0.58 (0.28, 1.22) | 0.152 | 1.34 (0.65, 2.76) | 0.426 |
Adjusted modelg | 0.96 (0.63, 1.47) | 0.857 | 0.54 (0.25, 1.18) | 0.120 | 1.53 (0.70, 3.37) | 0.289 | ||||
Rh2A9j | 9/145 (6.21%) | 3/140 (2.14%) | 2/147 (1.4%) |
0.044
| 0.46 (0.21, 0.99) |
0.047
| 0.63 (0.10, 3.83) | 0.616 | 0.33 (0.09, 1.23) | 0.098 |
Adjusted modelg | 0.48 (0.21, 1.06) | 0.070 | 0.79 (0.12, 5.42) | 0.814 | 0.34 (0.09, 1.30) | 0.114 | ||||
Schizont extract | 68/145 (46.9%) | 67/140 (47.86%) | 67/147 (45.6%) | 0.927 | 0.97 (0.77, 1.23) | 0.821 | 0.91 (0.57, 1.45) | 0.699 | 1.07 (0.67, 1.71) | 0.774 |
Adjusted modelg | 0.91 (0.70, 1.18) | 0.468 | 0.89 (0.53, 1.51) | 0.677 | 0.97 (0.58, 1.63) | 0.923 | ||||
VSAk of E8B parasite line | 31/145 (21.4%) | 39/140 (27.9%) | 35/147 (23.8%) | 0.437 | 1.09 (0.83, 1.43) | 0.552 | 0.80 (0.47, 1.36) | 0.402 | 1.52 (0.88, 2.64) | 0.134 |
Adjusted modelg | 1.01 (0.74, 1.37) | 0.957 | 0.70 (0.38, 1.26) | 0.233 | 1.55 (0.86, 2.80) | 0.146 | ||||
VSA of R29 parasite line | 14/145 (9.7%) | 12/140 (8.6%) | 11/147 (7.5%) | 0.803 | 0.86 (0.57, 1.30) | 0.470 | 0.83 (0.35, 1.94) | 0.659 | 0.88 (0.39, 1.98) | 0.756 |
Adjusted modelg | 0.76 (0.48, 1.20) | 0.234 | 0.69 (0.27, 1.74) | 0.427 | 0.91 (0.38, 2.14) | 0.822 | ||||
VSA of 3D7 parasite line | 27/145 (18.6%) | 33/140 (23.6%) | 34/147 (23.1%) | 0.530 | 1.16 (0.87, 1.54) | 0.313 | 0.97 (0.56, 1.69) | 0.924 | 1.35 (0.76, 2.41) | 0.301 |
Adjusted modelg | 1.04 (0.75, 1.43) | 0.829 | 0.89 (0.48, 1.65) | 0.721 | 1.24 (0.66, 2.31) | 0.501 |
Association between nutrient supplementation and antibody seroprevalence in 18 months old children
Outcome | Number of children seropositive/total number of children | Comparison between LNS and IFA group | Comparison between LNS and MMN group | Comparison between MMN and IFA group | ||||||
---|---|---|---|---|---|---|---|---|---|---|
IFAa | MMNb | LNSc | P valued | OR (95% CI) | P valuee | OR (95% CI) | P valuee | OR (95% CI) | P valuee | |
MSP-1 19kDf | 82/145 (56.5%) | 72/140 (51.4%) | 82/147 (55.7%) | 0.646 | 0.98 (0.78, 1.24) | 0.895 | 1.19 (0.75, 1.90) | 0.460 | 0.83 (0.52, 1.33) | 0.444 |
Adjusted modelg | 0.98 (0.77, 1.25) | 0.865 | 1.10 (0.67, 1.82) | 0.708 | 0.80 (0.48, 1.34) | 0.398 | ||||
MSP-2h | 42/145 (28.9%) | 39/140 (27.8%) | 36/147 (24.4%) | 0.669 | 0.88 (0.66, 1.16) | 0.359 | 0.79 (0.45, 1.40) | 0.428 | 0.95 (0.54, 1.66) | 0.851 |
Adjusted modelg | 0.82 (0.60, 1.13) | 0.226 | 0.63 (0.34, 1.18) | 0.149 | 0.96 (0.53, 1.76) | 0.906 | ||||
EBA-175i | 19/145 (13.1%) | 14/140 (10.0%) | 18/147 (12.2%) | 0.705 | 0.99 (0.67, 1.43) | 0.967 | 1.59 (0.69, 3.63) | 0.273 | 0.61 (0.27, 1.40) | 0.242 |
Adjusted modelg | 0.91 (0.60, 1.37) | 0.642 | 1.19 (0.48, 2.95) | 0.710 | 0.65 (0.27, 1.58) | 0.342 | ||||
Rh2A9j | 42/145 (28.9%) | 40/140 (28.5%) | 40/147 (27.2%) | 0.941 | 0.96 (0.74, 1.24) | 0.739 | 0.93 (0.56, 1.57) | 0.797 | 0.96 (0.57, 1.61) | 0.880 |
Adjusted modelg | 0.96 (0.73, 1.26) | 0.763 | 0.84 (0.48, 1.47) | 0.540 | 0.98 (0.56, 1.71) | 0.931 | ||||
Schizont extract | 73/145 (50.3%) | 78/140 (55.7%) | 82/147 (55.7%) | 0.568 | 1.12 (0.89, 1.40) | 0.352 | 1.003 (0.63, 1.60) | 0.991 | 1.24 (0.78, 1.99) | 0.365 |
Adjusted modelg | 1.18 (0.90, 1.54) | 0.223 | 0.87 (0.52, 1.46) | 0.600 | 1.40 (0.83, 2.35) | 0.208 | ||||
VSAk of E8B parasite line | 14/145 (9.6%) | 11/140 (7.9%) | 9/147 (6.1%) | 0.534 | 0.78 (0.51, 1.21) | 0.266 | 0.76 (0.30, 1.89) | 0.554 | 0.78 (0.33, 1.83) | 0.562 |
Adjusted modelg | 0.80 (0.50, 1.29) | 0.360 | 0.72 (0.27, 1.89) | 0.504 | 0.75 (0.29, 1.93) | 0.557 | ||||
VSA of R29 parasite line | 7/145 (4.8%) | 5/140 (3.5%) | 4/147 (2.7%) | 0.632 | 0.74 (0.40, 1.39) | 0.351 | 0.76 (0.20, 2.87) | 0.680 | 0.72 (0.22, 2.32) | 0.582 |
Adjusted modelg | 0.79 (0.39, 1.60) | 0.506 | 0.95 (0.22, 4.07) | 0.946 | 0.85 (0.23, 3.14) | 0.808 | ||||
VSA of 3D7 parasite line | 15/145 (10.3%) | 11/140 (7.8%) | 10/147 (6.8%) | 0.532 | 0.80 (0.52, 1.21) | 0.283 | 0.86 (0.35, 2.08) | 0.732 | 0.85 (0.37, 1.97) | 0.710 |
Adjusted modelg | 0.74 (0.46, 1.22) | 0.241 | 0.55 (0.20, 1.52) | 0.250 | 1.11(0.43, 2.83) | 0.830 |
Association between nutrient supplementation and antibody levels in 6 month old children
Outcome | Antibody levels by study group, median (IQR) | LNS and IFA | LNS and MMN | MMN and IFA | ||||||
---|---|---|---|---|---|---|---|---|---|---|
IFAa | MMNb | LNSc | P valued | Coeff (95% CI) | P valuee | Coeff (95% CI) | P valuee | Coeff (95% CI) | P valuee | |
Number of participants | N = 145 | N = 140 | N = 147 | |||||||
MSP-1 19kDf | 0.81 (0.38, 2.45) | 1.13 (0.37, 3.02) | 1.03 (0.40, 0.72) | 0.430 | 1.03 (0.85, 1.25) | 0.773 | 0.88 (0.60, 1.28) | 0.498 | 1.15 (0.78, 1.70) | 0.467 |
Adjusted modelg | 1.06 (0.87, 1.30) | 0.542 | 0.94 (0.63, 1.39) | 0.755 | 1.11 (0.75, 1.64) | 0.614 | ||||
MSP-2h | 2.36 (1.43, 3.57) | 2.02 (1.33, 4.13) | 1.98 (1.19, 3.27) | 0.313 | 0.99 (0.87, 1.12) | 0.833 | 0.87 (0.66, 1.15) | 0.334 | 1.08 (0.82, 1.42) | 0.592 |
Adjusted modelg | 0.99 (0.86, 1.13) | 0.834 | 0.88 (0.66, 1.19) | 0.417 | 1.06 (0.80, 1.40) | 0.703 | ||||
EBA-175i | 2.37 (1.34, 3.85) | 2.60 (1.50, 4.50) | 2.50 (1.42, 4.02) | 0.335 | 1.03 (0.92, 1.14) | 0.610 | 0.91 (0.74, 1.13) | 0.390 | 1.14 (0.91, 1.43) | 0.240 |
Adjusted modelg | 1.04 (0.93, 1.16) | 0.502 | 0.86 (0.69, 1.08) | 0.195 | 1.24 (0.99, 1.54) | 0.061 | ||||
Rh2A9j | 4.93 (1.53,18.55) | 5.97 (2.12, 39.95) | 5.86 (2.45, 33.70) | 0.245 | 1.11 (0.89, 1.38) | 0.364 | 1.00 (0.66, 1.53) | 0.986 | 1.23 (0.77, 1.95) | 0.382 |
Adjusted modelg | 1.08 (0.85, 1.37) | 0.532 | 0.99 (0.63, 1.57) | 0.990 | 1.16 (0.70, 1.93) | 0.559 | ||||
Schizont extract | 1.85 (0.80, 4.93) | 2.11 (0.82, 8.08) | 2.06 (0.89, 7.23) | 0.569 | 1.07 (0.89, 1.28) | 0.465 | 0.97 (0.68, 1.40) | 0.875 | 1.21 (0.85, 1.73) | 0.282 |
Adjusted modelg | 1.06 (0.89, 1.27) | 0.481 | 0.88 (0.61, 1.26) | 0.475 | 1.30 (0.91, 1.85) | 0.155 | ||||
VSAk of E8B parasite line | 0.17 (0.03, 0.46) | 0.26 (0.06, 0.47) | 0.19 (0.02, 0.44) | 0.453 | 1.04 (0.87, 1.24) | 0.688 | 1.00 (0.70, 1.42) | 0.995 | 1.07 (0.76, 1.51) | 0.709 |
Adjusted modelg | 1.00 (0.82, 1.21) | 0.996 | 0.99 (0.68, 1.47) | 0.987 | 1.02 (0.71, 1.47) | 0.925 | ||||
VSA of R29 parasite line | 0.16 (0, 0.59) | 0.25 (0, 0.81) | 0.12 (0, 0.55) | 0.452 | 0.93 (0.75, 1.15) | 0.496 | 0.70 (0.46, 1.07) | 0.098 | 1.21 (0.80, 1.82) | 0.358 |
Adjusted modelg | 0.91 (0.73, 1.13) | 0.407 | 0.63 (0.41, 0.97) | 0.063 | 1.30 (0.88, 1.91) | 0.187 | ||||
VSA of 3D7 parasite line | 0.19 (0.01, 0.48) | 0.24 (0.02, 0.64) | 0.26 (0.01,0.59) | 0.544 | 1.19 (0.98, 1.46) | 0.081 | 1.06 (0.72, 1.55) | 0.774 | 1.34 (0.91, 1.99) | 0.138 |
Adjustedg | 1.13 (0.92, 1.39) | 0.245 | 1.05 (0.69, 1.61) | 0.810 | 1.18 (0.81, 1.73) | 0.382 |
Association between nutrient supplementation and antibody levels in 18 month old children
Outcome | Antibody levels by study group, median (IQR) | LNS and IFA | LNS and MMN | MMN and IFA | ||||||
---|---|---|---|---|---|---|---|---|---|---|
IFAa | MMNb | LNSc | P valued | Coeff (95% CI) | P valuee | Coeff (95% CI) | P valuee | Coeff (95% CI) | P valuee | |
Number of participants | N = 145 | N = 140 | N = 147 | |||||||
MSP-1 19kDf | 2.59 (0.83, 6.09) | 2.95 (0.75, 6.37) | 2.64 (1.00, 6.59) | 0.877 | 1.05 (0.87, 1.26) | 0.603 | 1.02 (0.70, 1.49) | 0.909 | 1.09 (0.75, 1.58) | 0.663 |
Adjusted modelg | 1.04 (0.86, 1.26) | 0.681 | 0.97 (0.65, 1.42) | 0.857 | 1.07 (0.72, 1.58) | 0.745 | ||||
MSP-2h | 3.10 (0.97, 9.81) | 2.74 (0.64, 8.57) | 3.21 (1.38, 9.05) | 0.334 | 1.01 (0.83, 1.22) | 0.938 | 1.12 (0.77, 1.64) | 0.548 | 0.92 (0.61, 1.38) | 0.683 |
Adjusted modelg | 0.99 (0.82, 1.22) | 0.984 | 1.17 (0.79, 1.74) | 0.434 | 0.86 (0.56, 1.31) | 0.477 | ||||
EBA-175i | 4.06 (2.32, 19.29) | 3.39 (1.88, 20.11) | 3.62 (2.29, 18.47) | 0.425 | 0.94 (0.80, 1.10) | 0.427 | 0.99 (0.07, 1.38) | 0.973 | 0.89 (0.64, 1.24) | 0.489 |
Adjusted modelg | 0.90 (0.77, 1.06) | 0.217 | 0.98 (0.70, 1.36) | 0.894 | 0.84 (0.60, 1.17) | 0.294 | ||||
Rh2A9j | 8.96 (4.66,13.50) | 8.38 (4.77, 14.46) | 8.76 (4.86,15.17) | 0.952 | 1.02 (0.92, 1.12) | 0.723 | 1.02 (0.85, 1.22) | 0.848 | 1.02 (0.83, 1.24) | 0.869 |
Adjusted modelg | 1.03 (0.93, 1.14) | 0.566 | 1.03 (0.84, 1.25) | 0.790 | 1.05 (0.85, 1.29) | 0.679 | ||||
Schizont extract | 3.13 (1.69, 6.19) | 3.94 (1.40, 8.18) | 2.96 (1.28, 6.35) | 0.407 | 0.94 (0.80, 1.10) | 0.433 | 0.79 (0.56, 1.12) | 0.185 | 1.10 (0.80, 1.49) | 0.564 |
Adjusted modelg | 0.91 (0.78, 1.09) | 0.332 | 0.78 (0.54, 1.12) | 0.179 | 1.10 (0.80, 1.51) | 0.559 | ||||
VSAk of E8B parasite line | 0.00 (0.00, 0.27) | 0.00 (0.00, 0.25) | 0.00 (0.00, 0.12) |
0.043
| 0.82 (0.60, 1.11) | 0.189 | 0.62 (0.35, 1.10) | 0.099 | 0.99 (0.60, 1.61) | 0.953 |
Adjusted modelg | 0.83 (0.61, 1.14) | 0.250 | 0.61 (0.34, 1.11) | 0.102 | 0.95 (0.60, 1.51) | 0.818 | ||||
VSA of R29 parasite line | 0.00 (0.00, 0.07) | 0.00 (0.00, 0.24) | 0.00 (0.00, 0.004) | 0.223 | 0.86 (0.58, 1.29) | 0.469 | 0.89 (0.39, 1.98) | 0.756 | 0.85 (0.39, 1.84) | 0.671 |
Adjusted modelg | 0.82 (0.53, 1.28) | 0.382 | 0.73 (0.32, 1.70) | 0.465 | 0.95 (0.43, 2.06) | 0.889 | ||||
VSA of 3D7 parasite line | 0.002 (0.00, 0.39) | 0.00 (0.00, 0.24) | 0.00 (0.00, 0.28) | 0.150 | 1.05 (0.78, 1.43) | 0.731 | 1.18 (0.64, 2.19) | 0.592 | 0.98 (0.56, 1.71) | 0.930 |
Adjustedg | 1.14 (0.82, 1.59) | 0.441 | 1.11 (0.55, 2.25) | 0.765 | 0.94 (0.50, 1.75) | 0.834 |