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. 2017 Apr;139(4):e20162781.
doi: 10.1542/peds.2016-2781. Epub 2017 Mar 16.

Pneumococcal Vaccine Response After Exposure to Parasites in Utero, in Infancy, or Mid-Childhood

Affiliations

Pneumococcal Vaccine Response After Exposure to Parasites in Utero, in Infancy, or Mid-Childhood

Monica Nayakwadi Singer et al. Pediatrics. 2017 Apr.

Abstract

Background and objective: Streptococcus pneumoniae is a leading cause of mortality before age 5, but few studies examine details of childhood response to pneumococcal vaccine in less-developed settings. Although malnutrition, HIV, and concurrent infections can impair response, evidence suggests that chronic parasitic infections can also contribute to poor vaccination results. The objective of this study was to determine whether response to pneumococcal vaccine varied among children either exposed to parasitic infections in utero, previously infected in infancy, or infected at the time of immunization.

Methods: Children from a 2006 to 2010 maternal-infant cohort were eligible for the current study. Children were screened for malaria, schistosomiasis, filariasis, intestinal helminths, and protozoa. Data on in utero exposure and early life infections were linked, and baseline antipneumococcal immunoglobulin G levels and nasopharyngeal carrier status were determined. Participants received decavalent pneumococcal vaccine, and 4 weeks later, serology was repeated to assess vaccine response.

Results: A total of 281 children were included. Preimmunity was associated with greater postvaccination increments in anti-pneumococcal polysaccharide immunoglobulin G, especially serotypes 4, 7, 9, 18C, and 19. Present-day growth stunting was independently associated with weaker responses to 1, 4, 6B, 7, 9V, and 19. Previous exposure to Trichuris was associated with stronger responses to 1, 5, 6B, 7, 18C, and 23, but other parasite exposures were not consistently associated with response.

Conclusions: In our cohort, hyporesponsiveness to pneumococcal conjugate vaccine was associated with growth stunting but not parasite exposure. Parasite-related vaccine response deficits identified before age 3 do not persist into later childhood.

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Conflict of interest statement

POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Figures

FIGURE 1
FIGURE 1
Study design: Parasitic exposures in utero and during early infancy were abstracted from 2006 to 2010 cohort study records. In 2014, reenrolled subjects, 4 to 7 years old, were retested for infection and for anti-PPS IgG and S pneumoniae carriage. Subjects were then retested 4 to 6 weeks after their first dose of decavalent conjugate vaccine.
FIGURE 2
FIGURE 2
Study enrollment and follow-up: Of 547 subjects enrolled in the 2006 to 2010 cohort, 450 completed full follow-up through 2010. Fifty-six subjects could not participate for reasons indicated. In 2014, 385 of 450 subjects were reconsented and reenrolled, 44 were lost to follow-up, and 281 subjects provided complete data for final analysis.
FIGURE 3
FIGURE 3
Prevalence of parasite exposures at 3 time points: in utero, during early infancy, and at midchildhood. Bars represent the percentage of participating children having S hematobium, hookworm, Trichuris trichiura, Ascaris lumbricoides, Strongyloides stercoralis, any STH, malaria, or filaria (Wuchereria bancrofti). STH, soil-transmitted helminths (hookworm, Trichuris, Ascaris, or Strongyloides infection).
FIGURE 4
FIGURE 4
Prevalence of significant preimmunization anti–S pneumoniae IgG levels by vaccine serotype. The greatest frequency of vaccine-specific preimmunity in the Msambweni, Kenya cohort children was to pneumococcal serotypes 14, 19, 9V, 4, and 23.
FIGURE 5
FIGURE 5
Mean antiantigen IgG levels before and after delivery of PCV, and the amount of change in IgG, according to S pneumoniae serotype. Black bars represent mean preimmunization IgG levels, shaded bars represent mean postimmunization IgG levels, and stippled bars represent the difference between preimmunization and postimmunization IgG levels.
FIGURE 6
FIGURE 6
Impact of growth stunting (age-adjusted height z score <−2) on postvaccination antipneumococcal IgG levels. Subgroup analysis indicated significantly lower anti-PPS IgG against vaccine serotypes 1, 4, 6B, 7, 9V, 14, 18C, 19, and 23 among stunted children. *P < .05, **P < .01.
FIGURE 7
FIGURE 7
Differences between high- and low-responder subgroups identified by cluster analysis of anti-PPS response across all serotypes. Shown are representative changes to 18C antigen before to after a single dose of 10-valent PCV. Children in the high-response group (N = 67) are shown in color. The low-response group (N = 214) is shown in black.

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