Epivac Pink Book Netconference

EpiVac Pink Book Netconference

Pneumococcal 2017

JoEllen Wolicki

MODERATOR: Welcome to this week’s session of our Pink Book webinar series. We’re coming to you from Atlanta and the title of today’s session is pneumococcal 2017. My name is JoEllen Wolicki and I am a Nurse Educator in the Immunization Services Division, which is part of CDC’s National Center for Immunization and Respiratory Diseases or NCIRD. And I will be the moderator for today’s session. The learning objectives for this webinar series are one, describe the different forms of immunity; two, describe the different types of vaccines; three, for each vaccine-preventable disease, identify those for whom routine immunization is recommended; four, for each vaccine-preventable disease describe characteristics of the vaccine used to prevent the disease; five, describe an emerging immunization issue; six, locate resources relevant to current immunization practice and finally, implement disease detection and prevention health care services, such as, smoking cessation, weight reduction, diabetes screening, blood pressure screening and immunization services to prevent health problems and maintain health. Our presenter today is Dr. Andrew Kroger. He is a Medical Officer in the Immunization Services Division in NCIRD here at CDC. We will have a question and answer session following his presentation. Continuing Education or CE is available only through the CDC ATSDR Training and Continuing Education online system at the web address at the top of this slide. You can click on the web address and save it to your web browser for future reference. The course number for today’s session is WC2645-100417. CE for this session will be available through November 6th, 2017. You can also see information for the enduring course that will be available on the Pink Book series website. Enduring CE will expire on Jun 1st, 2018. Instructions on how to register and obtain for CE for the webinar are available in the resource pod. An image of a computer screen is on this slide with the resource pod highlighted with a red circle. Please note, a verification code is no longer needed. In compliance with Continuing Education requirements, all presenters must disclose any financial or other associations with the manufacturers of commercial products, suppliers of commercial services or commercial supporters, as well as any use of unlabeled products or products under investigational use. CDC, our planners, content experts and their spouses or partners wish to disclose they have no financial interest or other relationships with the manufacturers of commercial products, suppliers of commercial services or commercial supporters. Planners have reviewed content to ensure there is no bias. Today’s presentation 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. If you have a question during this presentation and it’s related to this presentation, please enter your question into the QA pod, highlighted by the red circle. We will address questions during the question and answer period that will follow the presentation. Now I would like to turn the program over to Dr. Kroger.

DR. ANDREW KROGER: Thank you JoEllen. It’s a pleasure to present to you today from Atlanta. Today I will discuss pneumococcal disease and pneumococcal vaccines. The flow of my presentation will correspond to the chapter entitled Pneumococcal Disease on page 279 of the Pink Book, as well as the pneumococcal section of the Pink Book supplement. Pneumococcal disease is caused by Streptococcus pneumoniae bacteria, which are lancet-shaped, gram-positive, facultative anaerobic organisms. They’re typically observed in pairs, but they may also occur singularly or in short chains. There are 92 known serotypes. Some pneumococci are encapsulated; their surfaces are composed of complex polysaccharides. Now, the polysaccharide capsule is an important virulence factor, which means that encapsulated organisms can be deadly for humans and experimental animals, whereas organisms without capsular polysaccharides are not. Capsular polysaccharides are the primary basis for the pathogenicity of the organism. They are antigenic and they form the basis for classifying pneumococci by serotypes. Type specific antibody to capsular polysaccharide is protective. These antibodies and complement interact to opsonize pneumococci, which facilitates phagocytosis and clearance of the organism of the same serotype. Antibodies to some pneumococcal capsular polysaccharides may cross-react with related serotypes as well as with other bacteria providing protection against these organisms. Most streptococcus pneumoniae serotypes have been shown to cause serious disease, but only a few serotypes produce the majority of pneumococcal infections. The ten most common serotypes are estimated to account for about 62% of invasive disease worldwide. The ranking and serotype prevalence differ by patient age group and geographic area. In the United States, prior to the widespread use of the 7-valent pneumococcal conjugate vaccine, the seven most common serotypes isolated from blood or cerebrospinal fluid or CSF in children younger than six years of age accounted for 80% of infections. These seven serotypes account for only about 50% of isolates from older children and adults. Pneumococcal disease is the second most common cause of vaccine-preventable death in the United States, causing over 5,000 preventable deaths every year. Pneumococcal pneumonia is the most common clinical presentation of pneumococcal disease among adults, although pneumonia alone is not considered to be invasive disease. The incubation period of pneumococcal pneumonia is short, about one to three days. Symptoms generally include an abrupt onset of fever and chills or rigors. Typically there’s a single rigor and repeated shaking chills are uncommon. Other common symptoms of pneumonia include pleuritic chest pain, cough productive of a mucopurulent, rusty sputum, dyspnea, which is shortness of breath, tachypnea, which is rapid breathing, hypoxia, poor oxygenation, tachycardia, which is a rapid heart rate, malaise and weakness. Nausea and vomiting and headaches occur less frequently. Now the other clinic syndromes include the two most common forms of invasive disease, bacteremia and meningitis. Bacteremia is a bloodstream infection and meningitis is infection of the meninges, the lining covering the brain. The clinical symptoms, CSF profile and neurologic complications of pneumococcal meningitis are similar to other forms of purulent bacterial meningitis. Symptoms may include headache, lethargy, vomiting, irritability, fever, neck rigidity, cranial nerve signs, seizures and coma. This slide should have a graph of invasive pneumococcal disease, which shows the rate of pneumococcal disease, invasive disease, per 100,000 population by age group and demonstrates that the highest rates of invasive disease occur in those younger than two years of age and those 65 years of age or older. These data are generated by the Active Bacterial Core Surveillance System or ABCs data and highlight age as an important risk factor for invasive disease. There are also medical risk factors for invasive disease; these include functional or anatomic asplenia. Functional asplenia includes sickle cell disease because children with sickle cell disease slowly destroy their own spleen. Altered immunocompetence is a risk factor for invasive disease, also other underlying medical conditions like chronic renal disease, nephrotic syndrome and conditions that predispose to cerebral spinal fluid or CSF leak. Other underlying medical conditions are risk factors for invasive disease, but the risk is lower. These include chronic heart disease, chronic lung disease, diabetes, alcoholism, chronic liver disease and solid organ transplant. There are behavioral risk factors that predispose to invasive disease primarily due to the effect on the immune system. This has been observed in cigarette smokers 19 years of age and older. Also patients with cochlear implants have an increased risk of pneumococcal meningitis. Other non-medical risk factors for invasive pneumococcal disease include childcare attendance, American Indian, Alaskan Native race and African American race. The reservoir for pneumococcal disease are human carriers. Pneumococci are common inhabitants of the respiratory tract and may be isolated from the nasopharynx of 5% to 90% of healthy adults. Rates of asymptomatic carriage vary with age, environment and the presence of upper respiratory infections. Only 5 to 10% of adults without children are carriers. On military installations, as many as 50% to 60% of service personnel may be carriers. The duration of carriage varies and is generally longer in children than adults. In addition, the relationship of carriage to the development of natural immunity is poorly understood. Transmission of strep pneumoniae occurs as a result of direct person-to-person contact via respiratory droplets and by autoinoculation in persons carrying the bacteria in their upper respiratory tract. Pneumococcal infections are more common during the winter and in early spring when respiratory diseases are more prevalent. The period of communicability for pneumococcal disease is unknown, but presumably transmission can occur as long as the organism appears in respiratory secretions.

I’m now going to talk about pneumococcal vaccines; these vaccines are composed of pneumococcal polysaccharide. The first vaccines licensed were considered pure polysaccharide vaccines. The first contained polysaccharide from 14 different types of pneumococcus and was licensed in 1977. In 1983, a 23-valent polysaccharide vaccine was licensed and replaced the 14-valent form. In 2000, the first pneumococcal conjugate vaccine was licensed, consisting of polysaccharide from 7 types of pneumococcus conjugated to a protein. In 2010, an expanded 13-valent conjugate vaccine replaced the 7 serotype conjugate vaccine. The pneumococcal polysaccharide vaccine or PPSV23 contains polysaccharide antigen from 23 types. These types cause 60 to 76% of invasive disease generally. However, this vaccine is not effective in children younger than two years of age because it does not generate lasting immune memory. It also has not been demonstrated to provide protection against pneumococcal pneumonia. For this reason, providers should avoid referring to PPSV23 as pneumonia vaccine. The pneumococcal conjugate vaccine or PCV13 contains 13 serotypes, seven of which were also in PCV7, 4, 6b, 9v, 14, 18c, 19f, and 23f as well as six additional serotypes, 1, 3, 5, 6a, 7f, and 19a conjugated to a nontoxic diphtheria cross-reactive material 197 carrier protein. This vaccine contains one serotype, type 6a, that is not in PPSV23. More importantly, because this is a conjugate vaccine, it generates a long-lasting immune response that is useful in children as well as adults. Now it was approved by FDA based on demonstration of immunologic noninferiority to PCV7 rather than clinical efficacy. PCV7 was introduced into the routine schedule in the year 2000 and has been tremendously successful in reducing the rate of invasive pneumococcal disease or IPD. Between 1998 and 2009, PCV7 reduced rates of PCV7 type invasive disease along with serotype 6a by 99% and reduced rates of invasive disease caused by all serotypes by 76%. In 2008, 61% of invasive pneumococcal disease cases among children younger than five years of age were attributable to the serotypes in PCV13, but those types contained in PCV7 only accounted for 2% of cases. The remainder were accounted for by the additional six serotypes and serotype 19a accounted for 43% of cases. In 2013, 20 to 25% of invasive pneumococcal disease cases among adults 65 years old and older were attributable to PCV13 serotypes. PCV13 serotypes accounted for 10% of community-acquired pneumonia cases in adults and this includes pneumonias with no bacteremia. You may wonder how it is possible to identify the specific serotype of streptococcus pneumoniae in patients that have only pneumonia diagnosed with x-ray or clinically with no organism obtained from the blood. Well, the way this was done, the manufacturer of PCV13, Pfizer, was able to determine type specific non-bacteremic pneumonia cases with the use of a urinary antigen test based on an immunochromatographic membrane technique.

So having discussed burden of disease, I’ll now move on to discuss immunogenicity and effectiveness beginning with PSV23 vaccine. While 80% of healthy adults who received PPSV23 vaccine develop antibodies against the serotypes contained in the vaccine, most estimates of effectiveness range between 60 to 70% against invasive disease among immunocompetent older persons and adults with underlying illnesses. Effectiveness among immunocompromised or very older persons is not demonstrated. The confidence intervals become very wide in most studies looking at adults 40 years old or older and some effectiveness estimates are as low as 10%. As mentioned, the vaccine is not thought to prevent pneumococcal pneumonia. Pneumococcal conjugate vaccine is highly immunogenic in infants and young children, including those with high-risk medical conditions. The efficacy of PCV7 was 97% for prevention of invasive disease caused by vaccine serotypes. Furthermore, children who received PCV7 had 7% fewer episodes of acute otitis media and underwent 20% fewer tympanostomy tube placements than did unvaccinated children. PCV13 was licensed in the United States based upon studies that compared the serologic response of children who received PCV13 to those who received PCV7. These studies showed that PCV13 induced levels of antibodies that were comparable to those induced by PCV7 and shown to be protective against invasive disease. In another study of PCV13, children 7 through 11 months, 12 through 23 months, and 24 through 71 months of age who had not received pneumococcal conjugate vaccine doses previously were administered one, two or three doses of PCV 13 according to age appropriate immunization schedules that existed for PCV7. This is essentially bridging to reduce dose complete series of PCV7. The schedules resulted in antibody responses to each of the 13 serotypes that were comparable to those achieved after the three-dose infant PCV13 series. In the U.S. Immunogenicity Trial, except for serotype 1, for which IgG antibody levels were lower among children aged 24 to 71 months. Now looking at efficacy in adults for PCV13, a randomized placebo controlled trial, the CAPiTA trial, was conducted in the Netherlands among approximately 85,000 adults 65 years old or older during 2008 through 2013 to evaluate the clinical benefit of PCV13 and the prevention of pneumococcal pneumonia. PCV13 demonstrated 75% efficacy against vaccine type invasive pneumococcal disease and 45% efficacy against PCV13 serotype nonbacteremic pneumonia.

I will now discuss recommendations for the use of these two pneumococcal vaccines. The PCV13 recommendations, as well as the PPSV23 recommendations, for infants and children were published in the MMWR on December 10th, 2010. I will begin with talking about PCV13 vaccine. A note on the complexity of recommendations for PCV13, PCV13 is approved by the Food and Drug Administration for children 6 weeks through 17 years of age and for adults 50 years of age and older.