How to cite this article: Albarrán-Sánchez A, Ramírez-Rentería C, Huerta-Montiel F, Martínez-Jerónimo A, Herrera-Landero A, García-Álvarez JL, Ortiz-Rodríguez E, Palmas-Pineda L. [Clinical features of patients with influenza-like illness who went to a third level center in the winter of 2013-2014]. Rev Med Inst Mex Seguro Soc. 2016;54 Suppl 2:S162-7.
Received: November 2nd 2015
Judged: May 2nd 2016
Alejandra Albarrán-Sánchez,a Claudia Ramírez-Rentería,b Fernando Huerta-Montiel,a Angélica Martínez-Jerónimo,a Alejandro Herrera-Landero,a José Luis García-Álvarez,a Elia Ortiz-Rodríguez,a Lorena Palmas-Pinedaa
aServicio de Admisión Continua
bServicio de Endocrinología Experimental
Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Ciudad de México, México
Communication with: Alejandra Albarrán Sánchez
Background: between October 2013 and April 2014, the Centers for Disease Control and Prevention reported a high incidence of AH1N1 influenza cases. Not all suspicious cases of influenza are confirmed; however, all patients need treatment and generate additional costs to the institutions. Our objective was to describe the characteristics of the patients treated for influenza suspicion at Hospital de Especialidades in Centro Médico Nacional Siglo XXI during a new epidemic.
Methods: Cross-sectional study of all cases admitted at the Emergency Service (of the aforementioned hospital) for influenza-like illness, defined according to current guidelines. Based on these guidelines, we analyzed the risk factors that may have increased the severity of the infection.
Results: We registered a total of 109 patients with a mean age of 44 years, 78 % were under 60 years of age, 62 % were women, 75 % had at least one comorbidity, such as obesity (26 %) or hypertension (27 %). Only 65 patients had results from a confirmatory test, 33.8 % had positive diagnosis, and 21 % of them eventually died.
Conclusions: The frequency of confirmed cases for influenza infection is low. The risk factors associated with complications and increased mortality are hypertension, leukocytosis and clinical presentation of severe acute respiratory syndrome.
Keywords: Influenza A virus H1N1 subtype; Mortality
The effects of influenza epidemics on morbidity and mortality worldwide are considerable.1 The epidemiology of these events still leaves us with several questions, such as the ubiquity of the virus, how outbreaks begin and end, the presence of synchronous epidemics in similar latitudes of the planet, and secondary infection rate.2 In developing countries confirmatory diagnostic tests are not readily available in all centers and where they are carried out; therefore the results are often delayed due to high demand.3 This means patients receive treatment and are hospitalized by purely clinical judgment, which can have varying degrees of accuracy4 since laboratory and imaging studies (including rapid tests) have low sensitivity for differential diagnosis with other respiratory infections. The severity of the outbreak is variable and is estimated to increase in association with pneumonia and mortality.5 In Mexico there have been two recent outbreaks of importance: one associated with the pandemic of 2009 and another in 2013.6 In 2009, Neri et al.7 conducted a study that found that lymphocyte values > 1000/mm3, creatine phosphokinase (CPK) > 500 U/L, and lactate dehydrogenase (LDH) > 1000 U/L predict the likelihood of requiring mechanical ventilatory support, and that this LDH level predicted mortality with a sensitivity of 80% and a specificity of 60%. The Clinical Practice Guidelines for the Prevention, Diagnosis and Treatment of Influenza A (H1N1)8 was made with the data obtained in 2009, considering the limitations in our country. It addresses the possibility of treating patients suspected of having influenza, even when in cases lacking all the confirmatory elements. Patients with influenza type illness (ILI) are recorded in mild cases and cases of severe acute respiratory failure (SARF) and acute respiratory distress syndrome (ARDS) in severe cases. Patients in these groups, in addition to confirmed cases, should be evaluated closely. The diagnosis requires experience by the doctor and knowledge of the criteria of clinical severity.9 The classification allows patients at high risk of complications to be promptly referred to specialized centers, including Hospital de Especialidades del Centro Médico Nacional Siglo XXI. Our center welcomes adults who make up a large percentage of the Mexican population with multiple comorbidities, and the most critical patients are admitted through the Continuous Admission Service. The Emergency and Continuous Admission departments play a vital role in the initial care, generating the clinical suspicion, initiating management, and finally in patient referral, so the training of personnel and facilities is a priority, especially in epidemics.10 To this end, the criteria must be based on local evidence and cost-effective practices adapted to the particular needs of the center.11 This center hosts patients who require highly specialized management, while others can be managed at another level of hospital care and even at home. Therefore, our goal is to describe the characteristics of patients seeking care for suspected influenza in the Continuous Admission service, and to analyze the risk factors associated with the signs during a new outbreak.
A cross-sectional study was performed, collecting the records of suspected cases of influenza seen from February 2013 to March 2014 in Continuous Admission. We included those who met the criteria for suspected influenza, classified as follows: influenza-like illness (ILI), severe acute respiratory failure (SARF), and confirmed cases of influenza, according to the Clinical Practice Guide for the Prevention, Diagnosis and Treatment of Influenza A (H1N1). Medical history and clinical patient data and laboratory and imaging results were reviewed. The patients’ final diagnosis and outcome was recorded. The data obtained were analyzed according to the variable type and distribution, using the statistical package SPSS 21.0, and p < 0.05 was considered significant.
Features of suspected cases of influenza
Data from 109 patients were analyzed with a mean age of 44.4 ± 16.7 years (range 16-91 years); 78% of patients were younger than 60. 62% were women. 22% of cases occurred in health workers (11 doctors, three nurses, and 11 other hospital workers), and 58% occurred in February 2014.
Upon admission, most patients had on average more than 72 hours from the onset of symptoms. The most common clinical and laboratory data are presented in Table I.
|Table I Characteristics of suspected cases of influenza (n = 109)|
|Fever (> 38 °C)||35.3|
|Environmental oxygen saturation < 95%||53.8|
|Leukocytosis (> 12 000 per µL)||30.1|
|Neutrophilia (> 7500 per µL)||39.4|
|Thrombocytopenia (< 140 000 per µL)||14.3|
|High LDH (u/l)|
|LDH = lactic dehydrogenase|
Of the factors traditionally described as risks for complications, it was determined that only 48% of the population had normal weight (body mass index or BMI of 18.5-24.9 kg/m2); obesity was 26% (BMI > 30 kg/m2), hypertension in 27%, 16% post-transplant status, diabetes in 12%, and chronic obstructive pulmonary disease (COPD) in 11%. Smoking was recorded in 13% of patients, with a median smoking history of 2 (RIC 1-12). 75% of patients had at least one of the risk factors mentioned above.
Almost half of patients (48.7%) had at least one drug considered as a risk factor for complications of influenza infection. The most frequent were steroids with 32.5%, 17.4% were taking azathioprine, 15.6% mycophenolate, 6.4% tacrolimus, 4.6% cyclosporine, 2.8% sirolimus, 1.8% methotrexate, and 11.9% omeprazole taken chronically.
Features of confirmed cases of influenza
Influenza screening tests were performed in 68 patients (59.6%), 42 of which were reported negative; 20 were positive for H1N109 (17 5%), and three for H3. In comparing patients who had tests taken versus those without, it was found that patients who underwent other confirmatory tests more frequently had a history of COPD (11.8% versus 0%, p = 0.047) and had a higher respiration rate (25 versus 21 breaths per minute, p = 0.027). There were no differences between other clinical or laboratory parameters between patients with and without tests, nor was the outcome different between these patient groups.
The 23 patients who tested positive for influenza (20%) were almost equal to the total group regarding the epidemiological, clinical, laboratory, and imaging features. 47.8% were women with a mean age of 45 ± 19 years, 14.3% had diabetes, and 26.8% were in a post-transplant state, which is similar to the entire group. Of these, only 25% reported having been immunized in the past year. At admission, the LDH in this group was reported at 466 (393-657), leukocytes at 9350 (6875-13875), and neutrophils at 7320 (5010-11580). Chest x-rays of these patients were found normal in 39.1%; 21.7% had interstitial pneumonia; 17.5% suffered lobar pneumonia, and 21.7% had multifocal foci pneumonia. As for the fate of confirmed cases of influenza, nine of them (39%) were discharged home after the initial evaluation, while the remaining 14 (61%) remained hospitalized in this unit; two of them required hospitalization in intensive care, and five died during hospitalization (21% mortality). Patients with abnormal chest x-rays were more likely to be receive confirmatory tests (Chi-squared = 13.7, p < 0.001), as they were asked to 85% of patients with lobar pneumonia, as that 93% of cases with pneumonia of multiple foci and 88% of those who had infiltrated other, while only 51% of those who had normal plates were asked that test. Similarly, it was more likely that the test was sought in over 65 years than in other age groups (Chi-squared = 5.5, p = 0.029). None of the other variables analyzed showed statistically significant differences compared to the group without confirmatory tests, nor with the group with negative tests.
Within the group of patients with positive tests, other differences were found between patients who died those who did not. Patients with positive influenza tests had the highest frequency of death; however, they did not have a significant difference from the negative test group (p = 0 12). Patients who died had higher total leukocytes (15900 versus 8550, p = 0.035), higher neutrophils (5910 versus 15280; p = 0.014) and lower hemoglobin (12.3 versus 14.8, p = 0.035). Also, among patients who died, multifocal pneumonia was the most common (80% versus 6%, p = 0.003). Among the patients who died, the most frequent comorbid diseases found were: hypertension (100%) and heart disease (44.4%). Comparisons with the positive test group of those who died versus those who did not die can be seen in Table II.
|Table II Comparison of characteristics of confirmed cases of influenza who died versus those who did not die (n = 23)|
( n = 5)
(n = 18)
|Age (in years)||55||41-66||37||29-50||0.155|
|BMI (in kg/m2)||31.9||30-32||25||23.9-26 8||0.444|
|ABP (in mm Hg)||78.3||71.6-80||90||82.5-100.4||0.255|
|Leukocytes (normal 4600 to 10200 per mL)||15900||13500-19850||8550||6650-10600||0.035|
|Neutrophils (normal 1500 to 7000 per mL)||15280||11340-15960||5910||4852-7885||0.014|
|Hemoglobin (normal 13.0 to 18.0 g/dL)||12.3||9.8-13.4||14.8||13.5-16.6||0.035|
|LDH (normal 240-480 u/l)||509||431-1276||462||377-558||0.999|
|Obesity (BMI > 25kg/M2 )||40||5.9||0.067|
|Diagnosis of type 2 diabetes mellitus||40||5.9||0.128|
|Multi-focal pneumonia upon admission||80||5.6||0.003|
|Patient with influenza-like illness (ILI) upon admission||0||83.3||0.002|
|Patient with severe acute respiratory infection (SARF) upon admission||100||16.7||0.002|
|Patient with acute respiratory failure syndrome (ARFS) upon admission||100||11.1||0.001|
|History of immunization against influenza in the last year||40||23.5||0.529|
|IR = interquartile range; BMI = body mass index; ABP = blood pressure average; LDH = lactic dehydrogenase; ILI = influenza-like illness; SARF = severe acute respiratory failure; ARFS = acute respiratory failure syndrome|
Patients who died were most frequently rated among categories of SARF and ARDS, while patients who did not die were at lower risk categories. No significant differences were found between immunization frequencies; however, they were low in all groups.
Despite their behavior being unpredictable, recent influenza epidemics are handled more efficiently and mortality has declined worldwide.11,12 In Mexico there are still limitations to confirm early diagnoses, so the guides say that the accepted treatment (currently oseltamivir) should not be delayed until test results.8 The most recent epidemic in Mexico reported a total of 7886 events of severe respiratory symptoms, with 3.2 hospitalizations with confirmed A/H1N1 per 100,000 inhabitants and 0.52 confirmed positive tests in patients with A/H1N1 per 100,000 deaths.13 Our study reported a 21% hospital mortality among patients who had positive tests (confirmed cases of influenza), which represents a decrease from the 2009 pandemic, when Mexico reported mortalities over 40% for the serotype H1N1; however, this compares with a figure of 0.52 per 100,000 inhabitants reported by WHO,13 which could be due to selection bias of these being a hospital patient population with significant comorbidities and polypharmacy, which does not represent the full spectrum of the disease. Severe forms were presented in adults whose average age was 55 years, most of them under 65.14,15
Despite the mortality in high-risk groups in previous epidemics, only 32.3% of patients had been vaccinated, an even lower percentage than reported nationally, which is 56.5%,15 which shows that strategies are yet to be implemented and more information on the importance of vaccination must be disseminated in our country, especially in patients at risk who are in frequent contact with health services due to their comorbidities.
The international literature mentions that hospitalization for influenza occurs in fewer than 5% of cases,16 and shows that more patients are hospitalized in Mexico (60% in this study); however, it is thought that this also because patients in this center have high comorbidity and because infection from other agents is not eliminated, plus only patients with high suspicion of infection and risk of complications are tested, unlike the systematic screening that is done in other countries. For example, the CDC recommends the use of rapid tests whenever there are influenza outbreaks, when testing has greater predictive power.17 These frequencies are beginning to also be presented in other countries, where some health insurers do not cover the cost of the test unless it justified by the severity of symptoms.
It is noteworthy that not many differences were detected between the confirmed and suspected cases of influenza. This may reflect the limitations of retrospective studies and the fact that, in immunocompromised patients, all respiratory disease occurs similarly regardless of the associated pathogen, representing a diagnostic challenge.18 Although no significant differences were found between the groups in most variables, certain differences were found in the approach, management, and outcomes. The clinical judgment of the evaluating physician was important in the decision to perform the confirmatory test. Patients with positive tests were more likely to die, compared to those who had other respiratory infections or infections not confirmed as influenza.
Despite the potential cost of the current management, the end result was a reduction in mortality compared to studies published in 2009. Whereas all patients confirmed for influenza who died had at least two comorbidities, hypertension in all plus another disease, these results suggest that mortality is limited to higher-risk groups.
Despite the fact that the clinical findings and laboratory and imaging studies do not distinguish influenza from severe cases caused by other pathogens, they do establish with a good degree of certainty which patients may have severe symptoms and are at risk for complications and even death. Our results suggest that all patients with more than two comorbidities, elevated LDH, abnormal X-rays, and low saturation had the main risk factors for complications. Although these risk factors have been analyzed in other publications,19-21 the value of LDH or radiographic patterns that best predicts the risk remains controversial and may need to be standardized for each center and population. In addition, other risk factors and predictive cutoff points for complications from influenza or severe respiratory illness remain controversial, partly due to the variation between populations, studies, and characteristics of the different epidemics.
At the moment efforts to alert the public to take preventive measures and pursue vaccination at all levels of care should continue. Our center must continue monitoring changes in the normal behavior of this virus and report them to take the necessary actions.
Confirmed cases of influenza are low in all patients who come for care with suspicion of the disease. Mortality in confirmed cases of influenza has declined. Factors associated with complications and death are the presence of two comorbidities, obesity, and clinical presentation of severe acute respiratory failure (SARF) or acute respiratory distress syndrome (ARDS).
We thank the engineer Alejandro Hinojosa Rojas from the Nephrology Disease Research Unit of the Hospital de Especialidades of the Centro Médico Nacional Siglo XXI for his support in data capture.
This study was derived from the project with the same title registered on April 4, 2014 before the Local Ethics Committee of the Hospital de Especialidades "Dr. Bernardo Sepúlveda" Centro Médico Nacional Siglo XXI, authorized with the registration number R-2014-3601-35.
Conflict of interest statement: The authors have completed and submitted the form translated into Spanish for the declaration of potential conflicts of interest of the International Committee of Medical Journal Editors, and none were reported in relation to this article.