Influenza


Table 1: Epidemiologic Data from the 2009 Influenza A (H1N1) Pandemic4–14


Attack rate (illness)


Attack rate (overall infection) Overall case fatality rate Patients <65 years of age Patients with risk factors Median age of fatal cases


Case fatality rate for symptomatic illness 28-day ICU mortality rate


Cumulative excess mortality rate in children Overall ICU admittance rate Pregnant women


Severe acute respiratory infections (in Europe) Fatalities


ICU = intensive care unit.


Table 2: Frequency and Distribution of Underlying Medical Conditions Associated with Complicated Disease13,18,19


Total


Number of Comorbidities 0 1


≥2


Underlying Medical Conditions Pulmonary Asthmaa COPD Other


Immunosuppression Cardiovascular disease Diabetes


Neurologic disease Obesity Pregnancyb


20 6 6 –


20 11 8


22


Cerebral palsy/developmental delay 0.99 6 7


Adults %


49 34 17


%


40 31 6 3 –


16 12 3 – 2


18


Children %


66 29 5


%


19 16 0 3 – 2 1 4 – 0 0


a. In children, asthma was a significant risk factor for severe disease; however, a relationship with asthma severity has not yet been established. In pregnant women, asthma was associated with a six- to 22-fold increased risk for hospitalisation, and the risk increased as pregnancy advanced. b. General population pregnant women represent 7% of all adults and 18% of all women 15–44 years of age, with an estimated pregnancy rate of 6.2% in the healthy population.


COPD = chronic obstructive pulmonary disease.


The time interval from the onset of symptoms to the initiation of antivirals was the strongest correlate of severity of disease in intensive care unit (ICU) patients (odds ratio [OR] 12 if there were more than two days of delay). Pregnant women represented 7–10% of those who were hospitalized, 6–9% of ICU patients, and 6–10% of those who died.20–22


The


most important factor associated with increased risk for severe disease was delayed initiation of antiviral therapy (relative risk [RR] 4.3% for admission to the ICU or death).17,23


There was at least one underlying disease in 90% of ICU patients; discounting those with minor comorbidities not associated with an increased risk for viral pneumonia, the rate was 40%, representing an OR of 3.19 for ICU admittance. Obesity was present in 30–61% of ICU patients.11,20,24,25


Obesity acted as an independent risk factor for mortality, 66


7.5% 11%


<0.5% (0.0004–1.47%) 80–90% 77%


43 years


0.026–0.048% 14–46%


1 per 100,000 9–31% 6–9%


11,489 cases 570 cases


prolonged ICU stay and mechanical ventilation. The incidence of severe disease in patients with severe and morbid obesity was five- to 15-fold higher than in the general population, excluding comorbidities and complications related to the obesity itself.8,26,27


Nosocomial transmission was responsible for 50% of cases of H1N1v infection in healthcare workers28


infection in 17% of hospitalized patients.10 Pathogenesis


Transmission occurred via respiratory droplets (person to person) and aerosol (airborne), similar to the transmission of seasonal influenza viruses. Aerosol transmission occurred in people exposed to intubation or mechanical ventilation.7,8,16


Viral shedding was more profuse than with seasonal H1N1 and was prolonged by up to 28 days in very young or very old patients, patients with underlying conditions, immunocompromized patients or those with mechanical ventilation.16


In intubated patients,


viral RNA levels were higher and lasted longer in specimens from both the upper and lower respiratory tract. Heavy viral loads were detected in the periphery of the lungs as well as in the nasopharyx.7,8


The immune response is still incompletely characterized. The inflammatory response was similar to that seen with seasonal influenza, with activation of typical but ineffective innate antiviral responses in human dendritic cells and macrophages.29


H1N1v binds to receptors in the conjunctivae, distal airways and alveolar pneumocytes. The incubation period lasted for 24–72 hours but in some cases was as long as seven days. H1N1v replicated more efficiently than seasonal H1N1. High rates were seen in the nasal cavity, trachea, bronchi and bronchioles and lung tissues, with these areas affected the most severely.1


and was reported to be the source of


Cytokine patterns were found


in patients who died or developed acute respiratory distress syndrome (ARDS), both throughout the illness and during the late phase.8 Symptomatic re-infections have been reported despite the rise of neutralising antibodies. Early secretion of Th1 and Th17 cytokines was associated with respiratory involvement and severe disease, a similar immune pattern to that seen in cell-mediated-immunity inflammatory and autoimmune diseases.29


Target cells included the upper respiratory and tracheobronchial epithelium and mucosal glands, with the alveolar lining cells becoming infected. Initially, pulmonary vascular congestion occurred, sometimes accompanied by alveolar hemorrhage.7


In primary viral pneumonia, there


was widespread infection of the airway characterized by necrotizing tracheobronchitis. Lung involvement, which mainly occurred only in severe cases, was seen as intra-alveolar hemorrhage, inflammatory occupation of the alveolar space, septal edema, tracheitis, and necrotizing bronchiolitis, and in severe cases pulmonary thromboemboli. Myocarditis and hemophagocitosis were also reported.8


Bronchopneumonia with bacterial co-infection has been found in 26–38% of fatal cases.10


This may be attributed to the synergy between


viral and bacterial pathogens, which involves cell damage with exposure of binding sites for bacterial adhesion and bacterial neuraminidase enhancing viral infection. This is consistent with the findings in animal


US RESPIRATORY DISEASE


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58  |  Page 59  |  Page 60  |  Page 61  |  Page 62  |  Page 63  |  Page 64  |  Page 65  |  Page 66  |  Page 67  |  Page 68  |  Page 69  |  Page 70  |  Page 71  |  Page 72  |  Page 73  |  Page 74  |  Page 75  |  Page 76  |  Page 77  |  Page 78  |  Page 79  |  Page 80  |  Page 81  |  Page 82  |  Page 83  |  Page 84