The 2009 Influenza A (H1N1) Pandemic—A Blast from the Past


models of better survival when the infection is treated with an antineuraminidase antiviral in combination with antibacterials.30,31


Clinical Presentation


There was a wide variety of clinical presentation, from upper respiratory ‘illness’ without fever to fulminant pneumonia. Mild afebrile disease occurred in 8–32% of cases. Fever may have been masked by antipyretic medication, advanced age, or immunosupression.10


The


majority of patients presented with typical influenza symptoms. ILI, defined as fever with cough and/or sore throat, had very low sensitivity (21–43%) and positive predictive value (23–50%) but high specificity (86–93%) for influenza infection among hospitalized patients.10


Nausea, vomiting, and diarrhea were common, especially in adults and young children.


There was typically rapid progression within four to five days of the onset of illness. Community-acquired pneumonia (CAP) algorithms were not helpful because they have not been validated in pandemic conditions. Therefore, there should be a high suspicion of severe disease in young patients presenting with clinical signs of tachypnea, hypoxemia, hypotension and/or diarrhea and high levels of lactate dehydrogenase (LDH), creatine kinase (CK), and creatinine.7,8,32,33 Lymphopenia was common (68.1%), usually appearing on the second day and lasting until the seventh day.34


Radiographic findings generally involved diffuse alveolar–interstitial infiltrates, rarely with lobar and multilobar distribution; the latter chiefly occurred in those with bacterial co-infection. Pleural effusions were sometimes present.7


to initiation of antiviral therapy was six days (longer than in those with uncomplicated disease).17,21


The gender predominance varied.11,17,24


Patients requiring intensive care represented 49–72% of all-cause ICU admissions in 2009. These patients presented mainly with diffuse pneumonitis (without bacterial co-/super-infection), severe hypoxemia and ARDS, and occasionally renal failure and shock. Primary viral pneumonitis was the most frequent presentation (90.6%). Patients presenting with primary viral pneumonitis more frequently had an underlying cardiopulmonary disease.7,10,26


Suspected or confirmed


bacterial co-infection occurred in 15–24% of ICU patients, contributing to higher mortality rates. Bacterial pathogens were the same as those seen in co-infecting seasonal pneumonia, CAP, and healthcare-associated pneumonia (HAP). In one autopsy-based study, 29% of subjects had histopathological, immunohistochemical and molecular evidence of bacterial co-infection. The most common pathogens were Streptococcus pneumoniae (45%), Staphylococcus aureus (30% and frequently found to be methicillin-resistant [MRSA]), and S. pyogenes (30%). MRSA was associated with rapidly progressing fulminant disease.8,11,17,38 multiple bacteria were isolated in 18% of patients.38


Furthermore, Exacerbation of underlying respiratory diseases accounted for fewer than 10% of cases.


There was a need for inhaled nitric oxide (iNO) in 13.7% and prone positioning in 33%, and in some cases even extracorporeal membrane oxygenation (ECMO).11,42


In a prospective study of 97 patients with


confirmed H1N1v, 60% had a normal chest radiograph, of whom 3% had an adverse outcome (mechanical ventilation and/or death); of the 40% with abnormal findings (similar to those described above), 72% had involvement of multiple lung zones and 62% had bilateral opacities. Multizonar (four or more) and bilateral peripheral opacities were more common among people with adverse outcomes (60% versus 6–15% in those with good outcomes).35


Computed tomography (CT) scans showed


multiple areas of ground-glass opacities, air bronchograms and alveolar consolidations, mostly in the lower lobes. Discrete pleural effusions have been described; however, most effusions were related to volume overload.


Complicated Disease


Severe lung disease in influenza infection includes primary viral pneumonitis, secondary bacterial pneumonia and acute lung injury, and is usually seen as a rapidly progressive decline in respiratory function requiring mechanical respiratory support.40


An alarming feature of the 2009 H1N1v pandemic was the shift in the age trend for complicated illness compared with seasonal influenza. In the five- to 59-year-old age range there was a significant increase in severe disease (from 32 to 71%) and mortality (from 17 to 87%) in the 2009 H1N1v pandemic compared with seasonal influenza.36,37 Respiratory failure associated with H1N1v has been described extensively.8,10,17,26,37–41


The need for vassopresssor support was related to the need


Intubation was often necessary in the first 24 hours after admission, with the need for prolonged and advanced mechanical ventilation techniques in 75–81%.24,37 days.11


The median duration of mechanical ventilation was 12 Respiratory failure was accompanied by


refractory septic shock and multiple-organ dysfunction syndrome (MODS). Renal replacement techniques were used in 21.9% of ICU patients.37


for high-dose sedation.11


The overall 28-day mortality rate in ICU patients was 14.3% (confidence interval [CI] 9.5–20.7%). Greater organ dysfunction and severe illness at presentation were common characteristics among those who did not survive. The primary causes of death were ARDS and hypoxemia. Laboratory findings associated with poor prognosis included elevated levels of creatinine, CK, and LDH as well as thrombocytopenia and metabolic acidosis.8,11


Special Considerations


In two case series, 79% of hospitalized children had comorbidities, 20% were admitted to the ICU, and 10–12% required mechanical ventilation. Children who were hospitalized were older than those generally hospitalized for seasonal influenza (six versus three years of age). The median length of hospital stay was four days. The vast majority of children presented with clinical features of seasonal influenza and 50% had clinical and radiographic findings of pneumonia; however, there were others who presented with gastrointestinal or neurological symptoms, all of whom also had fever.4,43


Neurological involvement has


In the 2009 pandemic, in those with complicated disease the mean time from hospitalization to ICU admittance was one day (interquartile range [IQR] zero to two days)11


US RESPIRATORY DISEASE


been reported but in this case was uncommon and characterized by seizures, encephalitis, aseptic meningitis, and acute necrotizing meningoencephalomyelitis.44


Prolonged recurrent fever, alteration of and the mean time from the onset of symptoms


consciousness, and recurring pulmonary illness were associated with complicated disease.8


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