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Transcript of Dr. Atmar on Swine (H1N1) Flu
Influenza is a major cause of morbidity and mortality among humans. It has two major epidemiologic patterns: seasonal (or interpandemic) influenza and pandemic influenza. As the name implies seasonal influenza occurs on an annual basis in countries with a temperate climate. Pandemic influenza occurs much less frequently, with 3 pandemics occurring in the last century (in 1918, 1957 and 1968). The recent emergence of a novel influenza strain that is cause outbreaks of influenzal illness in multiple countries on several continents raises the concern that a new pandemic of influenza is imminent. In fact, the World Health Organization raised the worldwide pandemic alert level to Phase 5 on April 29, 2009, indicating that there is a “strong signal that a pandemic is imminent and that the time to finalize the organization, communication, and implementation of the planned mitigation measures is short.” In the rest of this presentation I will describe the virus, what we know about its origin and epidemiology, and various aspects of diagnosis, treatment, prevention and infection control strategies.
In March and early April an increase in the number of acute febrile respiratory illnesses were noted in Mexico. By the end of the third week in April, more than 850 cases of pneumonia had been reported with more than 50 deaths. A novel virus was identified in some of the affected patients and around the same time the novel virus was also identified in persons with influenzal illnesses in southern California. This novel virus was initially identified as a swine influenza virus, for reasons I will discuss in a moment, but because no outbreaks of illness associated with this virus have been identified in swine populations, the novel virus is now being referred to as an H1N1 virus.
The virus was initially identified as a swine virus because analysis of the sequence of the hemagglutinin gene showed that it is most closely related to swine influenza viruses. Further analyses of all of the gene segment of this novel strain has suggested that it is the result of a reassortment with two different swine influenza viruses, a North American strain and a Eurasian strain. At some point, a cell was infected with both parental virus strains, and the virus that came out of the infected cells had 6 gene segments from the North American strain, including the hemagglutinin gene, and 2 gene segments from the Eurasian strain, including the neuraminidase gene.
Influenza A/H1N1 viruses were among the most commonly identified cause of seasonal influenza in the past year in the United States, so what makes this virus novel if it is an H1N1 virus? Well, the answer is that the sequence of the hemagglutinin protein is very different than that of the recently circulating human H1 strains, and antisera raises against the recent H1 strains has little reactivity against the novel H1 strain. Since antibody to the hemagglutinin protein is one of the best correlates of immunity against influenza virus infection, the lack of cross-reactivity suggests that infection with recent human H1N1 strains or receipt of recent seasonal influenza vaccines may provide no protection against infection with the novel strain. The lack of cross-reactivity raises the possibility that a large proportion of the population may be susceptible to infection with the new strain.
As of April 30, 11 different countries have reported 257 cases of infection with the novel H1N1 strain. In addition to the cases in the US and Mexico, cases have been identified in Canada, several countries in Europe, in Israel and in New Zealand. In the United States there have been 109 confirmed cases in 11 states, with the largest numbers being in New York, Texas and California. Unlike the cases in Mexico, thus far the cases in the US appear to be less severe, although typical influenzal symptoms of fever, cough, nasal congestion, sore throat, headache, and myalgias are usually present. In addition gastrointestinal symptoms, including nausea, vomiting and diarrhea are also being reported commonly. The incubation period is likely to be the same as for seasonal influenza, 1 to 4 days. To date, there has been one death in a 22 month old child in Texas. Whether the illness outside of Mexico is truly milder or whether an insufficient number of cases in the US have occurred to identify more severe outcomes and complications is currently unknown – however, if the current pace of identifying cases continues, we should soon be better able to assess the virulence of this virus.
Diagnosis of infection with the novel H1N1 virus can be more complicated than that caused by seasonal influenza strains. Infection should be suspected in persons with a febrile respiratory illness who has had close contact with a person who has had a confirmed infection with the novel strain or who has traveled to a community where one or more confirmed cases have occurred or who resides in a community where one or more confirmed cases have been identified. A series of tests can be performed to further evaluate suspected cases. Nasal specimens (nasal wash, nasopharyngeal swab or nasal swab) are preferred over throat swabs, but lower respiratory samples may also be used for diagnosis. Rapid antigen tests and immunofluorescent studies are positive in some patients, but the sensitivity of these assays may be less than that seen for seasonal influenza. Thus, a positive test for influenza A in the setting of epidmiologic exposure currently suggests infection with the novel strain, but a negative test does not exclude the diagnosis. As part of their influenza surveillance program the CDC has distributed a real-time RT-PCR assay for influenza virus detection to regional and state public health laboratories. This assay can identify the presence of an influenza A virus and further identify such viruses as typical seasonal H1 or H3 strains or as H5 strains. However, the novel H1 strain is not recognized by the subtyping primers, so the assay identifies the infecting strain as influenza A, not H1, not H3 and not H5. Currently, samples yielding these results are forwarded to the CDC for confirmatory testing with a newly developed assay for the novel strain. The whole process currently takes several days. It is expected that the CDC will soon distribute the confirmatory assay to regional and state labs, shortening the time to make a confirmed diagnosis.
The novel H1N1 virus is resistant to adamantanes, meaning that neither amantadine nor rimantadine will have any clinical utility. However, it is susceptible to both neuraminidase inhibitors, zanamivir (or Relenza) and oseltamivir (or Tamiflu). Currently, the CDC recommends treatment for patients with either confirmed, probable or suspected infection with the novel H1N1 strain and with illness of less than 48 hours duration. Treatment at later times, especially for hospitalized patients may also have some benefit. If the availability of antiviral medication is limited, treatment may be reserved for more severely ill patients or for those at greatest risk for complications (such a pregnant women, immunocompromised patients and patients with chronic heart and lung disease). Clinicians should be guided by their local public health authorities on the availability of antiviral medications. At this time, the CDC is also recommending post-exposure prophylaxis for household close contacts of a confirmed or probable case and who are at high-risk for complications of influenza and for health care workers or public health workers who were not using appropriate personal protective equipment during close contact with an ill confirmed, probable, or suspect case during the case’s infectious period. The FDA has issued an Emergency Use Authorization to make the prescription of these two antivirals easier during this public health emergency and to allow the off-label use of oseltamivir to treat and prevent influenza in children less than one year of age.
Vaccines for the novel H1N1 are currently under development, but they are not expected to be available for general use before the fall of this year. Thus, other methods of prevention are needed. Nonpharmaceutical measures can be taken to prevent the transmission of the novel H1N1 strain. The CDC recommends the following meaures for persons who develop an influenza like illness, or ILI:
- These persons should be strongly encouraged to self-isolate in their home for 7 days after the onset of illness or at least 24 hours after symptoms have resolved, whichever is longer. Persons who experience ILI and wish to seek medical care should contact their health care providers to report illness (by telephone or other remote means) before seeking care at a clinic, physician’s office, or hospital. Persons who have difficulty breathing or shortness of breath or are believed to be severely ill should seek immediate medical attention.
- If ill persons must go into the community (e.g., to seek medical care) they should wear a face mask to reduce the risk of spreading the virus in the community when they cough, sneeze, talk or breathe. If a face mask is unavailable, ill persons needing to go into the community should use a handkerchief or tissues to cover any coughing.
- Persons in home isolation and their household members should be given infection control instructions: including frequent hand washing with soap and water.Use alcohol-based hand gels (containing at least 60% alcohol) when soap and water are not available and hands are not visibly dirty. When the ill person is within 6 feet of others at home, the ill person should wear a face mask if one is available and the ill person is able to tolerate wearing it.
Household contacts who are well should:
- remain home at the earliest sign of illness;
- minimize contact in the community to the extent possible;
- designate a single household family member as the ill person’s caregiver to minimize interactions with asymptomatic persons.
Social distancing, such as closure of schools or daycares where confirmed cases are identified are currently being pursued. Additional social distancing measures may be recommended if the epidemic continues to increase. Specific recommendations for such measures are posted on the CDC website.
Infection control measures also play an important role in preventing transmission of virus infection to other patients and to healthcare workers. Ill patients should be provided a surgical mask at presentation and segregated into a single room and if possible with negative pressure. Healthcare workers should practice both contact and droplet precautions at a minimum, although the CDC recommendations call for practices that are essentially airborne precautions (HCW use of an N-95 mask, use of a negative pressure room) in addition to contact precautions (gown, gloves). Eyewear protection (goggles or faceshield) should also be worn, especially if collecting clinical samples. Hand hygiene should be practiced. In our hospital, we are currently maintaining patients with these isolation precautions until we receive the results of the RT-PCR assay from the local health department.
There are a number of other issues that have come up and are likely to continue to come up that the CDC is addressing by posting guidances for clinicians on the website. I strongly encourage you to visit the site for additional information. Some of the measures suggested by these guidances may have to be modified based upon local factors and recommendations by local health authorities, but this website is an excellent source of information. You can access it at http://www.cdc.gov/h1n1flu/guidance/ .
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