antiviral medications, H1N1, immunization, influenza A



  1. Kapustin, Jane Faith PhD, BC-ADM, CRNP, FAANP


The 2011-2012 season will hit while the United States is still recovering from the 2009-2010 novel H1N1 pandemic. Signs and symptoms, high-risk groups, immunization recommendations, and the latest guidelines from the CDC are reviewed.


Article Content

After coming home from school early due to complaints of headache, sore throat, and fever, 6-year-old SR appears sleepy and her face is flushed. She has not eaten all day and is afraid she will vomit in the car. After getting in bed, she falls fast asleep but her mother is uneasy about her daughter's appearance and behavior. Usually vivacious SR now looks lethargic and is very quiet. Her breathing is labored and she sounds like she is wheezing slightly.

Figure. No caption a... - Click to enlarge in new windowFigure. No caption available.

Normally, SR is healthy, although she does experience mild upper respiratory infections several times per year. She has a history of mild asthma, requiring occasional use of a rescue inhaler when she develops a respiratory infection.


By supper time, SR's mother has trouble waking her up and she notes that her fever is 104[degrees]F (40[degrees]C)-higher now in spite of taking acetaminophen several hours ago. She is now coughing continuously, wheezing, and seems unable to catch her breath. Her mother takes her to the closest ED for evaluation.


In the ED, SR's oxygen saturation is only 84% and her nail beds appear bluish. She is wheezing audibly, and her rapid antigen test for influenza A is positive. Arterial blood gases on 100% non-rebreather mask reveal mild hypoxemia and hypercapnia, and her chest X-ray shows bilateral pleural effusions and suspicious infiltrate in the right lower lobe. She is started on I.V. antibiotics and antiviral medication, given frequent nebulizer treatments, and finally admitted to the pediatric ICU for close observation with the diagnosis of H1N1 influenza with pneumonia. Following 5 days of I.V. fluids, antibiotics, oxygen, nebulizer treatments, and antipyretics, SR is finally transferred out of ICU and eventually recovers well enough to return home. The discharging nurse advised her mother to get the influenza vaccine for SR annually in the future.


The 2009-2010 influenza season in review

This case illustrates the conundrum of H1N1 influenza (also known as "swine flu") that was rampant in 2009-2010. The new strain first emerged in Mexico and caused more disease in younger adults and children. It spread quickly with high numbers of cases seen in South America and ultimately in the United States. In fact, widespread international travel has contributed to the development of new viral strains.1


Seasonal flu usually occurs in late fall and lasts into spring, and most people display some natural immunity. Approximately 5% to 20% of the population will contract seasonal flu and an average of 23,600 will die annually.1 In 2009, a flu pandemic occurred when the new influenza A virus, H1N1, emerged and most of the population had little to no natural immunity. The novel influenza virus was able to spread unchecked from person to person by airborne or droplet transmission.1,2


Seasonal flu usually affects the very young and the very old, but the H1N1 flu affected young adults, with the average age around 35. Children who were adversely affected by H1N1 typically suffered from at least one underlying medical condition such as asthma, immunosuppression, chronic lung disease, neurologic disorders, or heart disease.3


Unlike SR many children eventually required mechanical ventilation to effectively reverse the hypoxemia associated with the high viral load. In addition, some children developed pneumonia (usually Staphylococcus aureus, Streptococcus pneumoniae, or Haemophilus influenzae).4 The 2009 H1N1 flu settled more in the lower respiratory tract whereas seasonal flu usually only rests in the upper airways. Additionally, the viral load H1N1 flu found on autopsy in victims of H1N1 flu was incredibly high, particularly in the lung tissue.5 Many infants with preexisting medical illnesses who contracted H1N1 developed severe respiratory distress from pneumonia or coinfection with respiratory syncytial virus. Sadly, many of these infants eventually died from refractory hypoxemia.4


However, the H1N1 flu outbreak resulted in far fewer deaths or hospitalizations than the typical seasonal flu causes. According to the CDC, approximately 274,000 were hospitalized and 12,470 died-far fewer than in a typical flu season. Of those who required hospitalization, over 90% were people under the age of 65. It is speculated that the 2009 H1N1 influenza affected older adults less virulently because many had benefited from prior lifetime exposure to the virus. The majority of those who sustained severe morbidity with the H1N1 flu had underlying medical conditions such as pregnancy, obesity, or lung disease.1,5,6 The 2010-2011 flu season was less severe than the pandemic year (2009-2010), and influenza A (H3N2) was the most prevalent virus. However, H1N1 levels were also high and are expected to circulate again in 2011-2012. In fact, almost all (99.8%) of the influenza virus A H1N1 submitted to the CDC were similar to the antigenic components of the 2010-2011 vaccine.


In a study involving H1N1 flu, Belongia and colleagues5 found that the virus disproportionately affected young adults and children most likely because they lacked immunity to it. Children who developed pneumonia were more likely to suffer from H1N1 than regular seasonal flu, but the statistics verified that H1N1 was a milder virus than first thought. H1N1 was deemed unpredictable due to the lack of previously formed antibodies, but the complications that most patients experienced were no greater than those experienced during seasonal flu outbreaks.


In another study of H1N1 patients, researchers found that 93% had underlying chronic diseases, 42% were obese, and pregnant women were more likely to contract H1N1. More younger people (ages 18 to 49 years) were affected more, reflecting lack of immunity in that cohort.3,7


In spite of the unpredictable nature of H1N1 flu, the response to the crisis in the United States was robust. Vaccines were developed in record time and more than 90 million people received vaccination. As with any influenza season, monitoring the disease burden is difficult due to the nonspecific nature of the symptoms. In addition, many affected individuals do not seek medical attention or are tested for influenza.8,9


The 2011-2012 vaccine

It is expected that H1N1 will continue to spread among infants, children, pregnant women, and other high-risk people. Fortunately, H1N1 is one of the three viruses covered again in this year's flu vaccine (A/California/7/09 [H1N1]-like virus); the others are A/Perth/16/2009 (H3N2)-like and B/Brisbane/60/2008-like strains.10 The CDC recommends that all persons age 6 months and older get vaccinated in 2011-2012 even if they received the vaccine during last year's season.10 There is a risk that the selected strains are not optimal matches for the season, but the severity of illness will still be lessened. If more people are vaccinated in 2011-2012, acquired and herd immunity may prevent many of the complications seen last season.1,9,10


At-risk populations

The incidence of complications among adults 19 to 64 years of age who had 2009-2010 pandemic H1N1 was greater than the incidence in those who had seasonal flu. Younger people were adversely affected due to the lack of natural immunity. Pregnant women and obese people were also at higher risk.1,9


The CDC actually simplified the task of identifying at-risk populations for the 2010-2011 season, and the same recommendations will pertain to the 2011-2012 season.10 Everyone age 6 months and older are considered high-risk and should get vaccinated. The call for universal vaccination will prevent the need for healthcare providers to refer to high-risk group lists and rationing vaccine supplies. The main reason for the change, however, is to capture the populations who are at high-risk for the complications of flu illness-obese people and postpartum women, for example. Healthcare workers are also considered high-risk because they are likely to come into contact with people infected with influenza virus and can easily spread virus to others.9


Influenza facts

Influenza is clearly distinguished from the common cold in several ways. In general, flu symptoms include marked fever, cough, chills, myalgias, headaches, fatigue, sore throat, and coryza. In addition, influenza has an abrupt onset (see Physical exam findings associated with influenza). Children may also suffer vomiting and diarrhea, and some people will not develop a fever with the flu. Cyanosis, wheezing, or shortness of breath may be seen if pneumonia is also present.9


The most common, significant complications associated with influenza are:


* Viral pneumonia or mixed viral/bacterial pneumonia


* Secondary respiratory tract complications (sinusitis, croup, otitis media), asthma


* Sepsis, septic shock


* Carditis (myocarditis or pericarditis)


* Neurologic conditions such as Guillain-Barre syndrome, encephalitis, seizures


* Reye syndrome (especially in children given aspirin).9



Influenza is diagnosed in a variety of ways. Screening for influenza A includes a rapid influenza diagnostic test enzyme assay with a sensitivity of 50% to 90% and specificity of 80% to 95%.12 Results take approximately 15 minutes. Real-time reverse transcription polymerase chain reaction is another diagnostic test with sensitivity and specificity of 98% and takes 2 to 4 hours to get results. A culture can be done as well but it is expensive and results can take up to 10 days. It is normally recommended to manage patients with flulike symptoms without conducting diagnostic tests.12



The 2009-2010 influenza virus maintained sensitivity to the antiviral medications oseltamivir and zanamivir. H1N1 displayed resistance to more traditional antivirals such as rimantadine and amantadine. Interestingly, previous influenza seasons displayed opposite profiles with almost complete resistance to oseltamivir and sensitivity to rimantadine and amantadine.9,10


Other important measures to treat and control the spread of influenza A include supportive care, isolation of patients, use of protective equipment, and telephone triage to minimize office visits and further spread of virus in busy waiting rooms. Additionally, patients need to be instructed about appropriate hygiene for hand washing and cough protection.9,10


Immunization recommendations

As with any influenza season, it is best to vaccinate as many people as possible to prevent the spread of virus and its complications. The trivalent inactivated influenza vaccine (TIV) can be used for anyone age 6 months or older without contraindications to the vaccine (known allergy to eggs or other components of the vaccine) because it does not contain live virus. This includes people with high-risk conditions such as immunosupression.9


Because it has the potential for causing mild flulike symptoms (fever, nasal congestion, and sore throat), live, attenuated influenza vaccine (LAIV) can only be used for nonpregnant people between the ages of 2 and 49 years. LAIV is not recommended for people with underlying medical conditions as they should receive TIV only. It is anticipated that more people will consent to LAIV since it is given intranasally.9


Because vaccination is beneficial even when given later in the influenza season, people can receive the vaccine as late as March, although the CDC recommends the vaccination be given as early as possible. Protective antibody formation usually occurs within 2 weeks following vaccination. As with any influenza season, it is best to avoid giving the vaccine to people who have moderate to severe illness with fever.9


Overall, vaccination rates in the United States are low, especially among minority ethnic groups, low-income groups, and young people with chronic diseases. Surprisingly, healthcare providers also have a low rate of compliance with CDC recommendations.11,12 The CDC recommends vaccination for all healthcare providers to help prevent widespread disease, but even the H1N1 pandemic demonstrated low vaccination rates among clinicians.13


Some healthcare agencies required workers to get the flu vaccine before they can work to overcome this problem; however, offering the vaccines for free did not significantly affect immunization rates. Estimated at 49% to 53% for 2009-2010, rates of influenza vaccination among healthcare workers were disappointedly low, even for a novel virus H1N1.13 Several techniques that have been somewhat successful include making the vaccine free for healthcare workers and educating them about the importance of protecting their patients.11,13 Recently, the American Academy of Pediatrics14 and the Society for Healthcare Epidemiology of America15 published position papers to endorse a policy that requires influenza vaccination for healthcare workers. Widespread mandatory policies have not been adopted, however.16


The CDC's Advisory Committee on Immunization Practices made some modifications based on last season's experiences:9,17


* All persons age 6 months and older should receive vaccination.


* Inactivated influenza vaccines were approved for expanded age-groups:


- Fluarix-ages 3 and up


- Agriflu-ages 18 and up.


* Afluria should not be used in children between ages 6 months and 8 years because of a higher incidence of fever and febrile seizures.


* High-dose Fluzone was approved as an alternative inactivated vaccine for persons 65 years and older.There are several other special points about vaccination in the upcoming season:


* Children between 6 months and 8 years need two doses of vaccine if they have not already had seasonal influenza vaccine or if their history is unknown. These children need two doses if they only received one dose in the previous season.


* Children between 6 months and 8 years also need two doses if they did not get at least one dose of H1N1 vaccine in 2009-2010 or 2010-2011.


* For all children, the second dose needs to be given at least 4 weeks after the initial vaccine.9



Encourage vaccination

Even though more people will have some immunity to H1N1 in the 2011-2012 influenza season, the CDC continues to recommend widespread vaccination for all people age 6 months and older to help achieve population-wide immunity (see 2011-2012 influenza prevention and control recommendations). Particular emphasis is placed on vaccinating high-risk populations such as pregnant women, obese people, and healthcare workers. NPs have an obligation to recommend vaccination for all patients as well as to get themselves vaccinated. It is important for healthcare providers to emphasize vaccination as the best means to control the spread of influenza. Patient education and widespread vaccination campaigns to encourage the benefits of vaccination as well as to dispel myths are the preferred methods for preventing morbidity and mortality associated with the seasonal flu.


Physical exam findings associated with influenza1,8


* Facial flushing


* Cervical lymphadenopathy


* Injected pharynx


* Rhinitis, congestion


* Fever


* Injected conjunctiva


* Tachycardia


* Cough


* Dehydration related to fever (dry mucous membranes, poor skin turgor, postural hypotension)


* Cyanosis, hypoxia if severe


2011-2012 influenza prevention and control recommendations9

Summary of influenza vaccination recommendations for 2011-2012:


* All persons age 6 months and older should be vaccinated annually.


* Protecting people at higher risk for influenza-related complications should continue to be a focus of vaccination efforts as providers and programs transition to routine vaccination of all persons age 6 months and older.


* When vaccine supply is limited, vaccination efforts should focus on people who:



- are age 6 months to 4 years (59 months);


- are age 50 years and older;


- have chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus);


- are immunosuppressed (including immunosuppression caused by medications or by human immunodeficiency virus);


- are or will be pregnant during the influenza season;


- are of ages 6 months to18 years and receiving long-term aspirin therapy and who, therefore, might be at risk for experiencing Reye syndrome after influenza virus infection;


- are residents of long-term-care facilities and other chronic-care facilities;


- are American Indians/Alaska Natives;


- are morbidly obese (body mass index is 40 or greater);


- are healthcare personnel;


- are household contacts and caregivers of children age younger than 5 years and adults age 50 years and older, with particular emphasis on vaccinating contacts of children age younger than 6 months; and


- are household contacts and caregivers of persons with medical conditions that put them at higher risk for severe complications from influenza.



Updates from 2010 remain current for 2011.




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3. Memoli MJ. pH1N1 influenza A: timing is everything. Crit Care Med. 2010;38(10):2081-2082. [Context Link]


4. Libster R, Bugna J, Coviello S, et al. Pediatric hospitalizations associated with 2009 pandemic influenza A (H1N1) in Argentina. N Engl J Med. 2010;362(1):45-55. [Context Link]


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14. Bernstein HH, Starke JR, American Academy of Pediatrics Committee on Infectious Diseases. Policy statement-recommendations for mandatory influenza immunization of all health care personnel. Pediatrics. 2010;126(4):809-815.;126/4/809. [Context Link]


15. Talbot TR, Babcock H, Caplan AL, et al. Revised SHEA position paper: influenza vaccination of healthcare personnel. Infect Control Hosp Epidemiol. 2010;31(10):987-995. [Context Link]


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