Effectiveness of Seasonal Influenza Vaccination in Children in Senegal During a Year of Vaccine Mismatch: A Cluster-randomized Trial

Abstract

Background: The population effects of influenza vaccination in children have not been extensively studied, especially in tropical, developing countries. In rural Senegal, we assessed the total (primary objective) and indirect effectiveness of a trivalent inactivated influenza vaccine (IIV3).

Methods: In this double-blind, cluster-randomized trial, villages were randomly allocated (1:1) for the high-coverage vaccination of children aged 6 months through 10 years with either the 2008-09 northern hemisphere IIV3 or an inactivated polio vaccine (IPV). Vaccinees were monitored for serious adverse events. All village residents, vaccinated and unvaccinated, were monitored for signs and symptoms of influenza illness using weekly home visits and surveillance in designated clinics. The primary outcome was all laboratory-confirmed symptomatic influenza.

Results: Between 23 May and 11 July 2009, 20 villages were randomized, and 66.5% of age-eligible children were enrolled (3918 in IIV3 villages and 3848 in IPV villages). Follow-up continued until 28 May 2010. There were 4 unrelated serious adverse events identified. Among vaccinees, the total effectiveness against illness caused by the seasonal influenza virus (presumed to all be drifted A/H3N2, based on antigenic characterization data) circulating at high rates among children was 43.6% (95% confidence interval [CI] 18.6-60.9%). The indirect effectiveness against seasonal A/H3N2 was 15.4% (95% CI -22.0 to 41.3%). The total effectiveness against illness caused by the pandemic influenza virus (A/H1N1pdm09) was -52.1% (95% CI -177.2 to 16.6%).

Conclusions: IIV3 provided statistically significant, moderate protection to children in Senegal against circulating, pre-2010 seasonal influenza strains, but not against A/H1N1pdm09, which was not included in the vaccine. No indirect effects were measured. Further study in low-resource populations is warranted.

Clinical trials registration: NCT00893906.

Keywords: developing countries; herd immunity; human influenza; influenza vaccines; randomized controlled trial.

Figure 1.

Geographic distribution of villages randomized to IIV3 and IPV campaigns and achieved village-level vaccination coverage among age-eligible children for the campaigns during the trial, from the Niakhar Demographic Surveillance System. The IIV3 campaigns were conducted in the 10 villages that are shaded gray and the IPV campaigns were conducted in the 10 villages that are shaded white. Coverage is shown as the percent of age-eligible children—6 months through 10 years of age—receiving at least 1 dose. Enhanced, passive surveillance was conducted in the 3 health posts marked with triangles. Abbreviations: IIV3, trivalent inactivated influenza vaccine; IPV, inactivated polio vaccine.

Figure 2.

Study profile. The profile is designed for the primary objective of total effectiveness. Abbreviations: DSS, Demographic Surveillance System; IIV3, trivalent inactivated influenza vaccine; IPV, inactivated polio vaccine.

Figure 3.

Influenza detection, by type and subtype, from Week 28 of 2009 to Week 21 of 2010, Niakhar Demographic Surveillance System. The graph is a stacked column chart where numbers of real-time reverse transcription polymerase chain reaction–positive detections for each strain, each week, are stacked and can be visually summed. Of the 1559 A/H3N2 detections, 61 were from residents of the 10 Niakhar villages not randomized to study vaccines who presented to health posts. Additionally, 99 detections from residents of the 20 Niakhar villages randomized to study vaccines were excluded from the effectiveness analyses (82 were from residents whose signs and symptoms did not meet the clinical case definition and 17 were from residents with a previous A/H3N2 detection that season). Determination of B lineage was not routine practice for the National Influenza Centers in 2009–2010.