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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 malaria, LF, and S. haematobium sensitization and tolerization on response to vaccine antigens.Adjusted mean antibody responses to Hib polyribitol phosphate (PRP) and diphtheria toxoid antigens among infants who were unexposed to parasite infections in utero(black line), exposed-sensitized (green line), or exposed-tolerized (red line), based on cord blood anti-parasite reactivity at birth; Row A: maternal malaria; Row B: maternal filariasis; Row C: maternal schistosomiasis.
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pntd.0003466.g005: Effects of malaria, LF, and S. haematobium sensitization and tolerization on response to vaccine antigens.Adjusted mean antibody responses to Hib polyribitol phosphate (PRP) and diphtheria toxoid antigens among infants who were unexposed to parasite infections in utero(black line), exposed-sensitized (green line), or exposed-tolerized (red line), based on cord blood anti-parasite reactivity at birth; Row A: maternal malaria; Row B: maternal filariasis; Row C: maternal schistosomiasis.

Mentions: Children were classified as either sensitized, tolerized, or unexposed to the individual parasite pathogens studied, as described in detail in the methods. With respect to Hib vaccine, classification of children by cord blood response to prenatal malaria had no effect on anti-Hib Ab levels (Fig. 5, row A), however offspring who developed a tolerogenic response to filarial antigens had significantly reduced anti-Hib responses at 12, 18, and 24 months of age (P = 0·052, 0·033, and 0·035, respectively, Fig. 5, row B). There was no impact of cord blood response to prenatal schistosome exposure on anti-Hib IgG levels (Fig. 5, row C). By contrast immunophenotype acquired by prenatal exposure to malaria antigens had significant effects of development anti-DT IgG levels following vaccination. Children classified as malaria-tolerant showed significantly reduced DT-specific IgG levels at 12 and 18 months of age, (P = 0·032 and 0·048, respectively) when compared to unexposed infants. There were increased anti-DT IgG levels in malaria-sensitized infants at 6 and 12 months (P = 0·006 and 0·04 respectively, Fig. 5, row A).


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 malaria, LF, and S. haematobium sensitization and tolerization on response to vaccine antigens.Adjusted mean antibody responses to Hib polyribitol phosphate (PRP) and diphtheria toxoid antigens among infants who were unexposed to parasite infections in utero(black line), exposed-sensitized (green line), or exposed-tolerized (red line), based on cord blood anti-parasite reactivity at birth; Row A: maternal malaria; Row B: maternal filariasis; Row C: maternal schistosomiasis.
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003466.g005: Effects of malaria, LF, and S. haematobium sensitization and tolerization on response to vaccine antigens.Adjusted mean antibody responses to Hib polyribitol phosphate (PRP) and diphtheria toxoid antigens among infants who were unexposed to parasite infections in utero(black line), exposed-sensitized (green line), or exposed-tolerized (red line), based on cord blood anti-parasite reactivity at birth; Row A: maternal malaria; Row B: maternal filariasis; Row C: maternal schistosomiasis.
Mentions: Children were classified as either sensitized, tolerized, or unexposed to the individual parasite pathogens studied, as described in detail in the methods. With respect to Hib vaccine, classification of children by cord blood response to prenatal malaria had no effect on anti-Hib Ab levels (Fig. 5, row A), however offspring who developed a tolerogenic response to filarial antigens had significantly reduced anti-Hib responses at 12, 18, and 24 months of age (P = 0·052, 0·033, and 0·035, respectively, Fig. 5, row B). There was no impact of cord blood response to prenatal schistosome exposure on anti-Hib IgG levels (Fig. 5, row C). By contrast immunophenotype acquired by prenatal exposure to malaria antigens had significant effects of development anti-DT IgG levels following vaccination. Children classified as malaria-tolerant showed significantly reduced DT-specific IgG levels at 12 and 18 months of age, (P = 0·032 and 0·048, respectively) when compared to unexposed infants. There were increased anti-DT IgG levels in malaria-sensitized infants at 6 and 12 months (P = 0·006 and 0·04 respectively, Fig. 5, row A).

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