Widespread sharing of pneumococcal strains in a rural African setting: proximate villages are more likely to share similar strains that are carried at multiple timepoints

Abstract

The transmission dynamics of Streptococcus pneumoniae in sub-Saharan Africa are poorly understood due to a lack of adequate epidemiological and genomic data. Here we leverage a longitudinal cohort from 21 neighbouring villages in rural Africa to study how closely related strains of S. pneumoniae are shared among infants. We analysed 1074 pneumococcal genomes isolated from 102 infants from 21 villages. Strains were designated for unique serotype and sequence-type combinations, and we arbitrarily defined strain sharing where the pairwise genetic distance between strains could be accounted for by the mean within host intra-strain diversity. We used non-parametric statistical tests to assess the role of spatial distance and prolonged carriage on strain sharing using a logistic regression model. We recorded 458 carriage episodes including 318 (69.4 %) where the carried strain was shared with at least one other infant. The odds of strain sharing varied significantly across villages (χ²=47.5, df=21, P-value <0.001). Infants in close proximity to each other were more likely to be involved in strain sharing, but we also show a considerable amount of strain sharing across longer distances. Close geographic proximity (<5 km) between shared strains was associated with a significantly lower pairwise SNP distance compared to strains shared over longer distances (P-value <0.005). Sustained carriage of a shared strain among the infants was significantly more likely to occur if they resided in villages within a 5 km radius of each other (P-value <0.005, OR 3.7). Conversely, where both infants were transiently colonized by the shared strain, they were more likely to reside in villages separated by over 15 km (P-value <0.05, OR 1.5). PCV7 serotypes were rare (13.5 %) and were significantly less likely to be shared (P-value <0.001, OR -1.07). Strain sharing was more likely to occur over short geographical distances, especially where accompanied by sustained colonization. Our results show that strain sharing is a useful proxy for studying transmission dynamics in an under-sampled population with limited genomic data. This article contains data hosted by Microreact.

Keywords: pneumococcal transmission dynamics; rural African setting.

Fig. 1.

Relationship between pairwise genetic distance of colonizing strains and spatial distance between villages where infants reside. (a) The plot shows normalized proportion of pairwise comparisons within a given spatial proximity range (three categories:0–5 km, 5–15 km and 15+km) below a SNP threshold. (b) Distribution of pairwise SNP distances across the three spatial distance ranges. (c) Frequency density distribution of pairwise SNP distances by spatial distance range. (****=P-value <0.0001).

Fig. 2.

Effect of spatial distance on the dynamics of strain sharing involving infants with sustained colonization, transient colonization or a mixed pair of infants. (a) Spatial distribution of strains shared between infants with sustained carriage of shared strains, transient colonization in both or a mixed pair of two infants with sustained and transient carriage respectively. (b–d) Distribution of mean pairwise SNP differences across all variants of the strain among infant pairs by spatial distance in the three categories: sustained carriers, mixed pairs and transient carriers, respectively. (P-value; *<0.05; **<0.005; ****<0.0001).

Fig. 3.

Trends in strain sharing across villages. A network of strain sharing across villages, each node represents a village and villages are plotted based on the GPS latitude and longitude coordinates. Each undirected edge represents strain sharing between the two villages and edges are weighted based on the number of shared strains. Edges are coloured based on the distance between the villages.