1887

Abstract

The transmission dynamics of 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 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 (χ=47.5, df=21, -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 (-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 (-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 (-value <0.05, OR 1.5). PCV7 serotypes were rare (13.5 %) and were significantly less likely to be shared (-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.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-02-04
2022-08-10
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References

  1. Bogaert D, De Groot R, Hermans PWM. Streptococcus pneumoniae colonisation: the key to pneumococcal disease. Lancet Infect Dis 2004; 4:144–154 [View Article] [PubMed]
    [Google Scholar]
  2. Usuf E, Bottomley C, Adegbola RA, Hall A, Trotter CL. Pneumococcal carriage in Sub-Saharan Africa—A systematic review. PLoS ONE 2014; 9:e85001 [View Article]
    [Google Scholar]
  3. Lloyd-Evans N, O’Dempsey TJ, Baldeh I, Secka O, Demba E et al. Nasopharyngeal carriage of pneumococci in Gambian children and in their families. Pediatr Infect Dis J 1996; 15:866–871 [View Article] [PubMed]
    [Google Scholar]
  4. Hill PC, Townend J, Antonio M, Akisanya B, Ebruke C et al. Transmission of Streptococcus pneumoniae in rural Gambian villages: a longitudinal study. Clin Infect Dis 2010; 50:1468–1476 [View Article] [PubMed]
    [Google Scholar]
  5. Read AF. The evolution of virulence. Trends Microbiol 1994; 2:73–76 [View Article] [PubMed]
    [Google Scholar]
  6. Bull JJ. VIRULENCE. Evolution John Wiley & Sons, Ltd 1994; 48:1423–1437
    [Google Scholar]
  7. Ypma RJF, Bataille AMA, Stegeman A, Koch G, Wallinga J et al. Unravelling transmission trees of infectious diseases by combining genetic and epidemiological data. Proc Biol Sci 2012; 279:444–450 [View Article] [PubMed]
    [Google Scholar]
  8. De Maio N, Worby CJ, Wilson DJ, Stoesser N, Koelle K. Bayesian reconstruction of transmission within outbreaks using genomic variants. PLoS Comput Biol 2018; 14:e1006117 [View Article]
    [Google Scholar]
  9. Didelot X, Fraser C, Gardy J, Colijn C. Genomic infectious disease epidemiology in partially sampled and ongoing outbreaks. Mol Biol Evol 2017; 34:997–1007 [View Article] [PubMed]
    [Google Scholar]
  10. Stimson J, Gardy J, Mathema B, Crudu V, Cohen T et al. Beyond the SNP threshold: identifying outbreak clusters using inferred transmissions. Mol Biol Evol 2019; 36:587–603 [View Article]
    [Google Scholar]
  11. Worby CJ, Lipsitch M, Hanage WP. Within-host bacterial diversity hinders accurate reconstruction of transmission networks from genomic distance data. PLoS Comput Biol. Public Library of Science 2014; 10:e1003549 [View Article] [PubMed]
    [Google Scholar]
  12. Leitner T. Phylogenetics in HIV transmission: taking within-host diversity into account. Curr Opin HIV AIDS 2019; 14:181–187 [View Article] [PubMed]
    [Google Scholar]
  13. Lee RS, Proulx J-. F, McIntosh F, Behr MA, Hanage WP. Previously undetected super-spreading of Mycobacterium tuberculosis revealed by deep sequencing. eLife. eLife Sciences Publications Limited 20209 9: [View Article]
    [Google Scholar]
  14. Hall MD, Holden MT, Srisomang P, Mahavanakul W, Wuthiekanun V et al. Improved characterisation of MRSA transmission using within-host bacterial sequence diversity. eLife. eLife Sciences Publications Limited 201988 [View Article]
    [Google Scholar]
  15. Campbell F, Cori A, Ferguson N, Jombart T, Pitzer VE. Bayesian inference of transmission chains using timing of symptoms, pathogen genomes and contact data. PLoS Comput Biol 2019; 15:e1006930 [View Article]
    [Google Scholar]
  16. Bhutta ZA, Sommerfeld J, Lassi ZS, Salam RA, Das JK. Global burden, distribution, and interventions for infectious diseases of poverty. Infect Dis Poverty 2014; 3:21 [View Article] [PubMed]
    [Google Scholar]
  17. Ombelet S, Ronat J-B, Walsh T, Yansouni CP, Cox J et al. Clinical bacteriology in low-resource settings: today’s solutions. Lancet Infect Dis 2018; 18:e248–e258 [View Article] [PubMed]
    [Google Scholar]
  18. Croucher NJ, Finkelstein JA, Pelton SI, Mitchell PK, Lee GM et al. Population genomics of post-vaccine changes in pneumococcal epidemiology. Nat Genet. Nature Publishing Group 2013; 45:656–663 [View Article] [PubMed]
    [Google Scholar]
  19. Chang H-. H, Dordel J, Donker T, Worby CJ, Feil EJ et al. Identifying the effect of patient sharing on between-hospital genetic differentiation of methicillin-resistant Staphylococcus aureus. Genome Med 2016; 8:10–18 [View Article] [PubMed]
    [Google Scholar]
  20. Kwambana-Adams B, Hanson B, Worwui A, Agbla S, Foster-Nyarko E et al. Rapid replacement by non-vaccine pneumococcal serotypes may mitigate the impact of the pneumococcal conjugate vaccine on nasopharyngeal bacterial ecology. Sci Rep Nature Publishing Group 2017; 7:8127–11 [View Article] [PubMed]
    [Google Scholar]
  21. Lourenço J, Obolski U, Swarthout TD, Gori A, Bar-Zeev N et al. Determinants of high residual post-PCV13 pneumococcal vaccine-type carriage in Blantyre, Malawi: a modelling study. BMC Med BioMed Central 2019; 17:219–11 [View Article] [PubMed]
    [Google Scholar]
  22. Kwambana-Adams BA, Asiedu-Bekoe F, Sarkodie B, Afreh OK, Kuma GK et al. An outbreak of pneumococcal meningitis among older children (≥5 years) and adults after the implementation of an infant vaccination programme with the 13-valent pneumococcal conjugate vaccine in Ghana. BMC Infect Dis. BioMed Central 2016; 16:575 [View Article] [PubMed]
    [Google Scholar]
  23. Gladstone RA, Lo SW, Lees JA, Croucher NJ, van Tonder AJ et al. International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact. EBioMedicine 2019; 43:338–346 [View Article] [PubMed]
    [Google Scholar]
  24. J. Page A, Taylor B, A. Keane J. Multilocus sequence typing by blast from de novo assemblies against PubMLST. J Open Source Softw 2016; 1:118 [View Article]
    [Google Scholar]
  25. Lees JA, Harris SR, Tonkin-Hill G, Gladstone RA, Lo SW et al. Fast and flexible bacterial genomic epidemiology with PopPUNK. Genome Res 2019; 29:304–316 [View Article] [PubMed]
    [Google Scholar]
  26. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article] [PubMed]
    [Google Scholar]
  27. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article] [PubMed]
    [Google Scholar]
  28. Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom 2016; 2:e000056 [View Article] [PubMed]
    [Google Scholar]
  29. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015; 43:e15–5 [View Article] [PubMed]
    [Google Scholar]
  30. Argimón S, Abudahab K, Goater RJE, Fedosejev A, Bhai J et al. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microb Genom 2016; 2:e000093 [View Article] [PubMed]
    [Google Scholar]
  31. Gouy M, Guindon S, Gascuel O. SeaView version 4: a multiplatform graphical user interface for sequence alignment and phylogenetic tree building. Mol Biol Evol 2010; 27:221–224 [View Article] [PubMed]
    [Google Scholar]
  32. Kwambana BA, Barer MR, Bottomley C, Adegbola RA, Antonio M. Early acquisition and high nasopharyngeal co-colonisation by Streptococcus pneumoniae and three respiratory pathogens amongst Gambian new-borns and infants. BMC Infect Dis 2011; 11:1 [View Article]
    [Google Scholar]
  33. Jusot J-F, Neill DR, Waters EM, Bangert M, Collins M et al. Airborne dust and high temperatures are risk factors for invasive bacterial disease. J Allergy Clin Immunol 2017; 139:977–986 [View Article] [PubMed]
    [Google Scholar]
  34. Mackenzie GA, Vilane A, Salaudeen R, Hogerwerf L, van den Brink S et al. Respiratory syncytial, parainfluenza and influenza virus infection in young children with acute lower respiratory infection in rural Gambia. Sci Rep 2019; 9:17965–10 [View Article] [PubMed]
    [Google Scholar]
  35. Numminen E, Chewapreecha C, Turner C, Goldblatt D, Nosten F et al. Climate induces seasonality in pneumococcal transmission. Sci Rep 2015; 5:11344–15 [View Article] [PubMed]
    [Google Scholar]
  36. Hill PC, Cheung YB, Akisanya A, Sankareh K, Lahai G et al. Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian infants: a longitudinal study. Clin Infect Dis 2008; 46:807–814 [View Article] [PubMed]
    [Google Scholar]
  37. Althouse BM, Hammitt LL, Grant L, Wagner BG, Reid R et al. Identifying transmission routes of Streptococcus pneumoniae and sources of acquisitions in high transmission communities. Epidemiol Infect 2017; 145:2750–2758 [View Article] [PubMed]
    [Google Scholar]
  38. Tigoi CC, Gatakaa H, Karani A, Mugo D, Kungu S et al. Rates of acquisition of pneumococcal colonization and transmission probabilities, by serotype, among newborn infants in Kilifi District, Kenya. Clin Infect Dis 2012; 55:180–188 [View Article] [PubMed]
    [Google Scholar]
  39. Numminen E, Cheng L, Gyllenberg M, Corander J. Estimating the transmission dynamics of Streptococcus pneumoniae from strain prevalence data. Biom. John Wiley & Sons, Ltd 2013; 69:748–757 [View Article]
    [Google Scholar]
  40. Kamng’ona AW, Hinds J, Bar-Zeev N, Gould KA, Chaguza C et al. High multiple carriage and emergence of Streptococcus pneumoniae vaccine serotype variants in Malawian children. BMC Infect Dis 2015; 15:234–11 [View Article]
    [Google Scholar]
  41. Soininen A, Pursiainen H, Kilpi T, Käyhty H. Natural development of antibodies to pneumococcal capsular polysaccharides depends on the serotype: association with pneumococcal carriage and acute otitis media in young children. J Infect Dis 2001; 184:569–576 [View Article] [PubMed]
    [Google Scholar]
  42. Brugger SD, Frey P, Aebi S, Hinds J, Mühlemann K et al. Multiple colonization with S. pneumoniae before and after Introduction of the seven-valent conjugated pneumococcal polysaccharide vaccine. PLoS ONE 2010; 5:e11638 [View Article]
    [Google Scholar]
  43. Swarthout TD, Gori A, Bar-Zeev N, Kamng’ona AW, Mwalukomo TS et al. Evaluation of pneumococcal serotyping of nasopharyngeal-carriage isolates by latex agglutination, whole-genome sequencing (PneumoCaT), and DNA microarray in a high-pneumococcal-carriage-prevalence population in Malawi. J Clin Microbiol 2020; 59:e02103-20. [View Article] [PubMed]
    [Google Scholar]
  44. Mackenzie GA, Hill PC, Jeffries DJ, Hossain I, Uchendu U et al. Effect of the introduction of pneumococcal conjugate vaccination on invasive pneumococcal disease in The Gambia: a population-based surveillance study. Lancet Infect Dis 2016; 16:703–711 [View Article] [PubMed]
    [Google Scholar]
  45. Pneumonia Etiology Research for Child Health (PERCH) Study Group Causes of severe pneumonia requiring hospital admission in children without HIV infection from Africa and Asia: the PERCH multi-country case-control study. Lancet 2019; 394:757–779 [View Article] [PubMed]
    [Google Scholar]
  46. Lipsitch M. Bacterial vaccines and serotype replacement: lessons from haemophilus influenzae and prospects for Streptococcus pneumoniae . Emerg Infect Dis 1999; 5:336–345 [View Article]
    [Google Scholar]
  47. Usuf E, Bottomley C, Bojang E, Cox I, Bojang A et al. Persistence of nasopharyngeal pneumococcal vaccine serotypes and increase of nonvaccine serotypes among vaccinated infants and their mothers 5 years after introduction of pneumococcal conjugate vaccine 13 in The Gambia. Clin Infect Dis 2019; 68:1512–1521 [View Article]
    [Google Scholar]
  48. Brueggemann AB, Jansen van Rensburg MJ, Shaw D, McCarthy ND, Jolley KA et al. Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data. Lancet Digit Health 2021e360–e370 [View Article] [PubMed]
    [Google Scholar]
  49. Wesolowski A, Buckee CO, Engø-Monsen K, Metcalf CJE. Connecting mobility to infectious diseases: the promise and limits of mobile phone data. J Infect Dis 2016; 214:S414–S420 [View Article] [PubMed]
    [Google Scholar]
  50. Leimkugel J, Adams Forgor A, Gagneux S, Pflüger V, Flierl C et al. An outbreak of serotype 1 Streptococcus pneumoniae meningitis in Northern Ghana with features that are characteristic of Neisseria meningitidis meningitis epidemics. J Infect Dis 2005; 192:192–199 [View Article] [PubMed]
    [Google Scholar]
  51. Brown SP, Cornforth DM, Mideo N. Evolution of virulence in opportunistic pathogens: generalism, plasticity, and control. Trends Microbiol 201220336–342 [View Article] [PubMed]
    [Google Scholar]
  52. Hanage WP, Kaijalainen TH, Syrjänen RK, Auranen K, Leinonen M et al. Invasiveness of serotypes and clones of Streptococcus pneumoniae among children in Finland. Infect Immun 2005; 73:431–435 [View Article] [PubMed]
    [Google Scholar]
  53. Yamaguchi M, Goto K, Hirose Y, Yamaguchi Y, Sumitomo T et al. Identification of evolutionarily conserved virulence factor by selective pressure analysis of Streptococcus pneumoniae . Commun Biol 2019; 2:96 [View Article] [PubMed]
    [Google Scholar]
  54. Browall S, Norman M, Tångrot J, Galanis I, Sjöström K et al. Intraclonal variations among Streptococcus pneumoniae isolates influence the likelihood of invasive disease in children. J Infect Dis 2014; 209:377–388 [View Article] [PubMed]
    [Google Scholar]
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