Adult Vaccinations: Practicing Preventive Medicine In The Family Physician's Office

By Thomas Shima, DO

Introduction
Vaccinations are the centerpiece of today’s preventive medicine care. Edward Jenner was the first person in recorded medical history to use the term vaccination in 1796.1 However, vaccination ideology was around for centuries prior to that date. Attempts at prevention through inoculation can be traced back as far as 200 B.C., when persons were reported to have tried to inoculate themselves with other diseases to prevent smallpox infection.2

Today, vaccinations are an important part of most public health campaigns across the United States. These campaigns have primarily targeted the pediatric population and have been hugely successful in the United States. For example, the number of measles cases in the U.S. averaged 300,000 to 750,000 cases annually from 1950-1963. The introduction of the measles vaccine had an immediate impact causing a dramatic decline in the number of infections (Figure 1).3 On a more global scale, smallpox has been eradicated through the use of vaccinations. The last reported case occurred in Somalia in 1977. The last reported case in the United States was in 1947.

Despite the success with pediatric vaccinations, the area of adult vaccination has received much less emphasis. According to the Center for Disease Control (CDC), 600,000 adult deaths worldwide are reported each year attributable to Hepatitis B virus infections.5 Pneumonia and influenza are the fifth leading cause of death in adults greater than 65 in the U.S (Figure 2). The underutilization of vaccinations in the adult population continues to have a direct effect on healthcare costs. Despite the fact that many modern day patients are highly educated on health care issues, most are still unaware of the recommendations for adult immunization. Family physicians can play a key role in educating their patients on the role of vaccinations and in dispelling any concerns about vaccine safety.

Types Of Vaccines
Vaccines used today are one of two types: live attenuated and inactivated vaccines (Table 1). Live attenuated vaccines are derived from genetically-altered whole viruses that cause a subclinical form of illness, but also allow for development of an immunologic response by the recipient of the vaccine. In this form, replication of the virus in the host is continuous, causing an IgG-mediated response. The advantage of this type of vaccine is the production of a sustained immune response, often leading to long-term immunity without the need for booster vaccinations. Approximately 90-95 percent of recipients of a single dose of live attenuated vaccines administered by injection at the recommended age (i.e., measles, rubella, and yellow fever) have protective antibodies, generally within two weeks of the dose.

Inactivated vaccines are derived either from whole viruses that are killed viruses or bacteria, purified proteins from the virus or bacteria, or DNA replicated material in a nonpathogenic carrier. The inactivated vaccine is then injected into the host. This form initiates an IgG mediated response as well as an IgA mediated response and carries less likelihood of illness as a result of the vaccination than does a live attenuated vaccine. However, over time there is a greater risk of loss of immunity, thus requiring re-vaccination.

Adult Vaccine Schedule
Each year the Department of Health and Human Services Center for Disease Control and Prevention (CDC) publishes a recommended guideline for Adult immunization (Figure 3 pdf). This guideline is approved by a committee comprised of the CDC’s Advisory Committee on Immunization Practices (ACIP), the American Academy of Family Physicians (AAFP), the American College of Obstetricians and Gynecologists (ACOG), and the American College of Physicians (ACP). This article highlights the most common adult vaccinations recommended by the CDC. A detailed list of all vaccines discussed in this article along with costs can be found in Table 2.

Tetanus Vaccination
Tetanus is a disease caused by the bacteria Clostridium Tetani found in the soil as spores as well as in farm animals and humans. It cannot be transmitted from person to person. On average, there are 43 reported cases per year of Tetanus in the United States.6 Symptoms of Tetanus include muscle spasms, especially of the jaw (trismus), difficulty swallowing, fever and profuse sweating. Unfortunately, there is no cure for tetanus once the person becomes symptomatic. Supportive care, including wound debridement if necessary, is the primary therapy.

The first Tetanus toxoid vaccine was produced and utilized in 1924 during World War I. Because it is an inactivated vaccine, a booster is required at seven to ten year intervals, based primarily on the immune status of the individual and/or their occupational exposure or risk. Those individuals at high risk include agricultural workers, persons who have a high risk of cuts, and travelers to tropical areas with rich, damp soils. Persons greater than 50 are at greatest risk, due in part to their waning antibody status and non-compliance with getting a booster vaccine.

If the vaccination history of the patient is unknown, the recommended guideline is that the individual undergo a series of three doses of Tetanus diphtheria (Td) vaccinations, with four weeks between the first and second doses and six to twelve months between the second and third doses. The Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination is recommended as a one-time substitution for the Td for adults younger than 65 years old. This substitution can be either for those receiving the three dose series or in the normal course of the booster vaccination for those previously immunized.

Reported adverse events of the tetanus vaccine include, but are not limited to, a localized rash, edema, hives, and an arthrus-type hypersensitivity reaction.7 Other neurological adverse events have also been reported including neuropathies, nerve paralysis, encephalopathy and Guillian Barre Syndrome. The Td vaccine is manufactured for adults by Massbiologics. The Tdap is manufactured under the name of Boostrix® by GlaxoSmithKline and under the name of Adacel® by Sanofi Pasteur.

Human Papilloma Virus (Hpv) Vaccination
HPV is a virus with over 100 known strains. Some strains are more virulent than others. Of particular concern are strains that are sexually transmitted. If left untreated, these high-risk strains can lead to cancer of the cervix, vulva, vagina, anus or penis. Those high risk strains identified include types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, 69, 73, and 82.8 Approximately 10,000 women each year are diagnosed with cervical cancer in the U.S. and roughly 3,700 of these die as a result. More than 70 percent of these cancers are caused by serotypes 16 and 18. 9

The HPV vaccine was first licensed by the Food and Drug Administration in June 2006 and is currently indicated for females age nine to twenty seven. It is an inactivated quadrivalent vaccine produced against the four most common HPV strains ( 6, 11, 16, & 18) most likely to cause cervical cancer. In clinical trials the incidence of HPV associated cervical cancer dropped 20-66 percent in those individuals receiving the vaccine.10,11 The vaccine is given as a series of three injections at zero, two and six months. The vaccine is not effective, however, once infection with these strains has already occurred. However, the CDC recommends that if a patient tests positive for only one of the high risks strain, they should still receive the HPV vaccine to reduce the risk of the remaining three strains covered in the vaccine.

Of all the available vaccines in use today in the U.S., HPV vaccine is the only vaccine that is gender specific. This vaccination is not yet approved for males; however, clinical studies are currently underway to determine the efficacy of such a vaccine in adult males.12 The HPV vaccine is manufactured under the name Gardasil® by Merck.

Varicella Vaccination
Varicella infection (chickenpox) is caused by the Varicella Zoster virus. It is typically transmitted by inhalation of respiratory droplets from an infected host. Typical infection with this virus occurs in childhood; however, adults who have not had prior exposure can also develop this infection. Patients acquiring this virus as an adult typically experience a more severe course of illness than the pediatric.13 Symptoms usually appear 10 to 21 days after exposure to the virus. Symptoms include: small blisters on the skin, which later break open, form a crust (scab), and begin to itch; tiredness, fever and generalized aches and pains. Chickenpox is contagious 1 to 2 days before the rash appears. It continues to be contagious until all of the blisters have crusted over, which usually takes 4 to 5 days. If there are no complications, adults have the chickenpox infection for 3 to 7 days. Varicella pneumonia is the most common and serious complication of chickenpox infection in adults 14-15, with a reported incidence in healthy adults that is 25-fold greater than in children and also carries a higher mortality in adults.16

The varicella vaccine is a live attenuated vaccine first licensed for use in 1995. If prior immunity to the varicella infection is properly demonstrated by documentation of prior varicella vaccination series, history of prior varicella infection, or laboratory evidence of immunity, then the varicella vaccine is not required. The vaccine can be given as a two-dose series with an interval time of four weeks between doses. The varicella vaccine is manufactured under the name Varivax® by Merck.

Herpes Zoster (Shingles) Vaccination
Shingles is caused by the reactivation of the varicella zoster virus, the same virus that causes chickenpox. The annual incidence of shingles in the United States is approximately one million cases.17 Adults are frequently infected with this virus in childhood which becomes dormant in cells of the nervous system and is reactivated by as of yet unknown triggers as an adult, causing a potentially debilitating illness. Shingles occurs more frequently in adults above the age of fifty.18 Complications of a shingles infection in addition to the potentially debilitating rash that develops include bacterial skin infections, eye pain and infections, motor neuropathy, meningitis, herpes zoster oticus, and postherpetic neuralgia.19

The Shingles vaccine is a live attenuated vaccine that was licensed in May 2006. The vaccination is recommended for adults greater than sixty years in age, regardless of prior zoster infections. This vaccine does not prevent development of Shingles, as the virus is frequently in dormant form. Rather, it can reduce the side effects that arise from a shingles infection along with the duration of symptoms in the individual patient. The vaccine is given as a single one-time dose. The Zoster vaccine is manu­factured under the name Zostavax® by Merck.

Measles, Mumps And Rubella (Mmr) Vaccination
MMR are viral respiratory infections that are spread either in the air or by respiratory droplets. Despite the availability of a safe and effective measles vaccine since 1963, an estimated 750,000 measles deaths occurred worldwide as recently as 2000.20 Measles usually lasts about 10 to 14 days. In parts of the developing world, the disease is more severe. People with measles may become quite ill, but most people recover completely. However, complications may include: ear infections, encephalitis, pneumonia, diarrhea/vomiting, bronchitis, laryngitis/croup, and thrombocytopenia. Rubella (also know as German measles or the 3-day measles) occurs in much the same manner. Symptoms appear typically two to three weeks post exposure and include a rash that starts on the chest or face, spreads to other parts of the body, and lasts three days or less (the most common symptom). Other symptoms experienced include mild fever, runny nose and cough, red, watery eyes, headache, tiredness, joint aches, and tender, swollen lymph nodes on the back of the neck, behind & in front of the ears. Prior to the licensure of the Rubella vaccine, during 1962-1965, there were an estimated 12.5 million cases of rubella in the United States, causing approximately 2,000 cases of encephalitis and numerous birth defects and fetal as well as neonatal deaths.21

The MMR vaccine is a live attenuated trivalent vaccine first licensed for use in 1963. The Rubella vaccine is available as a separate vaccine, often used in pregnancy for those females whose immune status is unknown or testing shows a poor immune response. Those born before 1957 are already considered immune to both the Measles and Mumps components. Those born after 1957 require one or more doses of the vaccine, depending upon certain conditions such as recent exposure to other persons with measles or mumps, persons attending college/post secondary education, persons traveling internationally, and health care workers. Special consideration of the rubella component is imperative in the pregnant patient (see discussion under special adult patient populations). The MMR vaccine is manufactured under the name MMRII® by Merck.

Influenza Vaccination
Influenza is caused by an RNA virus from the family Orthomyxoviridae that currently has multiple strains worldwide. Documentation of an influenza infection can be traced back as far a Hippocrates nearly 2,400 years ago. Influenza cases can range from very mild to severe or even fatal. Several epidemics in the 20th century resulted in tens of millions of deaths worldwide. The CDC reports that 20 percent of the United States population gets the flu each year and an estimated 36,000 people die each year from influenza and accompanying opportunistic infections and complications.

The influenza virus has several strains, each with multiple subtypes. The most common strains are Influenza A and Influenza B. A third major strain, Influenza C, is rare. Each year, the number of influenza cases vary, depending in part upon the degree of mutation that the strains have undergone. Some mutated strains will only cause a mild local epidemic, while others undergo a large antigenic drift resulting in a mass pandemic worldwide. The world health organization (WHO) constantly monitors influenza outbreaks and makes recommendations for subsequent vaccine development, both for the Northern Hemisphere and for the Southern Hemisphere. In February of this year the WHO delegation met and has since made recommendations for the influenza vaccine for the 2009-2010 season. Their recommendations can be found at www.who.int.

The vaccine used in the United States is traditionally developed against two of the most prevalent subtypes of the Influenza A and one subtype of the Influenza B, based on data collected by the WHO regarding the influenza season the year prior. Adults with chronic medical conditions (such as diabetes, cardiovascular disease, or chronic pulmonary conditions) should be counseled as to the benefits of the vaccine, and strongly advised to receive it. However, the live attenuated form is not recommended for immunocompromised patients. Additionally, all health care workers and residents of nursing homes or assisted living facilities should receive the vaccine on a yearly basis. Currently, the Influenza vaccine can be administered in the U.S. in two separate forms: an inactivated trivalent form and a live attenuated trivalent form. The inactivated form is an intramuscular injection, and the live attenuated form is intranasal. Both are recommended for revaccination on a yearly basis, due largely in part to the rapid mutation rate of the influenza virus. The influenza vaccine is manufactured as an injectable under the name Fluvirin® by Novartis and as a nasal spray under the name FluMist® by Medimmune.

Pneumococcal Vaccination
Pneumococcus is a bacterium from the Streptoccal family that has the potential to cause life-threatening pneumonia, bacteremia, or menin­gitis. It carries a high mortality rate in the adult population and among those with chronic medical conditions. More people die from pneumococcal infections than from any other vaccine preventable disease.22 It is primarily transmitted from person to person by air droplets. The CDC reports an average of approximately 175,000 persons are hospitalized each year with pneumococcal pneumonia. Additionally there are approximately 50,000 reported cases of pneumococ­cal bacteremia and around 4,500 cases of meningitis reported on a yearly basis. Symptoms of infection vary based on type of infection contracted.

The pneumococcal vaccine is an inactivated vaccine first licensed in 1977. An improved version was licensed in 1983 which contains purified proteins from 23 types of pneumococcal bacteria. Adults age 65 years or older, those with chronic health problems (such as diabetes, cirrhosis, sickle cell anemia, or lung disease), and immunocompromised patients should receive this vaccine. Most recently, in 2008 the CDC’s Advisory Committee on Immunization Practices (ACIP) added that adults with asthma also receive this vaccine. It is given as a single dose with a second booster given in five years if immunity cannot be demonstrated. The pneumococcal vaccine is manufactured under the name Pneumovax® by Merck.

Hepatitis A Vaccination
Hepatitis A, a disease caused by the Hepatitis A virus, causes significant morbidity; however, mortality from Hepatitis A is rare. There were approximately 3,500 cases of Hepatitis A in the U.S. in 2006.5 Hepatitis A is spread from person to person primarily by the fecal oral route. Symptoms of Hepatitis A infection include jaundice, “flu-like” symptoms, abdominal pain and diarrhea. Hepatitis A infection has an equal propensity to affect adults as it does children.

The Hepatitis A vaccine is an inactivated viral vaccine first approved for use in 1995. Adults recommended to receive the Hepatitis A vaccination include individuals with chronic liver disease, homosexual males, persons who use illegal injectable drugs, individuals who plan to travel to Hepatitis A endemic areas, and persons working with Hepatitis A infected primates. It is given in a two dose schedule with the second dose six months after the first. For those traveling to endemic areas, it is recommended that they receive the initial dose at least one month prior to travel. It is manufactured under the Havrix© by GlaxoSmithKline or VAQTA© by Merck. It is also available as a combination of Hepatitis A and B vaccines under the name Twinrix© by GlaxoSmithKline. The Twinrix® requires a three-dose schedule at zero, one and six months between injections.

Hepatitis B Vaccination
Hepatitis B is a disease caused by the Hepatitis B virus which primarily affects the liver. It is one of the primary sexually transmitted diseases in the United States. It infects over 140,000 persons per year and is responsible for over 5,000 adult deaths each year.5 Although infected, many patients with Hepatitis B may remain asymptomatic and unaware they have contracted the disease. Others may feel fatigue, loss of appetite, joint pain, nausea and vomiting, and jaundice. Persons with chronic Hepatitis B may only become symptomatic once cirrhosis has developed. The incidence of Hepatitis B in adults has decreased dramatically, due largely to initiation of the Hepatitis vaccine in infants and children.

The Hepatitis B vaccine is an inactivated vaccine produced by recombinant DNA technology. It was first approved for use in 1982. Those at risk for development of this infection include persons with end-stage renal disease on dialysis, persons with HIV disease, health care providers who are potentially exposed to Hepatitis B, and homosexual males. All persons in these categories should receive this vaccine. The Hepatitis B vaccine is manufactured under the name RECOMBIVAX® by Merck and ENGERIX-B® by GlaxoSmithKline.

Meningococcal Vaccination
Meningococcal disease is caused by the the bacterium Neisseria meningitides which currently has over 13 different identified serogroups based on the chemical structures of their capsular polysaccharide coat.23 Of the 13 serogroups, five (serogroups A, B, C, Y, and W135) are responsible for most of the disease worldwide. The meningococcal infection is spread by person to person contact with respiratory and throat secretions. Each year the CDC reports over 2,000 cases. Bacterial meningitis can be quite severe and may result in brain damage, hearing loss, learning disability or death. Adults are at a much greater risk for mortality due to meningococcal infection than pediatric patients.

The Meningococcal vaccine is an inactivated vaccine that is currently licensed in two forms in the U.S.—the Meningococcal conjugate vaccine (MCV4) and the meningococcal polysaccharide vaccine (MPSV4). Both protect against four of the most common serogroups— A, C, Y, W-135. The Meningococcal vaccine is recommended for all patients who are asplenic for any reason, any college students living in dormitories, military recruits, and persons who travel to or live in countries with an endemic meningococcal population. Many states have adopted health policies recommending that schools of higher learning, especially those with dormitories, provide educational material to their students of the importance of getting the meningococcal vaccine. The American College Health Association (ACHA) have assisted many campuses in implementing and conducting on-campus vaccine clinics, which has become very successful in appropriately educating and vaccinating at risk students (go to www.acha.org).

The MCV4 vaccination is recommended for adults less than 55 years of age. The MPS4 is recommended for persons age 55 and older. For adults, the vaccine is administered as a single dose. Protective antibody levels may be achieved within 7 to 10 days after vaccination. Antibody levels have been shown to decline rapidly over 2-3 years. 24 Revaccination may be considered for students who were vaccinated more than 3-5 years earlier.25 The MCV4 vaccine and the MPS4 vaccine is manufactured under the name Menactra® by Sanofi Pasteur.

Special Patient Populations
Certain patient populations warrant special consideration when discussing vaccine needs and requirements.

Pregnancy: Pregnant patients should not receive any live attenuated vaccines including the Zoster vaccine, the MMR vaccine, the Varicella vaccine, or the live Influenza vaccine. Proper documentation of the immune status is imperative for any newly pregnant female presenting to your clinic. For those pregnant patients who are not immune to rubella, as documented by serology testing, vaccination should be withheld until conclusion of the pregnancy. Additionally, the current recommendations state any female receiving the MMR vaccine should wait a minimum of one month before becoming pregnant. This is because the MMR vaccine is a live vaccine and the association between the rubella virus and congenital rubella syndrome. Although no teratogenic effects have currently been reported with the administration of the Td vaccine during the first trimester, current guidelines recommend that the Td vaccine should not be given until the second or third trimester if the previous Td vaccine was greater than ten years.26 Alternatively, one can wait until the postpartum period. The Tdap booster may be substituted for the Td vaccine only in the postpartum period. The pneumococcal, Hepatitis A, Hepatitis B, and meningococcal vaccines are only recommended if some other risk factor is present. No current recommendations are made for the HPV vaccine in pregnancy.

Immunocomprimised Patients: Immunocompromised patients (excluding HIV patients) represent an additional population warranting special consideration when deciding to vaccinate. As in pregnancy, any live attenuated vaccines are contraindicated including herpes zoster, MMR, varicella, or live influenza vaccines. For the HIV patient, if their CD4 count is greater than 200, they may receive the varicella and MMR vaccines, but not the zoster vaccine. These patients should receive the pneumococcal vaccine. However an individual risk:benefit decision should be weighed first prior to administration of the Hepatitis A, Hepatitis B or Meningococcal vaccines. Additional recommendations for other chronic conditions can be found in figure 3.

Neurologic Conditions: Patients with a fluctuating or progressive neurologic disorder, such as Guillain-Barré syndrome, should delay vaccination until their condition has been stable for at least one year due to potential cerebral irritation. If a neurologic disorder is stable, vaccinations can be given as per CDC recommendations.

Vaccine Safety And “Myths” Regarding Vaccines
Much of the scientific research and concern surrounding the topic of vaccine safety has centered on various adverse conditions reported following the administration of vaccines. Concerns with adult vaccines include: mercury poisoning with the use of thimerosal as a preservative in vaccine preparations, the incidence of Guillian-Barré (GBS) syndrome after the administration of the Meningococcal or the HPV vaccines, the association of multiple sclerosis and Hepatitis B vaccine, and the use of influenza vaccines in asthmatic patients.

Vaccine Preservatives. Thimerosal is a mercury-containing preservative used in older vaccine preparations as a preservative and in other products since the 1930s. There is no convincing scientific evidence of harm caused by the low doses of thimerosal in vaccines, except for minor reactions like redness and swelling at the injection site. However, in July 1999, the Public Health Service agencies, the American Academy of Pediatrics, and vaccine manufacturers agreed that thimerosal should be reduced or eliminated in vaccines as a precautionary measure. Since 2001, with the exception of some influenza vaccines, thimerosal is not used as a preservative in those routinely recommended vaccines. The influenza vaccine is also manufactured in a preservative free form, and can be administered should a patient request it.

Guillian-Barré Syndrome And Vaccines. As of February 25, 2008, more than 15 million doses of the Meningococcal vaccine have been distributed and there have been twenty-six confirmed case reports of GBS within six weeks of receipt of MCV4 meningococcal vaccination.27 The symptom onset was 2 to 33 days after vaccination. At the present time, however, there is no evidence to suggest that the MCV4 vaccination increases the patients’ risk of developing GBS. To date, there is no evidence that the currently licensed HPV vaccine has increased the rate of GBS above that expected in the population.

Multiple Sclerosis And The Hepatitis Vaccine. In 2002, the Institute of Medicine investigated the possible link between the Hepatitis vaccine and demyelinating neurological disorders, including multiple sclerosis (MS) in adults. The committee found that epidemiological evidence does not support a causal relationship between Hepatitis B vaccine in adults and multiple sclerosis.28

Asthma And The Influenza Vaccine. A study conducted by the American Lung Association Asthma Clinical Research Centers reported in the New England Journal of Medicine in 2001 found little risk in asthma exacerbation with subsequent administration of the influenze vaccine.29

Adverse events following any vaccine administration remains a critical link to providing accurate data on vaccine safety. All adverse events should be reported to the CDC and the Food and Drug Administration (FDA) under the Vaccine Adverse Events Reporting System (VAERS). The primary mandate of this department is to improve outcomes following vaccine administration. All potential adverse events from vaccines should be immediately reported to one of these governing bodies.

Concluding Remarks
Immunization of the adult population should become an active part of the family physicians’ office practice. Medicine in the 21st century centers around an evidence based medical practice. The benefits of providing vaccinations to your adult patients include better health and improved immunity. Ultimately this will then lead to less health care dollars spent.

The Immunization Action Coalition provides a free handout to assist the physician in determination of which vaccinations can and should be given to their adult patient population. The handout can be found at the following website: http://www.immunize.org/catg.d/p4065.pdf.30 Family physicians need to be proactive in their approach to adult vaccinations in order to strive towards eradication of vaccine preventable diseases.

DISCLAIMER—The information provided for the above adult vaccinations should not be considered comprehensive regarding adverse events or costs and coverage. To find additional information, visit the CDC at cdc.gov.

Dr. Shima is the Program Director of the Osteopathic Family Medicine Residency at Methodist Charlton Medical Center in Dallas, Texas. All correspondence can be sent to 3500 West Wheatland Road, Dallas 75224.

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References

  1. Plett PC (2006). “Peter Plett and other discoverers of cowpox vaccination before Edward Jenner“ (in German). Sudhoffs Arch 90 (2): 219–32.
  2. Lombard M, Pastoret PP, Moulin AM (2007). “A brief history of vaccines and vaccination“. Rev. - Off. Int. Epizoot. 26 (1): 29–48.
  3. Centers for Disease Control and Prevention. “Progress in global measles control and mortality reduction, 2000-2007” MMWR: Morb Mortal Wkly Rep 2008; 57: 1303-1306.
  4. Friedman, Harvey, MD and Isaacs, Stuart, MD. Smallpox. Up-To-Date.com. Last updated March 31, 2008
  5. Centers for Disease Control and Prevention. Surveillance for Acute Viral Hepatitis —United States, 2006. Morbidity and Mortality Weekly Report. March 21, 2008
  6. Pascual, FB, McGinley, EL, Zanardi, LR, et al. Tetanus surveillance—United States, 1998—2000. MMWR Surveill Summ 2003; 52:1.
  7. K. R. Broder et al. Preventing Tetanus, Diphtheria, and Pertussis Among Adolescents: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccines. MMWR Recommendations and Reports, March 24, 2006 / 55(RR03), 1–34.
  8. Munoz N, Bosch FX, de Sanjose S, et al. Epidemiologic classification of human papillomavirus types associated with cervical cancer. N Engl J Med 2003;348:518—27.
  9. Bosch FX, de SS. Human papillomavirus and cervical cancer—-burden and assessment of causality. J Natl Cancer Inst Monogr 2003;31:3—13
  10. Goldie SJ, Kohli M, Grima D, et al. Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine. J Natl Cancer Inst 2004;96:604—15.
  11. Update: Mumps Activity —- United States, January 1—October 7, 2006 Morb Mortal Wkly Report October 27, 2006 / 55(42);1152-1153
  12. HPV Vaccine shows Efficacy in Males, Family Practice News, Volume 39, Issue 6, March 15, 2009, Page 1.
  13. BCH Ho et al, Severe adult chickenpox infection requiring intensive care. Annals of academy of medicine Singapore 2004; 33 84-8
  14. Guess HA, Broughton DD, Melton LJ, Kurland LT. Chickenpox hospitalizations among residents of Olmsted Country, Minnesota, 1962 through 1981. Am J Dis Child 1984;138:1055–1057.
  15. Poltkin SA. Clinical and pathogenetic aspects of varicella-zoster. Postgrad Med J 1985;61:Suppl. 4, 7–14.
  16. Center for Disease Control. Varicella-zoster immune globulin for the prevention of chickenpox. Morb Mortal Wkly Rep 1984;33:84–90.
  17. Oxman MN, Levin MJ, Johnson GR, et al for the Shingles Prevention Study Group. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N Engl J Med 2005;352:2271-2284
  18. Yawn, BP, Saddier, P, Wollan, PC, St.Sauver, JL, Kurland, MJ, and Sy, LS. A Population-Based Study of the Incidence and Complication Rates of Herpes Zoster Before Zoster Vaccine Introduction. Mayo Clinic Proceedings November 2007 vol. 82 no. 11 1341-1349.
  19. Gnann, John and Whitley, Richard. Herpes Zoster, N Engl J Med 2002; 347: 340-6.
  20. Progress in Global Measles Control and Mortality Reduction, 2000-2007 Morb Mortal Wkly Report December 5, 2008. 57 (48); 1303-1306
  21. Centers for Disease Control and Prevention. Achievements in Public Health: Elimination of Rubella and Congenital Rubella Syndrome —- United States, 1969—2004. Morbidity and Mortality Weekly Report. March 25, 2005 / 54(11);279-282
  22. Gardner, P, Schaffner, W. Immunization of adults. N Engl J Med 1993; 328:1252.
  23. Knapp JS, Koumans EH. Neisseria and Branhamella. Murray PR, Baron EJ, Pfaller MA et al., eds. Manual of Clinical Microbiology. 7th ed. Washington DC: ASM Press; 1999:586-603.
  24. CDC. Control and prevention of meningococcal disease and Control and prevention of serogroup C meningococcal disease: evaluation and management of suspected outbreaks—- recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 1997;46(No. RR-5):1—21.
  25. CDC. Control and prevention of meningococcal disease and Meningococcal disease and college students: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR 2000;49(No. RR-7):1—22.
  26. Guidelines for vaccinating pregnant women. Recommendation of the Advisory Committee on Immunization Practices (ACIP), Atlanta, GA. Centers for Disease Control and Prevention, 2002.
  27. Centers for Disease Control and Prevention (CDC). Update: Guillain-Barré Syndrome among Recipients of Menactra® Meningococcal Conjugate Vaccine—United States, June 2005–September 2006. MMWR 2006;55(41):1120–1124.
  28. The American Lung Association Asthma Clinical Research Centers.. The safety of inactivated influenza vaccine in adults and children with asthma. N Engl J Med 2001;345,1529-1536
  29. Immunization Action Coalition—2009. http://www.immunize.org/catg.d/p4065.pdf. Accessed April 27,2009.