Immunization Update
Authors: Edward Onusko, MD, Assistant Professor of Family Medicine, Clinton Memorial Hospital, Family Practice Residency Program, Wilmington, Ohio; and Shira Katz, MD, Second-Year Resident Physician, Clinton Memorial Hospital, Family Practice Residency Program, Wilmington, Ohio.
Peer Reviewer: Theodore G. Ganiats, MD, Associate Professor, Department of Family and Preventive Medicine, University of California San Diego School of Medicine.
Editor’s Note—Recommendations for routine immunizations has been a dynamic and exciting topic in the field of preventive health services in recent years. This article will: present information concerning new vaccines for rotavirus and Lyme disease; update recommendations on established vaccines; highlight opportunities for vaccination at various stages in the life cycle; discuss some useful principles of vaccine administration; and explore various vaccines in development that may be available for clinical use in the near future.
Introduction
The advent of immunizations has greatly reduced the incidence of many infectious diseases. Smallpox has been eradicated worldwide.1 Poliomyelitis caused by the wild poliovirus has been virtually eliminated in the Western Hemisphere.2 In the United States, the incidence of many other vaccine-preventable diseases has dropped significantly (see Table 1).
| Table 1. The Maximum Number of Cases of Specified Vaccine-Preventable Diseases Ever Reported for a Calendar Year Compared With the Number of Cases of Disease and Vaccine Adverse Events Reported for 1995-United States | ||||||||
| Category | Maximum no. reported cases during prevaccine era |
Year(s) maximum no. cases reported |
Reported no. cases during 1995* |
Percentage change in morbidity |
||||
| Disease | ||||||||
| Congenital rubella syndrome | 20,000 | 1964-65 7 | 7 | (-99.96) | ||||
| Diphtheria | 206,939 | 1921 | 0 | (-99.99) | ||||
| Invasive Haemophilus influenzae | 20,000 | 1984 | 1164 | (-99.18) | ||||
| Measles | 894,134 | 1941 | 309 | (-99.97) | ||||
| Mumps | 152,209 | 1968 | 840 | (-99.45) | ||||
| Pertussis | 265,269 | 1934 | 4315 | (-99.99) | ||||
| Poliomyelitis (wild) | 21,269 | 1952 | 0 | (-99.99) | ||||
| Rubella | 57,686 | 1969 | 146 | (99.75) | ||||
| Tetnus | 601 | 1948 | 34 | (97.82) | ||||
| Vaccine adverse events | 10,594 | |||||||
| *Provisional totals. | ||||||||
| Estimated because national reporting did not exist in the prevaccine era. | ||||||||
| Total number reported to the Vaccine Adverse Events Reporting System (VAERS). | ||||||||
| Source: MMWR Morb Mort Wkly Rep 45(RR-12):2. | ||||||||
Available vaccines are not always used to their full advantage; however, there are many persons at risk who are not immunized for various reasons. Traditionally, it has been the pediatric population that was regularly immunized. Greater emphasis on adolescent and adult immunization programs has been a more recent development. Even in the pediatric population, there are many problems that contribute to incomplete or undervaccination. There are many studies that show that regular assessment and feedback of vaccination rates to providers result in a significant rise in immunization coverage both in public clinics and the private sector.3
It is important that health care providers be aware of the availability of new vaccines and new guidelines for use of older vaccines. This article will present a practical, clinically oriented update on immunizations, with an emphasis on recommendations that are new for 1999.
Immunization of Infants (0-2 years)
Each year, the American Academy of Family Physicians (AAFP), the American Academy of Pediatrics (AAP), and the Advisory Committee on Immunization Practices of the Centers for Disease Control (ACIP) collaborate to provide a recommended childhood immunization schedule (see Table 2). This yearly update provides information concerning the addition of newer vaccines and changes in guidelines for older vaccines.
Rotavirus (Rv). For 1999, the rotavirus vaccine (RotaShield—Wyeth Laboratories) has been added to the schedule. Rotavirus is considered to be the most common cause of severe diarrhea among infants and young children in the United States.4 It has been found to be the major etiology of diarrhea requiring hospitalization. From 1993 to 1995, nearly 500,000 diarrhea-associated hospitalizations were reported in children between the ages of 1 month and 4 years (> 160,000 per year and 13.5% of total hospitalizations in this age group). More than 80,000 of these diarrhea-related hospitalizations (> 26,000 annually) were associated with documented rotavirus infection.5 (See Table 3.)
| Table 3. Age-Specific Proportion of Reported Gastroenteritis (GE) Hospitalizations Associated with Rotavirus (RV) among Children aged 1-59 months, 1993-1995 | ||||
Age group(months) |
No. of GE hospitalizations |
No. of GE hospitalizations associated with RV(%) |
Cumulative no. of RV hospitalizations |
|
1-3 |
65,943 |
6761 (10.3) |
6761 (8.4) |
|
4-6 |
47,009 |
4666 (9.9) |
11,427 (14.2) |
|
7-11 |
88,674 |
17,245 (19.5) |
28,672 (35.7) | |
12-23 |
138,234 |
29,487(21.2) |
58,159 (72.3) |
|
24-35 |
73,164 |
14,053 (19.20) |
72.212 (89.8) |
|
36-47 |
41,898 |
6040 (14.4) |
78,242 (97.3) |
|
48-59 |
31,511 |
2141 (6.8) |
80,393 (100) |
|
Total |
487,433 |
80,393 (16.5) |
—— |
|
| Source: Parasher UD. J Infect Dis 1998; 177;13-17. | ||||
In addition, approximately one of every eight children will seek medical attention due to rotavirus diarrhea in the first five years of life.4 It has been estimated that a rotavirus immunization program would prevent 39% of cases of rotavirus diarrhea in the first five years of life, with a 55% reduction in physician visits, a 59% reduction in emergency department visits, a 67% reduction in hospitalizations, and a 65% reduction in deaths.6 (See Table 4.)
| Table 4. Rotavirus Health Outcomes and Costs With and Without a Rotavirus Immunization Program* | |||||
| Variable | No Vaccine Program |
With Vaccine Program |
Prevented by Vaccine Program |
Reduction, % |
|
| Events, No. | |||||
| Total rotavirus diarrhea | 2,730,000 |
1,652,000 |
1,078,000 |
39 |
|
| Physician visits | 410,000 |
183,000 |
227,000 |
55 |
|
| Emergency department visits | 160,000 |
65,000 |
95,000 |
59 |
|
| Hospitalizations | 50,000 |
16,400 |
33,600 |
67 |
|
| Deaths | 20 |
7 |
13 |
65 |
|
| Cost, $(thousands) | 20 |
7 |
13 |
65 |
|
| Medical costs | |||||
| Office visits | 51,777 |
23,144 |
28,633 |
55 |
|
| Emergency department visits | 37,264 |
15,185 |
22,079 |
59 |
|
| Hospital | 175,434 |
43,894 |
131,540 |
75 |
|
| Death (emergency department visits) | 15 |
5 |
10 |
67 |
|
| Vaccine administration | 0 |
192,660 |
-96,300 |
... |
|
| Cost of vaccine, $20 per dose | 0 |
— |
-192,660 |
... |
|
| Total Medical Costs | 264,490 |
371,218 |
-106,728 |
-40 |
|
| Nonmedical costs | |||||
| Loss of earnings by caregiver | 687,779 |
311,390 |
376,389 |
-55 |
|
| Other direct nonmedical | 28,577 |
311,390 |
12,923 |
-45 |
|
| Lifetime productivity loss of child to death | 19,912 |
6541 |
13,371 |
67 |
|
| Total Nonmedical Costs | 732,268 |
333,585 |
402,683 |
55 |
|
| Total Cost | 1,000,758 |
704,803 |
295,955 |
30 |
|
| *Data are five-year estimates for a birth cohort of 3.9 million. | |||||
| Ellipses indicate cost incurred. | |||||
| Source: Tucker AW. JAMA 1998;279(17):1371-1376. | |||||
Rotavirus infections are seasonal, with a peak during the winter months. The virus is highly contagious and most frequently affects children from 6 to 24 months of age. Nearly all children have at least one rotavirus infection before age 5 years. It has been shown that a degree of natural immunity is acquired after exposure to the virus at a young age, but that clinically protective immunity is often acquired only after several infections. It appears that infection can be symptomatic or asymptomatic with the same resulting degree of immunity. The immunity conferred by natural rotavirus infection can range from protection against asymptomatic infection to protection against moderate to severe diarrhea. The highest degree of protection is acquired after at least two infections.7
RotaShield is the first rotavirus vaccine to be clinically available. It is an oral, tetravalent vaccine, containing a rhesus rotavirus (serotype 3) and three rhesus-human reassortant viruses (serotypes 1, 2, and 4). These four rotavirus serotypes are responsible for the major portion of rotavirus disease in infants and young children in the United States. The RotaShield vaccine appears to have a good safety profile, with few adverse effects. Fever following administration of the first dose is the main adverse reaction (21% incidence vs 6% with placebo), with occasional excessive irritability or decreased activity. The second and third doses of the vaccine have an incidence of adverse reactions comparable to placebo.8-10
The immunity conferred by natural rotavirus infection appears to be most significant in preventing moderate to severe diarrhea.7 This also appears to be true for the vaccine. In one study in the United States, the efficacy of the vaccine over a single season was 49% for all gastroenteritis; 73% for gastroenteritis needing medical intervention; 80% for severe rotavirus gastroenteritis; and 100% for gastroenteritis with dehydration.8
RotaShield is an oral vaccine, scheduled to be given in three doses at 2, 4, and 6 months of age. Other recommendations include: 1) the first dose should not be given before 6 weeks of age; 2) the minimum interval between doses is three weeks; 3) the vaccination series should not be initiated at 7 months of age or older; and 4) all three doses should be completed prior to the first birthday. (Older children seem to have a higher incidence of adverse reactions.) (See Table 2.)6
The vaccine is contraindicated in infants with a known or suspected immunodeficiency, with an evolving neurological disorder, in acute moderate or severe febrile illnesses, and in infants with persistent vomiting. Precautions in the use of the rotavirus vaccine include prematurity, history of latex sensitivity, chronic gastrointestinal disorders or ongoing diarrhea, and close contact with an immunocompromised individual. The vaccine should not be readministered to a child who vomits, regurgitates, or spits out the dose he or she received (in contrast to oral polio vaccine, which may be readministered).
Due to the newness of the rotavirus vaccine, it may take time to incorporate its use into practice. At the present time, the AAFP is not recommending universal rotavirus immunization, but suggests that the parent or guardian make the decision as to the use of the rotavirus vaccine in consultation with their physician.11 The U.S. Advisory Committee on Immunization Practices (ACIP) recommends routine use of the vaccine. Cost of the vaccine to the health care provider is about $38 per dose.
Poliovirus—OPV vs. IPV. In 1997, the ACIP revised its recommendations for poliovirus vaccination to allow for three options: 1) sequential—two doses of inactivated poliovirus vaccine (IPV), followed by two doses of oral poliovirus vaccine (OPV); 2) four doses of all IPV; or 3) four doses of all OPV. IPV was first used in the United States in 1955 and was in widespread use until OPV was introduced in 1963. OPV had several advantages over the original IPV: 1) Efficacy—OPV had a more successful immunity profile than IPV (after 3 doses of OPV, 95% of those vaccinated developed long-lasting immunity); 2) Ease of administration—the oral dosing was more readily accepted than injection; 3) In addition to a humoral response, the oral route of administration resulted in the induction of mucosal immunity mediated by secretory IgA, theoretically giving enhanced protection over the IPV; and 4) Excretion of the attenuated poliovirus strain from the gut of the recipient results in secondary transmission and inoculation of susceptible household contacts in 73-96% of cases, depending on the person’s age.12
Poliovaccine has been effective in preventing wild poliomyelitis. The last naturally occurring case of polio in the United States was in 1979 and the last case in the Western Hemisphere occurred in 1991. Unfortunately, there has been a small incidence of spontaneous reversion of attenuated oral poliovirus to a more virulent form, resulting in vaccine-associated paralytic poliomyelitis (VAPP) at a rate of about one per 2.4 million doses of OPV since 1980. The profile of persons contracting VAPP is: 1) About two-thirds of the cases occur in vaccine recipients. Of these, two-thirds are healthy and one-third have an immunodeficiency (usually a B-cell disorder such as hypogammaglobulinemia, sometimes undiagnosed prior to administration of OPV); 2) About one-third of VAPP occur in contacts of vaccine recipients. Of these, about three-fourths are healthy and one-fourth are immunodeficient; 3) About 80% of VAPP occur after the first dose of OPV vs. subsequent doses. The risk of acquiring VAPP after the first dose of OPV is one case per 750,000. The overall risk of VAPP in healthy recipients (excluding their contacts) is one in 6.2 million doses; and 4) Adult recipients of OPV have a higher rate of VAPP than children. A newer, enhanced-potency IPV was licensed for use in the United States in 1987. It too confers long-lasting immunity in 90-100% of recipients. After several studies were done, the ACIP decided that two IPV followed by two OPV was also an acceptable alternative poliovirus vaccine series, in addition to the four OPV series and the four IPV series.13
The reason for using IPV (either exclusively or prior to using OPV) was to reduce the incidence of vaccine-associated paralytic poliomyelitis (VAPP). Two doses of IPV induce protective humoral immunity in more than 90% of recipients, thus preventing VAPP with subsequent doses of OPV. The OPV will then induce mucosal immunity as well, though some virus may be shed from the gut and result in exposure of household or community contacts. The prevalence of immunity following the sequential series ranged from 96% to 100%.14
In 1996, the results of an analysis were published suggesting that using IPV exclusively or in a sequential schedule would not be cost-effective despite the prevention of at least some cases of VAPP. It was eventually decided, however, to incorporate the option of the sequential series in the hopes that it would reduce the anxiety over OPV vaccination and increase public confidence in the safety of vaccination programs.15 This was also a compromise between "all OPV" advocates and "all IPV" advocates. Since then, the costs of IPV and OPV schedules are similar, so it is now probably cost-effective to use IPV.12
The 1999 recommendations now state that either an all-IPV or a sequential 2IPV/2OPV schedule should be used. This would prevent nearly all cases of OPV-associated VAPP in recipients, while ensuring both mucosal and humoral immunity.
OPV is not recommended for use for the first two vaccine doses except in special circumstances: 1) if the parents do not accept the recommended number of injections; 2) if the first dose is being administered late and would require an unacceptable number of injections; or 3) if the infant will be traveling shortly to a country where polio is endemic (therefore increasing the urgency to induce mucosal immunity).15
Previously, there had been some questions as to the efficacy and safety of administration of the OPV and the rotavirus vaccine simultaneously. When RRV-TV was used and three doses given, there was no significant suppression of rotavirus or poliovirus antibody response.16,17 This is less important now since the first two doses of poliovirus vaccine will usually be IPV. Both RotaShield and OPV are effective in inducing immunity in breastfed infants, despite the possible presence of maternal antibodies in the breast milk.
Diphtheria/tetanus/acellular pertussis (DTaP). Another change in the 1999 recommended immunization schedule is that the combination vaccine diphtheria, tetanus, and acellular pertussis (DTaP), is now the preferred vaccine, rather than the whole cell DTP (DTwP or DTP). The DTaP has one-fourth to one-half of the adverse effects of DTwP. The combination vaccine DTaP-Hib (H. influenzae type b) is not recommended for children younger than 1 year of age due to decreased efficacy of the Hib portion of the vaccine.11
The recommendations for the use of Hepatitis B vaccine have changed slightly. For infants, the third dose in the series should not be given prior to 6 months of age. (See Insert.) Previously, the third dose could be given as early as four months. H. influenzae type b (Hib), measles/mumps/rubella (MMR), and varicella vaccine recommendations for infancy are unchanged (see Table 2).
Immunization of Preschool Children (ages 4-6 years)
Some school systems and some states are mandating completion of Hepatitis B vaccination by 1 year of age or before entry into primary grades.18 For example, the Ohio legislature recently approved a law requiring that all kindergarten students show evidence of the Hepatitis B vaccination series beginning with the 1999-2000 school year. Those children in the process of being immunized will be able to enter school but will be monitored to ensure completion of the vaccination series.19
It is now recommended that the second dose of MMR be given at age 4-6 years rather than at the preteen years.
DTaP and polio boosters are still recommended at age 4-6 years. If the fourth dose of DTaP (or DTwP) is given after the fourth birthday, a fifth dose is not needed. If the third dose of polio is given after the fourth birthday in the all-IPV or all-OPV series, a fourth dose is not needed. If the sequential 2-IPV/2-OPV series is used, all four doses need to be administered.
Immunization of Adolescents/Preteens (ages 11-12 years)
Most vaccination programs focus on infants and children. Many adolescents continue to suffer from vaccine-preventable diseases because they have not been previously vaccinated or have not received indicated booster doses of vaccines. It is now recommended that a routine health care visit be scheduled for age 11-12 years in order to provide preventive health services and to immunize those adolescents who are not up-to-date on their vaccinations.20 (See Table 5.)
Hepatitis B is one of the vaccinations that many adolescents have not received, simply because the vaccine was not in use when they were infants. One of the most common sources of hepatitis B infection in adolescents is sexual activity. Therefore, it is important that those who are not immunized receive the vaccine before becoming sexually active or beginning high-risk behaviors.20 Many colleges and universities are requiring students to be immunized prior to admission.18 Universal vaccination with hepatitis B is recommended for all infants and adolescents, regardless of risk factors.
Varicella is another vaccine-preventable disease that most adolescents have not been vaccinated against. It is thought that approximately 20% of adolescents are still susceptible to varicella, despite a high incidence of exposure to natural infection in the community. The varicella vaccine became available in 199520 and since 1996 has been a part of the recommended routine immunization schedule.18 Varicella (chicken pox) can be a debilitating illness in persons 15 years of age or older, with many complications, including death.20 Therefore, it is recommended to vaccinate those without a convincing history of natural infection. Administering the vaccine by 12 years of age has the advantage that a single dose of vaccine is sufficient. Older than that age, two doses should be given, with at least four weeks between doses.18,20,21 Another advantage of the vaccine is that the development of herpes zoster (shingles) later in life seems much less likely in vaccine recipients vs. those who have had natural varicella infection.22
Recommendations for mumps, measles, and rubella (MMR) include two doses at 12 months of age or older. Some children have received both doses prior to reaching adolescence. Those who have not could be administered the vaccine at the 11-12 year visit. There are states that now require two doses of MMR before entering elementary school, while others require them prior to entering middle school.20
The 11-12 year visit is also a good time to administer a tetanus, diphtheria (Td) booster. If the DTaP was given at age 4-6 years, it is now thought that age 11-12 years is an appropriate time for a Td booster to ensure long-lasting immunity. It has been found that immunity is decreased in persons 9-13 years of age, with up to 36% unprotected. After this booster, doses are recommended at 10-year intervals.
Immunization of Adults
Adults who are not immunized can be at risk for many of the diseases that we consider "childhood diseases." These diseases can be devastating with severe complications, including death. Any adult not immunized against varicella (and without a clinical history of chicken pox) or measles/mumps/rubella should be vaccinated against these diseases. As mentioned with adolescents, a Td booster should be given every 10 years.18
The ACIP and AAFP are now recommending that physicians review the immunization status of their adult patients at age 50 in order to determine what routine vaccinations are necessary. In addition, the physician should determine what risk factors might be present, indicating a need for other less routine vaccinations. Among adults 50-65 years old, 30-40% have risk factors that necessitate immunizing with the pneumococcal vaccine and/or the influenza vaccine.18
Pneumococcal vaccine. The pneumococcal vaccine has been well documented to provide significant protection against invasive forms of pneumococcal disease, such as bacteremia and meningitis. It is not effective against upper respiratory infections such as otitis media and sinusitis.22 Likewise, the effectiveness of the vaccine in decreasing the incidence of pneumococccal pneumonia in middle-aged and elderly individuals has been questioned.24-26 Health care providers often promote this vaccine to their patients as "the pneumonia vaccine." Strictly speaking, it is a vaccine that provides significant protection against pneumococcal bacteremia and meningitis. Adults to be immunized include those 65 years of age or older and those at increased risk of invasive pneumococcal disease. Adults at increased risk are defined later in this article. Although the effectiveness of the vaccine has not been proven in all high-risk groups, vaccination is felt to be justified.23
Rates of pneumococcal vaccination (about 30% for individuals with approved indications) have been consistently lower than rates for influenza vaccine.
Influenza vaccine. As with pneumococcal disease, influenza can cause significant morbidity and mortality in individuals older than 65 years of age or in other high-risk groups. Influenza is estimated to cause 10,000-40,000 deaths and 200,000 hospitalizations in the United States annually.27 There are three strains of influenza virus, but only two cause the seasonal epidemics in the United States. Each year, a new influenza vaccine is prepared with a different antigenic makeup, determined by which virus strains are thought most likely to be circulating the coming winter.28,29 Influenza vaccination rates in persons aged 65 years or older have improved in recent years to approximately 66%, but rates among at-risk patients younger than 65 years have remained below 30%.27 The success of the vaccine in attenuating or preventing illness depends on both the extent of a successful match, and by the age and immunocompetence of the vaccine recipient. A recent retrospective cohort study of women aged 15-64 years enrolled in the Tennessee Medicaid program from 1974 to 1993 demonstrated a substantial increase in morbidity and mortality from acute cardiopulmonary events during influenza season, suggesting a possible need for routine influenza vaccination in this relatively low-risk population.27 The majority of persons hospitalized secondary to influenza are not those aged 65 years or older, but are persons younger than 65 years who have chronic underlying conditions—particularly chronic pulmonary disease.30 At times, the vaccine has been 70-90% effective in preventing disease. Other studies have shown it to be successful in preventing hospital complications and death, especially in nursing home patients.29
Immunization of High-Risk Populations
There are many children, adolescents, and adults younger than age 65 who have special needs when it comes to immunizations. These include those with: 1) chronic cardiovascular diseases (such as congestive heart failure or cardiomyopathy); 2) chronic pulmonary diseases (emphysema, chronic bronchitis, asthma); 3) metabolic disorders (including, but not only, diabetes mellitus); 4) chronic renal disorders; 5) chronic liver disorders; 6) sickle cell disease and other hemoglobinopathies; and 7) immunocompromised states, such as asplenia (functional and anatomic), malignancies (leukemia, lymphoma, etc.), patients on chemotherapy or chronic steroid treatment, and patients with HIV infections. (In this last group, the efficacy of immunization has not been proven, but the benefits probably outweigh the risks.) All of these patients need to be immunized with both the pneumococcal and influenza vaccines.23,28,29 Table 6 shows the recommendations for pneumococcal vaccine and for revaccination. In addition, there are some special indications for influenza vaccine, including children who are on chronic aspirin therapy and would, therefore, be at an increased risk for Reye’s syndrome. Also at risk are pregnant women who will be in their second or third trimester during the influenza season and health care workers who could potentially transmit influenza to persons at high risk.29 A recent randomized trial demonstrated the effectiveness of influenza vaccine in preventing serologically defined influenza A (88% effective) and influenza B (89% effective) in health care professionals.31
Groups for which vaccination is recommended
Strength of recommendation*
Revaccination
Immunocompetent personsd Persons aged ³ 65 yearsA
Second dose of vaccine if patient received vaccine ³ 5 years previously and were aged < 65 years at the time of vaccination.
Persons aged 2-64 years withh chronic cardiovascular disease,¶ chronic pulmonary disease, ** or diabetes mellitusA
Not recommended Persons aged 2-64 years with alcoholism, chronic liver disease, or cerebrospinal fluid leaksB
Not recommended Persons aged 2-64 years with functionalor anatomic aspleniaddA
If patient is aged > 10 years: single revaccination ³ 5 years after previous dose. If patient is aged ³ 10 years: consider revaccination 3 years after previous dose. Persons aged 2-64 years living in special environments or social settings.¶¶C
Not recommended Immunocompromised personsd Immunocompromised persons aged >=2 years, including those with HIV infection, leukemia, lymphoma, Hodgkin's disease, multiple myeloma, generalized malignancy, chronic renal failure, or nephrotic syndrome; those receiving immuno-suppressive chemotherapy (including corticosteroids); and those who have received an organ or bone marrow transplant.C
Single revaccination if >= 5 years have elapsed since receipt of first dose. If patient is aged >= 10 years: consider revaccination 3 years after previous dose. *The following categories reflect the strength of evidence supporting the recommendations for vaccination: A = Strong epidemiologic evidence and substantial clinical benefit support the recommendation for vaccine use. B = Moderate evidence supports the recommendation for vaccine use. C = Effectiveness of vaccination is not proven, but the high risk for disease and the potential benefits and safety of the vaccine justify vaccination. Strength of evidence for all revaccination recommendations is "C" dIf earlier vaccination status is unknown, patients in this group should be administered pneumococcal vaccine. ¶Including congestive heart failure and cardiomyopathies. **Including chronic obstructive pulmonary disease and emphysema. Including cirrhosis. ddIncluding sickle cell disease and splenectomy. ¶¶Including Alaskan Natives and certain American Indian populations. Source:MMWR Morb Mortal Wkly Rep 1997;46(RR-8).Those who should be immunized against hepatitis B are health care workers, hemodialysis patients, persons with high-risk sexual behavior, IV drug users, persons receiving clotting factor concentrates and other blood products, adoptees from countries where the disease is endemic, international travelers to those countries, those who are in close personal contact with hepatitis B carriers, and patients with hepatitis C or chronic liver disease.18,28
Hepatitis A vaccine is recommended for those with hepatitis C infections, other chronic liver disorders, illegal drug users, homosexual males, travelers to endemic areas, military personnel, and persons with an occupational risk.18
General Considerations
The Insert is a table of summaries of the recommended immunizations for children and adults, respectively. These tables include: 1) Indications for the vaccine; 2) The recommended dosing schedule; 3) The minimum dosing intervals. For example, MMR is recommended to be given in two doses at ages 12 months and 4-6 years. However, it is acceptable to give the first dose at 12 months and the second dose as early as 13 months, because the minimum interval between the first and second doses is 28 days (as long as both doses are given after the first birthday); 4) Scheduling guidelines for those who are behind; and 5) Contraindications and precautions.
Live, attenuated-virus vaccines (OPV, MMR, Varicella, and Rv) in general are able to reproduce in the vaccine recipient, thereby increasing the antigenic stimulus and enhancing the body’s immune response. What is the risk, however, of these vaccines causing actual clinical infection in the immunized individual or their contacts? All four of the above live virus vaccines can rarely induce clinical infection in the vaccine recipient. (That’s why VAPP has occurred with OPV, as discussed previously, and why MMR and Varicella vaccines are contraindicated in pregnancy.) In contacts of vaccine recipients, it is also clear with OPV there is a small risk of contracting VAPP. With MMR administration, however, there is no associated risk of transmission of clinical infection to household or community contacts. Varicella vaccine seems to carry only a very slight risk of transmission—usually only from recipients who develop a herpetic-type rash following vaccine administration. Rotavirus replicates in the intestine of the recipient and is shed in the stool. Although numerous studies have failed to demonstrate transmission of significant infection to contacts of vaccine recipients, caution is still recommended in administering the vaccine if family members or other close contacts are immunocompromised.
New Vaccines on the Horizon
Lyme Disease. Lyme disease is a tick-borne infection that may result in chronic arthritic, neurologic, cardiac, and other symptoms. It is endemic primarily in the Northeast and Upper Midwest regions of the United States (see Figure 1). There is now a vaccine available against Lyme disease. LYMErix (SmithKline Beecham) was approved by the FDA in December 1998 for ages 15-70 years. It has been shown to be efficacious after a three-dose series (initial dose, followed by doses at 1 month and 12 months) of the vaccine.32-34 Efficacy of immune response was 49-68% after two doses and 76-92% after the third dose. The duration of protection is unknown. Eight months after the third injection, antibody levels had fallen to near the lower limit of protective levels, suggesting that frequent boosters may be necessary.35 The Lyme disease vaccine caused some adverse effects. These included soreness, redness, and swelling at the site of injection, and some systemic symptoms such as myalgias, fever, and chills. All of these adverse effects were minor and self limited—none lasting longer than several days.32,33
The development of this vaccine shows promise in the fight against Lyme disease, but antibiotics alone are generally effective in treating early disease and preventing complications, and the long-term safety and effectiveness of the vaccine are unknown.35 It should be considered for use in high-risk individuals (adults who live in endemic areas and live, work, or walk in grassy or wooded areas), though its role in this population is still uncertain. Vaccination does not reduce the need for preventive measures such as avoiding tick habitats, wearing protective clothing, promptly removing attached ticks, etc. The vaccine should probably not be used in low-risk populations. The ideal time for the third vaccine may be in March, just prior to the tick season. More studies are needed to test the efficacy and safety of the vaccine in children.
Conjugate Pneumococcal Vaccine. At the present time, research is being done on protein-polysaccharide conjugate vaccines against pneumococcal disease. A vaccine of this type would potentially be more immunogenic and would improve the efficacy of the vaccine. The vaccines being tested at this time include seven serotypes and could potentially protect against bacteremia, meningitis, and otitis media. Preliminary data also suggest that conjugate vaccines may also reduce the incidence of the nasopharyngeal carrier states of the specific serotypes in the vaccine. Although the research at present is focusing on a vaccine for children, it will probably be evaluated for use in adults—especially those who respond poorly to the present vaccine.23
Nasal spray influenza vaccine. Also on the horizon is a pediatric nasal spray vaccine for preventing influenza. It is a live, attenuated influenza virus vaccine. Preliminary studies show it to be 95% effective in children ages 1-6 years.36 It is awaiting FDA approval and may be available for use by the fall of 1999. It appears to have the potential advantage of inducing nasal mucosal immunity because of the route of administration.
Summary
Immunization is an important part of the arsenal in the fight against infectious diseases. It is the responsibility of health care providers to ensure that their patients receive the maximum benefit from available vaccinations. In order to do this, we must keep up-to-date with the development of new vaccines and with changes in the guidelines for established vaccines.
References
1. World Health Organization. The global eradication of smallpox: Final report of the Global Commission for the Certification of Smallpox Eradication. In: History of International Public Health. No. 4. Geneva, Switzerland: World Health Organization, 1980.
2. CDC. Certification of poliomyelitis eradication—the Americas, 1994. MMWR Morb Mort Wkly Rep 1994;43:720-722.
3. LeBaron CW, et al. Impact of measurement and feedback on vaccination coverage in public clinics, 1988-1994. JAMA 1997;277(8):631-635.
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Physician CME Questions
The rotavirus vaccine series would be appropriate to initiate in:
a. a 1-month-old at high risk of infection secondary to prematurity.
b. a healthy 4-month-old.
c. an immunosuppressed 2-month-old.
d. a 8-month-old with a previous mild rotavirus infection.
A feature of live virus vaccines vs. other types of vaccines is:
a. ease of storage secondary to better vaccine stability.
b. lower risk of transmission to household contacts of recipients.
c. ability to increase antigenic stimulus by replicating in the recipient.
d. fewer side effects.
Vaccination against Lyme disease is recommended for:
a. all infants in the continental United States who are not immunocompromised.
b. children who spend a lot of time outdoors in heavily-wooded areas.
c. adults living in areas where Lyme disease is endemic.
d. children living in areas where Lyme disease is endemic.
Recommendations for the immunization of adolescents include:
a. initiation of the three-dose hepatitis B series if not previously given.
b. hepatitis B booster if the initial three doses were given in infancy.
c. varicella booster if the patient develops a case of shingles (herpes zoster).
d. repeat MMR if the second dose of MMR was given prior to age 2 years.
One of the advantages of varicella vaccination vs. natural infection with chicken pox is:
a. natural infection tends to be more pronounced in children than in adults, making it important to immunize children.
b. vaccine recipients frequently spread the live varicella virus to household contacts, thereby inducing immunity in them.
c. lower lifetime risk of herpes zoster.
Current rates of vaccination for persons 65 years and older in the United States for influenza and pneumococcal vaccine are approximately:
a. influenza 65%, pneumococcal 66%.
b. influenza 95%, pneumococcal 65%.
c. influenza 65%, pneumococcal 30%.
An advantage of IPV (injectable, killed-virus polio vaccine) over OPV (live, attenuated polio virus) is:
a. induction of secretory (IgA) as well as humoral (IgG) immunity.
b. lower incidence of VAPP (Vaccine-Associated Paralytic Polio).
c. increased efficacy when administered to breastfed infants.
d. decrease in number of vaccine doses required.
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