KEY POINTS
■ On April 29, 2009, the World Health Organization declared a human influenza pandemic. The pandemic is the result of an influenza A virus that originated in pigs and has been categorized as a novel swine-origin influenza A(H1N1) virus. The term novel refers to a genetically unique influenza virus that transmitted from pig to human and is now able to transmit rapidly from human to human.
■ Signs and symptoms caused by influenza A infection usually manifest 1 to 4 days after exposure. The patient typically presents with sudden onset of fever and cough, but may also report chills, malaise, myalgias, headache, nasal congestion, coryza, sore throat, nausea, vomiting, and diarrhea.
■ Influenza can be diagnosed with throat swabs, nasopharyngeal washes, or sputum by rapid viral tests or reverse transcriptase-polymerase chain reaction. The subtype of influenza A virus can only be determined accurately in a designated laboratory with the use of subtypespecific antiserum.
■ Antiviral medications reduce the severity and duration of influenza symptoms if they are started within 48 hours of the onset of illness. If antiviral treatment is initiated, the first dose should be administered as soon as possible and should not be delayed awaiting laboratory confirmation of infection.
■ Specific guidelines for the treatment of novel H1N1 influenza may have changed by the time this article is published; therefore, PAs should refer to www.cdc.gov/h1n1flu/recommendations.htm for the most up-to-date recommendations.
The H1N1 influenza virus burst onto the global media stage this year and brought to the foreground viruses that have caused human disease on a pandemic scale since 1918. Clinicians who encounter patients with influenzalike illness (ILI) are responsible for identifying those who are at risk for flu complications, judiciously ordering laboratory studies, and dispensing antiviral medications. The goals of this article are to provide a clinically based review of influenza and to place the current H1N1 flu outbreak in historical and clinical context with other influenza viruses.
EPIDEMIOLOGY
Seasonal influenza outbreaks of widely varying severity are recorded annually. In the past century, however, three major influenza pandemics were recognized as a result of a genetic reassortment of human influenza A viruses with animal influenza A viruses.1 The most severe pandemic, in which an estimated 40 to 50 million people died, occurred in 1918. Other influenza pandemics occurred in 1957 and 1968 and to a lesser extent in 1977.2 In 1997, the discovery of avian influenza illness in humans in Hong Kong generated fear of a pandemic. Avian influenza is a highly pathogenic influenza A(H5N1) found in birds and, occasionally, in pigs. The virus transmitted easily from bird to bird but poorly from bird to human and human to human; therefore, the originally feared pandemic did not occur. Although pandemic influenza outbreaks do not appear to have any temporal pattern, they do seem to be decreasing in severity.3
On April 29, 2009, the World Health Organization (WHO) declared a human influenza pandemic. The pandemic is the result of an influenza A virus that originated in pigs and has been categorized as a novel swine-origin influenza A(H1N1) virus (S-OIV).4 Although swine H1N1 viruses and human H1N1 viruses have been documented in the past, the term novel refers to a genetically unique influenza virus that transmitted from pig to human and is now able to transmit rapidly from human to human.5 The first cases of this novel S-OIV were discovered in Mexico and the United States in March and April 2009; by June 2009, all 50 US states had reported cases of the virus. At press time, the United States was on the cusp of influenza season, and the full impact of this S-OIV was not known.
CLASSIFICATION AND PATHOPHYSIOLOGY
Influenza is a single-strand RNA virus found in the family Orthomyxoviridae (Figure 1). Influenza viruses are subdivided into three genera: A, B, and C. Influenza B and C viruses are not typically categorized further because they demonstrate very little genetic change and are not thought to cause disease in species other than humans.6,7 In contrast, influenza A virus is capable of rapid genetic evolution in multiple species. It requires further categorization by the species in which the virus resides (primarily avian, swine, or human) and by the genetic makeup of the two prominent surface glycoproteins (hemagglutinin [H] and neuraminidase [N]).
Influenza A viruses evade host antibodies to hemagglutinin and neuraminidase through mutations in the genes that code for these surface antigens (referred to as genetic drift). These minor mutations cause the yearly variation in influenza A viruses that circulate the globe. A more substantial mutation occurs when the genes that code for hemagglutinin and neuraminidase recombine with influenza virus segments from another animal species. The reassortment of genes between two species (called a genetic shift) may produce more severe infections because the surface antigens are wholly unrecognizable by the antibodies circulating in the immune system. A pandemic can occur when the influenza virus genes recombine between different species.7
CLINICAL MANIFESTATIONS
Signs and symptoms of influenza A infection usually manifest 1 to 4 days after exposure. The patient typically presents with sudden onset of fever and cough but may also report chills, malaise, myalgias, headache, nasal congestion, coryza, sore throat, nausea, vomiting, and diarrhea. Classic presentations are less likely to be seen in children, adults older than 60 years, and immunosuppressed patients. Symptoms of more severe illness may include shortness of breath, chest pain, headache, debilitating myalgias, or neurologic dysfunction.
Influenza B and C infections typically manifest with mild clinical symptoms and are most commonly found in children and people who reside in group settings. Healthy adult immune systems are able to develop an antibody response that confers future resistance because influenza B and C viruses demonstrate little genetic variation.
Clinical signs of uncomplicated influenza are few but may include pharyngeal injection, conjunctival injection, facial flushing, and cervical lymph node enlargement. Frequently, the patient's complaint of a severe sore throat is not consistent with the mild pharyngeal injection seen on examination. Findings that indicate a more severe illness may include frank dyspnea, hypoxia, cyanosis, diffuse rales, pulmonary consolidation, a fever that lasts for more than 5 days, or symptoms that last for more than 10 days.
The influenza virus causes the respiratory epithelium to break down, which increases the risk of a secondary bacterial infection (ie, acute bacterial sinusitis, otitis media, bronchitis, or pneumonia). Clinicians should be alert for these secondary bacterial infections when patients present with prolonged illness or worsening symptoms. The influenza virus itself can cause primary viral pneumonia, which has a significant mortality rate, particularly in high-risk populations.
Extrapulmonary complications of influenza include myositis; transverse myelitis; rhabdomyolysis; myocarditis; pericarditis; encephalitis; transverse myelitis; Guillain-Barré syndrome; and gradual deterioration of underlying cardiovascular, pulmonary, or renal function. The medical conditions that predispose patients to the highest risk of death from influenza virus infection are chronic cardiopulmonary diseases; pregnancy; advanced age; and, to a lesser extent, chronic metabolic, renal, or immunosuppressive diseases.