Morbidity and mortality from vaccine-preventable diseases remains substantial, particularly in adults. In the United States, between 50,000 and 90,000 adult deaths per year are caused by pneumococcal disease, influenza, and hepatitis B, whereas 300-500 deaths in children are due to vaccine-preventable diseases.¹ Research on the reasons for vaccine underutilization, and strategies to increase levels of vaccination coverage in the adult population, are areas of active endeavor.^2-6

Several national organizations and other groups have provided detailed guides to immunization in adults, both regarding specific vaccines and proposed comprehensive vaccination schedules.^1,5-31 The Centers for Disease Control and Prevention (CDC)'s Advisory Committee on Immunization Practices (ACIP) is the source of many monographs containing definitive recommendations for immunization in general, ^6,14,24 vaccine adverse effects,¹⁷ safety and efficacy of specific vaccines,^{16,18-20, 22-23,25-26,} vaccination in immunocompromised persons^15,27-28 and in health care workers.²¹ The American Academy of Pediatrics,^12,24 the American Public Health Association,¹³ the Infectious Diseases Society of America,^9-10 the American College of Physicians-American Society of Internal Medicine, ^9,11 the American Medical Association,²⁴ and the American Association of Family Physicians²⁴ have all participated in the formulation of guidelines for immunization. The Institute of Medicine (IOM) has convened a panel of experts to review specific vaccine safety issues,²⁹ and the National Coalition for Adult Immunization,³⁰ has been formed for the purpose of increasing vaccination coverage and meeting national "Healthy People" goals.³¹ The US Preventive Services Task Force has included immunizations among recommendations for general preventive measures.⁶ Detailed recommendations for adult immunization have also been issued by the Mayo Vaccine Research Group.¹ The March 2001 issue of Infectious Disease Clinics of North America was devoted to "Vaccine Recommendations: Challenges and Controversies." This compendium of reviews by experts is highly recommended for additional in-depth reading on these topics.^7-8,32-33

In 1994, the National Vaccine Advisory Committee (NVAC) reported on the status of adult vaccination in the United States and cited missed opportunities to vaccinate adults during health-care visits.⁵ The American College of Physicians Task Force on Adult Immunization and the Infectious Diseases Society of America recommended linking an assessment of vaccination status with other preventive measures at age 50 years.⁹ This approach has been endorsed by the Advisory Committee on Immunization Practices of the CDC, who recommends that all primary care physicians schedule a prevention visit at age 50 years,³⁴ at which time the patient's vaccination status can be reviewed, tetanus-diphtheria toxoid vaccine can be updated, and it can be determined whether the patient has an indication for the pneumococcal vaccine²² and/or initiation of annual influenza vaccination. The preventive visit at age 50 is all the more important since new recommendations from the CDC include influenza vaccination annually beginning at age 50.²³

In 1991, the US Public Health Service introduced national goals for health promotion and disease prevention under the heading of "Healthy People 2000."³¹ At the start of this campaign, in the 50-64 year old age group, only 9% and 15% of persons with cardiac or pulmonary high-risk conditions, respectively, had ever received pneumococcal vaccination, and only 21% and 28%, respectively, had received influenza vaccine the previous year ³⁴ although vaccination levels were higher in the over-65 age group.³⁴ The Healthy People 2000 national goals included an increase to 60% vaccination levels for these vaccines. Although many states met this objective with regard to influenza vaccination, pneumococcal vaccine coverage lagged considerably behind. The recently released Healthy People 2010 goals include achievement of 90% pneumococcal vaccination coverage in the elderly and high risk younger individuals.³²

Current ACIP recommendations for adult immunization, endorsed by the IDSA and many of the above organizations, are summarized in Table 1.

Pneumococcal Vaccine
The complex issues surrounding pneumococcal vaccination have been well summarized by Poland.³² The pneumococcus is responsible for 500,000 cases of pneumonia, 50,000 cases of sepsis, 3000 cases of meningitis, 40,000 deaths, and 7 million cases of otitis media annually in the United States.³² Unfortunately, pneumococcal vaccination is severely underutilized. The 23-valent pneumococcal polysaccharide vaccine, licensed in 1980, contains the serotypes responsible for 85-90% of invasive pneumococcal disease in adults, including the 6 pneumococcal serotypes which are most frequently drug-resistant.³² The reported efficacy of the pneumococcal polysaccharide vaccine has ranged from 55-80% and varies between different risk groups, but its benefits in preventing invasive disease are significant despite less than 100% efficacy.³² A recent 7-valent conjugated pneumococcal vaccine was licensed in 2000 and has been recommended for young children in whom it is more immunogenic than the standard vaccine, but data in adults are limited.³²

Current ACIP recommendations²² (Table 1) state that the pneumococcal vaccine should be administered to all adults of age 65 or older; individuals age 2-64 with chronic cardiovascular or pulmonary disease, diabetes, alcoholism, chronic liver disease, CSF leaks, functional or anatomic asplenia, immunocompromise, and those in high-risk environments including residents of nursing homes or long-term care facilities, Alaskan Natives and other Native American populations (who have high rates of pneumococcal disease). Reimmunization is recommended after 5 years, in patients over 65, if the patient is immunocompromised, has chronic renal failure or nephrotic syndrome, organ or bone marrow transplant, or had the first dose prior to age 65. Patients aged 10-65 with splenic dysfunction or immunocompromise should receive reimmunization after 5 years.²²

A recent report highlighted the fact that the smoking is a major risk factor for pneumococcal disease.³⁵ Given that approximately 1/3 of adults smoke, and other risk factors are common in the age 50-64 group, some experts anticipate that recommendations for universal pneumococcal vaccination may be extended to the age 50-64 group in the future, on analogy with influenza vaccination.³²

As with influenza vaccine, strategies such as standing orders at hospital discharge and in long-term care facilities have the potential to increase pneumococcal vaccination levels significantly.⁶

Tetanus-Diphtheria Toxoid
Tetanus and diphtheria are rare diseases in the US today, but there has been a recent widespread outbreak of diphtheria in the states of the former Soviet Union, prompting concerns about the possibility of transmission to other populations with waning immunity such as the elderly in the US.

The tetanus-diphtheria toxoid vaccine (Td) is composed of bacterial toxins rendered inactive by chemical treatment. It is safe and efficacious and is currently recommended to be administered as a booster every 10 years (or may be given earlier if a tetanus-prone wound occurs.)¹⁹ Some experts have questioned the need for a booster every 10 years, instead recommending a single booster dose at midlife for persons who received a full primary immunization series previously.⁷ For individuals not previously immunized, a 3-dose primary series should be administered (Table 1).

Meningococcal Vaccine
Meningococcal vaccine is a polysaccharide vaccine which covers serogroups A, C, Y, and W-135 but not B. This vaccine is not required for all adults. Recent recommendations from the American College Health Association and the ACIP²⁰ encourage physicians to inform incoming college freshmen about the vaccine. The risk for meningococcal disease is higher among college freshmen than among other college students. Arguments for and against routinely vaccinating college-bound freshmen have been summarized recently by Gordon.³⁶ Arguments for vaccination include the devastating nature of the illness, the safety and efficacy of the vaccine, the higher risk among college freshmen, the experience with vaccination of military recruits, and the fact that the serogroup distribution in the United States is moving towards those serotypes covered by the vaccine. Arguments against routine vaccination of freshmen include the cost of the vaccine ($54-88 per person) for 2 million incoming freshmen and 500,000 freshmen already living in dormitories; the lack of protection against serogroup B, the fact that antibody levels decline over 2-3 years, and the fact that only 5% of all cases occur in college students.³⁶ At the present time, counseling and offering the vaccine to interested incoming and current freshmen is recommended, but administration of the vaccine is not required.²⁰

Influenza Vaccine
There are few cost-effective, efficacious medical interventions which are subject to more mythology than the influenza vaccine. Barriers to immunization include patient concerns about potential adverse effects and/or induction of illness. Sadly, these concerns are reinforced by some clinicians. In actuality, the trivalent influenza vaccine is extremely safe and effective. It is an inactivated vaccine, not a live vaccine, and therefore cannot transmit infection. Since the swine flu vaccine of 1976, no vaccine preparations have been associated with a significantly increased risk of Guillain-Barre syndrome.³³ The trivalent influenza vaccine is composed of two strains of influenza A and one strain of influenza B, which are the strains predicted to be circulating during the upcoming influenza season. Because these strains vary from year to year, annual immunization is recommended. Allergic hypersensitivity to egg proteins is a contraindication.

Influenza accounts for approximately 20,000 deaths and 200,000 hospitalizations each year, and additionally is responsible for many days of work lost and many visits to health care providers.³³ About 10% of adults develop influenza each year.³³ The burden of illness is most significant in the elderly, in whom mortality can result from post-influenzal bacterial pneumonia and exacerbations of cardiopulmonary conditions.³³ The efficacy of influenza vaccine has been estimated to be 70-90% in healthy persons²³ and, though lower in the elderly, it still has significant benefit in prevention of overall mortality.²³

Although past recommendations focused on individuals age 65 and over, and younger individuals with chronic medical conditions, the most recent ACIP recommendations target individuals age 50 and over, since it was noted that age-based recommendations result in higher immunization rates than do risk-based recommendations. Immunization continues to be recommended for persons under age 50 who are residents of nursing homes or other chronic care facilities, who have chronic cardiac or pulmonary conditions, chronic metabolic disease including diabetes, renal dysfunction, hemoglobinopathies, or immunosuppression. In addition, women who will be in the 2nd or 3rd trimester of pregnancy during the influenza season, and children and adolescents receiving long-term aspirin who are at risk for Reye syndrome are among those for whom vaccination is recommended.²³

Strategies for increasing immunization rates are of paramount importance⁶ and are discussed below. The importance of immunization of health care workers cannot be overemphasized. Immunosuppressed patients such as transplant recipients may not develop adequate antibody titers after immunization, and are at risk for nosocomial transmission of influenza when hospitalized during the influenza season as well as community-acquired infection. Therefore, immunization of health care workers and family members can be an effective means of augmenting the protection of immunocompromised patients.

Varicella Vaccine
The varicella vaccine is a live, attenuated vaccine which provides long-lasting immunity. Although most adults are seropositive from prior infection, seronegative adults are susceptible to varicella primary infection which is often more severe in adults than in healthy children. Current recommendations are to immunize susceptible adults (not immunocompromised adults), with priority given to those who are at increased risk of exposure, or those who could expose persons at risk for serious complications of varicella. These groups include seronegative health care workers, family members of immunocompromised patients, teachers and child care workers, residents and staff of long-term care facilities or prisons, college students, military personnel, nonpregnant women of childbearing age, adolescents and adults in households with children, and international travelers.^10,16 Since the varicella vaccine is a live vaccine, it is not administered to immunocompromised patients. Although the fraction of vaccinees who develop a rash after vaccination could theoretically transmit the vaccine strain of the virus to household contacts, such transmission is considered to be a very unlikely event and the disease would most likely be mild. In addition, the risk of exposing an immunocompromised family member to actual varicella is much more serious, so administration of the varicella vaccine to seronegative household contacts of immunocompromised patients is encouraged rather than contraindicated.¹²

Postexposure prophylaxis with varicella-zoster immune globulin (VZIG) is not recommended routinely for all susceptible adults exposed to varicella, but is indicated for immunocompromised or pregnant seronegative patients. VZIG should be given within 96 hours for maximum effectiveness.^13,16 Some clinicians also administer antiviral therapy to exposed seronegative immunocompromised patients.

Measles-Mumps-Rubella Vaccine (MMR)
The MMR vaccine is a live vaccine and prevents potentially serious diseases including congenital rubella syndrome. A measles outbreak in 1989-91 in undervaccinated inner city residents was a reminder that these diseases remain a threat and reinforced the need to maintain high immunization levels in the general population.

Persons born before 1956 are considered to have natural immunity to these infections. Traditionally a single dose of MMR vaccine was given but more recent childhood recommendations are for two doses, one at 12-15 months and the second dose at 4-6 years or 11-12 years, as waning immunity can occur after a single dose. For adults born after 1956 who are not immune, a single dose of MMR should be administered, but high-risk groups such as college students, health care workers, and international travelers should receive two doses.¹⁰

Since MMR is a live vaccine, it is not generally administered to immunocompromised patients, with the exception of HIV patients with early disease27and stable BMT recipients 2 years or more after transplant without graft-versus-host disease.²⁸

Hepatitis A vaccine
There are currently two formulations of hepatitis A vaccine, which are inactivated, safe, and immunogenic. Administration of a two-dose series is recommended for adults in high-risk groups, which include international travelers, residents of communities with high rates of infection (Native Americans, Alaskan natives and Pacific Islanders), homosexual and bisexual men, injection drug users, persons with chronic liver disease, and food handlers.¹⁰ Persons with chronic liver disease appear to be particularly susceptible to fulminant disease when they develop hepatitis A infection and should be high priority candidates for vaccination.³⁷

Hepatitis B vaccine
Two formulations of recombinant hepatitis B vaccine are available in the US. A strategy of vaccinating high risk groups was originally employed, but current recommendations are for universal infant vaccination, and catchup vaccination of nonimmune older children and adolescents. For adults, high-risk groups should be the top priority for vaccination with a three-dose series. These groups include health care workers and others who may be exposed to blood and blood products; residents and staff of long-term care facilities or prisons, homosexual or bisexual men or heterosexuals with multiple partners, injection drug users, recipients of clotting factor concentrates, household or sexual contacts of HBV carriers, and persons from high-risk populations (Pacific Islanders, Alaskan natives, and immigrants from countries of high endemicity.)¹⁰ International travelers planning lengthy stays in endemic areas should be vaccinated.

With the events of the past year, attention has been focused on the possibility of deliberately induced larger outbreaks of infectious diseases. Vaccines exist for some of the pathogens mentioned as possible agents of bioterrorism, including anthrax, smallpox, and plague (Yersinia pestis). The Working Group on Civilian Biodefense has published recommendations for management of anthrax³⁸ and smallpox³⁹ as public health threats, and updated information on all topics related to bioterrorism can be found on the CDC website.⁴⁰ The anthrax vaccine is a cell-free inactivated vaccine given in a 6-dose series, and is currently available in the US only for military personnel or certain high-risk individuals such as laboratory workers working directly with Bacillus anthracis.¹³ However, with the recent episode of anthrax organisms sent via the postal system, it is likely that indications for vaccination will be expanded. Currently, efforts to manufacture much larger numbers of doses of vaccine are underway. The safety of the vaccine remains a controversial issue. For up-to-date information on the indications and safety of anthrax vaccine, the reader is referred to the CDC website.⁴⁰

Smallpox was the first disease for which vaccination was found to be effective, and now has been certified as eradicated with the last naturally acquired case in the world having occurred in 1977.¹³ However, the specter of smallpox has again been raised with the threat of bioterrorism. The current vaccine for smallpox is derived from vaccinia virus, which is a live attenuated viral vaccine, of which supplies are currently limited and not available for the general public.¹³ During the era when smallpox vaccination was universal, adverse reactions to the vaccine were not uncommon, including neurologic effects, and inadvertent vaccination of immunocompromised individuals sometimes resulted in severe progressive or disseminated vaccinia infection.⁴¹ Current efforts are focused on dramatically increasing production of smallpox vaccine, and measures to render the vaccine safer.

An inactivated whole cell bacterial vaccine is available for prevention of bubonic plague, but may not be effective against pneumonic plague¹³ and is currently recommended only for persons at high risk such as laboratory workers working with the organism.

Bacillus Calmette-Guerin (BCG) vaccination is not routinely recommended in the United States for prevention of tuberculosis, though it is administered in childhood in many other countries in which the prevalence of tuberculosis is higher. BCG is a live attenuated vaccine and should not be administered to immunocompromised persons including those with HIV. The efficacy of BCG for prevention in adults has varied in different studies, and currently is recommended in the US only for infants and children who reside in settings in which the likelihood of TB transmission is high, and for health care workers highly likely to be exposed to multidrug-resistant TB (MDR-TB) in settings where other TB prevention measures have failed. If the incidence of MDR-TB rises, these indications could be expanded in future.²⁵

There are currently 3 rabies vaccines licensed in the United States, of which the human diploid cell vaccine (HDCV) is most commonly used. It is indicated for pre-exposure prophylaxis, and also for post-exposure prophylaxis in conjunction with rabies immune globulin (RIG). Persons at high risk due to potential occupational exposures or travel are candidates for pre-exposure prophylaxis.¹³

Vaccines for international travel are discussed in more detail in the chapter, Travel Medicine for the Primary Care Physician.

Given the morbidity and mortality of vaccine-preventable diseases in adults, and the documented underutilization of safe and cost-effective vaccines, it is appropriate that significant attention has been drawn to strategies to increase vaccination rates.^{1-6, 30-34} Many of the organizations involved in the development of guidelines for immunization have published or endorsed such measures. Standing orders at hospital discharge or in long-term care facilities have the potential to decrease missed opportunities for vaccination. Within the context of individual clinical practices, patient reminder/recall systems have been found to be very effective. Increased educational materials for both clinicians and patients and other interventions are actively promoted by organizations such as the National Coalition for Adult Immunization, and details can be found on the NCAI website. ³⁰

Adult immunizations are extremely important. Guidelines for immunization standards from national organizations should be implemented and the preventive visit at age 50 should be used to update vaccination status. Interventions such as standing orders at hospital discharge and in long-term care facilities should be pursued. Educational efforts to reduce barriers to vaccination on both the clinician's and the patient's side should be actively pursued. Changing recommendations for vaccination can be found in the recommendations of the Advisory Committee on Immunization Practice (ACIP) which are frequently updated. Further information and recommendations on vaccines against agents of bioterrorism will undoubtedly be forthcoming.

Return to Medicine Index

1. Reid KC, Grizzard TA, Poland GA. Adult immunizations: recommendations for practice. Mayo Clin Proc. 1999; 74:377-384.
   
   
2. Williams WW, Hickson MA, Kane MA, et al. Immunization policies and vaccination coverage among adults. The risk for missed opportunities. Ann Intern Med. 1988; 108:616-625.
   
   
3. Zimmerman RK, Silverman M, Janosky JE, et al. A comprehensive investigation of barriers to adult immunization: a methods paper. J Fam Pract. 2001; 50:703.
   
   
4. Szilagyi PG, Bordley C, Vann JC, et al. Effect of patient reminder/recall interventions on immunization rates: a review. JAMA. 2000; 284:1820-1827.
   
   
5. Fedson DS. Adult immunization: Summary of the National Vaccine Advisory Committee Report. JAMA. 1994; 272:1133-1137.
   
   
6. Centers for Disease Control and Prevention. Vaccine-preventable diseases: improving vaccination coverage in children, adolescents, and adults. A report on recommendations from the Task Force on Community Preventive Services. MMWR Morb Mortal Wkly Rep. 1999; 44 (RR-8):1-15.
   
   
7. Gardner P, Peter G. Recommended schedules for routine immunization of children and adults. Infect Dis Clin N Am 2001;15:1-8.
   
   
8. Peter G, Gardner P. Standards for immunization practice for vaccines in children and adults. Infect Dis Clin N Am 2001;15:9-19.
   
   
9. American College of Physicians Task Force on Adult Immunization and Infectious Diseases Society of America. Guide for adult immunization. American College of Physicians, Philadelphia, 1994.
   
   
10. Gershon AA, Gardner P, Peter G, Nichols K, Orenstein W. Quality standards for immunization. Guidelines from the Infectious Diseases Society of America. Clin Infect Dis. 1997; 25:782-786. or see http://www.idsociety.org
    
    
11. Gardner P, Eickhoff T, Poland GA, et al. Adult immunizations. Ann Intern Med. 1996; 124:35-40.
    
    
12. American Academy of Pediatrics. Red Book 2000: Report of the Committee on Infectious Diseases. American Academy of Pediatrics, Elk Grove, Il, 2000.
    
    
13. Benenson, AS, ed. Control of Communicable Diseases Manual. American Public Health Association, Washington, DC, 1995.
    
    
14. Centers for Disease Control and Prevention: General recommendations on immunization: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1994; 43(RR-1): 1-38.
    
    
15. Centers for Disease Control and Prevention: Recommendations of the Advisory Committee on Immunization Practices (ACIP): Use of vaccines and immune globulins in persons with altered immunocompetence. MMWR Morb Mortal Wkly Rep. 1993; 42(RR-4):1-18.
    
    
16. Centers for Disease Control and Prevention: Prevention of varicella - recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1996; 45 (RR-11):1-36.
    
    
17. Centers for Disease Control and Prevention: Update: vaccine side effects, adverse reactions, contraindications, and precautions - recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1996; 45 (RR-12):1-35.
    
    
18. Centers for Disease Control and Prevention: Prevention of hepatitis A through active or passive immunization - recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1996; 45 (RR-15):1-30.
    
    
19. Centers for Disease Control and Prevention: Diphtheria, tetanus, and pertussis: recommendations for vaccine use and other preventive measures; recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1991; 40(RR-10), 1-28.
    
    
20. Centers for Disease Control and Prevention: Meningococcal disease and college students. (and) Prevention and control of meningococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2000; 49(RR-7): 1-10, 13-20.
    
    
21. Centers for Disease Control and Prevention. Immunization of health-care workers: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HICPAC). MMWR Morb Mortal Wkly Rep. 1997; 46 (RR-18):1-42.
    
    
22. Centers for Disease Control and Prevention: Prevention of pneumococcal disease: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 1997; 46 (RR-8): 1-24.
    
    
23. Centers for Disease Control and Prevention: Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Morb Mortal Wkly Rep. 2001; 50(RR-4): 1-44.
    
    
24. Centers for Disease Control and Prevention. Immunization of adolescents: recommendations of the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association. MMWR Morb Mortal Wkly Rep. 1996; 45(RR-13):1-16.
    
    
25. Centers for Disease Control and Prevention. The role of BCG vaccine in the prevention and control of tuberculosis in the United States. A joint statement by the Advisory Council for the Elimination of Tuberculosis and the Advisory Committee on Immunization Practices. MMWR Morb Mortal Wkly Rep. 1996; 44 (RR-4):1-18.
    
    
26. Centers for Disease Control and Prevention. Update: recommendations to prevent hepatitis B virus transmission - United States. MMWR Morb Mortal Wkly Rep. 1999; 48 (2):33-34.
    
    
27. Centers for Disease Control and Prevention. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. USPHS/IDSA Prevention of Opportunistic Infections Working Group. MMWR Morb Mortal Wkly Rep. 1999; 48 (RR-10):1-59,61-66.
    
    
28. Centers for Disease Control and Prevention. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR Morb Mortal Wkly Rep. 2000; 49:1-125.
    
    
29. Institute of Medicine: www.iom.edu
    
    
30. National Coalition for Adult Immunization: www.nfid.org/ncai/info
    
    
31. U.S. Department of Health and Human Services, Public Health Service. Immunization and Infectious Disease in Healthy People 2000. DHHS Publication No. (PHS) 91-50212. Superintendent of Documents, U.S. Government Printing Office, Washington, DC, 1991: 512-28.
    
    
32. Poland GA. The prevention of pneumococcal disease by vaccines: promises and challenges. Infect Dis Clin N Am. 2001; 15(1):97-122.
    
    
33. Neuzil KM, Griffin MR, Schaffner W. Influenza vaccine: issues and opportunities. Infect Dis Clin N Am 2001; 15(1):123-141.
    
    
34. Centers for Disease Control and Prevention. Notice to readers assessing adult vaccination status at age 50 years. MMWR Morb Mortal Wkly Rep.1995; 44:561-563.
    
    
35. Nuorti JP, Butler JC, Farley MM, et al. Cigarette smoking and invasive pneumococcal disease. N Engl J Med. 2000; 342:681-689.
    
    
36. Gordon SM. Should all college-bound freshmen receive meningococcal vaccine? Cleve Clin J Med. 2001; 68:9-10.
    
    
37. Vento S, Garofano T, Renzini C, et al. Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C [see comments]. N Engl J Med. 1998; 338:286-290.
    
    
38. Inglesby TV, Henderson DA, Bartlett JG, et al. Anthrax as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 1999; 281:1735-1745.
    
    
39. Henderson DA, Inglesby TV, Bartlett JG, et al. Smallpox as a biological weapon: medical and public health management. Working Group on Civilian Biodefense. JAMA. 1999; 281:2127-2137.
    
    
40. Centers for Disease Control and Prevention website: www.cdc.gov.
    
    
41. Goldstein JA, Neff JM, Lane JM, Koplan JP. Smallpox vaccination reactions, prophylaxis, and therapy of complications. Pediatrics. 1975; 55:342-347.

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