Belman Sophie, Lefrancq Noémie, Nzenze Susan, Downs Sarah, du Plessis Mignon, Lo Stephanie, McGee Lesley, Madhi Shabir A, von Gottberg Anne, Bentley Stephen D, Salje Henrik
Parasites and Microbes, Wellcome Sanger Institute; Hinxton, UK.
Department of Genetics, University of Cambridge; Cambridge, UK.
bioRxiv. 2023 Jan 18:2023.01.18.524577. doi: 10.1101/2023.01.18.524577.
is a leading cause of pneumonia and meningitis worldwide. Many different serotypes co-circulate endemically in any one location. The extent and mechanisms of spread, and vaccine-driven changes in fitness and antimicrobial resistance (AMR), remain largely unquantified. Using geolocated genome sequences from South Africa (N=6910, 2000-2014) we developed models to reconstruct spread, pairing detailed human mobility data and genomic data. Separately we estimated the population level changes in fitness of strains that are (vaccine type, VT) and are not (non-vaccine type, NVT) included in the vaccine, first implemented in 2009, as well as differences in strain fitness between those that are and are not resistant to penicillin. We estimated that pneumococci only become homogenously mixed across South Africa after about 50 years of transmission, with the slow spread driven by the focal nature of human mobility. Further, in the years following vaccine implementation the relative fitness of NVT compared to VT strains increased (RR: 1.29 [95% CI 1.20-1.37]) - with an increasing proportion of these NVT strains becoming penicillin resistant. Our findings point to highly entrenched, slow transmission and indicate that initial vaccine-linked decreases in AMR may be transient.
是全球肺炎和脑膜炎的主要病因。许多不同血清型在任何一个地区地方性共同流行。传播的范围和机制，以及疫苗驱动的适应性变化和抗菌药物耐药性（AMR），在很大程度上仍未得到量化。利用来自南非的地理定位基因组序列（N = 6910，2000 - 2014年），我们开发了模型来重建传播情况，将详细的人类流动数据和基因组数据相结合。我们分别估计了2009年首次实施的疫苗中包含的菌株（疫苗型，VT）和不包含的菌株（非疫苗型，NVT）在群体水平上的适应性变化，以及对青霉素耐药和不耐药的菌株之间的适应性差异。我们估计，肺炎球菌在传播约50年后才在南非实现均匀混合，其缓慢传播是由人类流动的局部性所驱动的。此外，在疫苗实施后的几年里，NVT菌株相对于VT菌株的相对适应性增加（RR：1.29 [95% CI 1.20 - 1.37]），并且这些NVT菌株中对青霉素耐药的比例不断增加。我们的研究结果表明传播高度顽固、缓慢，并且表明最初与疫苗相关的AMR下降可能是短暂的。
