The Effect of Live Attenuated Influenza Vaccine on Pneumococcal Colonisation Densities Among Children Aged 24-59 Months in the Gambia - A Phase IV, Open Label, Randomised Controlled Trial

Chikondi Peno, Edwin Armitage, Melanie Clerc, Carlos Lopez Balcazar, Ya Jankey Jagne, Sainabou Drammeh, Sheikh Jarju, Hadijatou Sallah, Elina Senghore, Benjamin B. Lindsey, Janko Camara, Sulayman Bah, Nuredin I. Mohammed, David H. Dockrell, Beate Kampmann, Debby Bogaert, Thushan I. De Silva

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Background: Influenza and other respiratory viruses promote Streptococcus pneumoniae proliferation in the upper respiratory tract. We investigated the effect of intranasal live attenuated influenza vaccine (LAIV) on nasopharyngeal S. pneumoniae density in Gambian children, to study LAIV-pneumococcal interactions for the first time in a low and middle-income country (LMIC) with high pneumococcal carriage rates.

Methods: In an open-label, randomised controlled trial (NCT02972957) in The Gambia, 330 healthy children aged 24-59 months were randomised 2:1 to receive one trivalent LAIV dose at enrolment (day 0, intervention) or at the end of active follow up (day 21, control). The primary outcome was PCR-quantified day 7 and 21 pneumococcal density. Generalised mixed-effects models were used to assess the impact of LAIV and other co-variates on pneumococcal densities.

Findings: Between Feb-April, 2017, and Jan-March, 2018, 213 intervention and 108 control group children completed the study protocol. The baseline S. pneumoniae carriage rate was high (74.9%) and did not increase significantly following LAIV. LAIV administration at enrolment was associated with higher pneumococcal density during the study period (p=0.0097), with a small increase in mean density observed from day 0 (18197 copies/ml) to day 7 (28840 copies/ml) and day 21 (32359 copies/ml). Younger age (p=0.0030), baseline asymptomatic respiratory viral infection (p=0.017), and greater LAIV shedding at day 7 (p=0.024) were associated with higher pneumococcal density.

Interpretation: LAIV led to an increased nasopharyngeal pneumococcal density in the 21 days following vaccination, but at a lower magnitude (1.78-fold) than in the only previous study, conducted in children from the UK (6-fold); providing reassurance for LAIV use in LMIC with high pneumococcal carriage. This increase was accelerated when LAIV was administered in the presence of pre-existing asymptomatic respiratory viruses, suggesting that nasopharyngeal S. pneumoniae proliferation is driven by the integration of net viral interactions.

Clinical Trial Registration Details: NCT02972957.

Funding Information: This study was funded by a Wellcome Trust 514 Intermediate Clinical Fellowship award (to TIdS; 110058/Z/15/Z).

Declaration of Interests: The authors declare no competing interests.

Ethics Approval Statement: The study was approved by The Gambia Government and UK Medical Research Council joint ethics committee and the Medicines Control Agency of The Gambia. Parents provided written or thumbprinted informed consent for their children to participate. If parents were not English literate, an impartial witness was present during the informed consent discussion performed in a local language, who signed to confirm completeness of the consent provided.
Original languageEnglish
JournalSSRN Electronic Journal
Early online date10 Sept 2021
DOIs
Publication statusE-pub ahead of print - 10 Sept 2021

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