Research Article: Effect of Antenatal Parasitic Infections on Anti-vaccine IgG Levels in Children: A Prospective Birth Cohort Study in Kenya

Date Published: January 15, 2015

Publisher: Public Library of Science

Author(s): Indu Malhotra, Maxim McKibben, Peter Mungai, Elisabeth McKibben, Xuelei Wang, Laura J. Sutherland, Eric M. Muchiri, Charles H. King, Christopher L. King, A. Desiree LaBeaud, Jessica N. Ricaldi.

Abstract: BackgroundParasitic 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 Findings450 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.ConclusionsThere 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.

Partial Text: Vaccine-preventable diseases (VPD) continue to kill an estimated one to two million children each year, comprising about 14% of global mortality in children under 5 years of age [1, 2]. Vaccination studies have repeatedly shown that children in developing nations are less responsive to vaccines than children from developed countries [3–7]. Recent outbreaks of polio in Africa and Syria have also shown that vaccine failures can result in resurgence of vaccine preventable diseases even in countries with high vaccination coverage [8, 9]. This suggests that vaccine efficacy can be lower in certain settings. That is, failure to respond appropriately to vaccination is likely to be associated with poverty-related conditions, including malnutrition and chronic infection, particularly chronic parasitic infections [10, 11]. Animal models suggest that nematode infections decrease vaccine efficacy and contribute to risk for infection by vaccine preventable diseases [12, 13]. Concurrent schistosomiasis infection in humans has a negative impact on vaccination for tetanus [14] and tuberculosis (BCG vaccination) [15]. Chronic parasitic infections other than helminths can impair immune responses, resulting in decreased tetanus, Haemophilus influenzae type b (Hib), and typhoid vaccine efficacy in the presence of malaria infection [16, 17].

This study shows that there is an impaired ability to develop IgG antibody responses to key protective antigens of Hib and diphtheria among infants of mothers infected with malaria and/or helminths during pregnancy, as compared to infants of uninfected mothers. This association with maternal infection was most pronounced for anti-Hib antibody responses, with some evident effects on diphtheria antibody response, but no measurable effect on acquisition of antibodies to TT and hepatitis B. Independently, antenatal malaria, LF, and hookworm each lowered the IgG response to Hib, but schistosomiasis had no effect. Most pregnant women were infected with more than one of these parasitic infections, yet having multiple infections did not increase the observed impaired levels of antibody responses, suggesting that single species-specific mechanisms may be responsible for this vaccine-response impairment.



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