Immunology

To the Editor: In the February 2015 issue of Cleveland Clinic Journal of Medicine, Dr. David A. Katzka reviewed the major clinical features of eosinophilic esophagitis and, having presented its allergic component, rightly assessed the inherent difficulties of detecting and eliminating food allergens involved in the development and course of this disease.¹ The inadequacies of serologic testing were mentioned, as well as the difficulties of endoscopy and biopsy “painstakingly performed with the removal and reintroduction of every suspected food allergen, requiring multiple biopsies weekly, which is impractical for safety and economic reasons.”¹

In a meta-analysis, Arias et al² showed that such an individualized approach for each food is not really necessary. Elemental diets with graded reintroduction of grouped foods were effective in detecting and treating the responsible food allergies in 90.8% of cases (95% confidence interval [CI] 84.7–95.5). In fact, the more pragmatic, simple, and inexpensive six-food-elimination diet was also reasonably effective (72.1% of cases, 95% CI 65.8–78.1). Both outcomes are far superior to elimination strategies directed at immunoglobulin E (IgE), which were effective in only 45.5% of cases (95% CI 35.4–55.7%).²

Franciosi and Liacouras³ described a practical and comprehensive elimination-reintroduction protocol consisting of four steps that, in combination with symptom diaries, can easily identify responsible foods.

In our practice, graded elimination-reintroduction diets—which, depending on history, may range from the basic six-food-elimination diet to the fully developed Franciosi-Liacouras protocol—along with food IgE testing and judicial use of IgG testing against selected foods, have yielded detection and successful treatment rates comparable to the 90.8% rate reported by Arias et al.² Upon identification of food allergens, a dual approach of diet restrictions and food immunotherapy is initiated. As a result of this approach, patients only need to undergo a single endoscopy and biopsy to demonstrate decreased eosinophil counts, usually 1 year after initiation of allergy treatment.

Of course, pharmacologic management is necessary in the treatment of eosinophilic esophagitis. However, the inclusion of montelukast in the standard first-line regimen for eosinophilic esophagitis is not yet a firmly established practice. Not all eosinophilia can be equated to allergy, and not all allergic inflammation is leukotriene-dependent. Furthermore, too little is known about the secondary effects of leukotrienes on immune regulation and whether their blockade is really desirable in eosinophilic esophagitis. But it is known that leukotriene receptor antagonists, especially montelukast, can trigger Churg-Strauss vasculitis, a syndrome whose eosinophil activation, homing pattern, and subsequent proliferation—as well as its exclusive prevalence in allergic patients with asthma and chronic sinusitis—bear some similarity to those of eosinophilic esophagitis.

To the Editor: In the February 2015 issue of Cleveland Clinic Journal of Medicine, Dr. David A. Katzka reviewed the major clinical features of eosinophilic esophagitis and, having presented its allergic component, rightly assessed the inherent difficulties of detecting and eliminating food allergens involved in the development and course of this disease.¹ The inadequacies of serologic testing were mentioned, as well as the difficulties of endoscopy and biopsy “painstakingly performed with the removal and reintroduction of every suspected food allergen, requiring multiple biopsies weekly, which is impractical for safety and economic reasons.”¹

In a meta-analysis, Arias et al² showed that such an individualized approach for each food is not really necessary. Elemental diets with graded reintroduction of grouped foods were effective in detecting and treating the responsible food allergies in 90.8% of cases (95% confidence interval [CI] 84.7–95.5). In fact, the more pragmatic, simple, and inexpensive six-food-elimination diet was also reasonably effective (72.1% of cases, 95% CI 65.8–78.1). Both outcomes are far superior to elimination strategies directed at immunoglobulin E (IgE), which were effective in only 45.5% of cases (95% CI 35.4–55.7%).²

Franciosi and Liacouras³ described a practical and comprehensive elimination-reintroduction protocol consisting of four steps that, in combination with symptom diaries, can easily identify responsible foods.

In our practice, graded elimination-reintroduction diets—which, depending on history, may range from the basic six-food-elimination diet to the fully developed Franciosi-Liacouras protocol—along with food IgE testing and judicial use of IgG testing against selected foods, have yielded detection and successful treatment rates comparable to the 90.8% rate reported by Arias et al.² Upon identification of food allergens, a dual approach of diet restrictions and food immunotherapy is initiated. As a result of this approach, patients only need to undergo a single endoscopy and biopsy to demonstrate decreased eosinophil counts, usually 1 year after initiation of allergy treatment.

Of course, pharmacologic management is necessary in the treatment of eosinophilic esophagitis. However, the inclusion of montelukast in the standard first-line regimen for eosinophilic esophagitis is not yet a firmly established practice. Not all eosinophilia can be equated to allergy, and not all allergic inflammation is leukotriene-dependent. Furthermore, too little is known about the secondary effects of leukotrienes on immune regulation and whether their blockade is really desirable in eosinophilic esophagitis. But it is known that leukotriene receptor antagonists, especially montelukast, can trigger Churg-Strauss vasculitis, a syndrome whose eosinophil activation, homing pattern, and subsequent proliferation—as well as its exclusive prevalence in allergic patients with asthma and chronic sinusitis—bear some similarity to those of eosinophilic esophagitis.

To the Editor: In the February 2015 issue of Cleveland Clinic Journal of Medicine, Dr. David A. Katzka reviewed the major clinical features of eosinophilic esophagitis and, having presented its allergic component, rightly assessed the inherent difficulties of detecting and eliminating food allergens involved in the development and course of this disease.¹ The inadequacies of serologic testing were mentioned, as well as the difficulties of endoscopy and biopsy “painstakingly performed with the removal and reintroduction of every suspected food allergen, requiring multiple biopsies weekly, which is impractical for safety and economic reasons.”¹

In a meta-analysis, Arias et al² showed that such an individualized approach for each food is not really necessary. Elemental diets with graded reintroduction of grouped foods were effective in detecting and treating the responsible food allergies in 90.8% of cases (95% confidence interval [CI] 84.7–95.5). In fact, the more pragmatic, simple, and inexpensive six-food-elimination diet was also reasonably effective (72.1% of cases, 95% CI 65.8–78.1). Both outcomes are far superior to elimination strategies directed at immunoglobulin E (IgE), which were effective in only 45.5% of cases (95% CI 35.4–55.7%).²

Franciosi and Liacouras³ described a practical and comprehensive elimination-reintroduction protocol consisting of four steps that, in combination with symptom diaries, can easily identify responsible foods.

In our practice, graded elimination-reintroduction diets—which, depending on history, may range from the basic six-food-elimination diet to the fully developed Franciosi-Liacouras protocol—along with food IgE testing and judicial use of IgG testing against selected foods, have yielded detection and successful treatment rates comparable to the 90.8% rate reported by Arias et al.² Upon identification of food allergens, a dual approach of diet restrictions and food immunotherapy is initiated. As a result of this approach, patients only need to undergo a single endoscopy and biopsy to demonstrate decreased eosinophil counts, usually 1 year after initiation of allergy treatment.

Of course, pharmacologic management is necessary in the treatment of eosinophilic esophagitis. However, the inclusion of montelukast in the standard first-line regimen for eosinophilic esophagitis is not yet a firmly established practice. Not all eosinophilia can be equated to allergy, and not all allergic inflammation is leukotriene-dependent. Furthermore, too little is known about the secondary effects of leukotrienes on immune regulation and whether their blockade is really desirable in eosinophilic esophagitis. But it is known that leukotriene receptor antagonists, especially montelukast, can trigger Churg-Strauss vasculitis, a syndrome whose eosinophil activation, homing pattern, and subsequent proliferation—as well as its exclusive prevalence in allergic patients with asthma and chronic sinusitis—bear some similarity to those of eosinophilic esophagitis.

In Reply: I am most grateful to Drs. Theodoropoulos and Morris for their letter. I fully agree that we are getting smarter with diet elimination therapies by introducing more than one food at a time in the hope that we can lessen the number of endoscopies needed to isolate specific antigenic causes of eosinophilic esophagitis. This is not always successful, but in some of the more fortunate patients, we can get by with one or two endoscopies. It is my hope that with less-invasive tools such as the Cytosponge, the esophageal string test, and perhaps even serum evaluations, we can further embrace diet therapy as a standard treatment in more patients with eosinophilic esophagitis.

I think it is also important to note that although traditional radioallergosorbent and skin testing was only 45% accurate for eosinophilic esophagitis in the meta-analysis cited, this testing is still important, given the number of IgE-related allergies additionally uncovered in patients with eosinophilic esophagitis.

In Reply: I am most grateful to Drs. Theodoropoulos and Morris for their letter. I fully agree that we are getting smarter with diet elimination therapies by introducing more than one food at a time in the hope that we can lessen the number of endoscopies needed to isolate specific antigenic causes of eosinophilic esophagitis. This is not always successful, but in some of the more fortunate patients, we can get by with one or two endoscopies. It is my hope that with less-invasive tools such as the Cytosponge, the esophageal string test, and perhaps even serum evaluations, we can further embrace diet therapy as a standard treatment in more patients with eosinophilic esophagitis.

I think it is also important to note that although traditional radioallergosorbent and skin testing was only 45% accurate for eosinophilic esophagitis in the meta-analysis cited, this testing is still important, given the number of IgE-related allergies additionally uncovered in patients with eosinophilic esophagitis.

In Reply: I am most grateful to Drs. Theodoropoulos and Morris for their letter. I fully agree that we are getting smarter with diet elimination therapies by introducing more than one food at a time in the hope that we can lessen the number of endoscopies needed to isolate specific antigenic causes of eosinophilic esophagitis. This is not always successful, but in some of the more fortunate patients, we can get by with one or two endoscopies. It is my hope that with less-invasive tools such as the Cytosponge, the esophageal string test, and perhaps even serum evaluations, we can further embrace diet therapy as a standard treatment in more patients with eosinophilic esophagitis.

I think it is also important to note that although traditional radioallergosorbent and skin testing was only 45% accurate for eosinophilic esophagitis in the meta-analysis cited, this testing is still important, given the number of IgE-related allergies additionally uncovered in patients with eosinophilic esophagitis.

Vaccination is the standard of care as part of health maintenance for healthy people and for patients with myriad medical conditions. In an article in this issue of Cleveland Clinic Journal of Medicine, Drs. Faria Farhat and Glenn Wortmann¹ make recommendations about vaccinations in special populations, including people with a disordered immune system or who are otherwise at heightened risk of infection (eg, because of older age, international travel, comorbidities, and medications).

See related article

But special populations are not all the same in their responses to vaccination. For example, patients with systemic autoimmune diseases are a heterogeneous group with disease-specific immunologic perturbations and immunosuppression that vary by medication and dose, all affecting the response to vaccination. Also, two or more “special” situations may coexist in the same patient.

AREAS OF UNCERTAINTY FOR CLINICAL PRACTICE

Several groups have issued guidelines and recommendations about vaccination in immunocompromised patients, but many areas of uncertainty exist in clinical practice. Most of these arise from a lack of data on immunogenicity and outcomes.

For example, although two pneumococcal vaccines are used in adults, no studies have compared the immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13, which is T–cell-dependent) with that of the 23-valent pneumococcal polysaccharide vaccine (PPSV23, which is T–cell-independent) in immunocompromised adults.

Also, whether to use zoster vaccine in immunosuppressed patients ages 50 through 59 is debated. The vaccine is approved by the US Food and Drug Administration (FDA) for this age group, but the Advisory Committee on Immunization Practices (ACIP) does not recommend it, and the Infectious Diseases Society of America (IDSA) suggests that it be “considered” in patients on low-intensity immunosuppressive treatment.²

Testing to ensure optimal response to vaccination has been recommended in several articles and guidelines. However, antibody titers do not necessarily correlate with protection, and at this time no consensus exists about the timing of or need for testing for the response to immunization, the methods to use, how to interpret the results in terms of an adequate or inadequate response, or the role of booster immunization in routine clinical practice.

IS VACCINATION COST-EFFECTIVE?

Also relevant is whether vaccination is cost-effective.

Although vaccination with the PCV13 vaccine is possibly more cost-effective than PPSV23 in US adults based on a model that included immunosuppressed patients, the results of this study were sensitive to several assumptions, and the authors did not extrapolate their conclusion to immunocompromised individuals.³

In another cost-effectiveness analysis, immunocompromised patients were vaccinated with PCV13 at diagnosis and, starting a year later, were followed according to current PPSV23 vaccination guidelines. The PCV13 vaccine’s efficacy against invasive pneumococcal disease and pneumonia based on the modeled program led to cost savings, added quality-adjusted life-years, and prevented invasive pneumococcal disease, mostly in patients with human immunodeficiency virus  (HIV) infection and those on dialysis (unpublished data cited in a 2012 US Centers for Disease Control and Prevention [CDC] report).⁴

No cost-effectiveness studies of influenza vaccination in immunocompromised adults have been conducted in the United States.

The various recommendations by the FDA, the ACIP, and the IDSA regarding the appropriate age at which to give zoster vaccine may also have been influenced by cost-effectiveness studies. These have reported mixed results and have not specifically focused on special populations.⁵

IMPROVING VACCINATION RATES

Rates of vaccination in special populations are suboptimal, and remedial measures to improve coverage have been proposed. One-page vaccine questionnaires or handouts for patients as well as “pop-up” reminders for vaccination in the electronic health record for physicians have resulted in higher rates of indicated vaccinations. Both the CDC and the American College of Physicians (ACP) offer downloadable tools—the CDC Vaccine Schedules App⁶ and the ACP Immunization Advisor,⁷ respectively—that are based on the 2012 ACIP guidelines and are extremely useful for busy practitioners. The CDC also offers patients a vaccine questionnaire⁸ that allows them to determine which vaccinations they may need and also to learn about those vaccines.

MOVING AHEAD

The development of vaccines is ongoing and will be driven by identification of new molecular targets. Advances in therapies for immunocompromised patients such as those with HIV infection will, we hope, decrease the risk of opportunistic infections. The list of vaccine-preventable diseases may continue to grow, as may the list of special populations. Optimal vaccination and outcomes may emerge from expected improved vaccine coverage as a result of the increased health insurance coverage resulting from the much-maligned Patient Protection and Affordable Care Act and ongoing studies regarding efficacy, safety, and cost-effectiveness, especially pertaining to specific patient populations.

Vaccination is the standard of care as part of health maintenance for healthy people and for patients with myriad medical conditions. In an article in this issue of Cleveland Clinic Journal of Medicine, Drs. Faria Farhat and Glenn Wortmann¹ make recommendations about vaccinations in special populations, including people with a disordered immune system or who are otherwise at heightened risk of infection (eg, because of older age, international travel, comorbidities, and medications).

See related article

But special populations are not all the same in their responses to vaccination. For example, patients with systemic autoimmune diseases are a heterogeneous group with disease-specific immunologic perturbations and immunosuppression that vary by medication and dose, all affecting the response to vaccination. Also, two or more “special” situations may coexist in the same patient.

AREAS OF UNCERTAINTY FOR CLINICAL PRACTICE

Several groups have issued guidelines and recommendations about vaccination in immunocompromised patients, but many areas of uncertainty exist in clinical practice. Most of these arise from a lack of data on immunogenicity and outcomes.

For example, although two pneumococcal vaccines are used in adults, no studies have compared the immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13, which is T–cell-dependent) with that of the 23-valent pneumococcal polysaccharide vaccine (PPSV23, which is T–cell-independent) in immunocompromised adults.

Also, whether to use zoster vaccine in immunosuppressed patients ages 50 through 59 is debated. The vaccine is approved by the US Food and Drug Administration (FDA) for this age group, but the Advisory Committee on Immunization Practices (ACIP) does not recommend it, and the Infectious Diseases Society of America (IDSA) suggests that it be “considered” in patients on low-intensity immunosuppressive treatment.²

Testing to ensure optimal response to vaccination has been recommended in several articles and guidelines. However, antibody titers do not necessarily correlate with protection, and at this time no consensus exists about the timing of or need for testing for the response to immunization, the methods to use, how to interpret the results in terms of an adequate or inadequate response, or the role of booster immunization in routine clinical practice.

IS VACCINATION COST-EFFECTIVE?

Also relevant is whether vaccination is cost-effective.

Although vaccination with the PCV13 vaccine is possibly more cost-effective than PPSV23 in US adults based on a model that included immunosuppressed patients, the results of this study were sensitive to several assumptions, and the authors did not extrapolate their conclusion to immunocompromised individuals.³

In another cost-effectiveness analysis, immunocompromised patients were vaccinated with PCV13 at diagnosis and, starting a year later, were followed according to current PPSV23 vaccination guidelines. The PCV13 vaccine’s efficacy against invasive pneumococcal disease and pneumonia based on the modeled program led to cost savings, added quality-adjusted life-years, and prevented invasive pneumococcal disease, mostly in patients with human immunodeficiency virus  (HIV) infection and those on dialysis (unpublished data cited in a 2012 US Centers for Disease Control and Prevention [CDC] report).⁴

No cost-effectiveness studies of influenza vaccination in immunocompromised adults have been conducted in the United States.

The various recommendations by the FDA, the ACIP, and the IDSA regarding the appropriate age at which to give zoster vaccine may also have been influenced by cost-effectiveness studies. These have reported mixed results and have not specifically focused on special populations.⁵

IMPROVING VACCINATION RATES

Rates of vaccination in special populations are suboptimal, and remedial measures to improve coverage have been proposed. One-page vaccine questionnaires or handouts for patients as well as “pop-up” reminders for vaccination in the electronic health record for physicians have resulted in higher rates of indicated vaccinations. Both the CDC and the American College of Physicians (ACP) offer downloadable tools—the CDC Vaccine Schedules App⁶ and the ACP Immunization Advisor,⁷ respectively—that are based on the 2012 ACIP guidelines and are extremely useful for busy practitioners. The CDC also offers patients a vaccine questionnaire⁸ that allows them to determine which vaccinations they may need and also to learn about those vaccines.

MOVING AHEAD

The development of vaccines is ongoing and will be driven by identification of new molecular targets. Advances in therapies for immunocompromised patients such as those with HIV infection will, we hope, decrease the risk of opportunistic infections. The list of vaccine-preventable diseases may continue to grow, as may the list of special populations. Optimal vaccination and outcomes may emerge from expected improved vaccine coverage as a result of the increased health insurance coverage resulting from the much-maligned Patient Protection and Affordable Care Act and ongoing studies regarding efficacy, safety, and cost-effectiveness, especially pertaining to specific patient populations.

Vaccination is the standard of care as part of health maintenance for healthy people and for patients with myriad medical conditions. In an article in this issue of Cleveland Clinic Journal of Medicine, Drs. Faria Farhat and Glenn Wortmann¹ make recommendations about vaccinations in special populations, including people with a disordered immune system or who are otherwise at heightened risk of infection (eg, because of older age, international travel, comorbidities, and medications).

See related article

But special populations are not all the same in their responses to vaccination. For example, patients with systemic autoimmune diseases are a heterogeneous group with disease-specific immunologic perturbations and immunosuppression that vary by medication and dose, all affecting the response to vaccination. Also, two or more “special” situations may coexist in the same patient.

AREAS OF UNCERTAINTY FOR CLINICAL PRACTICE

Several groups have issued guidelines and recommendations about vaccination in immunocompromised patients, but many areas of uncertainty exist in clinical practice. Most of these arise from a lack of data on immunogenicity and outcomes.

For example, although two pneumococcal vaccines are used in adults, no studies have compared the immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13, which is T–cell-dependent) with that of the 23-valent pneumococcal polysaccharide vaccine (PPSV23, which is T–cell-independent) in immunocompromised adults.

Also, whether to use zoster vaccine in immunosuppressed patients ages 50 through 59 is debated. The vaccine is approved by the US Food and Drug Administration (FDA) for this age group, but the Advisory Committee on Immunization Practices (ACIP) does not recommend it, and the Infectious Diseases Society of America (IDSA) suggests that it be “considered” in patients on low-intensity immunosuppressive treatment.²

Testing to ensure optimal response to vaccination has been recommended in several articles and guidelines. However, antibody titers do not necessarily correlate with protection, and at this time no consensus exists about the timing of or need for testing for the response to immunization, the methods to use, how to interpret the results in terms of an adequate or inadequate response, or the role of booster immunization in routine clinical practice.

IS VACCINATION COST-EFFECTIVE?

Also relevant is whether vaccination is cost-effective.

Although vaccination with the PCV13 vaccine is possibly more cost-effective than PPSV23 in US adults based on a model that included immunosuppressed patients, the results of this study were sensitive to several assumptions, and the authors did not extrapolate their conclusion to immunocompromised individuals.³

In another cost-effectiveness analysis, immunocompromised patients were vaccinated with PCV13 at diagnosis and, starting a year later, were followed according to current PPSV23 vaccination guidelines. The PCV13 vaccine’s efficacy against invasive pneumococcal disease and pneumonia based on the modeled program led to cost savings, added quality-adjusted life-years, and prevented invasive pneumococcal disease, mostly in patients with human immunodeficiency virus  (HIV) infection and those on dialysis (unpublished data cited in a 2012 US Centers for Disease Control and Prevention [CDC] report).⁴

No cost-effectiveness studies of influenza vaccination in immunocompromised adults have been conducted in the United States.

The various recommendations by the FDA, the ACIP, and the IDSA regarding the appropriate age at which to give zoster vaccine may also have been influenced by cost-effectiveness studies. These have reported mixed results and have not specifically focused on special populations.⁵

IMPROVING VACCINATION RATES

Rates of vaccination in special populations are suboptimal, and remedial measures to improve coverage have been proposed. One-page vaccine questionnaires or handouts for patients as well as “pop-up” reminders for vaccination in the electronic health record for physicians have resulted in higher rates of indicated vaccinations. Both the CDC and the American College of Physicians (ACP) offer downloadable tools—the CDC Vaccine Schedules App⁶ and the ACP Immunization Advisor,⁷ respectively—that are based on the 2012 ACIP guidelines and are extremely useful for busy practitioners. The CDC also offers patients a vaccine questionnaire⁸ that allows them to determine which vaccinations they may need and also to learn about those vaccines.

MOVING AHEAD

The development of vaccines is ongoing and will be driven by identification of new molecular targets. Advances in therapies for immunocompromised patients such as those with HIV infection will, we hope, decrease the risk of opportunistic infections. The list of vaccine-preventable diseases may continue to grow, as may the list of special populations. Optimal vaccination and outcomes may emerge from expected improved vaccine coverage as a result of the increased health insurance coverage resulting from the much-maligned Patient Protection and Affordable Care Act and ongoing studies regarding efficacy, safety, and cost-effectiveness, especially pertaining to specific patient populations.

Most vaccinations are given during childhood, but some require boosting during adulthood or are indicated for specific patient populations such as international travelers or those with certain medical conditions. Although generally safe, some vaccines contain live, attenuated organisms that can cause disease in immunocompromised patients. Thus, knowledge of the indications for and contraindications to specific vaccinations is critical to protect adults in special circumstances who are at risk.

See related commentary

Vaccines have helped eliminate or significantly reduce the burden of more than a dozen illnesses.^1–3 The Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention  (CDC) makes recommendations about vaccinations for normal adults and children as well as for certain groups at high risk of vaccine-preventable infections.⁴ Tables 1 and 2 summarize the recommendations for vaccination by medical condition.⁴  In addition, several applications are available online, including downloadable apps from the (www.cdc.gov/vaccines/schedules/Schedulers/adult-scheduler.html) and the American College of Physicians (http://immunization.acponline.org/app/).

HUMANITY’S GREATEST ADVANCES IN PREVENTING INFECTIOUS DISEASE

Immunization and improved sanitation are humanity’s greatest advances in preventing sickness and death from infectious diseases. Since Jenner’s discovery in 1796 that milkmaids who had contracted cowpox (vaccinia) were immune to smallpox, vaccination has eliminated smallpox, markedly decreased the incidence of many infectious diseases, and, most recently, shown efficacy in preventing cervical cancer (with the human papillomavirus vaccine) and hepatocellular cancer (with the hepatitis B vaccine).^1–3

Unfortunately, vaccination rates remain low for most routine vaccinations indicated for adults. For example, about 60% of adults over age 65 receive pneumococcal vaccination, and fewer than 10% of black patients over age 60 receive zoster vaccination.⁵ Various factors may account for these low rates, including financial disincentives.⁶

Nevertheless, vaccination remains one of medicine’s most effective defenses against infectious diseases and is especially important in the special populations discussed below. By being steadfast proponents of vaccination, especially for the most vulnerable patients, physicians can help ensure the optimum protection for their patients.

VACCINATING PREGNANT PATIENTS

When considering vaccination during pregnancy, one must consider the risk and benefit of the vaccine and the risk of the disease in both the mother and the child.

In general, if a pregnant woman is at high risk of exposure to a particular infection, the benefits of vaccinating her against it outweigh the risks. Vaccinating the mother can also protect against certain infections in early infancy through transfer of vaccine-induced immunoglobin G (IgG) across the placenta.⁷ In general, inactivated vaccines are considered safe in pregnancy, while live-attenuated vaccines are contraindicated.⁴ Special considerations for pregnant women include:

Tetanus, diphtheria, and acellular pertussis (Tdap). One dose of Tdap vaccine should be given during each pregnancy, preferably at 27 to 36 weeks of gestation, regardless of when the patient received a previous dose.⁸

Inactivated influenza vaccine should be given as early as possible during the influenza season (October to March) to all pregnant women, regardless of trimester.

Inactivated polio vaccine may be considered for pregnant women with known exposure to polio or travel to endemic areas.

Hepatitis A, hepatitis B, pneumococcal polysaccharide, meningococcal conjugate, and meningococcal polysaccharide vaccines can be given to women at risk of these infections. If a pregnant patient requires pneumococcal polysaccharide vaccine, it should be given during the second or third trimester, as the safety of this vaccine during the first trimester has not been established.⁹

Smallpox, measles-mumps-rubella, and varicella-containing vaccines are contraindicated in pregnancy. Household contacts of a pregnant woman should not receive smallpox vaccine, as it is the only vaccine known to cause harm to the fetus.¹⁰

Human papillomavirus vaccination is not recommended during pregnancy.

Yellow fever live-attenuated vaccine. The safety of this vaccine during pregnancy has not been established, and it is in the US Food and Drug Administration (FDA) pregnancy category C. However, this vaccine is required for entry into certain countries, and it may be offered if the patient is truly at risk of contracting yellow fever. Because pregnancy may affect immunologic response, serologic testing is recommended to document an immune response. If the patient’s itinerary puts her at low risk of yellow fever, then writing her a vaccine waiver letter can be considered.¹¹

VACCINATING IMMUNOCOMPROMISED PATIENTS (NON-HIV)

People who do not have human immunodeficiency virus (HIV) but have a condition such as functional asplenia (sickle cell disease), anatomic asplenia, or complement component deficiency are at higher risk of infection with the encapsulated bacteria Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b.

Corticosteroids, chemotherapy, radiation for hematologic or solid-organ malignancies, and immune modulators can alter the immune system and pose a risk with the use of live-attenuated vaccines. A corticosteroid dosage equivalent to 2 mg/kg of body weight per day or higher or 20 mg/day of prednisone or higher is generally considered immunosuppressive.

Candidates for organ transplantation should receive vaccinations as early as possible during the disease course leading to transplantation. Vaccinations should be given as soon as the decision is made that the patient is a candidate for transplantation, which could be years or months before the patient actually receives the transplant. In addition to reviewing previously administered vaccinations, pretransplant serologic testing for hepatitis B, varicella, measles, mumps, and rubella antibodies helps to evaluate the need for vaccination.¹²

Recipients of hematopoietic stem cell transplantation are at risk of infections with encapsulated bacteria and certain other vaccine-preventable infections. Antibody titers are significantly reduced after stem cell transplantation because of ablation of bone marrow, and thus certain vaccines should be readministered 3 to 6 months after transplantation (eg, influenza, pneumococcal, and H influenzae vaccines). If the recipient is presumed to be immunocompetent, then varicella or measles-mumps-rubella vaccine can be given 24 months after transplantation.¹³

Apart from adhering to the routine vaccination schedule and avoiding live-attenuated vaccines, specific recommendations apply to persons with immunocompromising conditions¹⁴:

Quadrivalent meningococcal conjugate vaccine should be given to adults of all ages with asplenia or complement component deficiency. The schedule includes two doses at least 2 months apart initially and then revaccination every 5 years.

H influenzae type b vaccine should be given to people with asplenia and recipients of hematopoietic stem cells. One dose is recommended for those with asplenia (functional, anatomic, or elective splenectomy) or sickle cell disease if they have not already received it. A three-dose schedule is considered for hematopoietic stem cell transplant recipients 6 to 12 months after successful transplantation.

Pneumococcal conjugate (PCV13) and pneumococcal polysaccharide (PPSV23) vaccinations are recommended for people who have immunocompromising conditions. PCV13, the newer pneumococcal vaccine, was approved by the FDA in 2010 for use in children and was recommended by the ACIP in 2012 for adults age 19 and older with immunocompromising conditions.

People who have not previously received either of these vaccines and are age 19 or older with immunocompromising conditions including asplenia, chronic renal failure, nephrotic syndrome, cerebrospinal fluid leakage, or cochlear implant should receive a single dose of PCV13 followed by a dose of PPSV23 at least 8 weeks later. One-time revaccination 5 years after the first dose of PPSV23 is recommended for patients with immunocompromising conditions.

For those who have previously been vaccinated with PPSV23, a dose of PCV13 can be given 1 or more years after the last dose of PPSV23. These dosing intervals are important, as lower opsonophagocytic antibody responses have been noted if repeat doses of either pneumococcal vaccine are given sooner than the recommended interval.¹⁵

Inactivated influenza vaccine is recommended annually, except for patients who are unlikely to respond or those who have received anti-B-cell antibodies within 6 months. Live-attenuated influenza vaccine should not be given to immunocompromised patients.

VACCINATING PATIENTS WHO HAVE HIV

People with HIV should be routinely screened for immunity against certain infections and should be offered vaccination if not immune. The response to vaccines may vary depending on the CD4 count, with a good response in patients whose infection is well controlled with antiretroviral agents and with a preserved CD4 count.¹⁶ Special considerations for HIV patients include the following:

Hepatitis A vaccine may be offered to all HIV patients who have no evidence of immunity against hepatitis A, with negative antihepatitis A total and IgG antibodies.

Human papillomavirus vaccine is recommended for men and women with HIV through age 26.

Varicella and measles-mumps-rubella are live-attenuated vaccines and may be considered in patients who are nonimmune and with CD4 counts of 200 cells/µL or higher. However, the ACIP does not make a recommendation regarding the zoster vaccine in HIV patients with CD4 cell counts of 200 cells/µL or higher. In general, live-attenuated vaccines should be avoided in patients with CD4 counts less than 200 or with severe immunocompromised status because of risk of acquiring severe, life-threatening infections.

Pneumococcal vaccine should be given to HIV patients if they have not received it before. The schedule is one dose of PCV13, followed by a dose of PPSV23 at least 8 weeks later. If a patient has been previously vaccinated with PPSV23, then PCV13 is recommended at least 1 year after PPSV23.

Inactivated influenza vaccine is recommended annually. Live-attenuated influenza vaccine should not be given.

Hepatitis B vaccine should be given to nonimmune patients without past or present hepatitis B infection. These patients require higher doses of hepatitis B vaccine (40 μg/mL) than immunocompetent patients, who receive 20 μg/mL. The options include Recombivax HB 40 μg/mL given on a three-dose schedule at 0, 1, and 6 months, and Engerix B, two 20-μg/mL injections given simultaneously on a four-dose schedule at 0, 1, 2, and 6 months.

Meningococcal vaccine. HIV infection is not an indication for meningococcal vaccine unless the patient has other risk factors, such as anatomic or functional asplenia, persistent complement component deficiency, occupational exposure, and travel to endemic areas.

VACCINATING PATIENTS WHO ARE OLDER THAN 60

The immune system deteriorates with age, as does immunity gained from previous vaccinations. Vaccination in this age group reduces the risk of illness and death.¹⁷

Zoster vaccine should be offered to people age 60 and older regardless of previous episodes of herpes zoster unless there is a contraindication such as severe immunodeficiency. The zoster vaccine can reduce the incidence of postherpetic neuralgia by 66.5% and herpes zoster by 51% in patients over age 60.¹⁸

Pneumococcal conjugate vaccine. PCV13 should be offered to all adults age 65 or older. If a person age 65 or older has not received any pneumococcal vaccine before then, PCV13 should be given first, followed by a dose of PPSV23 at least 6 to 12 months after PCV13.

Pneumococcal polysaccharide vaccine. If PPSV23 was given before age 65 for another indication, a dose of PCV 13 should be given at age 65 or later, as long as 6 to 12 months have passed since the previous dose of PPSV 23. The patient should receive the last dose of PPSV23 vaccine 5 years after the first dose of PPSV23.⁴

Influenza vaccine. People 65 or older are at higher risk of complications from influenza, and vaccine should be offered annually. High-dose inactivated influenza vaccine can be used in this age group.⁴

Tdap. If never given before, Tdap is recommended regardless of the interval since the most recent Td vaccination, followed by a Td booster every 10 years.

VACCINATING PATIENTS WHO HAVE CHRONIC KIDNEY DISEASE

Patients with chronic kidney disease are at risk of certain infections, so vaccination is an important preventive measure.¹⁹ Immunizations should be offered to all patients with chronic kidney disease regardless of the disease stage, but they are recommended during the early stages of progressive renal disease to increase the likelihood of vaccine-induced immunity.²⁰

Pneumococcal conjugate vaccine. PCV13 is recommended for adults 19 or older with chronic renal disease or nephrotic syndrome. One dose of PCV13 should be given, followed by a dose of PPSV23 at least 8 weeks later. If the patient has been previously vaccinated with PPSV23, then PCV13 at least 1 year after PPSV23 is recommended.

Hepatitis B vaccine should be given to nonimmune patients without past or present hepatitis B infection. Adult patients on hemodialysis require higher doses of hepatitis B vaccine. The options include Recombivax HB 40 μg/mL given on a three-dose schedule at 0, 1, and 6 months, and Engerix B, two 20-μg/mL injections given simultaneously on a four-dose schedule at 0, 1, 2, and 6 months.

Influenza vaccine should be offered annually to patients with chronic kidney disease.

VACCINATING IMMUNOCOMPROMISED INTERNATIONAL TRAVELERS

International travel for business or pleasure is increasingly common, and immunocompromised patients require specific attention as they may face unanticipated pathogens or have special requirements. Transplant recipients should ideally receive routine and travel-related vaccines as early as possible before transplantation. Vaccination is generally avoided in the first 6 months after organ transplantation to avoid confusion with early graft dysfunction or rejection.²¹ However, it should be considered as soon as a patient develops an illness that might lead to transplantation.

Evaluation of patients for vaccination should include an assessment of the travel-specific epidemiologic risk, the nature of the vaccine (live-attenuated or other), and the immune status. As discussed above, live-attenuated vaccines should be avoided in immunocompromised patients, and thus the injectable typhoid vaccine should be given in lieu of the attenuated oral vaccine.

Yellow fever vaccine is required before entrance to certain countries but should not be given to immunocompromised patients, although it can probably be given to asymptomatic HIV-infected adults with a CD4 count higher than 200 cells/μL who are exposed to substantial risk.²² For patients who cannot receive the vaccine, some governments will accept a physician’s letter stating the patient has a contraindication to vaccination.

VACCINATING HOUSEHOLD MEMBERS OF IMMUNOCOMPROMISED PATIENTS

Protecting immunocompromised patients from infectious diseases involves vaccinating not only the patient but also household members so that they do not acquire infections and then bring them into the household. Immunocompetent members of a household can receive inactivated vaccines based on the recommended ACIP schedule.

Annual inactivated influenza vaccination is recommended, although the live-attenuated influenza virus vaccine can be substituted if the immunocompromised patient is not within 2 months of hematopoietic stem cell transplantation, does not have graft-vs-host disease, and does not have severe combined immune deficiency.

Other live-attenuated vaccines can usually be given if indicated, including measles-mumps-rubella vaccine, rotavirus vaccine in infants, varicella vaccine, and zoster vaccine.¹⁴

Most vaccinations are given during childhood, but some require boosting during adulthood or are indicated for specific patient populations such as international travelers or those with certain medical conditions. Although generally safe, some vaccines contain live, attenuated organisms that can cause disease in immunocompromised patients. Thus, knowledge of the indications for and contraindications to specific vaccinations is critical to protect adults in special circumstances who are at risk.

See related commentary

Vaccines have helped eliminate or significantly reduce the burden of more than a dozen illnesses.^1–3 The Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention  (CDC) makes recommendations about vaccinations for normal adults and children as well as for certain groups at high risk of vaccine-preventable infections.⁴ Tables 1 and 2 summarize the recommendations for vaccination by medical condition.⁴  In addition, several applications are available online, including downloadable apps from the (www.cdc.gov/vaccines/schedules/Schedulers/adult-scheduler.html) and the American College of Physicians (http://immunization.acponline.org/app/).

HUMANITY’S GREATEST ADVANCES IN PREVENTING INFECTIOUS DISEASE

Immunization and improved sanitation are humanity’s greatest advances in preventing sickness and death from infectious diseases. Since Jenner’s discovery in 1796 that milkmaids who had contracted cowpox (vaccinia) were immune to smallpox, vaccination has eliminated smallpox, markedly decreased the incidence of many infectious diseases, and, most recently, shown efficacy in preventing cervical cancer (with the human papillomavirus vaccine) and hepatocellular cancer (with the hepatitis B vaccine).^1–3

Unfortunately, vaccination rates remain low for most routine vaccinations indicated for adults. For example, about 60% of adults over age 65 receive pneumococcal vaccination, and fewer than 10% of black patients over age 60 receive zoster vaccination.⁵ Various factors may account for these low rates, including financial disincentives.⁶

Nevertheless, vaccination remains one of medicine’s most effective defenses against infectious diseases and is especially important in the special populations discussed below. By being steadfast proponents of vaccination, especially for the most vulnerable patients, physicians can help ensure the optimum protection for their patients.

VACCINATING PREGNANT PATIENTS

When considering vaccination during pregnancy, one must consider the risk and benefit of the vaccine and the risk of the disease in both the mother and the child.

In general, if a pregnant woman is at high risk of exposure to a particular infection, the benefits of vaccinating her against it outweigh the risks. Vaccinating the mother can also protect against certain infections in early infancy through transfer of vaccine-induced immunoglobin G (IgG) across the placenta.⁷ In general, inactivated vaccines are considered safe in pregnancy, while live-attenuated vaccines are contraindicated.⁴ Special considerations for pregnant women include:

Tetanus, diphtheria, and acellular pertussis (Tdap). One dose of Tdap vaccine should be given during each pregnancy, preferably at 27 to 36 weeks of gestation, regardless of when the patient received a previous dose.⁸

Inactivated influenza vaccine should be given as early as possible during the influenza season (October to March) to all pregnant women, regardless of trimester.

Inactivated polio vaccine may be considered for pregnant women with known exposure to polio or travel to endemic areas.

Hepatitis A, hepatitis B, pneumococcal polysaccharide, meningococcal conjugate, and meningococcal polysaccharide vaccines can be given to women at risk of these infections. If a pregnant patient requires pneumococcal polysaccharide vaccine, it should be given during the second or third trimester, as the safety of this vaccine during the first trimester has not been established.⁹

Smallpox, measles-mumps-rubella, and varicella-containing vaccines are contraindicated in pregnancy. Household contacts of a pregnant woman should not receive smallpox vaccine, as it is the only vaccine known to cause harm to the fetus.¹⁰

Human papillomavirus vaccination is not recommended during pregnancy.

Yellow fever live-attenuated vaccine. The safety of this vaccine during pregnancy has not been established, and it is in the US Food and Drug Administration (FDA) pregnancy category C. However, this vaccine is required for entry into certain countries, and it may be offered if the patient is truly at risk of contracting yellow fever. Because pregnancy may affect immunologic response, serologic testing is recommended to document an immune response. If the patient’s itinerary puts her at low risk of yellow fever, then writing her a vaccine waiver letter can be considered.¹¹

VACCINATING IMMUNOCOMPROMISED PATIENTS (NON-HIV)

People who do not have human immunodeficiency virus (HIV) but have a condition such as functional asplenia (sickle cell disease), anatomic asplenia, or complement component deficiency are at higher risk of infection with the encapsulated bacteria Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b.

Corticosteroids, chemotherapy, radiation for hematologic or solid-organ malignancies, and immune modulators can alter the immune system and pose a risk with the use of live-attenuated vaccines. A corticosteroid dosage equivalent to 2 mg/kg of body weight per day or higher or 20 mg/day of prednisone or higher is generally considered immunosuppressive.

Candidates for organ transplantation should receive vaccinations as early as possible during the disease course leading to transplantation. Vaccinations should be given as soon as the decision is made that the patient is a candidate for transplantation, which could be years or months before the patient actually receives the transplant. In addition to reviewing previously administered vaccinations, pretransplant serologic testing for hepatitis B, varicella, measles, mumps, and rubella antibodies helps to evaluate the need for vaccination.¹²

Recipients of hematopoietic stem cell transplantation are at risk of infections with encapsulated bacteria and certain other vaccine-preventable infections. Antibody titers are significantly reduced after stem cell transplantation because of ablation of bone marrow, and thus certain vaccines should be readministered 3 to 6 months after transplantation (eg, influenza, pneumococcal, and H influenzae vaccines). If the recipient is presumed to be immunocompetent, then varicella or measles-mumps-rubella vaccine can be given 24 months after transplantation.¹³

Apart from adhering to the routine vaccination schedule and avoiding live-attenuated vaccines, specific recommendations apply to persons with immunocompromising conditions¹⁴:

Quadrivalent meningococcal conjugate vaccine should be given to adults of all ages with asplenia or complement component deficiency. The schedule includes two doses at least 2 months apart initially and then revaccination every 5 years.

H influenzae type b vaccine should be given to people with asplenia and recipients of hematopoietic stem cells. One dose is recommended for those with asplenia (functional, anatomic, or elective splenectomy) or sickle cell disease if they have not already received it. A three-dose schedule is considered for hematopoietic stem cell transplant recipients 6 to 12 months after successful transplantation.

Pneumococcal conjugate (PCV13) and pneumococcal polysaccharide (PPSV23) vaccinations are recommended for people who have immunocompromising conditions. PCV13, the newer pneumococcal vaccine, was approved by the FDA in 2010 for use in children and was recommended by the ACIP in 2012 for adults age 19 and older with immunocompromising conditions.

People who have not previously received either of these vaccines and are age 19 or older with immunocompromising conditions including asplenia, chronic renal failure, nephrotic syndrome, cerebrospinal fluid leakage, or cochlear implant should receive a single dose of PCV13 followed by a dose of PPSV23 at least 8 weeks later. One-time revaccination 5 years after the first dose of PPSV23 is recommended for patients with immunocompromising conditions.

For those who have previously been vaccinated with PPSV23, a dose of PCV13 can be given 1 or more years after the last dose of PPSV23. These dosing intervals are important, as lower opsonophagocytic antibody responses have been noted if repeat doses of either pneumococcal vaccine are given sooner than the recommended interval.¹⁵

Inactivated influenza vaccine is recommended annually, except for patients who are unlikely to respond or those who have received anti-B-cell antibodies within 6 months. Live-attenuated influenza vaccine should not be given to immunocompromised patients.

VACCINATING PATIENTS WHO HAVE HIV

People with HIV should be routinely screened for immunity against certain infections and should be offered vaccination if not immune. The response to vaccines may vary depending on the CD4 count, with a good response in patients whose infection is well controlled with antiretroviral agents and with a preserved CD4 count.¹⁶ Special considerations for HIV patients include the following:

Hepatitis A vaccine may be offered to all HIV patients who have no evidence of immunity against hepatitis A, with negative antihepatitis A total and IgG antibodies.

Human papillomavirus vaccine is recommended for men and women with HIV through age 26.

Varicella and measles-mumps-rubella are live-attenuated vaccines and may be considered in patients who are nonimmune and with CD4 counts of 200 cells/µL or higher. However, the ACIP does not make a recommendation regarding the zoster vaccine in HIV patients with CD4 cell counts of 200 cells/µL or higher. In general, live-attenuated vaccines should be avoided in patients with CD4 counts less than 200 or with severe immunocompromised status because of risk of acquiring severe, life-threatening infections.

Pneumococcal vaccine should be given to HIV patients if they have not received it before. The schedule is one dose of PCV13, followed by a dose of PPSV23 at least 8 weeks later. If a patient has been previously vaccinated with PPSV23, then PCV13 is recommended at least 1 year after PPSV23.

Inactivated influenza vaccine is recommended annually. Live-attenuated influenza vaccine should not be given.

Hepatitis B vaccine should be given to nonimmune patients without past or present hepatitis B infection. These patients require higher doses of hepatitis B vaccine (40 μg/mL) than immunocompetent patients, who receive 20 μg/mL. The options include Recombivax HB 40 μg/mL given on a three-dose schedule at 0, 1, and 6 months, and Engerix B, two 20-μg/mL injections given simultaneously on a four-dose schedule at 0, 1, 2, and 6 months.

Meningococcal vaccine. HIV infection is not an indication for meningococcal vaccine unless the patient has other risk factors, such as anatomic or functional asplenia, persistent complement component deficiency, occupational exposure, and travel to endemic areas.

VACCINATING PATIENTS WHO ARE OLDER THAN 60

The immune system deteriorates with age, as does immunity gained from previous vaccinations. Vaccination in this age group reduces the risk of illness and death.¹⁷

Zoster vaccine should be offered to people age 60 and older regardless of previous episodes of herpes zoster unless there is a contraindication such as severe immunodeficiency. The zoster vaccine can reduce the incidence of postherpetic neuralgia by 66.5% and herpes zoster by 51% in patients over age 60.¹⁸

Pneumococcal conjugate vaccine. PCV13 should be offered to all adults age 65 or older. If a person age 65 or older has not received any pneumococcal vaccine before then, PCV13 should be given first, followed by a dose of PPSV23 at least 6 to 12 months after PCV13.

Pneumococcal polysaccharide vaccine. If PPSV23 was given before age 65 for another indication, a dose of PCV 13 should be given at age 65 or later, as long as 6 to 12 months have passed since the previous dose of PPSV 23. The patient should receive the last dose of PPSV23 vaccine 5 years after the first dose of PPSV23.⁴

Influenza vaccine. People 65 or older are at higher risk of complications from influenza, and vaccine should be offered annually. High-dose inactivated influenza vaccine can be used in this age group.⁴

Tdap. If never given before, Tdap is recommended regardless of the interval since the most recent Td vaccination, followed by a Td booster every 10 years.

VACCINATING PATIENTS WHO HAVE CHRONIC KIDNEY DISEASE

Patients with chronic kidney disease are at risk of certain infections, so vaccination is an important preventive measure.¹⁹ Immunizations should be offered to all patients with chronic kidney disease regardless of the disease stage, but they are recommended during the early stages of progressive renal disease to increase the likelihood of vaccine-induced immunity.²⁰

Pneumococcal conjugate vaccine. PCV13 is recommended for adults 19 or older with chronic renal disease or nephrotic syndrome. One dose of PCV13 should be given, followed by a dose of PPSV23 at least 8 weeks later. If the patient has been previously vaccinated with PPSV23, then PCV13 at least 1 year after PPSV23 is recommended.

Hepatitis B vaccine should be given to nonimmune patients without past or present hepatitis B infection. Adult patients on hemodialysis require higher doses of hepatitis B vaccine. The options include Recombivax HB 40 μg/mL given on a three-dose schedule at 0, 1, and 6 months, and Engerix B, two 20-μg/mL injections given simultaneously on a four-dose schedule at 0, 1, 2, and 6 months.

Influenza vaccine should be offered annually to patients with chronic kidney disease.

VACCINATING IMMUNOCOMPROMISED INTERNATIONAL TRAVELERS

International travel for business or pleasure is increasingly common, and immunocompromised patients require specific attention as they may face unanticipated pathogens or have special requirements. Transplant recipients should ideally receive routine and travel-related vaccines as early as possible before transplantation. Vaccination is generally avoided in the first 6 months after organ transplantation to avoid confusion with early graft dysfunction or rejection.²¹ However, it should be considered as soon as a patient develops an illness that might lead to transplantation.

Evaluation of patients for vaccination should include an assessment of the travel-specific epidemiologic risk, the nature of the vaccine (live-attenuated or other), and the immune status. As discussed above, live-attenuated vaccines should be avoided in immunocompromised patients, and thus the injectable typhoid vaccine should be given in lieu of the attenuated oral vaccine.

Yellow fever vaccine is required before entrance to certain countries but should not be given to immunocompromised patients, although it can probably be given to asymptomatic HIV-infected adults with a CD4 count higher than 200 cells/μL who are exposed to substantial risk.²² For patients who cannot receive the vaccine, some governments will accept a physician’s letter stating the patient has a contraindication to vaccination.

VACCINATING HOUSEHOLD MEMBERS OF IMMUNOCOMPROMISED PATIENTS

Protecting immunocompromised patients from infectious diseases involves vaccinating not only the patient but also household members so that they do not acquire infections and then bring them into the household. Immunocompetent members of a household can receive inactivated vaccines based on the recommended ACIP schedule.

Annual inactivated influenza vaccination is recommended, although the live-attenuated influenza virus vaccine can be substituted if the immunocompromised patient is not within 2 months of hematopoietic stem cell transplantation, does not have graft-vs-host disease, and does not have severe combined immune deficiency.

Other live-attenuated vaccines can usually be given if indicated, including measles-mumps-rubella vaccine, rotavirus vaccine in infants, varicella vaccine, and zoster vaccine.¹⁴

Most vaccinations are given during childhood, but some require boosting during adulthood or are indicated for specific patient populations such as international travelers or those with certain medical conditions. Although generally safe, some vaccines contain live, attenuated organisms that can cause disease in immunocompromised patients. Thus, knowledge of the indications for and contraindications to specific vaccinations is critical to protect adults in special circumstances who are at risk.

See related commentary

Vaccines have helped eliminate or significantly reduce the burden of more than a dozen illnesses.^1–3 The Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention  (CDC) makes recommendations about vaccinations for normal adults and children as well as for certain groups at high risk of vaccine-preventable infections.⁴ Tables 1 and 2 summarize the recommendations for vaccination by medical condition.⁴  In addition, several applications are available online, including downloadable apps from the (www.cdc.gov/vaccines/schedules/Schedulers/adult-scheduler.html) and the American College of Physicians (http://immunization.acponline.org/app/).

HUMANITY’S GREATEST ADVANCES IN PREVENTING INFECTIOUS DISEASE

Immunization and improved sanitation are humanity’s greatest advances in preventing sickness and death from infectious diseases. Since Jenner’s discovery in 1796 that milkmaids who had contracted cowpox (vaccinia) were immune to smallpox, vaccination has eliminated smallpox, markedly decreased the incidence of many infectious diseases, and, most recently, shown efficacy in preventing cervical cancer (with the human papillomavirus vaccine) and hepatocellular cancer (with the hepatitis B vaccine).^1–3

Unfortunately, vaccination rates remain low for most routine vaccinations indicated for adults. For example, about 60% of adults over age 65 receive pneumococcal vaccination, and fewer than 10% of black patients over age 60 receive zoster vaccination.⁵ Various factors may account for these low rates, including financial disincentives.⁶

Nevertheless, vaccination remains one of medicine’s most effective defenses against infectious diseases and is especially important in the special populations discussed below. By being steadfast proponents of vaccination, especially for the most vulnerable patients, physicians can help ensure the optimum protection for their patients.

VACCINATING PREGNANT PATIENTS

When considering vaccination during pregnancy, one must consider the risk and benefit of the vaccine and the risk of the disease in both the mother and the child.

In general, if a pregnant woman is at high risk of exposure to a particular infection, the benefits of vaccinating her against it outweigh the risks. Vaccinating the mother can also protect against certain infections in early infancy through transfer of vaccine-induced immunoglobin G (IgG) across the placenta.⁷ In general, inactivated vaccines are considered safe in pregnancy, while live-attenuated vaccines are contraindicated.⁴ Special considerations for pregnant women include:

Tetanus, diphtheria, and acellular pertussis (Tdap). One dose of Tdap vaccine should be given during each pregnancy, preferably at 27 to 36 weeks of gestation, regardless of when the patient received a previous dose.⁸

Inactivated influenza vaccine should be given as early as possible during the influenza season (October to March) to all pregnant women, regardless of trimester.

Inactivated polio vaccine may be considered for pregnant women with known exposure to polio or travel to endemic areas.

Hepatitis A, hepatitis B, pneumococcal polysaccharide, meningococcal conjugate, and meningococcal polysaccharide vaccines can be given to women at risk of these infections. If a pregnant patient requires pneumococcal polysaccharide vaccine, it should be given during the second or third trimester, as the safety of this vaccine during the first trimester has not been established.⁹

Smallpox, measles-mumps-rubella, and varicella-containing vaccines are contraindicated in pregnancy. Household contacts of a pregnant woman should not receive smallpox vaccine, as it is the only vaccine known to cause harm to the fetus.¹⁰

Human papillomavirus vaccination is not recommended during pregnancy.

Yellow fever live-attenuated vaccine. The safety of this vaccine during pregnancy has not been established, and it is in the US Food and Drug Administration (FDA) pregnancy category C. However, this vaccine is required for entry into certain countries, and it may be offered if the patient is truly at risk of contracting yellow fever. Because pregnancy may affect immunologic response, serologic testing is recommended to document an immune response. If the patient’s itinerary puts her at low risk of yellow fever, then writing her a vaccine waiver letter can be considered.¹¹

VACCINATING IMMUNOCOMPROMISED PATIENTS (NON-HIV)

People who do not have human immunodeficiency virus (HIV) but have a condition such as functional asplenia (sickle cell disease), anatomic asplenia, or complement component deficiency are at higher risk of infection with the encapsulated bacteria Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type b.

Corticosteroids, chemotherapy, radiation for hematologic or solid-organ malignancies, and immune modulators can alter the immune system and pose a risk with the use of live-attenuated vaccines. A corticosteroid dosage equivalent to 2 mg/kg of body weight per day or higher or 20 mg/day of prednisone or higher is generally considered immunosuppressive.

Candidates for organ transplantation should receive vaccinations as early as possible during the disease course leading to transplantation. Vaccinations should be given as soon as the decision is made that the patient is a candidate for transplantation, which could be years or months before the patient actually receives the transplant. In addition to reviewing previously administered vaccinations, pretransplant serologic testing for hepatitis B, varicella, measles, mumps, and rubella antibodies helps to evaluate the need for vaccination.¹²

Recipients of hematopoietic stem cell transplantation are at risk of infections with encapsulated bacteria and certain other vaccine-preventable infections. Antibody titers are significantly reduced after stem cell transplantation because of ablation of bone marrow, and thus certain vaccines should be readministered 3 to 6 months after transplantation (eg, influenza, pneumococcal, and H influenzae vaccines). If the recipient is presumed to be immunocompetent, then varicella or measles-mumps-rubella vaccine can be given 24 months after transplantation.¹³

Apart from adhering to the routine vaccination schedule and avoiding live-attenuated vaccines, specific recommendations apply to persons with immunocompromising conditions¹⁴:

Quadrivalent meningococcal conjugate vaccine should be given to adults of all ages with asplenia or complement component deficiency. The schedule includes two doses at least 2 months apart initially and then revaccination every 5 years.

H influenzae type b vaccine should be given to people with asplenia and recipients of hematopoietic stem cells. One dose is recommended for those with asplenia (functional, anatomic, or elective splenectomy) or sickle cell disease if they have not already received it. A three-dose schedule is considered for hematopoietic stem cell transplant recipients 6 to 12 months after successful transplantation.

Pneumococcal conjugate (PCV13) and pneumococcal polysaccharide (PPSV23) vaccinations are recommended for people who have immunocompromising conditions. PCV13, the newer pneumococcal vaccine, was approved by the FDA in 2010 for use in children and was recommended by the ACIP in 2012 for adults age 19 and older with immunocompromising conditions.

People who have not previously received either of these vaccines and are age 19 or older with immunocompromising conditions including asplenia, chronic renal failure, nephrotic syndrome, cerebrospinal fluid leakage, or cochlear implant should receive a single dose of PCV13 followed by a dose of PPSV23 at least 8 weeks later. One-time revaccination 5 years after the first dose of PPSV23 is recommended for patients with immunocompromising conditions.

For those who have previously been vaccinated with PPSV23, a dose of PCV13 can be given 1 or more years after the last dose of PPSV23. These dosing intervals are important, as lower opsonophagocytic antibody responses have been noted if repeat doses of either pneumococcal vaccine are given sooner than the recommended interval.¹⁵

Inactivated influenza vaccine is recommended annually, except for patients who are unlikely to respond or those who have received anti-B-cell antibodies within 6 months. Live-attenuated influenza vaccine should not be given to immunocompromised patients.

VACCINATING PATIENTS WHO HAVE HIV

People with HIV should be routinely screened for immunity against certain infections and should be offered vaccination if not immune. The response to vaccines may vary depending on the CD4 count, with a good response in patients whose infection is well controlled with antiretroviral agents and with a preserved CD4 count.¹⁶ Special considerations for HIV patients include the following:

Hepatitis A vaccine may be offered to all HIV patients who have no evidence of immunity against hepatitis A, with negative antihepatitis A total and IgG antibodies.

Human papillomavirus vaccine is recommended for men and women with HIV through age 26.

Varicella and measles-mumps-rubella are live-attenuated vaccines and may be considered in patients who are nonimmune and with CD4 counts of 200 cells/µL or higher. However, the ACIP does not make a recommendation regarding the zoster vaccine in HIV patients with CD4 cell counts of 200 cells/µL or higher. In general, live-attenuated vaccines should be avoided in patients with CD4 counts less than 200 or with severe immunocompromised status because of risk of acquiring severe, life-threatening infections.

Pneumococcal vaccine should be given to HIV patients if they have not received it before. The schedule is one dose of PCV13, followed by a dose of PPSV23 at least 8 weeks later. If a patient has been previously vaccinated with PPSV23, then PCV13 is recommended at least 1 year after PPSV23.

Inactivated influenza vaccine is recommended annually. Live-attenuated influenza vaccine should not be given.

Hepatitis B vaccine should be given to nonimmune patients without past or present hepatitis B infection. These patients require higher doses of hepatitis B vaccine (40 μg/mL) than immunocompetent patients, who receive 20 μg/mL. The options include Recombivax HB 40 μg/mL given on a three-dose schedule at 0, 1, and 6 months, and Engerix B, two 20-μg/mL injections given simultaneously on a four-dose schedule at 0, 1, 2, and 6 months.

Meningococcal vaccine. HIV infection is not an indication for meningococcal vaccine unless the patient has other risk factors, such as anatomic or functional asplenia, persistent complement component deficiency, occupational exposure, and travel to endemic areas.

VACCINATING PATIENTS WHO ARE OLDER THAN 60

The immune system deteriorates with age, as does immunity gained from previous vaccinations. Vaccination in this age group reduces the risk of illness and death.¹⁷

Zoster vaccine should be offered to people age 60 and older regardless of previous episodes of herpes zoster unless there is a contraindication such as severe immunodeficiency. The zoster vaccine can reduce the incidence of postherpetic neuralgia by 66.5% and herpes zoster by 51% in patients over age 60.¹⁸

Pneumococcal conjugate vaccine. PCV13 should be offered to all adults age 65 or older. If a person age 65 or older has not received any pneumococcal vaccine before then, PCV13 should be given first, followed by a dose of PPSV23 at least 6 to 12 months after PCV13.

Pneumococcal polysaccharide vaccine. If PPSV23 was given before age 65 for another indication, a dose of PCV 13 should be given at age 65 or later, as long as 6 to 12 months have passed since the previous dose of PPSV 23. The patient should receive the last dose of PPSV23 vaccine 5 years after the first dose of PPSV23.⁴

Influenza vaccine. People 65 or older are at higher risk of complications from influenza, and vaccine should be offered annually. High-dose inactivated influenza vaccine can be used in this age group.⁴

Tdap. If never given before, Tdap is recommended regardless of the interval since the most recent Td vaccination, followed by a Td booster every 10 years.

VACCINATING PATIENTS WHO HAVE CHRONIC KIDNEY DISEASE

Patients with chronic kidney disease are at risk of certain infections, so vaccination is an important preventive measure.¹⁹ Immunizations should be offered to all patients with chronic kidney disease regardless of the disease stage, but they are recommended during the early stages of progressive renal disease to increase the likelihood of vaccine-induced immunity.²⁰

Pneumococcal conjugate vaccine. PCV13 is recommended for adults 19 or older with chronic renal disease or nephrotic syndrome. One dose of PCV13 should be given, followed by a dose of PPSV23 at least 8 weeks later. If the patient has been previously vaccinated with PPSV23, then PCV13 at least 1 year after PPSV23 is recommended.

Hepatitis B vaccine should be given to nonimmune patients without past or present hepatitis B infection. Adult patients on hemodialysis require higher doses of hepatitis B vaccine. The options include Recombivax HB 40 μg/mL given on a three-dose schedule at 0, 1, and 6 months, and Engerix B, two 20-μg/mL injections given simultaneously on a four-dose schedule at 0, 1, 2, and 6 months.

Influenza vaccine should be offered annually to patients with chronic kidney disease.

VACCINATING IMMUNOCOMPROMISED INTERNATIONAL TRAVELERS

International travel for business or pleasure is increasingly common, and immunocompromised patients require specific attention as they may face unanticipated pathogens or have special requirements. Transplant recipients should ideally receive routine and travel-related vaccines as early as possible before transplantation. Vaccination is generally avoided in the first 6 months after organ transplantation to avoid confusion with early graft dysfunction or rejection.²¹ However, it should be considered as soon as a patient develops an illness that might lead to transplantation.

Evaluation of patients for vaccination should include an assessment of the travel-specific epidemiologic risk, the nature of the vaccine (live-attenuated or other), and the immune status. As discussed above, live-attenuated vaccines should be avoided in immunocompromised patients, and thus the injectable typhoid vaccine should be given in lieu of the attenuated oral vaccine.

Yellow fever vaccine is required before entrance to certain countries but should not be given to immunocompromised patients, although it can probably be given to asymptomatic HIV-infected adults with a CD4 count higher than 200 cells/μL who are exposed to substantial risk.²² For patients who cannot receive the vaccine, some governments will accept a physician’s letter stating the patient has a contraindication to vaccination.

VACCINATING HOUSEHOLD MEMBERS OF IMMUNOCOMPROMISED PATIENTS

Protecting immunocompromised patients from infectious diseases involves vaccinating not only the patient but also household members so that they do not acquire infections and then bring them into the household. Immunocompetent members of a household can receive inactivated vaccines based on the recommended ACIP schedule.

Annual inactivated influenza vaccination is recommended, although the live-attenuated influenza virus vaccine can be substituted if the immunocompromised patient is not within 2 months of hematopoietic stem cell transplantation, does not have graft-vs-host disease, and does not have severe combined immune deficiency.

Other live-attenuated vaccines can usually be given if indicated, including measles-mumps-rubella vaccine, rotavirus vaccine in infants, varicella vaccine, and zoster vaccine.¹⁴

Anaphylaxis is a relatively common occurrence for many adolescents. As primary care doctors, we normally see the patient after the acute phase, and then are required to do the detective work to figure out the causes of the episode. The cause may be obvious, but many times we have to hope for another occurrence with similar circumstances to identify it. Surprisingly, the cause may not be what you think. Factors that contribute to an anaphylaxis response may be related to activity, timing of food ingestion, an environmental factor, or medication.

Let’s look at just one type, exercise-induced anaphylaxis. It’s divided into two categories: food dependent and nonfood dependent. Both are described as an induction of itching, urticaria, and fatigue, with progression to angioedema and hypotension, associated with exercise (J. Allergy Clin. Immunol. 1980;66:106-11).

Food-dependent exercise-induced anaphylaxis occurs when exercise is started 30 minutes after ingesting food. This may be difficult to identify because patients react to the food only if they exercise, so food is usually eliminated as a cause. Wheat and wheat flour are common culprits for this type of reaction because of the omega-5 gliadin, which is the protein in gluten (J. Allergy Clin. Immunol. 1991;87:34-40). In one study, larger amounts of the suspected agent were given; hives and angioedema did start to occur in 20% of patients challenged, which suggested that there was likely a baseline allergy to the food, and exercise itself might be a cofactor in augmentation of the allergic reaction.

In nonfood-dependent exercise-induced anaphylaxis, symptoms of itching, urticaria, and fatigue can occur 5-30 minutes after the start of exercise. Although bronchospasm is rare, it can occur along with angioedema, nausea, vomiting, and hypotension, and can even be fatal if exercise continues. If exercise is stopped, it usually resolves. However, many people try to push through it, which only worsens the symptoms.

Cofactors associated with nonfood-dependent exercise-induced anaphylaxis are ingestion of alcohol and an NSAID several hours beforehand. These agents also might be overlooked if well tolerated independently (Br. J. Dermatol. 2001;145:336-9).

Timing of the episode also plays a role. Premenstrual syndrome can be a factor in augmentation of anaphylaxis, so it also should be considered. Knowing the date of the last menstrual cycle and identifying if the anaphylaxis is episodic will identify premenstrual syndrome as a cause.

The work-up should include standard allergy testing and determination of tryptase levels. Skin testing is essential to identify offending agents, and is rarely negative. If a food is suspected and skin testing is negative, repeat the skin testing in 6 months. In one study, wheat extract was found to be positive in only 29% of persons suspected of having a wheat allergy, but when the paste of wheat flour was tested, 80% were identified. The ImmunoCAP Test also was found to have a sensitivity of 80%, so it is a valuable test to try along with the skin prick.

Tryptase levels should be evaluated because in nonfood-dependent exercise-induced anaphylaxis, these levels are slightly elevated at the time of the anaphylaxis, but return to normal. A patient with mastocytosis, a group of disorders characterized by pathologic mast cells infiltrating the skin, will consistently have elevated tryptase levels. Seasonal allergies associated with pollen, and asthma bronchospasm also should be considered as causes.

Although these exercise-induced anaphylaxis episodes can occur at any age, they are most frequent in the adolescent age group, probably because that’s the time most of this population are involved in organized sports. Upon presentation, a careful detailed history will help to identify the cause of anaphylaxis and result in quicker resolution.

Treatment includes avoidance of the offending agent if identified and an antihistamine, and if symptoms do occur, ceasing exercise immediately to avoid a full-blown anaphylactic reaction.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected].

Anaphylaxis is a relatively common occurrence for many adolescents. As primary care doctors, we normally see the patient after the acute phase, and then are required to do the detective work to figure out the causes of the episode. The cause may be obvious, but many times we have to hope for another occurrence with similar circumstances to identify it. Surprisingly, the cause may not be what you think. Factors that contribute to an anaphylaxis response may be related to activity, timing of food ingestion, an environmental factor, or medication.

Let’s look at just one type, exercise-induced anaphylaxis. It’s divided into two categories: food dependent and nonfood dependent. Both are described as an induction of itching, urticaria, and fatigue, with progression to angioedema and hypotension, associated with exercise (J. Allergy Clin. Immunol. 1980;66:106-11).

Food-dependent exercise-induced anaphylaxis occurs when exercise is started 30 minutes after ingesting food. This may be difficult to identify because patients react to the food only if they exercise, so food is usually eliminated as a cause. Wheat and wheat flour are common culprits for this type of reaction because of the omega-5 gliadin, which is the protein in gluten (J. Allergy Clin. Immunol. 1991;87:34-40). In one study, larger amounts of the suspected agent were given; hives and angioedema did start to occur in 20% of patients challenged, which suggested that there was likely a baseline allergy to the food, and exercise itself might be a cofactor in augmentation of the allergic reaction.

In nonfood-dependent exercise-induced anaphylaxis, symptoms of itching, urticaria, and fatigue can occur 5-30 minutes after the start of exercise. Although bronchospasm is rare, it can occur along with angioedema, nausea, vomiting, and hypotension, and can even be fatal if exercise continues. If exercise is stopped, it usually resolves. However, many people try to push through it, which only worsens the symptoms.

Cofactors associated with nonfood-dependent exercise-induced anaphylaxis are ingestion of alcohol and an NSAID several hours beforehand. These agents also might be overlooked if well tolerated independently (Br. J. Dermatol. 2001;145:336-9).

Timing of the episode also plays a role. Premenstrual syndrome can be a factor in augmentation of anaphylaxis, so it also should be considered. Knowing the date of the last menstrual cycle and identifying if the anaphylaxis is episodic will identify premenstrual syndrome as a cause.

The work-up should include standard allergy testing and determination of tryptase levels. Skin testing is essential to identify offending agents, and is rarely negative. If a food is suspected and skin testing is negative, repeat the skin testing in 6 months. In one study, wheat extract was found to be positive in only 29% of persons suspected of having a wheat allergy, but when the paste of wheat flour was tested, 80% were identified. The ImmunoCAP Test also was found to have a sensitivity of 80%, so it is a valuable test to try along with the skin prick.

Tryptase levels should be evaluated because in nonfood-dependent exercise-induced anaphylaxis, these levels are slightly elevated at the time of the anaphylaxis, but return to normal. A patient with mastocytosis, a group of disorders characterized by pathologic mast cells infiltrating the skin, will consistently have elevated tryptase levels. Seasonal allergies associated with pollen, and asthma bronchospasm also should be considered as causes.

Although these exercise-induced anaphylaxis episodes can occur at any age, they are most frequent in the adolescent age group, probably because that’s the time most of this population are involved in organized sports. Upon presentation, a careful detailed history will help to identify the cause of anaphylaxis and result in quicker resolution.

Treatment includes avoidance of the offending agent if identified and an antihistamine, and if symptoms do occur, ceasing exercise immediately to avoid a full-blown anaphylactic reaction.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected].

Anaphylaxis is a relatively common occurrence for many adolescents. As primary care doctors, we normally see the patient after the acute phase, and then are required to do the detective work to figure out the causes of the episode. The cause may be obvious, but many times we have to hope for another occurrence with similar circumstances to identify it. Surprisingly, the cause may not be what you think. Factors that contribute to an anaphylaxis response may be related to activity, timing of food ingestion, an environmental factor, or medication.

Let’s look at just one type, exercise-induced anaphylaxis. It’s divided into two categories: food dependent and nonfood dependent. Both are described as an induction of itching, urticaria, and fatigue, with progression to angioedema and hypotension, associated with exercise (J. Allergy Clin. Immunol. 1980;66:106-11).

Food-dependent exercise-induced anaphylaxis occurs when exercise is started 30 minutes after ingesting food. This may be difficult to identify because patients react to the food only if they exercise, so food is usually eliminated as a cause. Wheat and wheat flour are common culprits for this type of reaction because of the omega-5 gliadin, which is the protein in gluten (J. Allergy Clin. Immunol. 1991;87:34-40). In one study, larger amounts of the suspected agent were given; hives and angioedema did start to occur in 20% of patients challenged, which suggested that there was likely a baseline allergy to the food, and exercise itself might be a cofactor in augmentation of the allergic reaction.

In nonfood-dependent exercise-induced anaphylaxis, symptoms of itching, urticaria, and fatigue can occur 5-30 minutes after the start of exercise. Although bronchospasm is rare, it can occur along with angioedema, nausea, vomiting, and hypotension, and can even be fatal if exercise continues. If exercise is stopped, it usually resolves. However, many people try to push through it, which only worsens the symptoms.

Cofactors associated with nonfood-dependent exercise-induced anaphylaxis are ingestion of alcohol and an NSAID several hours beforehand. These agents also might be overlooked if well tolerated independently (Br. J. Dermatol. 2001;145:336-9).

Timing of the episode also plays a role. Premenstrual syndrome can be a factor in augmentation of anaphylaxis, so it also should be considered. Knowing the date of the last menstrual cycle and identifying if the anaphylaxis is episodic will identify premenstrual syndrome as a cause.

The work-up should include standard allergy testing and determination of tryptase levels. Skin testing is essential to identify offending agents, and is rarely negative. If a food is suspected and skin testing is negative, repeat the skin testing in 6 months. In one study, wheat extract was found to be positive in only 29% of persons suspected of having a wheat allergy, but when the paste of wheat flour was tested, 80% were identified. The ImmunoCAP Test also was found to have a sensitivity of 80%, so it is a valuable test to try along with the skin prick.

Tryptase levels should be evaluated because in nonfood-dependent exercise-induced anaphylaxis, these levels are slightly elevated at the time of the anaphylaxis, but return to normal. A patient with mastocytosis, a group of disorders characterized by pathologic mast cells infiltrating the skin, will consistently have elevated tryptase levels. Seasonal allergies associated with pollen, and asthma bronchospasm also should be considered as causes.

Although these exercise-induced anaphylaxis episodes can occur at any age, they are most frequent in the adolescent age group, probably because that’s the time most of this population are involved in organized sports. Upon presentation, a careful detailed history will help to identify the cause of anaphylaxis and result in quicker resolution.

Treatment includes avoidance of the offending agent if identified and an antihistamine, and if symptoms do occur, ceasing exercise immediately to avoid a full-blown anaphylactic reaction.

Dr. Pearce is a pediatrician in Frankfort, Ill. E-mail her at [email protected].