Santiago Echevarría-Zuno

Infection and death from influenza A H1N1 virus in Mexico: a retrospective analysis

BACKGROUND In April, 2009, the first cases of influenza A H1N1 were registered in Mexico and associated with an unexpected number of deaths. We report the timing and spread of H1N1 in cases, and explore protective and risk factors for infection, severe disease, and death. METHODS We analysed information gathered by the influenza surveillance system from April 28 to July 31, 2009, for patients with influenza-like illness who attended clinics that were part of the Mexican Institute for Social Security network. We calculated odds ratios (ORs) to compare risks of testing positive for H1N1 in those with influenza-like illness at clinic visits, the risk of admission for laboratory-confirmed cases of H1N1, and of death for inpatients according to demographic characteristics, clinical symptoms, seasonal influenza vaccine status, and elapsed time from symptom onset to admission. FINDINGS By July 31, 63 479 cases of influenza-like illness were reported; 6945 (11%) cases of H1N1 were confirmed, 6407 (92%) were outpatients, 475 (7%) were admitted and survived, and 63 (<1%) died. Those aged 10-39 years were most affected (3922 [56%]). Mortality rates showed a J-shaped curve, with greatest risk in those aged 70 years and older (10.3%). Risk of infection was lowered in those who had been vaccinated for seasonal influenza (OR 0.65 [95% CI 0.55-0.77]). Delayed admission (1.19 [1.11-1.28] per day) and presence of chronic diseases (6.1 [2.37-15.99]) were associated with increased risk of dying. INTERPRETATION Risk communication and hospital preparedness are key factors to reduce mortality from H1N1 infection. Protective effects of seasonal influenza vaccination for the virus need to be investigated. FUNDING None.

Characterizing the Epidemiology of the 2009 Influenza A/H1N1 Pandemic in Mexico

Gerardo Chowell and colleagues address whether school closures and other social distancing strategies were successful in reducing pandemic flu transmission in Mexico by analyzing the age- and state-specific incidence of influenza morbidity and mortality in 32 Mexican states.

Mortality Burden of the A/H1N1 Pandemic in Mexico: A Comparison of Deaths and Years of Life Lost to Seasonal Influenza

BACKGROUND The mortality burden of the 2009 A/H1N1 influenza pandemic remains controversial, in part because of delays in reporting of vital statistics that are traditionally used to measure influenza-related excess mortality. Here, we compare excess mortality rates and years of life lost (YLL) for pandemic and seasonal influenza in Mexico and evaluate laboratory-confirmed death reports. METHODS Monthly age- and cause-specific death rates from January 2000 through April 2010 and population-based surveillance of influenza virus activity were used to estimate excess mortality and YLL in Mexico. Age-stratified laboratory-confirmed A/H1N1 death reports were obtained from an active surveillance system covering 40% of the population. RESULTS The A/H1N1 pandemic was associated with 11.1 excess all-cause deaths per 100,000 population and 445,000 YLL during the 3 waves of virus activity in Mexico, April-December 2009. The pandemic mortality burden was 0.6-2.6 times that of a typical influenza season and lower than that of the severe 2003-2004 influenza epidemic. Individuals aged 5-19 and 20-59 years were disproportionately affected relative to their experience with seasonal influenza. Laboratory-confirmed deaths captured 1 of 7 pandemic excess deaths overall but only 1 of 41 deaths in persons >60 years of age in 2009. A recrudescence of excess mortality was observed in older persons during winter 2010, in a period when influenza and respiratory syncytial virus cocirculated. CONCLUSIONS Mexico experienced higher 2009 A/H1N1 pandemic mortality burden than other countries for which estimates are available. Further analyses of detailed vital statistics are required to assess geographical variation in the mortality patterns of this pandemic.

Epidemiological Characterization of a Fourth Wave of Pandemic A/H1N1 Influenza in Mexico, Winter 2011–2012: Age Shift and Severity

BACKGROUND AND AIMS A substantial recrudescent wave of pandemic influenza A/H1N1 affected the Mexican population from December 1, 2011-March 20, 2012 following a 2-year period of sporadic transmission. METHODS We analyzed demographic and geographic data on all hospitalizations with severe acute respiratory infection (SARI) and laboratory-confirmed A/H1N1 influenza, and inpatient deaths, from a large prospective surveillance system maintained by a Mexican social security medical system during April 1, 2009-March 20, 2012. We also estimated the reproduction number (R) based on the growth rate of the daily case incidence by date of symptoms onset. RESULTS A total of 7569 SARI hospitalizations and 443 in-patient deaths (5.9%) were reported between December 1, 2011, and March 20, 2012 (1115 A/H1N1-positive inpatients and 154 A/H1N1-positive deaths). The proportion of laboratory-confirmed A/H1N1 hospitalizations and deaths was higher among subjects ≥60 years of age (χ(2) test, p <0.0001) and lower among younger age groups (χ(2) test, p <0.04) for the 2011-2012 pandemic wave compared to the earlier waves in 2009. The reproduction number of the winter 2011-2012 wave in central Mexico was estimated at 1.2-1.3, similar to that reported for the fall 2009 wave, but lower than that of spring 2009. CONCLUSIONS We documented a substantial increase in the number of SARI hospitalizations during the period December 2011-March 2012 and an older age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and deaths relative to 2009 A/H1N1 pandemic patterns. The gradual change in the age distribution of A/H1N1 infections in the post-pandemic period is consistent with a build-up of immunity among younger populations.

Epidemiological characteristics and underlying risk factors for mortality during the autumn 2009 pandemic wave in Mexico.

Background Elucidating the role of the underlying risk factors for severe outcomes of the 2009 A/H1N1 influenza pandemic could be crucial to define priority risk groups in resource-limited settings in future pandemics. Methods We use individual-level clinical data on a large series of ARI (acute respiratory infection) hospitalizations from a prospective surveillance system of the Mexican Social Security medical system to analyze clinical features at presentation, admission delays, selected comorbidities and receipt of seasonal vaccine on the risk of A/H1N1-related death. We considered ARI hospitalizations and inpatient-deaths, and recorded demographic, geographic, and medical information on individual patients during August-December, 2009. Results Seasonal influenza vaccination was associated with a reduced risk of death among A/H1N1 inpatients (OR = 0.43 (95% CI: 0.25, 0.74)) after adjustment for age, gender, geography, antiviral treatment, admission delays, comorbidities and medical conditions. However, this result should be interpreted with caution as it could have been affected by factors not directly measured in our study. Moreover, the effect of antiviral treatment against A/H1N1 inpatient death did not reach statistical significance (OR = 0.56 (95% CI: 0.29, 1.10)) probably because only 8.9% of A/H1N1 inpatients received antiviral treatment. Moreover, diabetes (OR = 1.6) and immune suppression (OR = 2.3) were statistically significant risk factors for death whereas asthmatic persons (OR = 0.3) or pregnant women (OR = 0.4) experienced a reduced fatality rate among A/H1N1 inpatients. We also observed an increased risk of death among A/H1N1 inpatients with admission delays >2 days after symptom onset (OR = 2.7). Similar associations were also observed for A/H1N1-negative inpatients. Conclusions Geographical variation in identified medical risk factors including prevalence of diabetes and immune suppression may in part explain between-country differences in pandemic mortality burden. Furthermore, access to care including hospitalization without delay and antiviral treatment and are also important factors, as well as vaccination coverage with the 2008–09 trivalent inactivated influenza vaccine.

Recrudescent wave of pandemic A/H1N1 influenza in Mexico, winter 2011-2012: Age shift and severity

BACKGROUND A substantial recrudescent wave of pandemic influenza A/H1N1 that began in December 2011 is ongoing and has not yet peaked in Mexico, following a 2-year period of sporadic transmission. Mexico previously experienced three pandemic waves of A/H1N1 in 2009, associated with higher excess mortality rates than those reported in other countries, and prompting a large influenza vaccination campaign. Here we describe changes in the epidemiological patterns of the ongoing 4th pandemic wave in 2011-12, relative to the earlier waves in 2009. The analysis is intended to guide public health intervention strategies in near real time. METHODS We analyzed demographic and geographic data on all hospitalizations with acute respiratory infection (ARI) and laboratory-confirmed A/H1N1 influenza, and inpatient deaths, from a large prospective surveillance system maintained by the Mexican Social Security medical system during 01-April 2009 to 10-Feb 2012. We characterized the age and regional patterns of A/H1N1-positive hospitalizations and inpatient-deaths relative to the 2009 A/H1N1 influenza pandemic. We also estimated the reproduction number (R) based on the growth rate of the daily case incidence by date of symptoms onset. RESULTS A total of 5,795 ARI hospitalizations and 186 inpatient-deaths (3.2%) were reported between 01-December 2011 and 10-February 2012 (685 A/H1N1-positive inpatients and 75 A/H1N1-positive deaths). The nationwide peak of daily ARI hospitalizations in early 2012 has already exceeded the peak of ARI hospitalizations observed during the major fall pandemic wave in 2009. The mean age was 34.3 y (SD=21.3) among A/H1N1 inpatients and 43.5 y (SD=21) among A/H1N1 deaths in 2011-12. The proportion of laboratory-confirmed A/H1N1 hospitalizations and deaths was higher among seniors >=60 years of age (Chi-square test P<0.001) and lower among younger age groups (Chi-square test, P<0.03) for the 2011-2012 pandemic wave, compared to the earlier waves in 2009. The reproduction number of the winter 2011-12 wave in central Mexico was estimated at 1.2-1.3, similar to that reported for the fall 2009 wave, but lower than that of spring 2009. CONCLUSIONS We have documented a substantial and ongoing increase in the number of ARI hospitalizations during the period December 2011-February 2012 and an older age distribution of laboratory-confirmed A/H1N1 influenza hospitalizations and deaths, relative to 2009 A/H1N1 pandemic patterns. The gradual change in the age distribution of A/H1N1 infections in the post-pandemic period is reminiscent of historical pandemics and indicates either a gradual drift in the A/H1N1 virus, and/or a build-up of immunity among younger populations.

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

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.

Survey on physicians' knowledge and attitudes towards clinical practice guidelines at the Mexican Institute of Social Security

OBJECTIVE A survey was organized to determine the general level of knowledge and attitudes of medical personnel towards clinical practice guidelines (CPG). METHODS A questionnaire modified from two validated instruments was used. Multi-stratified sampling was applied, and 1782 questionnaires were completed. RESULTS A total of 80.4% of physicians had regular employment contract, 8.6% managerial post and 9.3% temporary work contract. Average age and working time were 43.7 and 15 years respectively; 64.3% were male. It was reported that 47.9% participated in academic activities, 70.8% belonged to a medical association, 40.3% identified CPG as steps towards arriving at a diagnosis and/or treatment and 14.9% thought that CPG were norms. A total of 10.7% of the physicians believed that guidelines are based on scientific evidence, 10% perceived them as supporting tools, 10.8% had no knowledge of them, 65% said that they used them, 76.7% thought that personal experience was as important as CPG recommendations and 57.4% thought that CPG were necessary for good medical practice. Physicians preferred that CPG be produced by personnel from outside the Mexican Institute of Social Security, or who had followed validity criteria. CONCLUSIONS The majority of physicians considered CPG to be useful tools. It was evident that few knew where to acquire CPG, and this would lead to their limited use. Findings from this study enabled procuring a broader idea of the level of knowledge and attitudes of Mexican Institute of Social Security physicians towards CPG. This information is relevant when planning strategies for the purpose of sharing and implementing CPG.