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Keywords:

  • Complications;
  • H1N1;
  • pneumonia;
  • risk factors

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Transparency Declaration
  9. References

Clin Microbiol Infect 2011; 17: 247–250

Abstract

Eighty-one patients affected by the novel influenza A (H1N1), hospitalized in North-western Italy, were studied. The median age was 32 years (range 1–81 years). Fifty-six (69%) had an underlying medical condition, including lung disorders (asthma or chronic obstructive pulmonary disease) in 34% and obesity in 25%. Fifty percent of them had pneumonia, 12% were admitted to the intensive care unit and 3% died. Antiviral treatment was initiated in 75% of patients started within 48 h. Older age and lung and neurocognitive disorders were associated with severe disease and death.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Transparency Declaration
  9. References

Subsequent to the identification of the novel influenza virus A (H1N1) in the USA and Mexico, cases of influenza-like illness and pneumonia due to this virus have been detected in an increasing number of countries [1,2]. To date, human infection with the novel A (H1N1) virus has been identified in 191 countries and territories [2]. The influenza A (H1N1) virus contains a unique combination of gene segments that has not previously been identified in humans or animals [3,4]; thus, information on the clinical spectrum of illness, risk factors for severity among persons hospitalized for the treatment of A (H1N1) influenza and clinical management is helpful [5–9]. The great majority of individuals infected with the A (H1N1) virus experience uncomplicated influenza-like illness, with full recovery within 1 week, even without medical treatment, whereas a small subset of patients develop severe progressive disease. Primary viral pneumonia is the most common finding in severe cases [5], but secondary bacterial infections play a role in approximately 30% of fatal cases [6]. Hospitalized patients are often affected by other medical conditions, such as diabetes and cardiovascular, neurological and pulmonary diseases [5,7,8]. In the present study, we report the main clinical findings and risk factors for severe diseases in patients hospitalized in the Liguria Region, in North-western Italy.

Patients and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Transparency Declaration
  9. References

Patients presenting with influenza-like illness (temperature ≥38°C and cough or sore throat) or other symptoms consistent with influenza, and who were hospitalized for at least 24 h between 1 July and 30 November 2009, were included in the study. In all these patients, infection with the novel influenza virus A (H1N1) was confirmed by real-time RT-PCR. The CDC RT-PCR protocol and block PCR (Seeplex FluA ACE subtyping; Seegene, Rockville, MD, USA) were used for detection and characterization of pandemic 2009 H1N1 influenza virus [10].

Clinical records of the study participants were reviewed in the five infectious diseases clinics participating in the study. A standardized form, including demographic data, underlying medical conditions, clinical signs and symptoms, selected laboratory tests, radiographic findings, treatment course, and outcome, was used for data collection. The body mass index (BMI; kg/m2) was calculated for patients for whom height and weight were available, aiming to determine whether the patient was obese (obesity was defined as a BMI >30 in adults 18 years of age or older or a BMI percentile of 95–100 in children aged 2–18 years); the BMI was not calculated for pregnant women. We performed a univariate analysis to compare the characteristics of patients who were admitted to the intensive care unit (ICU) or died with those who were admitted to other wards and survived.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Transparency Declaration
  9. References

Overall, 81 patients were studied. The clinical characteristics are outlined in Table 1. The median age was 32 years (range 1–81 years); most patients were Caucasian (85%) and 36 were female (only two women were pregnant). Symptoms at presentation included fever (100%) and cough (82%). Diarrhoea or vomiting was reported in 18% of the patients. The median time from the onset of illness to hospital admission was 2 days (range 0–9 days). Of the 81 patients, 56 (69%) had an underlying medical condition, including lung disorders (asthma or chronic obstructive pulmonary disease) in 34% and obesity in 25%. On admission, 25 patients (31%) had leucopaenia, 13 (16%) had leucocytosis and 22 (27%) had thrombocytopaenia. All the patients underwent a chest X-ray on admission and 51 (63%) had findings consistent with pneumonia. Radiographic findings included interstitial infiltrates in 31 patients and parenchymal lesions in 20 (an infiltrate limited to one lobe in 16 and multilobar infiltrates in four individuals).

Table 1.   Characteristics of hospitalized patients who were infected with the 2009 novel influenza A (H1N1) virus in Italy
CharacteristicN = 81 (100%)
  1. aNeutropenia, 3; heart transplant, 2; haematological malignancy and haematopoietic stem cell transplant, 2; HIV, 2; other, 3.

  2. ALT, alanine aminotranferease; AST, aspartate aminotransferase; BMI, body mass index; COPD, chronic obstructive pulmonary disease.

Male sex45 (55)
Age, median (range), years32 (1–81)
Age group (years)
 0–105 (6)
 11–1711 (14)
 18–4950 (62)
 50–649 (11)
 ≥656 (7)
Race or ethnic group
 Caucasian69 (85)
 Hispanic (South America)12 (15)
Underline medical conditions
 At least one56 (69)
 Lung disorders (asthma or COPD)19/56 (34)
 BMI >3014/56 (25)
 Immunosuppressiona12/56 (21)
 Cardiovascular disease12/56 (21)
 Neurocognitive disorders9/56 (16)
 Chronic renal failure6/56 (11)
 Diabetes5/56 (9)
Selected laboratory abnormalities
 Leucopaenia (<5000 per mm3)25 (31)
 Leucocytosis (>11 000 per mm3)13 (16)
 Trombocytopaenia (<150 000)22 (27)
 AST/ALT elevation (>2 fold normal)4 (5)
Pneumonia
 Any type51 (63)
 Interstitial infultrates31/51 (61)
 Lobar infiltrates20/51 (39)

Regarding the use of antiviral drugs, 69 (85%) received oseltamivir. Antiviral therapy was initiated within 1–9 days (median time of 2 days) after the onset of symptoms; 75% patients (52/69) started within 48 h. Overall, 62 patients (76%) also received antibacterial therapy. The median length of hospitalization was 5 days (range 1–21 days).

Ten patients (12%) were admitted to an ICU. The difference between patients who were admitted to the ICU and those who were not is shown in Table 2. Patients admitted to the ICU were older than the others. All ICU patients had underlying medical conditions (mostly lung disease, neurocognitive disorders and obesity) vs. only 65% of the other participants (χ2, p 0.02). Patients admitted to the ICU were more likely to be of older age, as well as have lung and neurocognitive disorders (Alzheimer’s disease, vascular neurocognitive disorder, schizophrenia, frontotemporal degeneration) and X-ray confirmed pneumonia.

Table 2.   Univariate analysis of hospitalized patients who were not admitted to intensive care unit (ICU) and survived and patients who were admitted to an ICU or died
CharacteristicNot ICU, N = 71, n (%)ICU or deceased, N = 10, n (%)p
Age, median (range), years29.5 (1–81)43.5 (20–79)0.04
At least one underline medical conditions46/71 (65%)10/10 (100%)0.02
Neurocognitive disorders5 (7%)3 (33.3%)0.02
BMI >3011 (15.5%)3 (33.3%)0.25
Lung disorders (asthma or COPD)14 (19.7%)5 (50%)0.03
Cardiovascular disease9 (12.3%)3 (33.3%)0.14
Chronic renal failure6 (8.5%)00.33
Diabetes5 (7.0%)0038
Immunosuppression11 (15%)1 (10%)0.64
Antibacterial treatment49 (69%)10 (100%)0.11
Pneumonia on admission31 (44%)10 (100%)0.0008
Days from onset of symptoms to treatment, median (range)2 (0–9)1.5 (0–6)0.35

Overall, two (3%) died; both of them had been admitted to the ICU for mechanical ventilation. Death occurred after 13 days in an heart transplant recipient who developed a mixed interstitial and alveolar radiographic lesions, and after 10 days in a resident of a long-term psychiatric facility who developed multi-organ failure and secondary bacterial pneumonia.

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Transparency Declaration
  9. References

Most information available on clinical presentation and outcome, and risk factors for severe disease associated with infection with the novel influenza virus, comes from the Americas and Oceania, whereas very limited information is available from European countries, especially from Italy and other Mediterranean countries. The comparison with Northern and Central American case series shows some difference. First, the median age of our patients was higher [7,8]. Furthermore, the rate of pneumonia was unexpectedly higher compared to previous studies [8]. With regard to risk factors for severe disease, we found age and lung and neurocognitive disorders to be associated with the need of intensive care. This is consistent with data from Mexico and the USA, showing that the risk of death increases with age [11] and that neurodevelopmental disorders are associated with a negative outcome in infected children [12]. Other underlying conditions, such as cardiological disorders and a high BMI, tended to be associated with severe disease, as defined by admission to the ICU, although the difference was not statistically significant, probably as a result of the limited number of patients. The present study has several limitations. We evaluated only patients with confirmed 2009 H1N1 infection, so the group may not be representative of hospitalized patients who may not have been tested. The hospitalization criteria in the participating centres were different and therefore were subject to reporting bias. With regard to age, it is possible that paediatric cases were under-represented as a result of pediatric departments not participating in the study.

In conclusion, with the exception of higher age and rate of pneumonia, our findings are consistent with those from the Americas. In particular, older age as well as lung and neurocognitive disorders were associated with severe diseases leading to admission to the ICU. The identification of these factors is key to guiding the prevention and management of the novel influenza A (H1N1).

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Transparency Declaration
  9. References

Liguria H1N1 Collaborative Group: Malgorzata Mikulska, Antonio Ferrazin, Barbara Wenda, Valerio Del Bono, Emanuele Malfatto, Elena Nicco (Infectious Diseases Division, San Martino Hospital and University of Genoa School of Medicine, Genoa, Italy); Filippo Ansaldi (Hygiene Unit, San Martino Hospital and University of Genoa, Genoa, Italy); Emanuele Pontali (Infectious Diseases Division, EO Galliera, Genova, Italy); Michele Guerra, Stefano Parmigiani (S. Andrea Hospital, Spezia, Italy); Rosa Riente (San Paolo Hospital, Savona, Italy).

Transparency Declaration

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Transparency Declaration
  9. References

All authors declare that there are no conflicts of interest. Funding: the work was carried out as part of the regular work of our department.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Patients and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Transparency Declaration
  9. References
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