Megan E. Wren
Screening for Disease
GENERAL PRINCIPLES
· The benefit of screening depends on the prevalence of the disease, the sensitivity and specificity of the screening test, the acceptability of the test to the patient, and, most importantly, the ability to change the natural course of disease with treatment.
· For many diseases, there is a lack of definitive evidence regarding the effect of screening on morbidity and mortality.
· Studies of the benefits of screening are susceptible to several forms of bias:
o Lead-time bias refers to the overestimation of survival duration among screen-detected cases when survival is measured from the time of diagnosis.
o Length bias refers to the fact that slow-growing cancers have a long period of time in which they are asymptomatic but potentially detectable by screening tests (preclinical period). Aggressive tumors have a shorter preclinical period, so they are less likely to be detected in a screening program. Therefore, screening programs tend to detect less aggressive disease.
o Overdiagnosis is an extreme form of length bias in which the diagnosed cancer is so slowly progressive that it never would have become clinically evident (and therefore would not have required treatment).
o Volunteer bias refers to the fact that people who sign up for screening studies are not necessarily representative of the general population. Some may have subtle symptoms or risk factors for the disease. Most study participants tend to be more concerned about their health, have healthier habits, and are more compliant with therapy, leading to improved outcomes.
· Statistics on screening efficacy are frequently misunderstood by both physicians and the public.1,2 Because of the biases outlined above, “x-year survival” is a misleading measure of the benefit of screening. Mortality rates are a more appropriate measure of the effect of screening and treatment.
· Many areas of controversy exist, including ages to start and stop screening, which tests to use, or whether to screen at all.
· Various professional organizations have made recommendations regarding screening for disease; these guidelines apply only to asymptomatic patients at average risk, and they must be individualized. Some of the most widely cited organizations include the following:
o The American Cancer Society (ACS, www.cancer.org, last accessed December 23, 2014).
o The U.S. Preventive Services Task Force (USPSTF, www.ahrq.gov/clinic/uspstfix.htm, last accessed December 23, 2014).
o The American College of Physicians (ACP, www.acponline.org/clinical/guidelines/?hp, last accessed December 23, 2014).
o The National Cancer Institute (NCI, www.nci.nih.gov, last accessed December 23, 2014).
o The American Congress of Obstetrics and Gynecology (ACOG, www.acog.org, last accessed December 23, 2014).
· Table 5-1 presents a simplified screening schedule.
TABLE 5-1 Simplified Screening Schedule for Asymptomatic Average-Risk Persons
CANCER SCREENING
Research evidence has often been inadequate to reach definitive conclusions regarding how, when, whom, and whether to screen for various cancers. The guidelines below are a synthesis of the recommendations of the major organizations.
Breast Cancer Screening
· Breast cancer is common in the United States.
o Breast cancer is the most commonly diagnosed invasive cancer in US women: Approximately one in eight (12.5%) will develop breast cancer by age 90.3
§ Conversely, 88% will not develop breast cancer.
§ Many women greatly overestimate their risk of breast cancer. In one study, 89% of women overestimated their risk with an average estimate of 46% lifetime risk (more than triple the actual risk).4
o Breast cancer mortality in US women is second only to lung cancer; approximately 1 in 36 (2.8%) will die of breast cancer.3
o African American women have a lower incidence of breast cancer than white women, but a higher mortality rate.5
· Breast cancer mortality has declined approximately 30% over the past two decades, but there is controversy about the relative roles of screening versus improved treatments.
· Risk factors for breast cancer:
o Sex—breast cancer is 100 times more common in women than men.
o Age—about 75% of breast cancers occur after age 50.
o Family history—the risk is approximately doubled with one affected first-degree relative. The risk rises if there are multiple affected family members, especially if they had early-onset breast and/or ovarian cancer (suggestive of BRCA mutations).
o Estrogen—exogenous estrogen, early menarche, late menopause, nulliparity, or late first childbirth.
o Dense breast tissue.
o History of atypical hyperplasia on biopsy.
o History of radiation therapy to the chest in childhood/adolescence.
o Obesity.
o Drinking >2 alcoholic drinks/day.
o Protective factors include parity, breast-feeding, and exercise.
o The Gail model to estimate risk is available at www.cancer.gov/bcrisktool (last accessed December 23, 2014); it is less accurate in women with a strong family history.
· The benefits of screening are best proven for mammography in women ages 50 to 69.
o Women aged 40 to 49 have a lower incidence of breast cancer and denser breasts (thus lower sensitivity and specificity of screening), leading to lower predictive values. The USPSTF review stated that “for biennial screening mammography in women aged 40 to 49 years, there is moderate certainty that the net benefit is small.” They emphasized the lower incidence in this group and the adverse consequences of screening.6,7
o Data are limited for women ages 70 and over, and older women have competing causes of mortality, limiting the benefit of cancer screening.
· Potential harms from screening include the following:
o False positives leading to additional imaging.
o False positives leading to unnecessary biopsies (a decade of annual screening is estimated to result in almost 20% of women referred for a biopsy).8
o Overdiagnosis and subsequent treatment.
o Mammography is often uncomfortable and may be anxiety provoking.
· It has been shown in randomized trials that teaching breast self-examination (BSE) does not save lives.9 Many groups now endorse teaching “breast self-awareness” rather than formal BSE teaching.10
· Clinical breast exam (CBE) may modestly improve cancer detection rates if experienced clinicians use very careful technique.11
· Recommendations of some major groups are as follows.
o The USPSTF issued updated recommendations in 200912:
§ Women aged 50 to 74 years should have mammography every 2 years.
§ Screening mammography should not be done “routinely” for women ages 40 to 49 years. Women and their doctors should base the decision to start mammography before age 50 years on the risk for breast cancer and preferences about the benefits and harms.
§ Current evidence is insufficient to assess the benefits and harms of CBE or screening mammography in women 75 years or older.
§ The USPSTF recommends against teaching patients BSE.
o The ACS recommends the following13:
§ Ages 20 to 39: CBE every 3 years.
§ Ages 40 and over: annual CBE and annual mammography.
§ Optional BSEs.
§ No specific upper age limit is specified. “The decision to stop screening should be individualized based on the potential benefits and risks of screening within the context of overall health status and estimated longevity.”
§ Women at very high risk (>20% lifetime risk) should undergo magnetic resonance imaging (MRI) screening and mammography every year. Women at moderately increased risk (15% to 20% lifetime risk) should talk to their physicians about the benefits and limitations of MRI screening in addition to yearly mammography.
o The ACOG recommends the following10:
§ Ages 20 to 39: CBE every 1 to 3 years.
§ Ages 40 and over: annual CBE and annual mammography.
§ Over age 75, the decision to screen should be individualized.
§ “Breast self-awareness should be encouraged and can include breast self-examination.”
§ Women at very high risk (>20% lifetime risk) should have “enhanced screening” with annual mammography, CBE every 6 to 12 months, instruction in BSE, and possibly MRI.
Cervical Cancer Screening
· The effectiveness of cervical cancer screening has never been studied in a randomized trial but is supported by strong epidemiologic evidence: the cervical cancer death rate falls in proportion to the intensity of screening. Most cases of cervical cancer occur in unscreened or inadequately screened women.
· Cervical cytologic screening may be done with the conventional Pap smear or with liquid-based tests (method does not change screening frequency).
· For some age groups, cotesting with cytology plus testing for human papillomavirus (HPV) is an option.
· HPV vaccination does not change the screening guidelines.
· The ACS, USPSTF, and ACOG have similar recommendations, as summarized below.
· Do not begin screening until age 21 years regardless of sexual history.
o Under age 21, cervical cancer is quite rare (1 to 2 per million) while HPV infection is common and dysplasia may occur but both usually spontaneously remit.
o Early screening may lead to anxiety, expense, and morbidity (excisional procedures on the cervix).
· Women aged 21 to 29 years should be screened every 3 years with cytology only. HPV testing would detect many transient infections without carcinogenic potential.
· Women aged 30 and older may be screened by cytology plus HPV cotesting every 5 years (preferred) or with cytology alone every 3 years.
· Women who have had a total hysterectomy (including removal of the cervix) for benign disease may stop cervical cancer screening.
· Screening may be stopped at age 65 in women who have had adequate screening (three consecutive negative Pap tests or two consecutive negative HPV/Pap cotests within past 10 years and most recent test within 5 years).
· Risk factors and special cases:
o In women with HIV infection, the Centers for Disease Control and Prevention (CDC) recommends cervical cytology screening twice in the 1st year after diagnosis and annually thereafter while the ACOG recommends annual cytology starting at age 21.14
o ACOG recommends that women with a history of high-grade dysplasia or cancer should continue routine age-based testing for 20 years, even past age 65.
o More frequent screening may be required in women with a history of prenatal exposure to diethylstilbestrol (DES) and women who are immunocompromised (such as organ transplantation).
Colorectal Cancer Screening
· Colorectal cancer (CRC) has a lifetime incidence of about 5%, and about one-third of those will die from it, making CRC the third leading cancer killer of men and of women (second for men and women combined).
· Screening for CRC is associated with decreases in incidence as well as mortality, due to removal of premalignant adenomatous polyps, but only about two-thirds of Americans have been screened adequately.15
· CRC is more common in men (35% higher than in women), in African Americans (25% higher than in Whites), and with advancing age (90% diagnosed after age 50).5
· Other risk factors include:
o Personal history of CRC or adenomatous polyps (especially if polyps are multiple, large [>1 cm], or villous/tubulovillous).
o Family history of polyps or CRC. The risk is doubled for those with one first-degree relative with CRC and further increased for those with multiple affected relatives or relatives with early-onset CRC (age <50).
o Genetic syndromes including familial adenomatous polyposis (FAP) and the Lynch syndrome/hereditary nonpolyposis colorectal cancer (HNPCC) syndrome.
o Inflammatory bowel disease, especially ulcerative colitis with pancolitis.
o History of abdominal radiation therapy in childhood.
o There may be an increased risk of CRC associated with obesity, alcohol consumption, smoking, physical inactivity, and dietary factors (red meat, low fiber, few fruits and vegetables, low dairy).
· Data suggest a protective effect for the use of aspirin and other nonsteroidal anti-inflammatory drugs.
· Screening strategies fall into 2 main categories:
o Stool-based tests that primarily detect cancer: guaiac-based fecal occult blood testing (gFOBT), fecal immunochemical test (FIT), or stool DNA testing
o Tests that detect both cancer and adenomatous polyps, thus permitting polyp removal for cancer prevention: flexible sigmoidoscopy (FSIG), colonoscopy, barium enema, or CT colonography
· For any test other than colonoscopy, any abnormalities must be followed up with a full colonoscopy, not just repeat testing.
· A brief summary of screening tests and recommended intervals includes:
o Annual gFOBT with a high sensitivity test such as Hemoccult SENSA (not Hemoccult II):
§ Home collection of three specimens (in-office rectal exam is not an acceptable stool test for CRC screening).
§ Modest test sensitivity and specificity but has been shown in randomized controlled trials (RCTs) to lower CRC mortality.
o Annual FIT, which detects human globin from lower GI bleeding (globin from upper GI sources is digested) and is therefore more specific.
o Stool DNA test, interval uncertain.
o FSIG every 5 years:
§ Requires a limited bowel prep; no sedation required.
§ Colonic perforation is rare (<1 in 20,000).
§ Only examines the distal colon but has been shown to lower CRC mortality.
o Air contrast barium enema (ACBE) every 5 years:
§ Requires a full bowel prep; no sedation is used and the test may be uncomfortable.
§ Sensitivity is much lower than colonoscopy.
o Computed tomography colonography (CTC) or “virtual colonoscopy” every 5 years:
§ Requires a full bowel prep and air insufflation.
§ Sensitivity is probably comparable to colonoscopy.
§ Patients with large polyps must be referred for colonoscopic resection, but uncertainty exists about management of small (<6 mm) polyps.
o Colonoscopy every 10 years:
§ Requires a full bowel prep and sedation.
§ Regarded as the gold standard, but may miss 5% to 12% of lesions >1 cm.
§ Lesions can be resected during the procedure.
§ Risk of colonic perforation is about 1 in 1,000 and also can cause bleeding and cardiovascular complications.
· Current guidelines were published in 2012 by the ACP,16 in 2008 by the USPSTF,17 and in 2008 by a joint guideline18 published by ACS, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.
· The USPSTF recommendations include the following:
o Screen adults ages 50 to 75 using annual high-sensitivity gFOBT, or sigmoidoscopy every 5 years combined with high-sensitivity gFOBT every 3 years, or colonoscopy every 10 years.
o Do not routinely screen those aged 76 to 85 years, but there may be considerations that support screening in an individual patient.
o Screening is not recommended >85 years of age.
· The ACP recommends that
o Clinicians perform individualized assessment of risk for CRC in all adults.
o Average-risk adults should start CRC screening at age 50, using annual gFOBT, annual FIT, FSIG every 5 years, or colonoscopy every 10 years.
o High-risk adults should start screening with colonoscopy at age 40 or 10 years younger than the age at which the youngest affected relative was diagnosed with CRC.
o Screening should stop at age 75 or if life expectancy is <10 years.
· The joint guideline recommends that
o Screening for CRC in average risk, asymptomatic adults should begin at age 50.
o CRC screening is not appropriate if the patient is not likely to benefit from screening due to life-limiting comorbidity.
o Colon cancer prevention should be the primary goal of screening.
o Acceptable screening tests include annual gFOBT with a high sensitivity test, or annual FIT, or stool DNA test, interval uncertain.
o Preferred tests detect adenomatous polyps and can prevent cancer: FSIG every 5 years, ACBE every 5 years, CTC every 5 years, or colonoscopy every 10 years.
· High-risk persons need earlier and/or more frequent screening. These include those with a personal history of CRC or adenomatous polyps, inflammatory bowel disease, endometrial cancer before age 50, a hereditary CRC syndrome, or a strong family history of CRC or polyps.
o For those with CRC or adenomatous polyps in a first-degree relative <60 years or in two first-degree relatives of any age, they should be screened with colonoscopy every 5 years. Screening should begin at age 40, or 10 years before the youngest case in the immediate family, whichever is earlier.
o For those with CRC or adenomatous polyps in a first-degree relative at 60 or older, or two second-degree relatives with CRC, screening should begin at age 40 with any recommended form of testing at the usual intervals.
Lung Cancer Screening
· Lung cancer is the number one cause of cancer-related death in men and in women. Approximately 90% of cases occur in current or former smokers; smoking cessation is the single most important factor in reducing lung cancer mortality.
· Multiple randomized trials have demonstrated no mortality benefit to screening with plain chest radiography (CXR), with or without sputum cytology.
· Observational trials in the late 1990s showed that low-dose (2 mSv), single breath-hold, helical CT (LDCT) scans could detect early-stage lung cancers much more effectively than CXRs.
· The National Lung Screening Trial (NLST) published in 2011 was the first randomized trial to show a statistically significant benefit to CT screening for lung cancer.19
o The trial compared annual LDCT to CXR for 3 years in more than 50,000 people ages 55 to 74; participants had at least 30 pack-years of smoking, including current smokers and former smokers who had quit within 15 years.
o At a median follow-up of 6.5 years, there was a relative mortality reduction of 20% for lung cancer deaths and 6.7% reduction in all-cause mortality in the LDCT group.
o To prevent one lung cancer death, the number needed to screen with LDCT was 320.
o A substantial number of participants had an abnormal screening test (24% in the LDCT group and 6.9% in the CXR group), >90% of which were false positives. Most only required additional imaging, but some subjects required invasive procedures, including surgery. Complications from the diagnostic workup occurred at a low rate, about 1.5% of the participants who had abnormal screening tests.
· Lung cancer screening recommendations are in evolution. The USPSTF guidelines are undergoing review.
· A number of expert organizations have issued at least preliminary guidelines, including the ACS,20 the National Comprehensive Cancer Network,21 American College of Chest Physicians,22 and others. In general, they support LDCT screening in individuals similar to those in the NLST:
o Ages 55 to 74.
o At least 30-pack-years of smoking.
o Current smoker or quit within the past 15 years.
o Screening is not appropriate for patients with severe comorbidities that limit life expectancy or would preclude potentially curative treatment.
o The decision to start screening should be preceded by a process of informed and shared decision making, with discussion of the potential benefits, limitations, and harms associated with screening.
Prostate Cancer Screening
· Prostate cancer is the second leading cause of cancer-related death in US men and is the most commonly diagnosed cancer in US men, with a lifetime risk of about 1 in 6.
· The incidence increases with age. There is a higher incidence and earlier age of onset in African American men. The risk is higher in those with affected first-degree relatives or inherited cancer syndromes such as BRCA or Lynch syndrome (HNPCC).
· Although 17% of men will be diagnosed with prostate cancer, only 2.4% will die of it.
· Screening for prostate cancer is a controversial topic. Randomized controlled trials have shown small or no survival benefit in screened groups. Many men die “with” rather than “of” prostate cancer. Treatment has potential harms, including erectile dysfunction, urinary incontinence, and bowel problems.
· The USPSTF recommends against prostate-specific antigen (PSA) testing, concluding that screening produces more harms than benefits.23
· The ACS stresses the need for informed decision making with adequate provision of information about the uncertainties, risks, and potential benefits associated with prostate cancer screening.24
o This information should be provided starting at age 50 (at 40 to 45 in higher-risk men).
o Men with <10-year life expectancy should not be offered prostate cancer screening. At age 75, only about half of men have a life expectancy of 10 years or more.
o Key discussion points include the following:
§ Screening may be associated with a reduction in the risk of dying from prostate cancer; however, evidence is conflicting and experts disagree about the value of screening.
§ Not all men whose prostate cancer is detected through screening require immediate treatment. It is not currently possible to predict which men are likely to benefit from treatment.
§ Treatment for prostate cancer can lead to urinary, bowel, sexual, and other health problems. These problems may be significant or minimal, permanent, or temporary.
§ The PSA and digital rectal exam (DRE) may produce false-positive or false-negative results.
§ Abnormal results require prostate biopsies that can be painful, may lead to complications like infection or bleeding, and can miss clinically significant cancer.
o If screening is elected, the ACS recommends PSA with or without DRE.
§ Initial PSA <2.5 ng/mL: screen every 2 years.
§ Initial PSA ≥2.5 ng/mL: screen annually.
§ PSA >4.0 ng/mL: refer for biopsy (2.5 to 4.0 ng/mL, individualized assessment).
· The ACP recommends that PSA testing should only be done in patients with a clear preference for screening.25
o Clinicians should inform men ages 50 to 69 about the limited potential benefits and substantial harms of screening for prostate cancer.
o Screening should not be done in average-risk men aged <50 or >69 nor those with a life expectancy of <10 to 15 years.
· The American Urological Association (AUA) published its guideline online in 2013.26 Recommendations include:
o Men <40 years of age should not be screened.
o Average-risk men <55 years of age should not be routinely screened. For men 40 to 55 years of age who are at higher risk (family history or African American), decisions should be individualized.
o For men ages 55 to 69, they strongly recommend shared decision making, based on a man’s values and preferences after weighing the benefits against the known potential harms associated with screening and treatment. One prostate cancer death is averted for every 1,000 men screened for a decade.
o Men should not be routinely screened if they are >70 years of age or have a life expectancy <10 to 15 years. Some men aged >70 years who are in excellent health may benefit from prostate cancer screening.
o If men choose PSA screening, an interval of 2 years or more may be preferred over annual screening as it is expected that screening intervals of 2 years preserve the majority of the benefits and reduce overdiagnosis and false positives. Intervals for rescreening can be individualized by a baseline PSA level.
o There is no evidence that DRE is beneficial as a primary screening test.
Ovarian Cancer Screening
· Ovarian cancer is uncommon (2% lifetime risk) but often lethal because only 15% are diagnosed while still localized to the ovary.27 Detection is hampered by the deep anatomic location of the ovary and because ovarian cancer is often multifocal and extraovarian, even at early stages.
· Risk factors for ovarian cancer include:
o Family history, especially the inherited cancer syndromes (BRCA, Lynch syndrome). The BRCA1 gene mutation conveys a lifetime risk of about 40%, and the BRCA2 gene mutation conveys a lifetime risk of about 20%.
o Other risk factors include a history of infertility, polycystic ovarian syndrome, endometriosis, postmenopausal hormone replacement therapy, and cigarette smoking.
o Protective factors include past use of oral contraceptives, history of breast-feeding >12 months, previous pregnancy, tubal ligation, and hysterectomy.
· Pelvic examination is not effective for screening due to poor sensitivity and specificity.
· Ovarian cancer is occasionally found incidentally on a Pap smear (sensitivity <30%).
· The tumor marker CA 125 has limited sensitivity and specificity.
o Only about half of early ovarian cancers have elevated levels of CA 125.
o False positives are too common (about 1%) for an effective screening test. Levels vary with the menstrual cycle, age, ethnicity, and smoking, and CA 125 can be increased with endometriosis, uterine leiomyomata, cirrhosis, ascites from any cause, and a variety of cancers.
o Assessment of changes in CA 125 levels over time may have better test characteristics.
· Transvaginal ultrasound (TVU) has limited sensitivity and specificity for ovarian cancer screening.
· A large randomized trial in the US showed that screening with CA 125 and TVU did not improve ovarian cancer mortality (relative risk 1.18, screened vs. usual care).28 Positive predictive value was only about 1%. For every screen-detected ovarian cancer, approximately 20 women underwent surgery; 20% of those surgeries resulted in major complications.
· No organization recommends screening average-risk women for ovarian cancer.
o The USPSTF specifically recommends against screening due to lack of benefit and potential harms (unnecessary surgeries).29
o ACOG concluded that currently, there is no effective strategy for ovarian cancer screening.30 Clinicians should have a high index of suspicion when women present with symptoms commonly associated with ovarian cancer: pelvic or abdominal pain, increase in abdominal size or bloating, and difficulty eating or feeling full. High-risk women may be offered the combination of pelvic examination, TVU, and CA 125 testing.
Testicular Cancer
· USPSTF recommends against screening for testicular cancer in adolescent or adult males.
o The incidence is low (approximately 1% of cancers in men).
o Testicular germ cell tumors are one of the most curable solid neoplasms (overall cure rate >90%).
o No evidence has shown that routine screening would improve health outcomes.
· The AUA recommends monthly testicular self-exams.
Screening for Other Cancers
· Routine population screening is not recommended for the following cancers: endometrial, testicular, bladder, thyroid, oral cavity, or skin. Clinicians should be vigilant for early symptoms of possible cancer in those sites.
· The ACS recommends that “the cancer-related checkup should include examination for cancers of the thyroid, testicles, ovaries, lymph nodes, oral cavity, and skin, as well as health counseling about tobacco, sun exposure, diet and nutrition, risk factors, sexual practices, and environmental and occupational exposures.”
SCREENING FOR OTHER CONDITIONS
Hypertension
· The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends that all patients should have their blood pressure (BP) measured every 2 years.31 See Table 5-2 for the classification of BP levels. JNC 8 does not specifically address screening or classification.
· Lifestyle modification includes counseling on weight loss, aerobic exercise, limiting alcohol intake, and reduction in sodium intake.
· Treatment of hypertension is discussed in detail in Chapter 6.
TABLE 5-2 Classification, Follow-Up, and Treatment of Hypertension
Data from Chobanian AV, Bakris GL, Black HR, et al. National High Blood Pressure Education Program Coordinating Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560-2572.
Dyslipidemia
· The recent American College of Cardiology/American Heart Association (ACC/AHA) guidelines for cardiovascular risk assessment recommend screening those aged 20 to 79 years without atherosclerotic cardiovascular disease every 4 to 6 years and estimating the 10-year risk.32 The risk calculator may be found at http://tools.cardiosource.org/ASCVD-Risk-Estimator/ (last accessed December 23, 2014).
· The USPSTF strongly recommends screening for lipid disorders starting at age 35 in men and age 45 in women. Younger adults should be screened if they have other risk factors for coronary heart disease (CHD).
· The treatment of dyslipidemia is discussed in detail in Chapter 11.
Diabetes Mellitus
· The American Diabetes Association annually updates recommendations for diabetes mellitus (DM) care. The 2013 guidelines that recommend screening are presented here.33
· The A1C, fasting plasma glucose, or 75-g 2-hour oral glucose tolerance test (OGTT) are all acceptable screening tests. Healthy adults should be tested starting at age 45.
· Consider testing all adults who are overweight (BMI ≥25 kg/m2) and have additional risk factors: hypertension, HDL cholesterol <35 mg/dL or triglyceride level >250 mg/dL, cardiovascular disease, women with polycystic ovary syndrome, previous A1C ≥5.7%, impaired glucose tolerance or impaired fasting glucose, women who delivered a baby weighing >9 pounds or who were diagnosed with gestational DM, physical inactivity, first-degree relative with DM, high-risk ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander), and other risk conditions (e.g., severe obesity, acanthosis nigricans, or use of glucocorticoids or antipsychotics).
· If results are normal, testing should be repeated at least every 3 years, with consideration of more frequent testing depending on initial results and risk status.
· Those with prediabetes should be tested yearly:
o A1C 5.7% to 6.4%
o Fasting glucose 100 to 125 mg/dL
o OGTT 2-hour value of 140 to 199 mg/dL
Abdominal Aortic Aneurysm
· The USPSTF recommends one-time screening for abdominal aortic aneurysm (AAA) by ultrasonography in men aged 65 to 75 years who are current or former smokers.34
· They make no recommendation for or against screening for AAA in patients with no smoking history.
· They recommend against routine screening for AAA in women.
Coronary Heart Disease
· The USPSTF recommends against routine screening with resting ECG or exercise treadmill test for the prediction of CHD in low-risk adults and found insufficient evidence to recommend for or against routine screening in adults at intermediate or high risk for CHD events.35 The USPSTF found insufficient evidence to recommend for or against the use of nontraditional risk factors such as C-reactive protein (CRP), ankle-brachial index (ABI), coronary artery calcification (CAC) score on electron beam CT, homocysteine level, or lipoprotein(a) level.36
· As noted above, recent ACC/AHA guidelines for cardiovascular risk assessment recommend screening those ages 20 to 79 years without atherosclerotic cardiovascular disease every 4 to 6 years for risk factors and estimating the 10-year risk.32 Additionally, if a risk-based treatment decision is unclear, high-sensitivity CRP (hs-CRP) (≥2 mg/L), CAC scoring (≥300 Agatston units or ≥75th percentile for age, sex, and ethnicity), or ABI (<0.9) may provide further guidance. Lipoprotein(a), albuminuria, renal function, cardiorespiratory fitness testing, and carotid intima-media thickness (CIMT) are of unclear or limited value.
Peripheral Arterial Disease
· The USPSTF recommends against routine screening for peripheral arterial disease (PAD) because there is little evidence that treatment of PAD at this asymptomatic stage of disease, beyond treatment based on standard cardiovascular risk assessment, improves health outcomes.37
· As noted, the ACC/AHA has said that measurement of the ABI is reasonable for cardiovascular risk assessment in asymptomatic adults for whom risk-based treatment decisions are unclear.32
Thyroid Disease
Screening for thyroid disease is not routinely recommended, but clinicians should keep a low threshold for measurement of thyroid-stimulating hormone for subtle or nonspecific symptoms, especially in older women (see Chapter 21).
Obesity
· Periodic height and weight measurements are recommended for all patients.
· The body mass index (BMI) is the body weight in kilograms divided by the square of the height in meters.
o BMI 18.5 to 24.9 kg/m2 is considered normal.
o BMI >25 kg/m2 is considered overweight.
o BMI 30 to 34.9 kg/m2 is class I obesity.
o BMI 35 to 39.9 kg/m2 is class II obesity.
o BMI ≥40 kg/m2 is class III or morbid obesity.
· BMI may overestimate the degree of obesity in extremely muscular individuals (such as professional athletes).
· For persons with a BMI of 25 to 35, it can be useful to measure the waist circumference. Increased morbidity is associated with waist >102 cm (40 inches) in men and 88 cm (35 inches) in women.
Osteoporosis
· The USPSTF recommends screening for osteoporosis in38:
o Women age ≥65 years.
o Women <65 years whose risk factors put them at a fracture risk equivalent to a 65-year-old white woman.
o Evidence is insufficient to assess the balance of benefits and harms of screening for osteoporosis in men.
· National Osteoporosis Foundation (NOF) recommends39:
o All postmenopausal women and men ≥50 should be evaluated for osteoporosis risk and risk for falling.
o Bone mineral density (BMD) testing should be considered for
§ All women ≥65 and men ≥70
§ Persons with clinical risk factors for fracture if they are men ages 50 to 69 and postmenopausal or perimenopausal women
§ Adults with a fracture after age 50
§ Adults with a condition (e.g., rheumatoid arthritis) or taking a medication associated with bone loss (e.g., glucocorticoids equivalent to ≥5 mg/day prednisone for 3 or more months)
Sexually Transmitted Diseases
· The CDC website, www.cdc.gov (last accessed December 23, 2014), has up-to-date recommendations about screening for sexually transmitted disease (STD). Basic guidelines are as follows:
o Sexually active men who have sex with men (MSM) should be screened annually for HIV (in uninfected patients) and for bacterial STDs, such as syphilis, gonorrhea, and chlamydia.
o MSM who engage in higher-risk behaviors (such as multiple or anonymous partners, or sex in conjunction with illicit drug use) should be screened every 3 to 6 months.
o Sexually active females aged ≤25 years should be screened for chlamydia testing annually and gonorrhea testing annually for those at risk.
· HIV screening:
o HIV testing should be encouraged for adolescents who are sexually active and those who use injection drugs.
o Individuals aged 13 to 64 should get tested at least once in their lifetimes and those with risk factors get tested at least annually.
o The USPSTF also supports widespread HIV screening for persons aged 15 to 65 years (younger adolescents and older adults who are at increased risk should also be screened), and for all pregnant women.40
Hepatitis C
The CDC and USPSTF recommend that everyone born 1945–1965 be screened for hepatitis C.41
Alcohol Abuse and Dependence
· Screening for alcohol abuse and dependence is an important part of the routine checkup (see Chapter 46).
· Definitions (from the National Institute on Alcohol Abuse and Alcoholism at www.niaaa.nih.gov, last accessed December 23, 2014):
o Heavy or at-risk drinking is diagnosed in the following group:
§ Men who consume >14 drinks per week or >4 drinks per occasion
§ Women who consume >7 drinks per week or >3 drinks per occasion
§ Elderly who consume >7 drinks per week or >3 drinks per occasion
o One drink is 12 g ethanol, as in 12 oz of beer, 5 oz of wine, or 1.5 oz of distilled spirits.
o Alcohol abuse is a maladaptive pattern of use; manifested by continued or recurrent use despite failure in major role obligations at work, school, or home; of use in physically hazardous situations, or of use despite alcohol-related legal, social, or interpersonal problems.
o Alcohol dependence is marked by tolerance, the presence of withdrawal symptoms on cessation, impaired control (drinking more/longer than intended), persistent desire, and continued use despite physical or psychological problems related to alcohol.
· The CAGE questions are a useful screening tool for alcohol dependence. Two positive responses are considered a positive test and indicate further assessment is warranted.
o Have you ever felt that you should Cut down on drinking?
o Have people Annoyed you by criticizing your drinking?
o Have you ever felt bad or Guilty about your drinking?
o Eye-opener: Have you ever had a drink first thing in the morning to steady your nerves or to get rid of a hangover?
Adult Immunizations
GENERAL PRINCIPLES
· Guidelines are subject to change over time and according to local public health conditions.
· Each patient’s clinical context should be considered and risks and benefits weighed.
· The following are general guidelines, and manufacturer’s information should be consulted regarding individual products.
· Various professional organizations make recommendations regarding immunization practices. The official national policy is determined by the following:
o The Department of Health and Human Services (HHS)
o The Centers for Disease Control and Prevention (CDC)
o The Advisory Committee on Immunization Practices (ACIP)
· The ACIP makes recommendations that are then reviewed by the director of the CDC and HHS. They become official policy when published in CDC’s Morbidity and Mortality Weekly Reports.
· Table 5-3 lists abbreviations used in this chapter regarding immunizations.
TABLE 5-3 Glossary of Vaccine-Related Abbreviations
RESOURCES FOR INFORMATION
Immunization guidelines are quite detailed and are periodically updated. Useful resources for accessible, up-to-date information include the following:
· The CDC vaccine information website (www.cdc.gov/vaccines, last accessed December 23, 2014) has extensive information including the General Recommendations on Immunization and recommendations for specific vaccines.
· The CDC publishes an adult immunization schedule annually (www.cdc.gov/vaccines/schedules/hcp/adult.html, lasted accessed December 23, 2014).
· “The Pink Book: Epidemiology & Prevention of Vaccine-Preventable Diseases” contains a wealth of information and is available in PDF format at www.cdc.gov/vaccines/pubs/pinkbook/index.html (last accessed December 23, 2014).
· The Immunization Action Coalition (IAC) website has educational materials, camera-ready and copyright-free, at www.immunize.org. They also have many translated documents for non–English-speaking patients. They have comprehensive vaccine information for the public at www.vaccineinformation.org (last accessed December 23, 2014).
LEGAL RESPONSIBILITIES OF THE PROVIDER
· Serious or unusual adverse events must be reported to the Vaccine Adverse Events Reporting System (VAERS), whether or not the provider thinks they are causally associated. Forms are available from the Food and Drug Administration at www.fda.gov/cber/vaers/vaers.htm (last accessed December 23, 2014).
· Federally approved Vaccine Information Statement must be given to all patients prior to administering vaccines. Copies are available from the CDC or at www.immunize.org (last accessed December 23, 2014).
· Permanent vaccination records must be maintained by all vaccine providers.
TIMING OF ADMINISTRATION
· Specified times are minimum intervals.
o Doses that are administered at shorter intervals may not result in adequate antibody response and should not be counted as part of a primary series.
o Delay or interruption in the immunization schedule does not require starting over or extra doses.
· Simultaneous administration of multiple vaccines improves compliance.
o In general, inactivated (killed) and most live vaccines can be administered at the same time at separate anatomic sites.
o Live parenteral vaccines (see Table 5-4) and live intranasal influenza vaccine (LAIV) should be administered at the same visit or should be separated by at least 4 weeks.
o Live oral vaccines (such as oral typhoid) may be given at any time before or after live parenteral vaccines or LAIV.
o Tuberculin test response can be inhibited by live virus vaccines. Tuberculin skin testing can be done on the same day as the vaccination or 4 to 6 weeks later.
· Antibody-containing blood products can interfere with the response to live virus vaccines, particularly measles and varicella (but not the zoster vaccine). The interactions can be complex, so the clinician should consult the CDC website, specifically the Pink Book, Chapter 2.
TABLE 5-4 Adult Immunizations
aFirst dose at time “0 month.”
bSee text for schedule for hemodialysis patients.
DTap, full dose diphtheria/tetanus toxoid plus acellular pertussis (pediatric only); DTP, full dose diphtheria/tetanus toxoid plus whole killed pertussis (pediatric only, no longer available in US) HPV, human papillomavirus; GBS, history of Guillain-Barré syndrome; IM, intramuscularly; IIV, inactivated influenza vaccine (injected); LAIV, live attenuated intranasal influenza vaccine MMR, measles, mumps, and rubella; Tdap, tetanus and reduced dose diphtheria toxoid with acellular pertussis vaccine; Td, tetanus and reduced dose diphtheria toxoids.
DOCUMENTATION OF PRIOR VACCINATIONS
· If records cannot be located, an age-appropriate schedule of so-called catch-up immunizations should be started. Persons who have served in the military usually have been vaccinated against measles, rubella, tetanus, diphtheria, and polio.
· Self-reported doses of influenza vaccine and pneumococcal polysaccharide vaccine are acceptable.
· Vaccines received outside the US are usually of adequate potency. Foreign records are acceptable if they include written documentation of the date of vaccination, and the schedule (age and interval) was comparable with that recommended in the United States.
HYPERSENSITIVITY TO VACCINE COMPONENTS
· Persons with a history of anaphylactic reactions to any vaccine component should not receive that vaccine, except under the supervision of an experienced allergist. Vaccines may have traces of egg protein or antibiotics; the manufacturer’s insert should be carefully checked.
· Contact dermatitis to neomycin is a delayed-type (cell-mediated) immune response, not anaphylaxis, and is therefore not a contraindication to vaccine use.
· Hypersensitivity to thimerosal is usually a local delayed-type or an irritant effect.
· Many vaccines may cause mild-to-moderate local or systemic adverse effects such as low-grade fever or injection site swelling, redness, or soreness. These are not a contraindication to future doses of the vaccine.
SPECIFIC VACCINES AND IMMUNOBIOLOGIC AGENTS
See the Specific Patient Groups section for age-based checklists and recommendations for persons who have chronic illnesses, are immunocompromised, are pregnant or breast-feeding, or are health care workers or travelers. Table 5-4 provides an overview of the schedules and contraindications.
Measles, Mumps, and Rubella
Indications
· Ensure that all adults are immune to measles, mumps, and rubella (MMR). Documentation of physician-diagnosed disease is not adequate evidence of immunity.
· Adequate evidence of immunity to measles or mumps can include any of the following:
o Documentation of at least 1 dose of live measles/mumps vaccine on or after the first birthday.
o Serologic evidence of immunity.
o Persons born before 1957 are considered immune, unless they are health care workers.
· Adequate evidence of immunity to rubella requires the following:
o Documentation of at least 1 dose of rubella vaccine on or after the first birthday
o Serologic evidence of immunity
· Nonimmune persons should receive 1 dose of MMR, especially women of childbearing years.
· A second dose of MMR (>1 month after first dose) is recommended for:
o Prior recipients of a killed measles vaccine or an unknown type from 1963 to 1967
o Health care workers (unless serologic evidence of immunity)
o All students (unless serologic evidence of immunity)
o Persons who travel outside the US
o HIV-infected persons without immunity to measles, rubella, and mumps, if the CD4 lymphocytes are ≥15% and ≥200/μL for ≥6 months
Postexposure Prophylaxis
· Live measles vaccine may prevent disease if given within 72 hours of exposure.
· Immune globulin (IG) may prevent or modify disease and provide temporary protection if given within 6 days of exposure.
o The dose is 0.25 mL/kg IM (maximum of 15 mL).
o Immunocompromised persons, irrespective of evidence of measles immunity, should receive 0.5 mL/kg IM (maximum 15 mL).
o After administration of IG, the passively acquired measles antibodies can interfere with the immune response to measles vaccination, so vaccination should be delayed for 6 months.
Contraindications, Side Effects, and Precautions
· MMR is a live attenuated virus and is therefore contraindicated in pregnancy. Pregnancy should be avoided for 3 months after MMR-containing vaccine. Close contact with a pregnant woman or immunocompromised person is not a contraindication to MMR vaccination (the vaccine is not shed).
· MMR is generally contraindicated in immunocompromised hosts. HIV-infected persons may be vaccinated with MMR if they lack evidence of measles immunity, are asymptomatic, and are not severely immunosuppressed (for adults CD4 lymphocytes ≥200/μL or >14%).
· Persons who have experienced a severe allergic reaction to a vaccine component or following a prior dose of measles vaccine should generally not be vaccinated with MMR.
o In the past, persons with a history of anaphylaxis to eggs were considered to be at increased risk for serious reactions from measles or mumps vaccines. However, anaphylactic reactions to these vaccines are not associated with hypersensitivity to egg antigens but to other components of the vaccines (such as gelatin or neomycin).
o MMR may be administered to egg-allergic persons without prior routine skin testing or the use of special protocols.42
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
· Adverse reactions may include fever (5% to 15%), rash (5%), arthralgias (up to 25% of adult females), or rarely thrombocytopenia or lymphadenopathy.
· Because blood products can interfere with the antibody response, MMR administration should be delayed (consult the CDC for exact intervals). However, rubella-susceptible women should be vaccinated immediately postpartum even if anti-Rho(D) (RhoGAM, WinRho, etc.) or other blood products were administered during pregnancy or at delivery. Antibody levels should be measured 3 months later to assess response.
· Tuberculin test response can be inhibited by live virus vaccines; tuberculosis skin testing can be done on the same day as the vaccination or 4 to 6 weeks later.
Tetanus, Diphtheria, and Pertussis Vaccines
Indications
· All adults of any age should complete a primary series of 3 doses of Td if they have not done so during childhood or if the vaccination history is uncertain.
o Tetanus vaccine was first widely used in the 1940s, so elderly persons may have never received a primary series.
o Doses that are given as part of wound management do count toward the 3 doses needed.
· A tetanus booster is recommended every 10 years, lifelong. Many adults are overdue for boosters.
· Only about one-third of tetanus cases result from puncture wounds; other sources include minor wounds, burns, frostbite, bullet wounds, crush injuries, and even chronic wounds such as abscesses and chronic ulcers (14% of cases). Approximately 4% of patients with tetanus recall no antecedent wound.
· Because infection does not confer complete immunity, tetanus patients should be immunized after recovery.
· See Figure 5-1 for guidelines for postexposure prophylaxis.
Figure 5-1 Guidelines for postexposure prophylaxis to prevent tetanus. aTetanus-producing wounds are often not the classic puncture wounds but can include minor wounds, burns, frostbite, bullet wounds, crush injuries, and chronic wounds such as abscesses and chronic ulcers. TIG, tetanus immunoglobulin; Td, tetanus and diphtheria toxoids, adsorbed.
Formulations
· Vaccine terminology can be confusing; all formulations contain a full dose of tetanus toxoid.
· DPT: No longer available in the US; pediatric use only and full dose of diphtheria toxoid plus whole killed pertussis.
· DTaP (Daptacel, Infanrix, and Tripedia brands): Pediatric use only, full dose of diphtheria toxoid plus acellular pertussis, and take care to avoid confusion with Tdap.
· DT: Pediatric use only; full dose of diphtheria toxoid.
· Td: For persons over age 7 years, reduced dose of diphtheria toxoid.
· Tdap (Adacel and Boostrix brands): for adults and children over age 10 (Boostrix) or 11 (Adacel) years; reduced dose of diphtheria toxoid plus acellular pertussis; and take care to avoid confusion with DTaP.
Tdap
· In 2005, a tetanus/diphtheria toxoid with acellular pertussis vaccine (Tdap) was approved for use in adolescents and adults.
· Many adults are susceptible to pertussis, so the vaccine should help to reduce pertussis morbidity among adults and reduce the transmission of pertussis to infants and in health care settings.
· The ACIP recommends a single dose of Tdap in the following circumstances:
o All adults who have not received Tdap previously or for whom vaccine status is unknown. Tdap can be administered regardless of interval since the most recent tetanus or diphtheria-containing vaccine.
o Tdap is especially important for adults who are close contacts of infants <12 months of age (e.g., parents, grandparents, or child care providers).
o Administer 1 dose to pregnant women during EACH pregnancy (ideally at 27 to 36 weeks’ gestation).
o Health care personnel with direct patient contact should receive a dose of Tdap.
o Adults with unknown or incomplete history of completing a 3-dose primary series of tetanus vaccine should begin or complete a primary vaccination series. Tdap should be substituted for a single dose of Td in the series, preferably the first dose.
o For wound management, Tdap is preferred to Td if the patient has not previously received Tdap.
Contraindications, Side Effects, and Precautions
· Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component is a contraindication.
· Too frequent administration can produce increased rates of local or systemic reactions due to antigen-antibody complexes (Arthus-type reaction).
· Urticarial or anaphylactic reactions can occur but are rare. If such a history exists, then serologic testing to determine immunity to tetanus can be performed to evaluate the need for a booster dose. If additional doses are needed to ensure immunity, referral to an allergist is indicated.
· Local reactions are common and consist of erythema, induration, or tenderness.
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
Influenza
· Influenza-associated deaths range from 3,000 to 49,000 per year. Persons most at risk for serious complications include the elderly, the very young, pregnant women, and persons with chronic illness.
· Antibodies from previous infections or vaccinations are not fully protective against new strains because the virus undergoes constant antigenic drift (point mutations) and occasional antigenic shift (change in subtype).
· Those who are at highest risk of the disease and its complications are also the least able to respond to vaccination. Overall, the vaccine is about 60% to 80% effective against vaccine-type viruses.
· Influenza vaccines available in the US include the following:
o The inactivated influenza vaccine (IIV), trivalent or quadrivalent, the common flu shot.
o High-dose IIV (Fluzone High-Dose, Sanofi Pasteur Inc.) contains four times the amount of antigen as regular IIV.
o The intranasally administered live attenuated influenza vaccine (LAIV) (FluMist, MedImmune); formerly trivalent, the LAIV became quadrivalent in 2013.
Indications
· Since 2010, the ACIP has recommended annual influenza vaccination for ALL persons age 6 months or older.
· IIV may be used in anyone aged 6 months or more.
· LAIV is indicated for healthy, nonpregnant persons aged 2 to 49 years. Possible advantages of LAIV include its potential to induce a broad mucosal and systemic immune response and the acceptability of an intranasal rather than intramuscular route of administration.
· Adults aged 65 years or older can receive the standard dose IIV or the high-dose IIV (Fluzone High-Dose).
Contraindications, Side Effects, and Precautions
· A previous severe allergic reaction (anaphylaxis) to influenza vaccine, regardless of the component suspected to be responsible for the reaction, is a contraindication to future receipt of the vaccine.
· Persons who experience only hives with exposure to eggs should receive IIV (rather than LAIV) with additional safety precautions (health care provider should be familiar with the potential manifestations of egg allergy, and vaccine recipients should be observed for at least 30 minutes for signs of a reaction after administration of each vaccine dose).43
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
· Side effects of the flu shot are usually limited to mild arm soreness. Placebo-controlled trials have demonstrated no increase in systemic symptoms.
· The flu shot is not a live virus and cannot cause the flu, but the live attenuated intranasal vaccine may cause rhinorrhea, nasal congestion, headache, or sore throat.
· The intranasal LAIV should not be used in
o Those aged <2 or >50 years
o Pregnant women
o Persons with chronic health problems
o Persons with a history of Guillain-Barré syndrome (GBS)
o Persons with a history of hypersensitivity, including anaphylaxis, to any of the components of LAIV or to eggs
o Children or adolescents receiving aspirin or other salicylates (because of the association of Reye syndrome with wild-type influenza virus infection)
o Health care workers and others who have close contact with severely immunocompromised persons who require protective environment (such as patients with stem cell transplants)
· GBS has not been associated with the influenza vaccine since the 1976 to 1977 swine flu vaccine (which was associated with approximately 5 to 10 excess cases of GBS/million vaccines).
· Persons with a history of egg allergy who have experienced only hives after exposure to egg should receive influenza vaccine, with the following additional safety measures:
o The IIV should be used, not LAIV.
o Vaccine should be administered by a health care provider who is familiar with the potential manifestations of egg allergy.
o Vaccine recipients should be observed for at least 30 minutes after administration of each vaccine dose.
· Persons who report having had severe reactions to egg (angioedema, respiratory distress, light-headedness, recurrent emesis, or who required medical intervention) should be referred to an experienced allergist for further risk assessment.
Pneumococcal Vaccine
· Streptococcus pneumoniae is a major cause of pneumonia, bacteremia, and meningitis and of over 4,000 deaths per year in the United States.
· Efficacy of the vaccine is controversial and is estimated at 50% to 80%. Because polysaccharide vaccines do not induce T-cell–dependent responses associated with immunologic memory, there is no true anamnestic response to additional doses of vaccine (although antibody levels will rise).
Formulations
· Pneumovax 23 (Merck) is a 23-valent polysaccharide vaccine (PPSV23), which contains polysaccharide antigen from 23 types of pneumococcal bacteria that cause 88% of bacteremic pneumococcal disease.
· Prevnar 13 (Wyeth) is a 13-valent pneumococcal conjugate vaccine (PCV13). It is used for routine immunization of infants and for certain adults (see Indications for PSV13 below).
Indications for PPSV23
· When indicated, PPSV23 should be administered to patients who are uncertain of their vaccination status.
· When PCV13 is also indicated, the PCV13 should be given before the PPSV23.
· PPSV23 should be given to all healthy persons age 65 years or older if
o Not previously vaccinated
o Unknown vaccination status
o Vaccinated 5 or more years ago and were <65 years old at first vaccination
· PPSV23 should be given to all adults aged 19 to 64 years with risk factors for invasive pneumococcal disease:
o Chronic heart disease (excluding hypertension, but including congestive heart failure or cardiomyopathy)
o Cigarette smoking
o Chronic lung disease (including chronic obstructive pulmonary disease or asthma)
o DM
o Cerebrospinal fluid (CSF) leaks
o Cochlear implant
o Alcoholism
o Chronic liver disease, including cirrhosis
o Persons with functional or anatomic asplenia (including sickle cell disease, other hemoglobinopathies, splenectomy)
o Immunocompromised persons (a second dose of PPSV23 is recommended 5 years after the first dose for persons with functional or anatomic asplenia and for immunocompromised persons):
§ Congenital or acquired immunodeficiencies
§ HIV infection
§ Chronic renal failure or nephrotic syndrome
§ Hematologic malignancies (leukemia, lymphoma, Hodgkin disease, or multiple myeloma)
§ Generalized malignancy
§ Diseases requiring treatment with immunosuppressive drugs, including long-term systemic corticosteroids or radiation therapy
§ Solid organ transplantation
Revaccination
· Revaccination is not routinely recommended. ACIP does not recommend multiple revaccinations because of insufficient data regarding clinical benefit, particularly the degree and duration of protection, and safety.
· Revaccination is contraindicated if the patient had a severe reaction to the prior dose.
· A single revaccination should be considered after 5 years for those who are likely to have a rapid decline in antibody levels, including those with anatomic or functional asplenia, or those with immunocompromising conditions (see list above).
Indications for PCV13
· When indicated, PCV13 should be administered to patients who are uncertain of their vaccination status.
· In 2012, the ACIP recommended routine use PCV13 (Prevnar 13, Wyeth) for adults aged ≥19 years with the following44
o Immunocompromising conditions (as per list above)
o Functional or anatomic asplenia
o CSF leaks
o Cochlear implants
· For pneumococcal vaccine-naïve persons, ACIP recommends that adults with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants should receive a dose of PCV13 first, followed by a dose of PPSV23 at least 8 weeks later.
· Subsequent doses of PPSV23 should follow current PPSV23 recommendations for adults at high risk.
o Specifically, a second PPSV23 dose is recommended 5 years after the first PPSV23 dose for persons aged 19 to 64 years with functional or anatomic asplenia and for persons with immunocompromising conditions.
o Those who received PPSV23 before age 65 years for any indication should receive another dose of the vaccine at age 65 years, or later after at least 5 years have elapsed since their previous PPSV23 dose.
· Adults with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants, who did previously receive 1 or more doses of PPSV23 should be given a PCV13 dose ≥1 year after the last PPSV23 dose was received. For those who require additional doses of PPSV23, the first such dose should be given no sooner than 8 weeks after PCV13 and at least 5 years after the most recent dose of PPSV23.
· In late 2014 ACIP recommended PCV13 for all adults ≥65 years.
· See Table 5-5 for a summary.
TABLE 5-5 Pneumococcal Vaccine Guidelines
In late 2014 ACIP recommended PCV13 for all adults ≥65 years.
PCV13 is the 13-valent pneumococcal conjugate vaccine (Prevnar)
PPSV23 is the 23-valent pneumococcal polysaccharide vaccine (Pneumovax)
Contraindications, Side Effects, and Precautions
· Pneumococcal vaccine is contraindicated in those with a severe reaction to a previous dose (anaphylaxis or local Arthus-type reaction).
· Approximately half of patients experience injection site soreness, redness, or swelling; systemic symptoms are rare.
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
Hepatitis A Vaccine and Immune Globulin
The levels of antibody following hepatitis A vaccine (HAV) or immunoglobulin (IG) administration are much lower than those following natural infection and are usually below the level of detection of most commercial assays but are protective against infection (>90% effective by 1 month).
Formulations
· Two inactivated HAVs are available: HAVRIX (GlaxoSmithKline) and VAQTA (Merck); both are available in pediatric and adult formulations. Adults 19 years of age and older should receive 1 dose of adult formulation with a booster dose at least 6 months later.
· There is also a combination of hepatitis A and hepatitis B vaccine (Twinrix, GlaxoSmithKline), which is administered in a 3-dose series at 0, 1, and 6 months for adults 18 or more years of age. Single-antigen HAV may be used to complete a series that begun with Twinrix and vice versa (for a total of 3 doses, on the Twinrix schedule).
Indications for Vaccination for Preexposure Prophylaxis
· In high-prevalence populations, it may be reasonable (but not necessary) to check serology before offering HAV vaccine.
· Target groups for vaccination include the following:
o Persons traveling to/working in countries in which HAV is endemic.
o Men who have sex with men.
o Illicit drug users (injection or noninjection).
o Persons with HIV infection.
o Persons with an occupational risk (e.g., laboratory workers).
o Persons with chronic liver disease or liver transplant recipients (no increased risk of acquiring infection, but complications would be more likely).
o Persons who receive clotting factor concentrates.
o Vaccination can also be considered for food handlers to reduce potential transmission.
o Persons who anticipate close contact with an international adoptee during the first 60 days following arrival of the adoptee to the US from an endemic country. The first dose of the 2-dose HAV series should be administered as soon as adoption is planned, ideally 2 or more weeks before the arrival of the adoptee.
Travelers
· Travelers to Canada, Western Europe, Scandinavia, Australia, New Zealand, and Japan are at no greater risk for infection than in the US. Elsewhere, there is increased risk even if travelers observe precautions against enteric infection or stay in urban areas or luxury hotels.
· Ideally, travelers should receive HAV at least 4 weeks before travel. A second dose 6 to 12 months later is necessary for long-term protection.
· Unvaccinated adults >40 years of age, immunocompromised persons, and persons with chronic liver disease planning to travel in 2 weeks or sooner should receive the first dose of vaccine and also can receive immune globulin (IG, 0.02 mL/kg) at the same visit.
· Travelers who choose not to receive the vaccine should be administered a single dose of IG (0.02 mL/kg), which will provide protection for up to 3 months. For travel periods that exceed 2 months, the dose should be 0.06 mL/kg; administration must be repeated if the travel period exceeds 5 months.
Postexposure Prophylaxis
· In high-prevalence populations, it may be reasonable, but not necessary, to check serology before offering IG.
· The IG (0.02 mL/kg) should be given as soon as possible, but no later than 10 days to 2 weeks after exposure.
· Persons who received HAV vaccine at least 1 month before exposure do not need IG.
· Postexposure prophylaxis is indicated for household and sexual contacts of confirmed cases but not casual contacts.
· Day care center staff and attendees need prophylaxis if one or more cases are confirmed.
· If a food handler is diagnosed with hepatitis A, other food handlers at the same location need IG (and should consider vaccine). Transmission to patrons is unlikely, but prophylaxis can be considered if an infectious worker directly handled uncooked or previously cooked foods and had diarrhea or poor hygienic practices, and patrons can be contacted and treated within 2 weeks.
Contraindications, Side Effects, and Precautions
· Contraindications include history of a severe allergic reaction to a vaccine component, or hypersensitivity to alum or the preservative 2-phenoxyethanol.
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
· The most frequent side effects are injection site erythema and soreness and mild systemic symptoms such as malaise or low-grade fever.
· Vaccine and IG should be administered with separate syringes at different anatomic sites.
Hepatitis B Vaccine and Immune Globulin
Efficacy and Postvaccination Testing
· The vaccine is 80% to 100% effective in preventing infection.
o Protection is essentially complete for those with an adequate antibody response (≥10 mIU/mL).
o Protective antibody titers are developed after 3 doses of the vaccine in >90% of young adults but in only 75% of those over age 60.
o Efficacy is lower in hemodialysis patients.
· Postvaccination testing for serologic response (1 to 6 months after completion of the vaccine series) is advised only for persons whose subsequent clinical management depends on knowledge of their immune status or those who are expected to have a suboptimal response (e.g., infants born to hepatitis B surface antigen [HBsAg]–positive mothers, sex partners of HBsAg-positive persons, dialysis patients and staff, persons over age 50, persons with HIV infection). Postvaccination testing should also be considered for persons at occupational risk.
· When nonresponders are revaccinated, 30% to 50% produce an adequate antibody response after three additional doses. Persons who fail to develop detectable anti-HBs after 6 doses should be tested for HBsAg as they may be chronically infected.
· Antibody levels decline over time, but protection against disease appears to persist despite undetectable antibody. Therefore, booster doses of vaccine are not recommended for immunocompetent adults.
Formulations and Schedules
· Two hepatitis B vaccines are available: Recombivax HB (Merck) and Engerix-B (GlaxoSmithKline Pharmaceuticals), both in pediatric and adult formulations. Engerix-B is also available in combination with hepatitis A as Twinrix (GlaxoSmithKline) for adults 18 or more years of age.
o For adult dose schedules, the brands are interchangeable.
o All are recombinant in origin and contain no potentially infectious virions.
o Adults 20 or more years of age should receive 1 mL of any brand of HB vaccine.
o Adolescents <20 years of age may receive any of the following:
§ Recombivax HB: pediatric or adult formulation at 0.5 mL (5 μg) per dose
§ Engerix-B: pediatric formulation 0.5 mL (10 μg) or adult formulation 1 mL (20 μg) per dose
· The usual schedule is 2 doses separated by no <4 weeks and a third dose 4 to 6 months after the second dose (i.e., at time 0, 1 month, and 5 to 6 months).
o If an accelerated schedule is needed, the minimum interval between the first 2 doses is 4 weeks, and the minimum interval between the second and third doses is 8 weeks, with at least 16 weeks between the first and third doses.
o Doses given at less than these minimum intervals should not be counted as part of the vaccination series.
o Longer than minimum times are acceptable. It is not necessary to restart the series or add doses because of an extended interval between doses.
· Patients on hemodialysis require larger or increased number of doses, or both, to achieve adequate antibody levels. For dialysis patients aged ≥20 years, use either schedule:
o Recombivax-B: use 3 doses of the special 40-μg/mL formulation (1 mL IM at 0, 1, and 6 months)
o Engerix-B: use 4 double doses of the regular 20 μg/mL formulation (2 mL IM at 0, 1, 2, and 6 months)
o Measure titers 1 to 6 months after immunization.
o Antibody levels should be tested annually and a booster dose administered when <10 mIU/mL.
Indications
· Prevaccination serologic testing is usually cost-effective and should be considered for groups with a high risk of HBV infection:
o All persons born in Africa, Asia, the Pacific Islands, or other regions with endemic HBV infection
o Household, sex, and needle-sharing contacts of HBsAg-positive persons
o Men who have sex with men
o Injection drug users
o Incarcerated persons
o Certain persons receiving cytotoxic or immunosuppressive therapy
· There is no harm in vaccinating persons who are already immune.
· Hepatitis B vaccination is recommended for all unvaccinated adults at risk for HBV infection and for all adults requesting protection from HBV infection. Persons at risk for infection include the following:
o Household contacts and sex partners of persons with chronic HBV infection.
o Sexually active persons who are not in a long-term, mutually monogamous relationship.
o Persons seeking evaluation or treatment for a STD.
o Men who have sex with men.
o Current or recent injection drug users.
o Persons with HIV infection.
o Household contacts of HBsAg-positive persons.
o International travelers to regions of endemic HBV infection.
o Residents and staff of facilities for developmentally disabled persons, or correctional facilities.
o Health care and public safety workers with risk for exposure to blood or blood-contaminated body fluids.
o Persons with end-stage renal disease, including predialysis or any form of dialysis.
o Persons with chronic liver disease or liver transplant recipients (no increased risk of acquiring infection, but complications would be more likely).
o Adults with DM type 1 or 2. In 2011, ACIP recommended that all previously unvaccinated adults aged 19 to 59 years with DM be vaccinated against hepatitis B as soon as feasible after a diagnosis of DM is made (and may be considered in those aged 60 or older). Persons with DM are at increased risk of HBV infection, probably because of breaches in infection control during assisted blood glucose monitoring (e.g., reuse of single patient finger stick devices).
· Vaccinate all adults requesting protection from HBV infection, without requiring them to acknowledge a specific risk factor.
Contraindications, Side Effects, and Precautions
· A severe allergic reaction (anaphylaxis) to a vaccine component or following a prior dose of hepatitis B vaccine is a contraindication to further doses of vaccine. Such allergic reactions are rare.
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
· Pregnancy is not a contraindication.
· The most common adverse reactions are injection site pain or mild systemic complaints, such as fatigue or headache. Serious systemic adverse reactions are rare.
Postexposure Prophylaxis
· Hepatitis B immune globulin (HBIG) is used for postexposure prophylaxis in susceptible individuals (no vaccine or known nonresponder).
· Vaccine and HBIG can be administered at the same time, but at separate sites.
· After an occupational exposure to blood or body fluids, the source patient and the exposed person should be checked for HBsAg status; see Table 5-6 for the treatment algorithm.45
· In nonoccupational settings, HBV can be spread to household contacts, sexual partners, and needle-sharing contacts. Unvaccinated contacts should be tested for susceptibility to HBV infection and should receive the first dose of hepatitis B vaccine immediately after collection of blood for serologic testing.
o Management of nonoccupational exposure to a source known to be HBsAg positive:
§ Persons with written documentation of a complete HB vaccine series but no postvaccination testing should receive a single HB vaccine booster dose.
§ Persons who are not fully vaccinated should receive HBIG and should complete the vaccine series.
§ Unvaccinated persons should receive both HBIG and hepatitis B vaccine series as soon as possible after exposure (preferably within 24 hours).
o Management of nonoccupational exposure to source with unknown HBsAg status:
§ Persons with written documentation of a complete HB vaccine series require no further treatment.
§ Persons who are not fully vaccinated should complete the vaccine series.
§ Unvaccinated persons should receive the HB vaccine series with the first dose administered as soon as possible after exposure, preferably within 24 hours.
TABLE 5-6 Hepatitis B Prophylaxis Following Percutaneous Exposure to Blood
aAdequate anti-HBsAg level is 10 SRU by radioimmunoassay or positive by enzyme immunoassay.
HB, hepatitis B; HBIG, hepatitis B immune globulin; HBsAg, hepatitis B surface antigen.
Varicella (Chickenpox) Vaccine
· Approximately 10% of US adults are susceptible to the varicella-zoster virus (VZV) and its complications (bacterial infections of skin lesions, viral pneumonia, aseptic meningitis, encephalitis, thrombocytopenia, hepatitis and others). Prior to routine immunization, approximately 100 deaths occurred annually, mostly in healthy persons.
· Evidence of immunity to varicella in adults includes any of the following:
o Documentation of 2 doses of varicella vaccine
o Laboratory evidence of immunity or confirmation of disease (but commercial assays may yield false-negative results after vaccination)
o Born in the US before 1980 (but not adequate evidence of immunity for health care providers or pregnant women)
o A health care provider diagnosis of varicella disease or herpes zoster.
Efficacy
· In adolescents and adults, the seroconversion rate is 99% after 2 doses.
· Breakthrough infections in vaccinated persons are usually mild, with <50 lesions.
· The incidence of herpes zoster may be less after vaccination than after the natural disease.
Indications
Two doses of varicella vaccine are indicated for all susceptible adolescents and adults, with emphasis on the following groups:
· Susceptible adolescents
· Adults who live with young children
· All nonpregnant women of childbearing age
· Household contacts of immunocompromised persons
· Health care workers
· Workers in schools and day care centers
· Those who live in closed populations such as colleges or the military
· International travelers
Contraindications, Side Effects, and Precautions
· Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component is a contraindication. All VZV vaccines contain tiny amounts of neomycin and hydrolyzed gelatin but do not contain egg protein or preservative.
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
· Because it is a live attenuated virus vaccine, varicella vaccine is contraindicated in pregnancy (defer pregnancy 1 month after vaccination).
· Varicella vaccine is contraindicated in some immunocompromised individuals including those with leukemia, lymphoma, or generalized malignancy, immune deficiency disease, or on immunosuppressive therapy (including steroids at more than replacement dose).
· Varicella vaccine may be administered to persons with impaired humoral immunity (e.g., hypogammaglobulinemia), but the blood products used for treatment (IG) may interfere with the response to vaccination. Recommended spacing between administration of the blood product and receipt of varicella vaccine should be observed (consult CDC website).
· Approximately 25% to 33% of recipients had injection site soreness, swelling, erythema, or rash.
· In <1%, a diffuse rash developed with a median of five lesions, most caused by a coincidental wild-type virus.
· Vaccine-type virus from the varicella-like rash after immunization can infrequently be transmitted to susceptible contacts, but the secondary cases are subclinical or mild.
Herpes Zoster (Shingles) Vaccine
Latent VZV can cause herpes zoster, also known as shingles. About one in five cases of zoster leads to postherpetic neuralgia (increased incidence with aging), and rare complications include pneumonia, cranial nerve damage, or encephalitis.
Efficacy
· The zoster vaccine has an efficacy of about 50% in preventing herpes zoster and 66% in preventing postherpetic neuralgia. The efficacy declines with age.46
· The duration of protection is unknown, but is probably >4 years.
Indications
· The vaccine is FDA approved for use in adults >50 years of age, but ACIP recommends vaccination at age 60.
· Persons with a reported history of zoster can be vaccinated.
· Although both are made from live attenuated varicella zoster virus, the varicella vaccine (Varivax) and the zoster vaccine (Zostavax) are not interchangeable—the zoster vaccine is a much higher dosage (15×).
Contraindications, Side Effects, and Precautions
· The most common side effects are redness, pain and swelling at the injection site, and headache.
· Antiherpes medications (acyclovir, famciclovir, valacyclovir) might interfere with the response to the zoster vaccine; they should be discontinued 24 hours before administration of zoster vaccine, if possible. They may be restarted 14 days later.
· Because it is a live attenuated virus vaccine, zoster vaccine is contraindicated in pregnancy and in most immunocompromised patients, including those with hematologic malignancies, AIDS, HIV infection with CD4 cell count <200/μL, and more than 20 mg/day of prednisone (or equivalent).
· Other contraindications include a history of severe allergic reaction to gelatin, neomycin, or any component of the vaccine.
· The following are not contraindications:
o Topical, inhaled, or intra-articular steroids or long-term alternate-day treatment with low to moderate doses of short-acting systemic corticosteroids.
o Low doses of drugs used for the treatment of rheumatoid arthritis, inflammatory bowel disease, and other conditions, such as methotrexate, azathioprine, or 6-mercaptopurine, are also not considered sufficiently immunosuppressive to create safety concerns for zoster vaccine.
· The safety and efficacy of zoster vaccine administered concurrently with recombinant human immune mediators and immune modulators (such as the anti–tumor necrosis factor agents adalimumab, infliximab, and etanercept) is not known. It is preferable to administer zoster vaccine before, or 1 month after, treatment with these drugs. Otherwise, the immune status of the recipient should be assessed on a case-by-case basis.
· Blood products do not interfere with zoster vaccination because all persons with a history of varicella maintain high levels of antibody to VZV (comparable to those found in antibody-containing blood products).
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
Meningococcal Vaccine
Formulations
· All US vaccines contain 4 purified bacterial capsular polysaccharides: A, C, Y, and W-135 but not serogroup B (serogroup B polysaccharide is poorly immunogenic in humans).
· Menomune (Sanofi Pasteur) is an older quadrivalent meningococcal polysaccharide vaccine (MPSV4) and is preferred for persons aged 56 and older.
· The newer quadrivalent meningococcal conjugate vaccines (MCV4) contain the same capsular polysaccharides, conjugated to proteins for enhanced immunogenicity. It is preferred for persons aged 55 and younger. Brands include Menactra (Sanofi Pasteur) and Menveo (Novartis).
Indications and Schedules
· For healthy adolescents, ACIP recommends routine vaccination with MCV4 at age 11 or 12 years, with a booster dose at age 16 years to maintain protective immunity through ages 16 to 21 years, when their risk for disease is greatest.
o If the first dose was at ages 13 to 15, a booster dose should be administered at ages 16 to 18, before the peak in increased risk.
o If the first dose was at age 16 or later, a booster is not needed.
o First-year college students up through age 21 years who are living in residence halls should be vaccinated if they have not received a dose on or after their 16th birthday.
o Routine vaccination of healthy persons is not recommended after age 21 years.
· Persons aged 2 to 54 years with reduced immune response should receive 2 doses of MCV4 administered 2 months apart and then a booster dose every 5 years. Indications include persistent complement component deficiencies and functional or anatomic asplenia.
· Other persons at increased risk for meningococcal disease (e.g., microbiologists, military recruits, or travelers to endemic areas) should receive a single dose of MCV4.
· If persons with HIV infection need meningococcal vaccination, they should receive 2 doses of MCV4.
Contraindications, Side Effects, and Precautions
· Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component is a contraindication. MPSV4 contains thimerosal, but MCV4 does not.
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
· Systemic reactions, such as headache and malaise, occur in up to 60% of recipients, and up to 5% of recipients develop a fever within 7 days of vaccination.
· Safety in pregnancy is unknown, but pregnancy is not considered a contraindication.
· GBS has been associated with receipt of MCV4; therefore, a history of GBS is a relative contraindication to receiving MCV4. The nonconjugated MPSV4 may be used for short-term protection (3 to 5 years).
Human Papillomavirus (HPV) Vaccine
· HPV infection is associated with anogenital warts (90% have HPV types 6 or 11), recurrent respiratory papillomatosis, cervical cancer (70% have HPV types 16 or 18), and other cancers (anal, vaginal, vulvar, penile, and some head and neck cancers).
· HPV infection is common among adolescents and young adults (prevalence up to 64% in adolescent girls).
· Vaccination is not a substitute for routine cervical cancer screening (Pap smears).
Formulations
· Two inactivated HPV vaccines are available in the US.
o Quadrivalent HPV (HPV4) vaccine (Gardasil, Merck) contains types 16 and 18 (high risk) and types 6 and 11 (low risk). It is approved for females and males 9 to 26 years of age.
o Bivalent HPV (HPV2) vaccine (Cervarix, GlaxoSmithKline) contains types 16 and 18 (high risk). It is approved for females 10 to 25 years of age (not males).
· For both vaccines, >99% of recipients developed an antibody response, and the vaccines showed >90% efficacy in preventing cervical neoplasia or genital warts related to the HPV types included in the vaccine. The vaccines had no therapeutic effect on existing infection or disease. Prior infection with one HPV type did not diminish efficacy of the vaccine against other vaccine HPV types.
Indications and Schedules
· The vaccine is administered as a 3-dose series at 0, 2, and 6 months.
· ACIP recommends routine vaccination of
o Females 11 to 12 years of age (as young as 9 years at the clinician’s discretion)
o Catch-up vaccination for females 13 to 26 years of age
o Males 11 to 12 years of age (as young as 9 years at the clinician’s discretion)
o Catch-up vaccination for males 13 to 21 years of age (males age 22 to 26 may also be vaccinated)
o All immunocompromised males (including HIV infection) up to age 26
o Men who have sex with men up to age 26
Contraindications, Side Effects, and Precautions
· Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component is a contraindication.
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
· HPV vaccines are not recommended for use in pregnant women, but pregnancy testing is not needed before vaccination. If a woman is found to be pregnant after initiating the vaccination series, no intervention is needed; the remainder of the 3-dose series should be delayed until completion of pregnancy.
· Common adverse reactions include injection site pain, redness, or swelling. Systemic reactions are no more frequent than with placebo. Syncope has been reported among adolescents receiving vaccines, so recipients should be seated.
Haemophilus influenzae Type B (Hib) Conjugated Vaccine (HibCV)
· Most invasive H. influenzae disease occurs in very young children but can also occur in adults with chronic pulmonary disease and conditions that predispose to infections with encapsulated organisms.
· Most H. influenzae disease in adults is due to nontypeable strains, but HibCV can be considered for adults at increased risk for invasive Hib disease. Previously unvaccinated adults with one of these high-risk conditions should be given at least 1 dose of any Hib conjugated vaccine:
o HIV infection
o Functional or anatomic asplenia
o Immunodeficiency (especially IgG2 subclass deficiency)
o Immunosuppression from cancer chemotherapy
o Leukemia or receipt of a hematopoietic stem cell transplant
· Side effects of injection site swelling, redness, and/or pain have been reported in 5% to 30% of children; systemic reactions are infrequent.
· Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component is a contraindication.
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
Polio
Indications
· Wild-type polio has been eradicated from the entire Western Hemisphere.
· The oral polio vaccine (OPV) is a live attenuated virus that can cause vaccine-associated paralytic poliomyelitis (approximate rate: one in 2 to 3 million) and is shed in the stool. It is now recommended that OPV should not be used in the US, even in healthy children. Only inactivated (injected) polio vaccine (IPV) should be used.
· US adults do not need polio vaccination unless they plan travel to endemic areas or have occupational exposure to poliovirus. Unvaccinated adults who are at increased risk should receive a primary vaccination series with IPV (3 doses at time 0, 1 to 2 months later, and 6 to 12 months after the second dose).
· Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component is a contraindication (IPV contains trace amounts of streptomycin, polymyxin B, and neomycin).
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
Rabies Vaccine and Immune Globulin
· Most reported cases of animal rabies in the US occur among carnivores, primarily raccoons, skunks, foxes, and bats. The majority of human rabies cases in the US have resulted from variants of rabies viruses associated with insectivorous bats.
· Worldwide, wild dogs account for most cases; some US cases of rabies originate from dog bites sustained abroad, even >1 year earlier. Rabies prophylaxis in foreign countries may be inadequate.
· Vaccines available in the US include human diploid cell vaccine (HDCV, Imovax Rabies, Sanofi Pasteur) and purified chick embryo cell vaccine (PCECV, RabAvert, Novartis Vaccines and Diagnostics).
o A full 1-mL IM dose is used for both preexposure and postexposure prophylaxis regimens.
o Rabies vaccines induce an active immune response that requires approximately 7 to 10 days to develop; rabies virus–neutralizing antibodies generally persist for several years.
· Severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a vaccine component is a contraindication.
· Vaccine side effects include injection site soreness and erythema. Mild systemic symptoms (such as headache, nausea, myalgias) are common.
· Moderate or severe acute illness with or without fever is a precaution. Mild acute illness and low-grade fever are not contraindications to immunization.
Postexposure Prophylaxis
· After an exposure, all wounds require immediate and thorough washing with copious amounts of soap and water. Tetanus prophylaxis should also be considered.
· In all postexposure prophylaxis regimens, except for persons previously vaccinated, human rabies immune globulin (HRIG) should be administered concurrently with the first dose of vaccine.
· Use of HRIG provides a rapid, passive immunity that persists for a short time (half-life 21 days) for protection until the production of active immunity in response to vaccine administration. Two antirabies immune globulin formulations prepared from hyperimmunized human donors are available for use in the US: HyperRab S/D (Talecris Biotherapeutics) and Imogam Rabies-HT (Sanofi Pasteur).
· Previously immunized patients should receive 2 doses of vaccine: 1-mL IM in the deltoid on days 0 and 3.
· Persons not previously immunized should be treated with:
o A single 20 IU/kg dose of HRIG, up to half infiltrated in the area of the wound and half IM. HRIG should be given immediately but can be administered up to the eighth day after vaccine was started.
o Four doses of vaccine (1 mL IM in the deltoid on days 0, 3, 7, and 14).
· Immunocompromised persons should be tested for adequacy of antibody response.
· The local department of health should be notified.
· The decision to initiate postexposure prophylaxis should include the following considerations:
o Bites to the head or neck can result in rabies in <1 week; therefore, immediate prophylaxis is indicated.
o A healthy domestic dog, cat, or ferret should be held for observation for 10 days; if signs of illness develop in the animal, the human contact should be immediately treated with HRIG and vaccine while the animal is tested.
o Bites from a suspected rabid dog or cat require immediate prophylaxis. Casual contact (petting) does not require prophylaxis.
o Bats and wild carnivores should be regarded as rabid unless confirmed negative by laboratory tests.
o Bites by some animals, such as bats, can inflict very minor injury and thus be undetected. A bat found in a room with a sleeping person is considered an exposure.
o Small rodents (e.g., squirrels, hamsters, guinea pigs, gerbils, chipmunks, rats, and mice) and lagomorphs (rabbits and hares) are almost never found to be infected with rabies and have not been known to transmit rabies to humans.
Preexposure Prophylaxis
· Preexposure vaccination simplifies management of a rabies exposure by eliminating the need for HRIG and decreasing the number of doses of vaccine needed. It is indicated for persons whose jobs or hobbies bring them into contact with potentially rabid animals, such as the following:
o Animal handlers, veterinarians, and their staff.
o Rabies researchers and certain laboratory workers.
o Animal control and wildlife officers in areas where animal rabies is enzootic.
o International travelers if they are likely to come in contact with animals in areas where rabies is enzootic and immediate access to appropriate medical care might be limited.
· Preexposure vaccination consists of three 1-mL doses of HDCV or PCECV given IM on days 0, 7, and 21 or 28.
· Persons at ongoing risk of exposure to rabies virus should have periodic serum testing for rabies virus–neutralizing antibody. See CDC guidelines for details.
Specific Immunization Patient Groups
CHECKLISTS BY AGE
Young Adults (About 18 to 26 Years)
· Assure receipt of a primary series (3 doses) of tetanus (DPT, DTaP, or Tdap).
· Tetanus booster (Td) every 10 years; substitute Tdap for 1 dose of Td.
· Assure receipt of at least 1 dose of MMR.
o Students and health care workers need to have received 2 doses of MMR.
o Women of childbearing age should have laboratory evidence of immunity to rubella.
o Health care workers should have laboratory evidence of immunity to MMR.
· Offer varicella vaccine (2 doses) to those who are susceptible (never had chickenpox or the vaccine).
· Ensure receipt of meningococcal vaccine for those up to age 21 (or with risk factors).
o If the first dose was before age 13, give a booster at age 16.
o If the first dose was at ages 13 to 15 years, give a booster at ages 16 to 18.
o If the first dose was at age 16 or later, a booster is not needed.
· Offer HPV vaccine (Gardasil) for women and men up to age 26.
· Annual influenza vaccine is recommended for everyone over age 6 months.
· Assess risk factors that indicate the need for other vaccines: hepatitis A, hepatitis B, or pneumococcal vaccines.
Midlife Adults (About 27 to 49 Years)
· Assure receipt of a primary series (3 doses) of tetanus (DPT, DTaP, or Tdap).
· Tetanus booster (Td) every 10 years; substitute Tdap for 1 dose of Td.
· Assure receipt of at least 1 one dose of MMR.
o Students and health care workers need to have received 2 doses of MMR.
o Women of childbearing age should have laboratory evidence of immunity to rubella.
o Health care workers should have laboratory evidence of immunity to MMR.
· Offer varicella vaccine to those who are susceptible (never had chickenpox or vaccine).
· Annual influenza vaccine.
· Assess risk factors that indicate the need for other vaccines: hepatitis A, hepatitis B, meningococcal, influenza, or pneumococcal vaccines.
Adults Ages 50 Years and Older
· Assure receipt of a primary series (3 doses) of tetanus (DPT, DTaP, or Tdap). Tetanus vaccine was first widely used in the 1940s; many older adults are not immune.
· Tetanus booster (Td) every 10 years; substitute Tdap for 1 dose of Td.
· Assure receipt of at least 1 dose of MMR.
o Health care workers should have laboratory evidence of immunity to MMR.
o Students and health care workers need to have received 2 doses of MMR.
o Those born before 1957 generally are considered immune to measles and mumps.
· Annual influenza vaccination.
· A single dose of pneumococcal vaccine should be given at age 65.
· Offer varicella vaccine to those who are susceptible (never had chickenpox or vaccine).
· Offer zoster (shingles) vaccination to those aged 60 and older.
· Assess risk factors that indicate the need for other vaccines: hepatitis A, hepatitis B, meningococcal, or pneumococcal vaccines.
PREGNANCY AND BREAST-FEEDING
· Pregnancy is a contraindication for live virus vaccines. MMR and varicella may be administered to the children of a pregnant woman because these vaccines are not shed.
· All pregnant women should be tested for rubella antibodies; women who are susceptible to rubella should be vaccinated immediately after delivery.
· Influenza vaccine is recommended for all pregnant women.
· Administer 1 dose of Tdap in EACH pregnancy (ideally at 27 to 36 weeks’ gestation).
· Pregnant women who are not fully immunized against tetanus should begin the primary series to prevent neonatal tetanus (Tdap for first dose, Td for others).
· Vaccines against hepatitis B, hepatitis A, pneumococcus, and meningococcus are indicated for pregnant women who are at high risk for these infections or their complications.
· Breast-feeding is not a contraindication for any vaccine for infant or mother (except for smallpox vaccine).
IMMUNOSUPPRESSED PATIENTS
· Live vaccines are generally contraindicated in immunosuppressed patients, such as those with congenital immunodeficiency, HIV infection, leukemia, lymphoma, generalized malignancy or therapy with alkylating agents, antimetabolites, radiation, or supraphysiologic doses of corticosteroids (such as prednisone at 20 mg/day or more for 14 days or longer).
· Killed (inactivated) vaccines can be safely administered, but the response may be suboptimal. Vaccination during (or within 2 weeks before) chemotherapy or radiation therapy results in a poor antibody response and therefore should be delayed or repeated 3 months after therapy is discontinued.
· Patients with immune compromise other than HIV should receive
o Pneumococcal vaccines (PCV13 and PPSV23 as per Table 5-5)
o Annual IIV (not LAIV)
o One-time dose of Tdap for Td booster and then boost with Td every 10 yrs
o HPV vaccine if <27 years of age
o Should NOT receive live vaccines including MMR, varicella, or zoster vaccines.
· Persons with HIV infection who are not severely immunosuppressed (CD4 ≥200/μL) should receive
o Pneumococcal vaccines (PCV13 and PPSV23 as per Table 5-5)
o Annual IIV (not LAIV)
o One-time dose of Tdap for Td booster and then boost with Td every 10 years
o HPV vaccine if <27 years of age
o Hepatitis B vaccine
o May receive varicella vaccine or MMR if indicated
· Persons with HIV infection and severe immune compromise (CD4 <200/μL)
o Should receive pneumococcal vaccines (PCV13 and PPSV23 as per Table 5-5)
o Should receive annual IIV (not LAIV)
o Should receive one-time dose of Tdap for Td booster and then Td every 10 years
o Should receive HPV vaccine if <27 years of age
o Should receive hepatitis B vaccine
o Must NOT receive live vaccines including MMR, varicella, or zoster vaccines
o If exposed to measles, they should receive immunoglobulin (0.25 mL/kg; maximum dose 15 mL), regardless of prior vaccination status.
· Hematopoietic cell transplant recipients require revaccination with inactivated vaccines, starting 6 months after transplant (see General Recommendations on Immunization for details).
PERSONS WITH CHRONIC ILLNESS
· Persons with hemophilia, bleeding disorders, or taking anticoagulant medications usually tolerate IM injections if a 23-gauge needle is used and firm pressure is applied to the site for at least 2 minutes without rubbing. If the patient receives factor replacement therapy, IM vaccination can be scheduled shortly after such therapy.
· In addition to routine use of influenza, Tdap/Td, MMR, HPV, varicella, and zoster vaccines, persons with chronic illnesses may need additional vaccines as follows:
o Persons with liver disease are at increased risk of suffering complications and should be vaccinated against hepatitis A and hepatitis B. They also should receive pneumococcal vaccine PPSV23 (1 or 2 doses depending on age).
o Persons with chronic kidney disease and renal transplant recipients should receive hepatitis B and pneumococcal vaccines (PCV13 and PPSV23 as per Table 5-4).
o Persons with DM should receive hepatitis B and pneumococcal vaccines (PPSV23, 1 or 2 doses depending on age).
o Persons with splenic dysfunction, including sickle cell disease, or anatomic asplenia should receive meningococcal and pneumococcal vaccines (PCV13 and PPSV23 as per Table 5-5). Those scheduled for elective splenectomy should receive these vaccines at least 2 weeks before the operation.
PERSONS WITH ACUTE ILLNESS
· Mild illnesses (such as otitis media, upper respiratory infections, and diarrhea) are not contraindications to vaccination.
· With few exceptions, use of an antimicrobial agent is not a contraindication to vaccination.
o Oral typhoid vaccine should not be administered until 24 hours after the last dose of antibiotics.
o Anti-influenza drugs can interfere with the response to live attenuated (intranasal) influenza vaccine. Antiviral drugs active against herpes viruses (such as acyclovir) might reduce the efficacy of live attenuated varicella and zoster vaccines. Live attenuated virus vaccines should not be administered until at least 2 days after related antiviral drugs. If feasible, antiviral medication should not be administered for 14 days after vaccination.
HEALTH CARE WORKERS
· Health care workers and first responders are at risk for exposure to and possible transmission of vaccine-preventable diseases.
· Hepatitis B is an occupational hazard for any worker with possible exposure to blood or bloody fluids.
· Annual influenza vaccine is recommended for all adults and is especially important for health care workers. Those who care for severely immunosuppressed persons who require a protective environment should not receive LAIV given the theoretical risk for transmission of the live attenuated vaccine virus.
· All health care workers should document immunity to MMR, and varicella.
· Health care workers of any age should receive a single dose of Tdap to reduce transmission of pertussis.
· Additional vaccines are indicated for veterinarians, laboratory technicians, animal handlers, and others who may have occupational exposure to rabies, poliovirus, smallpox virus, Yersinia pestis (plague), or Bacillus anthracis(anthrax).
MEN WHO HAVE SEX WITH MEN (MSM)
In addition to routine use of influenza, Tdap/Td, MMR, HPV, varicella, and zoster vaccines, MSM should be vaccinated against hepatitis A and B. Those <27 years of age should be offered HPV vaccine. Other vaccines are as indicated by risk factors (such as zoster or pneumococcal).
TRAVELERS
· The risk of acquiring illness during international travel depends on the areas to be visited and the extent to which the traveler is likely to be exposed to diseases.
· Influenza is present in the Southern Hemisphere from April through September and year-round in the tropics.
· Hepatitis A is a risk for travelers in most of the world except the US, Australia, Canada, Western Europe, Japan, or New Zealand.
· Travelers should be counseled about safe sex practices.
· Selected travelers may need immunization against yellow fever, cholera, typhoid, plague, meningococcus, rabies, hepatitis B, or hepatitis A.
· Resources for up-to-date information for travelers include the CDC website (http://wwwnc.cdc.gov/travel, last accessed December 23, 2014), which has detailed information about worldwide destinations, and the CDC’s toll-free 24-hour Travelers’ Health Automated Information Line, 877-394-8747 (877-FYI-TRIP).
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