Principles of Ambulatory Medicine, 7th Edition

Chapter 18

Immunization to Prevent Infectious Disease

William H. Barker

Protection against infectious diseases can be conferred by active immunization with vaccines and by passive immunization with immune globulin (Ig) preparations. Additional vaccines will become available in the next few years, and additional information will be generated to improve our understanding of the mechanisms of immune response to vaccines. Thus it can be expected that recommendations appropriate today will be revised in the future. This chapter describes vaccines and Ig preparations available in the United States, focusing on several questions commonly considered in practice: Who should receive what specific immunization? When should they receive it? What are the common side effects or adverse reactions? Chapter 41 provides similar information on immunization for travelers to developing countries.

Patient Assessment

History

A history of immunizations should be obtained from all patients. In young adults, this information may be readily available, but in older persons, it is often hard to obtain. Patients may or may not keep personal records that are of use. People who have served in the military will have received routinely recommended immunizations and several additional vaccines not generally administered to the general population. People who travel abroad frequently should have this information recorded on their International Vaccination Card. Immunization history is particularly important in determining whether to give tetanus toxoid or antitoxin after an injury, whether diphtheria should be seriously considered in the diagnosis of acute pharyngitis (see Chapter 33), and what immunizations are needed by patients who plan to travel outside the United States (see Chapter 41).

A history of allergic reactions or other untoward reactions to vaccines or their components should always be excluded before giving an immunization. Most modern vaccines are highly purified, and allergic reactions after their use are rare. However, a history of a severe adverse reaction to a vaccine is a contraindication to its further use. Anyone with a history of severe allergic reactions after eating eggs should not receive vaccines made in eggs (e.g., influenza and yellow fever vaccines). Viral vaccines prepared in tissue culture often contain small amounts of antibiotics (especially neomycin) to which some patients may be allergic. For patients with previous allergic reactions to any vaccine, the contents of each vaccine should be determined from the package insert before administration.

Immunization with live virus vaccines is generally contraindicated in patients with known immunodeficiency syndromes or recent treatment with immunosuppressive drugs. Patients known to be infected with the human immunodeficiency virus (HIV) may be at increased risk when receiving live vaccines, although adverse effects have been documented infrequently. Chapter 39 outlines current recommendations for vaccines in HIV-infected persons. Pregnant women, in whom a vaccine virus might pose a risk to the fetus, should generally not be given live vaccines. In addition to ascertaining by history that a woman of childbearing age is not pregnant, it is important to counsel the patient to use contraceptive practices to prevent pregnancy for 3 months after immunization with a live vaccine (see Chapter 100). Prophylactic use of Ig and the various hyperimmune globulin preparations is considered safe in

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pregnancy. Pregnancy is not a contradiction to administering live vaccine to children with whom a pregnant woman (e.g., mother or classroom teacher) will come in contact.

Recent administration of Ig preparations requires that the use of live virus vaccines be postponed because passively acquired immunity can interfere with the active response to the vaccine (1). Ig preparations should not be administered earlier than 2 weeks after live virus vaccine so that the vaccine virus can stimulate an active immune response. Yellow fever is an exception because interference does not occur.

Minor illness (e.g., upper respiratory infection with or without a low-grade fever) is not a contraindication to necessary immunization. A patient with moderate or severe acute illness should generally not be immunized until after the illness has resolved, both because vaccine side effects might add to the patient's morbidity and because the effectiveness of the vaccination may be diminished.

Physical and Laboratory Evaluation

When immunization is contemplated, physical examination and laboratory testing usually add little to the assessment of the patient. Pregnancy or an acute illness (see above) may be confirmed on examination if the history suggests one of these, and findings suggestive of an immunodeficiency syndrome should be pursued with appropriate clinical laboratory studies.

Serologic tests are useful in deciding whether to immunize adults in selected situations. When considering the use of rubella vaccine in a woman of childbearing age, the presence of antibodies to rubella virus obviates the need for vaccination. When considering the use of hyperimmune globulin preparations or hepatitis B vaccine for protection against hepatitis B, the demonstration of preexisting antibody to hepatitis B makes additional protection superfluous. The decision regarding screening for antibodies before vaccination should be based on the estimated prevalence of markers for hepatitis B infections in the population from which the patient comes and the cost of serologic testing (see below).

Immunization Procedures

The package insert for a vaccine always includes information about dosage, route, site of administration, interval between immunizations, common and uncommon side effects, contraindications, potential trace contaminants that may cause hypersensitivity reactions, and appropriate storage conditions for the vaccine.

Many widely used vaccines can be given simultaneously. The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention lists the following guidelines for simultaneous vaccine administration: Inactivated vaccines can be administered simultaneously at separate sites or at the same site with combination preparations. Tetanus and diphtheria toxoids (Td) are most effectively given together as a combined vaccine. However, when vaccines commonly associated with side effects are given together, the side effects may be accentuated and consideration should be given to vaccinating on separate occasions. An inactivated vaccine and a live attenuated virus vaccine can be administered simultaneously at separate sites. Some live virus vaccines, such as measles, mumps, and rubella (MMR), are routinely given in combination.

Patients should be informed of the risks and benefits associated with any vaccine in understandable lay terms. The range of common side effects and appropriate symptomatic therapies should be explained. Because of the rare possibility of anaphylactic reactions, patients receiving any immunization should be observed for about 15 minutes after vaccine administration. Finally, patients should be clearly informed of the name of the immunizations they have received and encouraged to keep a written record of them. Official immunization cards are available in every state for this purpose.

Physicians and other health care providers are required to maintain permanent records of immunizations and to report certain adverse effects to the U.S. Department of Health and Human Services (2). These recording requirements are summarized in the U.S. Food and Drug Administration Drug Bulletin (3). A preventive care flowsheet, kept in the patient's office record, is an ideal location for vaccine history (seeFig. 14.3).

Current Recommendations For Vaccines

Table 18.1 summarizes the major vaccines approved for use in adults in the United States; annual updates of this table may be accessed at website of the Immunization Action Coalition (http://www.immunize.org; go to Favorites from IAC, Summary of Adult Rules). The table is based on recommendations of the ACIP (see http://www.hopkinsbayview.org/PAMreferences). Chapter 11 provides similar information for adolescents (4). The following sections provide practical information on selected infectious diseases for which immune protection of adults is most likely to be undertaken in ambulatory practice.

Delivery Systems and Continuing Medical Education for Providers

Underuse and missed opportunities to provide indicated vaccination among adults enrolled in medical practices have been repeatedly documented, particularly among minority groups

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(5). A variety of simple techniques for improving vaccination delivery, including reminder mailings, standing orders, staff nurse roles, and tracking systems, has been shown to be effective in both private office and clinic settings (6, 7, 8, 9). Figure 18.1 illustrates a novel strategy for tracking and promoting provision of annual influenza immunization to target patients in a practice population. Continuing medical education on such techniques for use in adult vaccination may be accessed from the Association of Teachers of Preventive Medicine at http://www.atpm.org (9).

TABLE 18.1 Summary of Recommendations for Adult Immunization

Vaccine Name and Route

For Whom Vaccination Is Recommended

Schedule for Vaccine Administration (Any Vaccine Can Be Given with Another)

Contraindications and Precautions (Mild Illness Is Not a Contraindication)

Influenza trivalent inactivated influenza vaccine (TIV) Give IM

·   Persons age 50 yrs and older.

·   Persons with medical problems (e.g., heart disease, lung disease, diabetes, renal dysfunction, hemoglobinopathy, immunosuppression) and/or people living in chronic-care facilities.

·   Persons with any condition that compromises respiratory function or the handling of respiratory secretions or that can increase the risk of aspiration (e.g., cognitive dysfunction, spinal cord injury, seizure disorder, or other neuromuscular disorder)

·   Persons working or living with at-risk people.

·   Women who will be pregnant during the influenza season.

·   All health care workers and other persons who provide direct care to at-risk people.

·   Household contacts and out-of-home caregivers of children ages O–23 m.

·   Travelers at risk for complications of influenza who go to areas where influenza activity exists or who may be among people from areas of the world where there is current influenza activity (e.g., on organized tours).

·   Persons who provide essential community services.

·   Students or other persons in institutional settings (e.g., dormitory residents).

·   Anyone wishing to reduce the likelihood of becoming ill with influenza.

·   Given every year.

·   October through November is theoptimal time to receive annual influenza vaccination to maximize protection; however vaccination may occur in December and throughout the influenza season (typically December through March) or at other times when the risk of influenza exists.

Contraindication

·   Previous anaphylactic reaction to this vaccine, to any of its components, or to eggs.


Precaution

·   Moderate or severe acute illness.

Influenza live attenuated influenza vaccine (LAIV) Give intranasally

·   Healthy, nonpregnant women age 49 yrs and younger who meet any of the conditions listed below.
   – Working or living with at-risk people as listed in the section above.
   – Health care workers or other persons who provide direct care to at-risk people (excluding persons in close contact with severely immunosupprissed persons).
   – Household contacts and out-of-home caregivers of children ages 0–23 m.
   – Travelers who may be among people from areas of the world where there is current influenza activity (e.g., on organized tours).
   – Persons who provide essential community services.
   – Students or other persons in Institutional settings (e.g., dormitory residents).
   – Anyone wishing to reduce the likelihood of becoming ill with influenza.

 

Contraindications

·   Previous anaphylactic reaction to this vaccine, to any of its components, or to eggs.

·   Pregnancy, asthma, reactive airway disease or other chronic disorder of the pulmonary or cardiovascular system; an underlying medical condition, including metabolic disease such as diabetes, renal dysfunction, and hemoglobinopathy; a known or suspected immune deficiency disease or receiving immunosuppressive therapy; history of Guillain-Barrésyndrome.


Precaution

·   Moderate or severe acute illness.

Pneumococcal polysaccharide (PPV23) Give IM or SC

·   Persons age 65 yrs and older.

·   Persons who have chronic illness or other risk factors, including chronic cardiac or pulmonary disease, chronic liver disease, alcoholism, diabetes, CSF leak, as well as people living in special environments or social settings (including Alaska Natives and certain American Indian populations). Those at highest risk of fatal pneumococcal infection are persons with anatomic asplenia, functional asplenia, or sickle cell disease; immunocompromised persons including those with HIV infection, leukemia, lymphoma, Hodgkin disease, multiple myeloma, generalized malignancy, chronic renal failure, or nephrotic syndrome; persons receiving immunosuppressive chemotherapy (including corticosteroids); and those who received an organ or bone marrow transplant and candidates for or recipients of cochlear implants.

·   Routinely given as a one-time dose; administer if previous vaccination history is unknown.

·   One-time revaccination is recommended 5 yrs later for persons at highest risk of fatal pneumococcal infection or rapid antibody loss (e.g., renal disease) and for persons age 65 yrs and older if the 1st dose was given prior to age 65 and 5 yrs or more have elapsed since the previous dose.

Contraindication

·   Previous anaphylactic reaction to this vaccine or to any of its components.


Precaution

·   Moderate or severe acute illness.


Note: Pregnancy and breastfeeding are not contraindications to the use of this vaccine.

Hepatitis B (Hep B) Give lMBrands may be used interchangeably

·   All adolescents.

·   High-risk persons, including household contacts and sex partners of HBsAg-positive persons; injecting drug users; heterosexuals with more than one sex partner in 6 months; men who have sex with men; persons with recently diagnosed STDs; patients receiving hemodialysis and patients with renal disease that may result in dialysis; recipients of certain blood products; health care workers and public safety workers who are exposed to blood; clients and staff of institutions for the developmentally disabled; inmates of long-term correctional facilities; and certain international travelers.

·   Persons with chronic liver disease.


Note: Provide serologic screening for immigrants from endemic areas. When HBsAg-positive persons are identified, offer appropriate disease management. In addition, screen their sex partners and household members, and give the first dose of vaccine at the same visit. If found susceptible, complete the vaccine series.

·   Three doses are needed on a 0, 1, 6 m schedule.

·   Alternative timing options for vaccination include 0, 2, 4 m and 0, 1, 4 m.

·   There must be 4 wks between doses #1 and #2, and 8 wks between doses #2 and #3. Overall, there must be at least 16 wks between doses #1 and #3.

·   Schedule for those who have fallen behind: If the series is delayed between doses, DO NOT start the series over. Continue from where you left off.

Contraindication

·   Previous anaphylactic reaction to this vaccine or to any of its components.


Precaution

·   Moderate or severe acute illness.


Note: Pregnancy and breastfeeding are not contraindications to the use of this vaccine.

Hepatitis A (Hep A) Give IMBrands may be used interchangeably

·   Persons who travel or work anywhere except the U.S., Western Europe, New Zealand, Australia, Canada, and Japan.

·   Persons with chronic liver disease, including persons with hepatitis B and C; illegal drug users; men who have sex with men; people with clotting-factor disorders; persons who work with hepatitis A virus in experimental lab settings (not routine medical laboratories); and food handlers when health authorities or private employers determine vaccination to be cost effective.

·   Anyone wishing to obtain immunity to hepatitis A.


Note: Prevaccination testing is likely to be cost effective for persons older than age 40 yrs, as well as for younger persons in certain groups with a high prevalence of hepatitis A virus infection.

For TwinrixTM(hepatitis A and B combination vaccine [GSK]), three doses are needed on a 0, 1, 6 m schedule. Recipients must be age 18 yrs or older.

·   Two doses are needed.

·   The minimum interval between dose #1 and #2 is 6 m.

·   If dose #2 is delayed, do not repeat dose #1. Just give dose #2.

Contraindication

·   Previous anaphylactic reaction to this vaccine or to any of its components.


Precautions

·   Moderate or severe acute illness.

·   Safety during pregnancy has not been determined, so benefits must be weighed against potential risk.


Note: Breastfeeding is not a contraindication to the use of this vaccine.

Td (Tetanus, diphtheria) Give lM Note: As of 8/24/05, ACIP has not issued recommendations for the use of acellular pertussis combination vaccines (Tdap). See note in next column.

·   All adolescents and adults.

·   After the primary series has been completed, a booster dose is recommended every 10 yrs. Make sure your patients nave received a primary series of 3 doses.

·   A booster dose for wound management may be needed as early as 5 yrs after receiving a previous dose, so consult ACIP recommendations.*

·   Use Td, not tetanus toxoid (TT), for all indications.


Note: Two Tdap products, Boostrix (GSK) and Adacel (sanofi pasteur), were licensed by the FDA in 2005 for use in adults and/or adolescents. Consult package inserts for more information. It is anticipated that ACIP will issue recommendations for these products in late 2005.

·   Give booster dose every 10yrs after the primary series has been completed.

·   For those who are unvaccinated or behind, complete the primary series (spaced at 0, 1–2 m, 6–12 m intervals). Don't restart the series, no matter how long since the previous dose.

Contraindication

·   Previous anaphylactic or neurologic reaction to this vaccine or to any of its components.


Precautions

·   Moderate or severe acute illness.

·   Guillain-Barré syndrome within 6wks of receiving a previous dose of tetanus toxoid-containing vaccine.


Note: Pregnancy and breastfeeding are not contraindications to the use of this vaccine.

Polio (IPV) Give lM or SC

Not routinely recommended for persons age 18 yrs and older.
Note: Adults living in the U.S. who never received or completed a primary series of polio vaccine need not be vaccinated unless they intend to travel to areas where exposure to wild-type virus is likely. Previously vaccinated adults can receive one booster dose if traveling to polio endemic areas.

·   Refer to ACIP recommendations*regarding unique situations, schedules, and dosing information.

Contraindication

·   Previous anaphylactic or neurologic reaction to this vaccine or to any of its components.


Precautions

·   Moderate or severe acute illness.

·   Pregnancy.


Note: Breastfeeding is not a contraindication to the use of this vaccine.

Varicella (Var) (Chickenpox)Give SC

All susceptible adults and adolescents should be vaccinated.
It is especially important to ensure varicella immunity among household cntacts of immunosuppressed persons and among health care workers. Note: At its June 2005 meeting, ACIP voted to regard birth in the U.S. in 1965 or earlier as presumptive evidence of varicella immunity, with or without a history of having had chickenpox. Persons's born in 1966–1997 with a reliable history of chickenpox (such as self or parental report of disease) can be assumed to be immune. For persons who have no reliable history, serologic testing may be cost effective, since most persons with a negative or uncertain history of varicella are immune.

·   Two doses are needed.

·   Dose #2 is given 4–8 wks after dose #1.

·   If varicella vaccine an MMR are both needed and are not administered on the same day, space them at least 4 wks apart.

·   If the second dose is delayed, do not repeat dose #1. Just give dose #2.

Contraindications

·   Previous anaphylactic reaction to this vaccine or to any of its components.

·   Pregnancy or possibility of pregnancy within 4 wks (use contraception).

·   Persons immunocompromised because of malignancies and primary or acquired cellular immunodeficiency including HIV/AIDS. (See MMWR 1999, Vol. 48, No. RR-6.) Note: For those on high-dose immunosuppressive therapy, consult ACIP recommendations regarding delay time.*


Precautions

·   If blood, plasma, and/or immune globulin (IG or VZIG) were given in past 11m, see ACIP statement General Recommendations on Immunization*regarding time to wait before vaccinating.

·   Moderate or severe acute illness.


Note: Breastfeeding is not a contraindication to the use of this vaccine.

Meningococcal Conjugate vaccine (MCV4) Give IM— Polysaccharide vaccine (MPSV4)Give SC

·   College freshmen living in dormitories.

·   Adolescents and adults with anatomic or functional asplenia or with terminal complement component deficiencies.

·   Persons who travel to or reside in countries in which meningococcal disease is hyperendemic or epidemic (e.g., the “meningitis belt” of Sub-Saharan Africa during the dry season [Dec–June]).

·   Microbiologists who are routinely exposed to isolates of N. meningitidis.

·   Military recruits.

·   MCV4 is preferred over MPSV4 for persons age 55 yrs and younger, although MPSV4 is an acceptable alternative.

·   Give one dose to persons with risk factors; revaccinate after 5 yrs if risk of disease continues and previous vaccine was MPSV4.

Contraindication

·   Previous anaphylactic or neurologic reaction to this vaccine or to any of its components, including diphtheria toxoid (for MCV4).


Precaution

·   Moderate or severe acute illness.


Note: Pregnancy and breastfeeding are not contraindications to the use of either vaccine.

MMR (Measles, mumps, rubella)Give SC

·   Persons born in 1957 or later (including those born outside the U.S.) should receive at least one dose of MMR if there is no serologic proof of immunity or documentation of a dose given on or after the first birthday.

·   Persons in high-risk groups, such as health care workers, students entering college and other post high school educational institutions, and international travelers, should receive a total of two doses.

·   Persons born before 1957 are usually considered immune, but proof of immunity may be desirable for health care workers.

·   Women of childbearing age (i.e., adolescent girls and premenopausal adult women) who do not have acceptable evidence of rubella immunity or vaccination.

·   Special attention should be given to immunizing women born outside the U.S. in 1957 or later.

·   One or two doses are needed.

·   If dose #2 is recommended, give it no sooner than 4 wks after dose #1.

·   If varicella vaccine and MMR are both needed and are not administered on the same day, space them at least 4 wks apart.

·   If a pregnant woman is found to be rubella susceptible, administer MMR postpartum.

Contraindications

·   Previous anaphylactic reaction to this vaccine or to any of its components.

·   Pregnancy or possibility of pregnancy within 4 wks (use contraception).

·   Persons immunocompromised because of cancer, leukemia, lymphoma, immunosuppressive drug therapy, including high-dose steroids or radiation therapy. Note: HIV positivity is NOT a contraindication to MMR except for those who are severely immunocompromised.


Precautions

·   If blood, plasma, and/or immune globulin were given in past 11 m, see ACIP statementGeneral Recommendations on Immunization* regarding time to wait before vaccinating.

·   Moderate or severe acute illness.

·   History of thrombocytopenia or thrombocytopenic purpura.


Note: Breastfeeding is not a contraindication to the use of this vaccine.
Note: MMR is not contraindicated if a tuberculin skin test (i.e., PPD) was recently applied. IF PPD and MMR not given on same day, delay PPD for 4–6 wks after MMR.

*For specific ACIP recommendations, refer to the official ACIP statements published in MMWR. To obtain copies of these statements, call the CDC-INFO Contact Center at (800) 232-4636; visit CDC's website at http://www.cdc.gov/nip/publications/ACIP-list.htm ; or visit the Immunization Action Coalition (IAC) website at http://www.immunize.org/acip .
This table is revised yearly. Visit IAC's website at http://www.immunize.org/ adultrules to make sure you have the most current version. IAC thanks William Atkinson, MD, MPH, from CDC's National Immunization Program, and Linda Moyer, RN, from CDC's Division of Viral Hepatitis, for their assistance. For more information, contact IAC at 1573 Selby Avenue, St. Paul, MN 55104, (651) 647-9009, or email admin@immunize.org .

 

FIGURE 18.1. Completed poster displayed in an office practice. Year refers to the immunization season and N is the target population of patients 65 years old and older. The weekly and cumulative numbers of immunizations are tallied below the graph, and the percentage of the target population immunized is plotted weekly. (From 

Buffington J, Bell KM, LaForce FM, et al. A target-based model for increasing influenza immunizations in private practice. J Gen Intern Med 1991;6:204

, with permission.)

Protection Against Selected Infections

Diphtheria

Fewer than five cases of diphtheria are reported each year in the United States. People who have never received diphtheria toxoid should be immunized, and diphtheria toxoid should be given as booster doses with tetanus toxoid whenever tetanus toxoid is indicated (10).

For unimmunized adults, adult type tetanus and diphtheria toxoids are used. This preparation contains only approximately 25% of the diphtheria toxoid contained in the pediatric diphtheria and tetanus toxoids and no pertussis antigen to minimize the risk of local reactions in sensitized adults. Primary immunization in adults consists of an initial dose, a 1-month dose, and a third dose at 6 to 12 months. A Td booster is recommended every 10 years to ensure protection. There is a 25% to 50% incidence of local soreness, swelling, and itching after Td injections; fever occurs in less than 10%, and urticaria in approximately 2%, of individuals. Serious reactions (swelling of the whole arm or anaphylaxis) occur rarely.

For asymptomatic unimmunized contacts of patients with diphtheria, management includes prophylactic antibiotics

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(600,000 units of benzathine penicillin intramuscularly or a 7-day course of erythromycin, 250 mg four times daily), primary vaccination as outlined above, and daily surveillance for 7 days for clinical evidence of diphtheria (see Chapter 33).

Tetanus

Approximately 1 cases of tetanus are reported each year in the United States. Although natural immunity to tetanus has been found in some adult populations, everyone should be regarded as susceptible unless actively immunized (10). This includes individuals who recover from clinical tetanus, because this illness does not evoke durable immunity to reinfection. Most cases of tetanus in the United States occur in people older than age 60 years, primarily in those who were never immunized. Tetanus usually occurs after penetrating wounds from accidents and animal bites (see Chapter 32). The incubation period is 4 to 21 days, with an average of 10 days.

In those who have received a primary series of three doses of toxoid at any time in their life, an injection of adsorbed toxoid (Td) once every 10 years is sufficient to boost antitoxin titers to protective levels. The need for booster doses of combined diphtheria–tetanus toxoids (Td) in people with wounds depends on the number of previous doses of tetanus toxoid received and the type of wound (Table 18.2). Only alum-adsorbed toxoids should be used. Fluid toxoids are still available in the United States, but these preparations are less immunogenic than alum-adsorbed preparations.

Patients who require tetanus Ig because they have not been adequately immunized (Table 18.2) should be given 250 units intramuscularly. Because this preparation is made from human serum, hypersensitivity reactions do not occur. Patients who require tetanus Ig should at the same time (but at a different site) be given their first dose of toxoid, followed by repeated doses of toxoid 1 month and 6 to 12 months later.

TABLE 18.2 Summary Guide to Tetanus Prophylaxis in Routine Wound Management (United States)

History of Adsorbed Tetanus Toxoid Doses

Clean Minor Wounds

All Other Woundsa

Tdb

TIg

Tdb

TIg

Uncertain or <3

Yes

No

Yes

Yes

≥3c

Nod

No

Noe

No

TIg, tetanus immune globulin.
aSuch as, but not limited to, wounds contaminated with dirt, feces, and saliva; puncture wounds; avulsions; and wounds resulting from missiles, crushing, burns, and frostbite.
bTd, tetanus and diphtheria toxoids, adsorbed (for adult use). For children <7 years old, diphtheria, tetanus toxoid, and acellular pertussis (DTP) (DT, if pertussis vaccine is contraindicated) is preferred to tetanus toxoid alone. For persons ≥7 years old, Td is preferred to tetanus toxoid alone.
cIf only three doses of fluid toxoid have been received, a fourth dose of toxoid, preferably an adsorbed toxoid, should be given.
dYes, >10 years since last dose.
eYes, >5 years since last dose. (More frequent boosters are not needed and can accentuate side effects.)
From Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures. Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1991;40(RR-10):1, with permission.

Hepatitis A

Hepatitis A is primarily transmitted by the fecal–oral route and constitutes a significant risk for people living in settings with potentially contaminated food or water or poor personal hygiene and in settings with high endemic rates of hepatitis A.

Two inactivated hepatitis A vaccines (Havrix, GlaxoSmithKline, and Vaqta, Merck) were licensed for use in the United States in the early 1990s. These vaccines are highly immunogenic and have shown greater than 90% effectiveness in preventing clinical disease in field experiences. Long-term duration of immunity has not been tested, given the relative recency of development of these vaccines.

Vaccines should replace Ig for preexposure prophylaxis against hepatitis A. However, vaccines have little to offer patients who have been exposed to active hepatitis A because of the relatively short incubation period of 2 to 8 weeks. Exposed persons should receive passive protection with pooled human Ig, optimally within 2 weeks of exposure (11). The usual dose is 0.02 mL/kg intramuscularly.

Active immunization with hepatitis A vaccine is recommended for international travelers to regions with poor sanitation and endemic hepatitis, children living in communities with known high endemic rate of hepatitis A, homosexually active men, users of illicit injectable drugs, people working closely with nonhuman primates, and patients who receive clotting factor replacement concentrates.

Vaccine should be administered intramuscularly in the deltoid muscle, generally in a two-dose schedule, with the second dose given at 6 to 12 months; the dosage of vaccine antigen varies by patient age and by specific product. Side effects include soreness and redness at injection site, usually within 3 days, and occasional headache. Serious adverse events have not been observed. Protective antibody levels develop in over 90% of recipients within 1 month after the first dose and in virtually 100% of the second dose of vaccine. These are sustained for at least 10 years.

Hepatitis B

The timing and patterns of appearance of antigens and antibodies after hepatitis B infection are illustrated in Fig. 47.1. Although Ig in large doses (two doses of 0.06 mL/kg intramuscularly 4 weeks apart) may be useful in preventing hepatitis B (12), a hyperimmune globulin preparation (hepatitis B Ig) is preferred and is

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approximately 75% effective in preventing hepatitis in patients known to have direct exposure to hepatitis B virus (13). When hepatitis B Ig is given at the same time as hepatitis B vaccine (see below), protection is enhanced. Exposed patients who already have antibody to the hepatitis B surface antigen (anti-HBsAg) do not require prophylaxis.

TABLE 18.3 Recommended Prophylaxis after Perinatal, Sexual, or Household Exposure to Hepatitis B Virus

Type of Exposure

Type of Infection in Contact

Type of Prophylaxis

Perinatal

Acute or chronic

Vaccination + HBIga

Sexual contact

Acute

HBIgb + vaccination

 

Chronic

Vaccination

Household contact

Chronic

Vaccination

 

Acute

 

 

   No exposure

None

 

   Known exposure

HBIgb ± vaccination

 

   Infant (<12 mo)

Vaccination

 

 

HBIga if not vaccinated

HBIg, hepatitis B immune globulin.
a0.5 mL.
b0.06 mL/kg.
From CDC 1997.

Recombinant HBsAg vaccines (Recombivax HB, Merck; Engerix-B, GlaxoSmithKline) made in yeast have replaced earlier plasma-derived vaccines in the United States. At all ages the vaccine is administered intramuscularly at 0, 1- to 2-, and 4- to 6-month intervals, and has been found in clinical trials to provide 80% to 95% protective efficacy against hepatitis B virus infection. Recommended doses vary according to age; patients who are immunocompromised or who are receiving hemodialysis should be given larger doses as specified in package inserts. The preferred vaccination site is the arm because suboptimal antibody responses have occurred when the vaccine was injected into the buttock. Soreness and redness may occur at the injection site, and anaphylaxis has been documented, but this is rare. Booster doses are not routinely recommended at present; however, after 5 to 8 years, 30% to 60% of vaccine responders experience decline in antibody titers to less than 10 mIU/mL. Subclinical infections have been shown to occur in vaccinated persons, but protection against developing the chronic carrier state after the completed immunization schedule has been shown to persist for at least 15 years. The few instances of chronic carrier state developing several years after an active antibody response have occurred in immunocompromised individuals, primarily people with HIV infection.

Table 18.3 summarizes the current recommendations of the ACIP for postexposure prophylaxis for infants born to mothers with acute or chronic hepatitis B infection and for sexual contacts or household contacts of persons with hepatitis B infections. Table 18.4 summarizes recommendations for postexposure prophylaxis for people who have had percutaneous, ocular, or mucous membrane exposure to blood from patients with known or suspected acute or chronic hepatitis B infections.

The American Academy of Pediatrics and the ACIP recommend routine three-dose hepatitis B vaccine for all infants, beginning preferably before the newborn is discharged from hospital, and routine vaccination of adolescents through age 18 years, if not previously vaccinated. Hepatitis B vaccine is also recommended for others who are at increased risk of exposure: health care professionals exposed frequently to blood or blood products (e.g., laboratory and blood bank personnel, operating room

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staff, surgeons, dentists, endoscopists, pathologists, staff in oncology, and dialysis units and emergency room staff); homosexually active men; family members or sexual partners of chronic HBsAg carriers; prostitutes; patients who frequently receive transfusions of blood or blood products; patients in hemodialysis units; inmates and staff of institutions for the mentally retarded; inmates of long-term correctional institutions; users of illicit injectable drugs; selected international travelers (see Chapter 41); people from countries with high endemic rates of hepatitis B virus infection; and members of a family that adopt HBsAg-positive children. The vaccine is not routinely recommended for individuals who come in contact with HBsAg carriers at work or school. Screening for antibodies to hepatitis B virus before immunization is cost effective only in populations in which the prevalence of such antibodies is high (e.g., intravenous drug abusers). Vaccination of individuals who have anti-HBs from previous infection does not result in increased adverse effects.

TABLE 18.4 Recommendations for Hepatitis B Prophylaxis after Percutaneous or Permucosal Exposure

Exposed Person

Treatment When Source Is Found To Be

HBsAg Positive

HBsAg Negative

Source Not Tested or Unknown

Unvaccinated

HBIg × 1a and initiate HB vaccineb

Initiate HB vaccineb

Initiate HB vaccineb

Previously vaccinated

 

 

 

   Known responder

No treatment

No treatment

No treatment

   Known nonresponder

HBIg × 2 or HBIg × 1 and initiate revaccination

No treatment

If high-risk source, treat as if HBsAg positive

   Response unknown

Test exposed for anti-HBs

No treatment

Test exposed for anti-HBs

 

   1. If inadequatec HBIg × 1 plus HB vaccine
   2. If adequate, no treatment

 

   1. If inadequate,c initiate revaccination
   2. If adequate, no treatment

Anti-HBs, hepatitis B surface antibody; HB, hepatitis B; HBIg, hepatitis B immune globulin.
aHBIg dose, 0.06 mL/kg i.m.
bAdult dose, product specific.
cAdequate anti-HBs is ≥10 mIU/mL by radioimmunoassay or positive by electroimmunoassay.
From CDC 1997.

People at high risk of repeated exposure to blood or blood products should consider testing for anti-HBs 1 to 3 months after the third dose of vaccine to ensure they have responded (Table 18.4, footnote c). Testing at intervals of 1 year or more after vaccination may not accurately determine whether some people have responded to the vaccine. The need for booster doses for adults who receive a primary series in infancy remains to be assessed.

Hepatitis C and Non-A, Non-B Hepatitis

There is no Ig preparation known to be protective against the multiple agents of non-A, non-B hepatitis, which is now the most common cause of posttransfusion hepatitis (14). Most non-A, non-B infection is caused by hepatitis C. All blood donors are now screened for hepatitis C. Hepatitis in ambulatory patients is discussed in Chapter 47.

Influenza

Inactivated virus vaccines have been available for the prevention of influenza for many years. Earlier vaccines often led to fever and malaise, but current preparations are highly purified (15); in carefully controlled placebo studies side effects are limited to short-lived soreness at the site of the injection in approximately 1 in 5 vaccinees. Specifically, there is no evidence of increased frequency of flulike upper respiratory illness after vaccination (16). Patients with egg allergy should not receive influenza vaccination. Whole- and split-virus vaccines are available; either may be used in adults. The vaccine recommended each year is polyvalent, which means that it contains antigens from the type A and B strains that are expected to prevail during that season. The efficacy of the vaccine depends on the closeness in matching between the vaccine strains and the viruses circulating that year. Influenza vaccine has had consistently high (70% to 80%) protective efficacy against acute influenza among healthy young adults in most years. Although somewhat less protective against acute upper respiratory tract influenza in older patients, influenza vaccine is generally 50% to 70% protective against life-threatening pneumonia and other cardiovascular complications in this vulnerable age group (17). A protective antibody response occurs within 2 to 3 weeks of vaccination. This response is not impaired in patients with chronic pulmonary disease who are on maintenance systemic corticosteroids.

The recommendation (15) is an annual immunization with the current year's vaccine between September and December, before influenza season, for those in whom influenza causes the highest morbidity and mortality. This includes children ages 6 to 23 months, all individuals older than age 50 years (officially modified in 2000 from previous ACIP recommendation, which targeted age 65 years and older), and patients of any age with significant heart, lung, metabolic, immunocompromising disease, or chronic debilitating conditions that increase the risk of pulmonary aspiration, and women who will be in the second or third trimester of pregnancy during the influenza season (November through April). The vaccine is also recommended for those involved in critical jobs in which absenteeism may be detrimental (e.g., firemen, policemen); health care workers in contact with patients in community and hospital or other institutional settings; close contacts and or caregivers interacting with the above groups; and for children or teenagers receiving chronic aspirin therapy because they are at risk of Reye syndrome. Trivial intercurrent illnesses, such as mild upper respiratory tract infections, should not be viewed as contraindications to timely influenza immunization of high-risk individuals. Medicare now reimburses health care practitioners for influenza vaccination of patients older than age 65 years and in younger disabled persons enrolled in Medicare. In 2003, live attenuated influenza vaccine (LAIV) was licensed for use in the United States (FluMist, MedImmune) among healthy persons 5 to 49 years of age. LAIV must be stored at 5°F (-15°C) or lower and is administered as a single intranasal dose.

The diagnosis and management of influenza in ambulatory patients, including the use of antiviral agents, is discussed in Chapter 33.

Pneumococcal Disease

Purified polyvalent polysaccharide vaccine is available for the prevention of disease caused by Streptococcus pneumoniae. Protective efficacy is estimated to be in the range of 50% to 80% against bacteremic illness with the pneumococcal serotypes in the vaccine that has been manufactured since 1983 (23 serotypes that are responsible for 80% to 90% of invasive pneumococcal disease in the United States, including the 6 serotypes responsible for

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most penicillin-resistant pneumococcal disease). The vaccine is given as a single 0.5-mL dose, administered intramuscularly or subcutaneously, and produces few untoward effects (18). It may be administered simultaneously with influenza vaccine, preferably in the opposite arm, without diminishing antibody response. It is recommended for all people age 65 years or older and for people ages 2 to 64 years with immunocompromising disease, chronic cardiac or pulmonary disease, diabetes, alcoholism, or functional (e.g., sickle cell disease) or anatomic asplenia.

One-time revaccination after 5 years or more is now recommended for the following two groups: people younger than 65 years of age who are at high risk (e.g., immunocompromised persons, because they have relatively rapid decline in antibody titer) and people 65 years of age or older who received their initial dose before they were 65 years of age. This recommendation is based on the finding that postvaccination antibody levels and/or protective efficacy may not be lifelong (19). Patients who are revaccinated are more likely to report a local reaction at the injection site than those receiving a first vaccination. In a study population, the incidence was 11% and 3%, respectively, and the reaction usually resolved within 3 days (20). Practitioners may administer a booster dose to those initially vaccinated after age 65 years, with no increased risk of side effects, although such boosters are not recommended by the ACIP (18).

Pneumococcal pneumonia in ambulatory practice is discussed in Chapter 33.

Measles

Measles is a moderately severe illness in most people and has been associated with an overall case fatality rate of 3 per 1,000 in recent years. Case fatality rates are higher in young infants and adults than in school-age children. Since 1963, inactivated, and subsequently live, attenuated measles vaccines have been available. From the 1960s, when measles vaccination of children was introduced generally in the United States, the number of cases reported annually fell from more than 400,000 to less than 1,500. However, from 1989 to 1991, more than 55,000 cases were reported, including 11,000 hospitalizations and 130 deaths (21). Although most cases in recent years have occurred in unvaccinated preschool children, measles continues to cause disease in adolescents and adults, especially in schools and other group settings.

In response to the evidence that immunity wanes in some vaccine recipients, the following two-dose vaccine schedule, using MMR vaccine (see below), is now recommended: initial dose at 12 to 15 months of age and second dose at 4 to 6 years of age (Table 18.5). For students entering college after high school who do not have documentation of two doses, a second dose is recommended. Measles vaccine is associated with transient fever (≥103°F [≥39.4°C]) or rash 7 to 12 days after vaccination in approximately 5% of vaccines recipients. Special attention should be directed toward ensuring immunity in all health care providers and providing measles vaccine to adolescents and young adults (22).

TABLE 18.5 Current Recommendations for Measles Vaccination

 

Criteria for Adequate Protection

Routine childhood schedule, United States

Two doses:a,b
   First dose at 12–15 mo

Most areas

   Second dose at 4–6 yr (entry to kindergarten or first grade)c

High-risk areasd

Two doses:a,b

 

   First dose at 12 mo; second dose at 4–6 yr (entry to kindergarten or first grade)c

Colleges and other educational institutions after high school

Documentation of receipt of two doses of measles vaccine after the first birthdayb or other evidence of measles immunitye

Medical personnel beginning employment

Documentation of receipt of two doses of measles vaccine after the first birthdayb or other evidence of measles immunitye

aBoth doses should preferably be given as combined measles, mumps, rubella (MMR) vaccine.
bNo less than 1 mo apart. If no documentation of any dose of vaccine, first dose of vaccine should be given at the time of school entry or employment and second dose no less than 1 mo later.
cSome areas may elect to administer the second dose at an older age or to multiple age groups.
dA county with more than five cases among preschool-aged children during each of at least 5 yr, a county with a recent outbreak among unvaccinated preschool-age children, or a county with a large inner-city urban population. These recommendations may be applied to an entire county or to identified risk areas within a county.
ePrior physician-diagnosed measles disease, laboratory evidence of measles immunity, or birth before 1957.
From CDC 1997.

Unimmunized household contacts of persons with measles, especially infants born to nonimmune women, should be given Ig 0.25 mL/kg (up to 15 mL maximum). Immunocompromised children and adults exposed to measles should receive 0.5 mL/kg (maximum dose 15 mL) of Ig.

Mumps

From 2 to 1995, the number of cases of mumps reported annually in the United States fell from more than 100,000 to less than 1,000 because of the widespread use of mumps vaccine in children. Live attenuated mumps virus vaccine, preferably given as MMR (see below), is recommended routinely for children and for unvaccinated young adults with no history of health care

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practitioner-diagnosed mumps (22). Most people born before 1957 can be considered immune. Because the mumps virus can cause severe illness in adults (orchitis, meningitis, or pancreatitis), there is good reason to provide protection to young adults who may be susceptible. Outbreaks of mumps have been reported among college and university students, and this group merits special attention. A single dose of mumps vaccine, alone or in MMR, yields durable protection in approximately 90% of recipients.

Rubella

Since 1970, live attenuated rubella virus vaccine has been administered routinely to children 1 year of age and older (22). The major rationale for use of this vaccine is prevention of the spread of rubella virus to pregnant women and thus reduction of the incidence of the congenital rubella syndrome (CRS). Reported cases of CRS remained constant at 50 to 60 from 1970 to 1980 and then fell dramatically to 1 in 1988; but in 1990 and 1991 a resurgence of rubella was observed, and there were more than 40 cases of CRS reported in the United States. Since 2001, rubella has ceased to be endemic in the United States and only four CRS cases were reported during 2001 to 2004.

Anyone working in a medical facility who does not have documentation of past rubella vaccination or serologic evidence of immunity should be vaccinated against rubella (MMR vaccine, see below) (22). Adults, and especially nonpregnant adolescent girls and women in the childbearing age group, should be offered rubella vaccine if they have not received vaccine or are not known to have serologic evidence of immunity. Serologic testing before vaccination is unnecessary because prior immunity does not increase the risks of vaccination. Vaccinated women should be cautioned against becoming pregnant (see Chapter 100) for the 3 months after receiving rubella vaccine because of the theoretical possibility of fetal damage. However, no cases of congenital abnormalities have been observed in more than 300 women who received rubella vaccine just before or during pregnancy, and the theoretical risk is less than 1%. Approximately 25% of postpubertal women receiving rubella vaccine experience arthralgias in the first 1 to 3 weeks after immunization. Frank arthritis is much less common and all symptoms are usually mild and transient.

Measles, Mumps, and Rubella Vaccine

In most cases, MMR is the vaccine of choice when any of its components is indicated, although the three vaccines are available separately. A two-dose schedule is now highly recommended for all children (22). The first dose of MMR should be administered at 12 to 15 months of age; the second dose is now recommended at 4 to 6 years, before school entry, but may be given at 11 to 12 years of age. The measles component is associated with the occurrence of fever or mild rash within 7 to 12 days after injection. MMR or its component vaccines should not be given to pregnant women. Anaphylaxis or other serious systematic adverse reactions are rare with MMR or any of the three individual component vaccines.

Most adults born before 1957 are assumed to be immune to mumps, measles, and rubella. Adults born in 1957 or later who do not have a medical contraindication should receive at least one dose of MMR vaccine unless they have documentation of vaccination or other acceptable evidence of immunity to these three diseases: laboratory evidence of immunity or health care practitioner documented diagnosis of the disease. Furthermore, it is now recommended that adolescents and college students who have no documentation of live MMR vaccinations or other acceptable evidence of immunity should receive a two-dose course of MMR vaccine, with the second dose administered no sooner than 1 month after the initial dose. Students with medical contraindications to vaccination with MMR and any of its component vaccines should be given a letter of explanation to present to the health officials of their educational institution.

Meningococcal Disease

Meningococcal disease is a serious potentially fatal infection that usually occurs sporadically, with the highest incidence in infants. Occurrence is relatively rare among the general population, but the incidence is increased among healthy young adults living in congregated circumstances, particularly military recruits in barracks and college students in dormitories (23). Two meningococcal vaccines for serotypes A, C, Y, and W-135 produced by Sanofi Pasteur are licensed for use in the United States. MPSV4, a polysaccharide vaccine (Menomune) is administered as a single subcutaneous injection that elicits protective antibody within 2 weeks. MCV4, a polysaccharide-protein conjugate vaccine (Menactra), licensed for use in the United States in 2005, is administered as a single intramuscular dose and elicits a more enduring immune response. Both vaccines cause sore arm at injection site in a small percent of recipients. Effective 2005, the ACIP recommended meningococcal vaccination for all adolescents, preferably at routine preadolescent health exam at 11 to 12 years of age, to all college freshmen living in dormitories, and to other high-risk groups (Table 18.1) (24). Vaccination is also recommended to control community outbreaks, defined as three or more cases within less than 3 months that result in an attack rate of 10 or more per 100,000 population at risk.

Chemoprophylaxis is recommended for close contacts of a patient with invasive meningococcal disease (Table 18.6) (24).

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Close contacts are defined as household members, child-care center contacts, anyone directly exposed to the patient's oral secretions (e.g., kissing, mouth-to-mouth resuscitation), and travelers who have had direct contact with respiratory secretions from an index-patient for a prolonged time (e.g., flight lasting longer than 8 hours).

TABLE 18.6 Schedule for Administering Chemoprophylaxis Against Meningococcal Disease

Drug

Age Group

Dosage

Duration and Route of Administrationa

Rifampinb

Children aged <1 mo

5 mg/kg body weight every 12 hrs

2 days

 

Children aged ≥1 mo

10 mg/kg body weight every 12 hrs

2 days

 

Adults

600 mg every 12 hrs

2 days

Ciprofloxacinc

Adults

500 mg

Single dose

Ceftriaxone

Children aged <15 yrs

125 mg

Single IMd dose

Ceftriaxone

Adults

250 mg

Single IM dose

aOral administration unless indicated otherwise.
bNot recommended for pregnant women because it is teratogenic in laboratory animals. Because the reliability of oral contraceptives might be affected by rifampin therapy, consideration should be given to using alternative contraceptive measures while rifampin is being administrated.
cNot usually recommended for persons aged <18 years or for pregnant and lactating women because it causes cartilage damage in immature laboratory animals. Can be used for chemoprophylaxis of children when no acceptable alternative therapy is available. Recent literature review identified no reports of irreversible cartilage toxicity or age-associated adverse events among children and adolescents (Source: Burstein GR, Berman SM, Blumer JL, Moran JS. Ciprofloxacin for the treatment of uncomplicated gonorrhea infection in adolescents: dose the benefit outweigh the risk? Clin infect Dis 2002;35:S191-9).
dIntramuscular.
From Recommendations of the Advisory Committee on Immunization Practices (ACIP). Prevention and control of meningococcal disease. MMWR Recomm Rep 2005;54(RR-7):1–21.

Polio

Wild poliovirus and new-onset poliomyelitis have been eradicated from the Western hemisphere and Europe, and global eradication is anticipated within several years. With a view to eliminating vaccine-associated paralytic polio (VAPP) caused by oral polio vaccine (OPV), which was accounting for all new domestically acquired polio in the United States, national vaccination policy changed in 1997 from first line use of OPV to a sequential schedule of inactivated poliovirus vaccine (IPV) followed by OPV (25). In 2000, an exclusively IPV schedule was adopted (26). No further cases of VAPP have occurred in the United States.

Polio vaccination for adults in the United States is recommended for travelers to remaining polio endemic parts of the world (see Chapter 41). Adult travelers who have previously completed a primary OPV or IPV series require a single booster dose of IPV; unvaccinated adults require a primary vaccination series with IPV (25).

Rabies

Indigenously acquired human rabies is rare in the United States. Theoretically, all clinical cases of rabies are preventable if protective treatment is given promptly after exposure. The incubation period is usually 2 to 8 weeks, but it may be as short as 10 days or as long as 1 year or more.

Since 1982, inactivated rabies virus vaccine produced in human diploid cells has been in use in the United States. It causes fewer and milder reactions than the older duck embryo-derived vaccine. Formulations for intramuscular or intradermal injection are available, as is a hyperimmune globulin derived from human sera (human rabies immune globulin [HRIg]).

For postexposure prophylaxis after an animal bite (see Chapter 32), the recommended treatment schedule is as follows (27): on day 1, simultaneous administration of HRIg (20 IU/kg, up to half infiltrated into the wound and the remainder intramuscularly), and the first dose of vaccine, also given intramuscularly; additional vaccine doses are given on days 3, 7, 14, and 28. The effectiveness of this regimen in protecting humans from rabies has been well established. Adverse reactions (urticaria, anaphylaxis, transient headache, and fever) occur in less than 0.5% of persons receiving this vaccine.

For preexposure prophylaxis, people working in areas where rabies is enzootic or in occupations where potential for rabies exposure is high (e.g., veterinarians) should be vaccinated before exposure. In this situation, the appropriate formulation may be given intradermally in 0.1-mL doses or intramuscularly in 1.0-mL doses on days 0, 7, and 21 or 28 with booster doses every 2 years (see Chapter 41 for details regarding frequency of vaccine for those living in high-risk areas outside of the United States).

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Preexposure immunization does not eliminate the need for postexposure prophylaxis, but it obviates the need for HRIg and decreases the number of vaccine doses required to two (days 0 and 3).

Tuberculosis

Efforts to control tuberculosis in the United States are based on early identification and treatment of active disease and on isoniazid prophylaxis of the contacts of tuberculous patients and other groups at increased risk (see Chapter 34). Because most new tuberculosis cases are reactivation of disease in older individuals and because efficacy has been questioned in the past, indications for immunization with bacillus Calmette-Guérin (BCG) vaccine in the United States have been limited (28). However, the recent spread of multiple-drug-resistant tuberculosis, unresponsive to isoniazid and rifampin, and a recent meta-analysis indicating an up to 50% reduction in the risk of tuberculosis in BCG-vaccinated individuals (29), have prompted reconsideration of the use of BCG in the United States.

At present, BCG should be considered for the following two groups:

  • Infants and children who have a negative tuberculin skin test and (a) who have repeated exposure to persistently untreated or unsuccessfully treated sputum-positive pulmonary tuberculosis and cannot be separated from the presence of the infectious patient or reliably receive isoniazid or (b) who have repeated exposure to active disease caused by multiple-drug-resistant tuberculosis organisms and cannot be separated from the infectious patient.
  • Health care workers who have negative tuberculin skin tests and work in settings with recurrent transmission of multiple-drug-resistant tuberculosis.

BCG is a live attenuated vaccine derived from Mycobacterium bovis. The Tice strain (Organon, Inc.) is the only BCG vaccine licensed in the United States. It is administered percutaneously through multiple punctures in the upper arm, with doses differing by age of recipient. A small ulcerating pustule typically occurs at the vaccination site several weeks after receiving the vaccine. BCG vaccine is contraindicated in people receiving immunosuppressive therapy or who have immunocompromising conditions, including HIV infection.

Varicella

Varicella (chickenpox) is a highly contagious generally self-limited disease of childhood caused by varicella zoster virus. Although varicella occurs infrequently among adolescents and adults, it is more severe among these groups and among immunocompromised people in all age groups. Complications include pneumonia, encephalitis, and occasionally death. In 1995, a live attenuated varicella virus vaccine (Varivax, Merck) was licensed for use in people 12 months of age or older in the United States.

Although primarily intended for children, varicella vaccination is recommended for everyone 12 years of age or older, particularly those who are susceptible (those with negative or unknown history of varicella) and who have close household or occupational (health care workers) contact with immunocompromised people or others at high risk of serious complications (30). Because 70% to 90% of adults without a reliable history of varicella are actually immune, serologic testing before vaccination is likely to be cost effective in these subjects.

Vaccination of children between 12 months and 12 years of age consists of a single dose, whereas vaccination of persons more than 12 years old consists of two doses, with the second dose administered subcutaneously 4 to 8 weeks after the initial dose. Adverse effects have been limited to pain and redness at the injection site.

For postexposure prophylaxis, varicella zoster Ig, available from American Red Cross distribution centers, is indicated for immunocompromised adolescents and adults who are susceptible to varicella (i.e., have a negative history for chickenpox and no history of receiving varicella vaccine) and who have been exposed to an active varicella case. It is effective in preventing or suppressing varicella if given within 96 hours of exposure. Healthy adults and pregnant women who are susceptible to varicella (see above) are at increased risk of varicella complications and may also be given varicella zoster Ig for postexposure prophylaxis. Recommended prophylactic dosage of varicella zoster Ig is 125 units/10 kg (22 lb), administered intramuscularly. The major adverse reaction is discomfort at the injection site; anaphylactic shock is rare.

Zoster

Zoster or “shingles” is an illness comprising unilateral radicular pain and accompanying vesicular rash involving a single dermatome, which is caused by reactivation of latent varicella-zoster virus (VSV) within sensory ganglia. Incidence and severity, including often debilitating postherpetic neuralgia are greatest in persons older than age 60 years. A large, multicentered, randomized clinical trial of live attenuated VZV vaccine (Oka/Merck) completed in 2005 demonstrated a 51% reduction in shingles incidence and a 66% reduction in postherpetic neuralgia among adults 60 years of age and older (31). It is anticipated that this vaccine will be licensed and recommended for use in adults.

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Specific References*

For annotated General References and resources related to this chapter, visit http://www.hopkinsbayview.org/PAMreferences.

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