Background
Methods
Ethics statement
Study sites
Burkina Faso: Balonghin–Sapone
Ghana: Asutsuare–Damgbe West
Study design, sample collection and follow-up
Malaria antigens
Antigen-specific antibody measurement
Statistical analysis
Results
Plasmodium falciparum infection in the study cohorts
Characteristics | Burkina Faso | Ghana | ||||||||
---|---|---|---|---|---|---|---|---|---|---|
N | Cumulative incidence (95 % CI)a
| Child-months at risk | Malaria cases | Rate per 100 child-months (95 % CI)b
| N | Cumulative incidence (95 %CI)a
| Child-months at risk | Malaria cases | Rate per 100 child-months (95 % CI)c
| |
Age group (months) | ||||||||||
6–23 | 99 | 83.7 % (75.7, 90.2) | 1071.2 | 191 | 17.8 (15.9, 19.7) | 16 | 43.8 % (23.8, 70.5) | 152.7 | 7 | 4.6 (2.2, 9.6) |
24–35 | 87 | 82.5 % (73.7, 89.7) | 947.0 | 176 | 18.6 (16.6, 20.6) | 54 | 5.6 % (1.8, 16.2) | 509.8 | 3 | 0.6 (0.2, 1.8) |
36–47 | 90 | 69.7 % (60, 78.8) | 982.0 | 120 | 12.2 (10, 14.4) | 54 | 5.6 % (1.8, 16.2) | 510.8 | 3 | 0.6 (0.2, 1.8) |
48–72 | 78 | 42.4 % (32.3, 54.2) | 851.0 | 52 | 6.1 (3.8, 8.4) | 85 | 5.9 % (2.5, 13.6) | 802.1 | 6 | 0.7 (0.3, 1.7) |
Baseline parasitaemia status | ||||||||||
Negative | 132 | 82.6 % (75.7, 88.5) | 1432.9 | 249 | 17.4 (15.8, 19) | 203 | 8.9 % (5.7, 13.7) | 1919.0 | 19 | 1.0 (0.6, 1.6) |
Positive | 219 | 63.8 % (57.4, 70.2) | 2386.5 | 288 | 12.1 (10.6, 13.6) | 6 | 0 % | 0 | 0 | – |
GLURP R2 IgG serological status | ||||||||||
Non-responder | 230 | 80 % (74.6, 84.9) | 2499.5 | 404 | 16.2 (14.9, 17.4) | 167 | 9 % (5.5, 14.5) | 1577.0 | 16 | 1.0 (0.6, 1.7) |
Responder | 124 | 52.6 % (44, 61.7) | 1351.7 | 135 | 10 (7.9, 12.1) | 42 | 7 % (2.4, 20.5) | 398.3 | 3 | 0.8 (0.2, 2.3) |
MSP1 hybrid IgG serological status | ||||||||||
Non-responder | 272 | 75.1 % (69.8, 80.2) | 2953.8 | 448 | 15.2 (13.9, 16.4) | 166 | 8.4 % (5.1, 13.8) | 1567.7 | 15 | 1.0 (0.6, 1.6) |
Responder | 82 | 56.1 % (45.8, 67) | 897.4 | 91 | 10.1 (7.7, 12.6) | 43 | 9.3 % (3.6, 22.9) | 407.6 | 4 | 1.0 (0.4, 2.6) |
AS202.11 IgG serological status | ||||||||||
Non-responder | 313 | 71 % (65.9, 75.9) | 3406.2 | 486 | 14.3 (13.1, 15.5) | 184 | 9.2 % (5.9, 14.4) | 1738.5 | 18 | 1.0 (0.7, 1.6) |
Responder | 41 | 68.1 % (53.4, 81.9) | 444.9 | 53 | 11.9 (9, 14.8) | 25 | 4 % (0.6, 25.2) | 236.8 | 1 | 0.4 (0.1, 3.0) |
Total | 354 | 70.7 % (65.8, 75.3) | 3851.2 | 539 | 14 (12.9, 15.1) | 209 | 8.6 % (5.5, 13.3) | 1975.3 | 19 | 1.0 (0.6, 1.5) |
Relationship between antibody levels and age of study participants
Burkina Faso | Ghana | ||||||
---|---|---|---|---|---|---|---|
Antibody | Antigen | Coefficient (95 % CI) |
p value | Adjusted R2
| Coefficient (95 % CI) |
p value | Adjusted R2
|
IgG | GLURP R2 | 6.69 (4.10, 10.91) | <0.0001 | 0.14 | 2.82 (0.97, 8.23) | 0.057 | 0.013 |
MSP1-hybrid | 9.28 (4.75, 18.13) | <0.0001 | 0.11 | 1.56 (4.10, 5.93) | 0.51 | 0 | |
AS202.11 | 2.23 (1.33, 4.28) | 0.0037 | 0.021 | 0.86 (0.35, 2.14) | 0.73 | 0 | |
IgG1 | GLURP R2 | 5.55 (2.91, 10.60) | <0.0001 | 0.069 | 3.09 (1.00, 9.61) | 0.051 | 0.014 |
MSP1-hybrid | 2.08 (0.63, 6.83) | 0.23 | 0.0013 | 0.71 (0.37, 1.36) | 0.3 | 0.0004 | |
IgG2 | GLURP R2 | 10.37 (6.00, 17.94) | <0.0001 | 0.16 | 2.39 (0.70, 8.12) | 0.16 | 0.0047 |
MSP1-hybrid | 21.88 (6.98, 68.57) | <0.0001 | 0.072 | 1.00 (0.28, 3.66) | 1 | 0 | |
IgG3 | GLURP R2 | 6.16 (4.02, 9.43) | <0.0001 | 0.16 | 2.93 (1.20, 7.16) | 0.019 | 0.021 |
MSP1-hybrid | 2.81 (1.85, 4.26) | <0.0001 | 0.061 | 3.09 (0.90, 1.06) | 0.073 | 0.011 | |
IgG4 | GLURP R2 | 2.76 (1.62, 4.71) | 0.00021 | 0.036 | 8.81 (0.94, 82.24) | 0.056 | 0.013 |
MSP1-hybrid | 1.88 (0.96, 3.68) | 0.064 | 0.0069 | 3.42 (0.62, 18.77) | 0.16 | 0.005 | |
IgM | GLURP R2 | 36.64 (14.83, 90.52) | <0.0001 | 0.15 | 35 (5.01, 248.77) | 0.0004 | 0.054 |
MSP1-hybrid | 8.76 (3.18, 24.12) | <0.0001 | 0.045 | 7.62 (1.05, 55.45) | 0.045 | 0.015 | |
AS202.11 | 3.60 (1.75, 7.41) | 0.00055 | 0.031 | 6.86 (1.20, 3.93) | 0.031 | 0.018 |
Antigen-specific antibodies in relation to risk of clinical malaria
Antibody | Antigens | Burkina Faso | Ghana | Overall | ||||||
---|---|---|---|---|---|---|---|---|---|---|
Crude HR (95 % CI) | HR adjusted for age (95 % CI)a
|
p value for adjusted HR | Crude HR (95 % CI) | HR adjusted for age (95 % CI)a
|
p value for adjusted HR | Crude HR (95 % CI)b
| HR adjusted for age (95 % CI)b
|
p value for adjusted HR | ||
IgG | GLURP R2 | 0.75 (0.66, 0.85) | 0.84 (0.73, 0.97) | 0.01 | 0.77 (0.44, 1.34) | 0.73 (0.41, 1.30) | 0.28 | 0.75 (0.66, 0.85) | 0.85 (0.74, 0.97) | 0.02 |
MSP1-hybrid | 0.73 (0.61, 0.87) | 0.83 (0.70, 0.98) | 0.03 | 1.40 (0.64, 3.08) | 1.19 (0.57, 2.50) | 0.64 | 0.75 (0.63, 0.89) | 0.85 (0.72, 1.01) | 0.06 | |
AS202.11 | 0.93 (0.82, 1.05) | 0.97 (0.87, 1.09) | 0.65 | 1.37 (0.89, 2.11) | 1.15 (0.85, 1.56) | 0.38 | 0.93 (0.82, 1.06) | 0.98 (0.88, 1.10) | 0.76 | |
IgG1 | GLURP R2 | 0.86 (0.73, 1.00) | 0.97 (0.82, 1.14) | 0.68 | 0.93 (0.47, 1.85) | 0.91 (0.45, 1.86) | 0.8 | 0.86 (0.74, 1.00) | 0.97 (0.83, 1.14) | 0.69 |
MSP1-hybrid | 0.96 (0.75, 1.23) | 0.96 (0.77, 1.21) | 0.76 | 1.22 (0.78, 1.92) | 1.03 (0.67, 1.58) | 0.91 | 1.00 (0.80, 1.25) | 1.01 (0.82, 1.24) | 0.94 | |
IgG2 | GLURP R2 | 0.74 (0.65, 0.83) | 0.85 (0.75, 0.96) | 0.01 | 1.45 (0.71, 2.97) | 1.24 (0.64, 2.43) | 0.52 | 0.74 (0.66,0.84) | 0.86 (0.76, 0.98) | 0.02 |
MSP1-hybrid | 0.73 (0.59, 0.91) | 0.87 (0.70, 1.08) | 0.2 | 1.19 (0.47, 3.01) | 1.17 (0.51, 2.67) | 0.72 | 0.74 (0.60, 0.92) | 0.89 (0.72, 1.10) | 0.27 | |
IgG3 | GLURP R2 | 0.73 (0.66, 0.81) | 0.81 (0.73, 0.90) | <0.0001 | 0.48 (0.25, 0.93) | 0.54 (0.30, 0.98) | 0.04 | 0.73 (0.66, 0.81) | 0.81 (0.73, 0.90) | <0.0001 |
MSP1-hybrid | 0.85 (0.78, 0.93) | 0.91 (0.84, 0.99) | 0.04 | 0.82 (0.38, 1.77) | 0.83 (0.33, 2.08) | 0.69 | 0.86 (0.78, 0.94) | 0.92 (0.84, 1.00) | 0.05 | |
IgG4 | GLURP R2 | 0.79 (0.68, 0.92) | 0.85 (0.73, 0.98) | 0.02 | 1.18 (0.31, 4.57) | 1.30 (0.38, 4.43) | 0.68 | 0.79 (0.68, 0.92) | 0.85 (0.73, 0.98) | 0.02 |
MSP1-hybrid | 0.95 (0.83, 1.09) | 0.97 (0.85, 1.11) | 0.65 | 1.14 (0.32, 4.03) | 0.82 (0.29, 2.31) | 0.7 | 0.95 (0.83, 1.09) | 0.98 (0.86, 1.11) | 0.73 | |
IgM | GLURP R2 | 0.66 (0.55, 0.79) | 0.77 (0.63, 0.95) | 0.01 | 0.70 (0.14, 3.57) | 1.14 (0.24, 5.40) | 0.87 | 0.66 (0.55, 0.79) | 0.78 (0.64, 0.95) | 0.02 |
MSP1-hybrid | 0.72 (0.63, 0.84) | 0.81 (0.70, 0.94) | 0.01 | 1.42 (0.25, 8.07) | 1.68 (0.36, 7.93) | 0.51 | 0.73 (0.63, 0.84) | 0.82 (0.70, 0.95) | 0.01 | |
AS202.11 | 0.86 (0.74, 0.99) | 0.92 (0.80, 1.05) | 0.23 | 0.58 (0.23, 1.45) | 0.70 (0.26, 1.90) | 0.49 | 0.85 (0.74, 0.98) | 0.92 (0.80, 1.06) | 0.23 |
Sites | Immunological/age variables | Adjusted HR (95 % CI) | Wald p value |
---|---|---|---|
Burkina Faso | GLURP R2 IgG3 (values transformed to log base 10) | 0.82 (0.74, 0.91) |
p < 0.0001 |
MSP1-hybrid IgM (values transformed to log base 10) | 0.85 (0.73, 0.98) |
p = 0.02 | |
Age group (months) | |||
6–23 | 1 |
p < 0.0001 | |
24–35 | 1.12 (0.91, 1.38) | ||
36–47 | 0.82 (0.62, 1.07) | ||
48–60 | 0.44 (0.31, 0.63) | ||
Ghana | GLURP R2 IgG3 (values transformed to log base 10) | 0.48 (0.25, 0.91) |
p = 0.02 |
AS202.11 IgG (values transformed to log base 10) | 1.29 (1.01, 1.65) |
p = 0.04 | |
Age group (months) | |||
6–23 | 1 |
p < 0.01 | |
24–35 | 0.14 (0.04, 0.48) | ||
36–47 | 0.14 (0.04, 0.48) | ||
48–72 | 0.19 (0.07, 0.55) |