EpiVac Pink Book Netconference
Dr. Jean Smith, presenter, Dr. Raymond Strikas, moderator
MODERATOR: Welcome to the Centers for Disease Control and Prevention EpiVac Pink Book Netconference series. Today we will be talking about DTaP and Tdap vaccines for 2017. I’m Dr. Raymond Strikas, your moderator for today’s program from the Immunization Services Division of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention in Atlanta, Georgia. The learning objectives for today’s program are 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 health care services such as smoking cessation, weight reduction, diabetes screening, blood pressure screening and importantly today, immunization services to prevent health problems and maintain health. Today’s agenda in our EpiVac Pink Book Netconference series, it will cover DTaP and Tdap vaccine, disease and vaccine recommendations for 2017. Our presenter is Dr. Jean Clare Smith, who is a Medical Officer at the National Center for Immunization and Respiratory Diseases at the CDC. Continuing Education information, I want to remind you that CE credit is available at http://www2a.cdc.gov/TCEOnline, as you see it on your screen. Search for the course number of WC2645-080217 for today’s live course. Those last six digits are today’s date. And for the enduring course, if you’re viewing this after today, WD2645-080217, again today’s date are the last six digits. The CE credit for today’s program, the live program expires September 4th of 2017; and for the enduring program, the CE credit expires in about 10 months, on June 1st, of 2018. Instructions for CE are also available in the resource pod on your screen. We no longer need a verification code, it is no longer required. CDC wishes to disclose that 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 the content to ensure there is no bias. The presentations will not include any discussion of the unlabeled use of a product or a product under investigational use with the exception of Dr. Smith’s discussion on DTaP and Tdap vaccines. Dr. Smith will be discussing use of DTaP and Tdap vaccines in a manner recommended by the Advisory Committee on Immunization Practices, but not approved by the Food and Drug Administration. CDC does not accept any commercial support. If you have a question, please type and enter your question into the QA pod on your screen and we will get to as many questions as time permits. Questions that we don’t answer on today’s program we will answer in writing on our webinar screen where this program will be archived. Let me now turn the program over to Dr. Smith for today’s presentation.
DR. SMITH: Good afternoon. I’m Dr. Jean Smith, a Medical Officer here at the CDC and I’ll be talking today about diphtheria, tetanus and pertussis. Diphtheria is a toxin-mediated disease that is transmitted mainly person to person via the respiratory tract and rarely through skin or fomites. It can affect almost any mucous membrane and is classified based on the site of infection. Most commonly it infects the nasal pharynx and causes an exudate and within two to five days, may form an adherent membrane on the pharynx and tonsils that can lead to respiratory obstruction. As they grow, the bacteria produce a toxin that is absorbed into the bloodstream. It is the absorbed toxin that causes most of the complications of diphtheria such as myocarditis or inflammation of the heart and neuritis, which leads to abnormal nerve condition. Diphtheria results in death in 5% to 10% of cases. This picture depicts the tough adherent membrane in the back of the throat that can occlude the airway. It can cause serious bleeding with efforts to remove it. This chart shows the number of diphtheria cases reported annually in the U.S. from 1980 through 2016. The majority of reported cases are among people 25 years and older. There is no current geographic concentration of cases observed in the U.S. However, the greatest risk of infection is during travel outside the U.S. where diphtheria is more prevalent. This slide shows a painting that is maintained at the Wellcome Library in London that shows a ghostly skeleton trying to strangle a child suffering from diphtheria. At first, I had difficulty seeing the skeleton, but if you look at the vapor that’s rising up over the child, you can see the skeletal figure trying to strangle the child. And gravestones from a Victorian era cemetery in England that show a family, a very unfortunate family where eight members of the same family died of diphtheria within a 17 day period. And there’s an article in the New England Journal published in 2012 about the Burden of Disease and Changing Task of Medicine that shows a graphic that shows the ten leading causes of death in the year 1900, diphtheria was number ten out of the one to ten, causing about 40.3 deaths per 100,000 population.
Now tetanus is an acute, often fatal disease caused by a toxin produced by the bacterium Clostridium tetani. The bacteria and its spores are found everywhere in the world that has dirt, animal feces and may persist from months to years. Because the causative agent is found in the environment, we will never be able to eradicate tetanus. One of the toxins, tetanospasmin, blocks the impulses in certain nerves, which leads to unopposed muscle contraction and spasm. It’s one of the most potent toxins known to man. The most common form is generalized tetanus. The disease usually presents with a descending pattern, the first sign is trismus or lockjaw, followed by stiffness of the neck, difficulty swallowing and rigidity of abdominal muscles. The complications of tetanus include spasms of the respiratory muscles, which can lead to respiratory arrest. But, muscle spasms can be so severe they break bones. If the person doesn’t die as a direct result of the tetanus, they may die from the complications that came with a long hospitalization and recovery. And I’d like to mention that one of the most dramatic cases I saw when I was a medical student at UCLA was a case of full blown tetanus. Being near the Mexico border, this man had gone across the border and had gotten a shot of vitamin B12 because he thought it would improve his health. He came into the ER and fortunately, a very sharp infectious disease fellow understood that he was in the very early stages of tetanus. He was taken to the ICU, intubated with muscle relaxants, but had full blown tetanus by just a few hours later. This chart shows the number of reported tetanus cases from 1900 through 2015. You can see that there has been an overall decline in cases since 1900. During 2001 through 2008, the last years for which data has been compiled, a total of 233 tetanus cases were reported; an average of about 29 cases per year. Among the 197 cases with known outcomes, the case fatality rate was 13%. Age of onset was reported for all 233 cases with the median age of 49 years and a range of 5 to 94 years; 49% of cases were among persons 50 years of age and older. And among the reported tetanus cases, 72% reported an acute wound before disease onset, such as a puncture or a contaminated wound; 13% reported a chronic wound before disease onset such as a diabetic ulcer or a dental abscess. The next picture shows a child with generalized tetanus and this shows the classic posturing of opisthotonos where because the back muscles are more powerful than the abdominal muscles, the person’s body is pulled into this crescent formation. The exotoxins are causing his back to curve, giving his body this contorted appearance.
Now we’ll turn to pertussis. Pertussis is a highly contagious respiratory infection caused by the bacterium Bordetella pertussis. Disease onset is insidious with a non-specific cough and minimal fever and an incubation period of five to ten days. There are three stages, the first; the catarrhal stage is characterized by runny nose, sneezing, low grade fever and mild cough, much like the common cold. This is the stage where maximum communicability occurs. During the paroxysmal stage, the diagnosis is usually suspected because of the characteristic burst of rapid coughs because the person is unable to get rid of thick mucus from the trachea and bronchi. This is followed by the characteristic whoop. Patients can turn blue and children can look very ill. The most common complication is secondary bacterial pneumonia, while other complications include seizures. Approximately 16% of patients require hospitalization. Finally, during the convalescence stage, the cough becomes less paroxysmal and gradually disappears. This phase can last weeks to months.
Following the introduction of whole cell pertussis vaccines or DTP, in the late 1940’s, there was a dramatic decline in cases reported through the National Notifiable Diseases Surveillance System, or NNDSS. In the 1990’s, due to concerns about the whole cell vaccine, the United States transitioned from whole cell to acellular pertussis or DTaP. By 1997, in the U.S., all five doses of the primary series were DTaP, although DTP continues to be used extensively in the developing world. Tdap vaccine was introduced in 2005. This graph illustrates the number of pertussis cases reported to CDC from 1922 through 2015. Following the introduction of pertussis vaccines in the 1940’s when case counts frequently exceeded 100,000 cases per year, reports declined dramatically to fewer than 10,000 by 1965. During the 1980’s, pertussis reports began increasing gradually. In 2012 almost 50,000 cases were reported and by 2015, more than 20,000 cases per year were reported nationwide. The increases in reported pertussis cases over the last two decades, and particularly in recent years, are likely the result of a number of factors including improved surveillance capacity, changes in diagnostic testing and reporting, increased public and provider awareness and probably most importantly, waning of protection from acellular pertussis vaccines. This slide is showing you the reported pertussis incidents by age group from 1990 through 2016. You can see that young infants less than age 12 months have the highest incidence and the most severe morbidity and mortality is seen in infants less than two months of age. From 2008 through 2014, a total of 118 deaths from pertussis were reported to the CDC. Of these 118 pertussis related deaths, 95 or 81% occurred in infants younger than three months of age. In 2015, there were over 20,000 cases of pertussis reported in the U.S. Over 50% of the cases in 2015 occurred in persons 11 years and older. Pertussis infection in this age group may be asymptomatic or present as classic pertussis. Disease in adolescents and adults is often milder than the disease in infants and children, but even persons with mild disease may transmit the infection. Older persons and household contacts such as parents, siblings, grandparents and babysitters are often a source of infection for infants and children. Pertussis in adolescents and adults is not without consequence. Illness can have a prolong cough that can persist for three months or longer. Posttussive vomiting may occur after a sever paroxysm of cough. Adolescents and adults may also develop complications of pertussis such as difficulty sleeping, urinary incontinence, pneumonia and even rib fracture. Adolescents and adults often have multiple medical visits and may undergo extensive medical evaluation for the persistent cough before pertussis is considered as the diagnosis and they may miss school or work. In summary, diphtheria, tetanus and pertussis are diseases that can occur throughout the lifetime, therefore, vaccination needs to occur throughout the lifetime to be protected.
Now let’s focus our attention to the vaccines. DTaP or DTaP vaccine, big D, big T, little a, big P is the pediatric formulation. DTaP is approved for children six weeks through six years of age, that is, up to the seventh birthday. DTaP should not be administered to anyone seven years of age or older. DTaP contains the same amount of diphtheria and tetanus toxoid as pediatric DT vaccine. As of April 2012, there are two pediatric DTaP products available in the United States, Daptacel and Infanrix. These vaccines have been studied in either blinded cohort studies or in case control studies. They have an estimated three dose vaccine efficacy of 80 to 85% against typical pertussis disease. Although the vaccines contain different formulations, there is no clear evidence that one is significantly more effective than the others. As a result, neither the ACIP nor the American Academy of Pediatrics has stated a preference for one of these vaccines. In addition, there are four combination vaccines that contain DTaP. First we have Pediarix. In December 2002, the U.S. FDA approved Pediarix, which is a combination vaccine containing DTaP, inactivated polio and hepatitis B vaccines and is produced by GlaxoSmithKline. The DTaP component is Infanrix and the hepatitis B component is Engerix-B, which were previously licensed in the United States. Pediarix is approved for the first three doses of the DTaP and IPV series, which are usually given at about two, four and six months of age. It is not approved for fourth or fifth doses of the DTaP series. The minimum age for the first dose of Pediarix is six weeks and it can’t be used for the birth dose of the hepatitis B series. The vaccine is not approved for use in children seven years of age or older. Pediarix can be given to infants who received a birth dose of hepatitis vaccine and these infants would receive a total of four doses of hepatitis B vaccine. An important fact to remember about Pediarix and any other combination vaccine, for that matter, is that the minimum intervals between doses are dictated by the single antigen with the longest minimum interval. Therefore, Pediarix minimum intervals are determined by the hepatitis B component. As with hepatitis B vaccine, the minimum interval between the first two doses of Pediarix is four weeks. The third dose must be administered at least eight weeks after the second dose and should follow the first dose by at least 16 weeks. Hepatitis B will be covered in a future module.