Immunization

Vaccines rank among the greatest achievements of medicine and public health (Box 25.1). Jenner commenced the era of immunization when he induced protection against smallpox by inoculating susceptible persons with vesicular fluid from cowpox lesions. Over the ensuing two centuries, vaccines have controlled major infectious diseases (in at least some areas of the world) including smallpox, diphtheria, tetanus, pertussis, yellow fever, measles, mumps, rubella, poliomyelitis, and Haemophilus influenzae type B disease. In addition, availability of vaccines has resulted in significant advances against hepatitis A, hepatitis B, varicella, influenza, and meningococcal infections. Vaccination has resulted in the eradication of smallpox from the world and it is anticipated that wild-type poliovirus may also be eradicated in the near future. Each year an estimated 5 million life years are saved worldwide through control of poliomyelitis, measles, and tetanus. Overall vaccine-preventable diseases in many developed countries have been reduced by 98% to 99% (Table 25.1).

Whereas childhood immunization in the United States is a great success story with immunization levels high and levels of vaccine-preventable diseases at record or near-record low levels, immunization levels among adults for vaccines that are universally recommended for more than one age group remain disappointingly low.

In the United States, deaths from vaccine-preventable diseases occur predominantly in adults, with an estimated 50,000 to 70,000 adults dying each year from such diseases. Predominantly, mortality is caused by pneumonococcal infection, influenza, and Hepatitis B (Table 25.2). In fact, vaccine-preventable deaths exceed those from motor vehicle accidents or AIDS. Clearly, immunization of adults has not received the same high priority as immunization of children. Factors that contribute to the poor record of adult immunization include (i) concerns regarding safety and efficacy of vaccines among the general public (and healthcare workers); (ii) uncertainty about specific recommendations; (iii) liability concerns; (iv) inadequate reimbursement for immunizations; (v) a poorly informed public; (vi) lack of a delivery system infrastructure for immunization of adults; (vii) inadequate mechanisms to remove financial burdens for uninsured adults (e.g., Vaccine for Children’s Program); and (viii) provider attitudes.

Currently, 10 major vaccines are designed for routine use in adults (Table 25.3). It is important that obstetriciangynecologists be involved in providing immunization of adults. Unfortunately, vaccination of adult patients has been inadequately addressed by obstetrician-gynecologists and other primary-care providers. For example, the American College of Physicians’ Task Force on immunizations has recommended that age 50 be established as the time to review preventive health measures including an emphasis on risk factors that identify patients in need of pneumococcal and hepatitis B vaccines and initiation of annual influenza immunization. The remainder of this chapter will discuss the general principles of immunization, specific details for use of these ten vaccines, and special circumstances related to immunizations such as pregnancy, occupational exposure, travel, postexposure immunizations, and immunocompromised states.

GENERAL PRINCIPLES OF IMMUNIZATION

Immunization is the process by which immunity is artificially induced or protection from disease is provided. Immunization can be active or passive. Active immunization induces the body to develop defenses against infection; it is accomplished with either vaccines or toxoids that stimulate the immune system to produce antibodies or cell-mediated immunity, or both, which in turn protect against an infectious disease. Passive immunization is a process that provides temporary protection against an infectious agent by administration of exogenously produced antibody. The most common methods of passive immunization are transplacental passage of maternal antibodies to the fetus and the use of immunoglobulins to prevent specific infectious diseases.

Immunizing agents include (i) vaccine: a suspension of attenuated live or killed microorganisms or fractions thereof (e.g., bacterial proteins, polysaccharides and protein-conjugated polysaccharides or recombinant protein) administered to induce immunity; (ii) toxoid: a modified bacterial toxin which has been rendered nontoxic but still capable of producing antitoxin; (iii) immunoglobulin: a solution containing antibody from human blood that can provide passive immunization against certain infections (e.g., measles and hepatitis A) or routine protection of immunodeficient patients; and (iv) specific immunoglobulin: special preparations obtained from donor pools with a high antibody content against a specific disease (e.g., hepatitis B immune globulin [HBIG] and varicella-zoster immune globulin [VZIG]).

Safety and Efficacy of Vaccines

While modern vaccines are very effective and safe, all vaccines are associated with some adverse effects and all vaccines are not 100% effective. Despite the demonstrated high efficacy of vaccines, controversy has arisen over adverse effects attributed to vaccine use. In response to these concerns, the Institute of Medicine (IOM) undertook an assessment in the early 1990s of the available data for 9 of the 11 vaccines universally recommended for children and the serious adverse events reported to
be associated with these vaccines. In most cases, there was insufficient evidence to establish causation. Table 25.4 summarizes the IOM findings for adverse events in which data was available to reach a conclusion. Subsequently, the IOM findings were reviewed by the Advisory Committee for Immunization Practices (ACIP) who assessed newer data related to Guillain-Barre syndrome. Based on this newer data the ACIP did not confirm a causal relationship between OPV, DTP, or tetanus toxoid and Guillain-Barre syndrome. Further studies failed to substantiate an increased risk for chronic arthritis among women vaccinated with RA 27/3 (rubella) vaccine. Most recently controversy has arisen over the role of measles, mumps, and rubella (MMR) vaccine in autism. Two large studies clearly refuted this suggestion: (i) a cohort study of all children born in Denmark from 1991 to 1998 (440,665 [82%] of 537,303 received MMR) demonstrated a relative risk for autistic disorder in vaccinated children vs. unvaccinated of 0.92 (0.68-1.24); and (ii) a case-control study from the UK General Practice Research Database reported no association between MMR use and pervasive developmental disorder (OR, 0.85; 95% CI, 0.68-1.09). In the later study, findings were similar when restricted to autism alone.

TABLE 25.1 ▪ HISTORICAL COMPARISON OF MORBIDITY AND MORTALITY FOR VACCINE-PREVENTABLE DISEASES: UNITED STATES

Vaccine-Preventable Disease	Annual Average Prevaccine		Post-vaccine		Decline %
Vaccine-Preventable Disease	Cases	Deaths	Cases^a	Deaths^b	Cases	Deaths
Diphtheria	21,053	1,822	0	0	100	100
Measles	530,217	440	55	0	99.9	100
Mumps	162,344	39	6,584	0	95.9	100
Pertussis	200,752	4,034	15,632	27	92.2	99.3
Poliomyelitis, acute	19,794	1,393	0	0	100	100
Poliomyelitis, paralytic	16,316	1,879	0	0	100	100
Rubella	47,745	17	11	0	99.9	100
Congenital rubella	152	NA	1	0	99.3	NA
Smallpox	29,105	337	0	0	100	100
Tetanus	580	472	41	4	92.9	99.2
Hepatitis A	117,333	137	3,579 (15,298)	18	87.0	86.9
Acute Hepatitis B	66,232	237	4,713 (13,169)	47	80.1	80.2
Invasive Haemophilus influenzae type B	20,000	1,000	208	<5	99.8	99.5
Invasive pneumococcal disease	63,067	6,500	5,169 (41,550)	4,850	34.1	25.4
Varicella	4,085,120	105	48,445 (612,768)	19	88.0	81.9
^a1996. ^bDiphtheria-tetanus, 1995; Hepatitis A-Varicella, 1996.

In the case of pregnancy, there is no direct evidence of risk to the fetus when pregnant women are inoculated with a particular vaccine. However, most live virus vaccines result in viremia, which can lead to infection of the fetus. Thus, live virus vaccines are not administered to pregnant women except in special circumstances.

Immunization Programs for Adults

In the United States, recommendations for vaccine use are developed by three bodies: (i) the ACIP of the Centers for Disease Control and Prevention (CDC) develops recommendations oriented toward the public health arena; (ii) the Committee on Infectious Diseases of the American Academy of Pediatrics (Red Book) develops recommendations for use in private pediatric practice; and (iii) the Task Force on Adult Immunization of the American College of Physicians and the Infectious Diseases Society of America develop recommendations for adults in the private sector. Currently, the ACIP, AAP, the American Academy of Family Physicians and the American College of Obstetricians and Gynecologists (ACOG) collaborate and issue a consensus schedule for adult immunizations that is updated annually.

The immunization schedule recommended for adults is divided into three age groups (Fig. 25.1). In the 19 to 49 years of age group it is recommended that (i) tetanus diphtheria (Td) booster be given every 10 years (tetanus, diphtheria,
and acellular pertussis [Tdap] should replace a single dose of Td for adults aged <65 years who have not previously received a dose of Tdap); (ii) MMR vaccination ≥1 dose if no documentation of vaccination or prior infection; (iii) influenza vaccine given to high risk groups and considered for all patients; (iv) varicella vaccine given to patients with no history of clinical varicella; and (v) HPV vaccine women ≤26 years who have not completed HPV vaccine series. Age group 50 to 64 years of age should receive: (i) Td booster every 10 years (substitute one-dose Tdap); (ii) influenzae vaccine annually for all persons in this age group; (iii) varicella vaccine in patients with no clinical history of varicella; and (iv) zoster vaccine, a single dose for adults ≥60 years. For those ≥65 years of age it is recommended that they receive influenzae vaccine annually, one dose of pneumococcal vaccine, one dose of zoster vaccine if not given before,
varicella vaccine if no previous infection or vaccination, and Td booster every 10 years. In all age groups, additional vaccines are recommended based on the presence of risk factors (e.g., medical, occupational, lifestyle) (Figs. 25.1 and 25.2). Figure 25.2 summarizes vaccines that are indicated for adults based on medical and occupational indications.

TABLE 25.2 ▪ ESTIMATES OF THE EFFECT OF FULL USE OF THE VACCINES ADVOCATED FOR ADULTS^a

Diseases	Estimated Annual Deaths	Estimated Vaccine Efficacy	Current Vaccine Use	Additional Preventable Deaths per Year
Influenza	20,000	70	30	9,800
Pneumococcal	40,000	60	14	20,640
Hepatitis B	5,000	90	10	4,050
Tetanus/diphtheria	<25	99	40	<15
MMR^b	<30	95	Varies	<30
^a Reproduced with permission from Gardner P, Schaffner W. Immunization of adults. N Engl J Med 1993;328:1252-1258. ^bMMR, measles-mumps-rubella.

TABLE 25.3 ▪ MAJOR VACCINES RECOMMENDED FOR ROUTINE USE IN ADULTS

Tetanus, diphtheria, pertussis

Human papillomavirus

Meningococcal

Zoster

Measles-mumps-rubella

Varicella vaccine

Influenza virus

Pneumococcal (polysaccharides)

Hepatitis A vaccine

Hepatitis B virus

TABLE 25.4 ▪ SUMMARY OF INSTITUTE OF MEDICINE FINDINGS ON THE RELATIONSHIP OF ADVERSE EVENTS TO INDIVIDUAL VACCINES^a

Vaccine	Establishes Causation	Favors Causation	Favors Rejection of Causation
DT/Td/T	Anaphylaxis	Guillain-Barre syndrome^b; brachial neuritis	Encephalopathy, infantile spasms
Pertussis (DTP)	Anaphylaxis; protracted inconsolable crying	Acute encephalopathy; shock and unusual shock-like state (hypotonic-hyporesponsive episodes)	Infantile spasms, hypsarrhythmia Reye syndrome
Measles		Anaphylaxis; death from measles vaccine strain in primarily immunocompromised	SIDS
MMR	Anaphylaxis, thrombocytopenia
OPV	Poliomyelitis; death from polio vaccine strain (mainly in immunocompromised individuals)	Guillain-Barre syndrome^b
Hepatitis B	Anaphylaxis
HIB conjugate			Early onset H. influenzae type B disease
Rubella	Acute arthritis	Chronic arthritis^c
^aModified from Reference 9 (Table 312.2). DT, diphtheria and tetanus toxoid; HIB, Haemophilus influenzae type BMMR-measles, mumps, rubella; OPV, oral polio vaccine. ^b,cAdvisory Committee for Immunization Practices did not confirm based on more recent studies.

FIGURE 25.1 ACIP-recommended adult immunization schedule by vaccine and age group.

Currently, five major types of vaccines are available. These include (i) live attenuated viruses or bacteria (e.g., cowpox, oral polio vaccine, typhoid, cholera); (ii) killed whole viruses (e.g., Salk polio vaccine, influenza); (iii) killed bacteria (e.g., Pertussis, typhoid, cholera); (iv) purified component vaccines such as polysaccharide vaccines (e.g., pneumococcal, H. influenzae type B) or toxins (e.g., tetanus, diphtheria); and (v) genetically engineered proteins produced by recombinant technology (e.g., Hepatitis B vaccine, HPV vaccine). In the future a sixth type, DNA vaccines will be available that will provide direct inoculation with purified DNA. The advantage of DNA vaccines is that they stimulate both the humoral and cell-mediated arms of the immune system, do not require new technology, are more stable, and
less expensive. This technology will allow for rapid creation of new vaccines.

FIGURE 25.2 ACIP vaccines indicated, based on medical and other conditions.

General Contraindications to Vaccines/Immune Therapy

The decision to use a vaccine must take into account the risks of disease, the benefits of vaccination, and the risks associated with vaccination. A contraindication means that a vaccine should not be administered. On the other hand, a precaution identifies a situation in which vaccine may be appropriate if after careful assessment, the benefit of vaccination is judged to outweigh the risk. Contraindications and/or precautions can be generic and applicable to all vaccines, or specific to a particular vaccine(s).

There are two contraindications which can be generalized to all vaccines: (i) previous anaphylactic reaction to the same vaccine; and (ii) allergy to a vaccine constituent. Presence of moderate or severe illness, with or without a fever is the only generalized precaution for vaccine administration. The specific contraindications and/or precautions are discussed in the sections for each vaccine.

While concern has been raised regarding the use of vaccines in pregnant and lactating women, the risks in pregnancy and lactation are primarily theoretic. In pregnancy the benefit is greater than the risk when (i) risk for disease exposure is high (e.g., travel to endemic areas); (ii) infection would pose a special risk to pregnant women (e.g., influenza); and (iii) vaccine is unlikely to cause harm. Breastfeeding is generally not a contraindication to vaccines or immune therapy. Killed and attenuated vaccines do not replicate. While live virus vaccines (e.g., Rubella) may replicate and be excreted in breast milk, the neonate is usually not infected and any infection is well tolerated.

From 1966 until recently vaccination in pregnant women was discouraged and not recommended. The rationale for such an approach was not based on scientific data but rather occurred as a “knee jerk” reaction to protect pregnant women and their fetuses. In actuality vaccination in pregnant women to protect both mother and offspring was practiced extensively in the United States from 1957 to 1966 at a time when immunization with influenza and poliovirus vaccines was recommended during pregnancy. The safety of vaccination during pregnancy was demonstrated by the Collaborative Perinatal Project which enrolled >50,000 pregnant women between 1959 and 1965 and evaluated over 9,000 vaccine doses administered during the first 4 months of pregnancy. The vaccines most commonly used were inactivated poliovirus vaccines (18,342 women), live attenuated oral poliovirus vaccine (3,056 women) and influenza vaccine (2,291 women). These immunizing agents were not associated with adverse outcomes. Moreover, the vaccines available currently are less reactogenic, more immunogenic, and better standardized. Fortunately, ACOG currently encourages immunization during pregnancy, when indicated, and emphasizes that the benefits of immunization to the pregnant woman and her neonate usually outweigh the theoretic risks of adverse effects.

Immunosuppression, either as a result of underlying disease or therapy, is a contraindication for use of most live virus or bacterial vaccines. Measles and varicella vaccination of HIV-infected persons who are not severely immunocompromised is an exception. In a similar vein, live virus vaccines should not be administered to individuals who have received high doses of systemic corticosteroids (e.g., prednisone 20 mg/day) for ≥14 days until one month or more after steroid therapy was discontinued. Steroid therapy either given in low to moderate doses or physiologic doses is not a contraindication for administration of live vaccines.

TETANUS AND DIPHTHERIA TOXOID AND PERTUSSIS VACCINE

Background

In the past diphtheria was a major cause of morbidity and mortality with death rates in the late 19^th century averaging nearly 200 per 100,000 population annually and the proportion of total deaths attributable to diphtheria annually ranged from 3% to 10%. With the introduction of diphtheria toxoid, the incidence of diphtheria fell dramatically from a peak of 30,508 cases and 3065 deaths annually prior to WWII. In 2007 no cases of diphtheria were reported in the United States.

Tetanus is caused by the bacterium Clostridium tetani and is unique among the vaccine-preventable diseases because it is not a communicable disease. Tetanus, despite the presence of a highly effective toxoid, remains a major public health problem worldwide, with an estimated 1 million deaths per year caused by neonatal tetanus and an estimated 310,000 to 700,000 non-neonatal cases resulting in 122,000 to 300,000 deaths annually in developing countries. In the United States <50 cases of tetanus are reported annually to the CDC.

Pertussis is caused by Bordetella pertussis and at one time was a major cause of morbidity and mortality in infants and children in the United States. From the time Pertussis became a reportable disease (1920s) through the early 1940s, 115,000 to 270,000 cases of pertussis were reported each year in the United States with 5,000 to 10,000 deaths annually. The availability and widespread use of Pertussis vaccine in children led to a dramatic decrease in the incidence of Pertussis (>90%). Following the change from whole-cell to acellular pertussis vaccines in the 1990s, excellent pertussis control was achieved in children.

However, since the 1980s the number of reported cases has steadily increased, especially among adolescents and adults (Fig. 25.3). In 2006, the incidence of pertussis decreased and 15,652 cases were reported to the CDC. According to the CDC there are an estimated 600,000 cases annually among adults 19 to 64 years of age. Thus, among the bacterial vaccine-preventable disease for which universal vaccination is recommended, pertussis is the least well controlled.

The epidemiologic profile of pertussis has changed with the recognition that pertussis is not just a disease of children. While most severe disease and mortality occur in infants, the overall disease burden has shifted to adolescents and adults. In large part, this is the result of waning vaccine-induced immunity to pertussis. Furthermore, until recently (see below) pertussis vaccine was not recommended for persons over the age of 6. Most adult cases are not suspected or diagnosed. As a result, there is a large pool of susceptible adolescents and adults as a source of infection in nonvaccinated young children.

With the recognition that pediatric immunization had not decreased the incidence of pertussis in adults, the occurrence of outbreaks, or transmission of infection to unimmunized children, the CDC (2006) issued recommendations for prevention of pertussis among adolescents and adults utilizing a single-dose booster of tetanus toxoid, diphtheria toxoid, and acellular pertussis vaccine (Tdap).

FIGURE 25.3 Number of reported pertussis cases, by year: United States, 1922 to 2005.

Indications

Diphtheria and tetanus toxoids combined with acellular Pertussis vaccine (DTaP) is the preferred vaccine and is recommended for all infants. A single dose of Tdap is recommended as a booster for adolescents aged 11 to 18 years of age (preferred age, 11-12 years) with subsequent boosters of Td recommended every 10 years. Adults aged 19 to 64 years should receive a single dose of Tdap to replace Td if their last dose of Td was ≥10 years earlier (intervals shorter than 10 years may be used to vaccinate against pertussis).

Specific Contraindications and Complications

Severe reactions to Dt, Td, or Tetanus toxoid alone are unusual. Anaphylaxis has rarely resulted from diphtheria and tetanus toxoid. The data favors a causative role of diphtheria and tetanus toxoid for brachial neuritis. However, brachial neuritis is usually self-limited and is not a precaution or contraindication to future vaccination. While initial data favored causation of Guillain-Barre syndrome, more recent assessments do not. ACIP considers Guillain-Barre syndrome ≤6 weeks after a tetanus toxoid-containing vaccine a precaution for subsequent tetanus toxoid-containing vaccine. The IOM found no evidence of causation for Dt, Td, or tetanus toxoid alone for encephalopathy or infantile spasms.

Two additional adverse events have been associated with vaccines containing tetanus toxoid, diphtheria toxoid, and/or pertussis antigens. Arthus reactions (type III hypersensitivity reaction) which rarely occur at the injection site following tetanus or diphtheria toxoid are characterized by severe pain, swelling, induration, edema, and hemorrhage that occur 4 to 12 hours after vaccination and usually resolve without sequelae. ACIP recommends that persons who experienced an Arthus reaction after a dose of tetanus toxoid containing vaccine not receive Td more frequently than every 10 years, even for tetanus prophylaxis with wound management. Extensive limb swelling (ELS) has been described following the fourth or fifth dose of the pediatric series of Dtap. It is not disabling and resolves without complications within 4 to 7 days. ELS is not a contraindication or precaution for Tdap.

The only contraindication specific for the use of Dtap/DTP is encephalopathy within 7 days of administration of a previous dose. The contraindications general for all vaccines also apply (see previous discussion). Precautions for use of Dtap/DTP include (i) Fever >40.5°C within 48 hours after vaccination with prior dose and not attributable to another identifiable cause; (ii) collapse or shock-like state within 48 hours of receiving prior dose; (iii) convulsions within 3 days of receiving prior dose; (iv) persistent inconsolable crying lasting ≥3 hours, within 48 hours of receiving prior dose; and (v) Guillain-Barre syndrome within 6 weeks of prior dose.

Dosage

Universal use of Dtap (five-injection series) in infancy and childhood is recommended unless contraindications exist (http://www.cdc.gov/nip/acip). In addition, at age 11 to 12 years a booster dose of Tdap is recommended. Tetanus and diphtheria toxoid (Td) (for adult use) is used in persons ≥19 years of age as a single-dose booster every 10 years. Tdap is recommended as a single-dose replacement for Td for adults <65 years who have not previously received a dose of Tdap.

In addition, ACIP recommends that adults who have or who anticipate having close contact with an infant aged <12 months (e.g., parents, grandparents aged <65 years, child-care providers, and healthcare personnel) should receive a single dose of Tdap at intervals <10 years since the last Td.

Use During Pregnancy or Lactation

As with other inactivated vaccines and toxoids, pregnancy is not a contraindication for Tdap vaccination. No increased risk to mother or fetus from vaccination with Dt or tetanus toxoid during pregnancy, including the first trimester has been demonstrated. Widespread vaccination with tetanus toxoid of pregnant women in developing countries with high rates of neonatal tetanus has demonstrated the safety as well as efficacy of this approach. In the United States administration of Td is recommended for pregnant women who have not completed a primary series of vaccination or who are due for a booster. In pregnancy, women who received their last Td vaccination ≥10 years previously should receive Td during the second or third trimester. If they received the last Td vaccination <10 years earlier, administer Tdap in the immediate postpartum period. When possible, women should receive Tdap before becoming pregnant.

MEASLES, MUMPS, AND RUBELLA

Background

Widespread vaccination of children against measles, mumps, and rubella has dramatically reduced the incidences of these
infections and their associated complications worldwide. Measles is a ubiquitous, highly contagious infection, which, prior to vaccine availability, affected nearly 100% of the population by adolescence. In the United States during the premeasles vaccine era there were approximately 500,000 cases of measles reported each year with an estimated actual 4 million cases annually. The morbidity and mortality associated with measles was also extensive with an estimated annual occurrence of 150,000 cases of pneumonia; 48,000 hospitalizations; 7,000 seizure episodes, 4,000 cases of encephalitis of which 25% had permanent neurologic sequelae or deafness; and 500 deaths. Subacute sclerosing panencephalitis (SSPE) is a progressive fatal disease of the central nervous system caused by persistent measles virus infection.

Following measles vaccine licensure in the United States in 1963, the incidence of measles was dramatically reduced to 55 cases in 2006 (<1 case per million population), of which almost all were associated with international importation. Whole school immunization requirements were very effective in reducing measles, a single dose of measles vaccine was not sufficient to prevent transmission in all settings. Therefore a second dose of measles-containing vaccine was recommended in 1989. In 2000, the CDC reported that measles was no longer endemic in the United States.

Prior to the licensing of live attenuated mumps vaccine in 1967, mumps was a common communicable disease of childhood. The morbidity of mumps is best appreciated when the disease is perceived as a respiratory infection that is often accompanied by viremia resulting in multi-organ involvement, predominantly salivary glands. Complications of mumps are more common in adults and include orchitis in postpubertal men, pancreatitis, central nervous system involvement (meningoencephalitis), mastitis, nephritis, arthropathy, and myocarditis (rare). In addition mumps is a major cause of sensorineural deafness. Post licensure of mumps vaccine, the reported cases of mumps in the United States declined from 152,209 in 1968 to 666 cases in 1998.

However, in 2006, there were 6,584 cases of mumps reported to the CDC which was the largest outbreak in the United States in decades. Six states (Iowa, Kansas, Wisconsin, Illinois, Nebraska, and South Dakota) accounted for 85% of cases with Iowa being the epicenter. In response to this mumps outbreak, ACIP recommendations for prevention and control of mumps were updated (see Indications).

While early trials with the Jeryl Lynn vaccine strain (mumps component in MMR in the United States) demonstrated an efficacy of 95%, in epidemic conditions, the effectiveness is much lower with rates as low as 62%. The majority of patients in the recent epidemic were aged 18 to 24 years and nearly 50% had received the recommended two doses of MMR vaccine. All isolates have been identified as genotype G, strongly suggesting that the epidemic was caused by a single strain. The source of the epidemic is unknown but a link has been suggested to the 2005 mumps epidemic in the United Kingdom in which 56,000 cases occurred, mostly in young adults, caused by a genotype G strain.

Rubella was also a common infection of children and young adults prior to vaccine availability. In the United States rubella was both endemic and epidemic with a cycle of major epidemics at 7-year intervals. The last major epidemic of rubella in the United States occurred in 1964 to 1965 and clearly demonstrated the significant adverse effects of rubella in pregnancy and congenital rubella. During the epidemic an estimated 12.5 million cases of rubella occurred with approximately 2,000 encephalitis cases reported. Congenital rubella syndrome was noted in 20,000 surviving infants of whom 11,600 were deaf, 3,580 were blind, and approximately 1,800 were mentally retarded. In addition, arthralgias and arthritis are common complications of rubella in adults; thrombocytopenia and encephalitis are less common.

Since licensing of the rubella vaccine in 1969 in the United States, no major epidemics of rubella have occurred and the incidence of disease (rubella and congenital rubella syndrome) has progressively declined. In 2006, there were only 11 cases of rubella reported to the CDC and 1 case of congenital rubella. Rubella is now at record-low numbers in the United States occurs mainly among immigrants who had not been vaccinated, and is no longer endemic in the United States.

Indication

Measles, mumps, and rubella vaccines are all live-attenuated vaccines. These three vaccines are combined into a combination vaccine, which has been licensed in the United States since 1971 as MMR. In the United States the ACIP has recommended two doses of MMR for all children and certain highrisk adolescents and adults. All children should receive the first dose of MMR vaccine at 12 to 15 months of age. The second dose should be administered at age 4 to 6 years; if the 4-to 6-year-old dose was missed it is recommended that MMR be given at age 11 to 12 years. While the second dose is primarily given to provide adequate protection against measles, it is recommended that both doses be given as MMR by both the Committee on Infectious Diseases of the AAP and the ACIP.

In 2006, ACIP updated criteria for mumps immunity and mumps vaccination recommendations (Table 25.5). Acceptable presumptive evidence of immunity to mumps includes one of the following: (i) documentation of adequate vaccination; (ii) laboratory evidence of immunity; (iii) birth before 1957; or (iv) documentation of physician-diagnosed mumps. In addition, the ACIP recommends that all healthcare workers should be immune to mumps.

In addition to the recommended routine schedule of immunization with MMR, vaccination is recommended for all
susceptible persons unless there is a contraindication (Figs. 25.1 and 25.2). Persons born prior to 1957 are likely to have been naturally infected with measles, mumps, and rubella and thus can be considered immune. However, in the case of rubella it is critical to ensure that women of childbearing age are immune to rubella. Thus, adult women prior to pregnancy and adult seronegative pregnant women in the postpartum period have been targeted for rubella vaccine administered as a single dose of MMR. In the United States, persons are considered susceptible to measles, mumps, and rubella unless they (i) have documentation of adequate vaccination (two doses after age 12 months); (ii) have laboratory proof of immunity, or (iii) have evidence of physician-diagnosed measles, mumps, or rubella. Among adults, particular groups have been the focus for vaccination of susceptible individuals. These include (i) attendees of college or other higher educational institutions; (ii) healthcare workers; (iii) military recruits; and (iv) international travelers. Susceptible adults should receive two doses of MMR separated by at least 28 days.

TABLE 25.5 ▪ KEY CHANGES IN THE 2006 ACIP RECOMMENDATIONS ON MUMPS

Acceptable Presumptive Evidence of Immunity

Documentation of adequate vaccination is now 2 doses of a live mumps virus vaccine instead of 1 dose for
- School-aged children (i.e., grades K-12).
- Adults at high risk (i.e., persons who work in healthcare facilities, international travelers, and students at post-high school educational institutions).

Routine Vaccination for Healthcare Workers

Persons born during or after 1957 without other evidence of immunity: 2 doses of a live mumps virus vaccine.
Persons born before 1957 without other evidence of immunity: consider recommending 1 dose of a live mumps virus vaccine.

For Outbreak Settings

Children aged 1-4 y and adults at low risk: if affected by the outbreak, consider a second dose^a of live mumps virus vaccine.
Healthcare workers born before 1957 without other evidence of immunity: strongly consider recommending 2 doses of live mumps virus vaccine

^aMinimum interval between doses = 28 days.

In regards to measles, a second dose of MMR is recommended for adults who (i) have been recently exposed to measles or are in an outbreak setting; (ii) have been previously vaccinated with killed measles vaccines; (iii) have been vaccinated with an unknown type of measles vaccine during 1963 to 1967; (iv) are students in post secondary educational institutions; (v) work in healthcare facility; or (vi) plan to travel internationally. For the mumps component, a second dose of MMR is recommended for adults who (i) are in an age group that is affected during a mumps outbreak; (ii) are students in post secondary educational institutions; (iii) work in healthcare facility; or (iv) plan to travel internationally.

Specific Contraindications/Complications

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