Epidemiology and Prevention of Vaccine Preventable Diseases

Welcome to the Epidemiology and Prevention of Vaccine Preventable Diseases webinar series. I’m Candice Robinson, a medical officer in the Immunization Services Division of the National Center for Immunization and Respiratory Diseases, or NCIRD, at the CDC and I’ll be your moderator for today’s session. To participate in today’s program all you will need is an internet connection. Here are our learning objectives. At the conclusion of this session the participant will be able to describe the different forms of immunity, describe the different types of vaccines, for each vaccine preventable disease identify those for whom routine immunization is recommended, for each vaccine preventable disease describe characteristics of the vaccine used to prevent the disease, describe an emerging immunization issue, locate resources relevant to current immunization practice, and implement disease detection and prevention healthcare services to prevent health problems and maintain health. Today is September 7, 2016 and on the agenda is the Epidemiology and Prevention of Vaccine Preventable Diseases Pink Book, specifically the topic Influenza which draws from the chapter on influenza. This will be presented by Dr. Raymond Strikas, a medical officer, in the Communication and Education Branch.

Continuing education or CE credit is available only through the CDC ATSDR training and continuing education online system at www2a.cdc.gov/TCEonline. If you are watching this version live, CE credit for this session will expire on October 11, 2016. If you’re watching the enduring archive version, CE credit for the session expires on June 1, 2018. When obtaining CE, you will be required to provide a verification code. Watch and listen for the verification code during the course. Verification codes will not be given outside of this presentation. CDC, our planners and our presenters wish to disclose they have no financial interests or other relationships with the manufacturers of commercial products, suppliers of commercial services or commercial supporters. Presentations will not include any discussion of the unlabeled use of a product or a product under investigational use. CDC does not accept any commercial support. A list of resources for influenza will be available and the web page is www2.cdc.gov/vaccines/ed/pinkbook/pb14.asp. If you have a question during this presentation and related to this presentation, please type your question in the QA pod. I will collect these questions during the presentation and then we will address them during the question and answer period which will follow Dr. Strikas’ presentation. I will now turn the session over to Dr. Strikas.

Thank you very much, Dr. Robinson. So let’s delve into the multifaceted topics of influenza viruses, disease and vaccines. Influenza is a highly infectious viral illness. The name influenza originated in 15th century Italy from an epidemic attributed to the influence of the stars, hence the name. The first pandemic or worldwide epidemic that clearly fits the description of influenza occurred in 1580. There have been at least four pandemics of influenza in the 19th century and three in the 20th century. The pandemic of Spanish influenza, perhaps the most notorious in 1918-1919 caused at least an estimated 21 million deaths worldwide and likely more. The pandemics in 1957 and 1968 were of lesser severity. The first pandemic of the 21st century occurred in 2009 with the H1N1 virus about which we’ll talk more later. The first influenza virus was isolated in a laboratory in 1933.

The virus is a single-stranded helically.?.-shaped RNA virus of the orthomyxovirus family. The nuclear material determines three basic antigen types: A, B, and C. Type A influenza has subtypes that are determined by the surface antigens or proteins. Hemagglutinin and neuraminidase are the H and the N that you commonly hear and we’ll use henceforth to talk about type A viruses. Three types of hemagglutinin in humans, H1, H2 and H3, have a role in virus attachment to cells. Two types of neuraminidase, N1 and N2, have a role in virus penetration into cells of humans. There are some differences in the three types. Type A influenza can cause moderate to severe illness and affects all age groups among humans and other animals. Type B influenza causes milder epidemics, changes less rapidly than type A, and affects only humans and primarily children. Type C influenza is rarely reported in humans and it does not cause epidemics or pandemics.

Here you can see an illustration of a type A influenza virus and this illustration is also on the cover of the 2015 Pink Book. Influenza viruses are named in order by the virus type, A or B, their geographic origin, the strain number and the laboratory identifying the virus, the year the virus was isolated, and for type A virus the subtype is defined by the hemagglutinin and neuraminidase. So the virus above is type A, California #7 in the lab for which it was isolated. The virus was isolated in 2009 and it is of the H1N1 subtype.

Antigenic drift and shift can affect the .influenza?. viruses that we see and cause disease. Antigenic drift is responsible for minor changes in the surface proteins caused by point mutations in the genes that originate those proteins and may result in an epidemic or serious disease. This type of mutation occurs in both influenza A and B viruses. However, antigenic shift can cause a major change and a new subtype, significant changes in the hemagglutinin and neuraminidase. This is caused by an exchange of gene segments between viruses and may result in a pandemic. Antigenic shift only occurs in influenza A viruses.

Only seven years ago in 2009, the H1N1 pandemic was declared by the World Health Organization or WHO. This pandemic was caused by an antigenic shift in the virus antigens of this H1N1 virus.

In April, 2009, the novel type A (H1N1) virus appeared and quickly spread across North America. By May 2009, the virus had spread to many areas of the world, so this was the first influenza pandemic since 1968. Pandemic monovalent influenza vaccine was rapidly produced in the United States and deployed a nationwide vaccination campaign that many of you listening may have participated in. This pandemic’s impact, while relatively modest compared to the 1918 and 1957 pandemics, was still significant. Sixty-one million people in the United States were estimated to become ill or about 20% of the population. Over 270,000 hospitalizations occurred, 80% of which were in persons less than 65 years of age and over 12,000 people are estimated to have died from the pandemic virus. These data are summarized in more detail in the CDC Influenza Pandemic A (H1N1) website.

Transmission of influenza virus is respiratory. Replication occurs in the respiratory epithelium with subsequent destruction of the cells, but viremia or circulation of the virus in the bloodstream has been rarely documented. Influenza viruses are shed in respiratory secretions usually droplets, most contagious within 6 feet of an infected person for 5-10 days after infection.

Clinical features of influenza illness include that the incubation period of influenza is usually 2 days though it may range from 1-4 days. Now 50% of infected persons will develop what are called classic symptoms of influenza disease and this is characterized by the abrupt onset of fever, myalgia, sore throat, nonproductive cough and headache. The fever is usually 101o to102o F and accompanied by extreme fatigue or prostration. The onset of fever is often so abrupt that the exact hour is recalled by the patient. Myalgias mainly affect the back muscles. Cough is believed to be the result of tracheal epithelia destruction. Additional symptoms may include rhinorrhea or runny nose, headache, substernal chest burning and ocular symptoms such as eye pain and sensitivity to light. The illness usually lasts between 3-7 days without complications. The severity of the illness depends on prior experience with related variants of the infecting virus.

Complications of influenza illness include most frequently pneumonia and most commonly secondary bacterial pneumonia usually from either Sstreptococcus pneumonia, Hhemophilus ptysis(?) influenzae of any type, or Sstaphylococcus aureus. Primary influenza viral pneumonia is an uncommon complication but has a high fatality rate. Reye syndrome is a complication that occurs almost exclusively in children taking aspirin primarily in association with influenza B or varicella zoster or chickenpox infection and presents with severe vomiting and confusion which may progress to coma due to swelling of the brain or encephalopathy. Other complications may include myocarditis or inflammation of the heart muscle and worsening of chronic bronchitis and other chronic pulmonary diseases. Death is reported in less than 1 per 1,000 cases and the majority of deaths typically occur among persons 65 years of age and older.

The number of influenza-associated deaths vary substantially by year, virus type, sub type and age group affected. In recent years an average of 23,607 deaths occurred due to influenza each year but with a wide range from 3,349 in 1985 to 48,614 deaths in 2003. Persons 65 years and older typically will account for 90% of deaths. Deaths are 2.7 times more common when type A (H3N2) influenza viruses were prominent.

The highest rates of complications and hospitalizations occur among persons 65 years and older, as I said, but also young children and among persons with certain underlying medical conditions, that is chronic diseases such as heart or lung disease. On average more than 200,000 hospitalizations are attributed to influenza each year. 37% of the hospitalizations are among persons younger than 65 years of age. And again, a greater number of hospitalizations as with deaths occur in years when type A (H3N2) influenza viruses circulate.

School-age children typically have the highest attack rates during community outbreaks and they serve as a major source of transmission of influenza within communities. There are numerous reports of influenza outbreaks beginning in schools and spreading to the schools’ communities and then these outbreaks slow or stop when schools close for the winter holidays and the children disperse.

The reservoirs for influenza disease and viruses are humans and animals only for type A and these can include various mammals such as horses and dogs and many species of birds. Transmission, again, is respiratory through airborne droplets and there’s a temporal pattern with a peak from December to March in temporal climates such as the United States. However, this pattern may shift earlier or later. Now, peak months for influenza activity in the United States since 1982 have been in descending order: February, December, March and January, but we often can see influenza activity begin as early as October and extend into May and sometimes beyond. The disease is communicable where people are infectious 1 day before symptoms begin to 5 days after the onset of symptoms in adults.

Influenza virus infection cannot be diagnosed accurately based on signs and symptoms alone. Laboratory testing is necessary to confirm the diagnosis. Virus isolation is essential for virologic surveillance. Appropriate clinical specimens used for virus isolation include nasal washes, nasopharyngeal aspirates, nasal and throat swabs, tracheal aspirates, and bronchoalveolar lavage. One disadvantage of virus isolation is that it requires several days so it is not very useful for clinical decision making. Paired serum specimens are required for serologic diagnosis of influenza virus infection and are generally a research tool. IgG or immune globulin G serologic testing is generally not useful for clinical diagnosis. One also needs to know the patient’s vaccination history. The acute phase serologic specimen should be collected within one week of the onset of illness and preferably within 2-3 days. The convalescent phase samples, so you need 2 samples for serologic diagnosis, should be collected approximately 2-3 weeks later. A positive result is a 4 fold or greater rise in titer between the acute and convalescent phase samples to 1 type or subtype of virus.

This table is adapted from the CDC Influenza Diagnostics website listed at the bottom of the slide and it lists most commonly used diagnostic tests for influenza beginning with what I already mentioned, traditional viral culture and cell culture. There are a number of other tests listed as well which can give results more quickly than the viral culture underlined at the top of the slide. I will only discuss 2 of the other kinds of tests now which are also underlined and in yellow text. The first of those 2 is real time polymerase preliminary(?) chain reaction or RTPCR and it is the most sensitive method for the detection of influenza virus and is the gold standard for influenza diagnosis. The use of these molecular techniques directly to detect virus and respiratory samples can provide rapid identification of viruses that is within hours if not faster. The second important category at the bottom of the slide are commercially available rapid diagnostic kits which test for the presence of viral antigens or proteins. Although these tests are usually less sensitive than RTPCR testing, they are highly specific. Currently available rapid influenza diagnostic testing fall into 2 groups which detect both influenza type A and B viruses but don’t differentiate between the virus types and those that detect both A and B viruses but can distinguish between the 2. Results from these rapid influenza antigen detection tests can be available in 15 minutes or less. Now, these rapid diagnostic tests for influenza are going to help in the diagnosis and management of patients who present with signs and symptoms compatible with influenza. They also are used for helping determine whether outbreaks of respiratory disease such as in nursing homes and other settings might be due to influenza. There are many brands of these tests which detect influenza antigens or proteins that are widely used in clinical settings and these are discussed in more detain on the CDC influenza website. Now, as I said, rapid influenza diagnostic tests are not terribly sensitive. Although about 50%-70% of influenza infections will be picked up by them, they are highly specific; that is false positives are unlikely. So if the test is positive, you can pretty well believe it. If it’s negative, you may opt to still treat the person as if they have influenza because false negatives do occur particularly when compared with viral culture or RTPCR.