Review 1: "Streptococcus Pneumoniae: Nasal Influenza Vaccination, Carriage Density and Transmission in Families"

Eliza Nikolaou

doi:doi:10.1162/2e3983f5.030a6c3c

Streptococcus pneumoniae: Nasal influenza vaccination, carriage density and transmission in families

by J. Metz, G Qian, B. Morales-Aza, J. Oliver, E. Oliver, K. Duale, P. Heath, S.N. Faust, M.D. Snape, S. Hughes, L. Hole, R. Mann, F. Shackley, P. Rudd, S. Ludman, BD. Gessner, L. Danon, and A. Finn

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Published on Apr 29, 2024
www.medrxiv.org

Description

Abstract The live attenuated influenza vaccine (LAIV) is offered in the United Kingdom to young children, protecting against influenza for those vaccinated and indirect protection for the wider community. It has also been shown to increase carriage density of Streptococcus pneumoniae, to an extent, in children. This study therefore investigates whether the vaccine leads to an increase in density in children and, if so, whether this augments transmission to household contacts.We implemented a randomised control study involving 405 two-year-old children and 958 household contacts. Nasopharyngeal swabs from all participants were taken over 5 visits, each two weeks apart, and tested for pneumococcal carriage. LAIV was given to 205 children at visit 1, and to 200 children at visit 2.We developed regression models to analyse the association between vaccination and whether an increase in pneumococcal density 14 and 28 days later was observed, as well as an increase in the odds of transmission to household members after administering LAIV.From regression analyses, there was a 2-fold (95%CI:1.0-3.1, p=0.01) increase in the odds of vaccinated children to have increased pneumococcal density 2 weeks later, compared with unvaccinated children, and a 1.8-fold (95%CI:1.0-3.1, p=0.01) increase in the odds of presumed transmission from children to their household contacts.Our results provide evidence that an attenuated influenza virus infection transiently increases the likelihood of pneumococcal transmission from children who are colonised with the bacterium to their contacts and that this increase is driven by an increase in bacterial abundance triggered by the vaccine.

RR:C19 Evidence Scale rating by reviewer:

Reliable. The main study claims are generally justified by its methods and data. The results and conclusions are likely to be similar to the hypothetical ideal study. There are some minor caveats or limitations, but they would/do not change the major claims of the study. The study provides sufficient strength of evidence on its own that its main claims should be considered actionable, with some room for future revision.

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Review: Streptococcus pneumoniae (pneumococcus) is a common member of the upper respiratory tract in healthy people. Colonising pneumococci can be shed into respiratory secretions and be transmitted to a new host. Pneumococcal carriage rates are highest among young children who are frequently the route of entry of the bacterium into households. Few studies have investigated household pneumococcal transmission, but we still not fully understand the factors that determine pneumococcal transmission between members (hosts). The authors presented a well-written report discussing the role of pneumococcal density on household transmission. In humans, viruses can increase nasopharyngeal pneumococcal carriage density which in turn contributes to pneumococcal disease progression, but it is still unclear how density contributes to transmission of this exclusively human pathogen. So, indeed this is an important study.

The manuscript is very informative. The study design was carefully planned and easy to follow. The data analysis was clear and presented in a logical manner. The study concluded that the attenuated influenza virus infection increases the likelihood of pneumococcal transmission from young children who are colonised with the bacterium to their home contacts and that this increase is driven largely by an increase in bacterial abundance triggered by the influenza vaccine. These main conclusions and claims were substantiated by the evidence presented. However, as well-noted by the authors, limitations on the methodology for pneumococcal detection carriage making it less certain that a pneumococcal transmission event from a study child to a family member occurred for any individual child. Detection of pneumococcus was conducted only by targeting the autolysin (lytA) gene. The lytA gene is not specific to pneumococcus as other alpha-hemolytic Streptococci may have this gene. As such one or even two additional gene targets (i.e. piaB, SP2020) could potentially have been used to confirm pneumococcal positivity. On top of that, no serotype confirmation was conducted making it harder to study transmission events.

Studying pneumococcal transmission is extremely challenging as it requires frequent longitudinal sampling alongside epidemiological data to identify transmission events. I was positively surprised with the participants’ compliance of collecting nasopharyngeal swabs as recently swabs are getting less accepted from study participants. As authors noted, more frequent sampling could potentially give better precision regarding density changes and transmission events, however I wouldn’t anticipate changing the overall conclusions.