In June 2009, for the first time in France, a confirmed outbreak of influenza A(H1N1)v without history of travel occurred in a secondary school in Toulouse district. A total of 15 cases were confirmed among students of which three were asymptomatic. This report describes the outbreak and its public health implications.

Outbreak of influenza A(H1N1)v without travel history in a school in the Toulouse district, France, June 2009.

The influenza M2 ectodomain (M2e) is well conserved across human influenza A subtypes, but there are few residue changes among avian and swine origin influenza A viruses. We expressed a tandem repeat construct of heterologous M2e sequences (M2e5x) derived from human, swine, and avian origin influenza A viruses using the yeast expression system. Intramuscular immunization of mice with AS04-adjuvanted M2e5x protein vaccines was effective in inducing M2e-specific antibodies reactive to M2e peptide and native M2 proteins on the infected cells with human, swine, or avian influenza virus, mucosal and systemic memory cellular immune responses, and cross-protection against H3N2 virus. Importantly, M2e5x immune sera were found to confer protection against different subtypes of H1N1 and H5N1 influenza A viruses in naive mice. Also, M2e5x-immune complexes of virus-infected cells stimulated macrophages to secrete cytokines via Fc receptors, indicating a possible mechanism of protection. The present study provides evidence that M2e5x proteins produced in yeast cells could be developed as a potential universal influenza vaccine.

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Cross Protection against Influenza A Virus by Yeast-Expressed Heterologous Tandem Repeat M2 Extracellular Proteins

We describe virus variations from patients with influenza-like illness before and after the appearance of influenza A(H1N1)pdm09 in Kenya during January 2008-July 2011. A total of 11,592 nasopharyngeal swabs were collected from consenting patients. Seasonal influenza B, A/H1N1, A/H3N2, A/H5N1, and influenza A(H1N1)pdm09 viruses were detected by real-time reverse transcription-polymerase chain reaction. Of patients enrolled, 2073 (17.9%) had influenza. A total of 1,524 (73.4%) of 2,073 samples were positive for influenza A virus and 549 (26.6%) were positive for influenza B virus. Influenza B virus predominated in 2008 and seasonal A(H1N1) virus predominated in the first half of 2009. Influenza A(H1N1)pdm09 virus predominated in the second half of 2009. Influenza A/H3N2 virus predominated in 2010, and co-circulation of influenza A(H1N1)pdm09 virus and influenza B virus predominated the first half of 2011. The reduction and displacement of seasonal A(H1N1) virus was the most obvious effect of the arrival of influenza A(H1N1)pdm09 virus. The decision of the World Health Organization to replace seasonal A(H1N1) virus with the pandemic virus strain for the southern hemisphere vaccine was appropriate for Kenya.

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Impact of Influenza A(H1N1)pdm09 Virus on Circulation Dynamics of Seasonal Influenza Strains in Kenya

Influenza A (H1N1) pdm09 virus emerged in North America in 2009 and has been established as a seasonal strain in humans. After an antigenic stasis of about six years, new antigenically distinct variants of the virus emerged globally in 2016 necessitating a change in the vaccine formulation for the first time in 2017. Herein, we analyzed thirty-eight HA sequences of influenza A (H1N1) pdm09 strains isolated in Kenya during 2015-2018 seasons, to evaluate their antigenic and molecular properties based on the HA1 sub-unit. Our analyses revealed that the A (H1N1) pdm09 strains that circulated in Kenya during this period belonged to genetic clade 6B, subclade 6B.1 and 6B.2. The Kenyan 2015 and 2016 isolates differed from the vaccine strain A/California/07/2009 at nine and fourteen antigenic sites in the HA1 respectively. Further, those isolated in 2017 and 2018 correspondingly varied from A/Michigan/45/2015 vaccine strain at three and fifteen antigenic sites. The predicted vaccine efficacy of A/California/07/2009 against Kenyan 2015/2016 was estimated to be 32.4% while A/Michigan/45/2015 showed estimated vaccine efficacies of 39.6% - 41.8% and 32.4% - 42.1% against Kenyan 2017 and 2018 strains, respectively. Hemagglutination-inhibition (HAI) assay using ferret post-infection reference antiserum showed that the titers for the Kenyan 2015/2016 isolates were 2-8-fold lower compared to the vaccine strain. Overall, our results suggest the A (H1N1) pdm09 viruses that circulated in Kenya during 2015/2016 influenza seasons were antigenic variants of the recommended vaccine strains, denoting sub-optimal vaccine efficacy. Additionally, data generated point to a swiftly evolving influenza A (H1N1) pdm09 virus in recent post pandemic era, underscoring the need for sustained surveillance coupled with molecular and antigenic analyses, to inform appropriate and timely influenza vaccine update.

Assessing antigenic drift and phylogeny of influenza A (H1N1) pdm09 virus in Kenya using HA1 sub-unit of the hemagglutinin gene

Background: Influenza infection is a serious public health problem that causes an estimated 3 to 5 million cases and 250,000 deaths worldwide every year. The epidemiology of influenza is well-documented in high- and middle-income countries, however minimal effort had been made to understand the epidemiology, burden and seasonality of influenza in Africa. This study aims to assess the state of knowledge of seasonal influenza epidemiology in Africa and identify potential data gaps for policy formulation following the 2009 pandemic.
Method: We reviewed articles from Africa published into four databases namely: MEDLINE (PubMed), Google Scholar, Cochrane Library and Scientific Research Publishing from 2010 to 2019.
Results: We screened titles and abstracts of 2070 studies of which 311 were selected for full content evaluation and 199 studies were considered. Selected articles varied substantially on the basis of the topics they addressed covering the field of influenza surveillance (n=80); influenza risk factors and co-morbidities (n=15); influenza burden (n=37); influenza vaccina- tion (n=40); influenza and other respiratory pathogens (n=22) and influenza diagnosis (n=5).
Conclusion: Significant progress has been made since the last pandemic in understanding the influenza epidemiology in Africa. However, efforts still remain for most countries to have sufficient data to allow countries to prioritize strategies for influenza prevention and control.
Keywords: Influenza; epidemiology; review; Africa; post pandemic.

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The epidemiology of seasonal influenza after the 2009 influenza pandemic in Africa: a systematic review

Phylogenetic analyses revealed that influenza B viruses were closely related to B/Brisbane/60/2008 vaccine strain while A (H1N1) pdm09 viruses were genetic variants of A/California/07/2009. The Kenyan A (H1N1) pdm09 isolates had P83S, D97N, S185T, I321V and E374K amino acid substitutions. Influenza A/H3N2 isolates showed K62E, T212A and S214I simultaneous amino acid substitutions when compared to A/Perth/10/2009. The K62E change occurred at antigenic site E. Majority of the Kenyan H3N2 isolates further had S45N and K144N amino acid substitutions at sites C and A respectively, which introduced N-glycosylation motifs absent in the vaccine strain.

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Were the WHO-recommended Human Influenza Vaccine Formulations Appropriate for Kenya During the 2010-2011 Season? Inferences from the HA1 Gene Analysis

Background The US Army Medical Research Unit-Kenya (USAMRU-K) conducts surveillance for influenza-like illness (ILI) in Kenya. We describe the temporal and geographic progression of A(H1N1)pdm09 as it emerged in Kenya and characterize the outpatient population with A(H1N1)pdm09 infection. Methods We included patients with ILI aged 2 months to 18 years enrolled during June 2009-August 2010. Respiratory specimens were tested by real-time reverse-transcription polymerase chain reaction for influenza virus. Patients with A(H1N1)pdm09 infection were compared to those with seasonal influenza A virus infection and those with ILI who had no virus or a virus other than influenza virus identified (hereafter, "noninfluenza ILI"). Results Of 4251 patients with ILI, 193 had laboratory-confirmed A(H1N1)pdm09 infection. The first pandemic influenza case detected by USAMRU-K surveillance was in August 2009; peak activity nationwide occurred during October-November 2009. Patients with A(H1N1)pdm09 infection were more likely to be school-aged, compared with patients with seasonal influenza A virus infection (prevalence ratio [PR], 2.0; 95% confidence interval [CI], 1.3-3.1) or noninfluenza ILI (PR, 3.2; 95% CI, 2.4-4.3). Conclusions USAMRU-K ILI surveillance detected the geographic and temporal distribution of pandemic influenza in Kenya. The age distribution of A(H1N1)pdm09 infections included more school-aged children, compared with seasonal influenza A virus infection and noninfluenza ILI.

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Finley Osuna

Papers

Were the WHO-recommended Human Influenza Vaccine Formulations Appropriate for Kenya During the 2010-2011 Season? Inferences from the HA1 Gene Analysis

Epidemiology of 2009 pandemic influenza A virus subtype H1N1 among Kenyans aged 2 months to 18 years, 2009-2010.