Evidence for the intermediate disturbance hypothesis and exponential decay in replacement in Streptococcus pneumoniae following use of conjugate vaccines

Understanding how pneumococci respond to pneumococcal conjugate vaccines (PCVs) is crucial to predict the impact of upcoming higher-valency vaccines. However, stages in pneumococcal community succession following disturbance are poorly understood as long-time series on carriage are scarce and mostly evaluated at end-point measurements. We used a 20-year cross-sectional dataset of pneumococci carried by Portuguese children, and methods from community ecology, to study community assembly and diversity following use of PCV7 and PCV13. Two successional stages were detected upon introduction of each PCV: one in which non-vaccine serotypes increased in abundance, fitted by a broken-stick model, and a second in which the community returned to the original structure, fitted by a geometric series, but with different serotype profile and a drop in richness as great as 24%. A peak in diversity was observed for levels of intermediate vaccine uptake (30-40%) in agreement with the intermediate disturbance hypothesis. Serotype replacement was fitted by an exponential decay model (R-2 = 80%, P < 0.001). The half-life for replacement was 8 years for PCV7 and 10 years for PCV13. The structure of the pneumococcal community is resilient to vaccine pressure. The increasing loss of diversity, however, suggests it could eventually reach a threshold beyond which it may no longer recover.

Automated summary

Understanding the response of pneumococci to pneumococcal conjugate vaccines (PCVs) is important for predicting the impact of future vaccines. This study used a 20-year dataset of pneumococci carried by Portuguese children and community ecology methods to examine community assembly and diversity following the introduction of PCV7 and PCV13. The results showed two successional stages, with a peak in diversity observed at intermediate vaccine uptake levels. Serotype replacement followed an exponential decay model and the half-life for replacement was longer for PCV13 than PCV7. The structure of the pneumococcal community is resilient to vaccine pressure, but the loss of diversity suggests a potential threshold beyond which recovery may be difficult.