Cleveland Clinic Journal of Medicine

The past 10 years have seen marked advances in vaccine research, resulting in more products being available. In 1983 the childhood vaccination schedule included protection against seven diseases: polio, tetanus, diphtheria, pertussis, measles, mumps, and rubella. The schedule in 2010 includes protection against organisms that cause seven more: Haemophilus influenzae, hepatitis A, hepatitis B, influenza, meningococcus, pneumococcus, and varicella.¹ In addition, new vaccine products are available for adolescents, offering protection against meningococcus, seasonal influenza, and human papillomavirus (HPV) and extending the length of protection against pertussis. For adults, a vaccine now protects against shingles, and several products offer boosting of pertussis immunity.

This rapid growth in the number of recommended vaccine products has made it challenging for practicing physicians to stay current on and to implement the ever-changing recommendations. The purpose of this article is to summarize the additions and changes over the past 3 years to the schedules of recommended vaccines for children, adolescents, and adults.

VACCINE UPDATE FOR CHILDREN

The recent changes to the childhood immunization schedule have added protection against rotavirus and seasonal influenza and have expanded the protection against hepatitis A and varicella.

Rotavirus vaccination for infants

Rotavirus is the leading cause of infectious gastroenteritis in infants. It causes significant morbidity and expense, accounting for 2.7 million episodes per year in the United States, 410,000 outpatient or office visits, 201,000 to 272,000 emergency department visits, 55,000 to 70,000 hospitalizations, and 20 to 60 deaths.² Although the number of deaths in the United States is not large, rotavirus is a leading cause of infant deaths around the world.

Rotavirus vaccination is challenging because of the time frame in which the series needs to be given. The first dose has to be given after 6 weeks of age but before 15 weeks of age, and the last dose should be given before 8 months of age, with a minimum of 4 weeks between doses. It is preferable to use the same product to finish the series. They can be used interchangeably, but this then requires three total doses.

The effectiveness of the vaccine in preventing rotavirus gastroenteritis in the first year after vaccination was greater than 80% in most studies and approached 100% in preventing serious gastroenteritis.²

Those vaccinated appear to have a slightly higher rate of diarrhea and vomiting in the first 42 days after vaccination. Safety monitoring after the products were licensed has not shown an increased rate of intussusception with either product.

The only contraindication to the vaccines is a serious allergic reaction to them or to one of their components. They should be used with caution in patients who have suppressed immunity, acute gastroenteritis, preexisting gastrointestinal disease, or previous intussusception.

Gradually, we seem to be moving toward vaccinating everyone every year against seasonal influenza. Previously, vaccination was recommended for children age 6 months through 4 years; in 2008, the Advisory Committee on Immunization Practices (ACIP) extended the recommendation to the age group 5 through 18 years.³

Two types of seasonal influenza vaccine are available: trivalent influenza vaccine (TIV), which contains killed virus and is given by injection, and live-attenuated seasonal influenza vaccine (LAIV), which is given by nasal spray. Both contain the same three seasonal influenza antigens, selected each year by a team of experts. TIV is licensed for those age 6 months and older, and LAIV is licensed for ages 2 through 49 years.⁴

Since LAIV contains a live-attenuated virus, it should not be used in anyone who has a chronic illness (including those under the age of 5 with recurrent wheezing, those with suppressed immunity, and those with a history of Guillain-Barré syndrome); in pregnant women; or those who have close contact with anyone who is immune-suppressed. The injection is contraindicated for those who have had a serious allergic reaction to eggs.

Children younger than 9 years should receive two doses of either type of vaccine the first year they are vaccinated. Those who receive only one dose the first year they are vaccinated should receive two doses the next year. If they fail to receive two doses in the next year, only a single dose is recommended after that. This is a slight modification of the previous recommendation that only one dose be given the second year if only one dose was given the first year.⁵

Hepatitis A vaccine at age 12–23 months

An inactivated hepatitis A vaccine (HepA) was first licensed in 1995; another was licensed in 1996. Recommendations for their use have been revised periodically, and their widespread use has resulted in a marked reduction in the incidence of hepatitis A virus infection.

The current recommendation is that all children be vaccinated at age 12 to 23 months. In addition, in areas of high prevalence, vaccine is recommended for older children who have not been vaccinated. Other target groups are those at higher risk of hepatitis A, including travelers to endemic areas, users of illicit drugs, and men who have sex with men.⁶ Indications for vaccination before travel, after exposure to hepatitis A infection, and in families of international adoptees are covered later in this paper in a discussion about vaccinations in adults.

Varicella at 12–15 months and 4–6 years, with catch-up for others

Before varicella vaccine was licensed in 1995, 4 million cases of varicella infection (chickenpox) were reported in the United States each year, resulting in thousands of hospitalizations and more than 100 deaths. The vaccine is now widely used, with a coverage rate of 88%, and it has proven to be 85% effective.⁷ The result was a marked decrease in the incidence of varicella and in varicella-related hospitalizations and deaths.

In spite of this success, the number of varicella cases has remained constant over the past few years, and sporadic outbreaks continue to occur, predominantly in schools, even schools in which a high percentage of the children are vaccinated.^7,8 These outbreaks have involved infections in unvaccinated children and also “breakthrough disease” in children who have been vaccinated. If someone who has received one dose of vaccine is exposed to varicella, the risk of a breakthrough infection is about 15%.⁹ A two-dose series of varicella vaccine reduces the risk by about 75%.⁷ Breakthrough disease is usually milder than infection in the unvaccinated, with fewer skin lesions, milder symptoms, and fewer complications, but those affected are still infectious to others.

In 2005 and 2006, this ongoing risk of varicella prompted the ACIP to consider and recommend several new control measures:

• Two doses of varicella vaccine for all children, the first dose at age 12 to 15 months and the second at age 4 to 6 years—the same schedule as for immunization against measles, mumps, and rubella
• Two doses of varicella vaccine, the second given 4 to 8 weeks after the first, for all adolescents and adults who have no evidence of immunity
• A catch-up second dose for everyone who received one dose previously
• Screening for varicella immunity in pregnant women and postpartum vaccination with two doses for those who are not immune, the first dose given before discharge and the second dose 4 to 8 weeks later.

VACCINE UPDATE FOR ADOLESCENTS

A number of vaccines are now available and recommended for routine use in adolescents.⁹ These include HPV vaccine for girls, quadrivalent meningococcal conjugate vaccine (MCV4), and combined tetanus toxoid, reduced-dose diphtheria toxoid, and acellular pertussis (Tdap). All these are now recommended routinely at age 11 or 12. Seasonal influenza vaccine is recommended annually through age 18.

Meningococcal conjugate vaccine for all at age 11–18

There is some evidence that MCV4 may be linked to a small risk of Guillain-Barré syndrome. Although this link has not been conclusively proven, a history of Guillain-Barré syndrome calls for caution in using MCV4. For those who have a history of this syndrome but need protection against meningococcal infection, the MPSV4 is an alternative.¹¹

Pertussis: A Tdap booster at age 11–18

From Broder KR, et al; ACIP. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the ACIP. MMWR Recomm Rep 2006; 55(RR–3):1–34

In addition, a greater percentage of cases now occurs in adolescents and young adults. Half of reported cases are now in those age 10 years and older. Most nonimmunized or incompletely immunized infants who develop pertussis were exposed to the disease by older household members, not by same-age cohorts. Since the disease presents as nonspecific cough in adolescents, it is often not diagnosed, and the incidence is probably much higher than the reported number of cases would indicate.

These trends were cause for public health concern and led to the development of pertussis-containing vaccine products for adolescents and adults. Two Tdap products are available: one is licensed for those ages 10 to 64 (Boostrix), the other for ages 11 to 64 (Adacel). Since 2005, the ACIP has recommended a single dose of Tdap for those age 11 to 18, preferably at 11 or 12 years.¹² The optimal interval from the last tetanus-diphtheria shot is 5 years, but a shorter interval is acceptable. Thereafter, boosters with the tetanus toxoid and reduced-dose diphtheria toxoid (Td) vaccine are recommended every 10 years. If an adolescent has not previously received a complete series of a tetanus-diphtheria product, he or she should be given the recommended number of doses, only one of which should be Tdap, the others Td. The number and timing of doses can be found at www.cdc.gov/mmwr/preview/mmwrhtml/rr55e223a5.htm.

HPV is sexually transmitted and causes genital warts, cervical cancer, and other oral, anal, and genital cancers.

HPV is the most common sexually transmitted infection in the United States, with over 6 million new cases each year.¹³ A study in 2003 to 2004 using HPV DNA typing of cervicovaginal swab specimens in a sample of women between the ages of 14 and 59 found an overall point prevalence of 26.8% of any HPV type.¹⁴ Those between 20 and 24 years had the highest prevalence at 44.8%. Those ages 14 to 19 had a prevalence of 24.5%. Several studies have reported a similar age-related increase in HPV prevalence.^15,16

One survey found that nearly 25% of girls in the United States are sexually active by age 15, 40% by age 16, and 70% by age 18.¹⁷ The 2005 Behavioral Risk Survey found that nearly 4% of girls were sexually active before age 13, and by the ninth grade 5.7% of those who were sexually active had had four or more partners.¹⁸ To receive the full benefit from the HPV vaccine, it should be given before this risk of acquiring HPV occurs.

A quadrivalent HPV vaccine (HPV4) was first licensed in the United States in 2006 for use in girls and women 9 to 26 years old to prevent cervical, vulvar, and vaginal precancerous lesions and cancer, and for prevention of anogenital warts. It contains viral proteins from HPV types 6, 11, 16, and 18, the types currently responsible for 70% of cervical cancers and 90% of anogenital warts. The vaccine is prepared in a yeast substrate and contains an aluminum-based adjuvant.

HPV4 has proven highly effective in women ages 16 to 26 not previously exposed to the four HPV types in the vaccine. The end points used in these studies were cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, anogenital warts, and vulvar and vaginal intraepithelial neoplasms.^13,19,20 The vaccine’s effectiveness has been 98% to 100% after 3 to 5 years. These trials are ongoing.

The vaccine’s efficacy in women with current or past HPV infection is less certain. Studies of this question have included only small numbers, and the confidence intervals are large and include 0. In intention-to-treat studies, its efficacy has been 39% to 46% for prevention of cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ caused by HPV-16 or HPV-18, 69% for prevention of HPV-16- or HPV-18-related vaginal intraepithelial neoplasia, and 68.5% for vaccine-type-related warts.¹³

The most common adverse effects of HPV4 have included redness, pain, and swelling at the injection site, which occur in about 20% of recipients.¹³ There is an increased risk of syncope immediately after the vaccine is given, and observation for 15 minutes after injection is recommended. A recent study suggested a link between the vaccine and venous thromboembolism. ²¹ The rate was 2 per million doses, and because many of the recipients also were taking oral contraceptives, their venous thromboembolism has not yet been definitively proven to be caused by the vaccine.

HPV4 is contraindicated in those who have experienced a severe allergic reaction to a previous dose or who have an allergy to a vaccine component. Vaccination should be deferred in those with moderate or severe acute illnesses.

In June 2006, the ACIP¹³ made the following recommendations for HPV4:

• Girls ages 11 to 12 years should be routinely vaccinated with three doses
• The series can start as early as age 9 years
• Women and girls age 13 to 26 who have not been previously vaccinated should receive catch-up vaccination
• Neither Papanicolaou (Pap) testing nor HPV screening is necessary before vaccination
• HPV4 can be given with other age-appropriate vaccines
• Vaccination does not change the recommendations for cervical cancer screening
• The recommendations remain the same regardless of abnormal Pap tests, positive HPV DNA tests, or warts.

There have been two very recent developments regarding HPV vaccines.

A bivalent vaccine (HPV2) has been licensed in the United States and approved for use in girls and women ages 10 to 25 for prevention of cervical cancer and precancerous lesions. It contains antigens against HPV-16 and HPV-18 but does not provide protection against genital warts. The ACIP has stated no preference for the bivalent or the quadrivalent vaccine for the prevention of cervical cancer and precancerous lesions.

HPV4 has also gained licensure for use in boys and men age 9 to 26 for the prevention of genital warts. The ACIP has not recommended it for routine use, leaving the decision to patients and physicians after weighing the potential benefits and costs.

VACCINE UPDATE FOR ADULTS

Four vaccines are now routinely recommended for adults:

• Seasonal influenza vaccine starting at age 50
• Pneumococcal polysaccharide vaccine (PPSV23) starting at age 65
• Herpes zoster vaccine starting at age 60
• A diphtheria and tetanus toxoid product every 10 years, with Tdap given once.²²

The rest of the adult schedule is based on catch-up (measles, mumps, rubella, varicella) or risk (hepatitis A and B and meningococccal disease). Seasonal influenza and pneumococcal vaccinations are also recommended before ages 50 and 65, respectively, for those with certain risk conditions. The complete adult immunization schedule can be found on the US Centers for Disease Control and Prevention (CDC) Web site.²²

One dose of Tdap instead of the next Td booster

The CDC now recommends that a single dose of Tdap should replace the next dose of Td for adults ages 19 to 64 as part of the every-10-year tetanus-diphtheria boosting recommendation and if indicated for wound management. ²³ In addition, a single dose of Tdap should be given to adults who have close contact with infants less than 6 months of age. The optimal interval between this Tdap shot and the last Td booster is 2 years or greater, but shorter intervals are acceptable. Women of childbearing age should receive Tdap preconception or postpartum if they have not previously received it. Tdap is not approved for use during pregnancy. Health care workers should also receive a dose of Tdap if they have never received it previously and if their last Td booster was more than 2 years ago, although less than 2 years is acceptable.

Contraindications to Tdap include anaphylaxis to a vaccine component and encephalopathy occurring within 7 days of previously receiving a pertussis vaccine.

Herpes zoster vaccine for those age 60 and older

Shingles causes considerable morbidity in older adults. The lifetime risk is 25%, and onefourth of those with shingles develop postherpetic neuralgia.

Herpes zoster vaccine is a live-attenuated vaccine that requires only a single injection. It is licensed for use in those ages 60 and older, and the ACIP recommends its routine use.²⁴ Its effectiveness is approximately 50% and is inversely related to age. The number of patients who need to be vaccinated to prevent one lifetime case of shingles is 17.

Contraindications to this vaccine include a prior anaphylactic reaction to gelatin or neomycin, compromised immunity due to disease or to immune-suppressive therapy including high-dose corticosteroids, and active tuberculosis.

Payment for this vaccine by Medicare is through Part D, creating some administrative difficulties for physicians’ offices.

Pneumococcal vaccination extended to smokers and people with asthma

The ACIP recently added two new groups for whom PPSV23 is recommended: smokers and those with asthma.²⁵ Smoking poses as much of a risk for pneumococcal pneumonia as do diabetes and other chronic illnesses that are currently indications for the vaccine. The number needed to vaccinate to prevent one case of pneumonia among smokers is 10,000 in people ages 18 to 44, and 4,000 in those ages 45 to 64.²⁶

The ACIP also clarified the recommendation for a second dose of PPSV23.²⁵ A second dose 5 years after the first is recommended for those who have immune suppression, sickle cell disease, or asplenia. People over age 65 should receive a second dose if they were vaccinated more than 5 years previously and before age 65.

New uses for hepatitis A vaccine

A combined hepatitis A and hepatitis B vaccine (Twinrix) has received approval for an alternate, four-dose schedule at 0, 7, 21 days, and 12 months.²⁷ It has previously only been approved for a three-dose schedule at 0, 1, and 6 months. The new alternative schedule allows greater protection for travelers who need to depart within less than 1 month.

For unvaccinated people who are acutely exposed to hepatitis A virus and for those traveling to areas of high prevalence who do not have time to complete the two doses of hepatitis A vaccine, the only prevention available until recently has been immune globulin. This has changed: hepatitis A vaccine can now be used in both groups. The new recommendations for postexposure prophylaxis is that either a single dose of hepatitis A vaccine or use of immune globulin is acceptable.²⁸ In ages 12 months to 40 years, vaccine is preferred. For those over age 40, immune globulin is preferred, but vaccine is acceptable. For children younger than 12 months, the immune-suppressed, and those with chronic liver disease, immune globulin should be used.

Those traveling or working in countries with high rates of hepatitis A can be protected with either hepatitis A vaccine or immune globulin. A single dose of the vaccine is sufficient for healthy people, with a second dose at the recommended interval to complete the series. Those younger than 12 months and those who choose not to receive the vaccine, including those who are allergic to it, should be offered immune globulin. Both immune globulin and hepatitis A vaccine should be considered for certain patients who plan to travel within 2 weeks of the first vaccine dose, ie, those over age 40, those with compromised immunity, and those with chronic liver disease or other chronic conditions.

Hepatitis A vaccine is now also recommended for all unvaccinated people who anticipate close personal contact with an international adoptee during the first 60 days following arrival from countries with high or intermediate hepatitis A endemicity.²⁹ The first dose should be given as soon as the adoption is planned and ideally at least 2 weeks before the child arrives.

The past 10 years have seen marked advances in vaccine research, resulting in more products being available. In 1983 the childhood vaccination schedule included protection against seven diseases: polio, tetanus, diphtheria, pertussis, measles, mumps, and rubella. The schedule in 2010 includes protection against organisms that cause seven more: Haemophilus influenzae, hepatitis A, hepatitis B, influenza, meningococcus, pneumococcus, and varicella.¹ In addition, new vaccine products are available for adolescents, offering protection against meningococcus, seasonal influenza, and human papillomavirus (HPV) and extending the length of protection against pertussis. For adults, a vaccine now protects against shingles, and several products offer boosting of pertussis immunity.

This rapid growth in the number of recommended vaccine products has made it challenging for practicing physicians to stay current on and to implement the ever-changing recommendations. The purpose of this article is to summarize the additions and changes over the past 3 years to the schedules of recommended vaccines for children, adolescents, and adults.

VACCINE UPDATE FOR CHILDREN

The recent changes to the childhood immunization schedule have added protection against rotavirus and seasonal influenza and have expanded the protection against hepatitis A and varicella.

Rotavirus vaccination for infants

Rotavirus is the leading cause of infectious gastroenteritis in infants. It causes significant morbidity and expense, accounting for 2.7 million episodes per year in the United States, 410,000 outpatient or office visits, 201,000 to 272,000 emergency department visits, 55,000 to 70,000 hospitalizations, and 20 to 60 deaths.² Although the number of deaths in the United States is not large, rotavirus is a leading cause of infant deaths around the world.

Rotavirus vaccination is challenging because of the time frame in which the series needs to be given. The first dose has to be given after 6 weeks of age but before 15 weeks of age, and the last dose should be given before 8 months of age, with a minimum of 4 weeks between doses. It is preferable to use the same product to finish the series. They can be used interchangeably, but this then requires three total doses.

The effectiveness of the vaccine in preventing rotavirus gastroenteritis in the first year after vaccination was greater than 80% in most studies and approached 100% in preventing serious gastroenteritis.²

Those vaccinated appear to have a slightly higher rate of diarrhea and vomiting in the first 42 days after vaccination. Safety monitoring after the products were licensed has not shown an increased rate of intussusception with either product.

The only contraindication to the vaccines is a serious allergic reaction to them or to one of their components. They should be used with caution in patients who have suppressed immunity, acute gastroenteritis, preexisting gastrointestinal disease, or previous intussusception.

Gradually, we seem to be moving toward vaccinating everyone every year against seasonal influenza. Previously, vaccination was recommended for children age 6 months through 4 years; in 2008, the Advisory Committee on Immunization Practices (ACIP) extended the recommendation to the age group 5 through 18 years.³

Two types of seasonal influenza vaccine are available: trivalent influenza vaccine (TIV), which contains killed virus and is given by injection, and live-attenuated seasonal influenza vaccine (LAIV), which is given by nasal spray. Both contain the same three seasonal influenza antigens, selected each year by a team of experts. TIV is licensed for those age 6 months and older, and LAIV is licensed for ages 2 through 49 years.⁴

Since LAIV contains a live-attenuated virus, it should not be used in anyone who has a chronic illness (including those under the age of 5 with recurrent wheezing, those with suppressed immunity, and those with a history of Guillain-Barré syndrome); in pregnant women; or those who have close contact with anyone who is immune-suppressed. The injection is contraindicated for those who have had a serious allergic reaction to eggs.

Children younger than 9 years should receive two doses of either type of vaccine the first year they are vaccinated. Those who receive only one dose the first year they are vaccinated should receive two doses the next year. If they fail to receive two doses in the next year, only a single dose is recommended after that. This is a slight modification of the previous recommendation that only one dose be given the second year if only one dose was given the first year.⁵

Hepatitis A vaccine at age 12–23 months

An inactivated hepatitis A vaccine (HepA) was first licensed in 1995; another was licensed in 1996. Recommendations for their use have been revised periodically, and their widespread use has resulted in a marked reduction in the incidence of hepatitis A virus infection.

The current recommendation is that all children be vaccinated at age 12 to 23 months. In addition, in areas of high prevalence, vaccine is recommended for older children who have not been vaccinated. Other target groups are those at higher risk of hepatitis A, including travelers to endemic areas, users of illicit drugs, and men who have sex with men.⁶ Indications for vaccination before travel, after exposure to hepatitis A infection, and in families of international adoptees are covered later in this paper in a discussion about vaccinations in adults.

Varicella at 12–15 months and 4–6 years, with catch-up for others

Before varicella vaccine was licensed in 1995, 4 million cases of varicella infection (chickenpox) were reported in the United States each year, resulting in thousands of hospitalizations and more than 100 deaths. The vaccine is now widely used, with a coverage rate of 88%, and it has proven to be 85% effective.⁷ The result was a marked decrease in the incidence of varicella and in varicella-related hospitalizations and deaths.

In spite of this success, the number of varicella cases has remained constant over the past few years, and sporadic outbreaks continue to occur, predominantly in schools, even schools in which a high percentage of the children are vaccinated.^7,8 These outbreaks have involved infections in unvaccinated children and also “breakthrough disease” in children who have been vaccinated. If someone who has received one dose of vaccine is exposed to varicella, the risk of a breakthrough infection is about 15%.⁹ A two-dose series of varicella vaccine reduces the risk by about 75%.⁷ Breakthrough disease is usually milder than infection in the unvaccinated, with fewer skin lesions, milder symptoms, and fewer complications, but those affected are still infectious to others.

In 2005 and 2006, this ongoing risk of varicella prompted the ACIP to consider and recommend several new control measures:

• Two doses of varicella vaccine for all children, the first dose at age 12 to 15 months and the second at age 4 to 6 years—the same schedule as for immunization against measles, mumps, and rubella
• Two doses of varicella vaccine, the second given 4 to 8 weeks after the first, for all adolescents and adults who have no evidence of immunity
• A catch-up second dose for everyone who received one dose previously
• Screening for varicella immunity in pregnant women and postpartum vaccination with two doses for those who are not immune, the first dose given before discharge and the second dose 4 to 8 weeks later.

VACCINE UPDATE FOR ADOLESCENTS

A number of vaccines are now available and recommended for routine use in adolescents.⁹ These include HPV vaccine for girls, quadrivalent meningococcal conjugate vaccine (MCV4), and combined tetanus toxoid, reduced-dose diphtheria toxoid, and acellular pertussis (Tdap). All these are now recommended routinely at age 11 or 12. Seasonal influenza vaccine is recommended annually through age 18.

Meningococcal conjugate vaccine for all at age 11–18

There is some evidence that MCV4 may be linked to a small risk of Guillain-Barré syndrome. Although this link has not been conclusively proven, a history of Guillain-Barré syndrome calls for caution in using MCV4. For those who have a history of this syndrome but need protection against meningococcal infection, the MPSV4 is an alternative.¹¹

Pertussis: A Tdap booster at age 11–18

From Broder KR, et al; ACIP. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the ACIP. MMWR Recomm Rep 2006; 55(RR–3):1–34

In addition, a greater percentage of cases now occurs in adolescents and young adults. Half of reported cases are now in those age 10 years and older. Most nonimmunized or incompletely immunized infants who develop pertussis were exposed to the disease by older household members, not by same-age cohorts. Since the disease presents as nonspecific cough in adolescents, it is often not diagnosed, and the incidence is probably much higher than the reported number of cases would indicate.

These trends were cause for public health concern and led to the development of pertussis-containing vaccine products for adolescents and adults. Two Tdap products are available: one is licensed for those ages 10 to 64 (Boostrix), the other for ages 11 to 64 (Adacel). Since 2005, the ACIP has recommended a single dose of Tdap for those age 11 to 18, preferably at 11 or 12 years.¹² The optimal interval from the last tetanus-diphtheria shot is 5 years, but a shorter interval is acceptable. Thereafter, boosters with the tetanus toxoid and reduced-dose diphtheria toxoid (Td) vaccine are recommended every 10 years. If an adolescent has not previously received a complete series of a tetanus-diphtheria product, he or she should be given the recommended number of doses, only one of which should be Tdap, the others Td. The number and timing of doses can be found at www.cdc.gov/mmwr/preview/mmwrhtml/rr55e223a5.htm.

HPV is sexually transmitted and causes genital warts, cervical cancer, and other oral, anal, and genital cancers.

HPV is the most common sexually transmitted infection in the United States, with over 6 million new cases each year.¹³ A study in 2003 to 2004 using HPV DNA typing of cervicovaginal swab specimens in a sample of women between the ages of 14 and 59 found an overall point prevalence of 26.8% of any HPV type.¹⁴ Those between 20 and 24 years had the highest prevalence at 44.8%. Those ages 14 to 19 had a prevalence of 24.5%. Several studies have reported a similar age-related increase in HPV prevalence.^15,16

One survey found that nearly 25% of girls in the United States are sexually active by age 15, 40% by age 16, and 70% by age 18.¹⁷ The 2005 Behavioral Risk Survey found that nearly 4% of girls were sexually active before age 13, and by the ninth grade 5.7% of those who were sexually active had had four or more partners.¹⁸ To receive the full benefit from the HPV vaccine, it should be given before this risk of acquiring HPV occurs.

A quadrivalent HPV vaccine (HPV4) was first licensed in the United States in 2006 for use in girls and women 9 to 26 years old to prevent cervical, vulvar, and vaginal precancerous lesions and cancer, and for prevention of anogenital warts. It contains viral proteins from HPV types 6, 11, 16, and 18, the types currently responsible for 70% of cervical cancers and 90% of anogenital warts. The vaccine is prepared in a yeast substrate and contains an aluminum-based adjuvant.

HPV4 has proven highly effective in women ages 16 to 26 not previously exposed to the four HPV types in the vaccine. The end points used in these studies were cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, anogenital warts, and vulvar and vaginal intraepithelial neoplasms.^13,19,20 The vaccine’s effectiveness has been 98% to 100% after 3 to 5 years. These trials are ongoing.

The vaccine’s efficacy in women with current or past HPV infection is less certain. Studies of this question have included only small numbers, and the confidence intervals are large and include 0. In intention-to-treat studies, its efficacy has been 39% to 46% for prevention of cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ caused by HPV-16 or HPV-18, 69% for prevention of HPV-16- or HPV-18-related vaginal intraepithelial neoplasia, and 68.5% for vaccine-type-related warts.¹³

The most common adverse effects of HPV4 have included redness, pain, and swelling at the injection site, which occur in about 20% of recipients.¹³ There is an increased risk of syncope immediately after the vaccine is given, and observation for 15 minutes after injection is recommended. A recent study suggested a link between the vaccine and venous thromboembolism. ²¹ The rate was 2 per million doses, and because many of the recipients also were taking oral contraceptives, their venous thromboembolism has not yet been definitively proven to be caused by the vaccine.

HPV4 is contraindicated in those who have experienced a severe allergic reaction to a previous dose or who have an allergy to a vaccine component. Vaccination should be deferred in those with moderate or severe acute illnesses.

In June 2006, the ACIP¹³ made the following recommendations for HPV4:

• Girls ages 11 to 12 years should be routinely vaccinated with three doses
• The series can start as early as age 9 years
• Women and girls age 13 to 26 who have not been previously vaccinated should receive catch-up vaccination
• Neither Papanicolaou (Pap) testing nor HPV screening is necessary before vaccination
• HPV4 can be given with other age-appropriate vaccines
• Vaccination does not change the recommendations for cervical cancer screening
• The recommendations remain the same regardless of abnormal Pap tests, positive HPV DNA tests, or warts.

There have been two very recent developments regarding HPV vaccines.

A bivalent vaccine (HPV2) has been licensed in the United States and approved for use in girls and women ages 10 to 25 for prevention of cervical cancer and precancerous lesions. It contains antigens against HPV-16 and HPV-18 but does not provide protection against genital warts. The ACIP has stated no preference for the bivalent or the quadrivalent vaccine for the prevention of cervical cancer and precancerous lesions.

HPV4 has also gained licensure for use in boys and men age 9 to 26 for the prevention of genital warts. The ACIP has not recommended it for routine use, leaving the decision to patients and physicians after weighing the potential benefits and costs.

VACCINE UPDATE FOR ADULTS

Four vaccines are now routinely recommended for adults:

• Seasonal influenza vaccine starting at age 50
• Pneumococcal polysaccharide vaccine (PPSV23) starting at age 65
• Herpes zoster vaccine starting at age 60
• A diphtheria and tetanus toxoid product every 10 years, with Tdap given once.²²

The rest of the adult schedule is based on catch-up (measles, mumps, rubella, varicella) or risk (hepatitis A and B and meningococccal disease). Seasonal influenza and pneumococcal vaccinations are also recommended before ages 50 and 65, respectively, for those with certain risk conditions. The complete adult immunization schedule can be found on the US Centers for Disease Control and Prevention (CDC) Web site.²²

One dose of Tdap instead of the next Td booster

The CDC now recommends that a single dose of Tdap should replace the next dose of Td for adults ages 19 to 64 as part of the every-10-year tetanus-diphtheria boosting recommendation and if indicated for wound management. ²³ In addition, a single dose of Tdap should be given to adults who have close contact with infants less than 6 months of age. The optimal interval between this Tdap shot and the last Td booster is 2 years or greater, but shorter intervals are acceptable. Women of childbearing age should receive Tdap preconception or postpartum if they have not previously received it. Tdap is not approved for use during pregnancy. Health care workers should also receive a dose of Tdap if they have never received it previously and if their last Td booster was more than 2 years ago, although less than 2 years is acceptable.

Contraindications to Tdap include anaphylaxis to a vaccine component and encephalopathy occurring within 7 days of previously receiving a pertussis vaccine.

Herpes zoster vaccine for those age 60 and older

Shingles causes considerable morbidity in older adults. The lifetime risk is 25%, and onefourth of those with shingles develop postherpetic neuralgia.

Herpes zoster vaccine is a live-attenuated vaccine that requires only a single injection. It is licensed for use in those ages 60 and older, and the ACIP recommends its routine use.²⁴ Its effectiveness is approximately 50% and is inversely related to age. The number of patients who need to be vaccinated to prevent one lifetime case of shingles is 17.

Contraindications to this vaccine include a prior anaphylactic reaction to gelatin or neomycin, compromised immunity due to disease or to immune-suppressive therapy including high-dose corticosteroids, and active tuberculosis.

Payment for this vaccine by Medicare is through Part D, creating some administrative difficulties for physicians’ offices.

Pneumococcal vaccination extended to smokers and people with asthma

The ACIP recently added two new groups for whom PPSV23 is recommended: smokers and those with asthma.²⁵ Smoking poses as much of a risk for pneumococcal pneumonia as do diabetes and other chronic illnesses that are currently indications for the vaccine. The number needed to vaccinate to prevent one case of pneumonia among smokers is 10,000 in people ages 18 to 44, and 4,000 in those ages 45 to 64.²⁶

The ACIP also clarified the recommendation for a second dose of PPSV23.²⁵ A second dose 5 years after the first is recommended for those who have immune suppression, sickle cell disease, or asplenia. People over age 65 should receive a second dose if they were vaccinated more than 5 years previously and before age 65.

New uses for hepatitis A vaccine

A combined hepatitis A and hepatitis B vaccine (Twinrix) has received approval for an alternate, four-dose schedule at 0, 7, 21 days, and 12 months.²⁷ It has previously only been approved for a three-dose schedule at 0, 1, and 6 months. The new alternative schedule allows greater protection for travelers who need to depart within less than 1 month.

For unvaccinated people who are acutely exposed to hepatitis A virus and for those traveling to areas of high prevalence who do not have time to complete the two doses of hepatitis A vaccine, the only prevention available until recently has been immune globulin. This has changed: hepatitis A vaccine can now be used in both groups. The new recommendations for postexposure prophylaxis is that either a single dose of hepatitis A vaccine or use of immune globulin is acceptable.²⁸ In ages 12 months to 40 years, vaccine is preferred. For those over age 40, immune globulin is preferred, but vaccine is acceptable. For children younger than 12 months, the immune-suppressed, and those with chronic liver disease, immune globulin should be used.

Those traveling or working in countries with high rates of hepatitis A can be protected with either hepatitis A vaccine or immune globulin. A single dose of the vaccine is sufficient for healthy people, with a second dose at the recommended interval to complete the series. Those younger than 12 months and those who choose not to receive the vaccine, including those who are allergic to it, should be offered immune globulin. Both immune globulin and hepatitis A vaccine should be considered for certain patients who plan to travel within 2 weeks of the first vaccine dose, ie, those over age 40, those with compromised immunity, and those with chronic liver disease or other chronic conditions.

Hepatitis A vaccine is now also recommended for all unvaccinated people who anticipate close personal contact with an international adoptee during the first 60 days following arrival from countries with high or intermediate hepatitis A endemicity.²⁹ The first dose should be given as soon as the adoption is planned and ideally at least 2 weeks before the child arrives.

The past 10 years have seen marked advances in vaccine research, resulting in more products being available. In 1983 the childhood vaccination schedule included protection against seven diseases: polio, tetanus, diphtheria, pertussis, measles, mumps, and rubella. The schedule in 2010 includes protection against organisms that cause seven more: Haemophilus influenzae, hepatitis A, hepatitis B, influenza, meningococcus, pneumococcus, and varicella.¹ In addition, new vaccine products are available for adolescents, offering protection against meningococcus, seasonal influenza, and human papillomavirus (HPV) and extending the length of protection against pertussis. For adults, a vaccine now protects against shingles, and several products offer boosting of pertussis immunity.

This rapid growth in the number of recommended vaccine products has made it challenging for practicing physicians to stay current on and to implement the ever-changing recommendations. The purpose of this article is to summarize the additions and changes over the past 3 years to the schedules of recommended vaccines for children, adolescents, and adults.

VACCINE UPDATE FOR CHILDREN

The recent changes to the childhood immunization schedule have added protection against rotavirus and seasonal influenza and have expanded the protection against hepatitis A and varicella.

Rotavirus vaccination for infants

Rotavirus is the leading cause of infectious gastroenteritis in infants. It causes significant morbidity and expense, accounting for 2.7 million episodes per year in the United States, 410,000 outpatient or office visits, 201,000 to 272,000 emergency department visits, 55,000 to 70,000 hospitalizations, and 20 to 60 deaths.² Although the number of deaths in the United States is not large, rotavirus is a leading cause of infant deaths around the world.

Rotavirus vaccination is challenging because of the time frame in which the series needs to be given. The first dose has to be given after 6 weeks of age but before 15 weeks of age, and the last dose should be given before 8 months of age, with a minimum of 4 weeks between doses. It is preferable to use the same product to finish the series. They can be used interchangeably, but this then requires three total doses.

The effectiveness of the vaccine in preventing rotavirus gastroenteritis in the first year after vaccination was greater than 80% in most studies and approached 100% in preventing serious gastroenteritis.²

Those vaccinated appear to have a slightly higher rate of diarrhea and vomiting in the first 42 days after vaccination. Safety monitoring after the products were licensed has not shown an increased rate of intussusception with either product.

The only contraindication to the vaccines is a serious allergic reaction to them or to one of their components. They should be used with caution in patients who have suppressed immunity, acute gastroenteritis, preexisting gastrointestinal disease, or previous intussusception.

Gradually, we seem to be moving toward vaccinating everyone every year against seasonal influenza. Previously, vaccination was recommended for children age 6 months through 4 years; in 2008, the Advisory Committee on Immunization Practices (ACIP) extended the recommendation to the age group 5 through 18 years.³

Two types of seasonal influenza vaccine are available: trivalent influenza vaccine (TIV), which contains killed virus and is given by injection, and live-attenuated seasonal influenza vaccine (LAIV), which is given by nasal spray. Both contain the same three seasonal influenza antigens, selected each year by a team of experts. TIV is licensed for those age 6 months and older, and LAIV is licensed for ages 2 through 49 years.⁴

Since LAIV contains a live-attenuated virus, it should not be used in anyone who has a chronic illness (including those under the age of 5 with recurrent wheezing, those with suppressed immunity, and those with a history of Guillain-Barré syndrome); in pregnant women; or those who have close contact with anyone who is immune-suppressed. The injection is contraindicated for those who have had a serious allergic reaction to eggs.

Children younger than 9 years should receive two doses of either type of vaccine the first year they are vaccinated. Those who receive only one dose the first year they are vaccinated should receive two doses the next year. If they fail to receive two doses in the next year, only a single dose is recommended after that. This is a slight modification of the previous recommendation that only one dose be given the second year if only one dose was given the first year.⁵

Hepatitis A vaccine at age 12–23 months

An inactivated hepatitis A vaccine (HepA) was first licensed in 1995; another was licensed in 1996. Recommendations for their use have been revised periodically, and their widespread use has resulted in a marked reduction in the incidence of hepatitis A virus infection.

The current recommendation is that all children be vaccinated at age 12 to 23 months. In addition, in areas of high prevalence, vaccine is recommended for older children who have not been vaccinated. Other target groups are those at higher risk of hepatitis A, including travelers to endemic areas, users of illicit drugs, and men who have sex with men.⁶ Indications for vaccination before travel, after exposure to hepatitis A infection, and in families of international adoptees are covered later in this paper in a discussion about vaccinations in adults.

Varicella at 12–15 months and 4–6 years, with catch-up for others

Before varicella vaccine was licensed in 1995, 4 million cases of varicella infection (chickenpox) were reported in the United States each year, resulting in thousands of hospitalizations and more than 100 deaths. The vaccine is now widely used, with a coverage rate of 88%, and it has proven to be 85% effective.⁷ The result was a marked decrease in the incidence of varicella and in varicella-related hospitalizations and deaths.

In spite of this success, the number of varicella cases has remained constant over the past few years, and sporadic outbreaks continue to occur, predominantly in schools, even schools in which a high percentage of the children are vaccinated.^7,8 These outbreaks have involved infections in unvaccinated children and also “breakthrough disease” in children who have been vaccinated. If someone who has received one dose of vaccine is exposed to varicella, the risk of a breakthrough infection is about 15%.⁹ A two-dose series of varicella vaccine reduces the risk by about 75%.⁷ Breakthrough disease is usually milder than infection in the unvaccinated, with fewer skin lesions, milder symptoms, and fewer complications, but those affected are still infectious to others.

In 2005 and 2006, this ongoing risk of varicella prompted the ACIP to consider and recommend several new control measures:

• Two doses of varicella vaccine for all children, the first dose at age 12 to 15 months and the second at age 4 to 6 years—the same schedule as for immunization against measles, mumps, and rubella
• Two doses of varicella vaccine, the second given 4 to 8 weeks after the first, for all adolescents and adults who have no evidence of immunity
• A catch-up second dose for everyone who received one dose previously
• Screening for varicella immunity in pregnant women and postpartum vaccination with two doses for those who are not immune, the first dose given before discharge and the second dose 4 to 8 weeks later.

VACCINE UPDATE FOR ADOLESCENTS

A number of vaccines are now available and recommended for routine use in adolescents.⁹ These include HPV vaccine for girls, quadrivalent meningococcal conjugate vaccine (MCV4), and combined tetanus toxoid, reduced-dose diphtheria toxoid, and acellular pertussis (Tdap). All these are now recommended routinely at age 11 or 12. Seasonal influenza vaccine is recommended annually through age 18.

Meningococcal conjugate vaccine for all at age 11–18

There is some evidence that MCV4 may be linked to a small risk of Guillain-Barré syndrome. Although this link has not been conclusively proven, a history of Guillain-Barré syndrome calls for caution in using MCV4. For those who have a history of this syndrome but need protection against meningococcal infection, the MPSV4 is an alternative.¹¹

Pertussis: A Tdap booster at age 11–18

From Broder KR, et al; ACIP. Preventing tetanus, diphtheria, and pertussis among adolescents: use of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccines recommendations of the ACIP. MMWR Recomm Rep 2006; 55(RR–3):1–34

In addition, a greater percentage of cases now occurs in adolescents and young adults. Half of reported cases are now in those age 10 years and older. Most nonimmunized or incompletely immunized infants who develop pertussis were exposed to the disease by older household members, not by same-age cohorts. Since the disease presents as nonspecific cough in adolescents, it is often not diagnosed, and the incidence is probably much higher than the reported number of cases would indicate.

These trends were cause for public health concern and led to the development of pertussis-containing vaccine products for adolescents and adults. Two Tdap products are available: one is licensed for those ages 10 to 64 (Boostrix), the other for ages 11 to 64 (Adacel). Since 2005, the ACIP has recommended a single dose of Tdap for those age 11 to 18, preferably at 11 or 12 years.¹² The optimal interval from the last tetanus-diphtheria shot is 5 years, but a shorter interval is acceptable. Thereafter, boosters with the tetanus toxoid and reduced-dose diphtheria toxoid (Td) vaccine are recommended every 10 years. If an adolescent has not previously received a complete series of a tetanus-diphtheria product, he or she should be given the recommended number of doses, only one of which should be Tdap, the others Td. The number and timing of doses can be found at www.cdc.gov/mmwr/preview/mmwrhtml/rr55e223a5.htm.

HPV is sexually transmitted and causes genital warts, cervical cancer, and other oral, anal, and genital cancers.

HPV is the most common sexually transmitted infection in the United States, with over 6 million new cases each year.¹³ A study in 2003 to 2004 using HPV DNA typing of cervicovaginal swab specimens in a sample of women between the ages of 14 and 59 found an overall point prevalence of 26.8% of any HPV type.¹⁴ Those between 20 and 24 years had the highest prevalence at 44.8%. Those ages 14 to 19 had a prevalence of 24.5%. Several studies have reported a similar age-related increase in HPV prevalence.^15,16

One survey found that nearly 25% of girls in the United States are sexually active by age 15, 40% by age 16, and 70% by age 18.¹⁷ The 2005 Behavioral Risk Survey found that nearly 4% of girls were sexually active before age 13, and by the ninth grade 5.7% of those who were sexually active had had four or more partners.¹⁸ To receive the full benefit from the HPV vaccine, it should be given before this risk of acquiring HPV occurs.

A quadrivalent HPV vaccine (HPV4) was first licensed in the United States in 2006 for use in girls and women 9 to 26 years old to prevent cervical, vulvar, and vaginal precancerous lesions and cancer, and for prevention of anogenital warts. It contains viral proteins from HPV types 6, 11, 16, and 18, the types currently responsible for 70% of cervical cancers and 90% of anogenital warts. The vaccine is prepared in a yeast substrate and contains an aluminum-based adjuvant.

HPV4 has proven highly effective in women ages 16 to 26 not previously exposed to the four HPV types in the vaccine. The end points used in these studies were cervical intraepithelial neoplasia grade 2 or 3, adenocarcinoma in situ, anogenital warts, and vulvar and vaginal intraepithelial neoplasms.^13,19,20 The vaccine’s effectiveness has been 98% to 100% after 3 to 5 years. These trials are ongoing.

The vaccine’s efficacy in women with current or past HPV infection is less certain. Studies of this question have included only small numbers, and the confidence intervals are large and include 0. In intention-to-treat studies, its efficacy has been 39% to 46% for prevention of cervical intraepithelial neoplasia grade 2 or 3 or adenocarcinoma in situ caused by HPV-16 or HPV-18, 69% for prevention of HPV-16- or HPV-18-related vaginal intraepithelial neoplasia, and 68.5% for vaccine-type-related warts.¹³

The most common adverse effects of HPV4 have included redness, pain, and swelling at the injection site, which occur in about 20% of recipients.¹³ There is an increased risk of syncope immediately after the vaccine is given, and observation for 15 minutes after injection is recommended. A recent study suggested a link between the vaccine and venous thromboembolism. ²¹ The rate was 2 per million doses, and because many of the recipients also were taking oral contraceptives, their venous thromboembolism has not yet been definitively proven to be caused by the vaccine.

HPV4 is contraindicated in those who have experienced a severe allergic reaction to a previous dose or who have an allergy to a vaccine component. Vaccination should be deferred in those with moderate or severe acute illnesses.

In June 2006, the ACIP¹³ made the following recommendations for HPV4:

• Girls ages 11 to 12 years should be routinely vaccinated with three doses
• The series can start as early as age 9 years
• Women and girls age 13 to 26 who have not been previously vaccinated should receive catch-up vaccination
• Neither Papanicolaou (Pap) testing nor HPV screening is necessary before vaccination
• HPV4 can be given with other age-appropriate vaccines
• Vaccination does not change the recommendations for cervical cancer screening
• The recommendations remain the same regardless of abnormal Pap tests, positive HPV DNA tests, or warts.

There have been two very recent developments regarding HPV vaccines.

A bivalent vaccine (HPV2) has been licensed in the United States and approved for use in girls and women ages 10 to 25 for prevention of cervical cancer and precancerous lesions. It contains antigens against HPV-16 and HPV-18 but does not provide protection against genital warts. The ACIP has stated no preference for the bivalent or the quadrivalent vaccine for the prevention of cervical cancer and precancerous lesions.

HPV4 has also gained licensure for use in boys and men age 9 to 26 for the prevention of genital warts. The ACIP has not recommended it for routine use, leaving the decision to patients and physicians after weighing the potential benefits and costs.

VACCINE UPDATE FOR ADULTS

Four vaccines are now routinely recommended for adults:

• Seasonal influenza vaccine starting at age 50
• Pneumococcal polysaccharide vaccine (PPSV23) starting at age 65
• Herpes zoster vaccine starting at age 60
• A diphtheria and tetanus toxoid product every 10 years, with Tdap given once.²²

The rest of the adult schedule is based on catch-up (measles, mumps, rubella, varicella) or risk (hepatitis A and B and meningococccal disease). Seasonal influenza and pneumococcal vaccinations are also recommended before ages 50 and 65, respectively, for those with certain risk conditions. The complete adult immunization schedule can be found on the US Centers for Disease Control and Prevention (CDC) Web site.²²

One dose of Tdap instead of the next Td booster

The CDC now recommends that a single dose of Tdap should replace the next dose of Td for adults ages 19 to 64 as part of the every-10-year tetanus-diphtheria boosting recommendation and if indicated for wound management. ²³ In addition, a single dose of Tdap should be given to adults who have close contact with infants less than 6 months of age. The optimal interval between this Tdap shot and the last Td booster is 2 years or greater, but shorter intervals are acceptable. Women of childbearing age should receive Tdap preconception or postpartum if they have not previously received it. Tdap is not approved for use during pregnancy. Health care workers should also receive a dose of Tdap if they have never received it previously and if their last Td booster was more than 2 years ago, although less than 2 years is acceptable.

Contraindications to Tdap include anaphylaxis to a vaccine component and encephalopathy occurring within 7 days of previously receiving a pertussis vaccine.

Herpes zoster vaccine for those age 60 and older

Shingles causes considerable morbidity in older adults. The lifetime risk is 25%, and onefourth of those with shingles develop postherpetic neuralgia.

Herpes zoster vaccine is a live-attenuated vaccine that requires only a single injection. It is licensed for use in those ages 60 and older, and the ACIP recommends its routine use.²⁴ Its effectiveness is approximately 50% and is inversely related to age. The number of patients who need to be vaccinated to prevent one lifetime case of shingles is 17.

Contraindications to this vaccine include a prior anaphylactic reaction to gelatin or neomycin, compromised immunity due to disease or to immune-suppressive therapy including high-dose corticosteroids, and active tuberculosis.

Payment for this vaccine by Medicare is through Part D, creating some administrative difficulties for physicians’ offices.

Pneumococcal vaccination extended to smokers and people with asthma

The ACIP recently added two new groups for whom PPSV23 is recommended: smokers and those with asthma.²⁵ Smoking poses as much of a risk for pneumococcal pneumonia as do diabetes and other chronic illnesses that are currently indications for the vaccine. The number needed to vaccinate to prevent one case of pneumonia among smokers is 10,000 in people ages 18 to 44, and 4,000 in those ages 45 to 64.²⁶

The ACIP also clarified the recommendation for a second dose of PPSV23.²⁵ A second dose 5 years after the first is recommended for those who have immune suppression, sickle cell disease, or asplenia. People over age 65 should receive a second dose if they were vaccinated more than 5 years previously and before age 65.

New uses for hepatitis A vaccine

A combined hepatitis A and hepatitis B vaccine (Twinrix) has received approval for an alternate, four-dose schedule at 0, 7, 21 days, and 12 months.²⁷ It has previously only been approved for a three-dose schedule at 0, 1, and 6 months. The new alternative schedule allows greater protection for travelers who need to depart within less than 1 month.

For unvaccinated people who are acutely exposed to hepatitis A virus and for those traveling to areas of high prevalence who do not have time to complete the two doses of hepatitis A vaccine, the only prevention available until recently has been immune globulin. This has changed: hepatitis A vaccine can now be used in both groups. The new recommendations for postexposure prophylaxis is that either a single dose of hepatitis A vaccine or use of immune globulin is acceptable.²⁸ In ages 12 months to 40 years, vaccine is preferred. For those over age 40, immune globulin is preferred, but vaccine is acceptable. For children younger than 12 months, the immune-suppressed, and those with chronic liver disease, immune globulin should be used.

Those traveling or working in countries with high rates of hepatitis A can be protected with either hepatitis A vaccine or immune globulin. A single dose of the vaccine is sufficient for healthy people, with a second dose at the recommended interval to complete the series. Those younger than 12 months and those who choose not to receive the vaccine, including those who are allergic to it, should be offered immune globulin. Both immune globulin and hepatitis A vaccine should be considered for certain patients who plan to travel within 2 weeks of the first vaccine dose, ie, those over age 40, those with compromised immunity, and those with chronic liver disease or other chronic conditions.

Hepatitis A vaccine is now also recommended for all unvaccinated people who anticipate close personal contact with an international adoptee during the first 60 days following arrival from countries with high or intermediate hepatitis A endemicity.²⁹ The first dose should be given as soon as the adoption is planned and ideally at least 2 weeks before the child arrives.

A 21-year-old man has had cough and hemoptysis for 3 days. For the past 3 years he has smoked one pack of cigarettes a day. His medical history is unremarkable, and he has had no chest trauma or thoracic surgery.

The patient says he was born full-term, and he has never been aware of any congenital anomalies.

Q: Which is the most likely diagnosis?

• Fractured rib
• Poland syndrome
• Paget disease
• Bifid rib

A: Bifid rib, a congenital anomaly, is the correct answer (see below).

Fractured rib. The patient has no history of chest trauma or thoracic surgery, nor any evidence on chest x-ray to suggest a fractured rib. Also, he has no evidence of osteoporosis to suspect a spontaneous rib fracture. His hemoptysis is most likely due to acute bronchitis.

Poland syndrome is a unilateral deficiency of the pectoralis muscle, variably associated with ipsilateral thoracic and upper limb anomalies. Bilateral hypoplasia or aplasia of the pectoralis muscle and upper-limb defects in association with variable thoracic muscles, chest wall deformities, and lower-limb defects has been infrequently reported in the literature. The diagnosis is usually based on the physical examination (asymmetric chest) or on chest x-ray (unilateral hyperlucent lung).¹ This is not the case in our patient.

Paget disease is a chronic, abnormal bone-remodeling process that leads to enlarged, less-dense, brittle bones. The spine, femur, pelvis, skull, clavicle, and humerus are most commonly affected. In the United States, the prevalence is 3% to 4% in people over age 40. Black Americans have a higher prevalence rate than black Africans, and the disease is rare in Asians.

Pain is the most common symptom, but Paget disease is usually asymptomatic. Paget disease can lead to insufficiency fractures, pathologic fractures, secondary arthritis, and nerve impingement in the spine or the base of the skull. Sarcomatous degeneration of the affected bone has been reported, but is rare.

Radiographic findings are often diagnostic. The skull and long bones typically show evidence of osteolysis from the epiphysis and advancing along the diaphysis. Radiographic findings in the sclerotic phase typically involve the axial skeleton and include trabecular coarsening and distortion and cortical thickening.

Rib abnormalities may be observed; these may either be isolated or may be a sign of multi-system malformations. However, in our patient, the radiographic finding of a bony bridge does not fit the description of Paget disease.²

BIFID RIB

The overall prevalence of bifid rib is estimated at 0.15% to 3.4% (mean 2%), and it accounts for up to 20% of all congenital rib anomalies.³ It is usually unilateral. Wattanasirichaigoon et al⁴ described patterns of rib defects in 47 cases, with bifid rib accounting for 28% of cases.

As with Paget disease, rib anomalies may occur in isolation or in association with multi-system malformations. Since the ribs originate from the mesoderm, it is not surprising that the costal defects are associated with malformations in other organs of the same origin, such as the heart and the kidneys.³ Bifid ribs are also seen in several genetic disorders such as Gorlin-Goltz (ie, basal cell nevus) syndrome, which affects multiple organs including bones, skin, eye, and neural system.⁵ Occasionally, it is encountered as a part of Jobs syndrome (ie, high levels of immunoglobulin E and recurrent infections),⁶ and Kindler syndrome, a rare genodermatosis.⁷

The literature contains little information about the clinical significance of bifid rib. Patients should undergo a thorough physical examination, including oral and cutaneous evaluation, to rule out a genetic syndrome. Physical findings such as palmar pits, subcutaneous calcifications, or odontogenic cyst warrant a more intensive radiologic and genetic investigation.⁵ If the physical examination is normal and if the patient is asymptomatic, additional clinical or radiologic investigation is of low yield. And as in our patient, the anomaly may go unnoticed on computed tomography of the chest.

A 21-year-old man has had cough and hemoptysis for 3 days. For the past 3 years he has smoked one pack of cigarettes a day. His medical history is unremarkable, and he has had no chest trauma or thoracic surgery.

The patient says he was born full-term, and he has never been aware of any congenital anomalies.

Q: Which is the most likely diagnosis?

• Fractured rib
• Poland syndrome
• Paget disease
• Bifid rib

A: Bifid rib, a congenital anomaly, is the correct answer (see below).

Fractured rib. The patient has no history of chest trauma or thoracic surgery, nor any evidence on chest x-ray to suggest a fractured rib. Also, he has no evidence of osteoporosis to suspect a spontaneous rib fracture. His hemoptysis is most likely due to acute bronchitis.

Poland syndrome is a unilateral deficiency of the pectoralis muscle, variably associated with ipsilateral thoracic and upper limb anomalies. Bilateral hypoplasia or aplasia of the pectoralis muscle and upper-limb defects in association with variable thoracic muscles, chest wall deformities, and lower-limb defects has been infrequently reported in the literature. The diagnosis is usually based on the physical examination (asymmetric chest) or on chest x-ray (unilateral hyperlucent lung).¹ This is not the case in our patient.

Paget disease is a chronic, abnormal bone-remodeling process that leads to enlarged, less-dense, brittle bones. The spine, femur, pelvis, skull, clavicle, and humerus are most commonly affected. In the United States, the prevalence is 3% to 4% in people over age 40. Black Americans have a higher prevalence rate than black Africans, and the disease is rare in Asians.

Pain is the most common symptom, but Paget disease is usually asymptomatic. Paget disease can lead to insufficiency fractures, pathologic fractures, secondary arthritis, and nerve impingement in the spine or the base of the skull. Sarcomatous degeneration of the affected bone has been reported, but is rare.

Radiographic findings are often diagnostic. The skull and long bones typically show evidence of osteolysis from the epiphysis and advancing along the diaphysis. Radiographic findings in the sclerotic phase typically involve the axial skeleton and include trabecular coarsening and distortion and cortical thickening.

Rib abnormalities may be observed; these may either be isolated or may be a sign of multi-system malformations. However, in our patient, the radiographic finding of a bony bridge does not fit the description of Paget disease.²

BIFID RIB

The overall prevalence of bifid rib is estimated at 0.15% to 3.4% (mean 2%), and it accounts for up to 20% of all congenital rib anomalies.³ It is usually unilateral. Wattanasirichaigoon et al⁴ described patterns of rib defects in 47 cases, with bifid rib accounting for 28% of cases.

As with Paget disease, rib anomalies may occur in isolation or in association with multi-system malformations. Since the ribs originate from the mesoderm, it is not surprising that the costal defects are associated with malformations in other organs of the same origin, such as the heart and the kidneys.³ Bifid ribs are also seen in several genetic disorders such as Gorlin-Goltz (ie, basal cell nevus) syndrome, which affects multiple organs including bones, skin, eye, and neural system.⁵ Occasionally, it is encountered as a part of Jobs syndrome (ie, high levels of immunoglobulin E and recurrent infections),⁶ and Kindler syndrome, a rare genodermatosis.⁷

The literature contains little information about the clinical significance of bifid rib. Patients should undergo a thorough physical examination, including oral and cutaneous evaluation, to rule out a genetic syndrome. Physical findings such as palmar pits, subcutaneous calcifications, or odontogenic cyst warrant a more intensive radiologic and genetic investigation.⁵ If the physical examination is normal and if the patient is asymptomatic, additional clinical or radiologic investigation is of low yield. And as in our patient, the anomaly may go unnoticed on computed tomography of the chest.

A 21-year-old man has had cough and hemoptysis for 3 days. For the past 3 years he has smoked one pack of cigarettes a day. His medical history is unremarkable, and he has had no chest trauma or thoracic surgery.

The patient says he was born full-term, and he has never been aware of any congenital anomalies.

Q: Which is the most likely diagnosis?

• Fractured rib
• Poland syndrome
• Paget disease
• Bifid rib

A: Bifid rib, a congenital anomaly, is the correct answer (see below).

Fractured rib. The patient has no history of chest trauma or thoracic surgery, nor any evidence on chest x-ray to suggest a fractured rib. Also, he has no evidence of osteoporosis to suspect a spontaneous rib fracture. His hemoptysis is most likely due to acute bronchitis.

Poland syndrome is a unilateral deficiency of the pectoralis muscle, variably associated with ipsilateral thoracic and upper limb anomalies. Bilateral hypoplasia or aplasia of the pectoralis muscle and upper-limb defects in association with variable thoracic muscles, chest wall deformities, and lower-limb defects has been infrequently reported in the literature. The diagnosis is usually based on the physical examination (asymmetric chest) or on chest x-ray (unilateral hyperlucent lung).¹ This is not the case in our patient.

Paget disease is a chronic, abnormal bone-remodeling process that leads to enlarged, less-dense, brittle bones. The spine, femur, pelvis, skull, clavicle, and humerus are most commonly affected. In the United States, the prevalence is 3% to 4% in people over age 40. Black Americans have a higher prevalence rate than black Africans, and the disease is rare in Asians.

Pain is the most common symptom, but Paget disease is usually asymptomatic. Paget disease can lead to insufficiency fractures, pathologic fractures, secondary arthritis, and nerve impingement in the spine or the base of the skull. Sarcomatous degeneration of the affected bone has been reported, but is rare.

Radiographic findings are often diagnostic. The skull and long bones typically show evidence of osteolysis from the epiphysis and advancing along the diaphysis. Radiographic findings in the sclerotic phase typically involve the axial skeleton and include trabecular coarsening and distortion and cortical thickening.

Rib abnormalities may be observed; these may either be isolated or may be a sign of multi-system malformations. However, in our patient, the radiographic finding of a bony bridge does not fit the description of Paget disease.²

BIFID RIB

The overall prevalence of bifid rib is estimated at 0.15% to 3.4% (mean 2%), and it accounts for up to 20% of all congenital rib anomalies.³ It is usually unilateral. Wattanasirichaigoon et al⁴ described patterns of rib defects in 47 cases, with bifid rib accounting for 28% of cases.

As with Paget disease, rib anomalies may occur in isolation or in association with multi-system malformations. Since the ribs originate from the mesoderm, it is not surprising that the costal defects are associated with malformations in other organs of the same origin, such as the heart and the kidneys.³ Bifid ribs are also seen in several genetic disorders such as Gorlin-Goltz (ie, basal cell nevus) syndrome, which affects multiple organs including bones, skin, eye, and neural system.⁵ Occasionally, it is encountered as a part of Jobs syndrome (ie, high levels of immunoglobulin E and recurrent infections),⁶ and Kindler syndrome, a rare genodermatosis.⁷

The literature contains little information about the clinical significance of bifid rib. Patients should undergo a thorough physical examination, including oral and cutaneous evaluation, to rule out a genetic syndrome. Physical findings such as palmar pits, subcutaneous calcifications, or odontogenic cyst warrant a more intensive radiologic and genetic investigation.⁵ If the physical examination is normal and if the patient is asymptomatic, additional clinical or radiologic investigation is of low yield. And as in our patient, the anomaly may go unnoticed on computed tomography of the chest.

Q: Which is the most likely diagnosis?

• Rheumatoid arthritis
• Nodular osteoarthritis
• Tophaceous gout
• Pseudogout
• Xanthoma tuberosum

A: Tophaceous gout is the diagnosis. This patient’s serum urate level was 9 mg/dL (normal range 4.0–8.0) despite allopurinol therapy, with normal levels of lipids, urea, and creatinine. Polarized light microscopy of aspirated synovial fluid showed monosodium urate crystals, thus confirming the diagnosis.

Rheumatoid arthritis is typically polyarticular and symmetrical and spares the distal interphalangeal joints. Subcutaneous rheumatoid nodules may mimic gouty tophi.

Pseudogout shares some of the features of gout. It results from deposits of calcium pyrophosphate crystals in and around the joints. The diagnosis is made by identifying the crystals on microscopy when calcinosis is seen on x-ray. Tophaceous nodules almost never occur.

Xanthoma tuberosum is associated with hypercholesterolemia, particularly with elevated levels of low-density lipoprotein cholesterol. Lesions occur on pressure areas such as the knees or elbows and vary in size and shape from small papules to firm, lobulated tumors. They are yellow or orange, often with an erythematous halo. They are not associated with chronic proliferative arthritis.

CLINICAL PRESENTATION OF GOUT

Gout is a common metabolic disease characterized by an intermittent course of acute inflammatory arthritis initially affecting one or a few joints. Almost all patients have hyperuricemia, but serum urate levels can be normal or low during an acute attack. On the other hand, many hyperuricemic patients never have a clinical event.

If the hyperuricemia is untreated, some patients develop chronic polyarthritis and nephrolithiasis.¹ Inadequate treatment of hyperuricemia may result in chronic tophaceous gout. Although tophaceous gout usually is a sign of long-standing hyperuricemia, tophi can in rare cases be a first symptom of the disorder.²

Even though our patient had been on allopurinol therapy, the dose was not high enough to achieve a serum urate level significantly below the saturation point of urate (about 6.7 mg/dL).

Q: Which is the most likely diagnosis?

• Rheumatoid arthritis
• Nodular osteoarthritis
• Tophaceous gout
• Pseudogout
• Xanthoma tuberosum

A: Tophaceous gout is the diagnosis. This patient’s serum urate level was 9 mg/dL (normal range 4.0–8.0) despite allopurinol therapy, with normal levels of lipids, urea, and creatinine. Polarized light microscopy of aspirated synovial fluid showed monosodium urate crystals, thus confirming the diagnosis.

Rheumatoid arthritis is typically polyarticular and symmetrical and spares the distal interphalangeal joints. Subcutaneous rheumatoid nodules may mimic gouty tophi.

Pseudogout shares some of the features of gout. It results from deposits of calcium pyrophosphate crystals in and around the joints. The diagnosis is made by identifying the crystals on microscopy when calcinosis is seen on x-ray. Tophaceous nodules almost never occur.

Xanthoma tuberosum is associated with hypercholesterolemia, particularly with elevated levels of low-density lipoprotein cholesterol. Lesions occur on pressure areas such as the knees or elbows and vary in size and shape from small papules to firm, lobulated tumors. They are yellow or orange, often with an erythematous halo. They are not associated with chronic proliferative arthritis.

CLINICAL PRESENTATION OF GOUT

Gout is a common metabolic disease characterized by an intermittent course of acute inflammatory arthritis initially affecting one or a few joints. Almost all patients have hyperuricemia, but serum urate levels can be normal or low during an acute attack. On the other hand, many hyperuricemic patients never have a clinical event.

If the hyperuricemia is untreated, some patients develop chronic polyarthritis and nephrolithiasis.¹ Inadequate treatment of hyperuricemia may result in chronic tophaceous gout. Although tophaceous gout usually is a sign of long-standing hyperuricemia, tophi can in rare cases be a first symptom of the disorder.²

Even though our patient had been on allopurinol therapy, the dose was not high enough to achieve a serum urate level significantly below the saturation point of urate (about 6.7 mg/dL).

Q: Which is the most likely diagnosis?

• Rheumatoid arthritis
• Nodular osteoarthritis
• Tophaceous gout
• Pseudogout
• Xanthoma tuberosum

A: Tophaceous gout is the diagnosis. This patient’s serum urate level was 9 mg/dL (normal range 4.0–8.0) despite allopurinol therapy, with normal levels of lipids, urea, and creatinine. Polarized light microscopy of aspirated synovial fluid showed monosodium urate crystals, thus confirming the diagnosis.

Rheumatoid arthritis is typically polyarticular and symmetrical and spares the distal interphalangeal joints. Subcutaneous rheumatoid nodules may mimic gouty tophi.

Pseudogout shares some of the features of gout. It results from deposits of calcium pyrophosphate crystals in and around the joints. The diagnosis is made by identifying the crystals on microscopy when calcinosis is seen on x-ray. Tophaceous nodules almost never occur.

Xanthoma tuberosum is associated with hypercholesterolemia, particularly with elevated levels of low-density lipoprotein cholesterol. Lesions occur on pressure areas such as the knees or elbows and vary in size and shape from small papules to firm, lobulated tumors. They are yellow or orange, often with an erythematous halo. They are not associated with chronic proliferative arthritis.

CLINICAL PRESENTATION OF GOUT

Gout is a common metabolic disease characterized by an intermittent course of acute inflammatory arthritis initially affecting one or a few joints. Almost all patients have hyperuricemia, but serum urate levels can be normal or low during an acute attack. On the other hand, many hyperuricemic patients never have a clinical event.

If the hyperuricemia is untreated, some patients develop chronic polyarthritis and nephrolithiasis.¹ Inadequate treatment of hyperuricemia may result in chronic tophaceous gout. Although tophaceous gout usually is a sign of long-standing hyperuricemia, tophi can in rare cases be a first symptom of the disorder.²

Even though our patient had been on allopurinol therapy, the dose was not high enough to achieve a serum urate level significantly below the saturation point of urate (about 6.7 mg/dL).

Closer to home, general internists and other primary care providers can use the awareness of global health concerns to the health advantage of our patients, including the young and healthy, who generally eschew preventive health visits to their physicians, and busy traveling executives, who only see a doctor for (hopefully) quick resolution to intermittent problems.

In this issue of the Journal, Powell and Ford offer a general primer on travel medicine, highlighting specific concerns that should be addressed to facilitate our patients’ safe and uninterrupted travels. But often, a pretravel visit is also a good time to introduce concepts of preventive health to patients who might not otherwise be accessible or amenable.

Just as the preoperative medical consultation can provide a “teaching moment” to address smoking cessation or reversible cardiac risks to a captive audience, the visit regarding “What shots do I need to go to Thailand?” can open the door for talk about general vaccinations (see the article by Campos-Outcalt of this issue), venereal disease, air-travel-associated thrombosis, excessive alcohol use, and perhaps other wellness issues. Creating a travel advisory service within most practices will not supplant the benefits of having travelers review the CDC travel Web site or the need to refer some patients to travel medicine experts regarding specific diseases and vaccinations. But it may create the opportunity for interaction, dialogue, and even a blood pressure check with patients who might not otherwise have the time or see the need to schedule a visit with a physician in the absence of an acute medical concern.

Closer to home, general internists and other primary care providers can use the awareness of global health concerns to the health advantage of our patients, including the young and healthy, who generally eschew preventive health visits to their physicians, and busy traveling executives, who only see a doctor for (hopefully) quick resolution to intermittent problems.

In this issue of the Journal, Powell and Ford offer a general primer on travel medicine, highlighting specific concerns that should be addressed to facilitate our patients’ safe and uninterrupted travels. But often, a pretravel visit is also a good time to introduce concepts of preventive health to patients who might not otherwise be accessible or amenable.

Just as the preoperative medical consultation can provide a “teaching moment” to address smoking cessation or reversible cardiac risks to a captive audience, the visit regarding “What shots do I need to go to Thailand?” can open the door for talk about general vaccinations (see the article by Campos-Outcalt of this issue), venereal disease, air-travel-associated thrombosis, excessive alcohol use, and perhaps other wellness issues. Creating a travel advisory service within most practices will not supplant the benefits of having travelers review the CDC travel Web site or the need to refer some patients to travel medicine experts regarding specific diseases and vaccinations. But it may create the opportunity for interaction, dialogue, and even a blood pressure check with patients who might not otherwise have the time or see the need to schedule a visit with a physician in the absence of an acute medical concern.

Closer to home, general internists and other primary care providers can use the awareness of global health concerns to the health advantage of our patients, including the young and healthy, who generally eschew preventive health visits to their physicians, and busy traveling executives, who only see a doctor for (hopefully) quick resolution to intermittent problems.

In this issue of the Journal, Powell and Ford offer a general primer on travel medicine, highlighting specific concerns that should be addressed to facilitate our patients’ safe and uninterrupted travels. But often, a pretravel visit is also a good time to introduce concepts of preventive health to patients who might not otherwise be accessible or amenable.

Just as the preoperative medical consultation can provide a “teaching moment” to address smoking cessation or reversible cardiac risks to a captive audience, the visit regarding “What shots do I need to go to Thailand?” can open the door for talk about general vaccinations (see the article by Campos-Outcalt of this issue), venereal disease, air-travel-associated thrombosis, excessive alcohol use, and perhaps other wellness issues. Creating a travel advisory service within most practices will not supplant the benefits of having travelers review the CDC travel Web site or the need to refer some patients to travel medicine experts regarding specific diseases and vaccinations. But it may create the opportunity for interaction, dialogue, and even a blood pressure check with patients who might not otherwise have the time or see the need to schedule a visit with a physician in the absence of an acute medical concern.

Before going abroad to areas that might pose a risk to their health, most people ought to visit their primary care physicians and many should be referred to a specialist in travel medicine.

In this article, we review the key elements of the pretravel consult as it relates to the prevention and self-treatment of the most common diseases that pose health risks for travelers. We also give guidelines for when to refer patients to a specialist.

WHY PRIMARY CARE PHYSICIANS NEED TO KNOW TRAVEL MEDICINE

International travel to exotic locations is becoming more popular. In 2008, one out of five Americans traveled abroad, and 38 million visits were to developing countries where there are significant health risks for travelers.¹

One third to one half of travelers to developing countries experience some kind of illness while abroad, most commonly diarrhea or upper respiratory infections, which typically lead to 3 lost days during a 2-week trip.

These illnesses are often preventable and self-treatable.² Unfortunately, studies suggest that most travelers do not seek adequate medical advice, and that when they do they often fail to complete courses of medication.^3,4

All these factors point to the need for primary care providers to become proficient in the pretravel consult and, if necessary, to refer patients to travel specialists and clinics.

WHY REFER TO A TRAVEL CLINIC?

In one study of travelers to areas of high risk for malaria or hepatitis A, 42% of those who consulted only their family doctor became ill, in contrast to 22% of those who attended a travel medicine clinic.⁴

As a rule of thumb, anyone traveling to an area where malaria is endemic should be referred to a specialist, as should anyone at risk of yellow fever or typhoid fever. As many as 8 per 1,000 travelers may return from areas of risk infected with malaria.⁵

Long-term travelers and people who will spend time in urban slums or rural or remote regions have an even greater need for referral to a travel clinic, as they are at higher risk of exposure to Japanese encephalitis, cholera, epidemic meningitis, dengue fever, and rabies.⁶

THE PRETRAVEL CONSULT: ESSENTIALS

A pretravel consult ought to be scheduled 4 to 6 weeks in advance of the trip, since many vaccines require that much time to induce immunity, and some require a series of shots.

Unfortunately, many patients who think of arranging a travel consult make the appointment at the last minute, and some come with an incomplete knowledge of their travel plans. However, even without enough advance notice, a consult can be beneficial.

Travelers sometimes change their itineraries in-country or engage in unanticipated risky behaviors. A good travel medicine physician tries to anticipate even these unplanned risks and changes in itinerary.

Where is the traveler going? When? For how long?

The pretravel consult starts with a detailed discussion of the patient’s itinerary. It needs to include length, dates, and location of travel, as well as anticipated activities and accommodations.

A remarkable number of travelers come to consults not knowing the names of specific countries they will visit, perhaps saying only that they are going to Africa or South America. An accurate itinerary is indispensible, as appropriate medical advice is highly specific to country and region. The incidence and geographic distribution of many travelers’ diseases change over time, and this requires physicians to consult the most current information available.

Tropical countries, in general, are risky, but each pathogen has a unique distribution that may vary between urban and rural areas or by season. Detailed, up-to-date information is available from the US Centers for Disease Control and Prevention (CDC) (www.cdc.gov) for individual countries and for specific provinces and locations within those countries. Physicians should consult the CDC whenever advising a patient preparing to travel. ⁷

How is the traveler’s current health?

Several immunizations cannot be given to the very young, the elderly, or those who are immunocompromised.

The greatest risk of death to travelers is not from tropical diseases but from cardiovascular disease, which according to one study is responsible for half of deaths abroad.⁸ Patients with heart disease or other known health concerns need to be counseled to avoid activities that will put them at further risk. The advice applies especially in situations such as remote travel or even cruises, where prompt emergency medical care may be difficult or impossible to obtain.

People infected with human immunodeficiency virus (HIV) face discriminatory travel prohibitions in 74 countries.⁹

Foreign-born travelers who are visiting family and friends in developing countries may have lost their immunity to local pathogens and thus can be more at risk because they are not prepared to take necessary health precautions.

Also, a significant number of travelers become infected but develop illnesses only after they return, so a posttravel visit may be necessary.⁶

Prescription and even over-the-the-counter drugs may be difficult or impossible to obtain in foreign countries, and ample supplies should be brought along.

Is the traveler up to date on routine immunizations?

A number of infectious diseases that have been controlled or eradicated in North America through regular childhood immunizations are still endemic in many remote areas and developing countries. All travelers should be up to date on routine immunizations, including those for measles-mumps-rubella, tetanus, polio, meningitis, and hepatitis A and B.

Polio. A one-time polio booster is recommended for adults traveling to certain countries or areas of the world.

Meningitis vaccine is now routinely given to young people, but adult patients may need it before they travel.

Hepatitis A is contracted through fecal contamination of food and water. Common sources are foods prepared in an unhygienic manner, raw fruits and vegetables, shellfish, and contaminated water.

Hepatitis B vaccine is also now routinely given to young people, but it should be offered to travelers planning to stay more than 1 month and to long-term expatriates. This vaccine is also recommended for travelers who may be exposed to blood or body fluids, who are contemplating sexual activity or tattooing in the host country, or who may require medical or dental care while traveling, as well as for adventure travelers or travelers to remote regions.

The vaccination is given in a three-dose schedule at 0, 1, and 6 months. For protection against both hepatitis A and B, the vaccine Twinrix can be used on the same schedule as for hepatitis B. An accelerated schedule of 0, 7, and 21 days with a booster at 12 months allows completion of the entire series in 4 weeks, thus putting completion of vaccination before travel in the same time frame as other vaccines in a series, such as those for rabies and Japanese encephalitis.

PREVENTIVE COUNSELING

In addition, travelers going abroad should be advised on measures to avoid diarrhea, insectvector diseases, accidents, excessive exposure to the sun, altitude sickness, and other risks their itineraries may expose them to.

Avoiding traveler’s diarrhea

Traveler’s diarrhea is by far the most common health problem experienced abroad. It is prevalent in Mexico, where 20 million visits by Americans occur each year. A quarter to half of visitors to developing countries contract traveler’s diarrhea and, on average, lose 2 to 3 days of their business trip or vacation.^3,10 The disease therefore imposes not only discomfort but also financial losses on travelers, especially business travelers.

Though many pathogens may be responsible, the most common one is Escherichia coli, usually transmitted by human fecal contamination of food or drink. Preventive measures against E coli are the same as for other foodborne and waterborne infections, such as hepatitis A, cholera, and typhoid fever.

The rule for avoiding traveler’s diarrhea may be summarized by the CDC-coined phrase, “boil it, cook it, peel it, or forget it.” Simple, written advice is most likely to be followed. ⁶ Thorough boiling or cooking kills bacteria in contaminated food, and food should be served steaming hot. Travelers should only eat foods they know have been well cooked, declining cold dishes like salsa or casseroles. They should avoid tap water for brushing teeth or in the form of ice cubes and should stick to drinking bottled beverages, preferably carbonated ones. No matter how appetizing a salad looks, travelers should avoid eating fresh fruits and vegetables unless they are sure that they were peeled under sanitary conditions. Simply eating at a high-priced restaurant is not a guarantee of uncontaminated food. Before meals or any hand-to-mouth contact, hands should be washed in soap and water or with sanitizers.

Travelers to remote areas may wish to acquire filtering devices, chlorine, or iodine for treating water. A combination of filtering and iodine treatment is most effective.

While this advice is undoubtedly wise, the evidence shows that, in practice, most travelers fail to take all precautions, and the benefits of this counseling have been difficult to demonstrate.¹¹ Therefore, physicians should prescribe drugs for prophylaxis and self-treatment of traveler’s diarrhea during travel.

Bismuth subsalicylate (Pepto-Bismol) taken as two tablets or 2 oz of liquid 4 times a day while traveling may reduce the risk of diarrhea by one half, though it should be avoided by patients with contraindications to aspirin.^3,6

Self-treating traveler’s diarrhea

Proper hydration is crucial, since dehydration can worsen and prolong symptoms.

Ciprofloxacin (Cipro) 500 mg orally two times daily for 3 to 5 days is effective.

Azithromycin (Zithromax) 500 mg daily for 3 to 5 days may be better in some areas of Southeast Asia, where fluoroquinolone-resistant bacteria are prevalent.

Rifaximin (Xifaxan), a nonsystemic antibiotic, is another option. The dosage is 200 mg three times a day for 3 days.

Avoiding insect bites

Malaria, yellow fever, tickborne encephalitis, and dengue fever are all transmitted by insect bites. Often the best protection is to avoid being bitten.

Bites can be avoided by using insect repellants containing diethyltoluamide (DEET) or picardin. If the traveler is going to be out in the sun, he or she should apply sunscreen first, then DEET on top of that. Anopheles, which transmits malaria, is a night-biting mosquito and may be avoided by staying in screened areas at dusk and dawn and by using bed netting. Permethrin, an insecticide, can be applied to clothing and mosquito netting.

Other things to avoid

Accidents are the second most common cause of death in travelers (after cardiovascular disease), accounting for as many as one-third of deaths.⁹ Several studies indicate road accidents are the major cause of accidental death, but also significant are drowning and air crashes. Travelers should be advised that transportation in developing countries is often more dangerous than at home. Seaside vacationers should be aware of the dangers of riptides and other threats to swimmers and should obey warnings posted at beaches.

Sexually transmitted diseases. When appropriate, physicians should warn travelers about the dangers of contracting HIV and other sexually transmitted diseases, especially in sub-Saharan Africa.

Sunburn, dehydration. Travelers should regularly use sunscreen and should remain hydrated.

Crimes against and involving tourists are a serious threat in many places, including some popular destinations. All of the 100,000 young people traveling to Mexico each year for spring break should read the US Department of State warnings against crime and possible arrest in that country.¹² Travelers who are victims of crimes in foreign countries should contact their national consulate as soon as possible. The US Department of State issues advisories on countries where there is danger to travelers because of political turmoil, crime, or other causes.¹³

Motion sickness and jet lag can be ameliorated by proper hydration, avoiding caffeine, and using a scopolamine patch or dimenhydrinate (Dramamine).¹

When traveling to wilderness areas

Wilderness and expedition medicine is a complex subset of travel medicine.¹⁴ All travelers need to understand the risks of whatever activities they undertake.

Mountain climbers and skiers have to contend with altitude sickness and frostbite. Scuba divers have the risks of decompression sickness, barotrauma, and hazardous marine life. Travelers on expeditions may have to deal with predatory animals, exotic parasites, and ethnic or political violence. People who participate in these activities should do so only when they are properly certified and educated in the associated health risks.

Ordinary tourists should enjoy safe adventures with well-established tour agencies and venues and should be cautioned against activities that expose them to dangers they may not be prepared to confront.

Insurance, evacuation, and emergency care

Health insurance often does not pay for preventive travel medicine. Unfortunately, cost can be a factor in immunizations and other health care. The cost of most travelers’ medications and vaccinations is generally comparable to that of other immunizations. The exceptions are two specialized vaccines—ie, for Japanese encephalitis ($1,000 or more for a full course) and for rabies, which can cost considerably more. Pricing by different providers can vary widely.

Travelers, especially those who are pregnant, elderly, disabled, or immunocompromised or who have preexisting diseases, need to review their insurance policies to make certain that care in foreign countries is covered. If not, evacuation insurance can be purchased at a relatively modest cost.