How predictive of SARS-CoV-2 infection are clinical characteristics at presentation among individuals with COVID-like symptoms treated at the Mexican Institute of Social Security.

BACKGROUND: The COVID-19 pandemic has progressed rapidly, with the emergence of new virus variants that pose challenges in treating infected individuals. In Mexico, four epidemic waves have been recorded with varying disease severity. To understand the heterogeneity in clinical presentation over time and the sensitivity and specificity of signs and symptoms in identifying COVID-19 cases, an analysis of the changes in the clinical presentation of the disease was conducted. AIM: To analyze the changes in the clinical presentation of COVID-19 among 3.38 million individuals tested for SARS-CoV-2 at the Mexican Social Security Institute (IMSS) from March 2020 to October 2021 and evaluate the predictivity of signs and symptoms in identifying COVID-19 cases. METHODS: A retrospective analysis of clinical presentation patterns of COVID-19 among individuals treated at IMSS was performed, contrasting the signs and symptoms among SARS-CoV-2-positive individuals with those who tested negative for the virus but had respiratory infection symptoms. The sensitivity and specificity of each sign and symptom in identifying SARS-CoV-2 infection were estimated. RESULTS: The set of signs and symptoms reported for COVID-19-suspected patients treated at IMSS were not highly specific for SARS-CoV-2 positivity. The signs and symptoms exhibited variability based on age and epidemic wave. The area under the receiver operating characteristic (ROC) curve was 0.62 when grouping the five main symptoms (headache, dyspnea, fever, arthralgia, and cough). Most of the individual symptoms had ROC values close to 0.5 (16 out of 22 between 0.48 and 0.52), indicating non-specificity. CONCLUSIONS: The results highlight the difficulty in making a clinical diagnosis of COVID-19 due to the lack of specificity of signs and symptoms. The variability of clinical presentation over time and among age groups highlights the need for further research to differentiate whether the changes are due to changes in the virus, who is becoming infected, or the population, particularly with respect to prior infection and vaccination status.

Evolution of differences in clinical presentation across epidemic waves among patients with COVID-like-symptoms who received care at the Mexican Social Security Institute.

Background: Timely monitoring of SARS-CoV-2 variants is crucial to effectively managing both prevention and treatment efforts. In this paper, we aim to describe demographic and clinical patterns of individuals with COVID-19-like symptoms during the first three epidemic waves in Mexico to identify changes in those patterns that may reflect differences determined by virus variants. Methods: We conducted a descriptive analysis of a large database containing records for all individuals who sought care at the Mexican Social Security Institute (IMSS) due to COVID-19-like symptoms from March 2020 to October 2021 (4.48 million records). We described the clinical and demographic profile of individuals tested (3.38 million, 32% with PCR and 68% with rapid test) by test result (positives and negatives) and untested, and among those tested, and the changes in those profiles across the first three epidemic waves. Results: Individuals with COVID-19-like symptoms were older in the first wave and younger in the third one (the mean age for those positive was 46.6 in the first wave and 36.1 in the third wave; for negatives and not-tested, the mean age was 41 and 38.5 in the first wave and 34.3 and 33.5 in the third wave). As the pandemic progressed, an increasing number of individuals sought care for suspected COVID-19. The positivity rate decreased over time but remained well over the recommended 5%. The pattern of presenting symptoms changed over time, with some of those symptoms decreasing over time (dyspnea 40.6 to 14.0%, cough 80.4 to 76.2%, fever 77.5 to 65.2%, headache 80.3 to 78.5%), and some increasing (odynophagia 48.7 to 58.5%, rhinorrhea 28.6 to 47.5%, anosmia 11.8 to 23.2%, dysgeusia 11.2 to 23.2%). Conclusion: During epidemic surges, the general consensus was that any individual presenting with respiratory symptoms was a suspected COVID-19 case. However, symptoms and signs are dynamic, with clinical patterns changing not only with the evolution of the virus but also with demographic changes in the affected population. A better understanding of these changing patterns is needed to improve preparedness for future surges and pandemics.

Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection.

BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78-.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.

Type 1 diabetes incidence in children and adolescents in Mexico: Data from a nation-wide institutional register during 2000-2018.

AIMS: To describe the annual incidence of type 1 diabetes in children and adolescents insured by the Mexican Institute of Social Security, the main health provider in Mexico, during 2000-2018. METHODS: We conducted a secondary data analyses using the incidence registers from the Epidemiological Surveillance Coordination of the Mexican Institute of Social Security collected during 2000-2018. Incident type 1 diabetes cases (age 19 years old and below) were identified using ICD-10-CM E10 diagnostic codes. Age, sex, and geographical region and seasonal-specific incidence were calculated with their corresponding annual percentage change (APC) as well. RESULTS: In the period 2000-2018, the number of incident cases with type 1 diabetes decreased from 3.4 to 2.8 per 100,000 in insured for subjects below 20 years old. We observed an increase in the 2000-2006, followed by a decrease for the 2006-2018 period (APC +16.1 and -8.7 respectively). Females and children <5 years old had a significant decrease in the incidence rate, while inhabitants in Central Mexico showed a significant increase. No difference was found in incidence between seasons. CONCLUSIONS: Our study describes significant fluctuations of the incidence of type 1 diabetes during the period 2000-2018, which appeared to correspond to influenza outbreaks, among Mexican children and adolescents.

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium.

BACKGROUND: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. METHODS: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. DISCUSSION: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017.

Night Shift Work and Risk of Breast Cancer in Women.

BACKGROUND: Night shift work involving circadian disruption has been associated with increased breast cancer rates in some epidemiological studies, but the evidence is still on debate. AIM OF THE STUDY: The objective of this study is to assess the association between night shift work and breast cancer in Mexican women. METHODS: A Case-control study was conducted with incident cases of breast cancer at the Instituto de Seguridad Social del Estado de México y Municipios. Cases were interviewed about past exposures prior to the final diagnosis. Controls were women without breast cancer matched on multiple sociodemographic characteristics. RESULTS: 101 cases and 101 matched controls were interviewed; this small sample size provided consistent, but wide estimates of the assessed associations. The multivariate conditional logistic regression showed that breast-feeding was associated with reduced risk for breast cancer (OR 0.12; 95% CI: 0.02-0.60); women who experienced early menarche (12 years) were more likely to develop breast cancer (OR 18.58; 95% CI 18: 2.19-148). Women who worked at night were more likely to develop breast cancer compared to women who never did (OR = 8.58; 95% CI: 2.19-33.8). CONCLUSIONS: Our results are consistent with studies from other countries, which positively associated night shift work with breast cancer.

[Prevalencia de complicaciones de la diabetes y comorbilidades asociadas en medicina familiar del Instituto Mexicano del Seguro Social].

Introduction: The prevalence of chronic complications and comorbidities in patients with type 2 diabetes (T2D) has increased worldwide. Objective: To compare the prevalence of complications and chronic comorbidities in patients with T2D at 36 family medicine units of five chapters of the Mexican Institute of Social Security (IMSS). Method: Complications (hypoglycemia, diabetic foot, kidney disease, retinopathy, ischemic heart disease, cerebrovascular disease and heart failure) and comorbidities (liver disease, cancer and anemia) were identified according to codes of the International Classification of Diseases, 10th Revision. Comparisons were made by chapter, age, gender and evolution time. Results: Complications and comorbidities were more common in subjects aged ≥ 62 years. Out of 297 100 patients, 34.9 % had any complication; microvascular complications (32 %) prevailed in the industrial North, whereas macrovascular complications (12.3 %) did in the rural East, and comorbidities (5 %) in southern Mexico City. Complications predominated in men (any complication, 30.2 %). Heart failure and comorbidities were more common in women (5.6 % and 4.9 %, respectively). Conclusions: T2D complications and comorbidities showed geographic and gender differences, and were greater with older age and longer evolution time. It is urgent for strategies for the prevention of complications and comorbidities to be reinforced in patients with T2D.

Introducción: La prevalencia de complicaciones crónicas y comorbilidades en pacientes con diabetes tipo 2 (DT2) se han incrementado en el mundo. Objetivo: Comparar la prevalencia de complicaciones y comorbilidades crónicas en pacientes con DT2 en 36 unidades de medicina familiar de cinco delegaciones del Instituto Mexicano del Seguro Social (IMSS). Métodos: Conforme los códigos de la Décima Revisión de la Clasificación Internacional de Enfermedades se identificaron las complicaciones (hipoglucemia, pie diabético, enfermedad renal, retinopatía, enfermedad cardiaca isquémica, enfermedad cerebrovascular y falla cardiaca) y comorbilidades (enfermedad hepática, cáncer, anemia) de DT2. Se compararon por delegación, edad, sexo y tiempo de evolución. Resultados: Las complicaciones y comorbilidades fueron más comunes en personas ≥ 62 años. De 297 100 pacientes, 34.9 % presentó cualquier complicación; microvasculares en el norte industrial (32 %), macrovasculares en el este rural (12.3 %) y comorbilidades (5 %) en el sur de la Ciudad de México; estas complicaciones predominaron en los hombres (cualquier complicación 30.2 %). La falla cardiaca y las comorbilidades fueron más comunes en mujeres (5.6 y 4.9 %). Conclusiones: Las complicaciones y comorbilidades de DT2 mostraron diferencias geográficas y de sexo y fueron mayores con la edad y el tiempo de evolución. Urge reforzar estrategias para la prevención de las complicaciones y comorbilidades en los pacientes con DT2.

Prevalencia de complicaciones de la diabetes y comorbilidades asociadas en medicina familiar del Instituto Mexicano del Seguro Social / Prevalence of complications of diabetes and associated comorbidities in family medicine of the Mexican Institute

Resumen Introducción: La prevalencia de complicaciones crónicas y comorbilidades en pacientes con diabetes tipo 2 (DT2) se han incrementado en el mundo. Objetivo: Comparar la prevalencia de complicaciones y comorbilidades crónicas en pacientes con DT2 en 36 unidades de medicina familiar de cinco delegaciones del Instituto Mexicano del Seguro Social (IMSS). Métodos: Conforme los códigos de la Décima Revisión de la Clasificación Internacional de Enfermedades se identificaron las complicaciones (hipoglucemia, pie diabético, enfermedad renal, retinopatía, enfermedad cardiaca isquémica, enfermedad cerebrovascular y falla cardiaca) y comorbilidades (enfermedad hepática, cáncer, anemia) de DT2. Se compararon por delegación, edad, sexo y tiempo de evolución. Resultados: Las complicaciones y comorbilidades fueron más comunes en personas ≥ 62 años. De 297 100 pacientes, 34.9 % presentó cualquier complicación; microvasculares en el norte industrial (32 %), macrovasculares en el este rural (12.3 %) y comorbilidades (5 %) en el sur de la Ciudad de México; estas complicaciones predominaron en los hombres (cualquier complicación 30.2 %). La falla cardiaca y las comorbilidades fueron más comunes en mujeres (5.6 y 4.9 %). Conclusiones: Las complicaciones y comorbilidades de DT2 mostraron diferencias geográficas y de sexo y fueron mayores con la edad y el tiempo de evolución. Urge reforzar estrategias para la prevención de las complicaciones y comorbilidades en los pacientes con DT2.

Abstract Introduction: The prevalence of chronic complications and comorbidities in patients with type 2 diabetes (T2D) has increased worldwide. Objective: To compare the prevalence of complications and chronic comorbidities in patients with T2D at 36 family medicine units of five chapters of the Mexican Institute of Social Security (IMSS). Method: Complications (hypoglycemia, diabetic foot, kidney disease, retinopathy, ischemic heart disease, cerebrovascular disease and heart failure) and comorbidities (liver disease, cancer and anemia) were identified according to codes of the International Classification of Diseases, 10th Revision. Comparisons were made by chapter, age, gender and evolution time. Results: Complications and comorbidities were more common in subjects aged ≥ 62 years. Out of 297 100 patients, 34.9 % had any complication; microvascular complications (32 %) prevailed in the industrial North, whereas macrovascular complications (12.3 %) did in the rural East, and comorbidities (5 %) in southern Mexico City. Complications predominated in men (any complication, 30.2 %). Heart failure and comorbidities were more common in women (5.6 % and 4.9 %, respectively). Conclusions: T2D complications and comorbidities showed geographic and gender differences, and were greater with older age and longer evolution time. It is urgent for strategies for the prevention of complications and comorbidities to be reinforced in patients with T2D.

Stepwise strategies to successfully recruit diabetes patients in a large research study in Mexican population.

AIMS: Describe stepwise strategies (electronic chart review, patient preselection, call-center, personnel dedicated to recruitment) for the successful recruitment of >5000 type 2 diabetes patients in four months. METHODS: Twenty-five family medicine clinics from Mexico City and the State of Mexico participated: 13 usual care, 6 specialized diabetes care and 6 chronic disease care. Appointments were scheduled from 11/3/2015 to 3/31/2016. Phone calls were generated automatically from an electronic database. A telephone questionnaire verified inclusion criteria, and scheduled an appointment, with a daily report of appointments, patient attendance, acceptance rate, and questionnaire completeness. Another recruitment log reviewed samples collected. Absolute number (percentage) of patients are reported. Means and standard deviations were estimated for continuous variables, χ2 test and independent "t" tests were used. OR and 95% CI were estimated. RESULTS: 14,358 appointments were scheduled, 9146 (63.7%) attended their appointment: 5710 (62.4%) fulfilled inclusion criteria and 5244 agreed to participate (91.8% acceptance). Those accepting participation were more likely women, younger and with longer disease duration (p<0.05). The cost of the call-center service was $3,010,000.00 Mexican pesos (∼$31.70 USD per recruited patient). CONCLUSIONS: Stepwise strategies recruit a high number of patients in a short time. Call centers offer a low cost per patient.

Impact of neuraminidase inhibitors on influenza A(H1N1)pdm09-related pneumonia: an individual participant data meta-analysis.

BACKGROUND: The impact of neuraminidase inhibitors (NAIs) on influenza-related pneumonia (IRP) is not established. Our objective was to investigate the association between NAI treatment and IRP incidence and outcomes in patients hospitalised with A(H1N1)pdm09 virus infection. METHODS: A worldwide meta-analysis of individual participant data from 20 634 hospitalised patients with laboratory-confirmed A(H1N1)pdm09 (n = 20 021) or clinically diagnosed (n = 613) 'pandemic influenza'. The primary outcome was radiologically confirmed IRP. Odds ratios (OR) were estimated using generalised linear mixed modelling, adjusting for NAI treatment propensity, antibiotics and corticosteroids. RESULTS: Of 20 634 included participants, 5978 (29·0%) had IRP; conversely, 3349 (16·2%) had confirmed the absence of radiographic pneumonia (the comparator). Early NAI treatment (within 2 days of symptom onset) versus no NAI was not significantly associated with IRP [adj. OR 0·83 (95% CI 0·64-1·06; P = 0·136)]. Among the 5978 patients with IRP, early NAI treatment versus none did not impact on mortality [adj. OR = 0·72 (0·44-1·17; P = 0·180)] or likelihood of requiring ventilatory support [adj. OR = 1·17 (0·71-1·92; P = 0·537)], but early treatment versus later significantly reduced mortality [adj. OR = 0·70 (0·55-0·88; P = 0·003)] and likelihood of requiring ventilatory support [adj. OR = 0·68 (0·54-0·85; P = 0·001)]. CONCLUSIONS: Early NAI treatment of patients hospitalised with A(H1N1)pdm09 virus infection versus no treatment did not reduce the likelihood of IRP. However, in patients who developed IRP, early NAI treatment versus later reduced the likelihood of mortality and needing ventilatory support.

Evaluation of the impact on non-communicable chronic diseases of a major integrated primary health care program in Mexico.

BACKGROUND: Primary health care is the best framework for implementing actions for the prevention and control of non-communicable diseases at an appropriate scale. In 2002, the Mexican Institute for Social Security (IMSS), which provides health care to half of the Mexican population, implemented a primary care-based integrated program that included the improvement of the family health care practice and a preventive strategy called PREVENIMSS, to reduce the burden of disease. OBJECTIVE: To asess the impact of this program on selected non-communicable chronic diseases. METHODS: Morbidity and mortality were compared before and after implementation of the program and time trends in IMSS affiliates and non-affiliates using the difference-in-differences (DD) method. RESULTS: Incidence rates of diabetes and hypertension increased whereas those of cervical cancer, breast cancer and other cerebrovascular diseases decreased from 2000 to 2013. The DD in mortality rates, expressed per 100000 persons, showed a decrease of 49.4 for diabetes mellitus, 9.1 for hypertensive disease, 42.9 for ischemic heart disease, 17.4 for cerebrovascular disease, 7.5 for cervical cancer and 5.8 for breast cancer. CONCLUSIONS: The reductions in mortality rates could be explained by both changes in incidence rates and changes in case fatality rates associated with early detection and treatment. These initial findings can be interpreted as the potential impact of integrated programs based on primary health care in a developing country.

Intense seasonal A/H1N1 influenza in Mexico, winter 2013-2014.

BACKGROUND AND AIMS: A recrudescent wave of pandemic influenza A/H1N1 affected Mexico during the winter of 2013-2014 following a mild 2012-2013 A/H3N2 influenza season. METHODS: We compared the demographic and geographic characteristics of hospitalizations and inpatient deaths for severe acute respiratory infection (SARI) and laboratory-confirmed influenza during the 2013-2014 influenza season compared to previous influenza seasons, based on a large prospective surveillance system maintained by the Mexican Social Security health care system. RESULTS: A total of 14,236 SARI hospitalizations and 1,163 inpatient deaths (8.2%) were reported between October 1, 2013 and March 31, 2014. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were significantly higher among individuals aged 30-59 years and lower among younger age groups for the 2013-2014 A/H1N1 season compared to the previous A/H1N1 season in 2011-2012 (χ(2) test, p <0.001). The reproduction number for the winter 2013-2014 influenza season in central Mexico was estimated at 1.3-1.4, in line with that reported for the 2011-2012 A/H1N1 season but lower than during the initial waves of pandemic A/H1N1 activity in 2009. CONCLUSIONS: We documented a substantial increase in the number of A/H1N1-related hospitalizations and deaths during the period from October 2013-March 2014 in Mexico and a proportionate shift of severe disease to middle-aged adults, relative to the preceding A/H1N1 2011-2012 season. In the absence of clear antigenic drift in globally circulating A/H1N1 viruses in the post-2009 pandemic period, the gradual change in the age distribution of A/H1N1 infections observed in Mexico suggests a slow build-up of immunity among younger populations, reminiscent of the age profile of past pandemics.

WITHDRAWN: Intense Seasonal A/H1N1 Influenza in Mexico, Winter 2013-2014.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.arcmed.2014.11.005. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Effectiveness of neuraminidase inhibitors in reducing mortality in patients admitted to hospital with influenza A H1N1pdm09 virus infection: a meta-analysis of individual participant data.

BACKGROUND: Neuraminidase inhibitors were widely used during the 2009-10 influenza A H1N1 pandemic, but evidence for their effectiveness in reducing mortality is uncertain. We did a meta-analysis of individual participant data to investigate the association between use of neuraminidase inhibitors and mortality in patients admitted to hospital with pandemic influenza A H1N1pdm09 virus infection. METHODS: We assembled data for patients (all ages) admitted to hospital worldwide with laboratory confirmed or clinically diagnosed pandemic influenza A H1N1pdm09 virus infection. We identified potential data contributors from an earlier systematic review of reported studies addressing the same research question. In our systematic review, eligible studies were done between March 1, 2009 (Mexico), or April 1, 2009 (rest of the world), until the WHO declaration of the end of the pandemic (Aug 10, 2010); however, we continued to receive data up to March 14, 2011, from ongoing studies. We did a meta-analysis of individual participant data to assess the association between neuraminidase inhibitor treatment and mortality (primary outcome), adjusting for both treatment propensity and potential confounders, using generalised linear mixed modelling. We assessed the association with time to treatment using time-dependent Cox regression shared frailty modelling. FINDINGS: We included data for 29,234 patients from 78 studies of patients admitted to hospital between Jan 2, 2009, and March 14, 2011. Compared with no treatment, neuraminidase inhibitor treatment (irrespective of timing) was associated with a reduction in mortality risk (adjusted odds ratio [OR] 0·81; 95% CI 0·70-0·93; p=0·0024). Compared with later treatment, early treatment (within 2 days of symptom onset) was associated with a reduction in mortality risk (adjusted OR 0·48; 95% CI 0·41-0·56; p<0·0001). Early treatment versus no treatment was also associated with a reduction in mortality (adjusted OR 0·50; 95% CI 0·37-0·67; p<0·0001). These associations with reduced mortality risk were less pronounced and not significant in children. There was an increase in the mortality hazard rate with each day's delay in initiation of treatment up to day 5 as compared with treatment initiated within 2 days of symptom onset (adjusted hazard ratio [HR 1·23] [95% CI 1·18-1·28]; p<0·0001 for the increasing HR with each day's delay). INTERPRETATION: We advocate early instigation of neuraminidase inhibitor treatment in adults admitted to hospital with suspected or proven influenza infection. FUNDING: F Hoffmann-La Roche.

Substantial Morbidity and Mortality Associated with Pandemic A/H1N1 Influenza in Mexico, Winter 2013-2014: Gradual Age Shift and Severity.

BACKGROUND: A recrudescent wave of pandemic influenza A/H1N1 is underway in Mexico in winter 2013-14, following a mild 2012-13 A/H3N2 influenza season. Mexico previously experienced several waves of pandemic A/H1N1 activity in spring, summer and fall 2009 and winter 2011-2012, with a gradual shift of influenza-related hospitalizations and deaths towards older ages. Here we describe changes in the epidemiology of the 2013-14 A/H1N1 influenza outbreak, relative to previous seasons dominated by the A/H1N1 pandemic virus. The analysis is intended to guide public health intervention strategies in near real time. METHODS: We analyzed demographic and geographic data on hospitalizations with severe acute respiratory infection (SARI), laboratory-confirmed A/H1N1 influenza hospitalizations, and inpatient deaths, from a large prospective surveillance system maintained by the Mexican Social Security medical system during 01-October 2013 to 31-Jan 2014. We characterized the age and regional patterns of influenza activity relative to the preceding 2011-2012 A/H1N1 influenza epidemic. We also estimated the reproduction number (R) based on the growth rate of daily case incidence by date of symptoms onset. RESULTS: A total of 7,886 SARI hospitalizations and 529 inpatient-deaths (3.2%) were reported between 01-October 2013 and 31-January 2014 (resulting in 3.2 laboratory-confirmed A/H1N1 hospitalizations per 100,00 and 0.52 laboratory-confirmed A/H1N1-positive deaths per 100,000). The progression of daily SARI hospitalizations in 2013-14 exceeded that observed during the 2011-2012 A/H1N1 epidemic. The mean age of laboratory-confirmed A/H1N1 patients in 2013-14 was 41.1 y (SD=20.3) for hospitalizations and 49.2 y (SD=16.7) for deaths. Rates of laboratory-confirmed A/H1N1 hospitalizations and deaths were significantly higher among individuals aged 30-59 y and lower among younger age groups for the ongoing 2013-2014 epidemic, compared to the 2011-12 A/H1N1 epidemic (Chi-square test, P<0.001). The reproduction number of the winter 2013-14 wave in central Mexico was estimated at 1.3-1.4 which is slightly higher than that reported for the 2011-2012 A/H1N1 epidemic. CONCLUSIONS: We have documented a substantial and ongoing increase in the number of A/H1N1-related hospitalizations and deaths during the period October 2013-January 2014 and a proportionate shift of severe disease to middle aged adults, relative to the preceding A/H1N1 2011-2012 epidemic in Mexico. In the absence of clear antigenic drift in globally circulating A/H1N1 viruses in the post-pandemic period, the gradual change in the age distribution of A/H1N1 infections observed in Mexico suggests a slow build-up of immunity among younger populations, reminiscent of the age profile of past pandemics.

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.