Background
Methods
Study design, setting, and participants
Laboratory methods
Study outcomes
Statistical methods
Results
Study profile and characteristics of study participants
Characteristic | Maternal IPTp arm | |
---|---|---|
Monthly SP (N = 327) | Monthly DP (N = 329) | |
Maternal characteristics at enrolment | ||
Age in years, mean (SD) | 24.0 (5.9) | 24.0 (5.7) |
Gravidity, n (%) | ||
Primigravida/secundigravida | 152 (46.5%) | 156 (47.4%) |
Multigravida | 175 (53.5%) | 173 (52.6) |
House-hold type, n (%) | ||
Modern House | 77 (23.6%) | 71 (21.6%) |
Traditional House | 250 (76.5%) | 258 (78.4%) |
Parasite prevalence by microscopy or qPCR, n (%) | ||
No parasites | 53 (16.2%) | 63 (19.2%) |
Sub-microscopic parasitaemia | 111 (33.9%) | 88 (26.8%) |
Microscopic parasitaemia | 163 (49.9%) | 178 (54.1%) |
Maternal characteristics during pregnancy | ||
Parasite prevalence by microscopy, n/N (%)a | 797/2212 (36.0%) | 355/2260 (15.7%) |
Incidence of malaria (episodes/ppy) | 0.59 | 0.09 |
Placental malaria status | ||
Placental malaria status, n (%) | ||
No PM | 119 (36.4%) | 232 (70.5%) |
Active PM | 71 (21.7%) | 7 (2.1%) |
Past PM (Mild-moderate pigment) | 97 (29.7%) | 84 (25.5%) |
Past PM (Severe pigment) | 40 (12.2%) | 6 (1.8%) |
Characteristics of infants at birth | ||
Preterm birth, n (%) | 25 (7.7%) | 17 (5.2%) |
Gestation age in weeks, mean (SD) | 39.4 (1.9) | 39.6 (1.6) |
Low birth weight, n (%) | 33 (10.1%) | 25 (7.6%) |
Birth weight in grams, mean (SD) | 3055 (505) | 3024 (409) |
Female sex, n (%) | 161 (49.2%) | 175 (53.2%) |
Association between placental malaria and the incidence of malaria in infants
Infant category | Placental malaria categories (N) | Malaria episodes | Person years of follow-up | Malaria incidencea | Unadjusted | Adjustedb | ||
---|---|---|---|---|---|---|---|---|
IRR (95% CI) | p value | IRR (95% CI) | p-value | |||||
All | No PM (351) | 574 | 327.4 | 1.75 | Reference group | Reference group | ||
Active PM (78) | 152 | 68.9 | 2.21 | 1.27 (0.99–1.62) | 0.06 | 1.30 (1.00-1.71) | 0.05 | |
Past PM (mild-mod) (181) | 271 | 157.8 | 1.72 | 0.97 (0.79–1.18) | 0.74 | 0.94 (0.76-1.16) | 0.55 | |
Past PM (severe) (46) | 91 | 42.5 | 2.14 | 1.22 (0.91–1.63) | 0.19 | 1.28 (0.89-1.83) | 0.18 | |
Male | No PM (168) | 255 | 154.5 | 1.65 | Reference group | Reference group | ||
Active PM (45) | 86 | 39.9 | 2.16 | 1.31 (0.93–1.87) | 0.13 | 1.27 (0.87–1.84) | 0.22 | |
Past PM (mild-mod) (70) | 129 | 77.7 | 1.66 | 0.98 (0.72–1.35) | 0.92 | 1.02 (0.76–1.36) | 0.90 | |
Past PM (severe) (17) | 49 | 15.3 | 3.20 | 1.87 (1.29–2.71) | 0.001 | 2.17 (1.45–3.25) | <0.001 | |
Female | No PM (183) | 319 | 172.9 | 1.84 | Reference group | Reference group | ||
Active PM (33) | 66 | 29.0 | 2.28 | 1.24 (0.89–1.73) | 0.21 | 1.29 (0.87–1.91) | 0.21 | |
Past PM (mild-mod) (91) | 142 | 80.1 | 1.77 | 0.96 (0.73–1.24) | 0.74 | 0.81 (0.61–1.08) | 0.15 | |
Past PM (severe) (29) | 42 | 27.1 | 1.55 | 0.85 (0.58–1.24) | 0.40 | 0.74 (0.46–1.20) | 0.22 |
Association between placental malaria and other malaria outcomes in infants
Outcome measure | Infant category | Placental malaria categories | Number of cases (incidence PPY) | Unadjusted | Adjusteda | ||
---|---|---|---|---|---|---|---|
IRR (95% CI) | p-value | IRR (95% CI) | p-value | ||||
Incidence of complicated malaria | All | No PM (351) | 30 (0.092) | Reference group | Reference group | ||
Active PM (78) | 12 (0.17) | 1.89 (0.93–3.87) | 0.08 | 1.72 (0.81–3.66) | 0.16 | ||
Past PM (mild-mod) (181) | 14 (0.09) | 0.97 (0.52–1.81) | 0.91 | 0.99 (0.52–1.92) | 0.98 | ||
Past PM (severe) (46) | 9 (0.21) | 2.30 (0.97–5.43) | 0.06 | 2.44 (0.93–6.37) | 0.07 | ||
Male | No PM (168) | 13 (0.08) | Reference group | Reference group | |||
Active PM (45) | 6 (0.04) | 1.78 (0.63–5.02) | 0.27 | 1.18 (0.39–3.62) | 0.77 | ||
Past PM (mild-mod) (90) | 11 (0.14) | 1.68 (0.76–3.68) | 0.20 | 1.54 (0.44–3.45) | 0.30 | ||
Past PM (severe) (17) | 6 (0.39) | 4.61 (1.50–14.22) | 0.008 | 3.88 (1.14–13.03) | 0.03 | ||
Female | No PM (183) | 17 (0.10) | Reference group | Reference group | |||
Active PM (33) | 6 (0.21) | 2.09 (0.78–5.64) | 0.15 | 2.60 (0.91–7.44) | 0.14 | ||
Past PM (mild-mod) (91) | 3 (0.04) | 0.38 (0.11–1.29) | 0.12 | 0.44 (0.13–1.54) | 0.20 | ||
Past PM (severe) (29) | 3 (0.11) | 1.12 (0.34–3.66) | 0.85 | 1.63 (0.46–5.81) | 0.45 |
Prevalence measures | Infant category | Placental malaria categories | Prevalence n/N (%) | Risk ratio (95% CI) | p-value | Risk ratio (95% CI) | p-value |
---|---|---|---|---|---|---|---|
Prevalence of prasitaemia | All | No PM (351) | 377/4170 (9.0%) | Reference group | Reference group | ||
Active PM (78) | 82/858 (9.6%) | 1.07 (0.76–1.52) | 0.70 | 1.19 (0.82–1.73) | 0.36 | ||
Past PM (mild-mod) (181) | 154/1993 (7.7%) | 0.85 (0.65–1.12) | 0.26 | 0.86 (0.65–1.14) | 0.28 | ||
Past PM (severe) (46) | 61/542 (11.3%) | 1.22 (0.84–1.77) | 0.30 | 1.38 (0.90–2.10) | 0.14 | ||
Male | No PM (168) | 170/1964 (8.7%) | Reference group | Reference group | |||
Active PM (45) | 50/498 (10.0%) | 1.17 (0.73–1.86) | 0.52 | 1.19 (0.71–2.00) | 0.51 | ||
Past PM (mild-mod) (90) | 70/976 (7.2%) | 0.81 (0.55–1.20) | 0.29 | 0.87 (0.58–1.31) | 0.50 | ||
Past PM (severe) (17) | 31/191 (16.2%) | 1.80 (1.08–2.99) | 0.02 | 2.24 (1.34–3.74) | 0.002 | ||
Female | No PM (183) | 207/2206 (9.4%) | Reference group | Reference group | |||
Active PM (33) | 32/360 (8.9%) | 0.97 (0.57–1.66) | 0.91 | 1.05 (0.61–1.83) | 0.85 | ||
Past PM (mild-mod) (91) | 84/1017 (8.3%) | 0.90 (0.61–1.31) | 0.57 | 0.79 (0.53–1.17) | 0.24 | ||
Past PM (severe) (29) | 31/351 (8.6%) | 0.90 (0.54–1.51) | 0.70 | 0.86 (0.48–1.52) | 0.60 |
Association between placental malaria and non-malarial outcomes in infancy
Outcome measure | Placental malaria category (N) | Number of cases (incidence PPY) | Unadjusted | Adjusteda | ||
---|---|---|---|---|---|---|
IRR (95% CI) | p-value | IRR (95% CI) | p-value | |||
Incidence of all-cause hospitalisations | No PM (351) | 9 (0.027) | Reference group | Reference group | ||
Active PM (78) | 3 (0.044) | 1.66 (0.40–7.00) | 0.49 | 1.14 (0.22–5.98) | 0.87 | |
Past PM (mild-mod) (181) | 7 (0.044) | 1.72 (0.58–5.12) | 0.33 | 1.26 (0.44–3.64) | 0.66 | |
Past PM (severe (46) | 6 (0.141) | 4.85 (1.38–17.00) | 0.01 | 2.90 (0.59–14.44) | 0.19 | |
Incidence of non-malarial febrile illnesses | No PM (351) | 1128 (3.45) | Reference group | Reference group | ||
Active PM (78) | 203 (2.95) | 0.86 (0.72–1.03) | 0.10 | 0.84 (0.64–1.10) | 0.20 | |
Past PM (mild-mod) (181) | 536 (3.40) | 0.98 (0.86–1.13) | 0.82 | 1.03 (0.84–1.25) | 0.79 | |
Past PM (severe (46) | 152 (3.58) | 1.04 (0.85–1.26) | 0.72 | 1.06 (0.72–1.57) | 0.76 |
Prevalence measures | Categories | Prevalence n/N (%) | Risk ratio (95% CI) | p-value | Risk ratio (95% CI) | p-value |
---|---|---|---|---|---|---|
Anaemiac | No PM (351) | 227/934 (24.3%) | Reference group | Reference group | ||
Active PM (78) | 48/190 (25.3%) | 1.07 (0.76–1.50) | 0.69 | 1.00 (0.69–1.47) | 0.98 | |
Past PM (mild-mod) (181) | 106/441 (24.0%) | 1.01 (0.80–1.29) | 0.92 | 0.94 (0.73–1.22) | 0.64 | |
Past PM (severe (46) | 37/118 (31.4%) | 1.29 (0.94–1.77) | 0.12 | 1.16 (0.79–1.70) | 0.44 |
Does prevention of PM explain the difference in infant malaria incidence between IPTp-DP and IPTp-SP?
Infant category | Total effect | Direct effect | Mediated effect | % of mediated effecta | |||
---|---|---|---|---|---|---|---|
IRR (95% CI) | p-value | IRR (95% CI) | p-value | IRR (95% CI) | p-value | ||
All sexes | 0.89 (0.75–1.04) | 0.16 | 0.94 (0.73–1.17) | 0.58 | 0.95 (0.77–1.16) | 0.61 | 43.5% |
Male | 0.77 (0.61–0.99) | 0.05 | 0.97 (0.67–1.36) | 0.89 | 0.79 (0.56–1.09) | 0.17 | 89.7% |
Females | 1.01 (0.81–1.26) | 0.96 | 0.92 (0.71–1.22) | 0.56 | 1.09 (0.87–1.38) | 0.45 | – |