EPIDEMIOLOGY

Influenza-like illness (ILI) is defined by the CDC as fever (temperature ≥ 100°F or 37.8°C) and either cough or sore throat in the absence of another known cause. A confirmed case of 2009 H1N1 infection is defined by ILI with positive test results for the 2009 H1N1 virus by either real-time reverse transcriptase polymerase chain reaction (RT-PCR) or viral culture. A probable case is ILI with positive influenza A test results but negative results for seasonal H1 and H3 by RT-PCR. A suspected case does not meet either definition but is either a person younger than 65 years hospitalized for ILI or a person of any age with ILI and an epidemiological link to a confirmed or probable case within 7 days of illness onset.

Because of resource limitations, both the CDC and WHO stopped reporting confirmed and probable cases of 2009 H1N1 on July 24, 2009. However, through traditional systems, including surveillance for new viral subtypes, new resistance patterns, geographic spread of the virus, visits to the physician for influenza-related symptoms, hospitalizations for confirmed cases of influenza, and deaths attributable to influenza or pneumonia, the CDC will continue to report weekly statistics on the number of hospitalizations and deaths that can be attributed to the virus. Between August 30, 2009, and November 28, 2009, 31,320 laboratory-confirmed influenza-associated hospitalizations and 1336 laboratory-confirmed influenza-related deaths were reported to the CDC, and more than 99% of the most recently sub-typed influenza viruses were 2009 H1N1 influenza. These data are published weekly in FluView and can be accessed at http://cdc.gov/h1n1flu/reportingqa.htm.

Like seasonal influenza, 2009 H1N1 is thought to be transmissible by 3 routes: contact exposure (when a contaminated hand is exposed to facial membranes), droplet spray exposure (when infectious droplets are projected onto mucous membranes), and airborne exposure (via inhalation of infectious airborne particles). The relative contribution of each of these modes is unknown and likely dependent on such factors as temperature and humidity. The complexities involved with human research to understand influenza transmissibility leave animal studies and mathematical models to inform us. One such model illustrated that the relative importance of each route of transmission differs with the concentration of the virus in saliva. Evidence exists for seasonal influenza transmission via fine particles generated during tidal breathing. Recent evidence suggests that the 2009 H1N1 virus is transmitted via large particle droplets. Because large droplets remain suspended in the air for a short time, transmission via this route requires close contact (< 1.83 m [< 6 ft]) between the source and the recipient. The possibility of indirect transmission from fomites and contaminated surfaces has prompted the CDC to recommend that all body fluids (eg, stool, respiratory secretions) be treated as potentially infectious. Given the uncertainties surrounding the relative importance of each of these routes of transmission, the Institute of Medicine convened, at the request of the CDC and of the Occupational Safety and Health Administration, to provide recommendations to protect health care workers against 2009 H1N1. These recommendations are discussed in the sections that follow.

The incubation period for the 2009 H1N1 virus has been estimated to be between 1 and 7 days, similar to that of seasonal influenza. Clinicians should assume that infected persons start shedding virus 1 day before the onset of symptoms and shed at least until symptoms resolve. Recent data have suggested that up to 80% of patients are still shedding virus at 5 days, 40% at 7 days, and 10% at 10 days. Children and younger adults may shed for as long as 10 or more days, and immunosuppressed persons may shed virus for weeks.

Most cases have occurred in patients with a median age of 12 to 17 years. However, severe cases also occur in slightly older populations. More recent reports indicate that the median age of cases may increase as infection becomes more widespread in the population.

To determine whether previous seasonal vaccinations provide cross-protection against the 2009 H1N1 (A/California/04/2009) virus, the CDC performed microneutralization assays on preseasonal and postseasonal stored sera in 100 recipients of the 2005-2006 through 2008-2009 seasonal influenza vaccines. Among children, investigators found no prevaccination or postvaccination cross-reactivity; among those aged 18 to 40 years, 6% prevaccination and 7% postvaccination cross-reactivity; among those aged 18 to 64 years, 9% prevaccination and 25% postvaccination cross-reactivity; and among those older than 60 years, 33% prevaccination and 43% postvaccination cross-reactivity. These results suggest that recent seasonal influenza vaccines would not provide adequate protection against the 2009 H1N1 virus, particularly among younger people.

However, virus neutralization test results alone do not fully represent the complex immune-mediated functions involved in protection from or amelioration of influenza disease. Current disease patterns suggest that, despite low levels of cross-reacting neutralizing antibodies, adults and older children who have experienced repeated natural exposure to seasonal H1N1 viruses have an immunologic advantage in protection against disease or in moderation of clinical response to a new H1N1 infection.

CLINICAL MANIFESTATIONS

Analyses have suggested that clinical manifestations of 2009 H1N1 influenza and seasonal influenza are similar. One review of 44 confirmed 2009 H1N1 cases in a New York City high school revealed that cough (98%), fever (96%), headache (82%), sore throat (82%), rhinorrhea (82%), chills (80%), and muscle aches (80%) were commonly reported. Fewer patients had nausea (55%), diarrhea (48%), dyspnea (48%), joint pain (46%), or stomach ache (36%).

Patients requiring hospitalization for 2009 H1N1 infection are much more likely to have underlying medical conditions, especially asthma, chronic obstructive pulmonary disease, immunosuppression, diabetes, obesity, or chronic heart conditions. Such patients present with fever, cough, dyspnea, vomiting, and/or abnormal chest radiographs and are typically released after short hospital stays.

Hypoxia and chest radiographs consistent with acute respiratory distress syndrome have been characteristic of patients requiring intensive care. A prospective observational study of 168 critically ill patients with 2009 H1N1 in Canada found a mean age of 32.3 years and a median time of 4 days between symptom onset and hospitalization. Overall mortality among this group was 17.3% at 90 days and correlated with a higher severity of illness and greater organ dysfunction at presentation. All these patients were severely hypoxic at presentation, with a mean PaO2 to fraction of inspired oxygen ratio of 147. Similarly, an observational study of 58 critically ill patients with 2009 H1N1 in Mexico revealed that nonsurvivors were more likely to present with severe organ dysfunction and hypoxia than survivors. Both studies validated the use of either SOFA (Sequential Organ Failure Assessment) or APACHE (Acute Physiology and Chronic Health Evaluation) II scores to identify patients at risk of death. A review of medical records of patients with confirmed 2009 H1N1 infection requiring intensive care in Spain showed that chest radiographic findings were abnormal in all patients, with most (72%) demonstrating patchy alveolar opacities affecting 3 of 4 quadrants. In all 3 analyses, obese patients (body mass index [calculated as the weight in kilograms divided by height in meters squared] >30 kg/m2) accounted for approximately one-third of the cases requiring intensive care.

Clinicians have been advised to expect that complications from the 2009 H1N1 virus will be similar to those of the seasonal influenza virus. These include exacerbations of underlying chronic illness; complications in both the upper (sinusitis, otitis media, croup) and lower (pneumonia, asthma exacerbation, and bronchiolitis) respiratory tracts; neurologic (encephalopathy, encephalitis, febrile seizures, status epilepticus), cardiac (pericarditis and myocarditis), and musculoskeletal (rhabdomyositis) complications; toxic shock syndrome; and secondary bacterial infections with sepsis.

Postmortem lung specimens of 77 fatal H1N1 cases were evaluated by the CDC to determine the role of bacterial coinfection in fatal outcomes. Evidence of bacterial coinfection was discovered in 22 cases (29%) by means of histopathologic, molecular, and immunohistochemical analyses. In these 22 cases, Streptococcus pneumoniae predominated (10 cases); however, both methicillin-resistant and -susceptible Staphylococcus aureus, Streptococcus pyogenes, Streptococcus mitis, and Haemophilus influenzae were also discovered, in decreasing order of frequency. These findings highlight the importance of early detection and treatment of bacterial pneumonia in patients with 2009 H1N1 influenza and underscore the importance of the pneumococcal vaccine for those in whom it is indicated. Classically, bacterial pneumonia complicates influenza infection 4 to 14 days after near resolution of influenza symptoms and presents with fever, dyspnea, productive cough, and abnormal chest radiographic findings. This complication should be treated in accordance with current treatment guidelines.

Those at highest risk of developing complications include children younger than 5 years, patients 65 years or older, pregnant women, and patients with chronic underlying medical conditions (particularly asthma, but including other pulmonary, cardiac, hematologic, hepatic, neurologic, and metabolic diseases). Also at increased risk are immunocompromised patients and residents of long-term care facilities. Clinicians should recall the risk of Reye syndrome, an acute, noninflammatory encephalopathy, in children or adolescents younger than 19 years with influenza who receive aspirin or aspirin-containing products. Obese patients may be at higher risk as well, although the nature of this risk is not yet completely understood.