Oral polio vaccine response in the MAL-ED birth cohort study: Considerations for polio eradication strategies

Abstract

Background: Immunization programs have leveraged decades of research to maximize oral polio vaccine (OPV) response. Moving toward global poliovirus eradication, the WHO recommended phased OPV-to-IPV replacement on schedules in 2012. Using the MAL-ED prospective birth cohort data, we evaluated the influence of early life exposures impacting OPV immunization by measuring OPV response for serotypes 1 and 3.

Methods: Polio neutralizing antibody assays were conducted at 7 and 15 months of age for serotypes 1 and 3. Analyses were conducted on children receiving ≥3 OPV doses (n = 1449). History of vaccination, feeding patterns, physical growth, home environment, diarrhea, enteropathogen detection, and gut inflammation were examined as risk factors for non-response [Log₂(titer) < 3] and Log₂(titer) by serotype using multivariate regression.

Findings: Serotype 1 seroconversion was significantly higher than serotype 3 (96.6% vs. 89.6%, 15 months). Model results indicate serotypes 1 and 3 failure was minimized following four and six OPV doses, respectively; however, enteropathogen detection and poor socioeconomic conditions attenuated response in both serotypes. At three months of age, bacterial detection in stool reduced serotype 1 and 3 Log₂ titers by 0.34 (95% CI 0.14-0.54) and 0.53 (95% CI 0.29-0.77), respectively, and increased odds of serotype 3 failure by 3.0 (95% CI 1.6-5.8). Our socioeconomic index, consisting of Water, Assets, Maternal education, and Income (WAMI), was associated with a 0.79 (95% CI 0.15-1.43) and 1.23 (95% CI 0.34-2.12) higher serotype 1 and 3 Log₂ titer, respectively, and a 0.04 (95% CI 0.002-0.40) lower odds of serotype 3 failure. Introduction of solids, transferrin receptor, and underweight were differentially associated with serotype response. Other factors, including diarrheal frequency and breastfeeding practices, were not associated with OPV response.

Interpretation: Under real-world conditions, improved vaccination coverage and socio-environmental conditions, and reducing early life bacterial exposures are key to improving OPV response and should inform polio eradication strategies.

Keywords: Enteropathogen infection; Home environment; Oral polio vaccination; Poliomyelitis.

Fig. 1

Child samples selected for OPV response study. Blood sample collection from each child was scheduled at seven and 15 months of age. All blood samples with sufficient volume were tested for poliovirus serotype 1, 2, and 3 serum neutralizing antibody assays. Children administered inactivated poliovirus vaccines were excluded, all of whom were from the MAL-ED cohort study site in South Africa. Blood samples collected from children receiving less than three documented doses of oral poliovirus vaccine prior to the date of blood collection were also excluded. The 2541 samples included in this analysis represent 1449 children from seven MAL-ED cohort study sites. 1092 of 1449 children (75%) contributed samples at both time points.

Fig. 2a

Poliovirus serotype 1 neutralization titer distributions by site and scheduled month of blood collection. Site locations; Dhaka, Bangladesh (BGD), Foratleza, Brazil (BRF); Vellore, India (INV); Bhaktapur, Nepal (NEB); Loreto, Peru (PEL); Naushero Feroze, Pakistan (PKN); Haydom, Tanzania (TZH).

Fig. 2b

Poliovirus serotype 3 neutralization titer distributions by site and scheduled month of blood collection. Site locations; Dhaka, Bangladesh (BGD), Foratleza, Brazil (BRF); Vellore, India (INV); Bhaktapur, Nepal (NEB); Loreto, Peru (PEL); Naushero Feroze, Pakistan (PKN); Haydom, Tanzania (TZH).

Fig. 3a

Polio serotype 1 titers by enteropathogen detection scores (bacteria, parasites, viruses, all combined) computed for diarrheal, non-diarrheal and all stools combined among children receiving at least 3 OPV doses at the scheduled 7 month blood draw. Scatter plots include penalized B-splines (10 knots) and 95% confidence intervals. A chi-square test was evaluated for each scatter plot comparing the percent of children who failed to seroconvert in a high vs. low enteropathogen score group where high was defined as the approximate 75^th percentile of the enteropathogen score (i.e., 1.0, 0.33, 0.15, and 1.25 for Bacteria, Parasite, Virus and All Pathogens Scores, respectively); † indicates p<0.05; †† indicates p<0.01.

Fig. 3b

Polio serotype 3 titers by enteropathogen detection scores (bacteria, parasites, viruses, all combined) computed for diarrheal, non-diarrheal and all stools combined among children receiving at least 3 OPV doses at the scheduled 7 month blood draw. Scatter plots include penalized B-splines (10 knots) and 95% confidence intervals. A chi-square test was evaluated for each scatter plot comparing the percent of children who failed to seroconvert in a high vs. low enteropathogen score group where high was defined as the approximate 75^th percentile of the enteropathogen score (i.e., 1.0, 0.33, 0.15, and 1.25 for Bacteria, Parasite, Virus and All Pathogens Scores, respectively); † indicates p < 0.05; †† indicates p < 0.01.

Fig. 4

Serotype 1 and 3 titer distributions and confidence intervals for WAMI component scores at 15 months. Penalized B-splines were fit using 10 knots. Pearson correlation coefficients (denoted r) are reported in the lower right corner of each scatter plot (all correlations have p < 0.0001 for the test of r being different from 0, except correlations with Maternal Education, which were not significant)

Fig. 5

Distribution of WAMI component and HOME Cleanliness scores by site. Sites are sorted by highest to lowest overall WAMI score. Symbol descriptions: the box represents the Interquartile Range (25^th to 75^th percentile); the black plus (+) is the mean; the median is indicated by the box notch; lines extending from the box with hash marks are 1.5 times the interquartile values; and circles represent potential outliers.