The H1N1 strain of influenza A (also known as swine flu) has spread worldwide since March 2009, when it is believed to have originated in Mexico, and is now of concern in many countries. Interestingly, the average person is likely able to identify H1N1 specifically as an “influenza virus,” an awareness that was never very prevalent before. Previously, most individuals were not aware that there are different strains or even different types of influenza viruses. The development of this pandemic has made the H1N1 strain a household term, familiar to adults and children alike.
Influenza is an infectious disease caused by viruses in the family Orthomyxoviridae. These viruses infect mammals and birds and can be transmitted from one type of animal to another. Though influenza is often confused with the common cold, it is a more severe disease and can, in some cases, lead to mortality of those infected. Symptoms in humans include chills, fever, sore throat, muscle pain or myalgia, headache, coughing, weakness, and overall general discomfort. Influenza viruses are transmitted through the air by coughing or sneezing, or through contact with contaminated surfaces (for example, transmission can occur during handshaking).
The viruses that cause influenza are similar in structure, consisting of a roughly spherical protein capsid that is 80–120 nanometers (nm) in diameter, surrounded by a viral envelope (Fig. 1). Two main types of glycoproteins are associated with the envelope's surface: hemagglutinin, or H protein, and neuraminidase, or N protein. There are 16 different types of H protein and 9 different types of N protein; each strain is named for the type of H and N proteins present on the envelope of the virus. These proteins are of vital importance in the infection process of these viruses. Hemagglutinin is used by the virus to bind to sialic acid sugar residues that are found on the surfaces of epithelial cells in the human respiratory tract. This allows the virus to be taken into the cell by endocytosis. Neuraminidase is used by the virus after replication, allowing it to escape from the host cell by cleaving the same host sialic acid residues.
The internal core of the virus contains a genome that consists of seven or eight pieces of RNA that are negative-sense; that is, the RNA sequences must be converted by an RNA-dependent RNA polymerase enzyme to positive-sense RNA strands before they can be used by the host cell machinery. This segmentation allows for the mixing of genetic information when two different viruses enter the same host cell, leading to a sudden change in the type of antigen present in a virus. This allows the new virus to infect naïve hosts, who will lack immunity to the new type of virus. This process is known as antigenic shift and can result in new influenza pandemics (Fig. 2).
There are three genera of influenza viruses: influenza A viruses, which are the most virulent or deadly influenza viruses for humans; influenza B viruses, which infect primarily humans but are less dangerous than influenza A infections; and influenza C viruses, which infect humans, dogs, and pigs. Of the different genera, only influenza A viruses have the ability to undergo antigenic shift, in which different influenza strains recombine during infection of a host cell to produce a “new” strain of virus. Antigenic shift led to the development of a new influenza virus in the spring of 2009, which then spread quickly, resulting in the 2009 H1N1 pandemic.
The “Spanish flu” pandemic of 1918 also was caused by an H1N1 strain of influenza; this pandemic led to the deaths of an estimated 20–50 million individuals worldwide. This strain of influenza virus was also unusual in that most of the people who died from it were less than 65 years of age and more than half of those were adults between 20 and 40 years of age. Usually, influenza is more deadly in the very young, such as babies and toddlers, and in the elderly. The fact that the 2009 virus is also an H1N1 strain may account for some of the panic about this particular pandemic.
Development of the H1N1 pandemic
In April 2009, an outbreak of influenza-like illness occurred in Mexico. Shortly thereafter, the Centers for Disease Control (CDC) reported cases of type A/H1N1 influenza in the southwest region of the United States. It soon became clear that the two outbreaks were related, and the World Health Organization (WHO) issued a health advisory about influenza-like illness in the United States and Mexico. The disease spread rapidly in Mexico, causing over 2000 confirmed cases by early May 2009, despite the measures put in place by the Mexican government. These measures included thermal scanners at airports to detect passengers with fever and the distribution of thousands of face masks to the public. A little more than a month later, the WHO declared H1N1 to be a pandemic, the first to be declared since the 1968 Hong Kong flu.
H1N1 traveled from Mexico to the United States, from which it has spread worldwide. More than 214 countries and territories of countries have reported H1N1 cases (Fig. 3). More than 18,000 deaths have been attributed to the H1N1 pandemic flu. The 2009 H1N1 strain of influenza differs from the 1918 Spanish flu strain because it causes primarily more severe disease in the very young (children under 5, but especially those under 2 years of age), adults over 65, pregnant women, and those with underlying medical conditions, such as patients with asthma, diabetes, chronic lung disease, or heart disease.
Influenza outbreaks peak in the wintertime; because there are seasonal variations between the Northern and Southern hemispheres, there are two different flu seasons. Therefore, two different vaccines are developed in preparation for each hemisphere. A recent study showed that influenza virus survives longer on surfaces at colder temperatures and that aerosol transmission of the virus is higher at cold temperatures with low relative humidity. This may account for seasonal flu variation in temperate climates, where there is less of a temperature difference from season to season. As a result of the two flu seasons, the spread of H1N1 worldwide has affected the two hemispheres at different times.
Prevention and treatment of H1N1 influenza
Influenza is prevented through vaccines that are produced as directed by the WHO, which predicts which virus strains are most likely to be circulating through the population in the upcoming season. As stated previously, two different vaccines are developed, based on the variations between the Southern and Northern hemispheres. After the 2009 H1N1 pandemic was declared, a vaccine based on its characteristics was rushed into production and distribution in an attempt to stem the number of cases that would occur in the United States. Two types of vaccines were developed: a live, attenuated virus vaccine that is administered using a nasal spray, and a killed-virus vaccine that is injected into the muscle of the arm. The use of the live vaccine is limited to immune-competent individuals; it is contraindicated in individuals with underlying medical conditions, because it can cause disease in these patients.
Severe cases of H1N1 influenza are treated using the neuraminidase inhibitors oseltamivir (Tamiflu®) and zanamivir (Relenz®) in individuals who have been symptomatic for no more than two days. A third neuraminidase inhibitor, peramivir, also was approved for use in hospitalized patients with 2009 H1N1 influenza. This treatment was approved for patients who did not respond to the other neuraminidase inhibitors and when the infection in those patients is life-threatening or critical. Amantadine and rimantadine are drugs used to inhibit the M2 ion channel that is required to allow viral uncoating after entry into the host cell; however, these drugs are both contraindicated in H1N1 infection, as the virus appears to be almost universally resistant to these antivirals.
Current status of the H1N1 pandemic
Presently, the most active areas of pandemic influenza are in West Africa, the Caribbean, and Southeast Asia. Pandemic influenza transmission is active in several countries of the tropical Americas, including Cuba and Guatemala. Cases of pneumonia in children under 5 years of age increased in Peru during March and April 2010; however, the extent to which these cases were caused by H1N1 viruses is unknown. In Southeast Asia, cases of H1N1 continue to increase in Malaysia and Singapore, whereas cases in Thailand peaked in March 2010 and have since steadily decreased. H1N1 activity in the United States and Europe has decreased since the beginning of April 2010.
When the H1N1 flu outbreak began in April 2009, the CDC began tracking and reporting lab-confirmed cases of H1N1 in the United States. This tracking was suspended in July 2009, when the CDC started using a system of estimating the prevalence of H1N1 cases by correcting for underascertainment of disease. Using this system, the CDC estimates that between 43 and 88 million cases of 2009 H1N1 infection occurred during the period from April 2009 to March 2010. Hospitalizations attributed to H1N1 infection within the same time period are estimated to have been between 192,000 and 398,000, and the number of deaths due to H1N1 is estimated to have been between 8720 and 18,050. Undoubtedly, case numbers, hospitalizations, and deaths from pandemic H1N1 will increase, especially as epidemiologists predict that the virus will return in the next flu season in both Europe and the United States.