Malaria in Early Infancy: Effect of Intermittent Preventive Treatment of Malaria in Pregnancy (IPTp) and Maternally Transferred Antibodies in the Kassena-Nankana District.

Abstract

Background Beneficial effects of Intermittent Preventive Treatment in pregnancy (IPTP-SP) on the mother and birth outcomes are known. The few studies on the effects of IPTp-SP beyond in utero have been contradictory and tended to focus on late infancy and beyond. Mechanisms and targets explaining effects of IPTp-SP beyond in utero remain largely unknown. This study determined if IPTp-SP use was associated with risk of malaria and all cause mortality in early infancy and if maternally transferred antibody levels (Total IgG) to malarial antigens could explain observed IPTp-SP effects or were independently associated with the aforementioned outcomes. Methods This study was undertaken by conducting secondary analyses of the whole data from a five year cohort of 2279 newborns enrolled between 2006 and 2007 in the Kassena-Nankana Districts. Analysis was restricted to early infancy. Survival techniques (Cox Proportional hazards and Kaplan-Meier plots) were used to estimate frequency of IPT-SP doses and risk of malaria and all cause mortality. ELISA assays performed on a subset of the cohort (672), measured total IgG antibody titres to selected malaria antigens and frequency of IPTp-SP doses. Analyses of variance (ANOVA), simple regression techniques and box plots were employed to determine associations between antibody titres and frequency of IPTp-SP doses. IPTp-SP dosing frequency, Antibody types and risk of malaria and all cause mortality were also measured. Statistical significance was set at 5% with 95% confidence interval. Results Infants of mothers who had one dose of IPTp-SP had 44% less risk of parasitaemia [Hazards Ratio (HR) =0.60(95%CI= 0.45, 0.79), P<001], 41% less riskof uncomplicated malaria, [HR=0.59(95%CI =0.40, 0.86), P=005], and 41% less risk of severe malaria [HR=0.58(95%CI =0.41, 0.80), P<0.001]. Higher dosing frequencies of IPTp-SP did not significantly impact risk of malaria in early infancy, compared to none. None of the dosing frequencies of IPTp-SP was significantly associated with a decrease in all cause mortality. Antibody titres to malarial antigens (MSP3, N-MSP3, C-MSP3, GLURP-R0, GLURP-R2, and GMZ2) did not differ with frequency of IPTp-SP dosing. . Antibodies to GLURP-R2 were associated with less risk of parasitaemia [HR=0.65 (95%CI =0.50,0 .84), P=001], uncomplicated malaria [HR=0.66 (95%CI =0.45,0.95), P=0.026] and severe malaria [HR=0.66 (95%CI= 0.49,0.90), P=0.009] . Antibodies to N-MSP3 and C-MSP3 were associated with less risk of uncomplicated malaria [HR=0.76 (95%CI= 0.62, 0.93), P=0.007] and [HR=0.64(95%CI= 0.46, 0.90), P=0.009], and respectively. Antibodies to MSP3 were associated with less risk of severe malaria [HR=0.80, (95%CI =0.67, 0.96), P=0.016]. Conclusions IPTp-SP beyond in utero reduces risk of malaria in early infancy in the KNDs but dosing frequency of IPTp-SP does not significantly alter titres of maternally transferred antibodies (total IgG) to the malaria antigens MSP3, N-MSP3, C-MSP3, GLURP-R0, GLURP-R2 and GMZ2. However, total IgG to N-MSP3, C-MSP3 and GLURP-R2 are independently associated with less risk of malaria in early infancy.