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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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Response to vaccines in infants of mothers with multiple infections.Adjusted mean anti-Hib polyribitol phosphate (PRP) (left panels) and anti-diphtheria toxoid antibody levels (right panels) from 6 to 30 months of age, according to the multiplicity of the mother’s pre-natal infections. Row A: No maternal infection (black line), one maternal parasitic infection (blue line), two maternal parasitic infections (red line), three or more maternal parasitic infections (grey line). Row B. No maternal infection (black line), maternal malaria infection alone (blue line), maternal malaria infection and one helminth (red line), maternal malaria and two or more helminth infections (grey line). Row C: No maternal infection (black line), single maternal helminth and no malaria (blue line), two helminth infections and no malaria (red line), and three or more helminth infections and no malaria (grey line).
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pntd.0003466.g004: Response to vaccines in infants of mothers with multiple infections.Adjusted mean anti-Hib polyribitol phosphate (PRP) (left panels) and anti-diphtheria toxoid antibody levels (right panels) from 6 to 30 months of age, according to the multiplicity of the mother’s pre-natal infections. Row A: No maternal infection (black line), one maternal parasitic infection (blue line), two maternal parasitic infections (red line), three or more maternal parasitic infections (grey line). Row B. No maternal infection (black line), maternal malaria infection alone (blue line), maternal malaria infection and one helminth (red line), maternal malaria and two or more helminth infections (grey line). Row C: No maternal infection (black line), single maternal helminth and no malaria (blue line), two helminth infections and no malaria (red line), and three or more helminth infections and no malaria (grey line).

Mentions: The presence and the multiplicity of prenatal parasitic infections were significantly associated with reduced IgG responses to vaccine antigens during infancy following pentavalent vaccination given at 6, 10, and 14 weeks of age. Compared to no prenatal maternal infection, the presence of single or double maternal infections during pregnancy resulted in significantly lower anti-Hib PRP-specific IgG levels in infants and young children to 2 years of age (Fig. 4 row A); (P = 0·04, <0·0001, 0·001, 0·04 with one infection for 6, 12, 18, and 24 month time points, and P = 0·008, 0·01, 0·04 with two infections at 12, 18, and 24 months of age, respectively). Offspring of mothers with 3 or more parasitic infections did not have reduced anti-Hib PRP-IgG (Fig. 4, row A). Prenatal parasitic infections had little impact on DT-specific IgG levels in infants of mothers with one or two infections, but there was an effect in infants of mothers with three or more infections at 6 and 12 months of age, (Fig. 4, row A, P = 0·002 and 0·03, respectively).


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)

Response to vaccines in infants of mothers with multiple infections.Adjusted mean anti-Hib polyribitol phosphate (PRP) (left panels) and anti-diphtheria toxoid antibody levels (right panels) from 6 to 30 months of age, according to the multiplicity of the mother’s pre-natal infections. Row A: No maternal infection (black line), one maternal parasitic infection (blue line), two maternal parasitic infections (red line), three or more maternal parasitic infections (grey line). Row B. No maternal infection (black line), maternal malaria infection alone (blue line), maternal malaria infection and one helminth (red line), maternal malaria and two or more helminth infections (grey line). Row C: No maternal infection (black line), single maternal helminth and no malaria (blue line), two helminth infections and no malaria (red line), and three or more helminth infections and no malaria (grey line).
© Copyright Policy
Related In: Results  -  Collection

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

pntd.0003466.g004: Response to vaccines in infants of mothers with multiple infections.Adjusted mean anti-Hib polyribitol phosphate (PRP) (left panels) and anti-diphtheria toxoid antibody levels (right panels) from 6 to 30 months of age, according to the multiplicity of the mother’s pre-natal infections. Row A: No maternal infection (black line), one maternal parasitic infection (blue line), two maternal parasitic infections (red line), three or more maternal parasitic infections (grey line). Row B. No maternal infection (black line), maternal malaria infection alone (blue line), maternal malaria infection and one helminth (red line), maternal malaria and two or more helminth infections (grey line). Row C: No maternal infection (black line), single maternal helminth and no malaria (blue line), two helminth infections and no malaria (red line), and three or more helminth infections and no malaria (grey line).
Mentions: The presence and the multiplicity of prenatal parasitic infections were significantly associated with reduced IgG responses to vaccine antigens during infancy following pentavalent vaccination given at 6, 10, and 14 weeks of age. Compared to no prenatal maternal infection, the presence of single or double maternal infections during pregnancy resulted in significantly lower anti-Hib PRP-specific IgG levels in infants and young children to 2 years of age (Fig. 4 row A); (P = 0·04, <0·0001, 0·001, 0·04 with one infection for 6, 12, 18, and 24 month time points, and P = 0·008, 0·01, 0·04 with two infections at 12, 18, and 24 months of age, respectively). Offspring of mothers with 3 or more parasitic infections did not have reduced anti-Hib PRP-IgG (Fig. 4, row A). Prenatal parasitic infections had little impact on DT-specific IgG levels in infants of mothers with one or two infections, but there was an effect in infants of mothers with three or more infections at 6 and 12 months of age, (Fig. 4, row A, P = 0·002 and 0·03, respectively).

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