Wesley Tang, DO, MPH, Internal Medicine Resident, Kettering Medical Center and Sycamore Hospital, Dayton, OH
Jeffrey W. Weinstein, MD, FIDSA, CPE, Kettering Health Network Patient Safety Officer, Dayton, OH
Dean L. Winslow, MD, Professor of Medicine, Division of General Medical Disciplines, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA
Vaccination in adults remains one of the most important means of preventing disease in vulnerable populations. Despite this fact, the rates of vaccine coverage for adults still are significantly lower than with routine childhood vaccination.
- The Advisory Commission on Immunization Practices (ACIP) is composed of medical and public health experts who are tasked with developing vaccine recommendations for use in the United States. The ACIP operates under the auspices of the Centers for Disease Control and Prevention and publishes the recommendations in Morbidity and Mortality Weekly Report.
- The effectiveness of many vaccines depends on the ability to vaccinate a large percentage of the population. Primary care providers can help reach these thresholds by following the ACIP recommendations.
- Most vaccines work by stimulating the humoral immune system to produce antibody to the pathogen. Then, a future challenge elicits a protective immune response. For many vaccines, the immunogenicity can be measured by determining the serologic response after vaccination. Large-scale efficacy of the vaccine in a population is measured by determining the rates of protection.
- Certain vaccines, such as influenza, tetanus/diphtheria/pertussis, and the new COVID-19 vaccine are recommended for all adults, while others are recommended in subsets of adults depending on age, comorbidities, and certain risk factors.
- Special considerations apply for immunosuppressed patients, since live vaccines may be contraindicated and such patients are at high risk for infectious diseases.
- Pregnant women also are relatively immunosuppressed and, therefore, should not receive live virus vaccines. All pregnant women should receive the tetanus/diphtheria/acellular pertussis vaccine during each pregnancy. Currently the ACIP recommends a shared decision-making approach to COVID-19 vaccination for pregnant women.
It started with a hypothesis. In the late 1700s, Edward Jenner had heard that milkmaids who frequently were exposed to cowpox seemed to be immune to smallpox (variola) infection. Although others had noted this, Jenner proved that immunity could be developed by injecting cowpox into subjects whom he later challenged with smallpox.1 The Latin word for cow is vacca — thus the medical term for vaccines.
Vaccines are among the most important scientific advances in human history, and Jenner’s work is credited with saving millions of lives. Over recent decades, new advances in vaccination continue to alter the epidemiology of common infectious diseases in ways previously unimaginable. For instance, childhood meningitis caused by Haemophilus influenzae type B essentially has been eradicated in the United States since universal childhood vaccination against this pathogen began in 1991.2 Likewise, chickenpox has been reduced 90% with the widespread uptake of varicella vaccination.3
Since adults and children live together in communities, the beneficial effects of childhood vaccines have extended to elders in significant ways. The death rates among both children and adults declined after the introduction of the varicella vaccine.4 Similarly, the rate of invasive pneumococcal disease in adults caused by the serotypes in the newer pneumococcal conjugate vaccine decreased after the vaccine was given to children. In part, these findings are explained by the concept of herd immunity. When a large enough proportion of a population is immune to a pathogen, even those in the community who have not been vaccinated are afforded some protection.
Vaccinations to directly prevent disease in adults likewise have reduced morbidity and mortality from a wide variety of viral and bacterial infections. This article will review the vaccines recommended for all adults as well as those vaccines recommended for special populations, such as immunosuppressed patients and pregnant women. In addition, the article will examine strategies that can be employed to increase vaccination rates in adults. These strategies have assumed a larger role in the era of value-based purchasing and pay for performance reimbursement methods, such as the Medicare Access and the Children’s Health Insurance Program (CHIP) Reauthorization Act.
Vaccinations Recommended for Healthy Adults
The vaccines recommended in healthy adults are listed in Table 1. This table, along with the detailed footnotes, can be found at www.cdc.gov/vaccines/schedules/downloads/adult/adult-combined-schedule.pdf.
Coronavirus Disease 2019 (COVID-19) Vaccines
Coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus, first identified in Wuhan, China, in December 2019. Like other beta coronaviruses, such as Middle Eastern respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus (SARS-CoV), these viruses originate from an animal reservoir. The main animal reservoir for SARS-CoV-2 likely is in bats; however, the exact intermediate host not been identified (the pangolin is a prime suspect). Reported manifestations range from asymptomatic infection to severe illness and death. The most common symptoms include fevers/chills, cough, shortness of breath, fatigue, headache, new loss of taste or smell, sore throat, nausea or vomiting, and diarrhea.5 Death rates from COVID-19 are variable but average about 1.7% in the United States, with half of all deaths occurring in those older than 80 years of age. The COVID-19 pandemic has been fueled in large part by the fact that asymptomatic persons are able to transmit the virus to contacts.
At the time of this writing, there currently are three vaccines available and given emergency use authorizations by the Food and Drug Administration (FDA) in the United States: one manufactured by Pfizer-BioNTech named BNT162b2 (authorized Dec. 11, 2020), one manufactured by Moderna named mRNA-1273 (authorized Dec. 18, 2020), and one manufactured by Johnson & Johnson’s Janssen named JNJ-78436735 (authorized Feb. 27, 2021).6 (See Table 2.)
The Pfizer-BioNTech COVID-19 vaccine is indicated in individuals 16 years of age and older and must be administered as a two-dose series separated by 21 days. A two-dose regimen of BNT162b2 was noted to confer 95% protection against COVID-19 in persons 16 years of age or older with safety over a median of two months, similar to that of other viral vaccines.7
The Moderna vaccine is indicated in individuals age 18 years of age and older and must be administered in a two-dose series separated by 28 days. A two-dose mRNA-1273 vaccine showed 94.1% efficacy at preventing COVID-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified.8 Currently, the series of COVID-19 vaccine is recommended to be completed with the same manufacturer and product.
The Advisory Committee on Immunization Practices (ACIP) convened on Dec. 1, 2020, and recommended that both healthcare personnel and residents of long-term care facilities be offered vaccination in the initial phase of the COVID-19 vaccination program.9
Unlike the vaccines manufactured by Pfizer-BioNTech and Moderna, the vaccine manufactured by Johnson & Johnson is a single-dose vaccine.10 In a Phase III trial, Johnson & Johnson’s vaccine candidate was found to be 85% effective overall in preventing moderate to severe COVID-19 by 28 days after vaccination.11 Unlike the Pfizer-BioNTech and Moderna vaccines, which leverage messenger ribonucleic acid (mRNA) technology, Johnson & Johnson’s vaccine makes use of a modified adenovirus as a vector to express the antigen’s genetic code.12 The two authorized mRNA vaccines by Pfizer-BioNTech and Moderna are the first-of-a-kind vaccines that have strands of mRNA inside a special coating, enabling genetic material to directly enter dendritic cells and macrophages near the site of vaccination. Once inside the cell, the mRNA provides the blueprint for host cells to manufacture a “spike protein” unique to SARS-CoV-2.13 It should be noted that only part of a protein is created, allowing it to be antigenic for the immune system without causing infection or direct harm. These proteins then are taken up by immune cells and displayed upon cell surfaces to trigger the immune system to produce antibodies.
Currently, the rollout of vaccines is composed of the following phases: Phase 1a includes healthcare workers and long-term care facility residents. Phase 1b includes individuals age 75 years and older in addition to frontline essential workers, such as teachers, child care staff, firefighters, police officers, postal service workers, and public transit workers. Phase 1c includes individuals age 65-74 years, those ages 16-64 years with increased risk for severe illness, and essential workers. Phase 2 will include the remaining population.14 At the time of this writing, approximately 72 million Americans have been fully vaccinated, or 21% of the country’s population. The most commonly reported side effects, which can last several days, are pain at the injection site, headache, chills, joint pain, and fever. There appear to be higher rates of side effects after the second dose compared to the first dose.15 The need and timing for booster doses for any of the COVID-19 vaccines have not yet been established.
As far as contraindications, the Centers for Disease Control and Prevention (CDC) recommends that anyone with a severe allergic reaction after a previous dose of either mRNA COVID-19 vaccine should not receive another dose.15 This also extends to individuals with immediate allergic reactions to components of these vaccines, such as polyethylene glycol or polysorbate. Although no trials in pregnant or breastfeeding women have been completed, there currently is no contraindication to receipt of either vaccine. It is recommended that pregnant or breastfeeding women should discuss their options with their healthcare providers.
ACIP will consider vaccine-specific recommendations and additional populations for vaccine allocation beyond Phase 1a and 1b when an FDA-authorized vaccine is available. As of April 2021, large-scale Phase III clinical trials are in progress in the United States from manufacturers Oxford-AstraZeneca and Novavax.
Influenza A and B cause annual epidemics worldwide, with severity determined by the degree of change in the hemagglutinin and, to a lesser degree, the neuraminidase antigens on the viral surface. Since 1968, the predominant strains have been H3N2, but a pandemic occurred in 2009, with an antigenic shift to the H1N1 (swine flu) strain.16 During interpandemic years, there is antigenic drift such that the prior year’s vaccine is unlikely to remain effective. Thus, influenza vaccination is recommended annually for all adults in the United States who lack a contraindication. The currently available vaccines include trivalent and quadrivalent intramuscular and intradermal preparations, as well as a high-dose form and a newer recombinant form that has no ovalbumin and, therefore, is safe for use in patients with severe egg allergies.17 ACIP does not state a preference of which vaccine should be given, although some experts favor high-dose influenza vaccination for those ≥ 65 years of age,18 since the efficacy may be better in this group. A live attenuated influenza vaccine that has been approved for use in those age 2-49 years no longer is recommended, since preliminary data show only 3% protective efficacy vs. 63% efficacy of the standard inactivated vaccines in children ages 2-17 years.19 In adults, the efficacy of influenza vaccination depends on the status of the host as well as how well-matched the vaccine is with circulating strains. A recent meta-analysis determined the vaccine efficacy to be 60% in healthy adults,20 whereas studies in human immunodeficiency virus (HIV)-infected patients suggest efficacy to prevent laboratory-confirmed influenza may be as high as 71% to 85%.21 The currently marketed influenza vaccines are extremely safe, with the most common side effect being pain at the injection site. Prior anaphylaxis to an influenza vaccine (which is a rare event) is the only absolute contraindication. As noted earlier, those with severe egg allergy can receive the recombinant influenza vaccine. The swine flu vaccine given in 1976 led to an increase in cases of Guillain-Barré syndrome (GBS), but a recent study suggests the current vaccine leads to very small increased rates of GBS that are lower than the rate of GBS seen after naturally occurring influenza infection.22
Tetanus, Diphtheria, and Pertussis
For several decades, the recommendation for diphtheria/tetanus (Td) vaccination in adults simply was for booster shots every 10 years. Although rare in the United States, tetanus is most common in older adults whose immunity has waned as a result of lack of receipt of the Td booster. Although diphtheria also remains rare in the United States, epidemics have occurred overseas in recent years. Vaccine refusal is one of the factors leading to a resurgence of pertussis in children and adults.23 This resurgence has led to a revision of the recommendations, since the Td booster does not protect against pertussis.
The ACIP now recommends one tetanus/diphtheria/acellular pertussis (Tdap) booster for all adults in the United States, followed by Td boosters every 10 years. (See Table 3, available at https://bit.ly/3xaIPAE.) Special consideration regarding Td boosters applies for tetanus-prone wounds. All patients who have received fewer than three doses of tetanus-containing vaccine should receive a booster. Those in this category with major tetanus-prone wounds also should receive tetanus immune globulin administered at a different site. Fully vaccinated patients with minor wounds only require a booster if the most recent tetanus-containing vaccine was given more than 10 years previously, while those with major wounds should receive a booster if their last dose was given more than five years previously. Neither of these groups requires tetanus immune globulin.24
As per the general ACIP recommendations, if adult patients with wounds in need of a booster have not had the Tdap, then this preparation should be given. Pain at the injection site is the most common side effect of Tdap vaccine in adults. Low-grade fever is relatively common, while a higher grade fever of > 102°F is more common among children. The acellular pertussis vaccine has fewer side effects than the older whole-cell pertussis vaccines. The use of Tdap vaccines in pregnant women is discussed later in this article.
Varicella and Zoster Vaccines
Varicella-zoster virus (VZV) is a herpesvirus that causes chickenpox in nonimmune individuals and shingles when it reactivates later in life. Primary chickenpox in children can be a mild disease, but it also can be associated with severe disease and even death in children, primarily from streptococcal toxic shock syndrome as a superinfection. Routine varicella vaccination not only can reduce morbidity and mortality in children,25 but by reducing the burden of disease in the community, there is lower likelihood of exposure in pregnant women and immunocompromised adults. This is an excellent example of the concept of herd immunity. These groups of adults not only have a higher risk for severe chickenpox but also have a contraindication to vaccination themselves. The ACIP does recommend varicella vaccination to all nonimmune adults who do not have such a contraindication. The main side effects of varicella vaccination are pain at the injection site and the development of a small number of nearby vesicles. A more diffuse rash can occur, and those affected should avoid close contact with nonimmune or immunocompromised individuals.26
The zoster vaccine was developed for use in adults to help prevent shingles, which is a reactivation of previously acquired VZV infection. As adults age or become immunocompromised, the risk of shingles increases. Shingles can present as dermatomal disease or disseminated disease. The latter can cause life-threatening manifestations, including pneumonia, ophthalmic infection, and central nervous system (CNS) involvement, in immunocompromised patients. In addition, postherpetic neuralgia with chronic pain is a complication more common in older adults. As of 2021, the ACIP recommends a two-dose series of recombinant zoster vaccine (brand name Shingrix) two to six months apart for adults older than 50 years of age regardless of previous herpes zoster or previous Zostavax vaccination.27 This vaccine provides longer-lasting immunity than the older live zoster vaccine (Zostavax), which no longer is available in the United States as of Nov. 18, 2020.27 The two-dose zoster vaccine has been shown to be 97% effective in preventing shingles and 91% effective in preventing postherpetic neuralgia in adults ages 50-69 years. Contraindications to Shingrix include a history of severe allergic reactions. The vaccine should not be given during an acute episode of herpes zoster, since the vaccine is not a treatment for herpes zoster or postherpetic neuralgia.28
Measles, Mumps, and Rubella
Measles and mumps are viral infections that had been nearly eliminated in the United States by the early 1980s because of successful vaccination strategies in children. Now, both diseases occur in epidemics related to underimmunization in certain religious groups and the children of those philosophically opposed to vaccination.29,30 The latter group has remained steadfastly against childhood vaccination for fear of a link to autism, despite multiple Institute of Medicine reports and other studies that have failed to find any causal links between either the measles, mumps, and rubella (MMR) vaccine or vaccine ingredients, such as thimerosal, and autism spectrum disorder.31 In fact, the original research purporting this link has been proven to be fraudulent.32
Measles, mumps, and rubella all can have serious health consequences in adults as well as children. In addition to the classic presentation with coryza, fever, and rash, measles can cause pneumonia, encephalitis, and subacute sclerosing panencephalitis. Mumps causes the classic parotitis and orchitis, but also can be associated with CNS disease. Although often mild in adults, rubella is feared, as it causes a variety of serious birth defects in infants born to mothers infected during pregnancy. The efficacy of the MMR vaccine approaches 95% to 100%.33 Because infection with measles and mumps was nearly universal before 1957, those born before that year generally are considered immune. Per the ACIP, all adults born in or after 1957 should have at least one dose of the MMR unless there is a contraindication, such as immunosuppression. A second dose four weeks later is recommended for college students, healthcare workers, and international travelers. Serologic testing should be performed on women of childbearing age, and those not immune to rubella should be vaccinated if not pregnant; vaccination is contraindicated during pregnancy. The most common side effects of MMR vaccination in adults include fever, rash, lymphadenopathy, and joint pain.
Human Papillomavirus Vaccines
Human papillomavirus (HPV) is the major cause of genital warts and urogenital cancers. Because types 16 and 18 are the major etiologic agents of cervical cancer, vaccines initially were developed and approved for use in girls and women. Now the vaccines are recommended for both sexes for several reasons. Obviously, reduction of infections in males likewise reduces infection in their sexual partners. Also, HPV is a cause of penile, anal, and oral cancers as well as respiratory papillomatosis.
Vaccination to prevent HPV infection is most effective if given before the period of risk — before the onset of sexual activity. For boys and girls, the vaccine series should be given at ages 11-12 years. However, since there are many different serotypes, catch-up vaccination is recommended for men and women up until age 26 years. Shared decision-making can be used to determine whether those up to age 45 years might benefit. (See Table 1.)
Much of the efficacy data on HPV vaccination comes from Australia, which was the first country to establish a national government-funded vaccine campaign. Rates of infection with the four vaccine serotypes (6, 11, 16, and 18) fell among women from 28.7% to 6.7% from the pre-vaccine period to the post-vaccine period.34 In the United States, the prevalence of infection in females with these serotypes has been reduced by 64% in the 14- to 19-year-old age group and by 34% in the 20- to 24-year-old age group.35 In males, the efficacy for preventing genital warts among the four vaccine serotypes was 65% in a large international trial.36
The HPV vaccines are very safe, with the main adverse effect being pain at the injection site. There have been reports of syncopal episodes after receipt of the vaccine, and the ACIP now recommends a 15-minute waiting period in a sitting or supine position following vaccination.37
Streptococcus pneumoniae is a virulent bacterial pathogen that causes pneumonia, bacteremia, and bacterial meningitis in adults and children. Initial pneumococcal vaccines were directed at capsular polysaccharides of the many serotypes of the bacteria. The polysaccharide vaccines are poorly immunogenic in younger children and the immunosuppressed and, therefore, pneumococcal conjugate vaccines have been developed. These vaccines include protein antigens to help induce type-specific antibody production. At present, the two major vaccines available in the United States are the pneumococcal polysaccharide 23 valent (PPSV23) and the pneumococcal conjugate 13 valent (PCV13) preparations. The serotypes covered include those most commonly associated with invasive pneumococcal disease in humans. Dosing and sequencing of these vaccines vary depending on the age of the patient and indication for vaccination. In general, the PPSV23 is recommended for adults age 65 years and older. Based on a recent change, the PCV13 is no longer routinely administered, but may be given based on shared clinical decision-making. PCV13 should be given to adults older than 19 years of age if they are immunocompromised, have a cerebrospinal fluid leak, or have a cochlear implant. The efficacy of the PPSV23 vaccine in older adults has been established in a number of trials and confirmed in a recent meta-analysis.38 The vaccine efficacy to prevent invasive pneumococcal disease was between 45% and 73% and it was between 48% and 64% to prevent pneumococcal pneumonia. A very large trial of the PCV13 vaccine in 85,000 adults 65 years of age and older found vaccine efficacy to be 45% at reducing vaccine-type pneumococcal pneumonia and 75% at preventing invasive pneumococcal disease.39
Adverse effects of the pneumococcal vaccine include pain, swelling, and/or erythema at the injection site. The only known contraindication to vaccination is a history of anaphylaxis to a previous pneumococcal vaccine.
Vaccinations for Special Adult Populations
Hepatitis B Vaccine
The hepatitis B vaccine is highly effective at preventing infection, as can be evidenced by the epidemiology of hepatitis B infection in healthcare workers, all of whom are vaccinated. Hepatitis B is much more transmissible than hepatitis C or HIV, but there has been an approximate 30-fold reduction in hepatitis B infections among healthcare workers since universal vaccination began.40 However, rates of vaccination in other adults are low, and those who were not vaccinated in childhood remain at risk via sexual exposure or the sharing of needles used for intravenous (IV) drug injection.41 Although a large proportion of patients with acute hepatitis B clear the infection spontaneously, those who develop chronic infection are at risk of progressing to cirrhosis or developing hepatocellular carcinoma. Given the safety of this vaccine, the high burden of disease, and the ease of transmission, the hepatitis B vaccine now is a routine childhood vaccine. Adults who should be vaccinated are described in Table 4 as well as in Tables 1 and 3.
The hepatitis B vaccine is given as a series of three injections over six months, alone or in combination with the hepatitis A vaccine. Response rates are high, although not universal, and titers should be drawn after vaccination of healthcare workers or others with ongoing risk, such as IV drug users or hemodialysis patients. In general, nonresponders require an additional three-dose series. Severe adverse reactions to hepatitis B vaccination are rare.42
Hepatitis A Vaccine
Hepatitis A virus does not cause chronic disease, but acute infection produces a miserable illness characterized by nausea, malaise, and, occasionally, severe liver dysfunction. Although less common in the United States than in developing countries, the virus is transmitted via the fecal oral route, so everyone is at risk. Most infections are transmitted by food handlers, so common source outbreaks occur. The vaccine is recommended as per Table 3 for patients with chronic liver disease, including hepatitis B or C infections; men who have sex with men; IV drug users; and travelers. For the latter group, the first injection provides protection for a trip, but a second shot six months after the first completes the series and provides prolonged protection.43 If more than six months has elapsed between doses, the series does not need to be restarted; the second shot is sufficient. Soreness at the injection site is the most common side effect of this vaccine. Severe reactions are extremely uncommon.
Neisseria meningitidis is a feared pathogen that can cause meningitis or severe sepsis with purpura fulminans. People with deficiencies in the terminal components of complement are at significantly elevated risk, but healthy adolescents and adults can be affected. The disease can be sporadic or can occur in outbreaks among those living in close quarters, such as a college dorm. For several decades, the available meningococcal vaccines covered only three of the main four strains: A, C, Y, and W. A vaccine for type B strains available in Europe was imported into the United States in 2013 to help contain meningococcal outbreaks at two major U.S. universities.44 Two meningococcal B vaccines are now FDA-approved in the United States, along with three quadrivalent vaccines for strains A, C, Y, and W. Current recommendations from the ACIP include the use of both meningococcal vaccines in adolescents and young adults, and most colleges require these for either all incoming students or those residing on campus. The routine childhood vaccine schedule calls for the initial quadrivalent meningococcal vaccine at 11-12 years of age and a booster at age 16 years, because efficacy seems to wane prior to the age of high school graduation.45
The meningococcal vaccines all are extremely safe, with minor reactions reported. There had been early concerns about a causal relationship between the Menactra quadrivalent meningococcal vaccine and GBS, but large-scale studies have revealed no significant increased risk.46
Haemophilus influenzae Type B Vaccine
The H. influenzae type B vaccine (Hib) is not indicated routinely for healthy adults. As noted previously, the vaccine has had a tremendous effect on childhood meningitis, but H. influenzae is not a common cause of bacterial meningitis in adults. The vaccine is recommended in limited situations for adults: asplenic patients (including those with sickle cell disease, since they are functionally asplenic) and adults status-post-hematopoietic stem cell transplantation. In patients undergoing splenectomy, the vaccine should be administered 14 days before surgery; if the surgery is for traumatic rupture, the vaccine should be given 14 days postoperatively.47 A full three-shot series is not required except following stem cell transplantation.
Vaccinations for Immunosuppressed Patients
Vaccines recommended for immunosuppressed patients are listed in Table 3. However, it always is critical to remember that not all immunosuppressed patients are alike. Asplenic patients are at unique risk for life-threatening infections with encapsulated organisms and, thus, require meningococcal and Hib vaccines in addition to pneumococcal vaccines. As a rule of thumb, live vaccines, such as MMR, zoster, and yellow fever, should be avoided in immunosuppressed patients. However, certain live attenuated vaccines are safe and recommended for HIV-infected patients with CD4 counts > 200 since their immune system is strong enough. Live vaccines also may be acceptable in patients status-post-hematopoietic stem cell transplant after two years, but never in solid organ transplant patients.48 The Hib vaccine also is recommended after hematopoietic stem cell transplant.49 All immunosuppressed adults should receive an annual influenza vaccination as well as pneumococcal vaccination, regardless of age. This includes cancer patients actively undergoing chemotherapy treatments.50 They also should receive the Tdap vaccine once, then the Td booster every 10 years.51
Vaccinations for Patients with Chronic Diseases
The recommended vaccines for patients with chronic diseases, such as cardiopulmonary, renal, or liver disease or alcoholism, also are listed in Table 3. In general, everyone should receive an annual influenza vaccination as well as pneumococcal vaccination as per the proper schedule. The recommendation for Tdap once, followed by the Td booster every 10 years, still applies. Based on the tables, the MMR vaccine should be given to those without proof of immunity. A zoster vaccine is safe to administer at age 50 years unless the patient is immunocompromised. The most significant difference among these groups is that patients with end-stage renal disease,52 chronic liver disease, and diabetes all should be vaccinated against hepatitis B if not already immune, whereas this is not universally needed for those patients with chronic cardiopulmonary diseases and alcoholism. Non-immune patients with chronic liver disease also should receive the hepatitis A vaccine series.
Vaccinations for Pregnant Women
Pregnancy is a relatively immunocompromising state and, as such, live vaccines, such as MMR and varicella, are contraindicated. Despite this recommendation, fetal infection in women who inadvertently were given a dose of MMR has never been documented.53 Influenza vaccine should be given to all pregnant women lacking a contraindication during the season when the vaccine is available. In addition, protection against diphtheria, pertussis, and tetanus is essential in pregnant women. Although diphtheria has re-emerged mainly outside of the United States, pertussis (whooping cough) has had a significant resurgence here this decade, affecting both young children and adults.54 Guidelines now recommend that all pregnant women be vaccinated against these pathogens. Those women who have not completed the vaccine series previously should have a full three-shot series, including one dose of the Tdap. All previously vaccinated pregnant women should have a Tdap booster with each pregnancy, even when there is a short time interval between pregnancies, since young infants need maternal antibody for protection during the first six months of life.55
Vaccinations for Healthcare Workers
Well-established guidelines have been published for the vaccinations recommended (and often required) for healthcare personnel.56 All healthcare workers should be vaccinated against hepatitis B, since this is the most transmissible virus in healthcare settings. Annual influenza vaccination also is critical for healthcare workers.
At this point in time, vaccination against SARS-CoV-2 also is strongly recommended to contain the current COVID-19 pandemic. It remains to be seen when and if booster vaccinations may be necessary.
Measles can be transmitted via an airborne route, and outbreaks have occurred in hospital settings in the United States. Since immunity from childhood vaccines often wanes, the MMR is recommended for nonimmune healthcare workers.53
All healthcare personnel also should be updated with the Tdap if they have not had this formulation previously. Immunity against varicella is important for healthcare workers, since this is an airborne virus and also because severe disease can ensue in adults.
Vaccinations for Travelers
International travelers may be at risk for a variety of infectious diseases, some of which are not present in the United States. Vaccination of travelers is beyond the scope of this review. Information for healthcare providers regarding travel medicine can be found at wwwnc.cdc.gov/travel/destinations/list/.
Increasing Adult Vaccination Coverage
It is well-documented that rates of adult vaccination in the United States are lower than desired. For example, 2017-2018 CDC data show that only 49.2% of adults older than 6 months of age received the influenza vaccine.57 This compares to goal rates of 70% vaccination under the Healthy People 2030 program.57 This problem is not new, and a variety of methods have been studied to increase vaccine coverage rates in adults in both outpatient and inpatient settings.
Recent data show that a program using the 4 Pillars Practice Transformation Program may reduce missed opportunities for vaccination in outpatient primary care practices.58 The strategies used included creating easy access to vaccine services; improving communication with patients about vaccination; enhancing office systems, including the use of electronic medical record alerts; and designating an office immunization champion. Other studies have looked at interventions as varied as sending patients leaflets/postcards, entering patients in a lottery to win free groceries, and even paying physicians.59
In the inpatient arena, the missed chances for vaccination also are well described. Prior to the push to take advantage of hospital stays as a chance to vaccinate, the rate of pneumococcal vaccination of inpatients was found to be only 0.4%.60
These concerns have been addressed in part by the IMM-2 Core Measure from the Centers for Medicare and Medicaid Services, which translate into financial penalties for hospitals that fall below a threshold influenza vaccination rate before patient discharge. Many hospitals now have standing orders not only for influenza vaccination in season but also for pneumococcal vaccination year-round for appropriate patients.
- Baxby D. Edward Jenner’s inquiry after 200 years. BMJ 1999;318:390.
- Centers for Disease Control and Prevention. Progress toward elimination of Haemophilus influenzae type b invasive disease among infants and children — United States, 1998-2000. MMWR Morb Mortal Wkly Rep 2002;51:234-237.
- Guris D, Jumaan AO, Mascola L, et al. Changing varicella epidemiology in active surveillance sites — United States, 1995-2005. J Infect Dis 2008;197:S71-S75.
- Nguyen HQ, Jumaan AO, Seward JF. Decline in mortality due to varicella after implementation of varicella vaccination in the United States. N Engl J Med 2005;352:450-458.
- Gandhi RT, Lynch JB, Del Rio C. Mild or moderate Covid-19. N Engl J Med 2020; 383:1757-1766.
- Centers for Disease Control and Prevention. Different COVID-19 vaccines. Updated April 3, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/different-vaccines.html
- Polack FP, Thomas SJ, Kitchin N, et al. Safety and efficacy of the BNT162b2 mRNA Covid-19 vaccine. N Engl J Med 2020;383:2603-2615.
- Baden LR, El Sahly HM, Essink B, et al. Efficacy and safety of the mRNA-1273 SARS-CoV-2 vaccine. N Engl J Med 2021;384;403-416.
- Dooling K, McClung N, Chamberland M, et al. The Advisory Committee on Immunization Practices’ interim recommendation for allocating initial supplies of COVID-19 vaccine – United States, 2020. MMWR Morb Mortal Wkly Rep 2020;69:1857-1859.
- Johnson & Johnson. Johnson & Johnson announces submission of application to the U.S. FDA for emergency use authorization of its investigational single-shot Janssen COVID-19 vaccine candidate. Feb. 4, 2021. https://www.jnj.com/johnson-johnson-announces-submission-of-application-to-the-u-s-fda-for-emergency-use-authorization-of-its-investigational-single-shot-janssen-covid-19-vaccine-candidate
- Johnson & Johnson. Johnson & Johnson COVID-19 vaccine authorized by U.S. FDA for emergency use – first single-shot vaccine in fight against global pandemic. J&J Press Release. Feb. 27, 2021. https://www.jnj.com/johnson-johnson-covid-19-vaccine-authorized-by-u-s-fda-for-emergency-usefirst-single-shot-vaccine-in-fight-against-global-pandemic
- Sadoff J, Le Gars M, Shukarev G, et al. Interim results of a phase 1-2a trial of Ad26.COV2.S Covid-19 vaccine. N Engl J Med 2021; Jan 13. doi: 10.1056/NEJMoa2034201. [Online ahead of print].
- Sahin U, Muik A, Derhovanessian E, et al. COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature 2020;586:594-599.
- Centers for Disease Control and Prevention. CDC’s COVID-19 vaccine rollout recommendations. Updated March 25, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/recommendations.html
- Centers for Disease Control and Prevention. Safety of COVID-19 vaccines. Updated April 6, 2021. https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/safety-of-vaccines.html
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