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The most widely used class of antivirals available for Influenza treatment are the neuraminidase inhibitors (NAI) Oseltamivir and Zanamivir. However, amino acid (AA) substitutions in the neuraminidase may cause reduced inhibition or high antiviral resistance. In Mexico, the current state of knowledge about NAI susceptibility is scarce, in this study we report the results of 14 years of Influenza surveillance by phenotypic and genotypic methods. A total of 255 isolates were assessed with the NAI assay, including Influenza A(H1N1)pdm09, A(H3N2) and Influenza B (IBV). Furthermore, 827 sequences contained in the GISAID platform were analyzed in search of relevant mutations.Overall, five isolates showed highly reduced inhibition or reduced inhibition to Oseltamivir, and two showed reduced inhibition to Zanamivir in the NAI assays. Additionally, five A(H1N1)pdm09 sequences from the GISAID possessed AA substitutions associated to reduced inhibition to Oseltamivir and none to Zanamivir. Oseltamivir resistant A(H1N1)pdm09 harbored the H275Y mutation. No genetic mutations were identified in Influenza A(H3N2) and IBV. Overall, these results show that in Mexico the rate of NAI resistance is low (0.6%), but it is essential to continue the Influenza surveillance in order to understand the drug susceptibility of circulating strains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: While vaccination may be relatively straightforward for regions with a well-defined winter season, the situation is quite different for tropical regions. Influenza activity in tropical regions might be out of phase with the dynamics predicted for their hemispheric group thereby impacting the effectiveness of the immunization campaign., Objective: To investigate how the climatic diversity of Mexico hinders its existing influenza immunization strategy and to suggest that the hemispheric vaccine recommendations be tailored to the regional level in order to optimize vaccine effectiveness., Methods: We studied the seasonality of influenza throughoutMexico by modeling virological and mortality data.De-trended time series of each Mexican state were analyzed by Fourier decomposition to describe the amplitude and timing of annual influenza epidemic cycles and to compare with each the timing of the WHO's Northern and Southern Hemispheric vaccination schedule., Findings: The timings of the primary (major) peaks of both virological and mortality data for most Mexican states are well aligned with the Northern Hemisphere winter (December-February) and vaccine schedule. However, influenza peaks in September in the three states of the Yucatan Peninsula. Influenza-related mortality also peaks in September in Quintana Roo and Yucatan whereas it peaks in May in Campeche. As the current timing of vaccination in Mexico is between October and November, more than half of the annual influenza cases have already occurred in the Yucatan Peninsula states by the time the Northern Hemispheric vaccine is delivered and administered., Conclusion: The current Northern Hemispheric influenza calendar adopted for Mexico is not optimal for the Yucatan Peninsula states thereby likely reducing the effectiveness of the immunization of the population. We recommend that Mexico tailor its immunization strategy to better reflect its climatologic and epidemiological diversity and adopt the WHO Southern Hemisphere influenza vaccine and schedule for the Yucatan Peninsula., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: The 2009 H1N1 influenza pandemic initially affected Mexico from April 2009 to July 2010. By August 2010, a fourth of the population had received the monovalent vaccine against the pandemic virus (A(H1N1)pdm09). To assess the proportion of the Mexican population who remained potentially susceptible to infection throughout the summer of 2010, we estimated the population seroprevalence to A(H1N1)pdm09 in a serosurvey of blood donors., Methods: We evaluated baseline cross-reactivity to the pandemic strain and set the threshold for seropositivity using pre-pandemic (2005-2008) stored serum samples and sera from confirmed A(H1N1)pdm09 infected individuals. Between June and September 2010, a convenience sample serosurvey of adult blood donors, children, and adolescents was conducted in six states of Mexico. Sera were tested by the microneutralization (MN) and hemagglutination inhibition (HI) assays, and regarded seropositive if antibody titers were equal or exceeded 1:40 for MN and 1:20 for HI. Age-standardized seroprevalence were calculated using the 2010 National Census population., Results: Sera from 1,484 individuals were analyzed; 1,363 (92%) were blood donors, and 121 (8%) children or adolescents aged ≤19 years. Mean age (standard deviation) was 31.4 (11.5) years, and 276 (19%) were women. A total of 516 (35%) participants declared history of influenza vaccination after April 2009. The age-standardized seroprevalence to A(H1N1)pdm09 was 48% by the MN and 41% by the HI assays, respectively. The youngest quintile, aged 1 to 22 years, had the highest the seroprevalence; 61% (95% confidence interval [CI]: 56, 66%) for MN, and 56% (95% CI: 51, 62%) for HI., Conclusions: Despite high transmission of A(H1N1)pdm09 observed immediately after its emergence and extensive vaccination, over a half of the Mexican population remained potentially susceptible to A(H1N1)pdm09 infection. Subsequent influenza seasons with high transmission of A(H1N1)pdm09, as 2011-2012 and 2013-2014, are compatible with these findings.

Background: Despite the potential to produce antibodies that can neutralize different virus (heterotypic neutralization), there is no knowledge of why vaccination against influenza induces protection predominantly against the utilized viral strains (homotypic response). Identification of structural patterns of the B cell repertoire associated to heterotypic neutralization may contribute to identify relevant epitopes for a universal vaccine against influenza., Methods: Blood samples were collected from volunteers immunized with 2008/2009 trivalent inactivated vaccine (TIV), pandemic H1N1 (pdmH1N1) monovalent inactivated vaccine (MIV) and the 2014/2015 TIV. Neutralization was assessed by hemagglutination and microneutralization test. IgG V(H) amplicons derived from peripheral blood RNA from pre-immune and 7 days post vaccination were subjected to 454-Roche sequencing. Full reconstruction of the sampled repertoires was done with ImmunediveRsity., Results: The TIV induced a predominantly homotypic neutralizing serologic response, while the 09 MIV induced a heterotypic neutralizing seroconversion in 17% of the individuals. Both the 08/09 and the 14/15 TIV were associated with a reduction in clonotypic diversity, whereas 09 MIV was the opposite. Moreover, TIV and MIV induced distinctive patterns of IGHV segment use that are consistent with B cell selection by conserved antigenic determinants shared by the pre-pandemic and the pandemic strains. However, low somatic hypermutation rates in IgG after 09 MIV immunization, but not after 08/09 and 14/15 TIV immunization were observed. Furthermore, no evidence of the original antigenic sin was found in the same individuals after vaccination with the three vaccines., Conclusions: Immunization with a new influenza virus strain (2009 pdmH1N1) induced unique effects in the peripheral B cell repertoire clonal structure, a stereotyped response involving distinctive IGHV segment use and low somatic hypermutation levels. These parameters were contrastingly different to those observed in response to pre-pandemic and post-pandemic vaccination, and may be the result of clonal selection of common antigenic determinants, as well as germinal center-independent responses that wane as the pandemic strain becomes seasonal. Our findings may contribute in the understanding of the structural and cellular basis required to develop a universal influenza vaccine.

In this work, nineteen influenza A/H3N2 viruses isolated in Mexico between 2003 and 2012 were studied. Our findings show that different human A/H3N2 viral lineages co-circulate within a same season and can also persist locally in between different influenza seasons, increasing the chance for genetic reassortment events. A novel minor cluster was also identified, named here as Korea, that circulated worldwide during 2003. Frequently, phylogenetic characterization did not correlate with the determined antigenic identity, supporting the need for the use of molecular evolutionary tools additionally to antigenic data for the surveillance and characterization of viral diversity during each flu season. This work represents the first long-term molecular epidemiology study of influenza A/H3N2 viruses in Mexico based on the complete genomic sequences and contributes to the monitoring of evolutionary trends of A/H3N2 influenza viruses within North and Central America.

Recent evidence suggests that most influenza A virus gene segments can contribute to the pathogenicity of the virus. In this regard, the hemagglutinin (HA) subtype of the circulating strains has been closely surveyed, but the reassortment of internal gene segments is usually not monitored as a potential source of an increased pathogenicity. In this work, an oligonucleotide DNA microarray (PhyloFlu) designed to determine the phylogenetic origins of the eight segments of the influenza virus genome was constructed and validated. Clades were defined for each segment and also for the 16 HA and 9 neuraminidase (NA) subtypes. Viral genetic material was amplified by reverse transcription-PCR (RT-PCR) with primers specific to the conserved 5' and 3' ends of the influenza A virus genes, followed by PCR amplification with random primers and Cy3 labeling. The microarray unambiguously determined the clades for all eight influenza virus genes in 74% (28/38) of the samples. The microarray was validated with reference strains from different animal origins, as well as from human, swine, and avian viruses from field or clinical samples. In most cases, the phylogenetic clade of each segment defined its animal host of origin. The genomic fingerprint deduced by the combined information of the individual clades allowed for the determination of the time and place that strains with the same genomic pattern were previously reported. PhyloFlu is useful for characterizing and surveying the genetic diversity and variation of animal viruses circulating in different environmental niches and for obtaining a more detailed surveillance and follow up of reassortant events that can potentially modify virus pathogenicity.

Objective: Influenza virus is the most common cause of Acute Respiratory Infections (ARI) world wide. In patients with chronic condition, infection by the influenza virus can cause complications such as pneumonia which may have fatal outcome. The aim of this work was to determine the frequency of human influenza virus in outpatients with influenza-like illness (ILI) and in those patients admitted to hospital with community acquired pneumonia (CAP) in Yucatan, Mexico (October 1998-July 1999)., Materials and Methods: Throat swabs were collected from ILI and CAP patients and processed to detect respiratory viruses. All clinical samples were tested for seven respiratory viruses using a rapid indirect immunofluorescence test (IFI). Clinical samples with positive results for influenza virus by IFI were inoculated into chick embryo eggs and/or MDCK cells for viral isolation. All influenza virus isolates were typed using the WHO influenza Kit 1998-1999., Results: A total of 288 clinical samples were collected. Influenza virus type A was diagnosed in 29 clinical samples (10%), no other respiratory viruses were identified. Influenza virus was present with 8.9% (17 out of 189) in ILI patients, whereas with 12.12% (12 out of 99) in CAP patients. Influenza virus was detected from December to July. Six viral isolates were obtained and identified as influenza A (H3N2)., Conclusion: Human influenza virus is certainly a cause of ARI and pneumonia in Yucatan, Mexico. The results showed that influenza virus contributes to at least 8.9% of the ARI, and more importantly to 12% of CAP patients. Positive cases were present in a different pattern to temperate zones where the peak of incidence occurs during autumn and winter.