Estimates of the reproductive numbers and demographic reconstruction of outbreak associated with C:P1.5-1,10-8:F3-6:ST-11(cc11) Neisseria meningitidis strains

Abstract

Background: Neisseria meningitidis can cause sporadic cases and outbreaks of invasive disease, including meningitis and sepsis. The meningococcal serogroup C (MenC) is the second most common serogroup in Italy after MenB. In this study we have estimated the reproductive numbers and the demographic reconstruction on the genomes of invasive N. meningitidis C:P1.5-1,10-8:F3-6:ST-11(cc11) strains isolated in Italy in 2012 - 2017, a period that includes the outbreak in Tuscany.

Methods: The genomes of N. meningitidis were sequenced using the Illumina MiSeq platform, through the whole genome sequencing (WGS) method and were analyzed by the core genome MLST (cgMLST) approach, using the BIGSdb Genome Comparator tool implemented on the PubMLST website. A Bayesian method was applied to study population dynamics across the entire N. meningitidis dataset. The basic reproduction number R_0, which indicates the average number of secondary cases generated by a single primary case, was calculated using a Bayesian method, on the dataset and on the two subsets. The effective reproduction number R(t), defined as the average number of secondary cases per infectious case in a population, made up of susceptible and non-susceptible hosts was studied on the Tuscany dataset, with a Bayesian method.

Results: An increase in the effective number of the N. meningitidis infections was observed between 2013 and 2016. The estimated R₀ parameter was 1.31 (95% HPD: 1.03 - 1.64), 1.22 (95% HPD: 0.90 - 1.64) and 1.4 (95% HPD: 0.91 - 1.9) for the entire dataset, first and second subset, respectively. The BDSKY estimated an initial R(t) of about 2.0 (95% HPD: 0.04 - 5.0), which showed a growing trend at the end of 2014, reaching an average value of 3.22 in 2015, and then declining below 1 from the year 2016.

Conclusion: Monitoring the effective reproduction number can help to inform future vaccination strategies. The increase in the reproductive number for the Tuscany dataset, was consistent with the amplification event that led to the Tuscany outbreak. Subsequently, the intervention that led to the decline of the cases was followed, suggesting a high effectiveness of the vaccination campaign.

Keywords: Demographic reconstruction; Invasive meningococcal disease; N. meningitidis; Reproductive number; Surveillance.