Evaluation of statistical models of carriage to predict the impact of the 10-valent pneumococcal conjugate vaccine on invasive pneumococcal disease in Nigeria

Background: A substantial fraction of the population-level impact of Pneumococcal Conjugate Vaccines (PCVs) on Invasive Pneumococcal Disease (IPD) is mediated through indirect effects, i.e., their capacity to protect against carriage acquisition of vaccine serotypes (VTs) among vaccinees, thereby proportionately reducing transmission and indirectly averting invasive disease in the whole population. Therefore, by relying on the consequent near elimination of VT carriage, early carriage-based models successfully captured the impact of seven-valent PCV (PCV7) in high-income settings. We sought to determine the applicability of three published statistical carriage-based models for the evaluation of PCV10 impact in Nigeria, where carriage prevalence data are available from urban and rural sites. Methods: We applied external data, with assumptions, to empirical carriage prevalence data to predict IPD incidence rate ratios (IRRs). The models assume PCV has no effect on serotype invasiveness among carriers because VT carriage is eliminated. Model 1 uses estimates of relative proportions of pre-PCV VT-IPD to predict IRRs. Model 2 uses pre-PCV serotype IPD incidence, while Model 3 uses measures of serotype invasiveness, the case-carrier ratio (CCR). Results: Model 1 estimates the largest PCV10 impact on overall IPD (IRR:0.38 and 0.50) in the urban and rural sites, respectively. Whereas estimates from Model 2 (IRR:0.69 and 0.78) and Model 3 (IRR:0.63 and 0.70) were more conservative. Conclusions: VT carriage was not eliminated in our setting, so Model 1 estimates the hypothetical maximum impact. Relying entirely on indirect effects, Models 2 and 3 represent the minimum impact of PCV. Predictions would be more accurate if they accounted for direct effects among vaccinated VT carriers. The study illustrates the importance of capturing vaccination data on individuals sampled in carriage prevalence surveys designed to estimate IPD burden at population level. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported through the DELTAS Africa Initiative (DEL-15- 003). The DELTAS Africa Initiative is an independent funding scheme of the African Academy of Sciences (AAS) Alliance for Accelerating Excellence in Science in Africa (AESA) and supported by the New Partnership for Africa Development Planning and Coordinating Agency (NEPAD Agency) with funding from the Wellcome Trust (107769/Z/10/Z) and the UK government. The views expressed in this publication are those of the author(s) and not necessarily those of AAS, NEPAD Agency, Wellcome Trust or the UK government. IMOA is funded by the UK Medical Research Council and Department For International Development through an African Research Leader Fellowship (MR/S005293/1) and by the NIHR-MPRU at UCL (grant 2268427 LSHTM). JAGS is funded by a Wellcome Trust Senior Research Fellowship (214320) and the NIHR Health Protection Research Unit in Immunisation. JO is funded by the NIHR Global Health Research Unit on Mucosal Pathogens (16/136/46). The funders had no role in the study design, data collection, data analysis, data interpretation or writing of the report. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used openly available human data that were originally located at: A. L. Adamu et al., The impact of introduction of the 10-valent pneumococcal conjugate vaccine on pneumococcal carriage in Nigeria. Nat. Commun. 14, 2666 (2023). H. L. Johnson et al., Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: the pneumococcal global serotype project. PLoS Med. 7 (2010), doi:10.1371/journal.pmed.1000348. A. Lochen, J. E. Truscott, N. J. Croucher, Analysing pneumococcal invasiveness using Bayesian models of pathogen progression rates. PLoS Comput. Biol. 18, e1009389 (2022). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced are available online at: A. L. Adamu et al., The impact of introduction of the 10-valent pneumococcal conjugate vaccine on pneumococcal carriage in Nigeria. Nat. Commun. 14, 2666 (2023). H. L. Johnson et al., Systematic evaluation of serotypes causing invasive pneumococcal disease among children under five: the pneumococcal global serotype project. PLoS Med. 7 (2010), doi:10.1371/journal.pmed.1000348. A. Lochen, J. E. Truscott, N. J. Croucher, Analysing pneumococcal invasiveness using Bayesian models of pathogen progression rates. PLoS Comput. Biol. 18, e1009389 (2022).