Basic reproduction number for pandemicEscherichia coliclones is comparable to typical pandemic viruses

Abstract

Extra-intestinal pathogenicEscherichia coli(ExPEC) ubiquitously colonize the human gut and are clinically the most significant bacterial species causing urinary tract infections and bacteremia in addition to contributing to meningitis in neonates. During the last two decades, newE. colimulti-drug resistant (MDR) clones such as ST131, particularly clades C2 and C1, have spread globally, as has their less resistant counterpart ST131-A and phylodynamic modeling has indicated exponential growth in their populations during the early 2000s. However, it remains unknown how their transmission dynamics compare to viral epidemics and pandemics in terms of key epidemiological quantities such as the basic reproduction number (R0). Estimation ofR0for opportunistic pathogenic bacteria poses a difficult challenge compared to viruses causing acute infections, since data onE. coliinfections accumulate with a much longer delay, even in the most advanced public health reporting systems. Here, we develop a compartmental model for asymptomatic gut colonization and onward transmission coupled with a stochastic epidemiological observation model for bacteremia and fit the model to Norwegian nationalE. colidisease surveillance and bacterial population genomics data for 2002-2017. Approximate Bayesian Computation (ABC) leveraged by the ELFI (Engine for Likelihood-Free Inference) Python package is used to inferR0for the pandemic ST131-A and MDR ST131-C2 clades. The resulting estimates for ST131-A and ST131-C2 are 2.00 and 1.35, respectively, where the ST131-A estimate is comparable to the basic reproduction number of typical pandemic influenza. In summary our results provide a fundamental advance in understanding the effective transmission rate of novelE. coliclones.Significance StatementSimilar to viruses, novel clones of pathogenic bacteria have the po-tential for pandemic spread and may impose a considerable public health burden of infections. Unlike viruses, opportunistic pathogenic bacteria are mostly carried asymptomatically and cause delayed infections making it difficult to infer their transmission rates in the general population. We estimated a key epidemiological quantity, the basic reproduction number, for two clades of the pandemicEscherichia coliST131 clone and show that their transmission rates differ markedly and are comparable to typical pandemic viruses, such as influenza. This provides a significant advance in understanding how rapidly new clones ofE. colican establish themselves, highlighting the need to identify the genetic factors that drive transmission efficiency.