What is H1N1 influenza?
In April 2009, the US Centers for Disease Control and Prevention (CDC) reported two cases of swine influenza A (H1N1) in children residing in Southern California. Neither child had any exposure to pigs or had traveled abroad in the weeks prior to illness. This strain was found to have a unique genetic code that had not previously been identified in either swine or human cases. Specimens collected from an outbreak of influenza in Mexico, beginning in early 2009, proved to be identical to the strains found in California. By May 5, there were 642 confirmed cases of human swine-origin influenza in forty-one states. By May 25, the virus had spread to forty-three countries with 12,515 reported cases and 95 deaths. On June 11, 2009, the World Health Organization (WHO) declared the start of a global pandemic, which lasted until August 2010. Overall, the 2009–2010 H1N1 pandemic caused nearly 15,000 confirmed deaths worldwide. The virus continues to circulate but has not caused widespread infections as it did from 2009 to 2010.
The genetic code of influenza A is sequenced on eight separate segments of single-stranded RNA. When multiple strains of influenza virus infect the same host, such as a pig, these segments of RNA can be exchanged between strains during viral replication, and new strains emerge. Genetic sequence analysis of the H1N1 swine influenza strain which emerged early in 2009 has multiple genetic precursors. Genes from swine H1N2 influenza virus circulating among the North America swine population in the 1990s, genes from H3N2 North American swine influenza, and genes from H1N1 Eurasian swine influenza all have similarity to portions of the 2009 pandemic H1N1 virus genome. The final reassortment of swine (Eurasian and North American), avian, and human influenza A genes may have occurred at a Mexican pig farm with spread of the new quadruple reassortment virus into the human population.
Shifts in the hemagglutinin and neuraminidase surface antigens yielding a novel influenza virus occur every ten to thirty years. In the intervening periods, smaller changes in the hemagglutinin (antigen drift) allow the virus to circulate in the human population, but it does not infect sufficient numbers to cause large epidemics or pandemics. These viruses cause severe disease in the very young and elderly individuals who become infected. However, when novel strains emerge after an antigenic shift, children and young adults join those at the extremes of age in having severe disease. This situation is the result of children and young adults having not been exposed to an influenza A subtype similar to the new strain, leaving them without an effective immune response. The 2009 H1N1 swine influenza A followed this pattern, with severe cases and deaths occurring in children and young adults. Infections are worse when there is an underlying illness, such as asthma or diabetes, but nearly half of the severe cases have no underlying medical illness. Obesity emerged as a risk factor for severe and fatal H1N1 disease.
Pregnant women are at high risk for severe influenza caused by any subtype, but the novel H1N1 swine influenza A seems to have struck this group of patients especially hard. Early data from the United States show that pregnant women infected with the H1N1 strain are significantly more likely to be admitted to the hospital or die as a result of their infection than the general population. Pregnancy ratchets down the immune response to allow the developing infant not to be rejected. Further into pregnancy, the enlarging uterus and fetus restrict movement of the diaphragm and facilitate the development of pneumonia. Additionally, these pregnant young adults join their nonpregnant peers in lacking immunity by virtue of having no prior exposure to the H1N1 influenza subtype.
The H1N1 virus's manner of spreading is similar to other strains of influenza. Large droplets from coughing and sneezing by an infected patient are spread to the mucosal surfaces (nose, mouth, and eyes) of uninfected individuals. This droplet spread is most intense when the distances are short, a few feet, but may occur up to ten feet. Direct contact with infected respiratory secretions is also important in the spread of infections and the virus can survive on surfaces and objects for a few hours. Small droplet aerosols may also have a role, but there is less evidence that this is a significant method of transfer. Infected persons can shed the virus and spread disease beginning one day before becoming ill and up to five to seven days after symptoms appear. Infection can result from contact with infected pigs, as probably occurred in the original cases in Mexico, but pork and pork products are not infective.
The incubation period (time between infection and illness) is two to seven days. The most common symptoms have been fever, cough, and sore throat, but 25 percent of patients have had diarrhea or vomiting, which are unusual symptoms for influenza. Headache, aching muscles, burning eyes, and other symptoms accompanying influenza infection may occur. While fever was reported to occur in 94 percent of the first 642 confirmed cases in April and May 2009, subsequent series of cases have reported the absence of fever in 10 to 50 percent of those infected. The severity of illness can vary widely from that of a self-limited mild illness to severe disease requiring admission to a hospital intensive care unit. Individuals that develop severe illness usually show rapid deterioration between day three and five. Respiratory failure from pneumonia, shock, and failure of other organs may follow.
Early diagnosis of H1N1 influenza is important as therapeutic intervention can reduce severity, shorten the course of the illness, and prevent further spread of the infection. A number of rapid influenza diagnostic tests (RIDTs) are available and provide results in thirty minutes or less. A molecular technique called reverse transcriptase polymerase chain reaction (RT-PCR) is able to detect specific influenza RNA in respiratory secretions. This test is highly sensitive and specific and can accurately diagnose infection with H1N1 influenza, but it is performed only in special laboratories and results can take days making them of little use for immediate diagnosis and therapeutic decision making.
Primary viral pneumonia is the most common type of pneumonia in severe cases, but secondary bacteria pneumonia has been found in 30 percent of fatal cases. The most common bacteria are Streptococcus pneumoniae and Staphylococcus aureus. Overall, it appears that 10 to 20 percent of patients with disease severe enough to require admission to a hospital intensive care unit will die.
The H1N1 influenza is treated with neuraminidase inhibitors. Oseltamivir, which is available as a capsule and an oral suspension, and zanamivir, which is supplied as an inhaled powder, are oral neuraminidase inhibitors that can be used for both treatment and prophylaxis. A new intravenous neuraminidase inhibitor, peramivir, was approved by the FDA for emergency treatment of H1N1 during the pandemic; however, the emergency-use authorization for peramivir expired in June 2010. Zanamivir is also available for oral use to treat H1N1. Antiviral therapy is most effective when started early in the course of the illness, but viral RNA has been detected in the lower respiratory tract for as long as two weeks, suggesting that antiviral therapy may be beneficial even in the later stages of the illness. Consequently, it is recommended by the CDC that any patient who is not improving receive antiviral therapy even if it is more than forty-eight hours after symptoms have begun.
Complex care in an intensive care unit is necessary for severely ill patients. Respiratory failure must be managed by intubation and mechanical ventilation often involving sophisticated equipment and techniques.
Secondary bacterial pneumonia occurs in some patients and staphylococci and streptococci have been found to be the most common invading pathogens. Antibacterial agents effective against these bacteria must be given in addition to the antiviral to successfully treat this complicated pneumonia.
Prevention of H1N1 disease can be accomplished by administration of the seasonal flu vaccine, which is available by shot or nasal spray. Vaccines against H1N1 are made from influenza virus that has been grown in chicken eggs and are not recommended for persons allergic to eggs. The nasal mist can be given to healthy individuals between the ages of two and forty-nine, except pregnant women. All others must receive the injectable killed vaccine, including high-risk patients, such as pregnant women and HIV patients who have decreased immunity. Since the protective immune response to H1N1 following vaccination takes two weeks to develop, oral antiviral therapy may be administered during this period to afford protection. In some cases, such as patients allergic to eggs, longer prophylaxis may be warranted and has been shown to be safe and effective for extended duration.
In 1936, Richard E. Shope first reported antibodies to swine influenza in humans, and shortly thereafter viruses isolated from swine and from humans were linked to the 1918 influenza virus. These viruses are now known to be H1N1 influenza A, and direct descendants of the 1918 virus still persist in pigs and humans. The human H1N1 virus undergoes continual and gradual antigenic drift, causing annual disease and even epidemics. The porcine enzootic H1N1 strain only rarely infects humans. An outbreak of swine H1N1 influenza at Fort Dix, New Jersey, in 1976 caused concern and led to a vaccination campaign, but further spread never occurred. In recent years, analysis of material preserved from fatal cases of 1918 influenza have resulted in complete sequencing of the viral genome. These data have demonstrated that all subsequent pandemic viruses are descendants of the 1918 virus, as are nearly all human influenza A viruses worldwide. Descendants of the 1918 virus resulting from antigenic shifts caused pandemics in 1957 (H2N2) and 1968 (H3N2). Intrasubtype reassortment caused pandemics in 1947 (H1N1), 1957 (H1N1), 1997 (H3N2), and 2003 (H3N2). The origin of the 1918 virus remains unclear, but it is thought to be derived from avian strains with simultaneous adaptation to both humans and swine with possible genetic contributions from an as-yet-to-be-identified different animal host.
Another interesting aspect of the 1918 pandemic is the occurrence of three waves in the Northern Hemisphere. The first wave, beginning in March, lasted six months and had high attack rates, but death rates remained at expected levels. The second wave, from September to November, and a third wave in early 1919 were both characterized by high mortality. Since the autopsy material used for genetic sequencing was from second-wave cases, it has not been possible to determine if any changes in the virus occurred from the less-fatal, first-wave virus.
The 2009 H1N1 virus had a number of similar features to the 1918 virus. The pandemic began in March and spread around the world with continuous activity throughout the summer in the Northern Hemisphere. In September, activity increased and continued to progress. However, there was no increased activity in the winter and into spring 2010, which is unlike the third wave of the 1918 pandemic that occurred in early 1919. While the fatality rate of the 2009 virus was much lower than the 1918 virus, many deaths occurred across all age groups. Vaccines, antivirals, and modern intensive care therapies provided measures to combat influenza that were unavailable in 1918. Demand for vaccines, antivirals, intensive care unit beds, ventilators, and health care providers was high, but resources kept pace. Some H1N1 activity continues worldwide, but the virus has not caused widespread infections since the 2009–2010 pandemic. Successful vaccination, along with handwashing and the use of respirators and masks in health care facilities, significantly slowed the spread of the virus.
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