Impact of antiviral treatment and hospital admission delay on risk of death associated with 2009 A/H1N1 pandemic influenza in Mexico

Abstract

BackgroundIncreasing our understanding of the factors affecting the severity of the 2009 A/H1N1 influenza pandemic in different regions of the world could lead to improved clinical practice and mitigation strategies for future influenza pandemics. Even though a number of studies have shed light into the risk factors associated with severe outcomes of 2009 A/H1N1 influenza infections in different populations (e.g., [1-5]), analyses of the determinants of mortality risk spanning multiple pandemic waves and geographic regions are scarce. Between-country differences in the mortality burden of the 2009 pandemic could be linked to differences in influenza case management, underlying population health, or intrinsic differences in disease transmission [6]. Additional studies elucidating the determinants of disease severity globally are warranted to guide prevention efforts in future influenza pandemics.In Mexico, the 2009 A/H1N1 influenza pandemic was characterized by a three-wave pattern occurring in the spring, summer, and fall of 2009 with substantial geographical heterogeneity [7]. A recent study suggests that Mexico experienced high excess mortality burden during the 2009 A/H1N1 influenza pandemic relative to other countries [6]. However, an assessment of potential factors that contributed to the relatively high pandemic death toll in Mexico are lacking. Here, we fill this gap by analyzing a large series of laboratory-confirmed A/H1N1 influenza cases, hospitalizations, and deaths monitored by the Mexican Social Security medical system during April 1 through December 31, 2009 in Mexico. In particular, we quantify the association between disease severity, hospital admission delays, and neuraminidase inhibitor use by demographic characteristics, pandemic wave, and geographic regions of Mexico.MethodsWe analyzed a large series of laboratory-confirmed pandemic A/H1N1 influenza cases from a prospective surveillance system maintained by the Mexican Social Security system, April-December 2009. We considered a spectrum of disease severity encompassing outpatient visits, hospitalizations, and deaths, and recorded demographic and geographic information on individual patients. We assessed the impact of neuraminidase inhibitor treatment and hospital admission delay (≤ > 2 days after disease onset) on the risk of death by multivariate logistic regression.ResultsApproximately 50% of all A/H1N1-positive patients received antiviral medication during the Spring and Summer 2009 pandemic waves in Mexico while only 9% of A/H1N1 cases received antiviral medications during the fall wave (P < 0.0001). After adjustment for age, gender, and geography, antiviral treatment significantly reduced the risk of death (OR = 0.52 (95% CI: 0.30, 0.90)) while longer hospital admission delays increased the risk of death by 2.8-fold (95% CI: 2.25, 3.41).ConclusionsOur findings underscore the potential impact of decreasing admission delays and increasing antiviral use to mitigate the mortality burden of future influenza pandemics.

Epidemiological Characteristics and Underlying Risk Factors for Mortality during the Autumn 2009 Pandemic Wave in Mexico

“…This result could be due to the small fraction of hospitalized patients that were treated with antivirals during the fall wave (∼9%) and the fact that decision to treat was not found to be related to symptoms severity [65]. We [65] recently reported a sharp drop in antiviral use from 50% in the spring and summer wave to 9% in the main fall pandemic in Mexico.…”

Neuraminidase inhibitors for influenza: a systematic review and meta-analysis of regulatory and mortality data

“…Three identified studies [110][111][112] were published versions of trials that were possibly unknown to us. We wrote to the first trial author to ask for CSRs, or equivalent, on 12 November 2013, and the author confirmed that the trials had not been completed.…”

“…Two RCTs were excluded from the meta-analysis because they were only synopsis reports 74,75 and another because it was not a full CSR. 76 We finally included 20 oseltamivir trials into stage 2: 11 on treatment in adults, 8,36,57,58,[60][61][62]66,67,69,[74][75][76][108][109][110][111][112] four in children 57,63,64 and five on prophylaxis: 51,61,65,68 two in adults, 51 two in the elderly 61,68 and one in households. 65 Of the 15 included treatment trials of oseltamivir, only three 8,36,63 were successful in recruiting the a priori planned sample size.…”

Antibody responses to influenza viruses in paediatric patients and their contacts at the onset of the 2009 pandemic in Mexico

“…These data could be relevant to improve vaccination coverage, and target groups not considered as high-risk subjects for complications of influenza infection. In Mexico, between April 1 through December 31, 2009, the mean case fatality ratio was 0.6% for those < 18 years, 2.8% for the group of 18-49 years and 8.5% for > 50 years [23].…”