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. 2025 Feb 20;231(2):e328-e336.
doi: 10.1093/infdis/jiae550.

A Potential Platform for Future Vaccine Trials Identifies a High Incidence of Symptomatic and Asymptomatic Influenza Infection Among Children Aged 6 to 23 Months in South Africa

Cheryl Cohen  1   2 , Mignon du Plessis  1   3 , Neil Martinson  4   5 , Jocelyn Moyes  1 , Sibongile Walaza  1   2 , Nicole Wolter  1   3 , Mvuyo Makhasi  1   2 , Fahima Moosa  1   3 , Myrna Charles  6 , Aaron M Samuels  6   7 , Stefano Tempia  7 , Tumelo Moloantoa  4 , Bekiwe Ncwana  4 , Louisa Phalatse  4 , Amelia Buys  1 , Alicia Fry  8 , Eduardo Azziz Baumgartner  6 , Anne von Gottberg  1   3 , Jackie Kleynhans  1   2
Affiliations

A Potential Platform for Future Vaccine Trials Identifies a High Incidence of Symptomatic and Asymptomatic Influenza Infection Among Children Aged 6 to 23 Months in South Africa

Cheryl Cohen et al. J Infect Dis. .

Abstract

Background: Approaches for determining whether influenza vaccination prevents infection, attenuates illness, or both are important for developing improved vaccines. We estimated influenza infection incidence and evaluated symptom ascertainment methodologies in children to inform future vaccine trial design.

Methods: We conducted a prospective cohort study among children aged 6 to 23 months from May to October 2022. Study nurses collected symptom and temperature data and midturbinate nasal swabs twice weekly irrespective of symptoms; caregivers entered symptom data daily and collected nasal swabs weekly. Samples were tested for influenza with polymerase chain reaction.

Results: Of 230 healthy screened children, 93 were enrolled, of whom 87 (94%) completed 6-month follow-up. In total, 95% (4245/4476) of scheduled nurses, 90% (2045/2276) of caregiver swabs, 99% (92/93) of baseline blood collections, and 67% (9245/13 768) of scheduled symptom diaries were completed. Polymerase chain reaction-confirmed influenza incidence was 65% (60/93) for ≥1 infection; 11 (18%) individuals had 2 episodes and 1 (2%) had 3. Of 73 episodes, 55 (75%) had ≥1 symptom and 37 (51%) had fever (measured and/or reported). Median infection duration was 7 days (IQR, 4-9). Human RNase P gene was detected in 99% (2032/2045) of caregiver-collected swabs, through which 5 additional episodes were identified. Per episode, caregivers' diaries of reported and measured fever were 19% (25/73, 34%) and 11% (15/73, 21%) higher than nurse-reported (11/73, 15%) and nurse-measured (7/73, 10%) fever, respectively.

Conclusions: The incidence of influenza infection was high and mainly symptomatic, suggesting that this platform could be suitable for future trials of vaccine efficacy and correlates of protection against infection and illness in children.

Keywords: South Africa; influenza; symptoms; transmission; vaccine.

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Conflict of interest statement

Potential conflicts of interest . C. C. has received grant support from Sanofi Pasteur, US Centers for Disease Control and Prevention, the Bill & Melinda Gates Foundation, and Wellcome. A. v. G. has received grant support from Sanofi Pasteur and Pfizer related to pneumococcal vaccine, US Centers for Disease Control and Prevention, and the Bill & Melinda Gates Foundation. N. W. report grants from Sanofi Pasteur and the Bill & Melinda Gates Foundation. N. M. has received a grant to his institution from Pfizer to conduct research in patients with pneumonia and from Roche to collect specimens to assess a novel tuberculosis assay. J. K. received travel support from the Fogarty International Center, National Institutes of Health, and the Bill & Melinda Gates Foundation. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Figures

Figure 1.
Figure 1.
Influenza detection among children aged 6 to 23 months, ISiT study, South Africa, 2022: A, influenza A(H1N1)pdm09; B, influenza A (H3N2); C, influenza B Victoria. Columns are individual follow-up visits, and rows are individual participants. Follow-up visits are colored white if no sample was tested and light gray if the sample tested negative for influenza. For nasopharyngeal swabs that tested positive for influenza, follow-up visits are colored according to the influenza types and subtypes indicated in the legend. First and last columns are colored according to hemaglutination inhibition titer <40. ISiT, Identifying Symptoms in Toddlers.
Figure 2.
Figure 2.
Influenza detection among children aged 6 to 23 months with repeat influenza infections, ISiT study, South Africa, 2022. Columns are individual follow-up visits, and rows are individual participants. Follow-up visits are colored white if no sample was tested and light gray if the sample tested negative for influenza. For nasopharyngeal swabs that tested positive for influenza, follow-up visits are colored according to the influenza types and subtypes indicated in the legend. ISiT, Identifying Symptoms in Toddlers.
See this image and copyright information in PMC

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