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Effect of antenatal parasitic infections on anti-vaccine IgG levels in children: a prospective birth cohort study in Kenya.

Malhotra I, McKibben M, Mungai P, McKibben E, Wang X, Sutherland LJ, Muchiri EM, King CH, King CL, LaBeaud AD - PLoS Negl Trop Dis (2015)

Bottom Line: Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination.Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib.These findings highlight the importance of control and prevention of parasitic infections among pregnant women.

View Article: PubMed Central - PubMed

Affiliation: Case Western Reserve University, Center for Global Health and Diseases, Cleveland, Ohio, United States of America.

ABSTRACT

Background: Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. We investigated whether prenatal exposure to malaria and/or helminths affects the pattern of infant immune responses to standard vaccinations against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and tetanus toxoid (TT).

Methods and findings: 450 Kenyan women were tested for malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their newborns were followed biannually to age 36 months and tested for absolute levels of IgG against Hib, DT, Hep B, and TT at each time point. Newborns' cord blood (CB) lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma haematobium worm antigen (SWAP), and filaria antigen (BMA) were also assessed. Three immunophenotype categories were compared: i) tolerant (those having Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA); ii) sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB recall response to respective parasite antigen); or iii) unexposed (no evidence of maternal infection or CB recall response). Overall, 78.9% of mothers were infected with LF (44.7%), schistosomiasis (32.4%), malaria (27.6%) or hookworm (33.8%). Antenatal maternal malaria, LF, and hookworm were independently associated with significantly lower Hib-specific IgG. Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination. Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib.

Conclusions: There is an impaired ability to develop IgG antibody responses to key protective antigens of Hib and diphtheria in infants of mothers infected with malaria and/or helminths during pregnancy. These findings highlight the importance of control and prevention of parasitic infections among pregnant women.

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Effects of maternal parasitic infections on post-vaccination IgG to Haemophilus influenzae b and to diphtheria.Shown are adjusted mean anti-Hib polyribitol phosphate (PRP) (left panels) and anti-diphtheria toxoid antibody levels (right panels) among infants born to mothers who had (red line), or did not have (black line) the indicated prenatal maternal infection; Row A: maternal malaria; Row B: maternal filariasis; Row C: maternal schistosomiasis; Row D: maternal hookworm. Estimates were obtained using a generalized non-linear mixed model that included fixed effects for maternal age, parity, occupation, education and child infections, a quadratic fixed effect for age of infant, and a random intercept. Hash lines indicate the standard error of the mean values.
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pntd.0003466.g003: Effects of maternal parasitic infections on post-vaccination IgG to Haemophilus influenzae b and to diphtheria.Shown are adjusted mean anti-Hib polyribitol phosphate (PRP) (left panels) and anti-diphtheria toxoid antibody levels (right panels) among infants born to mothers who had (red line), or did not have (black line) the indicated prenatal maternal infection; Row A: maternal malaria; Row B: maternal filariasis; Row C: maternal schistosomiasis; Row D: maternal hookworm. Estimates were obtained using a generalized non-linear mixed model that included fixed effects for maternal age, parity, occupation, education and child infections, a quadratic fixed effect for age of infant, and a random intercept. Hash lines indicate the standard error of the mean values.

Mentions: To determine whether the presence of individual infection during pregnancy was associated with impaired IgG responses to Hib, DT, Hep B, and TT in infancy and early childhood, children were stratified into groups whose mothers were independently malaria-, schistosomiasis-, LF-, or hookworm-infected, or not infected during pregnancy; other STH, such as Trichuris, Strongyloides were detected in <2% and Ascaris, was detected in <11% of the mothers and therefore were not considered further in the analysis. The presence of pre-natal maternal malaria, LF, and hookworm (Fig. 3, rows A, B, and D respectively) was associated with significantly lower post-vaccination levels of Hib-specific IgG (for malaria, P = 0•031, 0•005, 0•007, 043 at 6, 12, 18, 24 months of age; for LF, P = 0•007, 0•03 at 12, 18 months of age; and for hookworm, P = 0•034, 0•019 at 12, 18 months of age, respectively, controlling for maternal age, parity, education, income, and childhood parasitic infections). Maternal schistosomiasis alone (Fig. 3, row C) had no effect on vaccine-specific IgG levels. Malaria, LF, schistosomiasis and hookworm had no effect on DT, (Fig. 3), Hep B and TT (see Supporting Information, S1 Fig.).


Effect of antenatal parasitic infections on anti-vaccine IgG levels in children: a prospective birth cohort study in Kenya.

Malhotra I, McKibben M, Mungai P, McKibben E, Wang X, Sutherland LJ, Muchiri EM, King CH, King CL, LaBeaud AD - PLoS Negl Trop Dis (2015)

Effects of maternal parasitic infections on post-vaccination IgG to Haemophilus influenzae b and to diphtheria.Shown are adjusted mean anti-Hib polyribitol phosphate (PRP) (left panels) and anti-diphtheria toxoid antibody levels (right panels) among infants born to mothers who had (red line), or did not have (black line) the indicated prenatal maternal infection; Row A: maternal malaria; Row B: maternal filariasis; Row C: maternal schistosomiasis; Row D: maternal hookworm. Estimates were obtained using a generalized non-linear mixed model that included fixed effects for maternal age, parity, occupation, education and child infections, a quadratic fixed effect for age of infant, and a random intercept. Hash lines indicate the standard error of the mean values.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4295886&req=5

pntd.0003466.g003: Effects of maternal parasitic infections on post-vaccination IgG to Haemophilus influenzae b and to diphtheria.Shown are adjusted mean anti-Hib polyribitol phosphate (PRP) (left panels) and anti-diphtheria toxoid antibody levels (right panels) among infants born to mothers who had (red line), or did not have (black line) the indicated prenatal maternal infection; Row A: maternal malaria; Row B: maternal filariasis; Row C: maternal schistosomiasis; Row D: maternal hookworm. Estimates were obtained using a generalized non-linear mixed model that included fixed effects for maternal age, parity, occupation, education and child infections, a quadratic fixed effect for age of infant, and a random intercept. Hash lines indicate the standard error of the mean values.
Mentions: To determine whether the presence of individual infection during pregnancy was associated with impaired IgG responses to Hib, DT, Hep B, and TT in infancy and early childhood, children were stratified into groups whose mothers were independently malaria-, schistosomiasis-, LF-, or hookworm-infected, or not infected during pregnancy; other STH, such as Trichuris, Strongyloides were detected in <2% and Ascaris, was detected in <11% of the mothers and therefore were not considered further in the analysis. The presence of pre-natal maternal malaria, LF, and hookworm (Fig. 3, rows A, B, and D respectively) was associated with significantly lower post-vaccination levels of Hib-specific IgG (for malaria, P = 0•031, 0•005, 0•007, 043 at 6, 12, 18, 24 months of age; for LF, P = 0•007, 0•03 at 12, 18 months of age; and for hookworm, P = 0•034, 0•019 at 12, 18 months of age, respectively, controlling for maternal age, parity, education, income, and childhood parasitic infections). Maternal schistosomiasis alone (Fig. 3, row C) had no effect on vaccine-specific IgG levels. Malaria, LF, schistosomiasis and hookworm had no effect on DT, (Fig. 3), Hep B and TT (see Supporting Information, S1 Fig.).

Bottom Line: Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination.Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib.These findings highlight the importance of control and prevention of parasitic infections among pregnant women.

View Article: PubMed Central - PubMed

Affiliation: Case Western Reserve University, Center for Global Health and Diseases, Cleveland, Ohio, United States of America.

ABSTRACT

Background: Parasitic infections are prevalent among pregnant women in sub-Saharan Africa. We investigated whether prenatal exposure to malaria and/or helminths affects the pattern of infant immune responses to standard vaccinations against Haemophilus influenzae (Hib), diphtheria (DT), hepatitis B (Hep B) and tetanus toxoid (TT).

Methods and findings: 450 Kenyan women were tested for malaria, schistosomiasis, lymphatic filariasis (LF), and intestinal helminths during pregnancy. After three standard vaccinations at 6, 10 and 14 weeks, their newborns were followed biannually to age 36 months and tested for absolute levels of IgG against Hib, DT, Hep B, and TT at each time point. Newborns' cord blood (CB) lymphocyte responses to malaria blood-stage antigens, soluble Schistosoma haematobium worm antigen (SWAP), and filaria antigen (BMA) were also assessed. Three immunophenotype categories were compared: i) tolerant (those having Plasmodium-, Schistosoma-, or Wuchereria-infected mothers but lacking respective Th1/Th2-type recall responses at birth to malaria antigens, SWAP, or BMA); ii) sensitized (those with infected/uninfected mothers and detectable Th1/Th2-type CB recall response to respective parasite antigen); or iii) unexposed (no evidence of maternal infection or CB recall response). Overall, 78.9% of mothers were infected with LF (44.7%), schistosomiasis (32.4%), malaria (27.6%) or hookworm (33.8%). Antenatal maternal malaria, LF, and hookworm were independently associated with significantly lower Hib-specific IgG. Presence of multiple maternal infections was associated with lower infant IgG levels against Hib and DT antigens post-vaccination. Post-vaccination IgG levels were also significantly associated with immunophenotype: malaria-tolerized infants had reduced response to DT, whereas filaria-tolerized infants showed reduced response to Hib.

Conclusions: There is an impaired ability to develop IgG antibody responses to key protective antigens of Hib and diphtheria in infants of mothers infected with malaria and/or helminths during pregnancy. These findings highlight the importance of control and prevention of parasitic infections among pregnant women.

Show MeSH
Related in: MedlinePlus